Significance of antimicrobial synergism for the outcome of gram negative sepsis

Klastersky, Jean; Meunier-Carpentier, F.; Prevost, Jean-Marie

doi:10.1097/00000441-197703000-00005

Cited by 150 publications

(57 citation statements)

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“…Synergy between two antimicrobial agents is defined as a greater-than-2-log increase in bactericidal activity in vitro compared with the bactericidal activity of each agent alone (60,91,95,129,130). The rate of bacterial killing by a fixed concentration of a single agent or multiple agents in combination can be depicted by a time-kill curve.…”

Section: Synergymentioning

confidence: 99%

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Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

2012

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SUMMARY Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa , those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria.

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Section: Synergymentioning

confidence: 99%

“…Some believe that patients with significant neutropenia benefit from the enhanced bactericidal activity offered by ␤-lactam and aminoglycoside combination therapy (9,127,129). Clinical benefits of synergistic combinations were evident in early studies involving neutropenic patients (57).…”

Section: Neutropeniamentioning

confidence: 99%

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

2012

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“…A number of studies of gram-negative bacteremia have suggested (but not proved) that combination therapy which is synergistic in vitro is therapeutically superior to combination therapy which is not synergistic in vitro (2,22,48,53). However, few studies have focused only on P. aeruginosa infections (2,15,36).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial agent therapy for Pseudomonas aeruginosa

Korvick

1991

Antimicrob Agents Chemother

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“…Several animal (2,3,16,18,24) and human (1,17) studies have demonstrated that certain antibiotic combinations are more effective than single antibiotics in eradicating serious infections and preserving life. Moreover, those combinations resulting in a successful therapeutic outcome are more likely to demonstrate in vitro synergism against infecting strains than less successful combinations (1,9,10,14,19,25). Thus, it seems rational to use such in vitro data in selecting optimal combinations of antibiotics for the empirical therapy of serious bacterial infections.…”

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confidence: 99%

Synergism at clinically attainable concentrations of aminoglycoside and beta-lactam antibiotics

Hooton¹,

Blair²,

Turck³

et al. 1984

Antimicrob Agents Chemother

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We evaluated the in vitro synergistic activity at clinically attainable concentrations of combinations of aminoglycoside and ,-lactam antibiotics against 30 gentamicin-resistant clinical isolates of gram-negative bacilli. All 56 pairs of 4 aminoglycosides and 14 1-lactams were evaluated. Combinations with amikacin demonstrated inhibitory synergistic activity in 29% of the assays, as compared with 22% for netilmicin (P = 0.018), 17% for gentamicin (P < 0.001), and 13% for tobramycin (P < 0.001 Antimicrobial synergism is said to occur when two or more antibiotics in combination exert an inhibitory effect on microorganisms that is greater than the additive effects of the individual antibiotics. Several animal (2,3,16,18,24) and human (1, 17) studies have demonstrated that certain antibiotic combinations are more effective than single antibiotics in eradicating serious infections and preserving life. Moreover, those combinations resulting in a successful therapeutic outcome are more likely to demonstrate in vitro synergism against infecting strains than less successful combinations (1,9,10,14,19,25). Thus, it seems rational to use such in vitro data in selecting optimal combinations of antibiotics for the empirical therapy of serious bacterial infections. Most previous investigations of in vitro synergism have involved small numbers of different antibiotic combinations and bacterial species. In this study, we compared the in vitro synergistic activity of a large number of combinations of aminoglycoside and ,-lactam antibiotics against a group of 30 gram-negative bacilli. Because synergism obtained at concentrations higher than those achieved with usual dosage regimens probably has little practical value, we expressed our results in terms of synergism obtained at clinically attainable concentrations of antibiotics.(These studies were presented in part at the 13th International Congress of Chemotherapy, Vienna, Austria, 1983.) MATERIALS AND METHODS We selected for study 30 isolates of gentamicin-resistant (MIC, >8 pug/ml) gram-negative bacilli of several species from clinical specimens submitted to microbiology laboratories at the Seattle Veterans Administration Hospital and Harborview Medical Center in Seattle, Wash. Among the 30 isolates were (number of isolates in parentheses) species of Achromobacter (1), Acinetobacter (1), Citrobacter (2), Enterobacter (2), Escherichia (3), Klebsiella (5), Providencia (1), Pseudomonas (9), and Serratia (6). All isolates were identified by standard microbiological methods. We evaluated 4 aminoglycoside and 14 P-lactam antibiotics, including * Corresponding author. 8 cephalosporins and 6 non-cephalosporins. The antibiotics evaluated were amikacin, gentamicin, netilmicin, tob--ramycin, cefoperazone, ceforanide, cefotaxime, cefpiramide (SM-1652), cefsulodin, ceftazidime, ceftizoxime, ceftriaxone, imipenem, moxalactam, Sch 29482, apalcillin, mezlocillin, and piperacillin. Standard powders for these antibiotics were supplied by their manufacturers (see Acknowledgments).Antimicrobial su...

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Significance of antimicrobial synergism for the outcome of gram negative sepsis

Cited by 150 publications

References 0 publications

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

Antimicrobial agent therapy for Pseudomonas aeruginosa

Synergism at clinically attainable concentrations of aminoglycoside and beta-lactam antibiotics

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