A primer on anaerobic bacteria and anaerobic infections for the uninitiated. Veillonella sp. Empiric coverage for MRSA is indicated for patients known to be colonized with These are colorimetric tests that are very easy to perform, and results can be read quickly (5 to 30 min) and would be useful if penicillin or ampicillin therapy is being considered. All Rights Reserved. Microaerophilic streptococci, P. acnes, and Actinomyces spp. The Etest is a plastic strip with a predetermined antimicrobial concentration gradient on one side and an interpretative MIC scale on the other. Among the Gram-positive anaerobes, clinicians are also aware of Clostridium species, especially C. perfringens and Clostridium botulinum and, more recently, the great importance of C. difficile. Other factors that impact results reported in survey antibiograms include the particular makeup of the groups of strains included. This review describes the antimicrobial agents that are effective against anaerobic bacteria and the methods used to perform antimicrobial susceptibility testing of these organisms. On the other hand, changes in susceptibility that are known to be due to specific mechanisms (such as the presence of the nitroimidazole reductase gene [nim], which causes metronidazole resistance, or cfiA genes, which can result in carbapenem resistance) may begin to appear as relatively modest changes in resistance rates and then quickly increase as the resistance determinant becomes disseminated. In B. fragilis, 16 homologs of tripartite efflux pumps of the resistance nodulation division (RND) family have been described ( Resistance has also increased for many non-Bacteroides anaerobes. Therefore, when trying to evaluate or compare published studies, the method used should be taken into account. Goldstein et al. (33) observed that 90% of B. fragilis isolates recovered from nosocomial infections and bacteremias in Taiwan were susceptible to moxifloxacin. Tetracycline resistance.Tetracycline resistance is prevalent among Bacteroides species, Prevotella species, and many other anaerobic bacteria, limiting its clinical use (139). fragilis group species, and resistance to them is generally low, except that more than half of Prevotella species isolates may also produce BLAs. – Double anaerobic coverage is the combination of 2 or more of the following agents: Ampicillin/sulbactam Carbapenems (Doripenem, Ertapenem, Imipenem, Meropenem) Cefotetan Cefoxitin – 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. He founded, and served as President of, the Infectious Diseases Association of California and the Anaerobe Society of the Americas. Unnecessary “Double-coverage” of anaerobes is considered an important target for antimicrobial stewardship programs. C onsider for sepsis with gastrointestinal source -Cefepime can be use d for CNS infections and readily achieves therapeutic concentrations in the lungs. 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 Sensititre will also prepare custom panels which can be either frozen or air dried. There are occasions when clinicians are unsure of a specific drug's activity against anaerobes and may use redundant coverage with metronidazole, such as a carbapenem or a BL-BLIC. The carbapenem antibiotics imipenem, meropenem, ertapenem, and doripenem have a broad antimicrobial spectrum, 199 with activity against almost all aerobic and anaerobic pathogens, although Enterococcus faecium are resistant. The carbapenem ertapenem is one of several first-line agents recommended by the Infectious Disease Society of America for the empiric treatment of community-acquired intra-abdominal infections of mild-to-moderate severity. Meropenem, from the carbapenem class, is effective against most gram-positive, gram-negative, anaerobic, and even extended beta-lactamase–producing bacteria and has good CSF penetration. Laboratories used different media and different inoculum sizes and may have read results after different incubation times. An additional 40% (8/20) of laboratories surveyed would also perform susceptibility testing by special request. Meropenem was FDA-approved in the United States in July of 1996 and is used today for a variety of infections including pneumonia, bacteremia, osteomyelitis, urinary tract infection, and meningitis. Fortunately, the types of anaerobes involved in many anaerobic infections and their antimicrobial susceptibility patterns tend to be predictable (2, 3). Beta-lactam–beta-lactamase inhibitor combinations (BL-BLICs) are popular and appropriate choices for mixed aerobic-anaerobic infections. If made in-house, trays can be tailored to the particular needs of the laboratory, using the drugs and concentration ranges needed. 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 Metronidazole resistance.Although rare, resistance to metronidazole among B. fragilis group isolates has been observed worldwide (33, 135). Meropenem rated 8.0/10 vs Metronidazole rated 6.2/10 in overall patient satisfaction. Levofloxacin (po, IV – Levaquin) National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. A variety of studies (19, 22, 144) have reported increases in B. fragilis resistance to moxifloxacin. If needed, ancillary susceptibility testing can be performed for cefoxitin, tigecycline, and moxifloxacin, which have approved antianaerobe indications. However, it is clear that there is also a non-nim-based mechanism of resistance to metronidazole. Because anaerobic infection is often polymicrobial and is caused by aerobic and anaerobic organisms, antimicrobials that are effective against both components of the infection should be administered. In contrast, MICs for Pseudomonas and Proteus spp. Gal and Brazier (54) speculated that other mechanisms of resistance can occur and that prolonged exposure to metronidazole may select them. Other drug tests can be custom ordered (depending on the availability of the Etest strip). Meropenem is a structural analog of impipenem that is resistant to cleavage by renal dehydropeptidase I. Meropenem is a structural analog of impipenem that is resistant to cleavage by renal dehydropeptidase I. Resistance among some anaerobes has increased significantly over the past 3 decades. Please enable it to take advantage of the complete set of features! ClindamycinClindamycin has a broad range of activity against anaerobic organisms and has proven its efficacy in clinical trials. The CLSI has published an appendix to its recent document that reports the cumulative susceptibilities for B. fragilis group species collected from three U.S. medical centers from 2007 to 2009 (17). (especially C. difficile) (93). Some clinicians may not appreciate metronidazole's limited activity against anaerobic and microaerophilic Gram-positive cocci, especially the microaerophilic streptococci, which are often lumped together with anaerobes. However, with the reemergence of anaerobic bacteremia in the 1990s, many centers resumed processing of blood cultures for anaerobes. Meropenem. With certain antimicrobial agents, the MICs for a large percentage of B. fragilis group strains cluster within one 2-fold dilution range of the breakpoint. All the reference laboratories used broth microdilution for susceptibility testing, as did 40% (8/20) of hospital laboratories (all commercially prepared). The newer tetracycline analogs doxycycline and minocycline are more active than the parent compound. A study by Edmiston et al. They irreversibly inhibit beta-lactamase enzymes produced by some Enterobacteriaceae, staphylococci, and beta-lactamase-producing Fusobacterium spp. Six to nine drugs are offered routinely, depending on the organism being tested. Of the non-B. Broth microdilution. Organisms that should be considered for individual isolate testing include highly virulent pathogens for which susceptibility cannot be predicted, such as Bacteroides, Prevotella, Fusobacterium, and Clostridium spp. meropenem may also be used for purposes not listed in this... View more. Since then, nine nim genes were described for B. fragilis (nimA to nimI [nimA-I]), and an additional nimI gene was described for Prevotella (53, 54). 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). 4, middle). This agent is an effective single agent for the therapy of mixed aerobic-anaerobic infections. Logical choice for … The most recently published surveys of anaerobic susceptibility testing performed in a clinical laboratory indicated that, as of the time of the survey, only 21% (21/98) of hospital laboratories performed anaerobic susceptibility testing in-house (20). CLSI reference protocol M11-A8 has included extensive discussion on breakpoint interpretation and included several sets of photographs to aid in reading of breakpoints. The clindamycin treated mice died of sepsis. | Antibiotic stewardship personnel should review this practice. Spectrum: best gram negative coverage of FQs, but virtually no gram positive coverage. 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. The antimicrobial susceptibilities of some members of the B. fragilis group vary, especially to the second- and third-generation cephalosporins. reliably predicts outcome (specificity of 97% and positive predictive value of 82%). Antimicrobial agents with appreciable anaerobic activity include the following: Glycylcyclines are tetracycline antibiotics containing a glycylamido moiety attached to the 9-position of a tetracycline ring; tigecycline is a direct analog of minocycline with a 9-glycylamide moiety. doi: 10.1128/AAC.00542-18. 15). (140) found that 90% of 831 B. fragilis group isolates were susceptible to ≤8 μg/ml of tigecycline and that P. distasonis isolates were the most resistant. 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… These drugs are effective against Enterobacteriaceae and have good activity against most anaerobes in these concentrations. Anaerobes. Despite all of these factors, a correlation between the antimicrobial resistance of the anaerobic pathogens and poor clinical outcome has been reported in several retrospective studies (7 2007;67(7):1027-52. doi: 10.2165/00003495-200767070-00006. The CLSI method specifies the use of control strains including B. fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Clostridium difficile ATCC 700057. Other strains that may show resistance to penicillins are growing numbers of AGNB, such as the pigmented Prevotella and Porphyromonas spp., Prevotella oralis, Prevotella bivia, Bacteroides disiens, strains of clostridia, Fusobacterium spp. A recent study (143) reported a pooled analysis of 4 randomized clinical trials (2000 to 2010) that assessed the comparative efficacy of moxifloxacin in complicated intra-abdominal infections of 745 microbiologically evaluable cases and focused on its efficacy against B. fragilis. Many reference laboratories will use commercially prepared panels; in these cases, the agents tested will depend on whichever antibiotics are included in the commercial panel that the laboratories are using for testing. Chronic Kidney infections.....IV meropenem seems to be the only thing that clears them up. In comparison to other available carbapenems, ertapenem has a long half-life of 4.5 h and is given as a single daily dose. Cefoxitin is relatively inactive against most species of Clostridium, including C. difficile, with the exception of Clostridium perfringens (6, 7, 79). The panels are specifically designated for research purposes and not for diagnostic testing. Drugs. Studies using different proportions of the various B. fragilis group species may reflect different antibiograms for the B. fragilis group as a whole, when in reality, the only difference is the proportion of the various species used. Resistance has also increased among other anaerobes, such as Clostridium spp., that were previously very susceptible. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. (Left and right panels courtesy of Trek Diagnostics Systems, Inc., reproduced with permission.). The radius from the center of the plate to end of growth is measured and translated into an MIC by a software program. Most hospitals that send strains out for susceptibility testing are getting test results by using Etest methodology, which is within the expertise available in most hospitals. Other isolates have less predictable patterns, and certain anaerobes (some Clostridium, Fusobacterium, and Prevotella species, for example) may be penicillin-ampicillin resistant due to β-lactamase. It is indicated for complicated intra-abdominal and skin structure infections, including diabetic foot infections without osteomyelitis, and acute pelvic infections, including postpartum endomyometritis, septic abortion, and postsurgical gynecological infections. (150). He is the past chairman of the Anti-Infective Drug Advisory Committee of the Food and Drug Administration. In the last few decades, testing methodologies used have been standardized. Details of the procedure are described in the manufacturer's guidelines. Clinical experiences of adults (132) illustrated metronidazole's efficacy in the treatment of infections caused by anaerobes, including CNS infections (133). 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… For all anaerobes combined, the clinical success rates were 83.1% (466 of 561 patients) for an MIC of ≤2 mg/liter, 91.2% (31 of 34 patients) for an MIC of 4 mg/liter, 82.4% (14 of 17 patients) for an MIC of 8 mg/liter, 83.3% (5 of 6 patients) for an MIC of 16 mg/liter, and 66.7% (16 of 24 patients) for an MIC of ≥32 mg/liter. Infections caused by these bacteria are seldom reported, as they in most cases are regarded as normal flora or non-pathogenic microorganisms. Over 90% of obligate anaerobes are susceptible to less than 2 μg/ml metronidazole (79). (117). The mortality rate among those who received inactive therapy (45%) was higher than that among patients who received active therapy (16%; P = 0.04). Penicillin, ampicillin, and amoxicillin are of limited utility due to the production of beta-lactamases by many oral and most intra-abdominal anaerobes. (Right) Series of agar dilution plates. The antimicrobial spectrum of the narrow-spectrum cephalosporins against anaerobes is similar to that of penicillin G, although on a weight basis, they are less active. The choice will be based on published literature and surveys and local or specific patient data. Meropenem Antibiotic Class: Carbapenem Antimicrobial Spectrum: Aerobic gram-positive microorganisms: S. aureus including penicillinase-producing strains, Group D streptococcus including Enterococcus spp., Streptococcus pneumoniae, S. pyogenes, S. viridans group 4). Community-acquired anaerobic bacteremia in adults: one-year experience in a medical center, Antimicrobial resistance and clinical outcome of, Clinical significance and outcome of anaerobic bacteremia, Susceptibility test methods: anaerobic bacteria, Clinical and Laboratory Standards Institute, Methods for antimicrobial susceptibility testing of anaerobic bacteria. Table 1 illustrates the antimicrobials effective against anaerobic bacteria and their efficacy against both aerobic and anaerobic bacteria. Five genes conferring MLS resistance have been identified in anaerobes, including erm(B), erm(C), erm(F), erm(G), and erm(Q). Resistant B. fragilis group isolates carry one of nine known nim genes (nimA-I) on either the chromosome or a mobilizable plasmid that seems to encode a nitroimidazole reductase, which converts 4- or 5-Ni to 4- or 5-aminoimidazole, preventing the formation of toxic nitroso residues necessary for the agent's activity. Meropenem: a review of its use in patients in intensive care. There is evidence that suboptimal therapy can actually select for antibiotic resistance and even induce transfer of resistance determinants. eCollection 2018 Dec. Lee JM, Lee JW, Jeong TS, Bang ES, Kim SH. Because of metronidazole's lack of activity against aerobic bacteria, an antimicrobial effective against these organisms (e.g., a cephalosporin or a fluoroquinolone) needs to be added when treating a polymicrobial infection. Clinicians are less aware of all the taxonomic changes that have occurred and the names of new species. The standardization of testing methods by the CLSI allows for comparison of resistance trends among various laboratories (15 Laboratories should ideally include at least one agent from each antimicrobial class, even if it is not included on the formulary. Adverse reactions to metronidazole therapy are rare and include CNS toxicity, such as ataxia, vertigo, headaches, and convulsions, and peripheral neuropathy. Single-Center Pharmacokinetic Study and Simulation of a Low Meropenem Concentration in Brain-Dead Organ Donors. A multicenter survey (93) found penicillin resistance for Fusobacterium spp., Porphyromonas spp., and Peptostreptococcus spp. The panels can be prepared in advance, frozen, and used as needed. fragilis group species. The CLSI reference standard is not intended for testing of single isolates; rather, it provides a standard against which other methods may be measured. which carbapenem does not work well on gram - bugs. Its antimicrobial spectrum more closely resembles those of meropenem and imipenem than that of ertapenem (94). (Left) Sensititre pipette for filling microdilution plate. Clinicians are likely to be unaware of recent changes in CLSI breakpoints for any specific bacterium-drug combination (17). Despite the emergence of carbapenemase-resistant Enterobacteriaceae, it is also effective against most Enterobacteriaceae, with about 5% to 15% of Pseudomonas species strains being resistant (95). Quinolones with the greatest in vitro activity against anaerobes include clinafloxacin and sitafloxacin (142). Each individual cephalosporin may have either a class or specific inhibitor enzyme that is able to inactivate it. 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). The appearance of tetracycline resistance in P. acnes has been correlated with previous tetracycline therapy (127). Clinical outcome was correlated with results of in vitro susceptibility testing of Bacteroides isolates recovered from blood and/or other sites and was determined by three endpoints: mortality at 30 days, clinical response (cure versus failure), and microbiological response (eradication versus persistence). 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). Most studies conform to CLSI breakpoints, but certain EUCAST breakpoints are different. For the very resistant P. aeruginosa, doripenem and meropenem are highly potent because they require multiple drug resistance pathways. β-Lactamase TestAnaerobic organisms may be tested for the presence of the β-lactamase (BLA) enzyme by using a chromogenic cephalosporin test, such as nitrocefin disks. Methicillin, nafcillin, and the isoxazolyl penicillins (oxacillin, cloxacillin, and dicloxacillin) are ineffective against the B. fragilis group, have unpredictable activity, and frequently are inferior to penicillin G against anaerobes (73). Her work currently includes comparative genomic and transcriptomic studies of multidrug-resistant and virulent strains of Bacteroides fragilis. Tigecycline has been approved by the FDA for use in complicated skin and soft tissue infections, including those due to B. fragilis (153), and intra-abdominal infections, including those due to B. fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, C. perfringens, and Ps. Tinidazole may be better tolerated in patients with gastrointestinal side effects due to metronidazole. Consequently, they are employed in more serious anaerobic infections, such as intra-abdominal and skin and soft tissue infections (89 (Left) Dye representing the gradient application of antimicrobial stock solution, decreasing from the center of the plate. Aerobic and facultative anaerobes, such as coliforms, are usually highly resistant. The major concerns with expanding the use of fluoroquinolones to treat anaerobic infections have been reports of increasing resistance in strains of the B. fragilis group as well as anaerobic Gram-positive cocci and the impact of these antibiotics on the growing incidence of C. difficile-associated disease (142). He has done extensive research on anaerobic and respiratory tract infections, anthrax, and infections following exposure to ionizing radiation. Several multidrug-resistant isolates appear to have significantly increased efflux pump activity. There is a certain margin of error (usually ±1 2-fold dilution) for any of these techniques. He is currently a Section Editor for Clinical Infectious Diseases and chair of the publications committee of Anaerobe. Clindamycin resistance.Although the patterns differ by region, B. fragilis resistance to clindamycin is increasing worldwide. 5). Goldstein et al. Three genes encoding enzymes that inactivate tetracycline, i.e., tet(X1), tet(X2), and tet(32), have been identified in Bacteroides (62, 63). Resistance patterns have been monitored through national and local surveys, but susceptibility testing of anaerobic bacteria at individual hospitals is rarely done (20). -. Fusobacterium canifelinum, recovered from cat and dog bite wound infections, is intrinsically resistant to fluoroquinolones because of Ser79 replacement with leucine and Gly83 replacement with arginine on gyrA (148). The antibiograms of anaerobic bacteria have become increasingly unpredictable, and multiresistant clinical isolates are appearing, confounding the concept of foolproof anaerobic therapy (21, 23, 147). Susceptibility testing should be performed on isolates recovered from sterile body sites, those that are isolated in pure culture, or those that are clinically important and have a variable or unique susceptibility. Current recommendations of the CLSI limit the broth microdilution method to testing of the B. fragilis group. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax. Prescribed for Nosocomial Pneumonia, Skin and Structure Infection, Intraabdominal Infection, Meningitis, Skin or Soft Tissue Infection. It is likely that the levels of efflux pump genes transcribed and expressed are important. Routine anaerobic blood cultures: back where we started? Excellent gram-negative coverage, safe for use in patient with anaphylaxis to penicillin (but might cross-react with ceftazidime). The European Committee on Antimicrobial Susceptibility Testing (EUCAST) publishes its own breakpoints; these are not always equivalent to those of the CLSI (29). The results of the surveillance study should be maintained and recorded so that local trends in emerging resistance may be recognized and documented. 1995;96:11-6 Coverage would usually be for 72 hours to rule out VRE. Meropenem har et meget bredt spektrum omfattende næsten alle grampositive og gramnegative bakterier, aerobe såvel som anaerobe, dog ikke over for Stenotrophomonasmaltophilia og har ringe effekt op enterokokker. (Fusobacterium varium and Fusobacterium mortiferum), and microaerophilic streptococci. The addition of penicillin, cefoxitin, and cefotetan may be ordered for testing of Clostridium. FluoroquinolonesThe earlier fluoroquinolones, such as ciprofloxacin and ofloxacin, are inactive against most anaerobic bacteria. Another study evaluating antibiotic exposure in past 2 years and isolation of resistant anaerobes from stool samples had shown an association with meropenem exposure and reduced susceptibility to meropenem. Clindamycin does not cross the blood-brain barrier or eye efficiently and should not be administered in CNS infections. 2000 Mar;59(3):653-80. doi: 10.2165/00003495-200059030-00016. Print 2018 Oct. Naderi P, Shirani K, Soltani R, Khorvash F, Naji Esfahani SS. -Piperacillin/ tazobactam differs in spectrum with its ability to cover enterococcus and anaerobes. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses. However, these agents have improved activity against Enterobacteriaceae. Other adverse reactions include reversible neutropenia, phlebitis at intravenous infusion sites, and drug fever. This serious complication is unrelated to the reversible, dosage-dependent leukopenia. He is an editor, associate editor, and member of the editorial board of several medical journals and the Head and Neck Cancer Alliance. 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). The combo treatment prevented abscess and death. anaerobe. Organisms that should be considered for individual isolate testing include highly virulent pathogens for which susceptibility cannot be predicted, such as Bacteroides, Prevotella, Fusobacterium, and Clostridium spp. With some exceptions among some Clostridium spp., strains of Clostridium, Porphyromonas, and Fusobacterium have also been found to express resistance by one or more of the BLAs. Levels in the cerebrospinal fluid, with or without meningitis, usually are one-third to three-fourths of the serum concentrations.
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