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Sterile fecal filtrate effectively treated recurrent CDI
Sterile fecal filtrate transplantation (FFT) effectively treated five cases of symptomatic chronic-relapsing Clostridium difficile infection, investigators reported.
The procedure restored normal bowel habits and eliminated symptoms through the end of the study – that is, for at least 6 months – in all patients, Stephan J. Ott, MD, and his associates wrote (Gastroenterology. 2019. doi: 10.1053/j.gastro.2016.11.010).
Proteome analyses did not identify proteins likely to explain this efficacy, but 16S rRNA gene sequencing did demonstrate diverse bacterial DNA signatures in the filtrates, and tests of virus-like particles yielded “a complex signature of macrophages,” Dr. Ott and his associates reported. Additional tests suggested that recipients’ microbiomes continued to change weeks after FFT. “This open-label series strongly suggests that FFT should be evaluated in a controlled setting in comparison with standard fecal microbiota transplantation,” the researchers concluded.
Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), but even “the most rigorous and costly donor screening procedures, or defined panels of bacteria, cannot exclude the risk of transferring unknown pathogens or undetectable functional characteristics within the living microorganisms to the recipient, including bacterial or viral risk factors for metabolic diseases, cancer, atopy, or autoimmunity,” the investigators wrote.
Therefore, they performed sterile FFT in five patients who were positive on at least two of three tests: enzyme-linked immunosorbent assay for C. difficile–specific glutamate dehydrogenase; C. difficile toxin enzyme-linked immunosorbent assay; and culture of toxin-producing C. difficile. Patients chose their own stool donors, who were then screened based on published guidelines (Clin Gastroenterol Hepatol. 2011;9[12]:1044-49). Next, “slurries” were prepared from donor stool and filtered with a custom-built air pressure filtration system, yielding a “light brown, clear liquid with a subjectively less unpleasant and intensive odor” than conventional FMT stool preparations. Bacterial cultures of these filtrates yielded no growth, whereas donor stool cultures showed profuse growth of aerobic and anaerobic bacterial colonies, Dr. Ott and his associates said.
Patients became symptom-free 2-4 days after undergoing FFT. Notably, one patient had previously undergone FMT, which led to acute fever and diarrhea and recurrence of baseline symptoms after 3 months. This patient did not develop fever or diarrhea after FFT, was symptom-free after 3 days, and remained symptom-free until the study ended 2 years later, the researchers said. All other patients also remained symptom-free through the end of the study, that is, for 6 months to more than 2 years.
Analyses of 16S rRNA revealed substantial longitudinal shifts after FFT that often were present by week 1 and remained stable until week 6, the investigators said. Further tests confirmed marked shifts in bacterial phylotypes and in their relative abundance over time. Repeated virus analyses of one patient also showed that the phageome shifted over time to resemble that of the donor.
Patients were between 49 and 75 years old, three were female and two were male, and all had received more than one antibiotic before their first episode of CDI. Antibiotics for CDI had included metronidazole, vancomycin, and rifaximin. Comorbidities included pseudomembranous colitis, renal failure, HIV infection, epilepsy, and chronic heart failure, and medical histories included recurrent diverticulitis with sigmoid resection, gastric carcinoma, and colon cancer.
“It is important to keep in mind that, in contrast to conventional FMT, transferring sterile FFT filtrates cannot be expected to establish a microbiota similar to that of the donor in the receiving patient,” Dr. Ott and his associates noted. Instead, bacterial DNA in the filtrate might trigger the re-establishment of the recipient microbiome, they said. Bacterial cell wall fragments or bacteriophages also might play a role, they added.
The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.
The remarkable efficacy of fecal microbial transplant in recurrent C. difficile infection provides a compelling example of ecologic microbiome-based therapy. Its mechanism is widely considered to be the restoration of select microbial species that suppress C. difficile colonization and virulence in healthy individuals. Identification of such suppressive microbiota is still at an early stage, with empirical studies revealing effective synthetic microbial consortia, and evidence of some modes of action, such as bile salt metabolism (Nature 2015;517:205-8; PLoS Pathog. 2012;8:e1002995).
Clouding this elegant concept is the provocative new study of Dr. Ott and his colleagues. Prompted by long-term safety concerns, they evaluated the efficacy of a donor fecal microfiltrate lacking viable intact organisms. Indeed, in five patients, long-term eradication of C. difficile was achieved with a single dose. This observation indicates that the initial action of fecal transplant may not require restoration of viable organisms into the antibiotic-damaged ecosystem.
What mechanisms might account for the therapeutic action of organism-free fecal microfiltrate? First, this material is laden with a complex, potentially distinct mix of microbial products and particulates (Cell. 2016;165[5]:1106-19) from donor origin or ex vivo processing. These biologicals may induce immune processes to promote control of C. difficile directly or via changes in other commensals of the patient's microbiome. Second, the microfiltrate retains abundant and diverse bacteria-targeting viruses of the fecal stream. Perhaps certain viruses, deficient in patients, target C. difficile and/or beneficially reshape microbial composition (Cell Mol Gastroenterol Hepatol. 2015;1[1]:28-40). So, C. difficile challenges us once more into the breach with new insights ahead for the principles and practice of ecologic microbiome therapy.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine at the University of California, Los Angeles. He has no conflicts of interest.
The remarkable efficacy of fecal microbial transplant in recurrent C. difficile infection provides a compelling example of ecologic microbiome-based therapy. Its mechanism is widely considered to be the restoration of select microbial species that suppress C. difficile colonization and virulence in healthy individuals. Identification of such suppressive microbiota is still at an early stage, with empirical studies revealing effective synthetic microbial consortia, and evidence of some modes of action, such as bile salt metabolism (Nature 2015;517:205-8; PLoS Pathog. 2012;8:e1002995).
Clouding this elegant concept is the provocative new study of Dr. Ott and his colleagues. Prompted by long-term safety concerns, they evaluated the efficacy of a donor fecal microfiltrate lacking viable intact organisms. Indeed, in five patients, long-term eradication of C. difficile was achieved with a single dose. This observation indicates that the initial action of fecal transplant may not require restoration of viable organisms into the antibiotic-damaged ecosystem.
What mechanisms might account for the therapeutic action of organism-free fecal microfiltrate? First, this material is laden with a complex, potentially distinct mix of microbial products and particulates (Cell. 2016;165[5]:1106-19) from donor origin or ex vivo processing. These biologicals may induce immune processes to promote control of C. difficile directly or via changes in other commensals of the patient's microbiome. Second, the microfiltrate retains abundant and diverse bacteria-targeting viruses of the fecal stream. Perhaps certain viruses, deficient in patients, target C. difficile and/or beneficially reshape microbial composition (Cell Mol Gastroenterol Hepatol. 2015;1[1]:28-40). So, C. difficile challenges us once more into the breach with new insights ahead for the principles and practice of ecologic microbiome therapy.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine at the University of California, Los Angeles. He has no conflicts of interest.
The remarkable efficacy of fecal microbial transplant in recurrent C. difficile infection provides a compelling example of ecologic microbiome-based therapy. Its mechanism is widely considered to be the restoration of select microbial species that suppress C. difficile colonization and virulence in healthy individuals. Identification of such suppressive microbiota is still at an early stage, with empirical studies revealing effective synthetic microbial consortia, and evidence of some modes of action, such as bile salt metabolism (Nature 2015;517:205-8; PLoS Pathog. 2012;8:e1002995).
Clouding this elegant concept is the provocative new study of Dr. Ott and his colleagues. Prompted by long-term safety concerns, they evaluated the efficacy of a donor fecal microfiltrate lacking viable intact organisms. Indeed, in five patients, long-term eradication of C. difficile was achieved with a single dose. This observation indicates that the initial action of fecal transplant may not require restoration of viable organisms into the antibiotic-damaged ecosystem.
What mechanisms might account for the therapeutic action of organism-free fecal microfiltrate? First, this material is laden with a complex, potentially distinct mix of microbial products and particulates (Cell. 2016;165[5]:1106-19) from donor origin or ex vivo processing. These biologicals may induce immune processes to promote control of C. difficile directly or via changes in other commensals of the patient's microbiome. Second, the microfiltrate retains abundant and diverse bacteria-targeting viruses of the fecal stream. Perhaps certain viruses, deficient in patients, target C. difficile and/or beneficially reshape microbial composition (Cell Mol Gastroenterol Hepatol. 2015;1[1]:28-40). So, C. difficile challenges us once more into the breach with new insights ahead for the principles and practice of ecologic microbiome therapy.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine at the University of California, Los Angeles. He has no conflicts of interest.
Sterile fecal filtrate transplantation (FFT) effectively treated five cases of symptomatic chronic-relapsing Clostridium difficile infection, investigators reported.
The procedure restored normal bowel habits and eliminated symptoms through the end of the study – that is, for at least 6 months – in all patients, Stephan J. Ott, MD, and his associates wrote (Gastroenterology. 2019. doi: 10.1053/j.gastro.2016.11.010).
Proteome analyses did not identify proteins likely to explain this efficacy, but 16S rRNA gene sequencing did demonstrate diverse bacterial DNA signatures in the filtrates, and tests of virus-like particles yielded “a complex signature of macrophages,” Dr. Ott and his associates reported. Additional tests suggested that recipients’ microbiomes continued to change weeks after FFT. “This open-label series strongly suggests that FFT should be evaluated in a controlled setting in comparison with standard fecal microbiota transplantation,” the researchers concluded.
Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), but even “the most rigorous and costly donor screening procedures, or defined panels of bacteria, cannot exclude the risk of transferring unknown pathogens or undetectable functional characteristics within the living microorganisms to the recipient, including bacterial or viral risk factors for metabolic diseases, cancer, atopy, or autoimmunity,” the investigators wrote.
Therefore, they performed sterile FFT in five patients who were positive on at least two of three tests: enzyme-linked immunosorbent assay for C. difficile–specific glutamate dehydrogenase; C. difficile toxin enzyme-linked immunosorbent assay; and culture of toxin-producing C. difficile. Patients chose their own stool donors, who were then screened based on published guidelines (Clin Gastroenterol Hepatol. 2011;9[12]:1044-49). Next, “slurries” were prepared from donor stool and filtered with a custom-built air pressure filtration system, yielding a “light brown, clear liquid with a subjectively less unpleasant and intensive odor” than conventional FMT stool preparations. Bacterial cultures of these filtrates yielded no growth, whereas donor stool cultures showed profuse growth of aerobic and anaerobic bacterial colonies, Dr. Ott and his associates said.
Patients became symptom-free 2-4 days after undergoing FFT. Notably, one patient had previously undergone FMT, which led to acute fever and diarrhea and recurrence of baseline symptoms after 3 months. This patient did not develop fever or diarrhea after FFT, was symptom-free after 3 days, and remained symptom-free until the study ended 2 years later, the researchers said. All other patients also remained symptom-free through the end of the study, that is, for 6 months to more than 2 years.
Analyses of 16S rRNA revealed substantial longitudinal shifts after FFT that often were present by week 1 and remained stable until week 6, the investigators said. Further tests confirmed marked shifts in bacterial phylotypes and in their relative abundance over time. Repeated virus analyses of one patient also showed that the phageome shifted over time to resemble that of the donor.
Patients were between 49 and 75 years old, three were female and two were male, and all had received more than one antibiotic before their first episode of CDI. Antibiotics for CDI had included metronidazole, vancomycin, and rifaximin. Comorbidities included pseudomembranous colitis, renal failure, HIV infection, epilepsy, and chronic heart failure, and medical histories included recurrent diverticulitis with sigmoid resection, gastric carcinoma, and colon cancer.
“It is important to keep in mind that, in contrast to conventional FMT, transferring sterile FFT filtrates cannot be expected to establish a microbiota similar to that of the donor in the receiving patient,” Dr. Ott and his associates noted. Instead, bacterial DNA in the filtrate might trigger the re-establishment of the recipient microbiome, they said. Bacterial cell wall fragments or bacteriophages also might play a role, they added.
The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.
Sterile fecal filtrate transplantation (FFT) effectively treated five cases of symptomatic chronic-relapsing Clostridium difficile infection, investigators reported.
The procedure restored normal bowel habits and eliminated symptoms through the end of the study – that is, for at least 6 months – in all patients, Stephan J. Ott, MD, and his associates wrote (Gastroenterology. 2019. doi: 10.1053/j.gastro.2016.11.010).
Proteome analyses did not identify proteins likely to explain this efficacy, but 16S rRNA gene sequencing did demonstrate diverse bacterial DNA signatures in the filtrates, and tests of virus-like particles yielded “a complex signature of macrophages,” Dr. Ott and his associates reported. Additional tests suggested that recipients’ microbiomes continued to change weeks after FFT. “This open-label series strongly suggests that FFT should be evaluated in a controlled setting in comparison with standard fecal microbiota transplantation,” the researchers concluded.
Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), but even “the most rigorous and costly donor screening procedures, or defined panels of bacteria, cannot exclude the risk of transferring unknown pathogens or undetectable functional characteristics within the living microorganisms to the recipient, including bacterial or viral risk factors for metabolic diseases, cancer, atopy, or autoimmunity,” the investigators wrote.
Therefore, they performed sterile FFT in five patients who were positive on at least two of three tests: enzyme-linked immunosorbent assay for C. difficile–specific glutamate dehydrogenase; C. difficile toxin enzyme-linked immunosorbent assay; and culture of toxin-producing C. difficile. Patients chose their own stool donors, who were then screened based on published guidelines (Clin Gastroenterol Hepatol. 2011;9[12]:1044-49). Next, “slurries” were prepared from donor stool and filtered with a custom-built air pressure filtration system, yielding a “light brown, clear liquid with a subjectively less unpleasant and intensive odor” than conventional FMT stool preparations. Bacterial cultures of these filtrates yielded no growth, whereas donor stool cultures showed profuse growth of aerobic and anaerobic bacterial colonies, Dr. Ott and his associates said.
Patients became symptom-free 2-4 days after undergoing FFT. Notably, one patient had previously undergone FMT, which led to acute fever and diarrhea and recurrence of baseline symptoms after 3 months. This patient did not develop fever or diarrhea after FFT, was symptom-free after 3 days, and remained symptom-free until the study ended 2 years later, the researchers said. All other patients also remained symptom-free through the end of the study, that is, for 6 months to more than 2 years.
Analyses of 16S rRNA revealed substantial longitudinal shifts after FFT that often were present by week 1 and remained stable until week 6, the investigators said. Further tests confirmed marked shifts in bacterial phylotypes and in their relative abundance over time. Repeated virus analyses of one patient also showed that the phageome shifted over time to resemble that of the donor.
Patients were between 49 and 75 years old, three were female and two were male, and all had received more than one antibiotic before their first episode of CDI. Antibiotics for CDI had included metronidazole, vancomycin, and rifaximin. Comorbidities included pseudomembranous colitis, renal failure, HIV infection, epilepsy, and chronic heart failure, and medical histories included recurrent diverticulitis with sigmoid resection, gastric carcinoma, and colon cancer.
“It is important to keep in mind that, in contrast to conventional FMT, transferring sterile FFT filtrates cannot be expected to establish a microbiota similar to that of the donor in the receiving patient,” Dr. Ott and his associates noted. Instead, bacterial DNA in the filtrate might trigger the re-establishment of the recipient microbiome, they said. Bacterial cell wall fragments or bacteriophages also might play a role, they added.
The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Sterile fecal filtrate transplantation effectively treated symptomatic chronic-relapsing Clostridium difficile infection.
Major finding: For all patients, transplantation restored normal bowel habits within 2-4 days and eliminated symptoms for at least 6 months.
Data source: A single-center cases series of five patients with recurrent symptomatic CDI.
Disclosures: The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.
Carbapenem-resistant K. pneumoniae occurs in 25% of long-term acute care hospital cultures
Nearly one-quarter of Klebsiella pneumoniae cultures in a network of U.S. long-term acute care hospitals are resistant to carbapenem, according to Jennifer H. Han, MD, and her associates.
From a sample of 3,846 K. pneumoniae cultures taken from 64 long-term acute care hospitals in 16 states, 946, or 24.6%, of the cultures were carbapenem-resistant, and were taken from 821 patients. Just under 54% of CRKP isolates were taken from a respiratory source, with 37% coming from urine and the remaining 9.4% coming from blood. Nearly all CRKP isolates were resistant to fluoroquinolones, and 59.2% were resistant to amikacin.
Of the 16 states where cultures were taken from, California had the highest rate of carbapenem resistance, with 45.5% of K. pneumoniae cultures showing resistance. Other states with high rates of CRKP included South Carolina, Kentucky, and Indiana.
“Given the chronically, critically ill population, with convergence of at-risk patients from multiple facilities, future studies of optimal infection prevention strategies are urgently needed for this setting. In addition, expansion of national surveillance efforts and improved communication between [long-term acute care hospitals] and acute care hospitals will be critical for reducing the continued emergence and dissemination of CRKP across the health care continuum,” Dr. Han and her associates concluded.
Find the full study in Clinical Infectious Diseases (doi: 10.1 LTACHs 093/cid/ciw856)
Nearly one-quarter of Klebsiella pneumoniae cultures in a network of U.S. long-term acute care hospitals are resistant to carbapenem, according to Jennifer H. Han, MD, and her associates.
From a sample of 3,846 K. pneumoniae cultures taken from 64 long-term acute care hospitals in 16 states, 946, or 24.6%, of the cultures were carbapenem-resistant, and were taken from 821 patients. Just under 54% of CRKP isolates were taken from a respiratory source, with 37% coming from urine and the remaining 9.4% coming from blood. Nearly all CRKP isolates were resistant to fluoroquinolones, and 59.2% were resistant to amikacin.
Of the 16 states where cultures were taken from, California had the highest rate of carbapenem resistance, with 45.5% of K. pneumoniae cultures showing resistance. Other states with high rates of CRKP included South Carolina, Kentucky, and Indiana.
“Given the chronically, critically ill population, with convergence of at-risk patients from multiple facilities, future studies of optimal infection prevention strategies are urgently needed for this setting. In addition, expansion of national surveillance efforts and improved communication between [long-term acute care hospitals] and acute care hospitals will be critical for reducing the continued emergence and dissemination of CRKP across the health care continuum,” Dr. Han and her associates concluded.
Find the full study in Clinical Infectious Diseases (doi: 10.1 LTACHs 093/cid/ciw856)
Nearly one-quarter of Klebsiella pneumoniae cultures in a network of U.S. long-term acute care hospitals are resistant to carbapenem, according to Jennifer H. Han, MD, and her associates.
From a sample of 3,846 K. pneumoniae cultures taken from 64 long-term acute care hospitals in 16 states, 946, or 24.6%, of the cultures were carbapenem-resistant, and were taken from 821 patients. Just under 54% of CRKP isolates were taken from a respiratory source, with 37% coming from urine and the remaining 9.4% coming from blood. Nearly all CRKP isolates were resistant to fluoroquinolones, and 59.2% were resistant to amikacin.
Of the 16 states where cultures were taken from, California had the highest rate of carbapenem resistance, with 45.5% of K. pneumoniae cultures showing resistance. Other states with high rates of CRKP included South Carolina, Kentucky, and Indiana.
“Given the chronically, critically ill population, with convergence of at-risk patients from multiple facilities, future studies of optimal infection prevention strategies are urgently needed for this setting. In addition, expansion of national surveillance efforts and improved communication between [long-term acute care hospitals] and acute care hospitals will be critical for reducing the continued emergence and dissemination of CRKP across the health care continuum,” Dr. Han and her associates concluded.
Find the full study in Clinical Infectious Diseases (doi: 10.1 LTACHs 093/cid/ciw856)
FROM CLINICAL INFECTIOUS DISEASES
Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae ‘considerable’
Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae is “considerable,” according to genetic analyses of bacterial isolates obtained from patients at four large U.S. hospitals.
To better understand the “urgent threat” of carbapenem resistance – specifically, to obtain a “snapshot” of how the resistant enterobacteria evolve, diversify, and spread – the researchers performed genetic analyses on 122 carbapenem-resistant and 141 carbapenem-susceptible bacterial isolates from patients hospitalized during a 16-month period at three Boston and one California medical centers. The isolates were obtained from urine (44%), respiratory tract (16%), blood (11%), wound (11%), and other samples, said Gustavo C. Cerqueira, PhD, of the Broad Institute of MIT and Harvard University in Cambridge, Mass., and his associates.
They found 8 species of bacteria that exhibited carbapenem resistance, chiefly Klebsiella pneumoniae. There also was a significant degree of diversity among resistant Enterobacteria. Most importantly, the investigators found evidence of substantial asymptomatic carriage of resistant bacteria and discovered several previously unrecognized mechanisms that produced resistance. Taken together, the findings indicate “continued innovation by these organisms to thwart the action of this important class of antibiotics,” reported Dr. Cerqueira, also affiliated with Massachusetts General Hospital in Boston, and his associates (Proc Nat Acad Sci USA. 2017 Jan 16 [doi:10.1073/pnas.1616248114]).
The study findings underscore the need for “an aggressive approach to surveillance and isolation” to control this continuing threat, they added.
This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Cerqueira and his associates reported having no relevant financial disclosures.
Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae is “considerable,” according to genetic analyses of bacterial isolates obtained from patients at four large U.S. hospitals.
To better understand the “urgent threat” of carbapenem resistance – specifically, to obtain a “snapshot” of how the resistant enterobacteria evolve, diversify, and spread – the researchers performed genetic analyses on 122 carbapenem-resistant and 141 carbapenem-susceptible bacterial isolates from patients hospitalized during a 16-month period at three Boston and one California medical centers. The isolates were obtained from urine (44%), respiratory tract (16%), blood (11%), wound (11%), and other samples, said Gustavo C. Cerqueira, PhD, of the Broad Institute of MIT and Harvard University in Cambridge, Mass., and his associates.
They found 8 species of bacteria that exhibited carbapenem resistance, chiefly Klebsiella pneumoniae. There also was a significant degree of diversity among resistant Enterobacteria. Most importantly, the investigators found evidence of substantial asymptomatic carriage of resistant bacteria and discovered several previously unrecognized mechanisms that produced resistance. Taken together, the findings indicate “continued innovation by these organisms to thwart the action of this important class of antibiotics,” reported Dr. Cerqueira, also affiliated with Massachusetts General Hospital in Boston, and his associates (Proc Nat Acad Sci USA. 2017 Jan 16 [doi:10.1073/pnas.1616248114]).
The study findings underscore the need for “an aggressive approach to surveillance and isolation” to control this continuing threat, they added.
This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Cerqueira and his associates reported having no relevant financial disclosures.
Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae is “considerable,” according to genetic analyses of bacterial isolates obtained from patients at four large U.S. hospitals.
To better understand the “urgent threat” of carbapenem resistance – specifically, to obtain a “snapshot” of how the resistant enterobacteria evolve, diversify, and spread – the researchers performed genetic analyses on 122 carbapenem-resistant and 141 carbapenem-susceptible bacterial isolates from patients hospitalized during a 16-month period at three Boston and one California medical centers. The isolates were obtained from urine (44%), respiratory tract (16%), blood (11%), wound (11%), and other samples, said Gustavo C. Cerqueira, PhD, of the Broad Institute of MIT and Harvard University in Cambridge, Mass., and his associates.
They found 8 species of bacteria that exhibited carbapenem resistance, chiefly Klebsiella pneumoniae. There also was a significant degree of diversity among resistant Enterobacteria. Most importantly, the investigators found evidence of substantial asymptomatic carriage of resistant bacteria and discovered several previously unrecognized mechanisms that produced resistance. Taken together, the findings indicate “continued innovation by these organisms to thwart the action of this important class of antibiotics,” reported Dr. Cerqueira, also affiliated with Massachusetts General Hospital in Boston, and his associates (Proc Nat Acad Sci USA. 2017 Jan 16 [doi:10.1073/pnas.1616248114]).
The study findings underscore the need for “an aggressive approach to surveillance and isolation” to control this continuing threat, they added.
This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Cerqueira and his associates reported having no relevant financial disclosures.
FROM THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
Key clinical point: Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae is “considerable.”
Major finding: Researchers found eight species of bacteria that exhibited carbapenem resistance, a significant degree of diversity among resistant enterobacteria, evidence of substantial asymptomatic carriage of resistant bacteria, and several previously unrecognized mechanisms that produced resistance.
Data source: Genetic analyses of 122 carbapenem-resistant and 141 carbapenem-susceptible bacterial isolates obtained from patients at 4 large U.S. hospitals.
Disclosures: This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Cerqueira and his associates reported having no relevant financial disclosures.
Bezlotoxumab prevents recurrent C. difficile infection
Adding bezlotoxumab to standard antibiotic treatment of primary or recurrent Clostridium difficile infection reduces recurrences by 38% (10 percentage points), according to a report published in the New England Journal of Medicine.
As many as 35% of patients who complete initial antibiotic treatment have at least one recurrence of C. difficile infection, and the rate of repeat recurrence rate jumps to 60% after the initial recurrence. Researchers performed two parallel international phase III trials to assess the efficacy and safety of bezlotoxumab, alone or in combination with actoxumab, for preventing such recurrences. Both monoclonal antibodies work by binding to and neutralizing C. difficile toxins; bezlotoxumab targets toxin B and actoxumab targets toxin A, said Mark H. Wilcox, MD, of the division of microbiology, Leeds (England) General Infirmary, and his associates.
The primary efficacy endpoint – the proportion of patients with recurrent C. difficile infection during 12 weeks of follow-up – was substantially lower with bezlotoxumab (17%) than with placebo (28%) in the first trial and in the second trial (16% vs. 26%). This treatment benefit was evident as early as 2 weeks after infusion and persisted throughout follow-up, the investigators said (N Engl J Med. 2017 Jan 25. doi: 10.1056/NEJMoa1602615).
The agent’s persistent effect through 12 weeks is important to note because approximately 30% of the recurrences in this study “occurred beyond the conventional 4-week assessment period for treatment efficacy. The number needed to treat to prevent one episode of recurrent C. difficile infection was 10; it was 6 among participants 65 years of age or older and those with previous C. difficile infection,” Dr. Wilcox and his associates noted.
Bezlotoxumab was consistently effective in several sensitivity analyses. It also was effective in both trials individually as well as in pooled results. And the choice of oral antibiotic appeared to have no effect on bezlotoxumab’s efficacy.
In a post hoc analysis, bezlotoxumab was also effective in the subgroup of 1,964 patients at highest risk for C. difficile recurrence because they were elderly, had compromised immunity, had the most severe infections, had a history of C. difficile infection, or carried a strain of the organism associated with particularly poor outcomes. In this subgroup, 17% of patients given bezlotoxumab and 16% of those given bezlotoxumab plus actoxumab developed recurrences, compared with 30% of those given placebo.
Regarding adverse events, the agent had “a generally favorable safety profile,” and the rates of adverse events “were generally as expected, given the underlying disease severity, baseline coexisting conditions, and ages of the participants.” Two participants discontinued the infusion because of an adverse event. Drug-related adverse events occurred in 7% of the entire study population, serious drug-related adverse events occurred in 1%, and both occurred at similar rates across the study groups.
Both trials were funded by Merck, which also was involved in study design, data analysis and interpretation, and writing the reports. Dr. Wilcox and his associates reported ties to Merck and numerous other industry sources.
Bezlotoxumab must be placed in perspective, seen within the context of alternative options currently being evaluated in clinical trials.
These include recently developed drugs such as ridinilazole, surotomycin, cadazolid, RBX2660, and SER-109. Also under assessment is the oral administration of nontoxigenic C. difficile strains to compete with toxigenic strains, as well as three vaccines against the organism. Stool transplantation also is known to be highly successful in preventing recurrent C. difficile infection.
In addition, the cost-effectiveness of bezlotoxumab, especially in relation to these alternative treatments, hasn’t yet been determined.
John G. Bartlett, MD, is in the department of medicine at Johns Hopkins University, Baltimore. He reported having no relevant financial disclosures. Dr. Bartlett made these remarks in an editorial accompanying Dr. Wilcox’s report (N Engl J Med. 2017 Jan 25. doi: 10.1056/NEJMe1614726).
Bezlotoxumab must be placed in perspective, seen within the context of alternative options currently being evaluated in clinical trials.
These include recently developed drugs such as ridinilazole, surotomycin, cadazolid, RBX2660, and SER-109. Also under assessment is the oral administration of nontoxigenic C. difficile strains to compete with toxigenic strains, as well as three vaccines against the organism. Stool transplantation also is known to be highly successful in preventing recurrent C. difficile infection.
In addition, the cost-effectiveness of bezlotoxumab, especially in relation to these alternative treatments, hasn’t yet been determined.
John G. Bartlett, MD, is in the department of medicine at Johns Hopkins University, Baltimore. He reported having no relevant financial disclosures. Dr. Bartlett made these remarks in an editorial accompanying Dr. Wilcox’s report (N Engl J Med. 2017 Jan 25. doi: 10.1056/NEJMe1614726).
Bezlotoxumab must be placed in perspective, seen within the context of alternative options currently being evaluated in clinical trials.
These include recently developed drugs such as ridinilazole, surotomycin, cadazolid, RBX2660, and SER-109. Also under assessment is the oral administration of nontoxigenic C. difficile strains to compete with toxigenic strains, as well as three vaccines against the organism. Stool transplantation also is known to be highly successful in preventing recurrent C. difficile infection.
In addition, the cost-effectiveness of bezlotoxumab, especially in relation to these alternative treatments, hasn’t yet been determined.
John G. Bartlett, MD, is in the department of medicine at Johns Hopkins University, Baltimore. He reported having no relevant financial disclosures. Dr. Bartlett made these remarks in an editorial accompanying Dr. Wilcox’s report (N Engl J Med. 2017 Jan 25. doi: 10.1056/NEJMe1614726).
Adding bezlotoxumab to standard antibiotic treatment of primary or recurrent Clostridium difficile infection reduces recurrences by 38% (10 percentage points), according to a report published in the New England Journal of Medicine.
As many as 35% of patients who complete initial antibiotic treatment have at least one recurrence of C. difficile infection, and the rate of repeat recurrence rate jumps to 60% after the initial recurrence. Researchers performed two parallel international phase III trials to assess the efficacy and safety of bezlotoxumab, alone or in combination with actoxumab, for preventing such recurrences. Both monoclonal antibodies work by binding to and neutralizing C. difficile toxins; bezlotoxumab targets toxin B and actoxumab targets toxin A, said Mark H. Wilcox, MD, of the division of microbiology, Leeds (England) General Infirmary, and his associates.
The primary efficacy endpoint – the proportion of patients with recurrent C. difficile infection during 12 weeks of follow-up – was substantially lower with bezlotoxumab (17%) than with placebo (28%) in the first trial and in the second trial (16% vs. 26%). This treatment benefit was evident as early as 2 weeks after infusion and persisted throughout follow-up, the investigators said (N Engl J Med. 2017 Jan 25. doi: 10.1056/NEJMoa1602615).
The agent’s persistent effect through 12 weeks is important to note because approximately 30% of the recurrences in this study “occurred beyond the conventional 4-week assessment period for treatment efficacy. The number needed to treat to prevent one episode of recurrent C. difficile infection was 10; it was 6 among participants 65 years of age or older and those with previous C. difficile infection,” Dr. Wilcox and his associates noted.
Bezlotoxumab was consistently effective in several sensitivity analyses. It also was effective in both trials individually as well as in pooled results. And the choice of oral antibiotic appeared to have no effect on bezlotoxumab’s efficacy.
In a post hoc analysis, bezlotoxumab was also effective in the subgroup of 1,964 patients at highest risk for C. difficile recurrence because they were elderly, had compromised immunity, had the most severe infections, had a history of C. difficile infection, or carried a strain of the organism associated with particularly poor outcomes. In this subgroup, 17% of patients given bezlotoxumab and 16% of those given bezlotoxumab plus actoxumab developed recurrences, compared with 30% of those given placebo.
Regarding adverse events, the agent had “a generally favorable safety profile,” and the rates of adverse events “were generally as expected, given the underlying disease severity, baseline coexisting conditions, and ages of the participants.” Two participants discontinued the infusion because of an adverse event. Drug-related adverse events occurred in 7% of the entire study population, serious drug-related adverse events occurred in 1%, and both occurred at similar rates across the study groups.
Both trials were funded by Merck, which also was involved in study design, data analysis and interpretation, and writing the reports. Dr. Wilcox and his associates reported ties to Merck and numerous other industry sources.
Adding bezlotoxumab to standard antibiotic treatment of primary or recurrent Clostridium difficile infection reduces recurrences by 38% (10 percentage points), according to a report published in the New England Journal of Medicine.
As many as 35% of patients who complete initial antibiotic treatment have at least one recurrence of C. difficile infection, and the rate of repeat recurrence rate jumps to 60% after the initial recurrence. Researchers performed two parallel international phase III trials to assess the efficacy and safety of bezlotoxumab, alone or in combination with actoxumab, for preventing such recurrences. Both monoclonal antibodies work by binding to and neutralizing C. difficile toxins; bezlotoxumab targets toxin B and actoxumab targets toxin A, said Mark H. Wilcox, MD, of the division of microbiology, Leeds (England) General Infirmary, and his associates.
The primary efficacy endpoint – the proportion of patients with recurrent C. difficile infection during 12 weeks of follow-up – was substantially lower with bezlotoxumab (17%) than with placebo (28%) in the first trial and in the second trial (16% vs. 26%). This treatment benefit was evident as early as 2 weeks after infusion and persisted throughout follow-up, the investigators said (N Engl J Med. 2017 Jan 25. doi: 10.1056/NEJMoa1602615).
The agent’s persistent effect through 12 weeks is important to note because approximately 30% of the recurrences in this study “occurred beyond the conventional 4-week assessment period for treatment efficacy. The number needed to treat to prevent one episode of recurrent C. difficile infection was 10; it was 6 among participants 65 years of age or older and those with previous C. difficile infection,” Dr. Wilcox and his associates noted.
Bezlotoxumab was consistently effective in several sensitivity analyses. It also was effective in both trials individually as well as in pooled results. And the choice of oral antibiotic appeared to have no effect on bezlotoxumab’s efficacy.
In a post hoc analysis, bezlotoxumab was also effective in the subgroup of 1,964 patients at highest risk for C. difficile recurrence because they were elderly, had compromised immunity, had the most severe infections, had a history of C. difficile infection, or carried a strain of the organism associated with particularly poor outcomes. In this subgroup, 17% of patients given bezlotoxumab and 16% of those given bezlotoxumab plus actoxumab developed recurrences, compared with 30% of those given placebo.
Regarding adverse events, the agent had “a generally favorable safety profile,” and the rates of adverse events “were generally as expected, given the underlying disease severity, baseline coexisting conditions, and ages of the participants.” Two participants discontinued the infusion because of an adverse event. Drug-related adverse events occurred in 7% of the entire study population, serious drug-related adverse events occurred in 1%, and both occurred at similar rates across the study groups.
Both trials were funded by Merck, which also was involved in study design, data analysis and interpretation, and writing the reports. Dr. Wilcox and his associates reported ties to Merck and numerous other industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Adding bezlotoxumab to standard antibiotic treatment of primary or recurrent Clostridium difficile infection reduced recurrences by 38% (10 percentage points).
Major finding: The number needed to treat to prevent one episode of recurrent C. difficile infection was 10; it was 6 among high-risk participants who were 65 years of age or older or who had previous C. difficile infection.
Data source: Two parallel randomized double-blind placebo-controlled international trials involving 2,655 adults followed for 12 weeks.
Disclosures: Both trials were funded by Merck, which also was involved in study design, data analysis and interpretation, and writing the reports. Dr. Wilcox and his associates reported ties to Merck and numerous other industry sources.
VA MRSA Prevention Initiative reports continued health care–associated infection declines
The U.S. Department of Veterans Affairs MRSA Prevention Initiative, implemented in October 2007, has shown progress at limiting health care–associated infections of methicillin-resistant Staphylococcus aureus through 2011 and 2012.
A new report published in the January 2017 issue of the American Journal of Infection Control tracks continued declines in infection through September 2015.
Monthly rates of health care–associated infections fell significantly in all settings from October 2007 to September 2015: an 87% decrease in ICUs, 80.1% in non-ICUs, 80.9% in spinal cord injury units, and 49.4% in long-term care facilities (P for all less than .0001).
“The VA data suggest that active surveillance followed by contact precautions (with or without decolonization) may be most useful when MRSA [health care–associated infection] rates are unacceptably high (as they were in VA facilities during 2007) or to decrease infections in high-risk units such as ICUs,” Dr. Evans and his colleagues concluded.
Details about the implementation of the initiative were previously published in the New England Journal of Medicine in 2011, including the initiative’s goal to promote “a change in the institutional culture whereby infection control would become the responsibility of everyone who had contact with patients” (N Engl J Med. 2011;364:1419-30).
Dr. Evans and his colleagues had no relevant financial disclosures.
The U.S. Department of Veterans Affairs MRSA Prevention Initiative, implemented in October 2007, has shown progress at limiting health care–associated infections of methicillin-resistant Staphylococcus aureus through 2011 and 2012.
A new report published in the January 2017 issue of the American Journal of Infection Control tracks continued declines in infection through September 2015.
Monthly rates of health care–associated infections fell significantly in all settings from October 2007 to September 2015: an 87% decrease in ICUs, 80.1% in non-ICUs, 80.9% in spinal cord injury units, and 49.4% in long-term care facilities (P for all less than .0001).
“The VA data suggest that active surveillance followed by contact precautions (with or without decolonization) may be most useful when MRSA [health care–associated infection] rates are unacceptably high (as they were in VA facilities during 2007) or to decrease infections in high-risk units such as ICUs,” Dr. Evans and his colleagues concluded.
Details about the implementation of the initiative were previously published in the New England Journal of Medicine in 2011, including the initiative’s goal to promote “a change in the institutional culture whereby infection control would become the responsibility of everyone who had contact with patients” (N Engl J Med. 2011;364:1419-30).
Dr. Evans and his colleagues had no relevant financial disclosures.
The U.S. Department of Veterans Affairs MRSA Prevention Initiative, implemented in October 2007, has shown progress at limiting health care–associated infections of methicillin-resistant Staphylococcus aureus through 2011 and 2012.
A new report published in the January 2017 issue of the American Journal of Infection Control tracks continued declines in infection through September 2015.
Monthly rates of health care–associated infections fell significantly in all settings from October 2007 to September 2015: an 87% decrease in ICUs, 80.1% in non-ICUs, 80.9% in spinal cord injury units, and 49.4% in long-term care facilities (P for all less than .0001).
“The VA data suggest that active surveillance followed by contact precautions (with or without decolonization) may be most useful when MRSA [health care–associated infection] rates are unacceptably high (as they were in VA facilities during 2007) or to decrease infections in high-risk units such as ICUs,” Dr. Evans and his colleagues concluded.
Details about the implementation of the initiative were previously published in the New England Journal of Medicine in 2011, including the initiative’s goal to promote “a change in the institutional culture whereby infection control would become the responsibility of everyone who had contact with patients” (N Engl J Med. 2011;364:1419-30).
Dr. Evans and his colleagues had no relevant financial disclosures.
FROM THE AMERICAN JOURNAL OF INFECTION CONTROL
Streptococcal pneumonia’s resistance to macrolides increasing
The incidence of resistance of Streptococcus pneumoniae to the macrolide azithromycin – one of the most commonly prescribed antibiotics for treating pneumonia – was almost 50% in 2014, according to a report by Kara Keedy, PhD, executive director of microbiology at Cempra Pharmaceuticals, and her colleagues.
The researchers prospectively collected and investigated 4,567 nonreplicative community-acquired bacterial pneumonia (CABP) S. pneumoniae isolates between 2008 and 2014 in the United States, according to the report presented as a poster at IDWeek 2016. The isolates were tested for susceptibility by broth microdilution methods, according to Clinical and Laboratory Standards Institute breakpoint criteria. Macrolide resistance rates were based on azithromycin and/or clarithromycin minimal inhibitory concentrations as available, with only data on azithromycin having been collected in 2014.
The overall resistance of S. pneumoniae to azithromycin exceeded 30% in all of the nine geographical divisions of the Centers for Disease Control and Prevention (CDC), with the high-level resistance of this bacterial cause of CABP to azithromycin having been greater than 25% in eight of the CDC divisions.
The co-resistance of S. pneumoniae to azithromycin and penicillin was highest in the CDC’s East South Central division in 2014. The regions with the largest percentages of isolates with high-level macrolide resistance were the East South Central (43.2%), the West South Central (38.1%), and the Mid-Atlantic (35.0%). The regions with the largest percentages of overall macrolide resistance were the West South Central (62.9%), the East South Central (56.8%), and the South Atlantic (53.2%).
The analysis also determined that the 2014 overall rate of macrolide resistance in S. pneumoniae in the United States of 48.4% is higher than it was for any of the four earlier years examined. In 2008, 2009, 2010, and 2011, those macrolide resistance rates were 39.7%, 40.2%, 37.1%, and 44.3%, respectively.
The researchers concluded that S. pneumoniae is the most common bacterial cause of CABP and that antibiotic resistance to it is “a significant clinical challenge as highlighted by” the CDC having listed it as a threatening pathogen in the urgent category. Dr. Keedy and her associates noted that in the United States, macrolides, amoxicillin/clavulanate, and respiratory fluoroquinolones are the most frequent agents prescribed to treat almost all community-acquired respiratory infections.
“Macrolide resistance in S. pneumoniae is continuing to increase in the U.S.,” the researchers reported in the poster. “Both low- and high-level macrolide resistance have been reported to cause clinical failures and other negative outcomes including longer hospital stays and higher costs.”
The study also examined the abilities of several other drugs, including the fourth-generation macrolide solithromycin, to inhibit S. pneumoniae isolates. Solithromycin does not yet have approved Clinical and Laboratory Standards Institute breakpoints, so only minimum inhibitory concentrations (MICs) were presented.
According to the study, more than 50% of S. pneumoniae isolates were inhibited by 0.008 mcg/mL solithromycin. Additionally, solithromycin had one of the lowest MICs against S. pneumoniae of all of the drugs tested in the study. The higher end of the MICs against S. pneumoniae for solithromycin and moxifloxacin was 0.25, which was lower than the higher end of the MICs for any of the other drugs tested against S. pneumoniae isolates.
Solithromycin is the first fluoroketolide in Phase III clinical development. It “shows activity against all macrolide-resistant strains of S. pneumoniae isolates, irrespective of the location in the U.S.,” according to the poster.
The data included in the poster was extracted from a global study by JMI Laboratories. Cempra funded this study. Dr. Keedy and the other authors of the poster are employees of Cempra.
How many of us have heard that line? How many of us have done that ourselves? Did you do that today? Dr. Keedy and her colleagues report that in all geographic areas in the US, resistance to azithromycin for S pneumoniae now exceeds 30%. On average, 48.4% of S pneumoniae isolates display resistance in the US. Without antibiotic stewardship by all of us, azithromycin, along with other antibiotics, will become an expensive placebo.
How many of us have heard that line? How many of us have done that ourselves? Did you do that today? Dr. Keedy and her colleagues report that in all geographic areas in the US, resistance to azithromycin for S pneumoniae now exceeds 30%. On average, 48.4% of S pneumoniae isolates display resistance in the US. Without antibiotic stewardship by all of us, azithromycin, along with other antibiotics, will become an expensive placebo.
How many of us have heard that line? How many of us have done that ourselves? Did you do that today? Dr. Keedy and her colleagues report that in all geographic areas in the US, resistance to azithromycin for S pneumoniae now exceeds 30%. On average, 48.4% of S pneumoniae isolates display resistance in the US. Without antibiotic stewardship by all of us, azithromycin, along with other antibiotics, will become an expensive placebo.
The incidence of resistance of Streptococcus pneumoniae to the macrolide azithromycin – one of the most commonly prescribed antibiotics for treating pneumonia – was almost 50% in 2014, according to a report by Kara Keedy, PhD, executive director of microbiology at Cempra Pharmaceuticals, and her colleagues.
The researchers prospectively collected and investigated 4,567 nonreplicative community-acquired bacterial pneumonia (CABP) S. pneumoniae isolates between 2008 and 2014 in the United States, according to the report presented as a poster at IDWeek 2016. The isolates were tested for susceptibility by broth microdilution methods, according to Clinical and Laboratory Standards Institute breakpoint criteria. Macrolide resistance rates were based on azithromycin and/or clarithromycin minimal inhibitory concentrations as available, with only data on azithromycin having been collected in 2014.
The overall resistance of S. pneumoniae to azithromycin exceeded 30% in all of the nine geographical divisions of the Centers for Disease Control and Prevention (CDC), with the high-level resistance of this bacterial cause of CABP to azithromycin having been greater than 25% in eight of the CDC divisions.
The co-resistance of S. pneumoniae to azithromycin and penicillin was highest in the CDC’s East South Central division in 2014. The regions with the largest percentages of isolates with high-level macrolide resistance were the East South Central (43.2%), the West South Central (38.1%), and the Mid-Atlantic (35.0%). The regions with the largest percentages of overall macrolide resistance were the West South Central (62.9%), the East South Central (56.8%), and the South Atlantic (53.2%).
The analysis also determined that the 2014 overall rate of macrolide resistance in S. pneumoniae in the United States of 48.4% is higher than it was for any of the four earlier years examined. In 2008, 2009, 2010, and 2011, those macrolide resistance rates were 39.7%, 40.2%, 37.1%, and 44.3%, respectively.
The researchers concluded that S. pneumoniae is the most common bacterial cause of CABP and that antibiotic resistance to it is “a significant clinical challenge as highlighted by” the CDC having listed it as a threatening pathogen in the urgent category. Dr. Keedy and her associates noted that in the United States, macrolides, amoxicillin/clavulanate, and respiratory fluoroquinolones are the most frequent agents prescribed to treat almost all community-acquired respiratory infections.
“Macrolide resistance in S. pneumoniae is continuing to increase in the U.S.,” the researchers reported in the poster. “Both low- and high-level macrolide resistance have been reported to cause clinical failures and other negative outcomes including longer hospital stays and higher costs.”
The study also examined the abilities of several other drugs, including the fourth-generation macrolide solithromycin, to inhibit S. pneumoniae isolates. Solithromycin does not yet have approved Clinical and Laboratory Standards Institute breakpoints, so only minimum inhibitory concentrations (MICs) were presented.
According to the study, more than 50% of S. pneumoniae isolates were inhibited by 0.008 mcg/mL solithromycin. Additionally, solithromycin had one of the lowest MICs against S. pneumoniae of all of the drugs tested in the study. The higher end of the MICs against S. pneumoniae for solithromycin and moxifloxacin was 0.25, which was lower than the higher end of the MICs for any of the other drugs tested against S. pneumoniae isolates.
Solithromycin is the first fluoroketolide in Phase III clinical development. It “shows activity against all macrolide-resistant strains of S. pneumoniae isolates, irrespective of the location in the U.S.,” according to the poster.
The data included in the poster was extracted from a global study by JMI Laboratories. Cempra funded this study. Dr. Keedy and the other authors of the poster are employees of Cempra.
The incidence of resistance of Streptococcus pneumoniae to the macrolide azithromycin – one of the most commonly prescribed antibiotics for treating pneumonia – was almost 50% in 2014, according to a report by Kara Keedy, PhD, executive director of microbiology at Cempra Pharmaceuticals, and her colleagues.
The researchers prospectively collected and investigated 4,567 nonreplicative community-acquired bacterial pneumonia (CABP) S. pneumoniae isolates between 2008 and 2014 in the United States, according to the report presented as a poster at IDWeek 2016. The isolates were tested for susceptibility by broth microdilution methods, according to Clinical and Laboratory Standards Institute breakpoint criteria. Macrolide resistance rates were based on azithromycin and/or clarithromycin minimal inhibitory concentrations as available, with only data on azithromycin having been collected in 2014.
The overall resistance of S. pneumoniae to azithromycin exceeded 30% in all of the nine geographical divisions of the Centers for Disease Control and Prevention (CDC), with the high-level resistance of this bacterial cause of CABP to azithromycin having been greater than 25% in eight of the CDC divisions.
The co-resistance of S. pneumoniae to azithromycin and penicillin was highest in the CDC’s East South Central division in 2014. The regions with the largest percentages of isolates with high-level macrolide resistance were the East South Central (43.2%), the West South Central (38.1%), and the Mid-Atlantic (35.0%). The regions with the largest percentages of overall macrolide resistance were the West South Central (62.9%), the East South Central (56.8%), and the South Atlantic (53.2%).
The analysis also determined that the 2014 overall rate of macrolide resistance in S. pneumoniae in the United States of 48.4% is higher than it was for any of the four earlier years examined. In 2008, 2009, 2010, and 2011, those macrolide resistance rates were 39.7%, 40.2%, 37.1%, and 44.3%, respectively.
The researchers concluded that S. pneumoniae is the most common bacterial cause of CABP and that antibiotic resistance to it is “a significant clinical challenge as highlighted by” the CDC having listed it as a threatening pathogen in the urgent category. Dr. Keedy and her associates noted that in the United States, macrolides, amoxicillin/clavulanate, and respiratory fluoroquinolones are the most frequent agents prescribed to treat almost all community-acquired respiratory infections.
“Macrolide resistance in S. pneumoniae is continuing to increase in the U.S.,” the researchers reported in the poster. “Both low- and high-level macrolide resistance have been reported to cause clinical failures and other negative outcomes including longer hospital stays and higher costs.”
The study also examined the abilities of several other drugs, including the fourth-generation macrolide solithromycin, to inhibit S. pneumoniae isolates. Solithromycin does not yet have approved Clinical and Laboratory Standards Institute breakpoints, so only minimum inhibitory concentrations (MICs) were presented.
According to the study, more than 50% of S. pneumoniae isolates were inhibited by 0.008 mcg/mL solithromycin. Additionally, solithromycin had one of the lowest MICs against S. pneumoniae of all of the drugs tested in the study. The higher end of the MICs against S. pneumoniae for solithromycin and moxifloxacin was 0.25, which was lower than the higher end of the MICs for any of the other drugs tested against S. pneumoniae isolates.
Solithromycin is the first fluoroketolide in Phase III clinical development. It “shows activity against all macrolide-resistant strains of S. pneumoniae isolates, irrespective of the location in the U.S.,” according to the poster.
The data included in the poster was extracted from a global study by JMI Laboratories. Cempra funded this study. Dr. Keedy and the other authors of the poster are employees of Cempra.
FROM IDWEEK 2016
Key clinical point:
Major finding: S. pneumoniae isolates’ average resistance to the macrolide azithromycin was 48.4% in 2014.
Data source: A prospective collection and investigation of 4,567 non-replicative community-acquired bacterial pneumonia isolates.
Disclosures: The data included in the poster was extracted from a global study by JMI Laboratories. Cempra funded this study. Dr. Keedy and the other authors of the poster are employees of Cempra.
Surgical discharge data highlight stewardship need at transition
NEW ORLEANS – Most antibiotic prescriptions written at the time of patient discharge at an academic hospital were inappropriate, according to a retrospective review of 2014 discharge data.
These drugs were prescribed despite the existence of a robust inpatient antibiotic stewardship program (ASP) at the hospital, Sarah Scarpato, MD, reported at IDWeek, an annual scientific meeting on infectious diseases.
Of 9,750 prescriptions written during the study year, 86% were for oral antibiotics and 14% were for outpatient parenteral antibiotic therapy. Among a random sample of 150 patients discharged on antibiotics, 22.7% had no clinical indication of infection, 13% received an antibiotic with inappropriate spectrum of activity, 17% received an incorrect dose, 55% received an antibiotic course that was too long, and 7.3% received a course that was too short, Dr. Scarpato said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
A total of 57.7% of surgical patients and 57.6% of medical patients received an antibiotic prescription that was inappropriate.
“A whopping 70% of prescriptions had at least one error in drug choice, dose, indication, or duration,” she said.
“The most common scenarios in which an antibiotic use was not indicated were prolonged surgical prophylaxis and prolonged prophylaxis in patients who had neutropenic fever during their hospitalization but were no longer neutropenic on discharge. The most common infectious indications were consistent with previous data, with genitourinary, respiratory, and skin and soft tissue being the most common, followed by gastrointestinal,” Dr. Scarpato of the Hospital of the University of Pennsylvania, Philadelphia, said.
In addition, she noted, “100% of patients discharged from cardiothoracic surgery, ear/nose/throat surgery, oral and maxillofacial surgery, neurosurgery, and neurology had at least one error. Oncology was the medical service with the highest rate of inappropriate prescriptions at 80%. The rest, including infectious diseases, had error rates between 40% and 60%.”
Also in line with previous data, fluoroquinolones were the most commonly prescribed antibiotics, accounting for 23.5%, followed by cephalosporins, penicillins, trimethoprim-sulfamethoxazole, and metronidazole.
“Antibiotic prescription in the absence of an acceptable indication and inappropriate duration accounted for the vast majority – 76% – of inappropriate prescriptions,” Dr. Scarpato said, noting that this may be because of a failure by physicians to account for antibiotics given as an inpatient, a lack of familiarity with a patient’s course because of hand-offs, the writing of a prescription with a given duration expecting discharge on a different day, or a lack of familiarity with recommended treatment durations.
“On average, we saw an excess of 3.8 days of unnecessary antibiotics per patient,” she said. The range, however, was 18 days too few to 36 days too many. Further, readmission rates at days 7 and 30 were 6.4% and 19.4%, respectively, for patients discharged on antibiotics, compared with 3.70% and 13.79% hospital wide. The respective rates among those discharged on outpatient parenteral antibiotic therapy were 5.6% and 16.4%, compared with 6.5% and 19.9% among those on oral antibiotic therapy.
The higher rates among those on oral vs. parenteral therapy may be because patients on outpatient parenteral antibiotic therapy are followed closely by a team of infectious disease physicians and pharmacists, while those discharged on oral therapy are not routinely monitored, or it may reflect an unintended consequence of switching from parenteral to oral therapy at discharge, Dr. Scarpato said.
Transitions of care are vulnerable times for patients, she said, noting that “nearly a quarter of patients suffer an adverse event from an error in transition of care during hospital discharge, and up to half of those who suffer an adverse drug reaction at discharge are prescribed an antibiotic.”
Though limited by the retrospective and descriptive nature of the study, and the single-center design, the findings demonstrate “a significant and unmet need for antimicrobial stewardship at transition in care, even at institutions such as ours that have a substantial inpatient ASP,” Dr. Scarpato concluded.
Dr. Scarpato reported having no conflicts of interest.
NEW ORLEANS – Most antibiotic prescriptions written at the time of patient discharge at an academic hospital were inappropriate, according to a retrospective review of 2014 discharge data.
These drugs were prescribed despite the existence of a robust inpatient antibiotic stewardship program (ASP) at the hospital, Sarah Scarpato, MD, reported at IDWeek, an annual scientific meeting on infectious diseases.
Of 9,750 prescriptions written during the study year, 86% were for oral antibiotics and 14% were for outpatient parenteral antibiotic therapy. Among a random sample of 150 patients discharged on antibiotics, 22.7% had no clinical indication of infection, 13% received an antibiotic with inappropriate spectrum of activity, 17% received an incorrect dose, 55% received an antibiotic course that was too long, and 7.3% received a course that was too short, Dr. Scarpato said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
A total of 57.7% of surgical patients and 57.6% of medical patients received an antibiotic prescription that was inappropriate.
“A whopping 70% of prescriptions had at least one error in drug choice, dose, indication, or duration,” she said.
“The most common scenarios in which an antibiotic use was not indicated were prolonged surgical prophylaxis and prolonged prophylaxis in patients who had neutropenic fever during their hospitalization but were no longer neutropenic on discharge. The most common infectious indications were consistent with previous data, with genitourinary, respiratory, and skin and soft tissue being the most common, followed by gastrointestinal,” Dr. Scarpato of the Hospital of the University of Pennsylvania, Philadelphia, said.
In addition, she noted, “100% of patients discharged from cardiothoracic surgery, ear/nose/throat surgery, oral and maxillofacial surgery, neurosurgery, and neurology had at least one error. Oncology was the medical service with the highest rate of inappropriate prescriptions at 80%. The rest, including infectious diseases, had error rates between 40% and 60%.”
Also in line with previous data, fluoroquinolones were the most commonly prescribed antibiotics, accounting for 23.5%, followed by cephalosporins, penicillins, trimethoprim-sulfamethoxazole, and metronidazole.
“Antibiotic prescription in the absence of an acceptable indication and inappropriate duration accounted for the vast majority – 76% – of inappropriate prescriptions,” Dr. Scarpato said, noting that this may be because of a failure by physicians to account for antibiotics given as an inpatient, a lack of familiarity with a patient’s course because of hand-offs, the writing of a prescription with a given duration expecting discharge on a different day, or a lack of familiarity with recommended treatment durations.
“On average, we saw an excess of 3.8 days of unnecessary antibiotics per patient,” she said. The range, however, was 18 days too few to 36 days too many. Further, readmission rates at days 7 and 30 were 6.4% and 19.4%, respectively, for patients discharged on antibiotics, compared with 3.70% and 13.79% hospital wide. The respective rates among those discharged on outpatient parenteral antibiotic therapy were 5.6% and 16.4%, compared with 6.5% and 19.9% among those on oral antibiotic therapy.
The higher rates among those on oral vs. parenteral therapy may be because patients on outpatient parenteral antibiotic therapy are followed closely by a team of infectious disease physicians and pharmacists, while those discharged on oral therapy are not routinely monitored, or it may reflect an unintended consequence of switching from parenteral to oral therapy at discharge, Dr. Scarpato said.
Transitions of care are vulnerable times for patients, she said, noting that “nearly a quarter of patients suffer an adverse event from an error in transition of care during hospital discharge, and up to half of those who suffer an adverse drug reaction at discharge are prescribed an antibiotic.”
Though limited by the retrospective and descriptive nature of the study, and the single-center design, the findings demonstrate “a significant and unmet need for antimicrobial stewardship at transition in care, even at institutions such as ours that have a substantial inpatient ASP,” Dr. Scarpato concluded.
Dr. Scarpato reported having no conflicts of interest.
NEW ORLEANS – Most antibiotic prescriptions written at the time of patient discharge at an academic hospital were inappropriate, according to a retrospective review of 2014 discharge data.
These drugs were prescribed despite the existence of a robust inpatient antibiotic stewardship program (ASP) at the hospital, Sarah Scarpato, MD, reported at IDWeek, an annual scientific meeting on infectious diseases.
Of 9,750 prescriptions written during the study year, 86% were for oral antibiotics and 14% were for outpatient parenteral antibiotic therapy. Among a random sample of 150 patients discharged on antibiotics, 22.7% had no clinical indication of infection, 13% received an antibiotic with inappropriate spectrum of activity, 17% received an incorrect dose, 55% received an antibiotic course that was too long, and 7.3% received a course that was too short, Dr. Scarpato said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
A total of 57.7% of surgical patients and 57.6% of medical patients received an antibiotic prescription that was inappropriate.
“A whopping 70% of prescriptions had at least one error in drug choice, dose, indication, or duration,” she said.
“The most common scenarios in which an antibiotic use was not indicated were prolonged surgical prophylaxis and prolonged prophylaxis in patients who had neutropenic fever during their hospitalization but were no longer neutropenic on discharge. The most common infectious indications were consistent with previous data, with genitourinary, respiratory, and skin and soft tissue being the most common, followed by gastrointestinal,” Dr. Scarpato of the Hospital of the University of Pennsylvania, Philadelphia, said.
In addition, she noted, “100% of patients discharged from cardiothoracic surgery, ear/nose/throat surgery, oral and maxillofacial surgery, neurosurgery, and neurology had at least one error. Oncology was the medical service with the highest rate of inappropriate prescriptions at 80%. The rest, including infectious diseases, had error rates between 40% and 60%.”
Also in line with previous data, fluoroquinolones were the most commonly prescribed antibiotics, accounting for 23.5%, followed by cephalosporins, penicillins, trimethoprim-sulfamethoxazole, and metronidazole.
“Antibiotic prescription in the absence of an acceptable indication and inappropriate duration accounted for the vast majority – 76% – of inappropriate prescriptions,” Dr. Scarpato said, noting that this may be because of a failure by physicians to account for antibiotics given as an inpatient, a lack of familiarity with a patient’s course because of hand-offs, the writing of a prescription with a given duration expecting discharge on a different day, or a lack of familiarity with recommended treatment durations.
“On average, we saw an excess of 3.8 days of unnecessary antibiotics per patient,” she said. The range, however, was 18 days too few to 36 days too many. Further, readmission rates at days 7 and 30 were 6.4% and 19.4%, respectively, for patients discharged on antibiotics, compared with 3.70% and 13.79% hospital wide. The respective rates among those discharged on outpatient parenteral antibiotic therapy were 5.6% and 16.4%, compared with 6.5% and 19.9% among those on oral antibiotic therapy.
The higher rates among those on oral vs. parenteral therapy may be because patients on outpatient parenteral antibiotic therapy are followed closely by a team of infectious disease physicians and pharmacists, while those discharged on oral therapy are not routinely monitored, or it may reflect an unintended consequence of switching from parenteral to oral therapy at discharge, Dr. Scarpato said.
Transitions of care are vulnerable times for patients, she said, noting that “nearly a quarter of patients suffer an adverse event from an error in transition of care during hospital discharge, and up to half of those who suffer an adverse drug reaction at discharge are prescribed an antibiotic.”
Though limited by the retrospective and descriptive nature of the study, and the single-center design, the findings demonstrate “a significant and unmet need for antimicrobial stewardship at transition in care, even at institutions such as ours that have a substantial inpatient ASP,” Dr. Scarpato concluded.
Dr. Scarpato reported having no conflicts of interest.
AT IDWEEK 2016
Key clinical point:
Major finding: 70% of prescriptions had at least one error in drug choice, dose, indication, or duration.
Data source: A review of discharge data for 150 patients at an academic hospital.
Disclosures: Dr. Scarpato reported having no conflicts of interest.
When to discontinue contact precautions for patients with MRSA
Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital-acquired infection with significant morbidity and mortality. The CDC currently recommends contact precautions as a mainstay to prevent transmission of MRSA in health care settings. Most hospitals routinely screen patients for MRSA and use contact precautions for those who screen positive. The duration of these precautions vary across hospitals and no standard recommendation exists.
A recent study of members of the Society for Healthcare Epidemiology of America (SHEA) research network indicated that the majority of physicians (94%) and nurses (76%) dislike contact precautions (CP) and most (63%) were in favor of implementing CP in a different way than current practice.1 Patients also report less satisfaction and increased isolation.1
My colleagues and I recently published a study2 in the American Journal of Infection Control to explore the necessary duration of contact precautions for hospitalized patients with MRSA. Our goal was to maintain contact precautions as long as necessary to prevent undesired MRSA infections and colonization but minimize unnecessary days in contact isolation. We also sought to figure out whether patients with positive MRSA surveillance cultures should always remain in isolation and, if not, at what point they could be considered for rescreening and removal of precautions if culture negative.
Our hospital has been performing active surveillance cultures weekly to screen for MRSA among our hospitalized patients for many years; however from 2010 to 2014, we began screening patients who were previously known to be positive for MRSA colonization or infection for at least 1 year. We then assessed medical and demographic factors associated with persistent carriage of MRSA.
In our study, more than 400 patients with known MRSA were rescreened with an active surveillance culture at a subsequent hospital admission. Ultimately 20% of the patients remained MRSA positive on the active surveillance culture. Most patients who were culture positive for MRSA were found on the first active surveillance culture (16.4%) but the remaining positive cultures were found on a second active surveillance culture or a clinical culture.
The amount of time that passed since the patient was culture positive was significantly associated with a lower risk of a positive culture at screening. This continued to drop over time with only 12.5% of patients remaining active surveillance culture positive for MRSA at 5 years after the original positive culture.
Two factors were found to significantly impact the MRSA culture on the multivariate analysis: (1) Female sex reduced the risk of positivity, and (2) Presence of a foreign body increased the risk of positivity.
Most patients who remained positive for an MRSA culture were found with the first active surveillance culture, less than 4% were detected subsequently with a repeat surveillance or clinical culture and this percentage also decreased over time. This indicates that in the absence of a positive active surveillance culture it may be reasonable to discontinue contact precautions, which could result in a substantial cost savings for the hospital and improved patient and provider satisfaction without increasing the risk of MRSA transmission.
We concluded that in the absence of a foreign body and with at least a year from the last known positive culture, patients with known MRSA should be rescreened and, if negative on an active surveillance culture, should be removed from contact precautions.
Lauren Richey, MD, MPH, is assistant professor in the infectious diseases division at the Medical University of South Carolina.
References
1. Morgan DJ, Diekema DJ, Sepkowitz K, Perencevich EN. Adverse outcomes associated with contact precautions: A review of the literature. Am J Infect Control. 2009 Mar;37(2):85-93. doi: 10.1016/j.ajic.2008.04.257.
2. Richey LE, Oh Y, Tchamba DM, Engle M, Formby L, Salgado CD. When should contact precautions be discontinued for patients with Methicillin-resistant Staphylococcus aureus? Am J Infect Control. 2016 Aug 30. doi: 10.1016/j.ajic.2016.05.030.
Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital-acquired infection with significant morbidity and mortality. The CDC currently recommends contact precautions as a mainstay to prevent transmission of MRSA in health care settings. Most hospitals routinely screen patients for MRSA and use contact precautions for those who screen positive. The duration of these precautions vary across hospitals and no standard recommendation exists.
A recent study of members of the Society for Healthcare Epidemiology of America (SHEA) research network indicated that the majority of physicians (94%) and nurses (76%) dislike contact precautions (CP) and most (63%) were in favor of implementing CP in a different way than current practice.1 Patients also report less satisfaction and increased isolation.1
My colleagues and I recently published a study2 in the American Journal of Infection Control to explore the necessary duration of contact precautions for hospitalized patients with MRSA. Our goal was to maintain contact precautions as long as necessary to prevent undesired MRSA infections and colonization but minimize unnecessary days in contact isolation. We also sought to figure out whether patients with positive MRSA surveillance cultures should always remain in isolation and, if not, at what point they could be considered for rescreening and removal of precautions if culture negative.
Our hospital has been performing active surveillance cultures weekly to screen for MRSA among our hospitalized patients for many years; however from 2010 to 2014, we began screening patients who were previously known to be positive for MRSA colonization or infection for at least 1 year. We then assessed medical and demographic factors associated with persistent carriage of MRSA.
In our study, more than 400 patients with known MRSA were rescreened with an active surveillance culture at a subsequent hospital admission. Ultimately 20% of the patients remained MRSA positive on the active surveillance culture. Most patients who were culture positive for MRSA were found on the first active surveillance culture (16.4%) but the remaining positive cultures were found on a second active surveillance culture or a clinical culture.
The amount of time that passed since the patient was culture positive was significantly associated with a lower risk of a positive culture at screening. This continued to drop over time with only 12.5% of patients remaining active surveillance culture positive for MRSA at 5 years after the original positive culture.
Two factors were found to significantly impact the MRSA culture on the multivariate analysis: (1) Female sex reduced the risk of positivity, and (2) Presence of a foreign body increased the risk of positivity.
Most patients who remained positive for an MRSA culture were found with the first active surveillance culture, less than 4% were detected subsequently with a repeat surveillance or clinical culture and this percentage also decreased over time. This indicates that in the absence of a positive active surveillance culture it may be reasonable to discontinue contact precautions, which could result in a substantial cost savings for the hospital and improved patient and provider satisfaction without increasing the risk of MRSA transmission.
We concluded that in the absence of a foreign body and with at least a year from the last known positive culture, patients with known MRSA should be rescreened and, if negative on an active surveillance culture, should be removed from contact precautions.
Lauren Richey, MD, MPH, is assistant professor in the infectious diseases division at the Medical University of South Carolina.
References
1. Morgan DJ, Diekema DJ, Sepkowitz K, Perencevich EN. Adverse outcomes associated with contact precautions: A review of the literature. Am J Infect Control. 2009 Mar;37(2):85-93. doi: 10.1016/j.ajic.2008.04.257.
2. Richey LE, Oh Y, Tchamba DM, Engle M, Formby L, Salgado CD. When should contact precautions be discontinued for patients with Methicillin-resistant Staphylococcus aureus? Am J Infect Control. 2016 Aug 30. doi: 10.1016/j.ajic.2016.05.030.
Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital-acquired infection with significant morbidity and mortality. The CDC currently recommends contact precautions as a mainstay to prevent transmission of MRSA in health care settings. Most hospitals routinely screen patients for MRSA and use contact precautions for those who screen positive. The duration of these precautions vary across hospitals and no standard recommendation exists.
A recent study of members of the Society for Healthcare Epidemiology of America (SHEA) research network indicated that the majority of physicians (94%) and nurses (76%) dislike contact precautions (CP) and most (63%) were in favor of implementing CP in a different way than current practice.1 Patients also report less satisfaction and increased isolation.1
My colleagues and I recently published a study2 in the American Journal of Infection Control to explore the necessary duration of contact precautions for hospitalized patients with MRSA. Our goal was to maintain contact precautions as long as necessary to prevent undesired MRSA infections and colonization but minimize unnecessary days in contact isolation. We also sought to figure out whether patients with positive MRSA surveillance cultures should always remain in isolation and, if not, at what point they could be considered for rescreening and removal of precautions if culture negative.
Our hospital has been performing active surveillance cultures weekly to screen for MRSA among our hospitalized patients for many years; however from 2010 to 2014, we began screening patients who were previously known to be positive for MRSA colonization or infection for at least 1 year. We then assessed medical and demographic factors associated with persistent carriage of MRSA.
In our study, more than 400 patients with known MRSA were rescreened with an active surveillance culture at a subsequent hospital admission. Ultimately 20% of the patients remained MRSA positive on the active surveillance culture. Most patients who were culture positive for MRSA were found on the first active surveillance culture (16.4%) but the remaining positive cultures were found on a second active surveillance culture or a clinical culture.
The amount of time that passed since the patient was culture positive was significantly associated with a lower risk of a positive culture at screening. This continued to drop over time with only 12.5% of patients remaining active surveillance culture positive for MRSA at 5 years after the original positive culture.
Two factors were found to significantly impact the MRSA culture on the multivariate analysis: (1) Female sex reduced the risk of positivity, and (2) Presence of a foreign body increased the risk of positivity.
Most patients who remained positive for an MRSA culture were found with the first active surveillance culture, less than 4% were detected subsequently with a repeat surveillance or clinical culture and this percentage also decreased over time. This indicates that in the absence of a positive active surveillance culture it may be reasonable to discontinue contact precautions, which could result in a substantial cost savings for the hospital and improved patient and provider satisfaction without increasing the risk of MRSA transmission.
We concluded that in the absence of a foreign body and with at least a year from the last known positive culture, patients with known MRSA should be rescreened and, if negative on an active surveillance culture, should be removed from contact precautions.
Lauren Richey, MD, MPH, is assistant professor in the infectious diseases division at the Medical University of South Carolina.
References
1. Morgan DJ, Diekema DJ, Sepkowitz K, Perencevich EN. Adverse outcomes associated with contact precautions: A review of the literature. Am J Infect Control. 2009 Mar;37(2):85-93. doi: 10.1016/j.ajic.2008.04.257.
2. Richey LE, Oh Y, Tchamba DM, Engle M, Formby L, Salgado CD. When should contact precautions be discontinued for patients with Methicillin-resistant Staphylococcus aureus? Am J Infect Control. 2016 Aug 30. doi: 10.1016/j.ajic.2016.05.030.
Inpatient antibiotic use has not declined
Clinical question: How has inpatient antibiotic use changed in the United States in recent years?
Study design: Retrospective analysis.
Setting: Adult and pediatric data from 300 acute-care hospitals, 2006-2012.
Synopsis: Weighted extrapolation of data from a database was used to estimate national antibiotic use. Overall, 55.1% of discharged patients received antibiotics. The rate of antibiotic use was 755/1,000 patient-days over the study period. The small increase in antibiotic use over the years (5.6 days of therapy/1,000 patient-days increase; 95% CI, –18.9 to 30.1; P = .65) was not statistically significant. There was a significant decrease in the use of aminoglycosides, first- and second-generation cephalosporins, fluoroquinolones, sulfonamide, metronidazole, and penicillins. The use of third- and fourth-generation cephalosporins, macrolides, glycopeptides, beta-lactam/beta-lactamase inhibitor, carbapenems, and tetracyclines has increased significantly.
Limitations of the study include underrepresentation of pediatric hospitals and certain geographic regions.
Bottom line: Antibiotic-use rates have not changed during 2006-2012. However, broad-spectrum antibiotic use has increased significantly.
Citation: Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176(11):1639-1648.
Dr. Menon is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.
Clinical question: How has inpatient antibiotic use changed in the United States in recent years?
Study design: Retrospective analysis.
Setting: Adult and pediatric data from 300 acute-care hospitals, 2006-2012.
Synopsis: Weighted extrapolation of data from a database was used to estimate national antibiotic use. Overall, 55.1% of discharged patients received antibiotics. The rate of antibiotic use was 755/1,000 patient-days over the study period. The small increase in antibiotic use over the years (5.6 days of therapy/1,000 patient-days increase; 95% CI, –18.9 to 30.1; P = .65) was not statistically significant. There was a significant decrease in the use of aminoglycosides, first- and second-generation cephalosporins, fluoroquinolones, sulfonamide, metronidazole, and penicillins. The use of third- and fourth-generation cephalosporins, macrolides, glycopeptides, beta-lactam/beta-lactamase inhibitor, carbapenems, and tetracyclines has increased significantly.
Limitations of the study include underrepresentation of pediatric hospitals and certain geographic regions.
Bottom line: Antibiotic-use rates have not changed during 2006-2012. However, broad-spectrum antibiotic use has increased significantly.
Citation: Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176(11):1639-1648.
Dr. Menon is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.
Clinical question: How has inpatient antibiotic use changed in the United States in recent years?
Study design: Retrospective analysis.
Setting: Adult and pediatric data from 300 acute-care hospitals, 2006-2012.
Synopsis: Weighted extrapolation of data from a database was used to estimate national antibiotic use. Overall, 55.1% of discharged patients received antibiotics. The rate of antibiotic use was 755/1,000 patient-days over the study period. The small increase in antibiotic use over the years (5.6 days of therapy/1,000 patient-days increase; 95% CI, –18.9 to 30.1; P = .65) was not statistically significant. There was a significant decrease in the use of aminoglycosides, first- and second-generation cephalosporins, fluoroquinolones, sulfonamide, metronidazole, and penicillins. The use of third- and fourth-generation cephalosporins, macrolides, glycopeptides, beta-lactam/beta-lactamase inhibitor, carbapenems, and tetracyclines has increased significantly.
Limitations of the study include underrepresentation of pediatric hospitals and certain geographic regions.
Bottom line: Antibiotic-use rates have not changed during 2006-2012. However, broad-spectrum antibiotic use has increased significantly.
Citation: Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176(11):1639-1648.
Dr. Menon is an assistant professor at the University of Miami Miller School of Medicine and a hospitalist at University of Miami Hospital and Jackson Memorial Hospital.
Shorter-course antimicrobials do not reduce antimicrobial resistance in AOM
A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure and higher symptom scores but without any associated reduction in the rates of antimicrobial resistance or adverse events.
Alejandro Hoberman, MD, of the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center, and his coauthors report the results of a study in which 520 children aged 6-23 months were randomized to either 10 days of amoxicillin-clavulanate therapy, or 5 days of therapy followed by 5 days of placebo.
The children who received the full 10-day course also had lower mean symptom scores in the 6-14 days after initiation of therapy, compared with those who received 5 days of treatment (1.34 vs. 1.61; P = 0.07), while the number of children whose symptom scores decreased by 50% from baseline to the end of treatment was significantly lower in the 5-day group.
However, there were no significant differences between the two groups in the rate of nasopharyngeal colonization pathogens not susceptible to penicillin: 47% in the 10-day group, compared with 44% in the 5-day group (N Engl J Med. 2016 Dec 22;375[25]:2446-56).
Similarly, the rates of recurrence and adverse events were not significantly different between the two groups.
A shorter duration of treatment has been considered as a strategy for reducing the risk of antimicrobial resistance, but clinical trials so far have showed either modest difference favoring the standard duration of treatment, or no difference at all.
“The outcome differences we found were larger than the differences that have been reported previously, mainly because the rates of clinical failure among children who received reduced duration treatment were higher in our trial than in previous trials,” Dr. Hoberman and his associates wrote.
The researchers did note that clinical failure rates were higher among children with greater exposure to other children, and those with infection in both ears rather than a single ear.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.
The study of acute otitis media is challenging owing to antibiotic pharmacokinetics, age of the patients, variation in regional pathogens, polymicrobial infection, viral cofactors, antibiotic resistance, status of patients with regard to receipt of PCV7 or PCV13, and a high rate of spontaneous resolution.
The study was not designed to address outcomes in older children, children with less severe acute otitis media or with acute otitis media in one ear, or children with additional risk factors such as cleft palate or trisomy 21. In addition, there is a paucity of studies from resource-poor and low income countries.
But for now, 10 days of amoxicillin-clavulanate for children younger than 2 years of age who have a definite diagnosis of acute otitis media seems to be a reasonable option.
Margaret A. Kenna, MD, MPH, is from the department of otolaryngology and communication enhancement at the Boston Children’s Hospital. These comments are excerpted from an accompanying editorial (N Engl J Med. 2016 Dec 22;375[25]:2492-93). Dr. Kenna declared a grant from Agilis outside the submitted work.
The study of acute otitis media is challenging owing to antibiotic pharmacokinetics, age of the patients, variation in regional pathogens, polymicrobial infection, viral cofactors, antibiotic resistance, status of patients with regard to receipt of PCV7 or PCV13, and a high rate of spontaneous resolution.
The study was not designed to address outcomes in older children, children with less severe acute otitis media or with acute otitis media in one ear, or children with additional risk factors such as cleft palate or trisomy 21. In addition, there is a paucity of studies from resource-poor and low income countries.
But for now, 10 days of amoxicillin-clavulanate for children younger than 2 years of age who have a definite diagnosis of acute otitis media seems to be a reasonable option.
Margaret A. Kenna, MD, MPH, is from the department of otolaryngology and communication enhancement at the Boston Children’s Hospital. These comments are excerpted from an accompanying editorial (N Engl J Med. 2016 Dec 22;375[25]:2492-93). Dr. Kenna declared a grant from Agilis outside the submitted work.
The study of acute otitis media is challenging owing to antibiotic pharmacokinetics, age of the patients, variation in regional pathogens, polymicrobial infection, viral cofactors, antibiotic resistance, status of patients with regard to receipt of PCV7 or PCV13, and a high rate of spontaneous resolution.
The study was not designed to address outcomes in older children, children with less severe acute otitis media or with acute otitis media in one ear, or children with additional risk factors such as cleft palate or trisomy 21. In addition, there is a paucity of studies from resource-poor and low income countries.
But for now, 10 days of amoxicillin-clavulanate for children younger than 2 years of age who have a definite diagnosis of acute otitis media seems to be a reasonable option.
Margaret A. Kenna, MD, MPH, is from the department of otolaryngology and communication enhancement at the Boston Children’s Hospital. These comments are excerpted from an accompanying editorial (N Engl J Med. 2016 Dec 22;375[25]:2492-93). Dr. Kenna declared a grant from Agilis outside the submitted work.
A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure and higher symptom scores but without any associated reduction in the rates of antimicrobial resistance or adverse events.
Alejandro Hoberman, MD, of the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center, and his coauthors report the results of a study in which 520 children aged 6-23 months were randomized to either 10 days of amoxicillin-clavulanate therapy, or 5 days of therapy followed by 5 days of placebo.
The children who received the full 10-day course also had lower mean symptom scores in the 6-14 days after initiation of therapy, compared with those who received 5 days of treatment (1.34 vs. 1.61; P = 0.07), while the number of children whose symptom scores decreased by 50% from baseline to the end of treatment was significantly lower in the 5-day group.
However, there were no significant differences between the two groups in the rate of nasopharyngeal colonization pathogens not susceptible to penicillin: 47% in the 10-day group, compared with 44% in the 5-day group (N Engl J Med. 2016 Dec 22;375[25]:2446-56).
Similarly, the rates of recurrence and adverse events were not significantly different between the two groups.
A shorter duration of treatment has been considered as a strategy for reducing the risk of antimicrobial resistance, but clinical trials so far have showed either modest difference favoring the standard duration of treatment, or no difference at all.
“The outcome differences we found were larger than the differences that have been reported previously, mainly because the rates of clinical failure among children who received reduced duration treatment were higher in our trial than in previous trials,” Dr. Hoberman and his associates wrote.
The researchers did note that clinical failure rates were higher among children with greater exposure to other children, and those with infection in both ears rather than a single ear.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.
A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure and higher symptom scores but without any associated reduction in the rates of antimicrobial resistance or adverse events.
Alejandro Hoberman, MD, of the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center, and his coauthors report the results of a study in which 520 children aged 6-23 months were randomized to either 10 days of amoxicillin-clavulanate therapy, or 5 days of therapy followed by 5 days of placebo.
The children who received the full 10-day course also had lower mean symptom scores in the 6-14 days after initiation of therapy, compared with those who received 5 days of treatment (1.34 vs. 1.61; P = 0.07), while the number of children whose symptom scores decreased by 50% from baseline to the end of treatment was significantly lower in the 5-day group.
However, there were no significant differences between the two groups in the rate of nasopharyngeal colonization pathogens not susceptible to penicillin: 47% in the 10-day group, compared with 44% in the 5-day group (N Engl J Med. 2016 Dec 22;375[25]:2446-56).
Similarly, the rates of recurrence and adverse events were not significantly different between the two groups.
A shorter duration of treatment has been considered as a strategy for reducing the risk of antimicrobial resistance, but clinical trials so far have showed either modest difference favoring the standard duration of treatment, or no difference at all.
“The outcome differences we found were larger than the differences that have been reported previously, mainly because the rates of clinical failure among children who received reduced duration treatment were higher in our trial than in previous trials,” Dr. Hoberman and his associates wrote.
The researchers did note that clinical failure rates were higher among children with greater exposure to other children, and those with infection in both ears rather than a single ear.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure without a reduction in the rates of antimicrobial resistance.
Major finding: Children who received 5 days of antimicrobial experienced clinical failure rates of 35%, compared with 16% in those who received a full 10-day course.
Data source: Randomized controlled trial in 520 children aged 6-23 months with AOM.
Disclosures: The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.