Epidemiology of Resistance to Metronidazole in Clinical Isolates of Bacteroides fragilis in a New York City Hospital

Background:

Bacteroides fragilis (B. fragilis) is an important cause of clinical infection. Recently there have been increasing reports of resistance to metronidazole (MTZ), the antibiotic of choice. We reviewed the microbiologic and clinical epidemiology of B. fragilis to determine trends in resistance to MTZ at our institution.

Methods: Retrospective review of B. fragilis isolates from the NYU Langone Medical Center Clinical Microbiology Lab from 2010-2015. Sensitivity was performed by E-test using the CLSI breakpoints. MIC50, MIC90 and GM were calculated for each year and compared by ANOVA using SPSS 13.

Results:

There were 574 positive cultures of B. fragilis, of which 402 non-duplicate isolates were analyzed. The majority of cultures were from patients 50 years of age and above. 388 (96.5%) isolates were sensitive, 13 (3%) were resistant and 1 showed intermediate sensitivity to MTZ. MTZ-resistant isolates were found in all age groups. The overall distribution of MICs differed significantly by year (p<0.000). A trend towards increasing resistance and a gradual increase in MIC and GM over time was seen (Table 1).Isolates recovered from blood were more likely to be resistant to MTZ than those recovered from other sites of infection, 6.4 % vs 2 % 42% of the resistant strains were resistant to clindamycin , 92% to penicillin, 8% to amoxicillin-clavulonic acid. All strains were sensitive to carbapenems.

Table 1: Increase in MIC Range, GM, MIC₅₀, MIC₉₀ and Resistance by Year (MIC=µ/ml)

Year	Number of Isolates	Range	Geometric Mean	MIC50	MIC90	%Resistant (CLSI >16)
2010	67	0.02-256	0.55	0.5	1.5	1.5
2011	54	0.02-12	0.62	0.5	2	0
2012	60	0.09-512	0.76	0.5	2	5
2013	65	0.01-512	0.86	0.75	2	1.5
2014	75	0.09-512	1.33	1	4	6.6
2015	81	0.04-512	0.97	1	3	3.7

Conclusion: Over the last 5 years there has been a gradual increase in MIC to MTZ in B. fragilis isolates and increased frequency of high-level resistance. The rates of resistance at our institution were higher than those previously reported from Europe and North America. Further understanding of the mechanism of B. fragilis MTZ resistance and the factors that are associated with the development of MTZ resistance are critical to reversing this trend and preventing further spread of this problem, as well as providing improved antibiotic stewardship guidance.