IGNITE4 : Results of a phase 3, randomized, multicenter, prospective trial of eravacycline vs meropenem in the treatment of complicated intraabdominal infections

Funding Information: Financial support. This work was supported by Tetraphase Pharmaceuticals Inc. Funding Information: Potential conflicts of interest. J. S. S. has received support from Tetraphase Pharmaceuticals Inc. during the production of this manuscript and has served as a consultant to Merck, Pfizer, GlaxoSmithKline, and Melinta outside of the submitted work. A. S received support from Tetraphase Pharmaceuticals Inc. during the production of this manuscript. J. G. received research funding from Tetraphase Pharmaceuticals Inc. for his role as principal investigator of this study. K. L. and L. T. are employed by Tetraphase Pharmaceuticals Inc. D. E. reports grants from Tetraphase Pharmaceuticals Inc. during the conduct of the study and grants from Merck outside of the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Publisher Copyright: © 2018 The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.Background: Increasing antimicrobial resistance among pathogens that cause complicated intraabdominal infections (cIAIs) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae. Methods: IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg every 12 hours or meropenem 1 g every 8 hours intravenously for 4-14 days. The primary objective was to demonstrate statistical noninferiority (NI) in clinical cure rates at the test-of-cure visit (25-31 days from start of therapy) in the microbiological intent-to-treat population using a NI margin of 12.5%. Microbiological outcomes and safety were also evaluated. Results: Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference, -0.5%; 95% confidence interval [CI], -6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified ITT population (231/250 [92.4%] vs 228/249 [91.6%]; difference, 0.8; 95% CI, -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference, 0.8; 95% CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline had relatively low rates of adverse events for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively. Conclusions: Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens. Clinical Trials Registration: NCT01844856.publishersversionPeer reviewe

Methodology and Background for the World Health Organization Global Guidelines on the Prevention of Surgical Site Infection

Surgical site infections remain an important topic of concern for surgeons in all specialties and are currently the focus of global health agencies for prevention. Because patients have numerous co-morbidities that increase the risks of surgical site infections, and because of the emergence of more resistant pathogens, it is necessary to revise and update guidelines to assist surgeons in the prevention of these infections. This article will summarize the most recent WHO Global Guidelines for the prevention of Surgical Site Infection that will have applicability for surgeons in all countries

Prospective Cohort Study on Timing of Antimicrobial Prophylaxis for Post-Cesarean Surgical Site Infections

Background: Sepsis is the leading cause of maternal death in sub-Saharan Africa (SSA), a region that sees some of the highest rates of maternal death and morbidity in the world. As one of the most commonly performed surgical procedures in SSA and a proved risk factor for surgical site infection (SSI), cesarean section (CS) is an important operation to target because of its massive impact on maternal and neonatal health. There is currently insufficient published data available on the patient and facility-based context around SSI after CS to establish a true and clear understanding of this infectious category. The objective of this study was to collect accurate and valid data on the incidence of SSI after CS and the circumstances around SSI in two Kenyan hospitals. Hypothesis: Our primary analysis focused on the consequences of timing of peri-operative antimicrobial prophylaxis. We hypothesized that patients who were given antibiotics pre-operatively would show lower SSI rates than those given the agents post-operatively. Methods: This was an Institutional Review Board-approved observational study of 609 women who had CS operations at two Kenyan hospitals from September to December 2015. Thika provided antimicrobial prophylaxis prior to incision for all patients, and Kiambu provided only post-operative prophylaxis. It should be noted that this difference was the result of a previous intervention at Thika and not a part of this observational study. Results: Patients at the two hospitals had similar pre-operative characteristics indicating a relatively healthy population. The median age was 26 ± 6 years (range 18–43) at Thika and 26 ± 5 (18–44) at Kiambu. Median parity was 1 ± 1 (range 0–7) at Thika and 1 ± 1 (0–10). Patients also went through a comparable number of antenatal care visits (median 4 ± 1 at both hospitals). The number of patients with prolonged rupture of the membranes was 103 (34.4%) at Thika and 99 (32.9%) at Kiambu. There was a slightly higher number of patients with meconium-stained liquor at Kiambu Hospital (115) than at Thika (74). The SSI rate was 4.0% (12/299; 11 superficial, 1 deep) at Thika and 9.3% (28/301; 18 superficial, 7 deep, 3 organ/space) at Kiambu. Conclusions: The data show a striking difference between SSI rates in patients who were given properly timed pre-operative antibiotics and patients who were given only post-operative antibiotics. Administration of post-operative antibiotics is currently the norm in much of SSA, and there is strong evidence that many of the infectious problems encountered in this population would be reduced by the provision of antibiotic prophylaxis prior to the incision