Antibiotic Synergy and Antagonism Against Clinical Isolates of
            <i>Klebsiella</i>
            Species

R, D'Alessandri; McNeely, David J.; Kluge, Ronica M.

doi:10.1128/aac.10.6.889

Cited by 18 publications

(7 citation statements)

References 8 publications

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“…Multidrug resistance of bacteria against antimicrobials is a dangerous problem. Combination therapy is a commonly used treatment option especially for serious infections to provide synergistic effects, combat antibiotic resistance, reduce treatment time, and widen the therapeutic spectrum [13].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Drug Interactions: Systematic Evaluation of Protein and Nucleic Acid Synthesis Inhibitors

Yılancıoğlu

2019

Antibiotics

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Antimicrobial multidrug resistance and its transmission among strains are serious problems. Success rate is decreased and treatment options are narrowed due to increasing bacterial multidrug resistance. On the other hand, the need for long-term efforts to discover new antibiotics and difficulties finding new treatment protocols make this problem more complex. Combination therapy, especially with synergistic use of antimicrobials is a rational treatment option with huge benefits. Thus, screening antibiotic interactions is crucial for finding better treatment options. Clinicians currently use combinatorial antibiotic treatment as an effective treatment option. However, antibiotics can show synergistic or antagonistic interactions when used together. In our study, we aimed to investigate interactions of antibiotics with different mechanisms of action. Antibiotics, which act as protein synthesis inhibitors (P) and nucleic acid synthesis inhibitors (N) were used in our study. We tested 66 (PN), 15 (NN), and 55 (PP) drug pairs on the Escherichia coli strain. The Loewe additivity model was used and alpha scores were calculated for analysis of interactions of drug combinations. Drug interactions were categorized as synergistic or antagonistic. Accordingly, pairwise combinations of protein synthesis inhibitors (PP) showed stronger synergistic interactions than those of nucleic acid synthesis inhibitors (NN) and nucleic acid synthesis–protein synthesis inhibitors (PN). As a result, the importance of mechanisms of action of drugs is emphasized in the selection of synergistic drug combinations.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Drug Interactions: Systematic Evaluation of Protein and Nucleic Acid Synthesis Inhibitors

Yılancıoğlu

2019

Antibiotics

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“…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%

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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“…Forty-three of 50 strains tested against the combination of cefotaxime and gentami cin had a cefotaxime MBC less than or equal to 0.5 /zg/ml. The combination of a cephalosporin and an aminoglycoside is generally considered to be the treatment of choice for serious Klebsiella disease [29] based on previous reports [5,6] which dem onstrated synergistic killing in vitro of Klebsiella by the combination. In these previous studies the Klebsiella were not nearly as susceptible to the first generation cephalosporin used as to cefotaxime.…”

Section: Discussionmentioning

confidence: 99%

“…Jawetz and Gunnison [2] examined the concept of antibiotic combinations and made the observation that bacteriostatic antimicrobial agents may antagonize the action of bactericidal ones, and that some combinations of bactericidal agents may be 'synergistic'. Examples of combina tions of antimicrobial agents which are synergistic in vitro include penicillin and streptomycin against enterococci [3], ampicillin and gentamicin against Listeria [4], and cephalosporins and aminoglyco sides against Klebsiella [5,6].…”

Section: Introductionmentioning

confidence: 99%

Cefotaxime Aminoglycoside Interactions

Ma¹,

Elliott²,

Cg³

1985

Chemotherapy

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Minimum inhibitory concentrations and minimum bactericidal concentrations were determined for cefotaxime, gentamicin, tobramycin and amikacin and for the combination of cefotaxime and each of the aminoglycosides in vitro against 200 strains of Enterobacteriaceae. 91 % were susceptible to cefotaxime, 93.5% were susceptible to gentamicin, 89.5% were susceptible to amikacin and 68% were susceptible to tobramycin. There were 95 strains which could be evaluated for synergistic killing by the antimicrobial combinations. Synergism was shown against 78% of strains by cefotaxime and amikacin, against 71 % by cefotaxime and tobramycin and against 64% by cefotaxime and gentamicin. In 19 of 22 instances where a bacterial strain was resistant to both cefotaxime and the aminoglycoside, synergistic killing with clinically achievable levels of both antimicrobial agents was demonstrated. There was no significant decrease in concentration of any of the three aminoglycosides after incubation with cefotaxime at 37°C for 0,4 or 24 h.

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Antibiotic Synergy and Antagonism Against Clinical Isolates of Klebsiella Species

Cited by 18 publications

References 8 publications

Antimicrobial Drug Interactions: Systematic Evaluation of Protein and Nucleic Acid Synthesis Inhibitors

Antimicrobial Drug Interactions: Systematic Evaluation of Protein and Nucleic Acid Synthesis Inhibitors

Antibiotic combinations: should they be tested?

Cefotaxime Aminoglycoside Interactions

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