Clinical Microbiology Newsletter
Resistance Trends in Antimicrobial Susceptibility of Anaerobic Bacteria, Part I

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Abstract

Despite the suggestions of both the Clinical and Laboratory Standards Institute (CLSI) and the American Society for Microbiology (ASM) Manual of Clinical Microbiology that hospitals should test individual patient isolates to assist in their care, periodically establish patterns of resistance for certain anaerobes, and include these data in the hospital antibiogram, anaerobic susceptibility studies are performed in only a minority of clinical laboratories and their patterns of susceptibility are obtainable mostly from published surveys conducted by a small number of research centers scattered worldwide. The Bacteroides fragilis group species, the most frequently studied anaerobes, have been reported to vary in their frequencies of resistance to all antimicrobial agents worldwide. Limited data exist about the resistance patterns of other genera and species. Part I of this two-part article reviews the methods used for anaerobic susceptibility testing and the correlation of in vitro susceptibility test results with clinical data and antimicrobial resistance that has been reported for gram-negative and gram-positive anaerobes. Part II of this article will review mechanisms of resistance among anaerobes to commonly used antimicrobial agents.

Introduction

While anaerobic bacteria are important pathogens in a variety of clinical infections, many clinical laboratories are either unable or unwilling to culture anaerobes except from very specific sites; even fewer laboratories perform antimicrobial susceptibility testing (AST) (1). Consequently, the patterns of anaerobes' susceptibility and resistance remain virtually inaccessible to laboratorians and clinicians, except for those published surveys conducted by a small cadre of research centers scattered worldwide or contained in individual case reports. Resistance trends in anaerobes are therefore biased and sometimes anecdotal.

Both the Clinical and Laboratory Standards Institute (CLSI) (2) and the American Society for Microbiology's Manual of Clinical Microbiology (3) suggest that hospitals test individual patient isolates to assist in their care, periodically establish patterns of resistance for certain anaerobes, and include these data in the hospital antibiogram. AST data from at least 10 members of the Bacteroides fragilis group, Prevotella spp., Fusobacterium spp., and Clostridium spp. should be included. Because B. fragilis is a more common pathogen, more isolates, up to 30 for each species, should be included in the antibiogram. The antimicrobial agents tested should be those available on the hospital's formulary to help clinicians in their selection of empirical therapy. CLSI provides recommendations for testing of various antibiotics based upon the partial identification of the anaerobic isolate. Susceptibility testing on individual isolates from specific patients should be performed to assist patient care when (i) selecting an active agent is critical for disease management; (ii) the patient is likely to receive long-term therapy; (iii) isolates are recovered from the blood, brain, bone, or joint; (iv) therapy fails; or (v) organisms are known to have unpredictable susceptibility patterns.

Of note is the variation of breakpoints that may occur for selected antimicrobial agents between the U.S. Food and Drug Administration (FDA), CLSI, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). In addition, breakpoint changes have recently been proposed for carbapenems, cephalosporins, and β-lactam–β-lactamase inhibitor combinations for Enterobacteriaceae, which may ultimately impact breakpoints for anaerobes, as well.

Section snippets

Susceptibility Testing Methods and Quality Control for Anaerobes

CLSI has designated the agar dilution procedure using supplemented Brucella agar as the reference method (2). This method is not simple, practical, or economical to perform, but it allows different laboratories to compare MIC results (4). Susceptibility testing methods include the following.

Clinical Correlations with AST Results

Most information about resistance in anaerobic bacteria emanates from a plethora of in vitro studies that compare MICs of a variety of agents and sometimes correlate them with the accepted clinical breakpoints. Heseltine et al. (8) analyzed the effects of several antimicrobial agents on the clinical outcomes of patients with appendicitis and found that patients who received an agent active in vitro against anaerobes had a better outcome than those who did not.

In the late 1980s, two studies

Antimicrobial Resistance Among Anaerobes

Resistance among some anaerobes has increased significantly over the last few decades. Table 1 summarizes resistance trends from various sources at several institutions. Members of the B. fragilis group have developed resistance worldwide to all classes of antimicrobials (13, 14, 15, 16). The Tufts-New England Medical Center has coordinated ongoing in vitro surveillance studies that have reported significant increases in resistance among the B. fragilis group strains since the 1980s (17, 18).

Bacteroides fragilis Group

The B. fragilis group currently consists of 23 species, with B. fragilis generally being the most susceptible to antimicrobials, although greater than 95% are resistant to penicillin, principally due to β-lactamase production. Snydman et al. (18) reported on a survey of 5,223 B. fragilis group isolates from 10 geographically distributed U.S. medical centers and analyzed trends from 1997 to 2004 using the reference agar dilution method. The distribution of species isolated was as follows: B.

Non-spore forming gram-positive bacilli

The Eubacterium group, Actinomyces, Propionibacterium, and Bifidobacterium are usually susceptible to β-lactam agents, including the penicillins, cephalosporins, carbapenems, and β-lactam– β-lactamase inhibitor combinations. Lactobacillus spp. show species variations, resulting in widely variably susceptibility patterns to cephalosporins and other agents; penicillin and ampicillin are often active (34). Although there are no breakpoints for vancomycin and anaerobes, this agent has very good in

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    Editor's Note: Part II of this article will appear in the January 15, 2011 issue of CMN (Volume 33, No. 2).

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