Ronald N. Jones

Review of the in vitro spectrum of activity of imipenem

Imipenem (N-formimidoyl thienamycin, MK0787), a new carbapenem was found to have the widest antimicrobial activity of currently available beta-lactam drugs. Enterobacteriaceae had minimal inhibitory concentrations of imipenem of 8.0 micrograms/ml or less for 99.8 percent of clinical isolates. Only rare strains of Enterobacter species and Proteus mirabilis have higher imipenem minimal inhibitory concentration results. Hemophilus and Neisseria species were inhibited, but minimal inhibitory concentrations of imipenem were higher than those reported for third-generation cephalosporins. Only Pseudomonas maltophilia and Pseudomonas cepacia strains were imipenem resistant (MIC50 greater than 32 micrograms/ml) among the commonly isolated non-enteric gram-negative bacilli. All anaerobes were found susceptible to imipenem with the exception of some strains of Clostridium difficile. Staphylococcus species and non-enterococcal streptococci were very susceptible to imipenem. Streptococcus faecalis had higher minimal inhibitory concentrations of imipenem (MIC90 3.1 micrograms/ml) and S. faecium strains were frankly resistant. Methicillin-resistant S. aureus isolates had a MIC90 of 27.2 micrograms imipenem/ml. Imipenem was generally bactericidal except for marked minimal inhibitory and minimal bactericidal concentration differences with enterococci, Listeria, methicillin-resistant staphylococci, and some P. aeruginosa strains. The minimal inhibitory and minimal bactericidal concentrations of imipenem were not significantly influenced by organism inoculum size, probably because of its beta-lactamase stability to nearly all commonly encountered bacterial enzymes. Imipenem was found to be an excellent inhibitor of beta-lactamases and a potent enzyme inducer. The induction characteristic seems responsible for the antagonistic interactions of imipenem with some enzyme-labile beta-lactams in combination. Imipenem had limited stability in some in vitro susceptibility test systems. The 10 micrograms disk test or dry-form broth micro-dilution systems were preferred, applying the interpretive criteria from the National Committee for Clinical Laboratory Standards (M2-A3). Imipenem-resistant strains were rarely found in clinical practice and bacteria resistant to newer beta-lactams and aminoglycosides were generally very susceptible to this new carbapenem.

Cefotaxime single-dose surgical prophylaxis in a prepaid group practice. Comparisons with other cephalosporins and ticarcillin/clavulanic acid.

SummaryThe prophylactic efficacy of a single 1g dose of cefotaxime for a wide variety of clean and clean-contaminated surgical procedures was studied in a large prepaid medical practice setting. Regimens were evaluated in 3 successive prospective, randomised comparative trials involving 1950 evaluable patients between November 1983 and March 1986. Single-dose cefotaxime was initially compared with standard multiple-dose regimens of cephazolin and cefoxitin, and subsequently used as the control regimen for comparisons with single-dose cefoperazone and ticarcillin/clavulanic acid.Patients were observed for the development of wound infection, non-wound morbidity, and adverse reactions. The single-dose prophylaxis regimens resulted in fewer surgical wound infections (p <0.05) compared with multi-dose prophylaxis if colorectal procedures were excluded from the analyses. The limited effectiveness of single-dose prophylaxis in colorectal surgery occurred despite the co-administration of erythromycin and neomycin. More than half the infections in all groups were discovered after hospital discharge and were inconsequential. Organisms isolated from the various infections generally remained susceptible to the administered antimicrobial agents. Adverse reactions occurred significantly (p <0.001) less often in the patients receiving single-dose prophylaxis. Non-wound morbidity was comparable in all trial groups. The costs associated with single-dose regimens were much lower than those of the FDA-approved multiple-dose regimens.These data confirm that single-dose, broad spectrum β-lactam agents such as cefotaxime provide safe, effective and economical prophylaxis for a wide variety of surgical procedures.

In vitro activity and disk susceptibility of Timentin: current status.

Clavulanic acid is a beta-lactam compound with little or no antibacterial activity against most species, but it is a potent inhibitor of many bacterial beta-lactamases [1,2]. This characteristic has been exploited by combining clavulanic acid with beta-lactamase-susceptible beta-lactams, resulting in an enhanced spectrum of the latter drugs [3-51. The combination of ticarcillin and clavulanic acid (Timentin) has demonstrated significantly greater in vitro antibacterial activity than ticarcillin alone, particularly against certain beta-lactamase-producing species [6-91. In this article,, we summarize our experience and review the pertinent literature on the in vitro antibacterial activity of Timentin, with particular emphasis on proposed susceptibility testing criteria for both dilution and disk-diffusion susceptibility testing methods.

Gram-positive superinfections: A consequence of modern β-lactam chemotheraphy

Abstract This review of superinfections following β-lactam chemotherapy shows significant variations in the risks of gram-positive and all-organism secondary morbidity. Cefotaxime and structurally similar cephems appear to have the lowest rate of all-organism and incidence of gram-positive enterococcal superinfection. Several possible mechanisms for this favorable finding included synergistic interactions of cefotaxime and desacetylcefotaxime, in vitro activity against most significant pathogens, enhanced antienterococcal activity in the presence of human serum, and significant β-lactamase stability. Variations between cefotaximelike compounds as compared to superinfection rate may be caused by bowel flora alterations and subsequent development of drug-resistant populations. We eagerly await additional review reports on the risks of ceftizoxime, ceftriaxone, and cefmenoxime superinfection.

In vitro evaluations of amikacin: an assessment of the currently used methods of disk diffusion and dilution susceptibility, antimicrobial synergy, and the measurement of amikacin concentrations

The amikacin antimicrobial susceptibility tests were reviewed and found to be acceptable for clinical laboratory use. The early change from the 10-micrograms to the 30-micrograms diagnostic disk concentrations has resulted in reasonable accuracy, according to data from surveys of the College of American Pathologists, and acceptable discrimination between susceptible and resistant microorganisms. Similarly, standardized dilution susceptibility methods have proven acceptable, but great care must be exercised to select an agar medium in which performance was evaluated by the criteria of the National Committee for Clinical Laboratory Standards. Breakpoint concentrations selected as susceptible for amikacin (equal to or less than 16 micrograms/ml) were based on infected patient pharmacokinetics and previously correlated with patient bacteriologic outcome. Amikacin serum levels have been accurately measured by numerous procedures, including gas-liquid chromatography, radioimmunoassay, radioenzymatic assay, bioassay, and latex agglutination tests. Recent surveys of the College of American Pathologists support the earlier suspicions of lower accuracy and specificity with the bioassay method. Care must be taken to rapidly and appropriately process specimens from patients receiving concurrent high doses of antipseudomonal penicillins because of documented inactivation of some aminoglycosides by these penicillins. Amikacin is less affected by these beta-lactams. Evaluations of the antibacterial activity of amikacin in combination with other antimicrobial agents, principally the beta-lactams, continue to show high rates of enhanced killing or synergy. Although the methods for assessment of synergy have not been standardized, remarkably favorable and similar results between laboratories have been reported.

The impact of proficiency survey programs on laboratory antimicrobial susceptibility testing

“Much of the data cited is derived from Proficiency Surveys of the College of American Pathologists. The opinions and conclusions expressed are those of the authors and not of The College of American Pathologists. Such determinants include the immunologic and nutritional status of the host; the site of infection; the etiologic microbial agent; the susceptibility of the offending microbe to antimicrobial agents; the pharmacokinetics of the drug(s) being considered together with recognized adverse and beneficial interactions between host and infectious agent, host and antimicrobial, infectious agent and antimicrobial. The in vitro antimicrobial susceptibility test aids in the determination of only one of these factors, and when considered in isolation from the other determi-

Interpretive standards of cefbuperazone disk diffusion susceptibility tests

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