President Trump has reinstated and expanded the Mexico City policy prohibiting foreign nongovernmental organizations from offering counseling or referrals for abortion services if they receive funding from the U.S. government.

Mr. Trump’s executive order on Jan. 23 was not unexpected given his conservative platform on reproductive health care; however, he has taken the policy – also known as the global gag rule – further than his predecessors.

Originally instituted under President Reagan, the Mexico City Policy required overseas organizations to certify that they would not “perform or actively promote abortion as a method of family planning” using non–U.S. funds in order to receive family planning aid from the U.S. government. The policy has been rescinded and enforced periodically since 1984, based on the ideologic slant of successive U.S. administrations.

The Trump iteration of the Mexico City Policy “extends the requirements of the reinstated memorandum to global health assistance furnished by all departments and agencies,” according to the White House.

Planned Parenthood Global condemned the expanded policy, which now affects international organizations working on any U.S.–funded global health initiative, including HIV/AIDS prevention and treatment, maternal and child health, and Zika virus programs. These groups will be stripped of all U.S. aid if they also provide abortion counseling, referrals, or services for abortion, even with their own funds.

“This is an unprecedented move, and the most extreme executive action we’ve seen of its kind,” Latanya Mapp Frett, executive director, said in a statement. “The global gag rule, as it existed under previous anti–women’s health presidents, was deeply harmful. But this action will be catastrophic for all communities, especially those relying on U.S. funding to address HIV/AIDS and maternal health care, and the fight against Zika.”

The expansion of the Mexico City Policy “certainly does presage negative things for abortion and contraception” under the new administration, said Sarah W. Prager, MD, of the department of obstetrics and gynecology at the University of Washington, Seattle. “Another example is the [Jan. 24] passage in the House of Representatives of H.R. 7, which would make permanent the Hyde Amendment and deny our most disadvantaged women access to abortion.”

The American Association of Pro-Life Obstetricians and Gynecologists took a different stance. “The Mexico City Policy was instituted to prevent the U.S. from forcing taxpayers to fund abortion overseas,” said Donna J. Harrison, MD, executive director. “This policy has been intermittently in place since 1984 and represents no departure from previous policies implemented by pro-life presidents.”

AAPLOG supports reinstating this policy because elective abortion “is not a part of essential women’s health care, and, in fact, is an elective procedure,” Dr. Harrison said.

President Trump has reinstated and expanded the Mexico City policy prohibiting foreign nongovernmental organizations from offering counseling or referrals for abortion services if they receive funding from the U.S. government.

Mr. Trump’s executive order on Jan. 23 was not unexpected given his conservative platform on reproductive health care; however, he has taken the policy – also known as the global gag rule – further than his predecessors.

Originally instituted under President Reagan, the Mexico City Policy required overseas organizations to certify that they would not “perform or actively promote abortion as a method of family planning” using non–U.S. funds in order to receive family planning aid from the U.S. government. The policy has been rescinded and enforced periodically since 1984, based on the ideologic slant of successive U.S. administrations.

The Trump iteration of the Mexico City Policy “extends the requirements of the reinstated memorandum to global health assistance furnished by all departments and agencies,” according to the White House.

Planned Parenthood Global condemned the expanded policy, which now affects international organizations working on any U.S.–funded global health initiative, including HIV/AIDS prevention and treatment, maternal and child health, and Zika virus programs. These groups will be stripped of all U.S. aid if they also provide abortion counseling, referrals, or services for abortion, even with their own funds.

“This is an unprecedented move, and the most extreme executive action we’ve seen of its kind,” Latanya Mapp Frett, executive director, said in a statement. “The global gag rule, as it existed under previous anti–women’s health presidents, was deeply harmful. But this action will be catastrophic for all communities, especially those relying on U.S. funding to address HIV/AIDS and maternal health care, and the fight against Zika.”

The expansion of the Mexico City Policy “certainly does presage negative things for abortion and contraception” under the new administration, said Sarah W. Prager, MD, of the department of obstetrics and gynecology at the University of Washington, Seattle. “Another example is the [Jan. 24] passage in the House of Representatives of H.R. 7, which would make permanent the Hyde Amendment and deny our most disadvantaged women access to abortion.”

The American Association of Pro-Life Obstetricians and Gynecologists took a different stance. “The Mexico City Policy was instituted to prevent the U.S. from forcing taxpayers to fund abortion overseas,” said Donna J. Harrison, MD, executive director. “This policy has been intermittently in place since 1984 and represents no departure from previous policies implemented by pro-life presidents.”

AAPLOG supports reinstating this policy because elective abortion “is not a part of essential women’s health care, and, in fact, is an elective procedure,” Dr. Harrison said.

President Trump has reinstated and expanded the Mexico City policy prohibiting foreign nongovernmental organizations from offering counseling or referrals for abortion services if they receive funding from the U.S. government.

Mr. Trump’s executive order on Jan. 23 was not unexpected given his conservative platform on reproductive health care; however, he has taken the policy – also known as the global gag rule – further than his predecessors.

Originally instituted under President Reagan, the Mexico City Policy required overseas organizations to certify that they would not “perform or actively promote abortion as a method of family planning” using non–U.S. funds in order to receive family planning aid from the U.S. government. The policy has been rescinded and enforced periodically since 1984, based on the ideologic slant of successive U.S. administrations.

The Trump iteration of the Mexico City Policy “extends the requirements of the reinstated memorandum to global health assistance furnished by all departments and agencies,” according to the White House.

Planned Parenthood Global condemned the expanded policy, which now affects international organizations working on any U.S.–funded global health initiative, including HIV/AIDS prevention and treatment, maternal and child health, and Zika virus programs. These groups will be stripped of all U.S. aid if they also provide abortion counseling, referrals, or services for abortion, even with their own funds.

“This is an unprecedented move, and the most extreme executive action we’ve seen of its kind,” Latanya Mapp Frett, executive director, said in a statement. “The global gag rule, as it existed under previous anti–women’s health presidents, was deeply harmful. But this action will be catastrophic for all communities, especially those relying on U.S. funding to address HIV/AIDS and maternal health care, and the fight against Zika.”

The expansion of the Mexico City Policy “certainly does presage negative things for abortion and contraception” under the new administration, said Sarah W. Prager, MD, of the department of obstetrics and gynecology at the University of Washington, Seattle. “Another example is the [Jan. 24] passage in the House of Representatives of H.R. 7, which would make permanent the Hyde Amendment and deny our most disadvantaged women access to abortion.”

The American Association of Pro-Life Obstetricians and Gynecologists took a different stance. “The Mexico City Policy was instituted to prevent the U.S. from forcing taxpayers to fund abortion overseas,” said Donna J. Harrison, MD, executive director. “This policy has been intermittently in place since 1984 and represents no departure from previous policies implemented by pro-life presidents.”

AAPLOG supports reinstating this policy because elective abortion “is not a part of essential women’s health care, and, in fact, is an elective procedure,” Dr. Harrison said.

Individuals with hidradenitis suppurativa (HS) may be at significantly greater risk of inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis, according to a Danish populationwide cohort study.

“In HS patients presenting with gastrointestinal complaints, timely referral for gastroenterological evaluation of IBD [inflammatory bowel disease] may be appropriate,” Alexander Egeberg, MD, of the University of Copenhagen and his coauthors wrote.

Elsevier Inc.

Individuals with hidradenitis suppurativa (HS) may be at significantly greater risk of inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis, according to a Danish populationwide cohort study.

“In HS patients presenting with gastrointestinal complaints, timely referral for gastroenterological evaluation of IBD [inflammatory bowel disease] may be appropriate,” Alexander Egeberg, MD, of the University of Copenhagen and his coauthors wrote.

Elsevier Inc.

Individuals with hidradenitis suppurativa (HS) may be at significantly greater risk of inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis, according to a Danish populationwide cohort study.

“In HS patients presenting with gastrointestinal complaints, timely referral for gastroenterological evaluation of IBD [inflammatory bowel disease] may be appropriate,” Alexander Egeberg, MD, of the University of Copenhagen and his coauthors wrote.

Elsevier Inc.

MIAMI – Topical skin care products are evolving along with evidence in the literature supporting their efficacy; these products include serums, lotions, and cleansers with DNA repair enzymes or epidermal growth factor as active ingredients, according to Ron Moy, MD.

Importantly, some of these formulations not only show efficacy to reverse the signs of photodamage to skin and to promote rejuvenation, but may have a role in skin cancer prevention as well, said Dr. Moy, a dermatologist and facial plastic surgeon in private practice in Beverly Hills, Calif.

MIAMI – Topical skin care products are evolving along with evidence in the literature supporting their efficacy; these products include serums, lotions, and cleansers with DNA repair enzymes or epidermal growth factor as active ingredients, according to Ron Moy, MD.

Importantly, some of these formulations not only show efficacy to reverse the signs of photodamage to skin and to promote rejuvenation, but may have a role in skin cancer prevention as well, said Dr. Moy, a dermatologist and facial plastic surgeon in private practice in Beverly Hills, Calif.

MIAMI – Topical skin care products are evolving along with evidence in the literature supporting their efficacy; these products include serums, lotions, and cleansers with DNA repair enzymes or epidermal growth factor as active ingredients, according to Ron Moy, MD.

Importantly, some of these formulations not only show efficacy to reverse the signs of photodamage to skin and to promote rejuvenation, but may have a role in skin cancer prevention as well, said Dr. Moy, a dermatologist and facial plastic surgeon in private practice in Beverly Hills, Calif.

HOUSTON—Sudden unexpected death in epilepsy (SUDEP) in children is rare, but can it be avoided? The majority of pediatric SUDEP cases may occur in children with global developmental delay, early-onset epilepsy, or with seizures requiring polytherapy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

“Every death of a person with epilepsy is devastating, the death of a child even more so. If we can understand who is at higher risk of SUDEP, then our clinical and basic science researchers can work to find preventative techniques, and hopefully we can apply those techniques to patients who are most at risk,” said Elizabeth Donner, MD, Director of the Comprehensive Epilepsy Program at the Hospital for Sick Children and Associate Professor of Pediatrics at the University of Toronto.

The incidence of SUDEP in children is estimated to be 0.43 per 1,000 patient years of epilepsy, more than 10 times the rate of sudden death in children overall. Since the numbers are relatively low, it has been debatable whether doctors should discuss SUDEP with their patients. Recent studies, however, suggest that SUDEP may be more common and potentially avoidable. To determine potential risk factors for pediatric SUDEP, Dr. Donner and her colleagues developed a national, multicenter prospective population registry for SUDEP.

Researchers collected data from the Canadian Pediatric Epilepsy Network, the Canadian Pediatric Surveillance Program, and the Ontario Forensic Pathology Service. They reviewed demographics, clinical features, circumstances surrounding death, and autopsy findings.

Researchers sought to include children with epilepsy with an unexpected death between January 1, 2014, and December 31, 2015. Inclusion criteria were age 18 or younger at death; a history of two or more seizures; and death that was sudden, unexpected, and occurred during normal circumstances. Autopsies, when available, determined that there was no anatomical or toxicological cause of death. Investigators excluded deaths due to trauma and drowning and status epilepticus.

The majority of deaths occurred in children between the ages of 5 and 10, and 52% were boys. In addition, all children had seizure onset before age 5, and median age of seizure onset was about 6 months. Seven of the children had genetic abnormalities. One child was seizure-free for 12 months and was not being treated with antiepileptic medications.

The investigators identified 21 cases of definite, probable, or possible pediatric SUDEP: 10 cases of definite SUDEP, two cases of definite SUDEP plus, six cases of probable SUDEP, and three cases of possible SUDEP (ie, an autopsy was not performed). Additionally, 10 of 12 children were having tonic clonic seizures six months prior to death. Researchers also found that in 10 of 17 cases, the parents reported that their child had a recent infection. Nearly all of the deaths occurred during sleep and were unwitnessed.

“It may be worth looking at whether infection in children with epilepsy changes their risk of sudden death,” said Dr. Donner. “We really have a lot more work to do with this limited number of cases, and we are still identifying more cases and working to better understand the data.”

—Erica Tricarico

Suggested Reading

Donner EJ, Waddell B, Osland K, et al. After sudden unexpected death in epilepsy: Lessons learned and the road forward. Epilepsia. 2016;57(Suppl 1):46-53.

HOUSTON—Sudden unexpected death in epilepsy (SUDEP) in children is rare, but can it be avoided? The majority of pediatric SUDEP cases may occur in children with global developmental delay, early-onset epilepsy, or with seizures requiring polytherapy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

“Every death of a person with epilepsy is devastating, the death of a child even more so. If we can understand who is at higher risk of SUDEP, then our clinical and basic science researchers can work to find preventative techniques, and hopefully we can apply those techniques to patients who are most at risk,” said Elizabeth Donner, MD, Director of the Comprehensive Epilepsy Program at the Hospital for Sick Children and Associate Professor of Pediatrics at the University of Toronto.

The incidence of SUDEP in children is estimated to be 0.43 per 1,000 patient years of epilepsy, more than 10 times the rate of sudden death in children overall. Since the numbers are relatively low, it has been debatable whether doctors should discuss SUDEP with their patients. Recent studies, however, suggest that SUDEP may be more common and potentially avoidable. To determine potential risk factors for pediatric SUDEP, Dr. Donner and her colleagues developed a national, multicenter prospective population registry for SUDEP.

Researchers collected data from the Canadian Pediatric Epilepsy Network, the Canadian Pediatric Surveillance Program, and the Ontario Forensic Pathology Service. They reviewed demographics, clinical features, circumstances surrounding death, and autopsy findings.

Researchers sought to include children with epilepsy with an unexpected death between January 1, 2014, and December 31, 2015. Inclusion criteria were age 18 or younger at death; a history of two or more seizures; and death that was sudden, unexpected, and occurred during normal circumstances. Autopsies, when available, determined that there was no anatomical or toxicological cause of death. Investigators excluded deaths due to trauma and drowning and status epilepticus.

The majority of deaths occurred in children between the ages of 5 and 10, and 52% were boys. In addition, all children had seizure onset before age 5, and median age of seizure onset was about 6 months. Seven of the children had genetic abnormalities. One child was seizure-free for 12 months and was not being treated with antiepileptic medications.

The investigators identified 21 cases of definite, probable, or possible pediatric SUDEP: 10 cases of definite SUDEP, two cases of definite SUDEP plus, six cases of probable SUDEP, and three cases of possible SUDEP (ie, an autopsy was not performed). Additionally, 10 of 12 children were having tonic clonic seizures six months prior to death. Researchers also found that in 10 of 17 cases, the parents reported that their child had a recent infection. Nearly all of the deaths occurred during sleep and were unwitnessed.

“It may be worth looking at whether infection in children with epilepsy changes their risk of sudden death,” said Dr. Donner. “We really have a lot more work to do with this limited number of cases, and we are still identifying more cases and working to better understand the data.”

—Erica Tricarico

Suggested Reading

Donner EJ, Waddell B, Osland K, et al. After sudden unexpected death in epilepsy: Lessons learned and the road forward. Epilepsia. 2016;57(Suppl 1):46-53.

HOUSTON—Sudden unexpected death in epilepsy (SUDEP) in children is rare, but can it be avoided? The majority of pediatric SUDEP cases may occur in children with global developmental delay, early-onset epilepsy, or with seizures requiring polytherapy, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

“Every death of a person with epilepsy is devastating, the death of a child even more so. If we can understand who is at higher risk of SUDEP, then our clinical and basic science researchers can work to find preventative techniques, and hopefully we can apply those techniques to patients who are most at risk,” said Elizabeth Donner, MD, Director of the Comprehensive Epilepsy Program at the Hospital for Sick Children and Associate Professor of Pediatrics at the University of Toronto.

The incidence of SUDEP in children is estimated to be 0.43 per 1,000 patient years of epilepsy, more than 10 times the rate of sudden death in children overall. Since the numbers are relatively low, it has been debatable whether doctors should discuss SUDEP with their patients. Recent studies, however, suggest that SUDEP may be more common and potentially avoidable. To determine potential risk factors for pediatric SUDEP, Dr. Donner and her colleagues developed a national, multicenter prospective population registry for SUDEP.

Researchers collected data from the Canadian Pediatric Epilepsy Network, the Canadian Pediatric Surveillance Program, and the Ontario Forensic Pathology Service. They reviewed demographics, clinical features, circumstances surrounding death, and autopsy findings.

Researchers sought to include children with epilepsy with an unexpected death between January 1, 2014, and December 31, 2015. Inclusion criteria were age 18 or younger at death; a history of two or more seizures; and death that was sudden, unexpected, and occurred during normal circumstances. Autopsies, when available, determined that there was no anatomical or toxicological cause of death. Investigators excluded deaths due to trauma and drowning and status epilepticus.

The majority of deaths occurred in children between the ages of 5 and 10, and 52% were boys. In addition, all children had seizure onset before age 5, and median age of seizure onset was about 6 months. Seven of the children had genetic abnormalities. One child was seizure-free for 12 months and was not being treated with antiepileptic medications.

The investigators identified 21 cases of definite, probable, or possible pediatric SUDEP: 10 cases of definite SUDEP, two cases of definite SUDEP plus, six cases of probable SUDEP, and three cases of possible SUDEP (ie, an autopsy was not performed). Additionally, 10 of 12 children were having tonic clonic seizures six months prior to death. Researchers also found that in 10 of 17 cases, the parents reported that their child had a recent infection. Nearly all of the deaths occurred during sleep and were unwitnessed.

“It may be worth looking at whether infection in children with epilepsy changes their risk of sudden death,” said Dr. Donner. “We really have a lot more work to do with this limited number of cases, and we are still identifying more cases and working to better understand the data.”

—Erica Tricarico

Suggested Reading

Donner EJ, Waddell B, Osland K, et al. After sudden unexpected death in epilepsy: Lessons learned and the road forward. Epilepsia. 2016;57(Suppl 1):46-53.

Treatments designed to combat tropical infectious diseases are lacking, so the best thing travelers to these regions of the world can do is defend themselves against mosquito bites, according to Stephen K. Tyring, MD.

“We have no specific therapies for these infections,” explained Dr. Tyring of the University of Texas in Houston.

“Therefore, the best management is to avoid mosquito bites [by using] DEET, protective clothing, etc.,” he said in an interview prior to the Caribbean Dermatology Symposium.

Dr. Stephen K. Tyring, Dr. Zeena Nawas, The University of

©World Health Organization

Treatments designed to combat tropical infectious diseases are lacking, so the best thing travelers to these regions of the world can do is defend themselves against mosquito bites, according to Stephen K. Tyring, MD.

“We have no specific therapies for these infections,” explained Dr. Tyring of the University of Texas in Houston.

“Therefore, the best management is to avoid mosquito bites [by using] DEET, protective clothing, etc.,” he said in an interview prior to the Caribbean Dermatology Symposium.

Dr. Stephen K. Tyring, Dr. Zeena Nawas, The University of

©World Health Organization

Treatments designed to combat tropical infectious diseases are lacking, so the best thing travelers to these regions of the world can do is defend themselves against mosquito bites, according to Stephen K. Tyring, MD.

“We have no specific therapies for these infections,” explained Dr. Tyring of the University of Texas in Houston.

“Therefore, the best management is to avoid mosquito bites [by using] DEET, protective clothing, etc.,” he said in an interview prior to the Caribbean Dermatology Symposium.

Dr. Stephen K. Tyring, Dr. Zeena Nawas, The University of

©World Health Organization

Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Literature from a variety of patient populations reports nephrotoxicity associated with VAN, targeting troughs greater than 15 µg/mL, that occur in 5% to 43% of patients.¹ In a study of critically ill patients, acute kidney injury (AKI) was found in 21% of patients receiving VAN, with increasing duration of VAN treatment, greater VAN levels, concomitant vasoactive medication administration, and intermittent infusion methods being associated with higher odds of AKI.² A recent report from adult internal medicine patients estimated the incidence of VAN-associated nephrotoxicity at 13.6% and implicated concomitant PTZ therapy as a key factor in these patients.³

Further studies have explored the interaction between empiric beta-lactam and VAN therapy, showing mixed results. Reports of AKI associated with the combination of VAN and PTZ range from 16.3% to 34.8%,^4-8 while the cefepime-VAN combination is reported to range from 12.5% to 13.3%.^5,6 While VAN monotherapy groups were well represented, only 1 study⁷ compared the PTZ-VAN combination to a control group of PTZ monotherapy.

The primary objective of this study was to evaluate the differences in AKI incidence between patients treated with VAN and with PTZ, alone and in combination.

This is a retrospective cohort study of adult patients conducted at the University of Kentucky Chandler Medical Center (UKMC) from September 1, 2010 through August 31, 2014. Patients were included if they were at least 18 years of age on admission; remained hospitalized for at least 48 hours; received VAN combined with PTZ (VAN/PTZ), VAN alone, or PTZ alone; and had at least 48 hours of therapy (and 48 hours of overlapping therapy in the VAN/PTZ group). Patients were excluded if they had underlying diagnosis of chronic kidney disease according to the International Classification of Diseases 9 (ICD-9) code, were receiving renal replacement therapy before admission, had a diagnosis of cystic fibrosis, or were pregnant. Additionally, patients were excluded if they presented with AKI, defined as an initial creatinine clearance less than 30 mL/min, or if baseline creatinine clearance was greater than 4 times the standard deviation from the mean; serum creatinine values were not obtained during admission; and if AKI occurred prior to therapy initiation, within 48 hours of initiation, or more than 7 days after treatment was discontinued. Patients were followed throughout their stay until time of discharge.

Data Source

Patient data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust (EDT). The EDT contains clinical data from the inpatient population of UKMC from 2006 to present. Data stored and updated nightly by the EDT includes: demographics, financial classification (Medicare, Medicaid, private insurance), provider-level detail (service line), medical diagnosis (ICD-9 codes), medical procedures (Current Procedural Terminology [CPT] codes), lab tests and results, medication administration details, visit details (age, length of stay, etc), and vital signs. This study was approved by the UKMC Institutional Review Board.

Data collected for each patient included: demographic data, visit details (length of stay, admitting and primary diagnosis codes, etc.), severity of underlying illness as defined by the Charlson Comorbidity Index (CCI), all serum creatinine levels drawn per visit, medication administration information (dose, date, and time administered), all VAN trough levels, receipt of other nephrotoxic agents, blood pressures, and receipt of vasopressors.

Outcome Ascertainment

The definition of AKI was based on the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria,⁹ with risk defined as a 25% to 50% decrease in estimated glomerular filtration rate (GFR), injury as a 50% to 75% decrease in estimated GFR, and failure defined as a greater than 75% decrease in estimated GFR. Loss and end-stage classifications were not assessed because of this study’s follow-up period. The adjusted Cockcroft and Gault equation¹⁰ was used to estimate GFR due to the inconsistency of weight availability in the dataset and concordance with the institution’s practice. Baseline creatinine clearance was calculated with the first serum creatinine obtained, and the minimum creatinine clearance was calculated using the maximum serum creatinine during each patient’s visit. The percent decrease in creatinine clearance was calculated from these 2 values. AKI status was defined as meeting any of the RIFLE criteria. Mortality was assessed for all patients and defined as the composite of inhospital mortality and discharge or transfer to hospice care.

Exposure Ascertainment

Hypotension exposure was defined as experiencing 1 of the following: mean arterial blood pressure less than 60 mm Hg, a diagnosis of hypotension by a physician, or receipt of vasopressors or inotropic agents. Days of therapy for each drug were obtained and combination days of therapy were calculated by including only those days in which the patient received both medications. Total days of therapy were calculated by the sum of all days receiving at least 1 study agent. Exposure to other nephrotoxic agents (eg, acyclovir, angiotensin converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, aminoglycosides, amphotericin B, cyclosporine, foscarnet, loop diuretics, nonsteroidal anti-inflammatory drugs, sulfonamides, tacrolimus, and tenofovir) were defined as receipt of at least 1 dose of the agent during hospitalization.

Statistical Analysis

Characteristics between groups were described with basic descriptive statistics. Continuous variables were compared with 1-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Categorical variables were compared with chi-square or Fisher exact test. Yearly AKI trends were assessed with Pearson correlation coefficient. To control for differences in underlying severity of illness between groups, a subanalysis was performed in which the cohort was split into 4 groups (0, 1, 2 to 4, and ≥5 points) based on CCI. Univariate models for all covariates were created with probability of AKI as the outcome. Covariates significant after univariate were incorporated into the multivariate model, which was subsequently adjusted to achieve the highest predictive accuracy by minimizing the Akaike information criterion (AIC). Nephrotoxic agent exposures were included in the final multivariate model regardless of statistical significance in univariate analysis. Model fit was assessed with a standardized Hosmer-Lemeshow goodness-of-fit test.¹¹ All statistical analyses were completed with RStudio v 0.98 running R v 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria).¹² All tests were 2-tailed and significance was defined at an alpha of 0.05.

Of 17,879 patients initially screened, 11,650 patients were evaluated, of which 5,497 received VAN and PTZ (VAN/PTZ), 3,055 received VAN alone, and 3,098 received PTZ alone. Table 1 contains basic demographic information. The mean age of patients was 52.5 years ± 16.8 years with 6,242 (53.6%) males. Patients receiving VAN/PTZ had higher CCIs than either monotherapy group and had significantly increased length of hospitalization. While patients in the combination therapy group were more likely to experience hypotension, concomitant nephrotoxic agent exposure was more common in the VAN monotherapy group.

RIFLE-defined AKI occurred in 1,647 (14.1%) across the entire cohort. AKI occurred in 21% of VAN/PTZ patients, 8.3% of VAN patients, and 7.8% of PTZ patients (P < 0.0001). RIFLE-defined risk, injury, and failure occurred more frequently in the VAN/PTZ cohort compared to the VAN and PTZ monotherapy groups (Figure). There were no differences in AKI rates between years studied (r² = 0.4732, P = 0.2). Patients in the VAN/PTZ group experienced AKI on average of 8.0 days after treatment initiation, compared to 8.7 days and 5.2 days for VAN and PTZ monotherapy groups, respectively. The composite of inhospital mortality and transfer-to-hospice care was more common in VAN/PTZ patients (9.6%) compared to monotherapy groups (VAN, 3.9%; PTZ, 3.4%), most likely due to the increased severity of illness.

Acute kidney injury secondary to VAN therapy is a well-characterized adverse effect, while AKI incidence secondary to PTZ is less understood. Additionally, there appears to be an additive effect when these agents are used in combination. This is the largest review of AKI in patients receiving VAN,PTZ, or the combination of both agents.

There is increasing evidence suggesting greater nephrotoxicity in patients treated with the combination of VAN and antipseudomonal beta-lactams. The mechanism for the apparent increase in nephrotoxicity with this drug combination is not well understood and needs further study in both animal models and humans.

Acute kidney injury rates related to VAN vary widely, with recent studies in critically ill and internal medicine patients estimated at 21% and 13.6%, respectively.^2,3 In our VAN monotherapy cohort, the AKI rate was 8.3%, with 2.3% of patients experiencing a greater than 50% decrease in creatinine clearance. Piperacillin-tazobactam-related AKI rates are not well characterized; however, a small retrospective analysis estimated that 11.1% of PTZ patients experienced acute renal failure (defined as either increase in serum creatinine greater than 0.5 mg/dL or 50% increase from baseline).¹³ In the present study, we found the PTZ-related AKI rate to be 7.8%, which may be due to a more stringent definition of AKI. Additionally, Hellwig et al¹³ found that PTZ monotherapy was associated with higher AKI rates compared to VAN monotherapy (11.1% vs 4.9%; P = 0.014). This was not replicated in our study, with VAN and PTZ monotherapy having similar AKI rates (8.3% and 7.8%, respectively) and an adjusted aOR of 0.88 (95% CI 0.0.73-1.08) for AKI in PTZ- compared to VAN-treated patients. The estimated AKI incidence of 21% in the combination therapy group at our institution is consistent with literature that ranges from 16.3% to 34.8%.^4-8,13

To control for differences in baseline severity of illness, we performed a subgroup analysis of patients with similar CCI scores. The finding of increased AKI in patients receiving combination VAN and PTZ was consistent in each subgroup, suggesting that the increase in AKI is independent of illness severity.

This study is not without limitations. As with all retrospective studies, it is difficult to determine a causal link between VAN and PTZ combination therapy and increased AKI incidence due to confounding. We employed a rigorous study design that controlled for major confounders of AKI, such as concomitant nephrotoxic exposure, hypotension, and renal disease. Severity of illness was measured with CCI, which may not accurately capture the severity of illness at treatment initiation. Alternatives, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores, may more accurately reflect critical illness on presentation; however, this study was not focused specifically on critically ill patients. In addition to baseline comorbidity, we controlled for hypotension and dehydration as a surrogate marker for critical illness. In the subgroup analysis of patients with similar CCI, the effect of VAN/PTZ on AKI compared to VAN or PTZ monotherapy was consistent in each group. Nephrotoxic potential of agents was assumed to be equal, which is not necessarily true. Additionally, the binary representation of nephrotoxic exposure does not describe the amount of the agent received; as such, our estimations of AKI odds may be artificially elevated. Approximately one-quarter of the patients in this study were transferred from an outside hospital, for which no data regarding initial treatment are available. This may lead to exposure misclassification. We attempted to control for this factor in the regression model and found that, after controlling for other covariates, hospital transfer was associated with increasing odds of AKI. Finally, data were collected retrospectively from the electronic medical record and are subject to inaccuracies documented in the chart; however, any bias introduced should be nondifferential.

In our large retrospective study of combination empiric therapy with VAN and PTZ, we found that combination therapy was associated with more than double the odds of AKI occurring compared to either monotherapy with VAN or PTZ. Increasing duration of therapy was also associated with increases in AKI. These findings demonstrate the need for judicious use of combination therapy and strengthen the need for antimicrobial de-escalation when appropriate to avoid deleterious effects.

Acknowledgments

The authors thank Chantal Le Rutter, MPA, for copyediting services.

Disclosures

This project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant numbers UL1TR000117 and UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors report no conflicts of interest.

Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Literature from a variety of patient populations reports nephrotoxicity associated with VAN, targeting troughs greater than 15 µg/mL, that occur in 5% to 43% of patients.¹ In a study of critically ill patients, acute kidney injury (AKI) was found in 21% of patients receiving VAN, with increasing duration of VAN treatment, greater VAN levels, concomitant vasoactive medication administration, and intermittent infusion methods being associated with higher odds of AKI.² A recent report from adult internal medicine patients estimated the incidence of VAN-associated nephrotoxicity at 13.6% and implicated concomitant PTZ therapy as a key factor in these patients.³

Further studies have explored the interaction between empiric beta-lactam and VAN therapy, showing mixed results. Reports of AKI associated with the combination of VAN and PTZ range from 16.3% to 34.8%,^4-8 while the cefepime-VAN combination is reported to range from 12.5% to 13.3%.^5,6 While VAN monotherapy groups were well represented, only 1 study⁷ compared the PTZ-VAN combination to a control group of PTZ monotherapy.

The primary objective of this study was to evaluate the differences in AKI incidence between patients treated with VAN and with PTZ, alone and in combination.

This is a retrospective cohort study of adult patients conducted at the University of Kentucky Chandler Medical Center (UKMC) from September 1, 2010 through August 31, 2014. Patients were included if they were at least 18 years of age on admission; remained hospitalized for at least 48 hours; received VAN combined with PTZ (VAN/PTZ), VAN alone, or PTZ alone; and had at least 48 hours of therapy (and 48 hours of overlapping therapy in the VAN/PTZ group). Patients were excluded if they had underlying diagnosis of chronic kidney disease according to the International Classification of Diseases 9 (ICD-9) code, were receiving renal replacement therapy before admission, had a diagnosis of cystic fibrosis, or were pregnant. Additionally, patients were excluded if they presented with AKI, defined as an initial creatinine clearance less than 30 mL/min, or if baseline creatinine clearance was greater than 4 times the standard deviation from the mean; serum creatinine values were not obtained during admission; and if AKI occurred prior to therapy initiation, within 48 hours of initiation, or more than 7 days after treatment was discontinued. Patients were followed throughout their stay until time of discharge.

Data Source

Patient data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust (EDT). The EDT contains clinical data from the inpatient population of UKMC from 2006 to present. Data stored and updated nightly by the EDT includes: demographics, financial classification (Medicare, Medicaid, private insurance), provider-level detail (service line), medical diagnosis (ICD-9 codes), medical procedures (Current Procedural Terminology [CPT] codes), lab tests and results, medication administration details, visit details (age, length of stay, etc), and vital signs. This study was approved by the UKMC Institutional Review Board.

Data collected for each patient included: demographic data, visit details (length of stay, admitting and primary diagnosis codes, etc.), severity of underlying illness as defined by the Charlson Comorbidity Index (CCI), all serum creatinine levels drawn per visit, medication administration information (dose, date, and time administered), all VAN trough levels, receipt of other nephrotoxic agents, blood pressures, and receipt of vasopressors.

Outcome Ascertainment

The definition of AKI was based on the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria,⁹ with risk defined as a 25% to 50% decrease in estimated glomerular filtration rate (GFR), injury as a 50% to 75% decrease in estimated GFR, and failure defined as a greater than 75% decrease in estimated GFR. Loss and end-stage classifications were not assessed because of this study’s follow-up period. The adjusted Cockcroft and Gault equation¹⁰ was used to estimate GFR due to the inconsistency of weight availability in the dataset and concordance with the institution’s practice. Baseline creatinine clearance was calculated with the first serum creatinine obtained, and the minimum creatinine clearance was calculated using the maximum serum creatinine during each patient’s visit. The percent decrease in creatinine clearance was calculated from these 2 values. AKI status was defined as meeting any of the RIFLE criteria. Mortality was assessed for all patients and defined as the composite of inhospital mortality and discharge or transfer to hospice care.

Exposure Ascertainment

Hypotension exposure was defined as experiencing 1 of the following: mean arterial blood pressure less than 60 mm Hg, a diagnosis of hypotension by a physician, or receipt of vasopressors or inotropic agents. Days of therapy for each drug were obtained and combination days of therapy were calculated by including only those days in which the patient received both medications. Total days of therapy were calculated by the sum of all days receiving at least 1 study agent. Exposure to other nephrotoxic agents (eg, acyclovir, angiotensin converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, aminoglycosides, amphotericin B, cyclosporine, foscarnet, loop diuretics, nonsteroidal anti-inflammatory drugs, sulfonamides, tacrolimus, and tenofovir) were defined as receipt of at least 1 dose of the agent during hospitalization.

Statistical Analysis

Characteristics between groups were described with basic descriptive statistics. Continuous variables were compared with 1-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Categorical variables were compared with chi-square or Fisher exact test. Yearly AKI trends were assessed with Pearson correlation coefficient. To control for differences in underlying severity of illness between groups, a subanalysis was performed in which the cohort was split into 4 groups (0, 1, 2 to 4, and ≥5 points) based on CCI. Univariate models for all covariates were created with probability of AKI as the outcome. Covariates significant after univariate were incorporated into the multivariate model, which was subsequently adjusted to achieve the highest predictive accuracy by minimizing the Akaike information criterion (AIC). Nephrotoxic agent exposures were included in the final multivariate model regardless of statistical significance in univariate analysis. Model fit was assessed with a standardized Hosmer-Lemeshow goodness-of-fit test.¹¹ All statistical analyses were completed with RStudio v 0.98 running R v 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria).¹² All tests were 2-tailed and significance was defined at an alpha of 0.05.

Of 17,879 patients initially screened, 11,650 patients were evaluated, of which 5,497 received VAN and PTZ (VAN/PTZ), 3,055 received VAN alone, and 3,098 received PTZ alone. Table 1 contains basic demographic information. The mean age of patients was 52.5 years ± 16.8 years with 6,242 (53.6%) males. Patients receiving VAN/PTZ had higher CCIs than either monotherapy group and had significantly increased length of hospitalization. While patients in the combination therapy group were more likely to experience hypotension, concomitant nephrotoxic agent exposure was more common in the VAN monotherapy group.

RIFLE-defined AKI occurred in 1,647 (14.1%) across the entire cohort. AKI occurred in 21% of VAN/PTZ patients, 8.3% of VAN patients, and 7.8% of PTZ patients (P < 0.0001). RIFLE-defined risk, injury, and failure occurred more frequently in the VAN/PTZ cohort compared to the VAN and PTZ monotherapy groups (Figure). There were no differences in AKI rates between years studied (r² = 0.4732, P = 0.2). Patients in the VAN/PTZ group experienced AKI on average of 8.0 days after treatment initiation, compared to 8.7 days and 5.2 days for VAN and PTZ monotherapy groups, respectively. The composite of inhospital mortality and transfer-to-hospice care was more common in VAN/PTZ patients (9.6%) compared to monotherapy groups (VAN, 3.9%; PTZ, 3.4%), most likely due to the increased severity of illness.

Acute kidney injury secondary to VAN therapy is a well-characterized adverse effect, while AKI incidence secondary to PTZ is less understood. Additionally, there appears to be an additive effect when these agents are used in combination. This is the largest review of AKI in patients receiving VAN,PTZ, or the combination of both agents.

There is increasing evidence suggesting greater nephrotoxicity in patients treated with the combination of VAN and antipseudomonal beta-lactams. The mechanism for the apparent increase in nephrotoxicity with this drug combination is not well understood and needs further study in both animal models and humans.

Acute kidney injury rates related to VAN vary widely, with recent studies in critically ill and internal medicine patients estimated at 21% and 13.6%, respectively.^2,3 In our VAN monotherapy cohort, the AKI rate was 8.3%, with 2.3% of patients experiencing a greater than 50% decrease in creatinine clearance. Piperacillin-tazobactam-related AKI rates are not well characterized; however, a small retrospective analysis estimated that 11.1% of PTZ patients experienced acute renal failure (defined as either increase in serum creatinine greater than 0.5 mg/dL or 50% increase from baseline).¹³ In the present study, we found the PTZ-related AKI rate to be 7.8%, which may be due to a more stringent definition of AKI. Additionally, Hellwig et al¹³ found that PTZ monotherapy was associated with higher AKI rates compared to VAN monotherapy (11.1% vs 4.9%; P = 0.014). This was not replicated in our study, with VAN and PTZ monotherapy having similar AKI rates (8.3% and 7.8%, respectively) and an adjusted aOR of 0.88 (95% CI 0.0.73-1.08) for AKI in PTZ- compared to VAN-treated patients. The estimated AKI incidence of 21% in the combination therapy group at our institution is consistent with literature that ranges from 16.3% to 34.8%.^4-8,13

To control for differences in baseline severity of illness, we performed a subgroup analysis of patients with similar CCI scores. The finding of increased AKI in patients receiving combination VAN and PTZ was consistent in each subgroup, suggesting that the increase in AKI is independent of illness severity.

This study is not without limitations. As with all retrospective studies, it is difficult to determine a causal link between VAN and PTZ combination therapy and increased AKI incidence due to confounding. We employed a rigorous study design that controlled for major confounders of AKI, such as concomitant nephrotoxic exposure, hypotension, and renal disease. Severity of illness was measured with CCI, which may not accurately capture the severity of illness at treatment initiation. Alternatives, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores, may more accurately reflect critical illness on presentation; however, this study was not focused specifically on critically ill patients. In addition to baseline comorbidity, we controlled for hypotension and dehydration as a surrogate marker for critical illness. In the subgroup analysis of patients with similar CCI, the effect of VAN/PTZ on AKI compared to VAN or PTZ monotherapy was consistent in each group. Nephrotoxic potential of agents was assumed to be equal, which is not necessarily true. Additionally, the binary representation of nephrotoxic exposure does not describe the amount of the agent received; as such, our estimations of AKI odds may be artificially elevated. Approximately one-quarter of the patients in this study were transferred from an outside hospital, for which no data regarding initial treatment are available. This may lead to exposure misclassification. We attempted to control for this factor in the regression model and found that, after controlling for other covariates, hospital transfer was associated with increasing odds of AKI. Finally, data were collected retrospectively from the electronic medical record and are subject to inaccuracies documented in the chart; however, any bias introduced should be nondifferential.

In our large retrospective study of combination empiric therapy with VAN and PTZ, we found that combination therapy was associated with more than double the odds of AKI occurring compared to either monotherapy with VAN or PTZ. Increasing duration of therapy was also associated with increases in AKI. These findings demonstrate the need for judicious use of combination therapy and strengthen the need for antimicrobial de-escalation when appropriate to avoid deleterious effects.

Acknowledgments

The authors thank Chantal Le Rutter, MPA, for copyediting services.

Disclosures

This project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant numbers UL1TR000117 and UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors report no conflicts of interest.

Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Literature from a variety of patient populations reports nephrotoxicity associated with VAN, targeting troughs greater than 15 µg/mL, that occur in 5% to 43% of patients.¹ In a study of critically ill patients, acute kidney injury (AKI) was found in 21% of patients receiving VAN, with increasing duration of VAN treatment, greater VAN levels, concomitant vasoactive medication administration, and intermittent infusion methods being associated with higher odds of AKI.² A recent report from adult internal medicine patients estimated the incidence of VAN-associated nephrotoxicity at 13.6% and implicated concomitant PTZ therapy as a key factor in these patients.³

Further studies have explored the interaction between empiric beta-lactam and VAN therapy, showing mixed results. Reports of AKI associated with the combination of VAN and PTZ range from 16.3% to 34.8%,^4-8 while the cefepime-VAN combination is reported to range from 12.5% to 13.3%.^5,6 While VAN monotherapy groups were well represented, only 1 study⁷ compared the PTZ-VAN combination to a control group of PTZ monotherapy.

The primary objective of this study was to evaluate the differences in AKI incidence between patients treated with VAN and with PTZ, alone and in combination.

This is a retrospective cohort study of adult patients conducted at the University of Kentucky Chandler Medical Center (UKMC) from September 1, 2010 through August 31, 2014. Patients were included if they were at least 18 years of age on admission; remained hospitalized for at least 48 hours; received VAN combined with PTZ (VAN/PTZ), VAN alone, or PTZ alone; and had at least 48 hours of therapy (and 48 hours of overlapping therapy in the VAN/PTZ group). Patients were excluded if they had underlying diagnosis of chronic kidney disease according to the International Classification of Diseases 9 (ICD-9) code, were receiving renal replacement therapy before admission, had a diagnosis of cystic fibrosis, or were pregnant. Additionally, patients were excluded if they presented with AKI, defined as an initial creatinine clearance less than 30 mL/min, or if baseline creatinine clearance was greater than 4 times the standard deviation from the mean; serum creatinine values were not obtained during admission; and if AKI occurred prior to therapy initiation, within 48 hours of initiation, or more than 7 days after treatment was discontinued. Patients were followed throughout their stay until time of discharge.

Data Source

Patient data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust (EDT). The EDT contains clinical data from the inpatient population of UKMC from 2006 to present. Data stored and updated nightly by the EDT includes: demographics, financial classification (Medicare, Medicaid, private insurance), provider-level detail (service line), medical diagnosis (ICD-9 codes), medical procedures (Current Procedural Terminology [CPT] codes), lab tests and results, medication administration details, visit details (age, length of stay, etc), and vital signs. This study was approved by the UKMC Institutional Review Board.

Data collected for each patient included: demographic data, visit details (length of stay, admitting and primary diagnosis codes, etc.), severity of underlying illness as defined by the Charlson Comorbidity Index (CCI), all serum creatinine levels drawn per visit, medication administration information (dose, date, and time administered), all VAN trough levels, receipt of other nephrotoxic agents, blood pressures, and receipt of vasopressors.

Outcome Ascertainment

The definition of AKI was based on the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria,⁹ with risk defined as a 25% to 50% decrease in estimated glomerular filtration rate (GFR), injury as a 50% to 75% decrease in estimated GFR, and failure defined as a greater than 75% decrease in estimated GFR. Loss and end-stage classifications were not assessed because of this study’s follow-up period. The adjusted Cockcroft and Gault equation¹⁰ was used to estimate GFR due to the inconsistency of weight availability in the dataset and concordance with the institution’s practice. Baseline creatinine clearance was calculated with the first serum creatinine obtained, and the minimum creatinine clearance was calculated using the maximum serum creatinine during each patient’s visit. The percent decrease in creatinine clearance was calculated from these 2 values. AKI status was defined as meeting any of the RIFLE criteria. Mortality was assessed for all patients and defined as the composite of inhospital mortality and discharge or transfer to hospice care.

Exposure Ascertainment

Hypotension exposure was defined as experiencing 1 of the following: mean arterial blood pressure less than 60 mm Hg, a diagnosis of hypotension by a physician, or receipt of vasopressors or inotropic agents. Days of therapy for each drug were obtained and combination days of therapy were calculated by including only those days in which the patient received both medications. Total days of therapy were calculated by the sum of all days receiving at least 1 study agent. Exposure to other nephrotoxic agents (eg, acyclovir, angiotensin converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, aminoglycosides, amphotericin B, cyclosporine, foscarnet, loop diuretics, nonsteroidal anti-inflammatory drugs, sulfonamides, tacrolimus, and tenofovir) were defined as receipt of at least 1 dose of the agent during hospitalization.

Statistical Analysis

Characteristics between groups were described with basic descriptive statistics. Continuous variables were compared with 1-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Categorical variables were compared with chi-square or Fisher exact test. Yearly AKI trends were assessed with Pearson correlation coefficient. To control for differences in underlying severity of illness between groups, a subanalysis was performed in which the cohort was split into 4 groups (0, 1, 2 to 4, and ≥5 points) based on CCI. Univariate models for all covariates were created with probability of AKI as the outcome. Covariates significant after univariate were incorporated into the multivariate model, which was subsequently adjusted to achieve the highest predictive accuracy by minimizing the Akaike information criterion (AIC). Nephrotoxic agent exposures were included in the final multivariate model regardless of statistical significance in univariate analysis. Model fit was assessed with a standardized Hosmer-Lemeshow goodness-of-fit test.¹¹ All statistical analyses were completed with RStudio v 0.98 running R v 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria).¹² All tests were 2-tailed and significance was defined at an alpha of 0.05.

Of 17,879 patients initially screened, 11,650 patients were evaluated, of which 5,497 received VAN and PTZ (VAN/PTZ), 3,055 received VAN alone, and 3,098 received PTZ alone. Table 1 contains basic demographic information. The mean age of patients was 52.5 years ± 16.8 years with 6,242 (53.6%) males. Patients receiving VAN/PTZ had higher CCIs than either monotherapy group and had significantly increased length of hospitalization. While patients in the combination therapy group were more likely to experience hypotension, concomitant nephrotoxic agent exposure was more common in the VAN monotherapy group.

RIFLE-defined AKI occurred in 1,647 (14.1%) across the entire cohort. AKI occurred in 21% of VAN/PTZ patients, 8.3% of VAN patients, and 7.8% of PTZ patients (P < 0.0001). RIFLE-defined risk, injury, and failure occurred more frequently in the VAN/PTZ cohort compared to the VAN and PTZ monotherapy groups (Figure). There were no differences in AKI rates between years studied (r² = 0.4732, P = 0.2). Patients in the VAN/PTZ group experienced AKI on average of 8.0 days after treatment initiation, compared to 8.7 days and 5.2 days for VAN and PTZ monotherapy groups, respectively. The composite of inhospital mortality and transfer-to-hospice care was more common in VAN/PTZ patients (9.6%) compared to monotherapy groups (VAN, 3.9%; PTZ, 3.4%), most likely due to the increased severity of illness.

Acute kidney injury secondary to VAN therapy is a well-characterized adverse effect, while AKI incidence secondary to PTZ is less understood. Additionally, there appears to be an additive effect when these agents are used in combination. This is the largest review of AKI in patients receiving VAN,PTZ, or the combination of both agents.

There is increasing evidence suggesting greater nephrotoxicity in patients treated with the combination of VAN and antipseudomonal beta-lactams. The mechanism for the apparent increase in nephrotoxicity with this drug combination is not well understood and needs further study in both animal models and humans.

Acute kidney injury rates related to VAN vary widely, with recent studies in critically ill and internal medicine patients estimated at 21% and 13.6%, respectively.^2,3 In our VAN monotherapy cohort, the AKI rate was 8.3%, with 2.3% of patients experiencing a greater than 50% decrease in creatinine clearance. Piperacillin-tazobactam-related AKI rates are not well characterized; however, a small retrospective analysis estimated that 11.1% of PTZ patients experienced acute renal failure (defined as either increase in serum creatinine greater than 0.5 mg/dL or 50% increase from baseline).¹³ In the present study, we found the PTZ-related AKI rate to be 7.8%, which may be due to a more stringent definition of AKI. Additionally, Hellwig et al¹³ found that PTZ monotherapy was associated with higher AKI rates compared to VAN monotherapy (11.1% vs 4.9%; P = 0.014). This was not replicated in our study, with VAN and PTZ monotherapy having similar AKI rates (8.3% and 7.8%, respectively) and an adjusted aOR of 0.88 (95% CI 0.0.73-1.08) for AKI in PTZ- compared to VAN-treated patients. The estimated AKI incidence of 21% in the combination therapy group at our institution is consistent with literature that ranges from 16.3% to 34.8%.^4-8,13

To control for differences in baseline severity of illness, we performed a subgroup analysis of patients with similar CCI scores. The finding of increased AKI in patients receiving combination VAN and PTZ was consistent in each subgroup, suggesting that the increase in AKI is independent of illness severity.

This study is not without limitations. As with all retrospective studies, it is difficult to determine a causal link between VAN and PTZ combination therapy and increased AKI incidence due to confounding. We employed a rigorous study design that controlled for major confounders of AKI, such as concomitant nephrotoxic exposure, hypotension, and renal disease. Severity of illness was measured with CCI, which may not accurately capture the severity of illness at treatment initiation. Alternatives, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores, may more accurately reflect critical illness on presentation; however, this study was not focused specifically on critically ill patients. In addition to baseline comorbidity, we controlled for hypotension and dehydration as a surrogate marker for critical illness. In the subgroup analysis of patients with similar CCI, the effect of VAN/PTZ on AKI compared to VAN or PTZ monotherapy was consistent in each group. Nephrotoxic potential of agents was assumed to be equal, which is not necessarily true. Additionally, the binary representation of nephrotoxic exposure does not describe the amount of the agent received; as such, our estimations of AKI odds may be artificially elevated. Approximately one-quarter of the patients in this study were transferred from an outside hospital, for which no data regarding initial treatment are available. This may lead to exposure misclassification. We attempted to control for this factor in the regression model and found that, after controlling for other covariates, hospital transfer was associated with increasing odds of AKI. Finally, data were collected retrospectively from the electronic medical record and are subject to inaccuracies documented in the chart; however, any bias introduced should be nondifferential.

In our large retrospective study of combination empiric therapy with VAN and PTZ, we found that combination therapy was associated with more than double the odds of AKI occurring compared to either monotherapy with VAN or PTZ. Increasing duration of therapy was also associated with increases in AKI. These findings demonstrate the need for judicious use of combination therapy and strengthen the need for antimicrobial de-escalation when appropriate to avoid deleterious effects.

Acknowledgments

The authors thank Chantal Le Rutter, MPA, for copyediting services.

Disclosures

This project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant numbers UL1TR000117 and UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors report no conflicts of interest.

Magnetic resonance image

Researchers say they have developed new software that will analyze medical and scientific images faster and more accurately than ever before.

The team says this software, Tracking Equilibrium and Nonequilibrium shifts in Data (TREND), can analyze any series of images, including nuclear magnetic resonance images, computerized tomography scans, ultrasound images, video images, and imaging from scientific equipment of all kinds.

The researchers described the TREND software in Biophysical Journal.

The team said TREND can study sets of images to resolve and track the changes among the images.

And the software can analyze videos to plot and resolve changes as well as reconstruct videos to focus only on the individual processes and changes of interest.

“TREND allows accurate, rapid analysis of incredibly complex and nuanced images, which can potentially save doctors, patients, and scientists countless hours and money,” said Steve Van Doren, PhD, of the University of Missouri in Columbia, Missouri.

“TREND has allowed us to advance our own research into enzyme interactions considerably. Previously, it would take us weeks to analyze a single group of images. With TREND, that analysis now takes only a few minutes and is more accurate and consistent than if a human performed the work.”

Magnetic resonance image

Researchers say they have developed new software that will analyze medical and scientific images faster and more accurately than ever before.

The team says this software, Tracking Equilibrium and Nonequilibrium shifts in Data (TREND), can analyze any series of images, including nuclear magnetic resonance images, computerized tomography scans, ultrasound images, video images, and imaging from scientific equipment of all kinds.

The researchers described the TREND software in Biophysical Journal.

The team said TREND can study sets of images to resolve and track the changes among the images.

And the software can analyze videos to plot and resolve changes as well as reconstruct videos to focus only on the individual processes and changes of interest.

“TREND allows accurate, rapid analysis of incredibly complex and nuanced images, which can potentially save doctors, patients, and scientists countless hours and money,” said Steve Van Doren, PhD, of the University of Missouri in Columbia, Missouri.

“TREND has allowed us to advance our own research into enzyme interactions considerably. Previously, it would take us weeks to analyze a single group of images. With TREND, that analysis now takes only a few minutes and is more accurate and consistent than if a human performed the work.”

Magnetic resonance image

Researchers say they have developed new software that will analyze medical and scientific images faster and more accurately than ever before.

The team says this software, Tracking Equilibrium and Nonequilibrium shifts in Data (TREND), can analyze any series of images, including nuclear magnetic resonance images, computerized tomography scans, ultrasound images, video images, and imaging from scientific equipment of all kinds.

The researchers described the TREND software in Biophysical Journal.

The team said TREND can study sets of images to resolve and track the changes among the images.

And the software can analyze videos to plot and resolve changes as well as reconstruct videos to focus only on the individual processes and changes of interest.

“TREND allows accurate, rapid analysis of incredibly complex and nuanced images, which can potentially save doctors, patients, and scientists countless hours and money,” said Steve Van Doren, PhD, of the University of Missouri in Columbia, Missouri.

“TREND has allowed us to advance our own research into enzyme interactions considerably. Previously, it would take us weeks to analyze a single group of images. With TREND, that analysis now takes only a few minutes and is more accurate and consistent than if a human performed the work.”

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab), an anti-CD20 monoclonal antibody, and TGR-1202, a PI3K delta inhibitor, in the treatment of diffuse large B-cell lymphoma (DLBCL).

The combination is currently being evaluated in patients with relapsed or refractory DLBCL in the phase 2b UNITY-DLBCL trial.

Ublituximab and TGR-1202 are both products of TG Therapeutics, Inc.

Updated results from a phase 1 study of ublituximab and TGR-1202 in patients with DLBCL and other malignancies were presented at the 21st Congress of the European Hematology Association.

The data included 165 patients treated with varying doses of TGR-1202 alone (n=90) or in combination with ublituximab (n=75). The patients were heavily pretreated, with the majority having 3 or more prior lines of therapy.

There were 7 evaluable patients with DLBCL who received the combination at the phase 3 doses— ublituximab at 900 mg and TGR-1202 at 800 mg micronized.

The overall response rate for this group was 57%. Of the 4 responders, 1 patient had a complete response, and 3 had a partial response. Two patients had stable disease, and 1 progressed.

In the overall study population, the most common adverse events were diarrhea (47%), nausea (45%), fatigue (37%), vomiting (27%), and neutropenia (21%). The most common grade 3/4 adverse events were neutropenia (18%) and anemia (5%).

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to

treat, diagnose, or prevent rare diseases/disorders affecting fewer than

200,000 people in the US.

Orphan designation provides companies

with certain incentives to develop products for rare diseases. This

includes a 50% tax break on research and development, a fee waiver,

access to federal grants, and 7 years of market exclusivity if the

product is approved.

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab), an anti-CD20 monoclonal antibody, and TGR-1202, a PI3K delta inhibitor, in the treatment of diffuse large B-cell lymphoma (DLBCL).

The combination is currently being evaluated in patients with relapsed or refractory DLBCL in the phase 2b UNITY-DLBCL trial.

Ublituximab and TGR-1202 are both products of TG Therapeutics, Inc.

Updated results from a phase 1 study of ublituximab and TGR-1202 in patients with DLBCL and other malignancies were presented at the 21st Congress of the European Hematology Association.

The data included 165 patients treated with varying doses of TGR-1202 alone (n=90) or in combination with ublituximab (n=75). The patients were heavily pretreated, with the majority having 3 or more prior lines of therapy.

There were 7 evaluable patients with DLBCL who received the combination at the phase 3 doses— ublituximab at 900 mg and TGR-1202 at 800 mg micronized.

The overall response rate for this group was 57%. Of the 4 responders, 1 patient had a complete response, and 3 had a partial response. Two patients had stable disease, and 1 progressed.

In the overall study population, the most common adverse events were diarrhea (47%), nausea (45%), fatigue (37%), vomiting (27%), and neutropenia (21%). The most common grade 3/4 adverse events were neutropenia (18%) and anemia (5%).

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to

treat, diagnose, or prevent rare diseases/disorders affecting fewer than

200,000 people in the US.

Orphan designation provides companies

with certain incentives to develop products for rare diseases. This

includes a 50% tax break on research and development, a fee waiver,

access to federal grants, and 7 years of market exclusivity if the

product is approved.

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab), an anti-CD20 monoclonal antibody, and TGR-1202, a PI3K delta inhibitor, in the treatment of diffuse large B-cell lymphoma (DLBCL).

The combination is currently being evaluated in patients with relapsed or refractory DLBCL in the phase 2b UNITY-DLBCL trial.

Ublituximab and TGR-1202 are both products of TG Therapeutics, Inc.

Updated results from a phase 1 study of ublituximab and TGR-1202 in patients with DLBCL and other malignancies were presented at the 21st Congress of the European Hematology Association.

The data included 165 patients treated with varying doses of TGR-1202 alone (n=90) or in combination with ublituximab (n=75). The patients were heavily pretreated, with the majority having 3 or more prior lines of therapy.

There were 7 evaluable patients with DLBCL who received the combination at the phase 3 doses— ublituximab at 900 mg and TGR-1202 at 800 mg micronized.

The overall response rate for this group was 57%. Of the 4 responders, 1 patient had a complete response, and 3 had a partial response. Two patients had stable disease, and 1 progressed.

In the overall study population, the most common adverse events were diarrhea (47%), nausea (45%), fatigue (37%), vomiting (27%), and neutropenia (21%). The most common grade 3/4 adverse events were neutropenia (18%) and anemia (5%).

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to

treat, diagnose, or prevent rare diseases/disorders affecting fewer than

200,000 people in the US.

Orphan designation provides companies

with certain incentives to develop products for rare diseases. This

includes a 50% tax break on research and development, a fee waiver,

access to federal grants, and 7 years of market exclusivity if the

product is approved.

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

A study published in The BMJ suggests that higher levels of psychological distress (anxiety and depression) may be associated with an increased risk of death from leukemia and other cancers.

The findings are observational, so no firm conclusions about cause and effect can be drawn.

However, the researchers said the findings add to the growing evidence that psychological distress could have some predictive capacity for certain physical conditions.

There is some evidence that psychological distress (anxiety and depression) is related to increased rates of cardiovascular disease, but links with different types of cancer are either unclear or untested.

So David Batty, PhD, of University College London in the UK, and his colleagues set out to examine if psychological distress is a potential predictor of site-specific cancer mortality.

The researchers analyzed data from 16 studies (13 from England and 3 from Scotland), which started between 1994 and 2008. The data included 163,363 men and women age 16 or over who were free from cancer at the start of the study.

Psychological distress scores were measured using the general health questionnaire (GHQ-12), and participants were monitored for an average of 9.5 years. During this time, there were 4353 deaths from cancer.

Several factors that could have influenced the results were taken into account, including age, sex, education, socioeconomic status, body mass index, smoking, and alcohol intake.

“After statistical control for these factors, the results show that, compared with people in the least distressed group, death rates in the most distressed group were consistently higher for cancer of the bowel, prostate, pancreas, and esophagus and for leukemia,” Dr Batty said.

He and his colleagues pointed out that this association may also be affected by reverse causality, where undiagnosed (early) cancer might have had an underlying impact on mood.

In a bid to correct for this, the team conducted a further analysis excluding study participants who died in the first 5 years of follow-up, but this made no difference to the findings. The links between distress and cancer remained.

Specifically, compared to people in the least distressed group (GHQ-12 score 0-6), death rates in the most distressed group (score 7-12) were consistently increased for cancer of all sites combined, with a multivariable adjusted hazard ratio (HR) of 1.32.

Death rates were also increased for colorectal (HR=1.84), prostate (HR=2.42), pancreatic (HR=2.76), and esophageal cancers (HR=2.59), as well as for leukemia (HR=3.86).

“Our findings contribute to the evidence that poor mental health might have some predictive capacity for certain physical diseases,” Dr Batty said, “but we are a long way off from knowing if these relationships are truly causal.”

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

A study published in The BMJ suggests that higher levels of psychological distress (anxiety and depression) may be associated with an increased risk of death from leukemia and other cancers.

The findings are observational, so no firm conclusions about cause and effect can be drawn.

However, the researchers said the findings add to the growing evidence that psychological distress could have some predictive capacity for certain physical conditions.

There is some evidence that psychological distress (anxiety and depression) is related to increased rates of cardiovascular disease, but links with different types of cancer are either unclear or untested.

So David Batty, PhD, of University College London in the UK, and his colleagues set out to examine if psychological distress is a potential predictor of site-specific cancer mortality.

The researchers analyzed data from 16 studies (13 from England and 3 from Scotland), which started between 1994 and 2008. The data included 163,363 men and women age 16 or over who were free from cancer at the start of the study.

Psychological distress scores were measured using the general health questionnaire (GHQ-12), and participants were monitored for an average of 9.5 years. During this time, there were 4353 deaths from cancer.

Several factors that could have influenced the results were taken into account, including age, sex, education, socioeconomic status, body mass index, smoking, and alcohol intake.

“After statistical control for these factors, the results show that, compared with people in the least distressed group, death rates in the most distressed group were consistently higher for cancer of the bowel, prostate, pancreas, and esophagus and for leukemia,” Dr Batty said.

He and his colleagues pointed out that this association may also be affected by reverse causality, where undiagnosed (early) cancer might have had an underlying impact on mood.

In a bid to correct for this, the team conducted a further analysis excluding study participants who died in the first 5 years of follow-up, but this made no difference to the findings. The links between distress and cancer remained.

Specifically, compared to people in the least distressed group (GHQ-12 score 0-6), death rates in the most distressed group (score 7-12) were consistently increased for cancer of all sites combined, with a multivariable adjusted hazard ratio (HR) of 1.32.

Death rates were also increased for colorectal (HR=1.84), prostate (HR=2.42), pancreatic (HR=2.76), and esophageal cancers (HR=2.59), as well as for leukemia (HR=3.86).

“Our findings contribute to the evidence that poor mental health might have some predictive capacity for certain physical diseases,” Dr Batty said, “but we are a long way off from knowing if these relationships are truly causal.”

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

A study published in The BMJ suggests that higher levels of psychological distress (anxiety and depression) may be associated with an increased risk of death from leukemia and other cancers.

The findings are observational, so no firm conclusions about cause and effect can be drawn.

However, the researchers said the findings add to the growing evidence that psychological distress could have some predictive capacity for certain physical conditions.

There is some evidence that psychological distress (anxiety and depression) is related to increased rates of cardiovascular disease, but links with different types of cancer are either unclear or untested.

So David Batty, PhD, of University College London in the UK, and his colleagues set out to examine if psychological distress is a potential predictor of site-specific cancer mortality.

The researchers analyzed data from 16 studies (13 from England and 3 from Scotland), which started between 1994 and 2008. The data included 163,363 men and women age 16 or over who were free from cancer at the start of the study.

Psychological distress scores were measured using the general health questionnaire (GHQ-12), and participants were monitored for an average of 9.5 years. During this time, there were 4353 deaths from cancer.

Several factors that could have influenced the results were taken into account, including age, sex, education, socioeconomic status, body mass index, smoking, and alcohol intake.

“After statistical control for these factors, the results show that, compared with people in the least distressed group, death rates in the most distressed group were consistently higher for cancer of the bowel, prostate, pancreas, and esophagus and for leukemia,” Dr Batty said.

He and his colleagues pointed out that this association may also be affected by reverse causality, where undiagnosed (early) cancer might have had an underlying impact on mood.

In a bid to correct for this, the team conducted a further analysis excluding study participants who died in the first 5 years of follow-up, but this made no difference to the findings. The links between distress and cancer remained.

Specifically, compared to people in the least distressed group (GHQ-12 score 0-6), death rates in the most distressed group (score 7-12) were consistently increased for cancer of all sites combined, with a multivariable adjusted hazard ratio (HR) of 1.32.

Death rates were also increased for colorectal (HR=1.84), prostate (HR=2.42), pancreatic (HR=2.76), and esophageal cancers (HR=2.59), as well as for leukemia (HR=3.86).

“Our findings contribute to the evidence that poor mental health might have some predictive capacity for certain physical diseases,” Dr Batty said, “but we are a long way off from knowing if these relationships are truly causal.”

MIAMI – Clinicians have many options to treat and help people manage hidradenitis suppurativa, but for most patients, an early and accurate diagnosis remains elusive.

“The problem here is because it has so many mimickers, the diagnosis is often delayed, patients can be [treated for an incorrect diagnosis] and in many ways that treatment can be harmful,” said Adam Friedman, MD, of the George Washington University in Washington. Missed or ignored diagnoses can lead to more pain, impaired function, and wasted time and money.

“There are – no question – gaps in clinical care. Patients seek care outside of dermatology and go to urgent care centers, emergency rooms, [and other settings]. That’s why it’s not only important for us to recognize this, but to teach everyone else as well,” Dr. Friedman said at the Orlando Dermatology Aesthetic and Clinical Conference.

Elsevier Inc.

Tips for early detection

Look for chronicity in the disease’s presentation, Dr. Friedman said. “Chronicity is key, but the morphology will change, and lesions will look different over time.” Therefore, “the clinical presentation can be challenging, depending on when you catch the patient.”

Hidradenitis suppurativa is characterized by very purulent, indurated, abscesslike structures often on the underarms and groin. Ask patients where and how often they see lesions. Lesions in certain locations can be very disabling for patients not only because of pain, but also from a psychosocial impact. The groin and chest are prime examples. Also, there is a genetic predisposition so it is important to ask patients about family history as well.

Use combination therapy to hit disease ‘from all angles’

It is imperative to treat patients even when they present at a time of mild disease, Dr. Friedman said. “This is a chronic, snowballing disease that will get worse over time, because inflammation begets inflammation. Even if it’s mild disease, you still want to treat. Combinations are king, and we dermatologists are the synergy masters.”

Effective treatment strategies include medications that curtail inflammation and block hormonal influences; dietary changes (a minimal-dairy, low-carbohydrate diet helps some patients, for example); environmental changes and/or eliminating the invasive proliferative gelatinous mass (IPGM). “This is not step therapy,” Dr. Friedman emphasized. “You want to hit all these angles at once.”

In terms of nutritional support, “I usually put my patients on a combination of zinc and vitamin C, both anti-inflammatories, but also good for wound healing,” Dr. Friedman said. “I also get them on board with V-8, which can be a tough sell sometimes.” He recommends patients drink three small cans per week, adding that he has no financial disclosure related to the vegetable juice.

Patient education, smoking cessation, and keeping affected areas dry and cool are other important management strategies. Instruct patients that stress, friction, and obesity can each worsen the condition “I think obesity is an independent risk factor here, like it is in psoriasis, where obesity alone has been shown to increase the risk of psoriasis later on,” he said.

Ease the inflammation

Hidradenitis suppurativa is a disease of “inappropriate inflammation,” Dr. Friedman said, which explains why anti-inflammatory agents remain the mainstay of treatment. These include antibiotics, classic corticosteroids, and biologics, which all can have a role in therapy. He highlighted the potential role of the cutaneous microbiota and possible dysbiosis associated with disease activity. “I also use a lot chlorhexidine washes to wipe the microbial slate clean in high-risk areas; just be careful to avoid the face.”

Intralesional Kenalog (triamcinolone acetonide), in particular, is useful for its rapid results. “This is such a great and easy trick, and it really works quickly,” Dr. Friedman said. He added that a recent case series provides evidence for its efficacy as well (J Amer Acad Dermatol. 2016 Dec;75:1151-5).

Three take-home treatment pointers

Dr. Friedman shared these three take-aways for treatment of hidradenitis suppurativa with antibiotics:

• The combination of oral clindamycin 300 mg twice daily and oral rifampin 300 mg twice daily carries the most evidence for efficacy and safety, with no evidence of resistance.
• Rifampin also acts against Clostridium difficile infections, which decreases the risk of associated colitis.
• Do not give a tetracycline antibiotic as monotherapy.

In terms of retinoids, “I’ve been pretty disappointed. I find them effective [in other conditions], but for hidradenitis suppurativa, I’m just not impressed, unfortunately,” Dr. Friedman said. “Antihormonal therapies such as oral contraceptives and spironolactone for women and finasteride for men have been a useful adjuncts in my practice, with evidence supporting their use in the literature, he added. Biologics are among the new treatment options, but there are cost and insurance coverage issues, Dr. Friedman said. There are small case series evaluating biologics such as infliximab, which are very supportive – and he himself has had good responses – although the Food and Drug Administration indication has been the hurdle.

One exception is the recent FDA approval of adalimumab (Humira) for hidradenitis suppurativa. “Make sure you realize that the dosing is different, more like a ‘whopping’ Crohn’s disease dose. This is a very important medication in our armamentarium – the issue is when you start it,” Dr. Friedman said. He also cautioned, “if a patient has sinus tracts and scarring, it’s not going to be enough. You still need to address that. Adalimumab is only going to get rid of the inflammation. This is why early diagnosis is so important!”

When it comes to surgery, “my philosophy is it’s all or none. If you’re going to do surgery, do surgery. You better cut these things out. Do a wide global excision,” Dr. Friedman emphasized.

Dr. Friedman is a member of the Dermatology News editorial advisory board.

Dr. Friedman had no relevant financial disclosures.

MIAMI – Clinicians have many options to treat and help people manage hidradenitis suppurativa, but for most patients, an early and accurate diagnosis remains elusive.

“The problem here is because it has so many mimickers, the diagnosis is often delayed, patients can be [treated for an incorrect diagnosis] and in many ways that treatment can be harmful,” said Adam Friedman, MD, of the George Washington University in Washington. Missed or ignored diagnoses can lead to more pain, impaired function, and wasted time and money.

“There are – no question – gaps in clinical care. Patients seek care outside of dermatology and go to urgent care centers, emergency rooms, [and other settings]. That’s why it’s not only important for us to recognize this, but to teach everyone else as well,” Dr. Friedman said at the Orlando Dermatology Aesthetic and Clinical Conference.

Elsevier Inc.

Tips for early detection

Look for chronicity in the disease’s presentation, Dr. Friedman said. “Chronicity is key, but the morphology will change, and lesions will look different over time.” Therefore, “the clinical presentation can be challenging, depending on when you catch the patient.”

Hidradenitis suppurativa is characterized by very purulent, indurated, abscesslike structures often on the underarms and groin. Ask patients where and how often they see lesions. Lesions in certain locations can be very disabling for patients not only because of pain, but also from a psychosocial impact. The groin and chest are prime examples. Also, there is a genetic predisposition so it is important to ask patients about family history as well.

Use combination therapy to hit disease ‘from all angles’

It is imperative to treat patients even when they present at a time of mild disease, Dr. Friedman said. “This is a chronic, snowballing disease that will get worse over time, because inflammation begets inflammation. Even if it’s mild disease, you still want to treat. Combinations are king, and we dermatologists are the synergy masters.”

Effective treatment strategies include medications that curtail inflammation and block hormonal influences; dietary changes (a minimal-dairy, low-carbohydrate diet helps some patients, for example); environmental changes and/or eliminating the invasive proliferative gelatinous mass (IPGM). “This is not step therapy,” Dr. Friedman emphasized. “You want to hit all these angles at once.”

In terms of nutritional support, “I usually put my patients on a combination of zinc and vitamin C, both anti-inflammatories, but also good for wound healing,” Dr. Friedman said. “I also get them on board with V-8, which can be a tough sell sometimes.” He recommends patients drink three small cans per week, adding that he has no financial disclosure related to the vegetable juice.

Patient education, smoking cessation, and keeping affected areas dry and cool are other important management strategies. Instruct patients that stress, friction, and obesity can each worsen the condition “I think obesity is an independent risk factor here, like it is in psoriasis, where obesity alone has been shown to increase the risk of psoriasis later on,” he said.

Ease the inflammation

Hidradenitis suppurativa is a disease of “inappropriate inflammation,” Dr. Friedman said, which explains why anti-inflammatory agents remain the mainstay of treatment. These include antibiotics, classic corticosteroids, and biologics, which all can have a role in therapy. He highlighted the potential role of the cutaneous microbiota and possible dysbiosis associated with disease activity. “I also use a lot chlorhexidine washes to wipe the microbial slate clean in high-risk areas; just be careful to avoid the face.”

Intralesional Kenalog (triamcinolone acetonide), in particular, is useful for its rapid results. “This is such a great and easy trick, and it really works quickly,” Dr. Friedman said. He added that a recent case series provides evidence for its efficacy as well (J Amer Acad Dermatol. 2016 Dec;75:1151-5).

Three take-home treatment pointers

Dr. Friedman shared these three take-aways for treatment of hidradenitis suppurativa with antibiotics:

• The combination of oral clindamycin 300 mg twice daily and oral rifampin 300 mg twice daily carries the most evidence for efficacy and safety, with no evidence of resistance.
• Rifampin also acts against Clostridium difficile infections, which decreases the risk of associated colitis.
• Do not give a tetracycline antibiotic as monotherapy.

In terms of retinoids, “I’ve been pretty disappointed. I find them effective [in other conditions], but for hidradenitis suppurativa, I’m just not impressed, unfortunately,” Dr. Friedman said. “Antihormonal therapies such as oral contraceptives and spironolactone for women and finasteride for men have been a useful adjuncts in my practice, with evidence supporting their use in the literature, he added. Biologics are among the new treatment options, but there are cost and insurance coverage issues, Dr. Friedman said. There are small case series evaluating biologics such as infliximab, which are very supportive – and he himself has had good responses – although the Food and Drug Administration indication has been the hurdle.

One exception is the recent FDA approval of adalimumab (Humira) for hidradenitis suppurativa. “Make sure you realize that the dosing is different, more like a ‘whopping’ Crohn’s disease dose. This is a very important medication in our armamentarium – the issue is when you start it,” Dr. Friedman said. He also cautioned, “if a patient has sinus tracts and scarring, it’s not going to be enough. You still need to address that. Adalimumab is only going to get rid of the inflammation. This is why early diagnosis is so important!”

When it comes to surgery, “my philosophy is it’s all or none. If you’re going to do surgery, do surgery. You better cut these things out. Do a wide global excision,” Dr. Friedman emphasized.

Dr. Friedman is a member of the Dermatology News editorial advisory board.

Dr. Friedman had no relevant financial disclosures.

MIAMI – Clinicians have many options to treat and help people manage hidradenitis suppurativa, but for most patients, an early and accurate diagnosis remains elusive.

“The problem here is because it has so many mimickers, the diagnosis is often delayed, patients can be [treated for an incorrect diagnosis] and in many ways that treatment can be harmful,” said Adam Friedman, MD, of the George Washington University in Washington. Missed or ignored diagnoses can lead to more pain, impaired function, and wasted time and money.

“There are – no question – gaps in clinical care. Patients seek care outside of dermatology and go to urgent care centers, emergency rooms, [and other settings]. That’s why it’s not only important for us to recognize this, but to teach everyone else as well,” Dr. Friedman said at the Orlando Dermatology Aesthetic and Clinical Conference.

Elsevier Inc.

Tips for early detection

Look for chronicity in the disease’s presentation, Dr. Friedman said. “Chronicity is key, but the morphology will change, and lesions will look different over time.” Therefore, “the clinical presentation can be challenging, depending on when you catch the patient.”

Hidradenitis suppurativa is characterized by very purulent, indurated, abscesslike structures often on the underarms and groin. Ask patients where and how often they see lesions. Lesions in certain locations can be very disabling for patients not only because of pain, but also from a psychosocial impact. The groin and chest are prime examples. Also, there is a genetic predisposition so it is important to ask patients about family history as well.

Use combination therapy to hit disease ‘from all angles’

It is imperative to treat patients even when they present at a time of mild disease, Dr. Friedman said. “This is a chronic, snowballing disease that will get worse over time, because inflammation begets inflammation. Even if it’s mild disease, you still want to treat. Combinations are king, and we dermatologists are the synergy masters.”

Effective treatment strategies include medications that curtail inflammation and block hormonal influences; dietary changes (a minimal-dairy, low-carbohydrate diet helps some patients, for example); environmental changes and/or eliminating the invasive proliferative gelatinous mass (IPGM). “This is not step therapy,” Dr. Friedman emphasized. “You want to hit all these angles at once.”

In terms of nutritional support, “I usually put my patients on a combination of zinc and vitamin C, both anti-inflammatories, but also good for wound healing,” Dr. Friedman said. “I also get them on board with V-8, which can be a tough sell sometimes.” He recommends patients drink three small cans per week, adding that he has no financial disclosure related to the vegetable juice.

Patient education, smoking cessation, and keeping affected areas dry and cool are other important management strategies. Instruct patients that stress, friction, and obesity can each worsen the condition “I think obesity is an independent risk factor here, like it is in psoriasis, where obesity alone has been shown to increase the risk of psoriasis later on,” he said.

Ease the inflammation

Hidradenitis suppurativa is a disease of “inappropriate inflammation,” Dr. Friedman said, which explains why anti-inflammatory agents remain the mainstay of treatment. These include antibiotics, classic corticosteroids, and biologics, which all can have a role in therapy. He highlighted the potential role of the cutaneous microbiota and possible dysbiosis associated with disease activity. “I also use a lot chlorhexidine washes to wipe the microbial slate clean in high-risk areas; just be careful to avoid the face.”

Intralesional Kenalog (triamcinolone acetonide), in particular, is useful for its rapid results. “This is such a great and easy trick, and it really works quickly,” Dr. Friedman said. He added that a recent case series provides evidence for its efficacy as well (J Amer Acad Dermatol. 2016 Dec;75:1151-5).

Three take-home treatment pointers

Dr. Friedman shared these three take-aways for treatment of hidradenitis suppurativa with antibiotics:

• The combination of oral clindamycin 300 mg twice daily and oral rifampin 300 mg twice daily carries the most evidence for efficacy and safety, with no evidence of resistance.
• Rifampin also acts against Clostridium difficile infections, which decreases the risk of associated colitis.
• Do not give a tetracycline antibiotic as monotherapy.

In terms of retinoids, “I’ve been pretty disappointed. I find them effective [in other conditions], but for hidradenitis suppurativa, I’m just not impressed, unfortunately,” Dr. Friedman said. “Antihormonal therapies such as oral contraceptives and spironolactone for women and finasteride for men have been a useful adjuncts in my practice, with evidence supporting their use in the literature, he added. Biologics are among the new treatment options, but there are cost and insurance coverage issues, Dr. Friedman said. There are small case series evaluating biologics such as infliximab, which are very supportive – and he himself has had good responses – although the Food and Drug Administration indication has been the hurdle.

One exception is the recent FDA approval of adalimumab (Humira) for hidradenitis suppurativa. “Make sure you realize that the dosing is different, more like a ‘whopping’ Crohn’s disease dose. This is a very important medication in our armamentarium – the issue is when you start it,” Dr. Friedman said. He also cautioned, “if a patient has sinus tracts and scarring, it’s not going to be enough. You still need to address that. Adalimumab is only going to get rid of the inflammation. This is why early diagnosis is so important!”

When it comes to surgery, “my philosophy is it’s all or none. If you’re going to do surgery, do surgery. You better cut these things out. Do a wide global excision,” Dr. Friedman emphasized.

Dr. Friedman is a member of the Dermatology News editorial advisory board.

Dr. Friedman had no relevant financial disclosures.