Analysis of Aminoglycosides in the Treatment of Gram-negative Infections in Surgical Patients

Crabtree, Traves D.; Pelletier, Shawn J.; Gleason, Thomas G.; Pruett, Timothy L.; Sawyer, Robert G.

doi:10.1001/archsurg.134.12.1293

Cited by 19 publications

(6 citation statements)

References 15 publications

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“…A similar study focusing on Klebsiella bacteraemia found an advantage for combination therapy only among patients with hypotension,15 while other studies have not found such an advantage 10 – 12 88…”

Section: Discussionmentioning

confidence: 94%

“…In aiming for optimal antibiotic treatment of severe infections, hospital clinicians tend to use combination therapy despite the lack of direct evidence for its effectiveness. Observational studies show that 25-30% of patients with bacteraemia,10 11 surgical infections,12 or pneumonia,13 14 50% of those with klebsiella bacteraemia,15 and 56% of patients with septic shock in the intensive care unit16 are given β lactam-aminoglycoside combination therapy.…”

Section: Introductionmentioning

confidence: 99%

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β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

Paul

Benuri-Silbiger

Soares‐Weiser

et al. 2004

BMJ

420

184

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Objective To compare lactam monotherapy with lactam-aminoglycoside combination therapy for severe infections. Data sources Medline, Embase, Lilacs, Cochrane Library, and conference proceedings, to 2003; references of included studies; contact with all authors. No restrictions, such as language, year of publication, or publication status. Study selection All randomised trials of lactam monotherapy compared with lactam-aminoglycoside combination therapy for patients without neutropenia who fulfilled criteria for sepsis. Data selection Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary outcome assessed was all cause fatality by intention to treat. Relative risks were pooled with the random effect model (relative risk < 1 favours monotherapy). Results 64 trials with 7586 patients were included. There was no difference in all cause fatality (relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared the same lactam (1.02, 0.76 to 1.38), and 31 studies compared different lactams (0.85, 0.69 to 1.05). Clinical failure was more common with combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different lactams (0.76, 0.68 to 0.86). There was no advantage to combination therapy among patients with Gram negative infections (1835 patients) or Pseudomonas aeruginosa infections (426 patients). There was no difference in the rate of development of resistance. Nephrotoxicity was significantly more common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not significant for these comparisons. Conclusions In the treatment of sepsis the addition of an aminoglycoside to lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

Paul

Benuri-Silbiger

Soares‐Weiser

et al. 2004

BMJ

420

184

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“…Observational studies show that between 25 and 50% of patients with bacteremia, surgical site infections, or pneumonia and over 50% of patients with septic shock in the intensive care unit (ICU) are administered combination antibiotic therapy (20,54,100,117,134,138,152,173,228,246). The question of whether a combination of a ␤-lactam and an aminoglycoside or fluoroquinolone confers a benefit in patients beyond broadening the antimicrobial spectrum during the empiric treatment period before culture results are available is unsettled.…”

mentioning

confidence: 99%

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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“…Aminoglycoside/beta-lactam combinations have been reported to exhibit synergy and have historically been among the most frequently used clinically [21][22][23][24][25][26] . We analyzed the dataset for combinations involving one of 3 aminoglycosides (amikacin, gentamicin, tobramycin) and one of 7 beta-lactams (ampicillin, aztreonam, cefazolin, cefepime, ceftazidime, meropenem or the beta-lactam/beta-lactamase inhibitor, piperacillin/tazobactam).…”

mentioning

confidence: 99%

Antibiotic combinations that exploit heteroresistance to multiple drugs effectively control infection

et al. 2019

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Antibiotic resistant bacteria are a significant threat to human health, with one estimate suggesting they will cause 10 million worldwide deaths per year by 2050, surpassing deaths due to cancer 1. Since new antibiotic development can take a decade or longer, it is imperative to effectively use currently available drugs. Antibiotic combination therapy offers promise for treating highly resistant bacterial infections, but the factors governing the sporadic efficacy of such regimens have remained unclear. Dogma suggests that antibiotics ineffective as monotherapy can be effective in combination 2. Here, using carbapenemresistant Enterobacteriaceae (CRE) clinical isolates, we revealed the underlying basis for the majority of effective combinations to be heteroresistance. Heteroresistance is a poorly understood mechanism of resistance reported for different classes of antibiotics 3-6 in which only a subset of cells are phenotypically resistant 7. Within an isolate, the subpopulations resistant to different antibiotics were distinct, and over 88% of CRE isolates exhibited heteroresistance to multiple antibiotics ("multiple heteroresistance"). Combinations targeting multiple heteroresistance were efficacious, whereas those targeting homogenous resistance

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Analysis of Aminoglycosides in the Treatment of Gram-negative Infections in Surgical Patients

Cited by 19 publications

References 15 publications

β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

Antibiotic combinations that exploit heteroresistance to multiple drugs effectively control infection

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