Clinical Outcomes of Drug-resistant Shigellosis Treated With Azithromycin in Bangladesh.

Abstract

BACKGROUND:

Azithromycin is frequently used to treat shigellosis; however, clinical outcomes are uncertain.

METHODS:

We performed an observational cohort study in Bangladesh of patients with invasive diarrhea treated empirically with azithromycin. Susceptibility testing was performed by broth microdilution and disk diffusion post hoc on all Shigella isolates and clinical response was correlated with in vitro susceptibility.

RESULTS:

There were 149 Shigella culture-positive patients in the primary analysis. Infection with Shigella with decreased susceptibility to azithromycin was significantly associated with persistence of diarrhea at day 5 (31% vs 12%; relative risk [RR], 2.66; 95% confidence interval [CI], 1.34-5.28), culture positivity at day 5 or 6 (35% vs 5%; RR, 5.26; 95% CI, 1.84-14.85), and a higher rate of overnight hospitalization (58% vs 39%; RR, 1.49; 95% CI, 1.06-2.09). Shigella flexneri was more common than Shigella sonnei (58% vs 36%); however, S. sonnei constituted most of the isolates with decreased susceptibility to azithromycin (67%) and most of the multidrug-resistant strains (54%); thus, poor clinical outcomes were associated with S. sonnei. The current epidemiological cutoff for S. flexneri of ≥16 µg/mL to define decreased susceptibility to azithromycin was clinically predictive of poor outcome. Patients with S. sonnei and a low MIC (4 µg/mL) still had elevated rates of persistent diarrhea and culture positivity.

CONCLUSIONS:

This study documents worse clinical outcomes for S. flexneri with decreased susceptibility to azithromycin, as well as S. sonnei, and supports the utility of susceptibility testing and clinical breakpoints for azithromycin. S. sonnei is an emerging drug-resistant threat.

CLINICAL TRIALS REGISTRATION:

NCT03778125.

• Authors: Eric R Houpt, Tahsin Ferdous, Rifat Ara, Momena Ibrahim, Md Masud Alam, Mamun Kabir, James Platts-Mills, Tahmeed Ahmed, Abu Syed Golam Faruque, Mami Taniuchi, Rashidul Haque
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 72 Issue 10 Pg. 1793-1798 (05 18 2021) ISSN: 1537-6591 [Electronic] United States
• PMID: 32239137 (Publication Type: Journal Article, Observational Study, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• Pharmaceutical Preparations
• Azithromycin

Topics

• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Azithromycin (pharmacology, therapeutic use)
• Bangladesh (epidemiology)
• Drug Resistance, Bacterial
• Dysentery, Bacillary (drug therapy, epidemiology)
• Humans
• Microbial Sensitivity Tests
• Pharmaceutical Preparations
• Shigella
• Shigella sonnei