Chemical Genomics, Structure Elucidation, and in Vivo Studies of the Marine-Derived Anticlostridial Ecteinamycin.

A polyether antibiotic, ecteinamycin (1), was isolated from a marine Actinomadura sp., cultivated from the ascidian Ecteinascidia turbinata. 13C enrichment, high resolution NMR spectroscopy, and molecular modeling enabled elucidation of the structure of 1, which was validated on the basis of comparisons with its recently reported crystal structure. Importantly, ecteinamycin demonstrated potent activity against the toxigenic strain of Clostridium difficile NAP1/B1/027 (MIC = 59 ng/µL), as well as other toxigenic and nontoxigenic C. difficile isolates both in vitro and in vivo. Additionally, chemical genomics studies using Escherichia coli barcoded deletion mutants led to the identification of sensitive mutants such as trkA and kdpD involved in potassium cation transport and homeostasis supporting a mechanistic proposal that ecteinamycin acts as an ionophore antibiotic. This is the first antibacterial agent whose mechanism of action has been studied using E. coli chemical genomics. On the basis of these data, we propose ecteinamycin as an ionophore antibiotic that causes C. difficile detoxification and cell death via potassium transport dysregulation.

Serratia marcescens Bacteremia: Nosocomial Cluster Following Narcotic Diversion.

OBJECTIVE To describe the investigation and control of a cluster of Serratia marcescens bacteremia in a 505-bed tertiary-care center. METHODS Cluster cases were defined as all patients with S. marcescens bacteremia between March 2 and April 7, 2014, who were found to have identical or related blood isolates determined by molecular typing with pulsed-field gel electrophoresis. Cases were compared using bivariate analysis with controls admitted at the same time and to the same service as the cases, in a 4:1 ratio. RESULTS In total, 6 patients developed S. marcescens bacteremia within 48 hours after admission within the above period. Of these, 5 patients had identical Serratia isolates determined by molecular typing, and were included in a case-control study. Exposure to the post-anesthesia care unit was a risk factor identified in bivariate analysis. Evidence of tampered opioid-containing syringes on several hospital units was discovered soon after the initial cluster case presented, and a full narcotic diversion investigation was conducted. A nurse working in the post-anesthesia care unit was identified as the employee responsible for the drug diversion and was epidemiologically linked to all 5 patients in the cluster. No further cases were identified once the implicated employee's job was terminated. CONCLUSION Illicit drug use by healthcare workers remains an important mechanism for the development of bloodstream infections in hospitalized patients. Active mechanisms and systems should remain in place to prevent, detect, and control narcotic drug diversions and associated patient harm in the healthcare setting. Infect Control Hosp Epidemiol 2017;38:1027-1031.

Macrolide and Clindamycin Resistance in Group a Streptococci Isolated From Children With Pharyngitis.

Group A streptococcus (GAS) is responsible for 15%-30% of cases of acute pharyngitis in children. Macrolides such as azithromycin have become popular for treating GAS pharyngitis. We report macrolide resistance rates in a primary care setting in our geographic area over the past 5 years and discuss the implications of resistance in making treatment decisions. Throat swabs were collected from children with pharyngitis from May 2011 to May 2015 in a primary care setting in Madison, Wisconsin. Susceptibility testing was performed for erythromycin and clindamycin using the Kirby-Bauer disk diffusion method. GAS was identified on 143 throat cultures. Overall, 15% of GAS isolates demonstrated nonsusceptibility for both clindamycin and erythromycin. Inducible resistance (positive D-test) was detected in 17 isolates (12%). The rate of detection of nonsusceptibility in each year of the study did not change over time. Azithromycin should only be used for patients with pharyngitis and substantial manifestations of penicillin hypersensitivity and when used, susceptibility testing should always be performed.