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ESBL-B before colorectal surgery ups risk of surgical site infection
MADRID – Patients who are carriers of , despite a standard prophylactic antibiotic regimen.
Surgical site infections (SSIs) occurred in 23% of those who tested positive for the pathogens preoperatively, compared with 10.5% of ESBL-B–negative patients – a significant increased risk of 2.25, Yehuda Carmeli, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual congress.
ESBL-B was not the infective pathogen in most infection cases, but being a carrier increased the likelihood of an ESBL-B SSI. ESBL-B was the pathogen in 7.2% of the carriers and 1.6% of the noncarriers. However, investigators are still working to determine if the species present in the wound infection are the same as the ones present at baseline, said Dr. Carmeli of Tel Aviv Medical Center.
All of these results are emerging from the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in Gram-Negative Organisms: Studying Intervention Strategies” is a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria. From 2012 to 2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures).
Several of the studies were reported at ECCMID 2018.
This portion of R-GNOSIS was intended to investigate the relationship between ESBL-B carriage and postoperative surgical site infections among colorectal surgery patients.
The study comprised 3,626 patients who were preoperatively screened for ESBL-B within 2 weeks of colorectal surgery. The ESBL-B carriage rate was 15.3% overall, but ranged from 12% to 20% by site. Of the carriers, 222 were included in this study sample. They were randomly matched with 444 noncarriers.
Anywhere from 2 weeks to 2 days before surgery, all of the patients received a standard prophylactic antibiotic. This was most often an infusion of 1.5 g cefuroxime plus 500 mg metronidazole. Other cephalosporins were allowed at the clinician’s discretion.
Patients were a mean of 62 years old. Nearly half (48%) had cardiovascular disease and about a third had undergone a prior colorectal surgical procedure. Cancer was the surgical indication in about 70%. Other indications were inflammatory bowel disease and diverticular disease.
A multivariate analysis controlled for age, cardiovascular disease, indication for surgery, and whether the procedure included a rectal resection, retention of drain at the surgical site, or stoma. The model also controlled for National Nosocomial Infection Surveillance score, a three-point scale that estimates surgical infection risk. Among this cohort, 48% were at low risk, 43% at moderate risk, and 10% at high risk.
Dr. Carmeli made no financial disclosures.
SOURCE: Carmeli et al, ECCMID 2018, Oral Abstract O1133.
MADRID – Patients who are carriers of , despite a standard prophylactic antibiotic regimen.
Surgical site infections (SSIs) occurred in 23% of those who tested positive for the pathogens preoperatively, compared with 10.5% of ESBL-B–negative patients – a significant increased risk of 2.25, Yehuda Carmeli, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual congress.
ESBL-B was not the infective pathogen in most infection cases, but being a carrier increased the likelihood of an ESBL-B SSI. ESBL-B was the pathogen in 7.2% of the carriers and 1.6% of the noncarriers. However, investigators are still working to determine if the species present in the wound infection are the same as the ones present at baseline, said Dr. Carmeli of Tel Aviv Medical Center.
All of these results are emerging from the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in Gram-Negative Organisms: Studying Intervention Strategies” is a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria. From 2012 to 2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures).
Several of the studies were reported at ECCMID 2018.
This portion of R-GNOSIS was intended to investigate the relationship between ESBL-B carriage and postoperative surgical site infections among colorectal surgery patients.
The study comprised 3,626 patients who were preoperatively screened for ESBL-B within 2 weeks of colorectal surgery. The ESBL-B carriage rate was 15.3% overall, but ranged from 12% to 20% by site. Of the carriers, 222 were included in this study sample. They were randomly matched with 444 noncarriers.
Anywhere from 2 weeks to 2 days before surgery, all of the patients received a standard prophylactic antibiotic. This was most often an infusion of 1.5 g cefuroxime plus 500 mg metronidazole. Other cephalosporins were allowed at the clinician’s discretion.
Patients were a mean of 62 years old. Nearly half (48%) had cardiovascular disease and about a third had undergone a prior colorectal surgical procedure. Cancer was the surgical indication in about 70%. Other indications were inflammatory bowel disease and diverticular disease.
A multivariate analysis controlled for age, cardiovascular disease, indication for surgery, and whether the procedure included a rectal resection, retention of drain at the surgical site, or stoma. The model also controlled for National Nosocomial Infection Surveillance score, a three-point scale that estimates surgical infection risk. Among this cohort, 48% were at low risk, 43% at moderate risk, and 10% at high risk.
Dr. Carmeli made no financial disclosures.
SOURCE: Carmeli et al, ECCMID 2018, Oral Abstract O1133.
MADRID – Patients who are carriers of , despite a standard prophylactic antibiotic regimen.
Surgical site infections (SSIs) occurred in 23% of those who tested positive for the pathogens preoperatively, compared with 10.5% of ESBL-B–negative patients – a significant increased risk of 2.25, Yehuda Carmeli, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual congress.
ESBL-B was not the infective pathogen in most infection cases, but being a carrier increased the likelihood of an ESBL-B SSI. ESBL-B was the pathogen in 7.2% of the carriers and 1.6% of the noncarriers. However, investigators are still working to determine if the species present in the wound infection are the same as the ones present at baseline, said Dr. Carmeli of Tel Aviv Medical Center.
All of these results are emerging from the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in Gram-Negative Organisms: Studying Intervention Strategies” is a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria. From 2012 to 2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures).
Several of the studies were reported at ECCMID 2018.
This portion of R-GNOSIS was intended to investigate the relationship between ESBL-B carriage and postoperative surgical site infections among colorectal surgery patients.
The study comprised 3,626 patients who were preoperatively screened for ESBL-B within 2 weeks of colorectal surgery. The ESBL-B carriage rate was 15.3% overall, but ranged from 12% to 20% by site. Of the carriers, 222 were included in this study sample. They were randomly matched with 444 noncarriers.
Anywhere from 2 weeks to 2 days before surgery, all of the patients received a standard prophylactic antibiotic. This was most often an infusion of 1.5 g cefuroxime plus 500 mg metronidazole. Other cephalosporins were allowed at the clinician’s discretion.
Patients were a mean of 62 years old. Nearly half (48%) had cardiovascular disease and about a third had undergone a prior colorectal surgical procedure. Cancer was the surgical indication in about 70%. Other indications were inflammatory bowel disease and diverticular disease.
A multivariate analysis controlled for age, cardiovascular disease, indication for surgery, and whether the procedure included a rectal resection, retention of drain at the surgical site, or stoma. The model also controlled for National Nosocomial Infection Surveillance score, a three-point scale that estimates surgical infection risk. Among this cohort, 48% were at low risk, 43% at moderate risk, and 10% at high risk.
Dr. Carmeli made no financial disclosures.
SOURCE: Carmeli et al, ECCMID 2018, Oral Abstract O1133.
REPORTING FROM ECCMID 2018
Key clinical point: ESBL-B colonization increased the risk of surgical site infections after colorectal surgery, despite use of standard preoperative antibiotics.
Major finding: ESBL-B carriage more than doubled the risk of a colorectal surgical site infection by (OR 2.25).
Study details: The prospective study comprised 222 carriers and 444 noncarriers.
Disclosures: The study is part of the R-GNOSIS project, a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria.
Source: Carmeli Y et al. ECCMID 2018, Oral Abstract O1130.
ESBL-resistant bacteria spread in hospital despite strict contact precautions
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
REPORTING FROM ECCMID 2018
Key clinical point: A protocol of strict contact precautions and hand hygiene was no better than standard contact precautions at preventing the spread of extended-spectrum, beta-lactamase–resistant Enterobacteriaceae.
Major finding: The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6, regardless of precaution.
Study details: The 25-month crossover trial comprised more than 11,000 patients.
Disclosures: Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
Source: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
CAZ-AVI appears safe, effective in pediatric complicated UTI, intra-abdominal infections
MADRID – Two randomized phase 2b trials show the combination of ceftazidime-avibactam (CAZ-AVI) is safe and effective in children with complicated intra-abdominal infections or complicated urinary tract infections (UTIs).
The combination already is approved for these conditions in adults, said John Bradley, MD, who presented the studies at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
However, Pfizer, which recently acquired the drug combination from AstraZeneca as part of its small-molecule anti-infectives sell-off, intends to go for a pediatric approval for these two indications. The studies, which had secondary efficacy endpoints, will be used as part of the application package to the Food and Drug Administration and the European Medicines Agency, said Dr. Bradley, professor of clinical pediatrics at the University of California, San Diego.
“For those of you who take care of adults and use these drugs, this seems like old news, but those of us who take care of children can rejoice, because these are the first pediatric data presented. And – no surprise – the combination appears to be as safe and effective in children as it is in adults.”
Both studies concluded in late 2017. “We have the data locked and it’s being cleaned and soon will be submitted to regulatory agencies,” Dr. Bradley said. “However, we do not yet have approval so if you do use it, it will still be considered an off-label use until regulatory agencies work with the sponsor to achieve approval.”
Both studies were international, conducted in the United States, Europe, Russia, South Korea, Taiwan, and Turkey.
The first study included 83 children, mean age 10 years, who had complicated intra-abdominal infections precipitated by ruptured appendicitis. About 90% already had been treated with other antibiotics. In this trial, the CAZ-AVI combination was augmented with metronidazole, and compared to meropenem, in 72-hour infusions. The microbiologic test of cure was conducted at 8-15 days with a late follow-up at 20-36 days after the last infusion.
Most of the patents (83%) had an infective organism identified; it was most often Escherichia coli or Pseudomonas aeruginosa. All pathogens were susceptible to the study drugs.
Five children in the combination group experienced a serious adverse event. These included one case each of ileus, intestinal obstruction, large intestine perforation, renal colic, and urethra meatus stenosis. There was one case of ileus in the meropenem group.
There was one case of diarrhea in the combination group. There were three allergic reactions in each group (cough, pruritus, and rash). The meropenem group also had two cases of anemia.
At the test-of-cure point, clinical response was similar in the combination and meropenem groups, both in clinical evidence (93% vs. 95%) and microbiological response (90% vs. 95%) At last follow-up, 100% of each group was clinically cured. The microbiological cure rates were 90% and 95%, respectively.
Success for complicated UTI
The complicated UTI study was likewise good news for CAZ-AVI, this time without metronidazole. This study included 95 children, mean age 6 years, in the same globally gathered cohorts. All of the children were hospitalized; they were randomized to CAZ-AVI at age-specific doses or cefepime, less than 2,000 mg/infusion for 72 hours. The test of cure was conducted at 8-15 days with a late follow-up at 20-36 days after the last infusion.
Most patients (83%) had acute pyelonephritis. About a quarter had at least one complicating factor, including obstructive uropathies due to functional or anatomic abnormalities of the urogenital tract, recurrent UTI, vesicoureteral reflex, or intermittent catheterization. About 20% of the group had a urological abnormality and 40% had been on a systemic antibiotic in the 2 weeks before study entry.
The most common infective organism was E. coli, (92%) followed by Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae.
Again, about half of each group had at least one adverse event. Serious adverse events occurred in 12% of the combination group and 7% of the cefepime group. Three patients taking the combination discontinued because of the reaction.
There were eight serious events in the combination group, including abdominal pain, constipation, cystitis, acute pyelonephritis, UTI (not considered related to the study drug) viral infection, nervous system disorder, and nephrolithiasis. There were two serious adverse events in the cefepime group (cystitis and acute pyelonephritis).
Favorable clinical outcomes occurred in 89% of the combination group and 82.6% of the cefepime group. A microbiological cure was evident in 79.6% and 60.9%, respectively.
The combination was more effective than was cefepime at eradicating E. coli (79.6% vs. 59.1%), although no statistical analysis was presented. The other, less-frequent pathogens did not co-occur in both groups, so comparisons were not made. However, the combination eradicated P. mirabilis in both patients who had it, and 50% of K. pneumoniae infections.
A sustained clinical cure occurred in 81% of the combination group and 82.6% of the cefepime group.
Dr. Bradley said the University of California, San Diego, received fees from both Pfizer or AstraZeneca relating to the studies.
SOURCE: Bradley J et al. ECCMID 2018 oral abstracts O1123 and O1124.
MADRID – Two randomized phase 2b trials show the combination of ceftazidime-avibactam (CAZ-AVI) is safe and effective in children with complicated intra-abdominal infections or complicated urinary tract infections (UTIs).
The combination already is approved for these conditions in adults, said John Bradley, MD, who presented the studies at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
However, Pfizer, which recently acquired the drug combination from AstraZeneca as part of its small-molecule anti-infectives sell-off, intends to go for a pediatric approval for these two indications. The studies, which had secondary efficacy endpoints, will be used as part of the application package to the Food and Drug Administration and the European Medicines Agency, said Dr. Bradley, professor of clinical pediatrics at the University of California, San Diego.
“For those of you who take care of adults and use these drugs, this seems like old news, but those of us who take care of children can rejoice, because these are the first pediatric data presented. And – no surprise – the combination appears to be as safe and effective in children as it is in adults.”
Both studies concluded in late 2017. “We have the data locked and it’s being cleaned and soon will be submitted to regulatory agencies,” Dr. Bradley said. “However, we do not yet have approval so if you do use it, it will still be considered an off-label use until regulatory agencies work with the sponsor to achieve approval.”
Both studies were international, conducted in the United States, Europe, Russia, South Korea, Taiwan, and Turkey.
The first study included 83 children, mean age 10 years, who had complicated intra-abdominal infections precipitated by ruptured appendicitis. About 90% already had been treated with other antibiotics. In this trial, the CAZ-AVI combination was augmented with metronidazole, and compared to meropenem, in 72-hour infusions. The microbiologic test of cure was conducted at 8-15 days with a late follow-up at 20-36 days after the last infusion.
Most of the patents (83%) had an infective organism identified; it was most often Escherichia coli or Pseudomonas aeruginosa. All pathogens were susceptible to the study drugs.
Five children in the combination group experienced a serious adverse event. These included one case each of ileus, intestinal obstruction, large intestine perforation, renal colic, and urethra meatus stenosis. There was one case of ileus in the meropenem group.
There was one case of diarrhea in the combination group. There were three allergic reactions in each group (cough, pruritus, and rash). The meropenem group also had two cases of anemia.
At the test-of-cure point, clinical response was similar in the combination and meropenem groups, both in clinical evidence (93% vs. 95%) and microbiological response (90% vs. 95%) At last follow-up, 100% of each group was clinically cured. The microbiological cure rates were 90% and 95%, respectively.
Success for complicated UTI
The complicated UTI study was likewise good news for CAZ-AVI, this time without metronidazole. This study included 95 children, mean age 6 years, in the same globally gathered cohorts. All of the children were hospitalized; they were randomized to CAZ-AVI at age-specific doses or cefepime, less than 2,000 mg/infusion for 72 hours. The test of cure was conducted at 8-15 days with a late follow-up at 20-36 days after the last infusion.
Most patients (83%) had acute pyelonephritis. About a quarter had at least one complicating factor, including obstructive uropathies due to functional or anatomic abnormalities of the urogenital tract, recurrent UTI, vesicoureteral reflex, or intermittent catheterization. About 20% of the group had a urological abnormality and 40% had been on a systemic antibiotic in the 2 weeks before study entry.
The most common infective organism was E. coli, (92%) followed by Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae.
Again, about half of each group had at least one adverse event. Serious adverse events occurred in 12% of the combination group and 7% of the cefepime group. Three patients taking the combination discontinued because of the reaction.
There were eight serious events in the combination group, including abdominal pain, constipation, cystitis, acute pyelonephritis, UTI (not considered related to the study drug) viral infection, nervous system disorder, and nephrolithiasis. There were two serious adverse events in the cefepime group (cystitis and acute pyelonephritis).
Favorable clinical outcomes occurred in 89% of the combination group and 82.6% of the cefepime group. A microbiological cure was evident in 79.6% and 60.9%, respectively.
The combination was more effective than was cefepime at eradicating E. coli (79.6% vs. 59.1%), although no statistical analysis was presented. The other, less-frequent pathogens did not co-occur in both groups, so comparisons were not made. However, the combination eradicated P. mirabilis in both patients who had it, and 50% of K. pneumoniae infections.
A sustained clinical cure occurred in 81% of the combination group and 82.6% of the cefepime group.
Dr. Bradley said the University of California, San Diego, received fees from both Pfizer or AstraZeneca relating to the studies.
SOURCE: Bradley J et al. ECCMID 2018 oral abstracts O1123 and O1124.
MADRID – Two randomized phase 2b trials show the combination of ceftazidime-avibactam (CAZ-AVI) is safe and effective in children with complicated intra-abdominal infections or complicated urinary tract infections (UTIs).
The combination already is approved for these conditions in adults, said John Bradley, MD, who presented the studies at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
However, Pfizer, which recently acquired the drug combination from AstraZeneca as part of its small-molecule anti-infectives sell-off, intends to go for a pediatric approval for these two indications. The studies, which had secondary efficacy endpoints, will be used as part of the application package to the Food and Drug Administration and the European Medicines Agency, said Dr. Bradley, professor of clinical pediatrics at the University of California, San Diego.
“For those of you who take care of adults and use these drugs, this seems like old news, but those of us who take care of children can rejoice, because these are the first pediatric data presented. And – no surprise – the combination appears to be as safe and effective in children as it is in adults.”
Both studies concluded in late 2017. “We have the data locked and it’s being cleaned and soon will be submitted to regulatory agencies,” Dr. Bradley said. “However, we do not yet have approval so if you do use it, it will still be considered an off-label use until regulatory agencies work with the sponsor to achieve approval.”
Both studies were international, conducted in the United States, Europe, Russia, South Korea, Taiwan, and Turkey.
The first study included 83 children, mean age 10 years, who had complicated intra-abdominal infections precipitated by ruptured appendicitis. About 90% already had been treated with other antibiotics. In this trial, the CAZ-AVI combination was augmented with metronidazole, and compared to meropenem, in 72-hour infusions. The microbiologic test of cure was conducted at 8-15 days with a late follow-up at 20-36 days after the last infusion.
Most of the patents (83%) had an infective organism identified; it was most often Escherichia coli or Pseudomonas aeruginosa. All pathogens were susceptible to the study drugs.
Five children in the combination group experienced a serious adverse event. These included one case each of ileus, intestinal obstruction, large intestine perforation, renal colic, and urethra meatus stenosis. There was one case of ileus in the meropenem group.
There was one case of diarrhea in the combination group. There were three allergic reactions in each group (cough, pruritus, and rash). The meropenem group also had two cases of anemia.
At the test-of-cure point, clinical response was similar in the combination and meropenem groups, both in clinical evidence (93% vs. 95%) and microbiological response (90% vs. 95%) At last follow-up, 100% of each group was clinically cured. The microbiological cure rates were 90% and 95%, respectively.
Success for complicated UTI
The complicated UTI study was likewise good news for CAZ-AVI, this time without metronidazole. This study included 95 children, mean age 6 years, in the same globally gathered cohorts. All of the children were hospitalized; they were randomized to CAZ-AVI at age-specific doses or cefepime, less than 2,000 mg/infusion for 72 hours. The test of cure was conducted at 8-15 days with a late follow-up at 20-36 days after the last infusion.
Most patients (83%) had acute pyelonephritis. About a quarter had at least one complicating factor, including obstructive uropathies due to functional or anatomic abnormalities of the urogenital tract, recurrent UTI, vesicoureteral reflex, or intermittent catheterization. About 20% of the group had a urological abnormality and 40% had been on a systemic antibiotic in the 2 weeks before study entry.
The most common infective organism was E. coli, (92%) followed by Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae.
Again, about half of each group had at least one adverse event. Serious adverse events occurred in 12% of the combination group and 7% of the cefepime group. Three patients taking the combination discontinued because of the reaction.
There were eight serious events in the combination group, including abdominal pain, constipation, cystitis, acute pyelonephritis, UTI (not considered related to the study drug) viral infection, nervous system disorder, and nephrolithiasis. There were two serious adverse events in the cefepime group (cystitis and acute pyelonephritis).
Favorable clinical outcomes occurred in 89% of the combination group and 82.6% of the cefepime group. A microbiological cure was evident in 79.6% and 60.9%, respectively.
The combination was more effective than was cefepime at eradicating E. coli (79.6% vs. 59.1%), although no statistical analysis was presented. The other, less-frequent pathogens did not co-occur in both groups, so comparisons were not made. However, the combination eradicated P. mirabilis in both patients who had it, and 50% of K. pneumoniae infections.
A sustained clinical cure occurred in 81% of the combination group and 82.6% of the cefepime group.
Dr. Bradley said the University of California, San Diego, received fees from both Pfizer or AstraZeneca relating to the studies.
SOURCE: Bradley J et al. ECCMID 2018 oral abstracts O1123 and O1124.
REPORTING FROM ECCMID 2018
Key clinical point: The CAZ-AVI combination was as good as the standard comparator drug in both studies.
Major finding: The combination cured close to 90% of infections in both studies.
Study details: Together, the phase 2b studies comprised 178 children.
Disclosures: Pfizer sponsored the studies.
Source: Bradley J et al. ECCMID 2018 oral abstracts O1123 and O1124.
Don’t shorten therapy for older, sicker cellulitis patients
MADRID – An attempt to balance effective treatment with good antibiotic stewardship fell short when patients with cellulitis who got 6 days of flucloxacillin relapsed significantly sooner and more frequently than did those who received the standard 12 days of treatment.
While cellulitis cure rates at 14 and 28 days were similar between the two groups, 90-day relapse rates were significantly higher for those who took the 6-day course (23.5% vs. 6%), Duncan R. Cranendonk, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual conference. The cohort demographics perhaps played into this finding: Most of the group was elderly, hospitalized, and had comorbid conditions.
“However, this is the population clinicians are most likely to see,” said Dr Cranendonk of the University of Amsterdam. “It appears that therapy cannot be safely shortened in this population.”
In light of recent antibiotic trials showing that shorter courses can be as effective as prolonged treatment, Dr. Cranendonk and his colleagues conducted the DANCE (Duration of Antibiotic Therapy for Cellulitis) trial. The study investigated the efficacy of an abbreviated course of intravenous flucloxacillin among 248 patients with cellulitis admitted to 11 Dutch hospitals. At treatment day 6, those who had clinically improved after their initial treatment were randomized to 6 additional days of IV flucloxacillin or to placebo. The primary outcome was cure by day 14 without relapse by day 28.
A 2004 study successfully paved the way for DANCE, Dr. Cranendonk noted. That trial examined 5 versus 10 days of levofloxacin 500 mg for uncomplicated cellulitis in 87 patients. The outcome was positive: There was no significant difference in clinical outcome between the two arms, with a 98% cure rate in both groups.
However, Dr. Cranendonk noted, there were some important differences between the patients in that study and the DANCE cohort. They were, on the whole, younger and generally in better overall health. Also, only 15% of those patients were hospitalized for their infections, while all of the DANCE subjects were treated in the hospital.
Patients enrolled in DANCE were a mean of 62 years old, with a median 28 kg/m2 body mass index. About 40% had experienced cellulitis before, and 25% had diabetes. Most infections were on the leg (84%) and involved the lower leg or the lower leg and the foot. Fever was present in half of the group, lymphadenopathy in a third, and leukocytosis in 70%.
Upon enrollment, all 248 patients received 6 days of 1,000 mg/day IV flucloxacillin, with the option of a step-down to oral treatment (500 mg four times per day) at the treating physician’s discretion. At day 6, patients who were clinically improved (afebrile, no need to an antibiotic switch, no growth in blood culture, and improved symptoms of pain, ulceration, discharge, and fluctuance) were randomized to either another 6 days of flucloxacillin or placebo.
The primary endpoint was cure by day 14, with no relapse and no need for new antibiotics by day 28. The secondary endpoint was relapse by 90 days after initial cure.
After initial treatment, 151 patients entered the randomization phase. At 28 days, relapse-free cure rates were nearly identical: 49% of the 12-day group and 50% of the 6-day group. However, by 90 days, a significant difference became apparent: Patients who had received the 6-day course of flucloxacillin were significantly more likely to have experienced a relapse of cellulitis in the same region (23.5% vs. 6% in the 12-day group). A Kaplan-Meier analysis showed that these patients began to relapse as early as 35 days after the end of therapy. Most relapses occurred during days 60-90. The few relapses in the 12-day group occurred toward the end of the follow-up period, from day 75 onward.
Dr. Cranendonk said the investigation shows that older, less-healthy cellulitis patients can probably benefit from the longer course of antibiotics. “Short-term outcomes aren’t everything,” he noted.
He had no financial disclosures.
A video interview of Dr. Cranendock by ECCMID 2018 is available.
SOURCE: Cranendonk et al. ECCMID 2018, Abstract O1122
MADRID – An attempt to balance effective treatment with good antibiotic stewardship fell short when patients with cellulitis who got 6 days of flucloxacillin relapsed significantly sooner and more frequently than did those who received the standard 12 days of treatment.
While cellulitis cure rates at 14 and 28 days were similar between the two groups, 90-day relapse rates were significantly higher for those who took the 6-day course (23.5% vs. 6%), Duncan R. Cranendonk, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual conference. The cohort demographics perhaps played into this finding: Most of the group was elderly, hospitalized, and had comorbid conditions.
“However, this is the population clinicians are most likely to see,” said Dr Cranendonk of the University of Amsterdam. “It appears that therapy cannot be safely shortened in this population.”
In light of recent antibiotic trials showing that shorter courses can be as effective as prolonged treatment, Dr. Cranendonk and his colleagues conducted the DANCE (Duration of Antibiotic Therapy for Cellulitis) trial. The study investigated the efficacy of an abbreviated course of intravenous flucloxacillin among 248 patients with cellulitis admitted to 11 Dutch hospitals. At treatment day 6, those who had clinically improved after their initial treatment were randomized to 6 additional days of IV flucloxacillin or to placebo. The primary outcome was cure by day 14 without relapse by day 28.
A 2004 study successfully paved the way for DANCE, Dr. Cranendonk noted. That trial examined 5 versus 10 days of levofloxacin 500 mg for uncomplicated cellulitis in 87 patients. The outcome was positive: There was no significant difference in clinical outcome between the two arms, with a 98% cure rate in both groups.
However, Dr. Cranendonk noted, there were some important differences between the patients in that study and the DANCE cohort. They were, on the whole, younger and generally in better overall health. Also, only 15% of those patients were hospitalized for their infections, while all of the DANCE subjects were treated in the hospital.
Patients enrolled in DANCE were a mean of 62 years old, with a median 28 kg/m2 body mass index. About 40% had experienced cellulitis before, and 25% had diabetes. Most infections were on the leg (84%) and involved the lower leg or the lower leg and the foot. Fever was present in half of the group, lymphadenopathy in a third, and leukocytosis in 70%.
Upon enrollment, all 248 patients received 6 days of 1,000 mg/day IV flucloxacillin, with the option of a step-down to oral treatment (500 mg four times per day) at the treating physician’s discretion. At day 6, patients who were clinically improved (afebrile, no need to an antibiotic switch, no growth in blood culture, and improved symptoms of pain, ulceration, discharge, and fluctuance) were randomized to either another 6 days of flucloxacillin or placebo.
The primary endpoint was cure by day 14, with no relapse and no need for new antibiotics by day 28. The secondary endpoint was relapse by 90 days after initial cure.
After initial treatment, 151 patients entered the randomization phase. At 28 days, relapse-free cure rates were nearly identical: 49% of the 12-day group and 50% of the 6-day group. However, by 90 days, a significant difference became apparent: Patients who had received the 6-day course of flucloxacillin were significantly more likely to have experienced a relapse of cellulitis in the same region (23.5% vs. 6% in the 12-day group). A Kaplan-Meier analysis showed that these patients began to relapse as early as 35 days after the end of therapy. Most relapses occurred during days 60-90. The few relapses in the 12-day group occurred toward the end of the follow-up period, from day 75 onward.
Dr. Cranendonk said the investigation shows that older, less-healthy cellulitis patients can probably benefit from the longer course of antibiotics. “Short-term outcomes aren’t everything,” he noted.
He had no financial disclosures.
A video interview of Dr. Cranendock by ECCMID 2018 is available.
SOURCE: Cranendonk et al. ECCMID 2018, Abstract O1122
MADRID – An attempt to balance effective treatment with good antibiotic stewardship fell short when patients with cellulitis who got 6 days of flucloxacillin relapsed significantly sooner and more frequently than did those who received the standard 12 days of treatment.
While cellulitis cure rates at 14 and 28 days were similar between the two groups, 90-day relapse rates were significantly higher for those who took the 6-day course (23.5% vs. 6%), Duncan R. Cranendonk, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual conference. The cohort demographics perhaps played into this finding: Most of the group was elderly, hospitalized, and had comorbid conditions.
“However, this is the population clinicians are most likely to see,” said Dr Cranendonk of the University of Amsterdam. “It appears that therapy cannot be safely shortened in this population.”
In light of recent antibiotic trials showing that shorter courses can be as effective as prolonged treatment, Dr. Cranendonk and his colleagues conducted the DANCE (Duration of Antibiotic Therapy for Cellulitis) trial. The study investigated the efficacy of an abbreviated course of intravenous flucloxacillin among 248 patients with cellulitis admitted to 11 Dutch hospitals. At treatment day 6, those who had clinically improved after their initial treatment were randomized to 6 additional days of IV flucloxacillin or to placebo. The primary outcome was cure by day 14 without relapse by day 28.
A 2004 study successfully paved the way for DANCE, Dr. Cranendonk noted. That trial examined 5 versus 10 days of levofloxacin 500 mg for uncomplicated cellulitis in 87 patients. The outcome was positive: There was no significant difference in clinical outcome between the two arms, with a 98% cure rate in both groups.
However, Dr. Cranendonk noted, there were some important differences between the patients in that study and the DANCE cohort. They were, on the whole, younger and generally in better overall health. Also, only 15% of those patients were hospitalized for their infections, while all of the DANCE subjects were treated in the hospital.
Patients enrolled in DANCE were a mean of 62 years old, with a median 28 kg/m2 body mass index. About 40% had experienced cellulitis before, and 25% had diabetes. Most infections were on the leg (84%) and involved the lower leg or the lower leg and the foot. Fever was present in half of the group, lymphadenopathy in a third, and leukocytosis in 70%.
Upon enrollment, all 248 patients received 6 days of 1,000 mg/day IV flucloxacillin, with the option of a step-down to oral treatment (500 mg four times per day) at the treating physician’s discretion. At day 6, patients who were clinically improved (afebrile, no need to an antibiotic switch, no growth in blood culture, and improved symptoms of pain, ulceration, discharge, and fluctuance) were randomized to either another 6 days of flucloxacillin or placebo.
The primary endpoint was cure by day 14, with no relapse and no need for new antibiotics by day 28. The secondary endpoint was relapse by 90 days after initial cure.
After initial treatment, 151 patients entered the randomization phase. At 28 days, relapse-free cure rates were nearly identical: 49% of the 12-day group and 50% of the 6-day group. However, by 90 days, a significant difference became apparent: Patients who had received the 6-day course of flucloxacillin were significantly more likely to have experienced a relapse of cellulitis in the same region (23.5% vs. 6% in the 12-day group). A Kaplan-Meier analysis showed that these patients began to relapse as early as 35 days after the end of therapy. Most relapses occurred during days 60-90. The few relapses in the 12-day group occurred toward the end of the follow-up period, from day 75 onward.
Dr. Cranendonk said the investigation shows that older, less-healthy cellulitis patients can probably benefit from the longer course of antibiotics. “Short-term outcomes aren’t everything,” he noted.
He had no financial disclosures.
A video interview of Dr. Cranendock by ECCMID 2018 is available.
SOURCE: Cranendonk et al. ECCMID 2018, Abstract O1122
REPORTING FROM ECCMID 2018
Key clinical point: Elderly patients with cellulitis and comorbid conditions probably need a full 12-day course of treatment.
Major finding: Three-month relapse rates were significantly higher in those who received 6 days of flucloxacillin than they were among those who received 12 days (23.5% vs. 6%).
Study details: Patients who improved on 6 days of treatment were randomized to either placebo or another 6 days of therapy.
Disclosures: Dr. Cranendonk had no financial disclosures.
Source: Cranendonk DR et al. ECCMID 2018, Abstract O1122
Piperacillin-tazobactam tripled risk of death for patients with cephalosporin-resistant septicemia
MADRID – A study designed to test the benefit of piperacillin-tazobactam in cephalosporin-resistant bloodstream infections has showed just the opposite: The combination can be fatal for these patients, conferring a threefold increased risk of death compared with meropenem.
The piperacillin-tazobactam combination (PTZ) was associated with a significantly higher 30-day mortality than that of meropenem (12.3% vs. 3.7%; RR 3.4), Patrick Harris, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
The number needed to harm with PTZ treatment was 12, said Dr. Harris of the University of Queensland, Australia.
“This was really not the result we wanted. We were expecting to show noninferiority, but the answer we did get was quite compelling. We have to say that in patients with these kinds of bloodstream infections, the use of piperacillin-tazobactam is definitely not supported.”
The signal came on strongly and quickly in the 32-country MERINO trial, he said. An independent data safety monitoring board stopped the study at 75% recruitment after reviewing the alarming interim results last summer.
The trial was designed to test a seemingly sound hypothesis. PTZ is an effective weapon against increasingly extended spectrum beta-lactamase–producing (ESBL) Escherichia coli and Klebsiella infections. These have long been treated with carbapenems, including meropenem, but the widespread global use of that class is putting heavy environmental pressure on these bacteria and creating carbapenem resistance, Dr. Harris said.
“Carbapenems have for many years been the top therapy for these infections, but it may well be a strong selection driver for carbapenem resistance in Gram negative bacilli. We should be thinking about carbapenem-sparing therapy, and it seemed that piperacillin-tazobactam could be useful here.”
Some observational studies do suggest a use for it in this setting but the combination had never been formally investigated. MERINO was designed to do so; investigators hoped to show that PTZ would be noninferior to meropenem in patients with septicemias caused by ESBL E. coli and K. pneumoniae.
The enrollment target for MERINO was 454 patients. Between 2014 and 2017, the study enrolled 391, of whom 379 were included in the final analysis. Patients had to start treatment with the study drugs within 72 hours of confirmatory blood culture. Both arms underwent 4 days of treatment with either PTZ 4.5 g every 6 hours or meropenem 1 g every 8 hours.
The study’s primary outcome was 30-day all-cause mortality. Secondary outcomes were days to clinical and microbiological resolution, clinical and microbiological success at day 4, relapsing septicemia or secondary infection with a PTZ- or meropenem-resistant organism, or Clostridium difficile infection.
The mean age of the patients was 66 years. Most (86%) were infected with resistant strains of E. coli; the rest had K. pneumoniae. About 60% of the infections were acquired in a health care or hospital setting, and about 50% originated in the urinary tract. APACHE II scores were different between the meropenem and PTZ groups (21 vs. 17.9). More patients in PTZ arm had immune compromise (27% vs. 21%).
By 30 days, 23 of those randomized to the combination therapy (12.3%) and seven (3.7%) of those randomized to meropenem had died – a significant 8.6% difference. This translated to more than a threefold increase in the risk of death for those taking the combination (RR 3.4; P = .002). The number needed to harm was just 12.
All of the secondary endpoints also favored meropenem, although the differences were not statistically significant. Patients taking meropenem experienced clinical and microbiological improvement a mean of 1 day sooner (2 vs. 3 days). Microbiological relapse occurred in 2% of those taking meropenem compared with 4.8% of those taking PTZ. The meropenem group was also less likely to develop a multidrug resistant organism or C. difficile infection (4.2% vs. 8%).
The investigators performed several subgroup analyses looking for other trends in 30-day mortality. The difference remained significant no matter how the groups were analyzed.
“Patients with urinary tract infections had a slightly lower risk of mortality, but even after adjusting for risk in several multivariate regression models, the increased risk of 30-day mortality remained,” Dr. Harris said.
The Australasian Society for Antimicrobials and the International Society for Chemotherapy funded the work. Dr. Harris reported having no financial declarations.
MADRID – A study designed to test the benefit of piperacillin-tazobactam in cephalosporin-resistant bloodstream infections has showed just the opposite: The combination can be fatal for these patients, conferring a threefold increased risk of death compared with meropenem.
The piperacillin-tazobactam combination (PTZ) was associated with a significantly higher 30-day mortality than that of meropenem (12.3% vs. 3.7%; RR 3.4), Patrick Harris, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
The number needed to harm with PTZ treatment was 12, said Dr. Harris of the University of Queensland, Australia.
“This was really not the result we wanted. We were expecting to show noninferiority, but the answer we did get was quite compelling. We have to say that in patients with these kinds of bloodstream infections, the use of piperacillin-tazobactam is definitely not supported.”
The signal came on strongly and quickly in the 32-country MERINO trial, he said. An independent data safety monitoring board stopped the study at 75% recruitment after reviewing the alarming interim results last summer.
The trial was designed to test a seemingly sound hypothesis. PTZ is an effective weapon against increasingly extended spectrum beta-lactamase–producing (ESBL) Escherichia coli and Klebsiella infections. These have long been treated with carbapenems, including meropenem, but the widespread global use of that class is putting heavy environmental pressure on these bacteria and creating carbapenem resistance, Dr. Harris said.
“Carbapenems have for many years been the top therapy for these infections, but it may well be a strong selection driver for carbapenem resistance in Gram negative bacilli. We should be thinking about carbapenem-sparing therapy, and it seemed that piperacillin-tazobactam could be useful here.”
Some observational studies do suggest a use for it in this setting but the combination had never been formally investigated. MERINO was designed to do so; investigators hoped to show that PTZ would be noninferior to meropenem in patients with septicemias caused by ESBL E. coli and K. pneumoniae.
The enrollment target for MERINO was 454 patients. Between 2014 and 2017, the study enrolled 391, of whom 379 were included in the final analysis. Patients had to start treatment with the study drugs within 72 hours of confirmatory blood culture. Both arms underwent 4 days of treatment with either PTZ 4.5 g every 6 hours or meropenem 1 g every 8 hours.
The study’s primary outcome was 30-day all-cause mortality. Secondary outcomes were days to clinical and microbiological resolution, clinical and microbiological success at day 4, relapsing septicemia or secondary infection with a PTZ- or meropenem-resistant organism, or Clostridium difficile infection.
The mean age of the patients was 66 years. Most (86%) were infected with resistant strains of E. coli; the rest had K. pneumoniae. About 60% of the infections were acquired in a health care or hospital setting, and about 50% originated in the urinary tract. APACHE II scores were different between the meropenem and PTZ groups (21 vs. 17.9). More patients in PTZ arm had immune compromise (27% vs. 21%).
By 30 days, 23 of those randomized to the combination therapy (12.3%) and seven (3.7%) of those randomized to meropenem had died – a significant 8.6% difference. This translated to more than a threefold increase in the risk of death for those taking the combination (RR 3.4; P = .002). The number needed to harm was just 12.
All of the secondary endpoints also favored meropenem, although the differences were not statistically significant. Patients taking meropenem experienced clinical and microbiological improvement a mean of 1 day sooner (2 vs. 3 days). Microbiological relapse occurred in 2% of those taking meropenem compared with 4.8% of those taking PTZ. The meropenem group was also less likely to develop a multidrug resistant organism or C. difficile infection (4.2% vs. 8%).
The investigators performed several subgroup analyses looking for other trends in 30-day mortality. The difference remained significant no matter how the groups were analyzed.
“Patients with urinary tract infections had a slightly lower risk of mortality, but even after adjusting for risk in several multivariate regression models, the increased risk of 30-day mortality remained,” Dr. Harris said.
The Australasian Society for Antimicrobials and the International Society for Chemotherapy funded the work. Dr. Harris reported having no financial declarations.
MADRID – A study designed to test the benefit of piperacillin-tazobactam in cephalosporin-resistant bloodstream infections has showed just the opposite: The combination can be fatal for these patients, conferring a threefold increased risk of death compared with meropenem.
The piperacillin-tazobactam combination (PTZ) was associated with a significantly higher 30-day mortality than that of meropenem (12.3% vs. 3.7%; RR 3.4), Patrick Harris, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
The number needed to harm with PTZ treatment was 12, said Dr. Harris of the University of Queensland, Australia.
“This was really not the result we wanted. We were expecting to show noninferiority, but the answer we did get was quite compelling. We have to say that in patients with these kinds of bloodstream infections, the use of piperacillin-tazobactam is definitely not supported.”
The signal came on strongly and quickly in the 32-country MERINO trial, he said. An independent data safety monitoring board stopped the study at 75% recruitment after reviewing the alarming interim results last summer.
The trial was designed to test a seemingly sound hypothesis. PTZ is an effective weapon against increasingly extended spectrum beta-lactamase–producing (ESBL) Escherichia coli and Klebsiella infections. These have long been treated with carbapenems, including meropenem, but the widespread global use of that class is putting heavy environmental pressure on these bacteria and creating carbapenem resistance, Dr. Harris said.
“Carbapenems have for many years been the top therapy for these infections, but it may well be a strong selection driver for carbapenem resistance in Gram negative bacilli. We should be thinking about carbapenem-sparing therapy, and it seemed that piperacillin-tazobactam could be useful here.”
Some observational studies do suggest a use for it in this setting but the combination had never been formally investigated. MERINO was designed to do so; investigators hoped to show that PTZ would be noninferior to meropenem in patients with septicemias caused by ESBL E. coli and K. pneumoniae.
The enrollment target for MERINO was 454 patients. Between 2014 and 2017, the study enrolled 391, of whom 379 were included in the final analysis. Patients had to start treatment with the study drugs within 72 hours of confirmatory blood culture. Both arms underwent 4 days of treatment with either PTZ 4.5 g every 6 hours or meropenem 1 g every 8 hours.
The study’s primary outcome was 30-day all-cause mortality. Secondary outcomes were days to clinical and microbiological resolution, clinical and microbiological success at day 4, relapsing septicemia or secondary infection with a PTZ- or meropenem-resistant organism, or Clostridium difficile infection.
The mean age of the patients was 66 years. Most (86%) were infected with resistant strains of E. coli; the rest had K. pneumoniae. About 60% of the infections were acquired in a health care or hospital setting, and about 50% originated in the urinary tract. APACHE II scores were different between the meropenem and PTZ groups (21 vs. 17.9). More patients in PTZ arm had immune compromise (27% vs. 21%).
By 30 days, 23 of those randomized to the combination therapy (12.3%) and seven (3.7%) of those randomized to meropenem had died – a significant 8.6% difference. This translated to more than a threefold increase in the risk of death for those taking the combination (RR 3.4; P = .002). The number needed to harm was just 12.
All of the secondary endpoints also favored meropenem, although the differences were not statistically significant. Patients taking meropenem experienced clinical and microbiological improvement a mean of 1 day sooner (2 vs. 3 days). Microbiological relapse occurred in 2% of those taking meropenem compared with 4.8% of those taking PTZ. The meropenem group was also less likely to develop a multidrug resistant organism or C. difficile infection (4.2% vs. 8%).
The investigators performed several subgroup analyses looking for other trends in 30-day mortality. The difference remained significant no matter how the groups were analyzed.
“Patients with urinary tract infections had a slightly lower risk of mortality, but even after adjusting for risk in several multivariate regression models, the increased risk of 30-day mortality remained,” Dr. Harris said.
The Australasian Society for Antimicrobials and the International Society for Chemotherapy funded the work. Dr. Harris reported having no financial declarations.
REPORTING FROM ECCMID 2018
Key clinical point: PTZ more than tripled the risk of 30-day mortality in patients with cephalosporin-resistant bloodstream infections.
Major finding: Compared with meropenem, PZT increased the risk of death by 3.4, with a number needed to harm of 12.
Study details: The study randomized 391 patients.
Disclosures: The Australasian Society for Antimicrobials and the International Society for Chemotherapy funded the work. Dr. Harris has no financial declarations.
Source: Harris et al. ECCMID 2018, abstract O1121.
Ertapenem slashes surgical site infections in carriers of ESBL-producing bacteria
MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.
The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.
He presented the results of the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in gram-negative organisms: Studying intervention strategies” is a 12 million euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multidrug resistant Gram-negative bacteria. Several of the studies reported at ECCMID 2018.
During 2012-2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures). All patients were screened for ESBL-producing bacteria from 2 weeks to 2 days before their operation. In the first phase, carriers were treated with the standard presurgical prophylaxis of 1.5 g cefuroxime and 500 mg metronidazole intravenously. In phase 2, carriers received targeted prophylaxis with IV ertapenem 1 g. Both interventions were given 30 minutes before surgery commenced.
All patients underwent regular surgical site infection surveillance until hospital discharge, then followed up 30 days later by phone or in person.
The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.
ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.
Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.
Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.
Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.
There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:
- E. coli (thirteen in the routine and one in the ertapenem group).
- Klebsiella species (four and one, respectively).
- Proteus species (one in the ertapenem group).
Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.
In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).
Dr. Nutman made no financial declarations.
SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.
MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.
The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.
He presented the results of the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in gram-negative organisms: Studying intervention strategies” is a 12 million euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multidrug resistant Gram-negative bacteria. Several of the studies reported at ECCMID 2018.
During 2012-2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures). All patients were screened for ESBL-producing bacteria from 2 weeks to 2 days before their operation. In the first phase, carriers were treated with the standard presurgical prophylaxis of 1.5 g cefuroxime and 500 mg metronidazole intravenously. In phase 2, carriers received targeted prophylaxis with IV ertapenem 1 g. Both interventions were given 30 minutes before surgery commenced.
All patients underwent regular surgical site infection surveillance until hospital discharge, then followed up 30 days later by phone or in person.
The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.
ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.
Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.
Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.
Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.
There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:
- E. coli (thirteen in the routine and one in the ertapenem group).
- Klebsiella species (four and one, respectively).
- Proteus species (one in the ertapenem group).
Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.
In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).
Dr. Nutman made no financial declarations.
SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.
MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.
The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.
He presented the results of the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in gram-negative organisms: Studying intervention strategies” is a 12 million euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multidrug resistant Gram-negative bacteria. Several of the studies reported at ECCMID 2018.
During 2012-2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures). All patients were screened for ESBL-producing bacteria from 2 weeks to 2 days before their operation. In the first phase, carriers were treated with the standard presurgical prophylaxis of 1.5 g cefuroxime and 500 mg metronidazole intravenously. In phase 2, carriers received targeted prophylaxis with IV ertapenem 1 g. Both interventions were given 30 minutes before surgery commenced.
All patients underwent regular surgical site infection surveillance until hospital discharge, then followed up 30 days later by phone or in person.
The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.
ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.
Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.
Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.
Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.
There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:
- E. coli (thirteen in the routine and one in the ertapenem group).
- Klebsiella species (four and one, respectively).
- Proteus species (one in the ertapenem group).
Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.
In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).
Dr. Nutman made no financial declarations.
SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.
REPORTING FROM ECCMID 2018
Key clinical point: A targeted presurgical antibiotic prophylaxis significantly cut rates of surgical site infections in carriers of extended beta-lactamase–producing bacteria.
Major finding: Ertapenem reduced the rate of surgical site infection by 41% , and the rate of ESBL-producing infections by 87%, compared to routine prophylaxis.
Study details: The study comprised 468 patients.
Disclosures: The study was funded by the European Commission under the Seventh Framework Programme (FP7) for Research and Technology. Dr. Nutman had no financial disclosures.
Source: Nutman A et al. ECCMID 2018, Abstract O1129
Therapeutic endoscopy expands reach to deep GI lesions
BOSTON –
“The main difficulty with these procedures is closure,” Mouen A. Khashab, MD, said at the AGA Tech Summit, which was sponsored by the AGA Center for GI Innovation and Technology. “Sometimes you can create a large defect that you’re not sure you can close. You must have experience with large defect closure.”
In experienced hands, the endoscopic approaches spare adjacent large organs, have a complete resection rate approaching 95%, and an acceptable rate of adverse events. They can provide excellent surgical specimens that are more than adequate for histologic studies, although some cannot provide any information on margins, said Dr. Khashab, director of therapeutic endoscopy at Johns Hopkins University, Baltimore. “When doing a full-thickness endoscopic resection, you can’t comment on the margins. You’re not getting any normal tissue around the tumor, and this can create an issue with some patients.”
Dr. Khashab briefly described three endoscopic resection techniques that are suitable for the following deep GI tumors:
- Submucosal tunneling endoscopic resection. STER is most suitable for smaller tumors (4 cm or less). Tumors of this size are easily removed en bloc via the endoscopic tunnel. Larger tumors can also be resected this way, but need to be removed piecemeal after dissection off the muscle layer. This is an acceptable alternative in leiomyomas but not in gastrointestinal stromal tumors. “For this technique, you introduce the scope into the submucosal layer and create a space with tunneling,” Dr. Khashab said. “We then expose the tumor, dissect it off the wall of the muscularis propria, and pull it out of the tunnel.” A 2017 meta-analysis examined outcomes in 28 studies with data on 1,085 lesions. The pooled complete resection and en bloc resection rates were 97.5% and 94.6%, respectively. Common complications associated with STER were air leakage symptoms (15%) and perforation (5.6%). “The perforation rate is reasonable, I think. A lot of these complications can be managed intraoperatively with clipping or suturing,” Dr. Khashab noted.
- Endoscopic submucosal dissection: ESD is now being used to resect tumors that originate from the muscularis propria. “This is something I didn’t used to think was even possible,” Dr. Khashab said. “But we are seeing some literature on this now. A lot of these tumors originate from the superficial MP [muscularis propria], so we can dissect off the muscle without needing a full-thickness resection.” He presented findings from a large study comprising 143 patients with submucosal gastric or esophageal tumors that arose from the muscularis propria at the esophagogastric junction. These were large lesions, a mean 17.6 cm, but they ranged up to 50 cm. The en bloc resection rate was 94%. There were six perforations (4%), along with four pneumoperitoneum and two pneumothorax, which resolved without further surgery. There were no local recurrences or metastases when the 2012 study appeared, with a mean follow-up of 2 years.
- Endoscopic full-thickness resection: EFTR “is a technically demanding procedure, and we frequently have to work on these tumors in retroflexion,” Dr. Khashab said. He referred to a 2011 paper, which described the EFTR technique used in 26 patients with gastric cancers. The tumors (mean size, 2.8 cm) were located in the gastric corpus and in the gastric fundus. Although the procedures were lengthy, ranging from 60 to 145 minutes, they were highly successful, with a 100% complete resection rate. Nevertheless, there was also a 100% perforation rate, although all these were closed intraoperatively. There was no postoperative gastric bleeding, peritonitis sign, or abdominal abscess. No lesion residual or recurrence was found during the 6-24 month follow-up period.
Dr. Khashab is a consultant and medical advisory board member for Boston Scientific and Olympus.
BOSTON –
“The main difficulty with these procedures is closure,” Mouen A. Khashab, MD, said at the AGA Tech Summit, which was sponsored by the AGA Center for GI Innovation and Technology. “Sometimes you can create a large defect that you’re not sure you can close. You must have experience with large defect closure.”
In experienced hands, the endoscopic approaches spare adjacent large organs, have a complete resection rate approaching 95%, and an acceptable rate of adverse events. They can provide excellent surgical specimens that are more than adequate for histologic studies, although some cannot provide any information on margins, said Dr. Khashab, director of therapeutic endoscopy at Johns Hopkins University, Baltimore. “When doing a full-thickness endoscopic resection, you can’t comment on the margins. You’re not getting any normal tissue around the tumor, and this can create an issue with some patients.”
Dr. Khashab briefly described three endoscopic resection techniques that are suitable for the following deep GI tumors:
- Submucosal tunneling endoscopic resection. STER is most suitable for smaller tumors (4 cm or less). Tumors of this size are easily removed en bloc via the endoscopic tunnel. Larger tumors can also be resected this way, but need to be removed piecemeal after dissection off the muscle layer. This is an acceptable alternative in leiomyomas but not in gastrointestinal stromal tumors. “For this technique, you introduce the scope into the submucosal layer and create a space with tunneling,” Dr. Khashab said. “We then expose the tumor, dissect it off the wall of the muscularis propria, and pull it out of the tunnel.” A 2017 meta-analysis examined outcomes in 28 studies with data on 1,085 lesions. The pooled complete resection and en bloc resection rates were 97.5% and 94.6%, respectively. Common complications associated with STER were air leakage symptoms (15%) and perforation (5.6%). “The perforation rate is reasonable, I think. A lot of these complications can be managed intraoperatively with clipping or suturing,” Dr. Khashab noted.
- Endoscopic submucosal dissection: ESD is now being used to resect tumors that originate from the muscularis propria. “This is something I didn’t used to think was even possible,” Dr. Khashab said. “But we are seeing some literature on this now. A lot of these tumors originate from the superficial MP [muscularis propria], so we can dissect off the muscle without needing a full-thickness resection.” He presented findings from a large study comprising 143 patients with submucosal gastric or esophageal tumors that arose from the muscularis propria at the esophagogastric junction. These were large lesions, a mean 17.6 cm, but they ranged up to 50 cm. The en bloc resection rate was 94%. There were six perforations (4%), along with four pneumoperitoneum and two pneumothorax, which resolved without further surgery. There were no local recurrences or metastases when the 2012 study appeared, with a mean follow-up of 2 years.
- Endoscopic full-thickness resection: EFTR “is a technically demanding procedure, and we frequently have to work on these tumors in retroflexion,” Dr. Khashab said. He referred to a 2011 paper, which described the EFTR technique used in 26 patients with gastric cancers. The tumors (mean size, 2.8 cm) were located in the gastric corpus and in the gastric fundus. Although the procedures were lengthy, ranging from 60 to 145 minutes, they were highly successful, with a 100% complete resection rate. Nevertheless, there was also a 100% perforation rate, although all these were closed intraoperatively. There was no postoperative gastric bleeding, peritonitis sign, or abdominal abscess. No lesion residual or recurrence was found during the 6-24 month follow-up period.
Dr. Khashab is a consultant and medical advisory board member for Boston Scientific and Olympus.
BOSTON –
“The main difficulty with these procedures is closure,” Mouen A. Khashab, MD, said at the AGA Tech Summit, which was sponsored by the AGA Center for GI Innovation and Technology. “Sometimes you can create a large defect that you’re not sure you can close. You must have experience with large defect closure.”
In experienced hands, the endoscopic approaches spare adjacent large organs, have a complete resection rate approaching 95%, and an acceptable rate of adverse events. They can provide excellent surgical specimens that are more than adequate for histologic studies, although some cannot provide any information on margins, said Dr. Khashab, director of therapeutic endoscopy at Johns Hopkins University, Baltimore. “When doing a full-thickness endoscopic resection, you can’t comment on the margins. You’re not getting any normal tissue around the tumor, and this can create an issue with some patients.”
Dr. Khashab briefly described three endoscopic resection techniques that are suitable for the following deep GI tumors:
- Submucosal tunneling endoscopic resection. STER is most suitable for smaller tumors (4 cm or less). Tumors of this size are easily removed en bloc via the endoscopic tunnel. Larger tumors can also be resected this way, but need to be removed piecemeal after dissection off the muscle layer. This is an acceptable alternative in leiomyomas but not in gastrointestinal stromal tumors. “For this technique, you introduce the scope into the submucosal layer and create a space with tunneling,” Dr. Khashab said. “We then expose the tumor, dissect it off the wall of the muscularis propria, and pull it out of the tunnel.” A 2017 meta-analysis examined outcomes in 28 studies with data on 1,085 lesions. The pooled complete resection and en bloc resection rates were 97.5% and 94.6%, respectively. Common complications associated with STER were air leakage symptoms (15%) and perforation (5.6%). “The perforation rate is reasonable, I think. A lot of these complications can be managed intraoperatively with clipping or suturing,” Dr. Khashab noted.
- Endoscopic submucosal dissection: ESD is now being used to resect tumors that originate from the muscularis propria. “This is something I didn’t used to think was even possible,” Dr. Khashab said. “But we are seeing some literature on this now. A lot of these tumors originate from the superficial MP [muscularis propria], so we can dissect off the muscle without needing a full-thickness resection.” He presented findings from a large study comprising 143 patients with submucosal gastric or esophageal tumors that arose from the muscularis propria at the esophagogastric junction. These were large lesions, a mean 17.6 cm, but they ranged up to 50 cm. The en bloc resection rate was 94%. There were six perforations (4%), along with four pneumoperitoneum and two pneumothorax, which resolved without further surgery. There were no local recurrences or metastases when the 2012 study appeared, with a mean follow-up of 2 years.
- Endoscopic full-thickness resection: EFTR “is a technically demanding procedure, and we frequently have to work on these tumors in retroflexion,” Dr. Khashab said. He referred to a 2011 paper, which described the EFTR technique used in 26 patients with gastric cancers. The tumors (mean size, 2.8 cm) were located in the gastric corpus and in the gastric fundus. Although the procedures were lengthy, ranging from 60 to 145 minutes, they were highly successful, with a 100% complete resection rate. Nevertheless, there was also a 100% perforation rate, although all these were closed intraoperatively. There was no postoperative gastric bleeding, peritonitis sign, or abdominal abscess. No lesion residual or recurrence was found during the 6-24 month follow-up period.
Dr. Khashab is a consultant and medical advisory board member for Boston Scientific and Olympus.
EXPERT ANALYSIS FROM THE 2018 AGA TECH SUMMIT
With these pearls, the med-tech space can be your oyster
BOSTON – Having a great idea is just the first step to landing a financial partner in device development – backers also scrutinize more intangible qualities.
The willingness to work as part of a team, the ability to project realistic expectations, the fortitude to take risks and persevere when circumstances get tough – these attributes are critical to forging a strong strategic alliance with a financial partner, Brian Tinkham said at the 2018 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.
Put your own skin in the game
“To me, ‘skin in the game’ is mainly money. Investing your own money, your family’s money, changes the way you behave at the board meeting and when you spend that money,” Mr. Tinkham said. “We like people who are all in on this. When I see an entrepreneur who’s showing a return that’s not good enough for his own investment, I can lose confidence and trust. We want people who won’t walk away from their money, their family’s money, or my money; when times get tough and challenging, decisions need to be made.”
Be realistic
There’s a difference between confidence and irrational confidence, Mr. Tinkham said. “If you come to me presenting a game plan that says you’ll have a commercially viable product in 1 year for a $500,000 investment, you’ll shoot your credibility right off. We know exactly how hard it is to build a $10 million business, never mind a $100 million business. When you obviously don’t understand what lies ahead of you, it hurts your credibility. Work with people who have experience and let them help you present your ideas and goals in a realistic way, and that will help with raising capital so you can execute your plan.”
Be capital efficient
“The key takeaway here is that raising $100 million doesn’t necessarily make for a strong return for investors. The strong return comes with $20-$40 million raised. Most likely businesses that have raised that much have built a commercial structure, provided proof of concept with some actual sales, and generated enough customer interest to attract strategic partners.”
Location, location, location
“This is so important when you’re developing technology: You need to know where the people with high levels of competency are, and where the money is. If you don’t live near these localities, get on a plane and get there – that’s where the business is being done.”
California and the Philadelphia-Boston-New York corridor are the two biggest med-tech and investor hot spots in the United States, Mr. Tinkham noted. Smaller centers of innovation are scattered around the country, including Seattle, Denver, Minneapolis, Chicago, Pittsburgh, Washington, Raleigh-Durham, Atlanta, Austin, and Phoenix.
Be patient
“Adopting a new technology takes time, and the more disruptive the idea, the longer it takes to achieve market adoption. Translating that into med-tech, the time from founding a company to exit will take more than 5 years. Only 10% of companies do it in less time than that,” Mr. Tinkham said. “And you have to remember that not all of the exits we see are good ones – they can be exits in which investors lose most of the capital they’ve brought into the company.”
De-risk
Be the entrepreneur who takes a vision to a viable product.
“Most physician entrepreneurs come up with an idea and protect it – but don’t move it further. We want to see an idea that’s been created and then de-risked. You protect it, you prototype it, go into preclinical studies, then clinically validate it or obtain regulatory approval. And then in the end, to us the best measure is your revenue. Are customers buying it? Do they see in it the same value that you, the entrepreneur, sees? If you can get it there, you’ve got something. The further you de-risk something, the more attractive you become.”
Are you a physician innovator?
If you have an idea for a new technology to improve gastroenterology, the AGA Center for GI Innovation and Technology can help you through the device development and adoption process.
Get in touch with us at [email protected].
BOSTON – Having a great idea is just the first step to landing a financial partner in device development – backers also scrutinize more intangible qualities.
The willingness to work as part of a team, the ability to project realistic expectations, the fortitude to take risks and persevere when circumstances get tough – these attributes are critical to forging a strong strategic alliance with a financial partner, Brian Tinkham said at the 2018 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.
Put your own skin in the game
“To me, ‘skin in the game’ is mainly money. Investing your own money, your family’s money, changes the way you behave at the board meeting and when you spend that money,” Mr. Tinkham said. “We like people who are all in on this. When I see an entrepreneur who’s showing a return that’s not good enough for his own investment, I can lose confidence and trust. We want people who won’t walk away from their money, their family’s money, or my money; when times get tough and challenging, decisions need to be made.”
Be realistic
There’s a difference between confidence and irrational confidence, Mr. Tinkham said. “If you come to me presenting a game plan that says you’ll have a commercially viable product in 1 year for a $500,000 investment, you’ll shoot your credibility right off. We know exactly how hard it is to build a $10 million business, never mind a $100 million business. When you obviously don’t understand what lies ahead of you, it hurts your credibility. Work with people who have experience and let them help you present your ideas and goals in a realistic way, and that will help with raising capital so you can execute your plan.”
Be capital efficient
“The key takeaway here is that raising $100 million doesn’t necessarily make for a strong return for investors. The strong return comes with $20-$40 million raised. Most likely businesses that have raised that much have built a commercial structure, provided proof of concept with some actual sales, and generated enough customer interest to attract strategic partners.”
Location, location, location
“This is so important when you’re developing technology: You need to know where the people with high levels of competency are, and where the money is. If you don’t live near these localities, get on a plane and get there – that’s where the business is being done.”
California and the Philadelphia-Boston-New York corridor are the two biggest med-tech and investor hot spots in the United States, Mr. Tinkham noted. Smaller centers of innovation are scattered around the country, including Seattle, Denver, Minneapolis, Chicago, Pittsburgh, Washington, Raleigh-Durham, Atlanta, Austin, and Phoenix.
Be patient
“Adopting a new technology takes time, and the more disruptive the idea, the longer it takes to achieve market adoption. Translating that into med-tech, the time from founding a company to exit will take more than 5 years. Only 10% of companies do it in less time than that,” Mr. Tinkham said. “And you have to remember that not all of the exits we see are good ones – they can be exits in which investors lose most of the capital they’ve brought into the company.”
De-risk
Be the entrepreneur who takes a vision to a viable product.
“Most physician entrepreneurs come up with an idea and protect it – but don’t move it further. We want to see an idea that’s been created and then de-risked. You protect it, you prototype it, go into preclinical studies, then clinically validate it or obtain regulatory approval. And then in the end, to us the best measure is your revenue. Are customers buying it? Do they see in it the same value that you, the entrepreneur, sees? If you can get it there, you’ve got something. The further you de-risk something, the more attractive you become.”
Are you a physician innovator?
If you have an idea for a new technology to improve gastroenterology, the AGA Center for GI Innovation and Technology can help you through the device development and adoption process.
Get in touch with us at [email protected].
BOSTON – Having a great idea is just the first step to landing a financial partner in device development – backers also scrutinize more intangible qualities.
The willingness to work as part of a team, the ability to project realistic expectations, the fortitude to take risks and persevere when circumstances get tough – these attributes are critical to forging a strong strategic alliance with a financial partner, Brian Tinkham said at the 2018 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.
Put your own skin in the game
“To me, ‘skin in the game’ is mainly money. Investing your own money, your family’s money, changes the way you behave at the board meeting and when you spend that money,” Mr. Tinkham said. “We like people who are all in on this. When I see an entrepreneur who’s showing a return that’s not good enough for his own investment, I can lose confidence and trust. We want people who won’t walk away from their money, their family’s money, or my money; when times get tough and challenging, decisions need to be made.”
Be realistic
There’s a difference between confidence and irrational confidence, Mr. Tinkham said. “If you come to me presenting a game plan that says you’ll have a commercially viable product in 1 year for a $500,000 investment, you’ll shoot your credibility right off. We know exactly how hard it is to build a $10 million business, never mind a $100 million business. When you obviously don’t understand what lies ahead of you, it hurts your credibility. Work with people who have experience and let them help you present your ideas and goals in a realistic way, and that will help with raising capital so you can execute your plan.”
Be capital efficient
“The key takeaway here is that raising $100 million doesn’t necessarily make for a strong return for investors. The strong return comes with $20-$40 million raised. Most likely businesses that have raised that much have built a commercial structure, provided proof of concept with some actual sales, and generated enough customer interest to attract strategic partners.”
Location, location, location
“This is so important when you’re developing technology: You need to know where the people with high levels of competency are, and where the money is. If you don’t live near these localities, get on a plane and get there – that’s where the business is being done.”
California and the Philadelphia-Boston-New York corridor are the two biggest med-tech and investor hot spots in the United States, Mr. Tinkham noted. Smaller centers of innovation are scattered around the country, including Seattle, Denver, Minneapolis, Chicago, Pittsburgh, Washington, Raleigh-Durham, Atlanta, Austin, and Phoenix.
Be patient
“Adopting a new technology takes time, and the more disruptive the idea, the longer it takes to achieve market adoption. Translating that into med-tech, the time from founding a company to exit will take more than 5 years. Only 10% of companies do it in less time than that,” Mr. Tinkham said. “And you have to remember that not all of the exits we see are good ones – they can be exits in which investors lose most of the capital they’ve brought into the company.”
De-risk
Be the entrepreneur who takes a vision to a viable product.
“Most physician entrepreneurs come up with an idea and protect it – but don’t move it further. We want to see an idea that’s been created and then de-risked. You protect it, you prototype it, go into preclinical studies, then clinically validate it or obtain regulatory approval. And then in the end, to us the best measure is your revenue. Are customers buying it? Do they see in it the same value that you, the entrepreneur, sees? If you can get it there, you’ve got something. The further you de-risk something, the more attractive you become.”
Are you a physician innovator?
If you have an idea for a new technology to improve gastroenterology, the AGA Center for GI Innovation and Technology can help you through the device development and adoption process.
Get in touch with us at [email protected].
EXPERT ANALYSIS FROM 2018 AGA TECH SUMMIT
Nitrofurantoin beats fosfomycin for uncomplicated UTI
MADRID – (UTIs), a randomized study has determined.
By 28 days, clinical resolution had occurred in 70% of those who took nitrofurantoin and 58% of those who took fosfomycin – a statistically significant 12% difference, Angela Huttner, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
But the benefit was even more pronounced in women whose infections were caused by Escherichia coli, with a 28% spread in clinical resolution, (78% vs. 50%) and a 14-point spread in microbiological cure (72% vs. 58%), said Dr. Huttner of Geneva University, Switzerland.
The results were simultaneously published online in JAMA (2018 Apr 22. doi: 10.1001/jama.2018.3627).
Despite its success, nitrofurantoin did not live up to its purported 96% UTI cure rate – an established number based on study data from the 1950s-1970s.
Such efficacy was probably a false finding, she said. Studies of that era were much less rigorous than they are today, Dr. Huttner pointed out. The primary endpoint in those studies was typically defined not as complete resolution of symptoms – as it was in her study – but as resolution or improvement.
“Also, improvement was often defined microbiologically, often something like a decrease from 105 colony-forming units to 104, which is never something we would use today.”
The study was conducted in Geneva, Poland, and Israel. It randomized 512 women with an uncomplicated lower UTI to either 5 days of thrice-daily nitrofurantoin 100 mg or to a single 3-gram dose of fosfomycin. The women returned for clinical exam and urine culture at 14 and 28 days after they completed their treatment.
The primary outcome was 28-day clinical response. Success was defined as complete resolution of symptoms, a characterization that Dr. Huttner and her colleagues chose carefully. Many UTI studies include “improvement” in the clinical picture as part of a successful response. Dr. Huttner disagreed with that. “Our patients don’t want a partial response. They don’t want just an improvement. They want complete resolution of their symptoms.”
Failure was defined as the need for additional antibiotics or a change in antibiotic treatment. There was also an “indeterminate” category, for the small minority of patients who still felt some mild symptoms but were without microbiological signs of infection.
The mean age of the women was 44 years. All had an uncomplicated UTI characterized by dysuria, urgency, frequency, or suprapubic tenderness; 73% had a positive baseline urine culture. E. coli was the most common infective organism (about 60%) followed by different Klebsiella species, Proteus, and Enterococci. A few women had mixed pathogen infections. Only six patients had infective pathogens that were resistant to either of the study drugs.
After 28 days of treatment, a clinical cure was determined in 70% of those taking nitrofurantoin and 58% of those taking fosfomycin – an absolute difference of 12 points.
“The difference was obvious at 14 days,” Dr. Huttner noted. At that point, 75% of those taking nitrofurantoin and 66% of those taking fosfomycin reported resolution of their symptoms.
Pathology reflected the improving clinical picture: Microbiologic resolution occurred in 74% of the nitrofurantoin group and 63% of the fosfomycin group.
A post hoc analysis looked at results among the 214 women with confirmed E. coli infections.
The difference in clinical response was “even more pronounced” in these patients, Dr. Huttner said. Through day 28, clinical resolution occurred in 78% of those taking nitrofurantoin and 50% of those taking fosfomycin – a significant difference of 28 points.
Patients with E. coli infections were 4.48 times more likely to fail treatment if they received fosfomycin than if they received nitrofurantoin.
Adverse events were few and primarily gastrointestinal. The most common were mild to moderate nausea and diarrhea (less than 4% in each group).
Both of the antibiotics were popular from the 1950s on, but gradually fell out of favor as more powerful therapies were developed. However, as antibiotic resistance began to develop, infectious disease specialists began to support bringing nitrofurantoin and fosfomycin out of mothballs. In 2011, a panel of international experts convened by the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommended both of the medications as first-line therapy for women with acute uncomplicated cystitis and pyelonephritis.
The group recommended fosfomycin in a single 3-gram dose and a nitrofurantoin regimen of 100 mg twice daily for 5 days. The fosfomycin recommendation is clearly inadequate, Dr. Huttner said.
“Fosfomycin is not a bad drug. I just think it’s underdosed in this setting,” she said.
Dr. Huttner had no financial disclosures.
SOURCE: Huttner A et al. ECCMID 2018. Abstract O0479.
MADRID – (UTIs), a randomized study has determined.
By 28 days, clinical resolution had occurred in 70% of those who took nitrofurantoin and 58% of those who took fosfomycin – a statistically significant 12% difference, Angela Huttner, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
But the benefit was even more pronounced in women whose infections were caused by Escherichia coli, with a 28% spread in clinical resolution, (78% vs. 50%) and a 14-point spread in microbiological cure (72% vs. 58%), said Dr. Huttner of Geneva University, Switzerland.
The results were simultaneously published online in JAMA (2018 Apr 22. doi: 10.1001/jama.2018.3627).
Despite its success, nitrofurantoin did not live up to its purported 96% UTI cure rate – an established number based on study data from the 1950s-1970s.
Such efficacy was probably a false finding, she said. Studies of that era were much less rigorous than they are today, Dr. Huttner pointed out. The primary endpoint in those studies was typically defined not as complete resolution of symptoms – as it was in her study – but as resolution or improvement.
“Also, improvement was often defined microbiologically, often something like a decrease from 105 colony-forming units to 104, which is never something we would use today.”
The study was conducted in Geneva, Poland, and Israel. It randomized 512 women with an uncomplicated lower UTI to either 5 days of thrice-daily nitrofurantoin 100 mg or to a single 3-gram dose of fosfomycin. The women returned for clinical exam and urine culture at 14 and 28 days after they completed their treatment.
The primary outcome was 28-day clinical response. Success was defined as complete resolution of symptoms, a characterization that Dr. Huttner and her colleagues chose carefully. Many UTI studies include “improvement” in the clinical picture as part of a successful response. Dr. Huttner disagreed with that. “Our patients don’t want a partial response. They don’t want just an improvement. They want complete resolution of their symptoms.”
Failure was defined as the need for additional antibiotics or a change in antibiotic treatment. There was also an “indeterminate” category, for the small minority of patients who still felt some mild symptoms but were without microbiological signs of infection.
The mean age of the women was 44 years. All had an uncomplicated UTI characterized by dysuria, urgency, frequency, or suprapubic tenderness; 73% had a positive baseline urine culture. E. coli was the most common infective organism (about 60%) followed by different Klebsiella species, Proteus, and Enterococci. A few women had mixed pathogen infections. Only six patients had infective pathogens that were resistant to either of the study drugs.
After 28 days of treatment, a clinical cure was determined in 70% of those taking nitrofurantoin and 58% of those taking fosfomycin – an absolute difference of 12 points.
“The difference was obvious at 14 days,” Dr. Huttner noted. At that point, 75% of those taking nitrofurantoin and 66% of those taking fosfomycin reported resolution of their symptoms.
Pathology reflected the improving clinical picture: Microbiologic resolution occurred in 74% of the nitrofurantoin group and 63% of the fosfomycin group.
A post hoc analysis looked at results among the 214 women with confirmed E. coli infections.
The difference in clinical response was “even more pronounced” in these patients, Dr. Huttner said. Through day 28, clinical resolution occurred in 78% of those taking nitrofurantoin and 50% of those taking fosfomycin – a significant difference of 28 points.
Patients with E. coli infections were 4.48 times more likely to fail treatment if they received fosfomycin than if they received nitrofurantoin.
Adverse events were few and primarily gastrointestinal. The most common were mild to moderate nausea and diarrhea (less than 4% in each group).
Both of the antibiotics were popular from the 1950s on, but gradually fell out of favor as more powerful therapies were developed. However, as antibiotic resistance began to develop, infectious disease specialists began to support bringing nitrofurantoin and fosfomycin out of mothballs. In 2011, a panel of international experts convened by the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommended both of the medications as first-line therapy for women with acute uncomplicated cystitis and pyelonephritis.
The group recommended fosfomycin in a single 3-gram dose and a nitrofurantoin regimen of 100 mg twice daily for 5 days. The fosfomycin recommendation is clearly inadequate, Dr. Huttner said.
“Fosfomycin is not a bad drug. I just think it’s underdosed in this setting,” she said.
Dr. Huttner had no financial disclosures.
SOURCE: Huttner A et al. ECCMID 2018. Abstract O0479.
MADRID – (UTIs), a randomized study has determined.
By 28 days, clinical resolution had occurred in 70% of those who took nitrofurantoin and 58% of those who took fosfomycin – a statistically significant 12% difference, Angela Huttner, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
But the benefit was even more pronounced in women whose infections were caused by Escherichia coli, with a 28% spread in clinical resolution, (78% vs. 50%) and a 14-point spread in microbiological cure (72% vs. 58%), said Dr. Huttner of Geneva University, Switzerland.
The results were simultaneously published online in JAMA (2018 Apr 22. doi: 10.1001/jama.2018.3627).
Despite its success, nitrofurantoin did not live up to its purported 96% UTI cure rate – an established number based on study data from the 1950s-1970s.
Such efficacy was probably a false finding, she said. Studies of that era were much less rigorous than they are today, Dr. Huttner pointed out. The primary endpoint in those studies was typically defined not as complete resolution of symptoms – as it was in her study – but as resolution or improvement.
“Also, improvement was often defined microbiologically, often something like a decrease from 105 colony-forming units to 104, which is never something we would use today.”
The study was conducted in Geneva, Poland, and Israel. It randomized 512 women with an uncomplicated lower UTI to either 5 days of thrice-daily nitrofurantoin 100 mg or to a single 3-gram dose of fosfomycin. The women returned for clinical exam and urine culture at 14 and 28 days after they completed their treatment.
The primary outcome was 28-day clinical response. Success was defined as complete resolution of symptoms, a characterization that Dr. Huttner and her colleagues chose carefully. Many UTI studies include “improvement” in the clinical picture as part of a successful response. Dr. Huttner disagreed with that. “Our patients don’t want a partial response. They don’t want just an improvement. They want complete resolution of their symptoms.”
Failure was defined as the need for additional antibiotics or a change in antibiotic treatment. There was also an “indeterminate” category, for the small minority of patients who still felt some mild symptoms but were without microbiological signs of infection.
The mean age of the women was 44 years. All had an uncomplicated UTI characterized by dysuria, urgency, frequency, or suprapubic tenderness; 73% had a positive baseline urine culture. E. coli was the most common infective organism (about 60%) followed by different Klebsiella species, Proteus, and Enterococci. A few women had mixed pathogen infections. Only six patients had infective pathogens that were resistant to either of the study drugs.
After 28 days of treatment, a clinical cure was determined in 70% of those taking nitrofurantoin and 58% of those taking fosfomycin – an absolute difference of 12 points.
“The difference was obvious at 14 days,” Dr. Huttner noted. At that point, 75% of those taking nitrofurantoin and 66% of those taking fosfomycin reported resolution of their symptoms.
Pathology reflected the improving clinical picture: Microbiologic resolution occurred in 74% of the nitrofurantoin group and 63% of the fosfomycin group.
A post hoc analysis looked at results among the 214 women with confirmed E. coli infections.
The difference in clinical response was “even more pronounced” in these patients, Dr. Huttner said. Through day 28, clinical resolution occurred in 78% of those taking nitrofurantoin and 50% of those taking fosfomycin – a significant difference of 28 points.
Patients with E. coli infections were 4.48 times more likely to fail treatment if they received fosfomycin than if they received nitrofurantoin.
Adverse events were few and primarily gastrointestinal. The most common were mild to moderate nausea and diarrhea (less than 4% in each group).
Both of the antibiotics were popular from the 1950s on, but gradually fell out of favor as more powerful therapies were developed. However, as antibiotic resistance began to develop, infectious disease specialists began to support bringing nitrofurantoin and fosfomycin out of mothballs. In 2011, a panel of international experts convened by the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommended both of the medications as first-line therapy for women with acute uncomplicated cystitis and pyelonephritis.
The group recommended fosfomycin in a single 3-gram dose and a nitrofurantoin regimen of 100 mg twice daily for 5 days. The fosfomycin recommendation is clearly inadequate, Dr. Huttner said.
“Fosfomycin is not a bad drug. I just think it’s underdosed in this setting,” she said.
Dr. Huttner had no financial disclosures.
SOURCE: Huttner A et al. ECCMID 2018. Abstract O0479.
REPORTING FROM ECCMID 2018
Key clinical point: Nitrofurantoin was significantly more effective than was fosfomycin for a clinical and microbiological cure of uncomplicated UTI in women.
Major finding: By 28 days, clinical resolution had occurred in 70% of those who took nitrofurantoin and 58% of those who took fosfomycin .
Study details: The prospective study randomized 512 women.
Disclosures: Dr. Huttner had no financial disclosures.
Source: Huttner A et al. ECCMID 2018. Abstract O0479.
Measles exacts high toll among Europe’s youngest citizens
MADRID – Children younger than 2 years who contracted measles were significantly more likely to die of the disease than were older children, according to new data from the European Center for Disease Control and Prevention.
Infants younger than 12 months faced the worst mortality outcomes, with a sevenfold increased risk of death, compared with children aged 2 years or older, Emmanuel Robesyn, MD said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. Infants and children younger than 2 years also were much more likely to develop severe complications of the disease, including pneumonia and encephalitis.
The statistics should drive home the point that measles can be a life-threatening disease, especially for small children, said Dr. Robesyn, an expert in outbreak response at the European Center for Disease Prevention and Control, Stockholm.
“We want the population to understand that measles is much more than a nuisance illness of childhood,” he said. “Already this year we have recorded 13 deaths from measles,” which were not included in the data he presented.
“As you know, measles has been set for elimination” as a communicable disease, he said. “We need high immune coverage to achieve that, meaning 95% of the population covered with two doses. That is a challenge.”
Infants are especially vulnerable, and they fully reliant on the immunity of others to avoid measles.
“Vaccination recommendations begin at age 1, so before that, infants are dependent on their mothers’ antibodies, and on herd immunity. It’s very important that we have high vaccine coverage to protect them.”
Dr. Robesyn described measles outcomes in children 24 months and younger in 30 member states of the European Union and the European Economic Area from 2013 to 2017. Data were extracted from the European Surveillance System, which collects and analyzes infectious disease data across Europe.
During that period, there were 37,365 measles cases in people of all ages. Most were in Italy, Romania, Germany, the Netherlands, and the United Kingdom, with each reporting more than 5% of the cases. These countries also had the most cases that had not been connected with importation of the disease.
Overall, the patients were a mean of 12 years old. Less than 2% had been fully vaccinated against the disease. Complications (diarrhea, otitis media, pneumonia, or encephalitis) occurred in 13.6%, and about 33% of patients had to be hospitalized. Most cases (81%) occurred in people aged 2 years and older, 9% occurred in children who were 12-24 months old, and 10% occurred in children younger than 12 months. These younger children, however, accounted for 61% of the deaths in the cohort, Dr. Robesyn said.
Most of the cases occurred in unvaccinated or incompletely vaccinated patients. Forty-six died from measles, a mortality rate of about 1 per 1,000 who contracted the disease. Of these deaths, 16 were among children younger than 12 months, 12 among children aged 12-24 months, and the remainder among those older than 2 years.
These younger patients were also more susceptible to complications of measles, both mild (diarrhea and otitis media) and severe (pneumonia and encephalitis). Most of the uncomplicated cases (75%) occurred in children older than 24 months, with just 25% of uncomplicated cases occurring in the younger groups.
“When we looked at age as a continuous variable, we saw that the chance of having no complications or just mild complications increased with age, and the chance of having severe complications decreased with age,” Dr. Robesyn said.
“We definitely saw that these two groups are at increased risk. The consequences however, are different. For the children who are 1 year of age or older, the message is that it’s really important to strictly follow national recommendations and get timely and complete vaccination. For those younger than 1 year, we have to rely on the population to be vaccinated. It is very important that we reach this 95% coverage rate to protect these youngest children. We need adolescents and young adults who have missed vaccinations to get them completed,” he said.
Dr. Robesyn had no financial disclosures.
SOURCE: Robesyn E et al. ECCMID 2018, abstract O0060
MADRID – Children younger than 2 years who contracted measles were significantly more likely to die of the disease than were older children, according to new data from the European Center for Disease Control and Prevention.
Infants younger than 12 months faced the worst mortality outcomes, with a sevenfold increased risk of death, compared with children aged 2 years or older, Emmanuel Robesyn, MD said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. Infants and children younger than 2 years also were much more likely to develop severe complications of the disease, including pneumonia and encephalitis.
The statistics should drive home the point that measles can be a life-threatening disease, especially for small children, said Dr. Robesyn, an expert in outbreak response at the European Center for Disease Prevention and Control, Stockholm.
“We want the population to understand that measles is much more than a nuisance illness of childhood,” he said. “Already this year we have recorded 13 deaths from measles,” which were not included in the data he presented.
“As you know, measles has been set for elimination” as a communicable disease, he said. “We need high immune coverage to achieve that, meaning 95% of the population covered with two doses. That is a challenge.”
Infants are especially vulnerable, and they fully reliant on the immunity of others to avoid measles.
“Vaccination recommendations begin at age 1, so before that, infants are dependent on their mothers’ antibodies, and on herd immunity. It’s very important that we have high vaccine coverage to protect them.”
Dr. Robesyn described measles outcomes in children 24 months and younger in 30 member states of the European Union and the European Economic Area from 2013 to 2017. Data were extracted from the European Surveillance System, which collects and analyzes infectious disease data across Europe.
During that period, there were 37,365 measles cases in people of all ages. Most were in Italy, Romania, Germany, the Netherlands, and the United Kingdom, with each reporting more than 5% of the cases. These countries also had the most cases that had not been connected with importation of the disease.
Overall, the patients were a mean of 12 years old. Less than 2% had been fully vaccinated against the disease. Complications (diarrhea, otitis media, pneumonia, or encephalitis) occurred in 13.6%, and about 33% of patients had to be hospitalized. Most cases (81%) occurred in people aged 2 years and older, 9% occurred in children who were 12-24 months old, and 10% occurred in children younger than 12 months. These younger children, however, accounted for 61% of the deaths in the cohort, Dr. Robesyn said.
Most of the cases occurred in unvaccinated or incompletely vaccinated patients. Forty-six died from measles, a mortality rate of about 1 per 1,000 who contracted the disease. Of these deaths, 16 were among children younger than 12 months, 12 among children aged 12-24 months, and the remainder among those older than 2 years.
These younger patients were also more susceptible to complications of measles, both mild (diarrhea and otitis media) and severe (pneumonia and encephalitis). Most of the uncomplicated cases (75%) occurred in children older than 24 months, with just 25% of uncomplicated cases occurring in the younger groups.
“When we looked at age as a continuous variable, we saw that the chance of having no complications or just mild complications increased with age, and the chance of having severe complications decreased with age,” Dr. Robesyn said.
“We definitely saw that these two groups are at increased risk. The consequences however, are different. For the children who are 1 year of age or older, the message is that it’s really important to strictly follow national recommendations and get timely and complete vaccination. For those younger than 1 year, we have to rely on the population to be vaccinated. It is very important that we reach this 95% coverage rate to protect these youngest children. We need adolescents and young adults who have missed vaccinations to get them completed,” he said.
Dr. Robesyn had no financial disclosures.
SOURCE: Robesyn E et al. ECCMID 2018, abstract O0060
MADRID – Children younger than 2 years who contracted measles were significantly more likely to die of the disease than were older children, according to new data from the European Center for Disease Control and Prevention.
Infants younger than 12 months faced the worst mortality outcomes, with a sevenfold increased risk of death, compared with children aged 2 years or older, Emmanuel Robesyn, MD said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. Infants and children younger than 2 years also were much more likely to develop severe complications of the disease, including pneumonia and encephalitis.
The statistics should drive home the point that measles can be a life-threatening disease, especially for small children, said Dr. Robesyn, an expert in outbreak response at the European Center for Disease Prevention and Control, Stockholm.
“We want the population to understand that measles is much more than a nuisance illness of childhood,” he said. “Already this year we have recorded 13 deaths from measles,” which were not included in the data he presented.
“As you know, measles has been set for elimination” as a communicable disease, he said. “We need high immune coverage to achieve that, meaning 95% of the population covered with two doses. That is a challenge.”
Infants are especially vulnerable, and they fully reliant on the immunity of others to avoid measles.
“Vaccination recommendations begin at age 1, so before that, infants are dependent on their mothers’ antibodies, and on herd immunity. It’s very important that we have high vaccine coverage to protect them.”
Dr. Robesyn described measles outcomes in children 24 months and younger in 30 member states of the European Union and the European Economic Area from 2013 to 2017. Data were extracted from the European Surveillance System, which collects and analyzes infectious disease data across Europe.
During that period, there were 37,365 measles cases in people of all ages. Most were in Italy, Romania, Germany, the Netherlands, and the United Kingdom, with each reporting more than 5% of the cases. These countries also had the most cases that had not been connected with importation of the disease.
Overall, the patients were a mean of 12 years old. Less than 2% had been fully vaccinated against the disease. Complications (diarrhea, otitis media, pneumonia, or encephalitis) occurred in 13.6%, and about 33% of patients had to be hospitalized. Most cases (81%) occurred in people aged 2 years and older, 9% occurred in children who were 12-24 months old, and 10% occurred in children younger than 12 months. These younger children, however, accounted for 61% of the deaths in the cohort, Dr. Robesyn said.
Most of the cases occurred in unvaccinated or incompletely vaccinated patients. Forty-six died from measles, a mortality rate of about 1 per 1,000 who contracted the disease. Of these deaths, 16 were among children younger than 12 months, 12 among children aged 12-24 months, and the remainder among those older than 2 years.
These younger patients were also more susceptible to complications of measles, both mild (diarrhea and otitis media) and severe (pneumonia and encephalitis). Most of the uncomplicated cases (75%) occurred in children older than 24 months, with just 25% of uncomplicated cases occurring in the younger groups.
“When we looked at age as a continuous variable, we saw that the chance of having no complications or just mild complications increased with age, and the chance of having severe complications decreased with age,” Dr. Robesyn said.
“We definitely saw that these two groups are at increased risk. The consequences however, are different. For the children who are 1 year of age or older, the message is that it’s really important to strictly follow national recommendations and get timely and complete vaccination. For those younger than 1 year, we have to rely on the population to be vaccinated. It is very important that we reach this 95% coverage rate to protect these youngest children. We need adolescents and young adults who have missed vaccinations to get them completed,” he said.
Dr. Robesyn had no financial disclosures.
SOURCE: Robesyn E et al. ECCMID 2018, abstract O0060
REPORTING FROM ECCMID 2018
Key clinical point: Measles is most dangerous to children younger than 2 years.
Major finding: Children younger than 12 months who contracted measles were seven times more likely to die of the disease than were children 2 years and older.
Study details: The analysis involved 37,365 measles cases that occurred in the European Union from 2013 to 2017.
Disclosures: The analysis was conducted by the European Center for Disease Prevention and Control.
Source: Robesyn E et al. ECCMID 2018, abstract O0060.