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Study highlights burden of community-onset antimicrobial resistance in India

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March 16, 2017

A large prospective study of adults and children hospitalized with acute febrile illness in India revealed a high incidence of community-onset multidrug-resistant infections, which were associated with prior antibiotic use and increased risk for mortality.

Vidya Mave, MD, MPH, of Byramjee-Jeejeebhoy Government Medical College in India and Johns Hopkins University School of Medicine, and colleagues reported that India is among the countries with the greatest burden of bacterial disease in the world. However, there are limited data on antimicrobial resistance in inpatient and community settings in the country, where antimicrobial use is common and has substantially increased over the past 2 decades, according to the researchers.

“Understanding [antimicrobial resistance] in India may serve several purposes, including generating evidence to support advocacy for the regulation of currently unregulated antibiotic prescription; to develop evidence-based treatment guidelines; to guide policy for antibiotic stewardship programs, which are presently nonexistent in most settings; and to emphasize the need for universal, standardized infection control guidelines,” Mave and colleagues wrote in The Journal of Infectious Diseases.

The researchers conducted a prospective study of individuals hospitalized with acute febrile illnesses at Byramjee-Jeejeebhoy Government Medical College and Sassoon General Hospitals between July 2013 and December 2015 to describe the burden, risk factors and outcomes of community-onset bacterial infections. The analysis included 842 adults and adolescents (media age, 20 years) and 682 children at least 6 months of age (median age, 2 years).

Overall, 133 community-onset isolates were collected from 115 patients. Among them, 77% were gram-negative and primarily composed of Enterobacteriaceae (predominately Escherichia coli), Klebsiella, Acientobacter and Pseudomonas species. Half of the isolates had multidrug-resistant (MDR) organisms, and 38% of gram-negative isolates were resistant to carbapenems.

Further analyses showed that four gram-negative isolates were resistant to all antibiotics tested, and two isolates were resistant to colistin. In addition, 75% of Enterobacteriaceae isolates were resistant to third generation cephalosporins.

“As third-generation cephalosporins are currently commonly used as empiric antibiotics for suspected serious bacterial infections, these findings have major implications for empiric antimicrobial choice in inpatient settings,” Mave and colleagues wrote.

A multivariable logistic regression model adjusted for age, gender and working with animals showed that antibiotic use 1 month before admission was associated with an increased risk for having a MDR organism (adjusted odds ratio [aOR] = 4.17; 95% CI, 1.19-19.7). When assessing patient outcomes, the researchers found that mortality was more common in patients with MDR gram-negative isolates than those with drug-sensitive gram-negative isolates (23% vs. 6%; OR = 4.5; 95% CI, 0.9-12.6). After adjusting for age, gender and diagnosis, MDR gram-negative isolation was independently associated with mortality (aOR = 6.1; 95% CI, 1.2-55.7).

“Our findings support the urgent need to regulate antimicrobial use in the community as well as in health care settings so that existing antimicrobials may be preserved to combat serious bacterial infections,” Mave and colleagues concluded. “Future studies should assess the burden of bacterial infections and drug resistance patterns in outpatient settings to inform the choice of empiric antibiotics; risk factors associated with acquisition or emergence of resistance; long-term morbidity and mortality; [and] quality of life associated with drug-sensitive and drug-resistant organisms and [their] risk factors.” – by Stephanie Viguers

Disclosure: The researchers report no relevant financial disclosures.

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PERSPECTIVE
James Hughes
James M. Hughes

The prospective study by Mave and colleagues highlights the burden of antimicrobial resistance in community-onset acute bacterial infections in adults and children older than 6 months admitted for acute febrile illness to two hospitals in Pune, India between July 2013 and December 2015. The study demonstrated an association between infection with multidrug-resistant (MDR) organisms and prolonged length of stay and increased mortality as well as receipt of one or more antibiotics in the community during the previous month. Gram-negative MDR infections were more common than gram-positive MDR infections; E. coli followed by Acinetobacter species were the most common MDR organisms isolated. Among patients with community-onset MDR infections, 27 (38%) of organisms tested were carbapenem-resistant. Of 18 Acinetobacter species tested, 6 (33%) were carbapenem resistant and two were colistin-resistant.  

The results highlight the need for surveillance and antimicrobial stewardship in outpatient settings and raise questions about the impact of over-the-counter access to antimicrobials and the potential role of animal and environmental sources for MDR organisms in community settings, a reminder of the importance of a One Health approach. The results also support the recently released WHO prioritization of MDR pathogens causing acute bacterial infections. In light of these findings, the recently released Indian Council for Medical Research Guidelines for Antimicrobial Use in Common Syndromes (http://www.icmr.nic.in/guidelines/treatment%20guidelines%20for%20antimicrobial.pdf ) are very timely.


James M. Hughes, MD
Professor of Medicine (Infectious Diseases) and Public Health (Global Health)
Co-Director, Emory Antibiotic Resistance Center
Emory University School of Medicine and Rollins School of Public Health
Infectious Disease News Editorial Board member
Disclosure: Hughes is a past president of the Infectious Diseases Society of America, a vice chair of the National Academy of Medicine Forum on Microbial Threats, and a co-chair of the American Society for Microbiology Steering Committee for the Coalition on Antimicrobial Resistance. He serves on the boards of the One Health Commission and the EcoHealth Alliance.