These enzymes can be exoenzymes, inducible or constitutive, and genetically, they can be of either chromosomal or plasmid origin (101). The dried panels are stable at room temperature for 1 to 2 years. Although not all cfiA-positive B. fragilis strains are resistant to carbapenems, they all have the possibility of becoming resistant to this group of antibiotics by acquisition of an appropriate insertion sequence (IS) element for full expression of the cfiA gene, leading to possible treatment failure. Macrolides are active against pigmented Prevotella and Porphyromonas spp. Although these enzymes are generally chromosomally mediated, a plasmid-mediated metallo-BL has been reported in Japan (108). We do not retain these email addresses. In a study of ampicillin-sensitive E. faecalis isolates from hospitalized patients, only 36% of isolates were considered susceptible (MIC≤4 mg/L); activity against E. faecium… 59). Single-Center Pharmacokinetic Study and Simulation of a Low Meropenem Concentration in Brain-Dead Organ Donors. Even though the CLSI proposed that laboratories perform anaerobic susceptibility testing against certain major anaerobic pathogens (17), these recommendations are rarely followed and are performed at only a limited number of medical centers. A study of strains isolated from intra-abdominal infections (2001 to 2004) found 87% of B. fragilis and 87% of B. thetaiotaomicron isolates to be susceptible to moxifloxacin (143). Meropenem is approved for use in complicated intra-abdominal infection … Other factors that impact results reported in survey antibiograms include the particular makeup of the groups of strains included. The presence of the cfiA gene, as well as associated IS elements, can be determined by a PCR technique (57 anaerobe. – Penicillin, ampicillin, and amoxicillin are of limited utility due to the production of beta-lactamases by many oral and most intra-abdominal anaerobes. Anaerobes. New Window. Get the latest research from NIH: https://www.nih.gov/coronavirus. Taken together, these factors emphasize the need for antimicrobial susceptibility testing of anaerobes as well as periodic surveillance antimicrobial susceptibility testing to detect geographic or temporal trends. 2018 Apr-Jun;7(2):83-87. doi: 10.4103/jrpp.JRPP_17_86. FDA approval for a panel requires that all agents on the panel are FDA approved for use in anaerobic infections. Recently, the Infectious Diseases Society of America (IDSA) has removed ampicillin-sulbactam from the recommended list of treatments for intra-abdominal infections due to increased Escherichia coli resistance worldwide, although it has maintained good activity against B. fragilis and other anaerobes (76). Antimicrobial agents with appreciable anaerobic activity include the following: This indicated a steep decline from earlier rates; in 1990, 70% of hospital laboratories performed susceptibility testing (36), which declined to 33% in 1993 (37). Itzhak Brook, M.D., is an Adjunct Professor of Pediatrics at Georgetown University, Washington, DC. fragilis group species, and resistance to them is generally low, except that more than half of Prevotella species isolates may also produce BLAs. Cefoxitin is relatively inactive against most species of Clostridium, including C. difficile, with the exception of Clostridium perfringens (6, 7, 79). Unnecessary “Double-coverage” of anaerobes is considered an important target for antimicrobial stewardship programs. Focus Diagnostics (also a subsidiary of Quest Diagnostics, Inc.) has discontinued the microdilution test for anaerobic testing and now offers routine testing using Etest (anaerobic susceptibility panel 51477). Active against gram negative organisms, no anaerobe coverage, little to no strep coverage . Some studies refer to other method documents; a recent German multicenter study referred to a specific German document for testing methodology (24). The tolerance of metronidazole in patients is generally very good. Goldstein et al. Some of these strains show MICs of 8 to 32 units/ml of penicillin G. In these instances, administration of very high doses of penicillin G (for non-beta-lactamase producers) may eradicate the infection. A multicenter survey (93) found penicillin resistance for Fusobacterium spp., Porphyromonas spp., and Peptostreptococcus spp. Meropenem. These nim genes were found in 50/206 (24%) Bacteroides species isolates and resulted in MICs of 1.5 to >256 μg/ml for metronidazole, including 16 isolates with MICs of ≥32 μg/ml (54). After incubation, endpoints of growth are marked, and the distance is measured in millimeters from the center of the plate to the point where growth stops (Fig. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Recently, the IDSA has removed cefotetan from the recommended list of therapies for intra-abdominal infections due to poor B. fragilis group activity and resultant clinical failures (89 75). Performance of susceptibility testing for anaerobic bacterial isolates recovered from selected cases can provide important information that can influence the choice of antimicrobial therapy. It is not active against P. aeruginosa, Enterococcus spp., and Acinetobacter spp. No fetal toxicity or malformations were observed in pregnant rats and Cynomolgus monkeys administered intravenous meropenem during organogenesis at doses up to 2.4 and 2.3 times the maximum recommended human dose (MRHD) based on body surface area comparison, respectively; in rats administered intravenous meropenem in late pregnancy and during lactation period, there were no … 5). However, some anaerobic bacteria have become resistant to antimicrobial agents, and many can develop resistance while a patient is receiving therapy (111, 152). which carbapenem does not work well on gram - bugs. Meropenem and imipenem demonstrate good activity against Enterobacteriaceae, including strains producing ESBLs or AmpC (100% for E coli, 99% for other Enterobacteriaceae), meropenem usually being 2 to 4 fold more potent than imipenem [21–23]. Only six strains of the B. fragilis group were ever reported to be clinically resistant and associated with therapeutic failure (2). 1995;96:11-6 The spectrum of efficacy, antimicrobial resistance mechanisms, and resistance patterns against these agents are described. -, J Antimicrob Chemother. Antimicrobial therapy for anaerobic infections usually should be given for prolonged periods because of their tendency to relapse. If concern for MRSA, add vancomycin . Because of safety concerns, the FDA approved the use of metronidazole for the treatment of serious anaerobic infections only in adults. remain susceptible to penicillin. The antimicrobial susceptibilities of some members of the B. fragilis group vary, especially to the second- and third-generation cephalosporins. Levels exceeding 25 μg/ml are commonly considered potentially toxic in terms of reversible bone marrow suppression, and levels of 40 to 200 μg/ml have been associated with gray syndrome in neonates or encephalitis in adults (115). anaerobe. a, FDA-approved indications for antimicrobials for the treatment of anaerobic infections, Percent resistance of Bacteroides fragilis group isolates and other anaerobes to antimicrobial agents Ellie J. C. Goldstein, M.D., F.I.D.S.A., F.S.H.E.A., is Clinical Professor of Medicine at the David Geffen School of Medicine, UCLA; Director of the R. M. Alden Research Laboratory; and in private practice in Santa Monica, CA. Testing was performed by 85% (17/20) of laboratories for sterile body site isolates and by 70% (14/20) of laboratories for selected surgical wound isolates. Vancomycin and daptomycin are effective against all Gram-positive anaerobes but are inactive against AGNB (149). Fluoroquinolone resistance. This has become the most popular test for testing of individual isolates (Fig. 4 Can be used for many gram-negative infections (e.g. The most appropriate susceptibility test method will differ depending on whether the test is being done for a specific isolate in a hospital laboratory (or a commercial laboratory used by the hospital) or whether surveillance testing is being performed at a hospital or reference laboratory. Tigecycline is effective against anaerobic bacteria (137, 140). The limited medical education that students and residents receive about anaerobes and the limitations of microbiology laboratory culture, with delays in identification and anaerobic susceptibility testing, suggest that at best, the choice of an agent for a serious anaerobic infection is an empirical and educated guess (38). Premium Questions. Spiral gradient endpoint system.The Autoplate 4000 (Advanced Instruments, Inc., Boston, MA) spiral gradient endpoint (SGE) system deposits a specific amount of antimicrobial stock solution in a spiral pattern on a 150-mm agar plate, producing a concentration gradient that decreases radially from the center of the plate (Fig. Infections caused by these bacteria are seldom reported, as they in most cases are regarded as normal flora or non-pathogenic microorganisms. Most strains of the B. fragilis group and many Prevotella, Porphyromonas, and Fusobacterium spp. The appearance of tetracycline resistance in P. acnes has been correlated with previous tetracycline therapy (127). Furthermore, evidence of mutagenicity was never found in humans despite metronidazole use for over 2 decades for other diseases (131). The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. – It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug.