Synergism between Amikacin and Cefazolin against Klebsiella: In Vitro Studies and Effect on the Bactericidal Activity of Serum

Klastersky, Jean; Meunier-Carpentier, F.; Prevost, Jean-Marie; Staquet, Marie‐Jeanne

doi:10.1093/infdis/134.3.271

Cited by 49 publications

(13 citation statements)

References 7 publications

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“…On the other hand, several studies examining small numbers of strains have suggested rough correlations between results obtained by different methods (110,191). Klastersky et al (101) found agreement between time-kill and MBC checkerboard assessment of cefazolin-amikacin interactions for 60% (13 of 20) of Klebsiella isolates. Norden et al (141) illustrated discrepancies when various methods and criteria were applied in examining cephalothin-gentamicin interactions against Klebsiella, but, in general, synergism by MIC checkerboard testing did predict synergism by time-kill methods (although the reverse was not true).…”

Section: Correlation Of Results By Various Methodsmentioning

confidence: 99%

“…Since that time, numerous studies utilizing various techniques and definitions have provided evidence for beta-lactam-aminoglycoside synergism against gram-negative bacilli (64). Although considerable attention has been given to the study of interactions against the Enterobacteriaceae (40,66,67,95,101), much attention has also been focused on activities of combination regimens against P. aeruginosa, no doubt due to difficulties in treating many such infections in seriously ill patients (19).…”

Section: Mechanisms Of Bactericidal Synergismmentioning

confidence: 99%

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Antibiotic combinations: should they be tested?

1988

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When antibiotic combinations are used to provide a broader spectrum of antimicrobial activity or in an attempt to prevent the emergence of resistant organisms, it is rarely necessary or practical to perform tests of drug interactions in vitro. In vitro testing of combinations may be useful when combinations are used in an attempt to attain synergistic interactions. In some cases, screening methods can be used as substitutes for formal synergy testing. This paper examines the mechanisms of antibiotic interaction leading to synergism or antagonism, surveys attempts to correlate in vitro observations with efficacy in animal models, and reviews clinical data providing evidence for or against a useful role of synergistic antibiotic interactions in the treatment of human infections.

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Section: Correlation Of Results By Various Methodsmentioning

confidence: 99%

Section: Mechanisms Of Bactericidal Synergismmentioning

confidence: 99%

Antibiotic combinations: should they be tested?

1988

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“…This may be one explanation of the discrepancies described by Norden et al (22). A few investigators have used the MBC to study antibiotic synergism (1,13,30).…”

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confidence: 99%

Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method

Hallander¹,

Dornbusch²,

Gezelius³

et al. 1982

Antimicrob Agents Chemother

145

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Combinations of gentamicin with cefotaxime, moxalactam, and ceftazidime were tested against 43 bacterial strains, most of them blood isolates. With an interaction index of 0.5 as borderline, synergism was demonstrated against 30 to 40% of the strains by the fractional inhibitory concentration index and against 50 to 70% by the fractional bactericidal concentration index. The reproducibility of the index was within ±0.2 for two-thirds of 40 repetitive assays and within ±0.4 to 0.5 for all of these assays. Similar results were obtained when netilmicin was substituted for gentamicin. The killing curve system for studying antibiotic synergism was standardized to give results comparable to those obtained with the interaction index. This was achieved when one-half of a previously determined minimum bactericidal concentration was used for single drugs and the amount of antibiotic was at least halved again when drugs were used in combination. An initial bacterial concentration of 105 to 106 colony-forming units per ml is recommended. Given these conditions, synergism could be defined as a 2-log10 or more decrease in viable count given by both drugs together, as compared with the more active of the pair after 24 h. Prediction of killing curve results could then be obtained with the fractional bactericidal concentration index. When cephalosporins and gentamicin were combined from the start, the beta-lactam antibiotics were less susceptible to inactivation, as demonstrated in time-killing assays. If one of the antibiotics were added after 24 h, synergism was not demonstrable. The results indicate that the new cephalosporins may be advantageously combined with aminoglycosides.

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“…β-Lactam-aminoglycoside combination therapy was advocated long ago mainly because of an observation of synergy between these antibiotic classes in vitro, i.e. enhanced killing of bacteria in the plate or tube with the combination as compared to the sum of the individual activities of antibiotic constituents of the combination [2,3,4]. However, between the plate in the microbiology laboratory and the individual patient treated in the ward there is a huge gap.…”

Section: Asking the Right Clinical Questionmentioning

confidence: 99%

Infections in Hematogical Cancer Patients: The Contribution of Systematic Reviews and Meta-Analyses

2010

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Systematic reviews and meta-analyses have made a major contribution to the evidence-based management of infections in cancer patients. We review the contribution of systematic reviews with regard to antibiotic, antifungal, antiviral and Pneumocystis pneumonia prophylaxis; antibiotic and antifungal treatment of febrile neutropenia; use of intravenous immunoglobulins, and infection control strategies during neutropenia. We focus on limitations of randomized controlled trials and the way systematic reviews have addressed and resolved some of these limitations. Systematic reviews allow us to ask the right clinical question; consider the most relevant clinical outcome; address the problem of small trials and rare outcomes; address external validity and bias in randomized controlled trials, and point at gaps in evidence.

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Synergism between Amikacin and Cefazolin against Klebsiella: In Vitro Studies and Effect on the Bactericidal Activity of Serum

Cited by 49 publications

References 7 publications

Antibiotic combinations: should they be tested?

Antibiotic combinations: should they be tested?

Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method

Infections in Hematogical Cancer Patients: The Contribution of Systematic Reviews and Meta-Analyses

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