It is used for dental infections, especially in patients who are allergic to penicillin, and for aspiration pneumonia. 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. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. (100) The cephalosporinases are most often of the 2e class type and can be inhibited by three beta-lactamase inhibitors, clavulanic acid, sulbactam, and tazobactam. Of pretherapy anaerobes from moxifloxacin-treated patients, 561 (87.4%) were susceptible at ≤2 mg/liter, 34 (5.3%) were intermediate at 4 mg/liter, and 47 (7.3%) were resistant at ≥8 mg/liter. Veillonella sp. Meropenem acts against aerobes and anaerobes including Klebsiella, E. coli, Enterococcus, Clostridium sp.. (NCI04) It has low MICs for the B. fragilis group. 59). (Left) Dye representing the gradient application of antimicrobial stock solution, decreasing from the center of the plate. β-Lactams are generally effective against non-B. Pigmented Prevotella and Porphyromonas spp., Prevotella bivia, Prevotella disiens, and Fusobacterium nucleatum produce primarily penicillinases (107). In these cases, the antimicrobials tested can be tailored to reflect the hospital's particular formulary. To most clinicians, B. fragilis group species are recognized as the major anaerobic pathogen, but the individual B. fragilis group subspecies are less readily recognized. Epub 2016 Jan 19. HHS The tolerance of metronidazole in patients is generally very good. Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-, Conjugal transfer of imipenem resistance in. He is the author of 6 medical textbooks, 128 book chapters, and over 700 scientific publications. These findings suggest that some isolates possessed novel inactivation mechanisms, suggesting that more than one mechanism of inactivation exists. 82). However, with the reemergence of anaerobic bacteremia in the 1990s, many centers resumed processing of blood cultures for anaerobes. It has often been used for surgical prophylaxis at most body sites that are in proximity to mucus membranes. Some studies in mice (129) have shown possible mutagenic activity associated with administration of large doses of this drug. (96, 97). These pathogens include MRSA, penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci, Acinetobacter baumannii, beta-lactamase-producing strains of H. influenzae and M. catarrhalis, and extended-spectrum-beta-lactamase-producing strains of E. coli and Klebsiella pneumoniae. – 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. Hence, the clinician is likely to consider only the in vitro activity of specific agents against B. fragilis and assume that all the other anaerobes will likely be susceptible as well. Amplification was done with a set of primers designed for detecting five resistance genes, including carbapenems (cfiA), cephalosporins (cepA), clindamycin (ermF), metronidazole (nimA-F), and tetracycline (tetQ), plus a set of primers for the B. fragilis 16S rRNA gene (positive control). Susceptibility testing of anaerobic bacteria recovered from selected cases can influence the choice of antimicrobial therapy. (Left) Sensititre pipette for filling microdilution plate. Antimicrobial resistance among anaerobes has consistently increased in the past 3 decades, and the susceptibility of anaerobic bacteria to antimicrobial agents has become less predictable. The semisynthetic penicillins, the carboxypenicillins (carbenicillin and ticarcillin), and ureidopencillins (piperacillin, azlocillin, and mezlocillin) generally are administered in large quantities to achieve high serum concentrations. Routine anaerobic blood cultures: back where we started? The dried panels are stable at room temperature for 1 to 2 years. (150). – The overall spectrum is similar to that of imipenem, although meropenem is more active against Enterobacteriaceae and less active against Gram-positive bacteria. In practice, most hospitals that use microbroth panels order the panels that reflect the needs of their physicians based on hospital formulary and drug used and not on FDA approval. Meropenem has been effective in abdominal infections, meningitis in children and adults, community-acquired and nosocomial pneumonia, and neutropenic fever (98). If formal surveillance testing cannot be done, hospitals should collect and summarize their antimicrobial susceptibility test results and create a hospital-specific antibiogram that can be consulted if needed. Olsen I, Solberg CO, Finegold SM. a Thus, a clinical laboratory would have the option of either using Etest (which is FDA approved), using noncommercial panels with CLSI-approved methodology (thus, FDA approval would not be relevant), or sending the isolates to a commercial or reference laboratory for testing. Imipenem/cilastatin: an update of its antibacterial activity, pharmacokinetics and therapeutic efficacy in the treatment of serious infections. Clarithromycin showed similar activity to that of erythromycin against most AGNB (118). Specialty Laboratories (operated by Quest Diagnostics) provides testing services for 6 antimicrobials (cefoxitin, penicillin, clindamycin, piperacillin-tazobactam, metronidazole, and imipenem) using Etest methodology (anaerobic susceptibility panel 5711). There are different classifications of the enzymes. Only about 45% of all B. fragilis strains are presently susceptible to this drug (79). Excellent gram-negative coverage, safe for use in patient with anaphylaxis to penicillin (but might cross-react with ceftazidime). Bacteroides multidrug efflux [Bme] pumps 1 to 16) and are apparently important in conferring multidrug resistance (23, 65, 68); pump activity related to resistance has also been described for Clostridium (69 and Porphyromonas spp. Medical uses Intra-abdominal infections. In comparison to other available carbapenems, ertapenem has a long half-life of 4.5 h and is given as a single daily dose. However, it is clear that there is also a non-nim-based mechanism of resistance to metronidazole. Vancomycin and daptomycin are effective against all Gram-positive anaerobes but are inactive against AGNB (149). Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. If made in-house, trays can be tailored to the particular needs of the laboratory, using the drugs and concentration ranges needed. Anaerobes. Lacks good anaerobic coverage. Suggest alternative medication for Meropenem . ... All Staphylococci, Streptococci and anaerobes were susceptible to the three antibiotics. The spectrum of action includes many Gram-positive and Gram-negative bacteria (including Pseudomonas) and anaerobic bacteria. Mayo Medical Laboratories (Rochester, MN) also uses Etest methodology. Quinupristin-dalfopristin shows antibacterial activity against anaerobic organisms including C. perfringens, Lactobacillus spp., and Peptostreptococcus spp. Only six strains of the B. fragilis group were ever reported to be clinically resistant and associated with therapeutic failure (2). Although this type of test is not currently appropriate for clinical settings, there is increasing interest in using this technology for clinical laboratory identification (58), and it is conceivable that it could be potentially developed for testing. – Anaerobes (including the B. fragilis group) are conspicuous in their absence from the microbiological reports of most hospitals (17, 27, 78). Agents to test should include those on the hospital formulary, and the agent that is being considered or used for therapy should be included if at all possible. Carbapenems are active synergistically with aminoglycosides against P. aeruginosa. Tetracycline resistance and the inducible transfer of resistance determinants can occur after exposure to low levels of these agents. The routine susceptibility testing of all anaerobic isolates is extremely time-consuming and is not cost-effective. Over 90% of obligate anaerobes are susceptible to less than 2 μg/ml metronidazole (79). A study by Curtis Donskey’s group showed that 30% of all antimicrobials prescribed were unnecessary and inappropriate. Although identification of the infecting organisms and their antimicrobial susceptibility may be needed for selection of optimal therapy, the clinical setting and Gram stain preparation of the specimen may indicate the types of anaerobes present in the infection as well as the nature of the infectious process. (Left) A Steers replicator is used to apply inocula onto a agar plate. Dr. Brook is the recipient of the 2012 J. Conley Medical Ethics Award by the American Academy of Otolaryngology-Head and Neck Surgery. 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). 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 Anaerobic Coverage 1,2 All carbapenems have fairly good coverage against anaerobes. Antimicrob Agents Chemother. Meropenem. micros (138). The inadequate isolation, identification, and subsequent performance of susceptibility testing of anaerobes from an infected site can prevent detection of antimicrobial resistance. 1). express enzymes that are generally inhibited by clavulanic acid (110). Chronic Kidney infections.....IV meropenem seems to be the only thing that clears them up. 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. However, cefoxitin has poor activity against B. thetaiotaomicron isolates. All of these factors affect the clinician's cognitive choices in the selection of an antimicrobial agent to treat anaerobic infections. Using the right antibiotic when necessary is crucial to avoid using broad spectrum antibiotic so we have to know the coverage criteria for each antibiotic before utilizing it to the patient, […] Since that time, the CLSI (formerly NCCLS) procedures have been extensively revised and have been adopted by virtually all testing laboratories in the United States and even worldwide. In the last few decades, the need for testing of anaerobic isolates has been increasingly recognized, and the testing methodologies used have been standardized. cefotetan and cefoxitin. – CLSI policy does not permit it to advocate any commercial technique; rather, it describes two reference methods (agar dilution and broth microdilution) and emphasizes that other techniques, such as gradient techniques (generally referring to Etest) or commercial broth microdilution plates, may be used as long as equivalence to the reference methods is established. Coverage would usually be for 72 hours to rule out VRE. Isolates from patients likely to undergo long-term therapy should be tested so that any development of resistance can be recognized. At least 50 to 100 strains should be tested in order to obtain an accurate picture of the pattern of local isolates, and if isolates from different body sites are available, they should be included. Members of the Bacteroides fragilis group. Infections caused by anaerobic bacteria are common and may be serious and life-threatening. (37 [80.4%] of 46 patients). Isla A, Canut A, Arribas J, Asín-Prieto E, Rodríguez-Gascón A. Eur J Clin Microbiol Infect Dis. and Prevotella spp. 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 great majority of B. fragilis group isolates are β-lactamase producers; therefore, testing is generally not recommended for this group. The data are then entered into a computer software program provided by the manufacturer, which determines the concentration of drug from the radius of growth and the molecular weight (i.e., diffusion characteristics) of the antimicrobial agent. Erythromycin is effective in the treatment of mild to moderately severe anaerobic soft tissue and pleuropulmonary infections when combined with adequate debridement or drainage of infected tissue. Clindamycin resistance is conveyed by a macrolide-lincosamide-streptogramin (MLS)-type 23S methylase, typically encoded by one of several erm genes that are regulated and expressed at high levels (56). 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 pneumonia, soft tissue, urinary tract, bacteremia). Rashes, fever, anaphylaxis, erythema multiforme. Candida species are now the fourth most common cause of nosocomial bloodstream infections and are associated with a mortality of 30–40% 1. 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: a review of its use in patients in intensive care. The performance of susceptibility tests for individual isolates when indicated and obtaining local surveillance testing to monitor regional trends have been recommended by the CLSI. At least 20 isolates of Bacteroides spp. This gene codes for an enzyme that converts 4- or 5-nitroimidazole (4- or 5-Ni, respectively) to 4- or 5-aminoimidazole (thus avoiding the formation of toxic nitroso radicals that are essential for antimicrobial activity). Consequently, they are employed in more serious anaerobic infections, such as intra-abdominal and skin and soft tissue infections (89 Usually same anaerobic spectrum as imipenem; however, the drug has been used less often in clinical trials for anaerobic processes. Adverse reactions to metronidazole therapy are rare and include CNS toxicity, such as ataxia, vertigo, headaches, and convulsions, and peripheral neuropathy. Factors Contributing to Variability in MIC ResultsA 1991 review by Wexler (35) reported the major reasons for variability in reporting of MIC results. The most effective antimicrobials against anaerobic organisms are metronidazole, the carbapenems (imipenem, meropenem and ertapenem), chloramphenicol, the combinations of a penicillin and a beta-lactamase inhibitor (ampicillin or ticarcillin plus clavulanate, amoxicillin plus sulbactam, and piperacillin plus tazobactam), tigecycline and clindamycin. 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. 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). In addition, clinicians may be less aware of the variability between laboratories in their capabilities and interest in anaerobic bacteriology and the specific level of performance and capability of their own clinical microbiology laboratories to both isolate anaerobes and perform susceptibility testing (20, 36, 37). Use of any combination of the agents below is considered double-anaerobic coverage, which is not necessary. are markedly elevated. (33) observed that 90% of B. fragilis isolates recovered from nosocomial infections and bacteremias in Taiwan were susceptible to moxifloxacin. There is a dried anaerobic panel (AN02B; Sensititre [Trek Diagnostic Systems]) that includes 15 antimicrobials in a variety of dilution ranges, depending on the antibiotic (
2020 meropenem coverage anaerobes