Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumannii Clinical Strains

O’Hara, Jessica A.; Ambe, Lauretta A.; Casella, Leila G.; Townsend, Bethany M.; Pelletier, Mark; Ernst, Robert K.; Shanks, Robert M. Q.; Doi, Yohei

doi:10.1128/aac.02501-12

Cited by 68 publications

(66 citation statements)

References 33 publications

(43 reference statements)

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“…In an in vivo study, the authors studied the effect of combinations of vancomycin, colistin, and doripenem on clinical strains of CRAB and found promising results. Their findings suggested that regimens containing vancomycin may confer a therapeutic benefit against infections caused by CRAB [36].…”

Section: Combination Therapymentioning

confidence: 99%

Acinetobacter baumannii : A Brief Account of Mechanisms of Multidrug Resistance and Current and Future Therapeutic Management

Singh¹

2013

JCDR

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Section: Combination Therapymentioning

confidence: 99%

Acinetobacter baumannii : A Brief Account of Mechanisms of Multidrug Resistance and Current and Future Therapeutic Management

Singh¹

2013

JCDR

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“…This effect likely results from the action of colistin on the A. baumannii outer membrane, enabling glycopeptides access to cell wall targets from which they are usually excluded. Furthermore, such a combination was shown to be active against other MDR GNB that were heteroresistant to colistin (10,11). However, the main concern for the use of a colistin-glycopeptide combination is the potential for nephrotoxicity, and thus, to date, the evidence for its clinical efficacy is lacking.…”

mentioning

confidence: 99%

Clinical Experience of Colistin-Glycopeptide Combination in Critically Ill Patients Infected with Gram-Negative Bacteria

Petrosillo

Giannella

Antonelli

et al. 2014

Antimicrob Agents Chemother

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A colistin-glycopeptide combination (CGC) has been shown in vitro to be synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB), especially Acinetobacter baumannii, and to prevent further resistance. However, clinical data are lacking. We carried out a retrospective multicenter study of patients hospitalized in intensive care units (ICUs) who received colistin for GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30-day mortality after treatment onset among patients treated with and without CGC for >48 h. Of the 184 patients treated with colistin, GNB infection was documented for 166. The main causative agents were MDR A. baumannii (59.6%), MDR Pseudomonas aeruginosa (18.7%), and carbapenem-resistant Klebsiella pneumoniae (14.5%); in 16.9% of patients, a Gram-positive bacterium (GPB) coinfection was documented. Overall, 68 patients (40.9%) received CGC. Comparison of patients treated with and without CGC showed significant differences for respiratory failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus 71.4%), MDR A. baumannii infection (70.6% versus 52%), and GPB coinfection (41.2% versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and 30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who survived for >5 days after treatment onset showed that the Charlson index (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44; P ‫؍‬ 0.001) and MDR A. baumannii infection (HR, 2.51; 95% CI, 1.23 to 5.12; P ‫؍‬ 0.01) were independent predictors of 30-day mortality, whereas receiving CGC for >5 days was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93; P ‫؍‬ 0.03). We found that CGC was not associated with higher nephrotoxicity and was a protective factor for mortality if administered for >5 days.

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“…Most synergy studies against A. baumannii, however, are conducted in vitro by applying time-kill or checkerboard methodology, where only specific fixed concentrations of antibiotics are studied. Using this methodology, numerous studies have observed synergistic interactions between polymyxins and various other antibiotic classes, including carbapenems, tigecycline, rifampin, and most recently, vancomycin (15)(16)(17)(18)(19)(20)(21)(22). These time-kill and checkerboard experiments, however, ignore the contribution of human pharmacokinetics and the dynamic effects of varied drug concentrations over the duration of the experiment.…”

mentioning

confidence: 99%

In Vitro Pharmacodynamics of Polymyxin B and Tigecycline Alone and in Combination against Carbapenem-Resistant Acinetobacter baumannii

Hagihara

Housman

Nicolau

et al. 2014

Antimicrob Agents Chemother

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b Carbapenem-resistant Acinetobacter baumannii is increasing in prevalence. Polymyxin B and tigecycline are among the most active antibiotics used against this pathogen in vitro. Past in vitro studies, however, neglected the importance of simulating exposures observed in humans to determine their antibacterial effects. In this study, four carbapenem-resistant A. baumannii isolates were evaluated using an in vitro pharmacodynamic model. Free-drug exposures using 1 mg/kg of body weight of polymyxin B every 12 h (q12h), 100 and 200 mg tigecycline q12h, and the combination of these regimens were simulated. The microbiological responses to these treatments were measured by the change in log 10 CFU/ml over 24 h and the area under the bacterial killing and regrowth curve (AUBC). Resistance was assessed by a population analysis profile (PAP) conducted after 24 h of treatment. Polymyxin B achieved a reduction on the order of ؊2.05 ؎ 0.68 log 10 CFU/ml against these A. baumannii isolates, while all isolates grew to control levels with tigecycline monotherapy. Combination therapy with polymyxin B plus 200 mg tigecycline q12h achieved a greater reduction in bacterial density than did therapy with polymyxin B alone (؊3.31 ؎ 0.71 versus ؊2.05 ؎ 0.68 log 10 CFU/ml, P < 0.001) but not significantly different than combination therapy with 100 mg tigecycline q12h (؊2.45 ؎ 1.00 log 10 CFU/ml, P ‫؍‬ 0.370). Likewise, combination therapy with polymyxin B plus 200 mg tigecycline q12h significantly reduced the AUBC compared to that with polymyxin B alone (62.8 ؎ 8.9 versus 79.4 ؎ 10.5 log 10 CFU/ml, P < 0.05). No changes in the PAP from baseline were observed for either antibiotic alone. In this study, combination therapy with simulated exposures of polymyxin B and tigecycline at an aggressive dose of 200 mg q12h produced synergistic or additive effects on humans against these multidrug-resistant A. baumannii strains.

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Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumannii Clinical Strains

Cited by 68 publications

References 33 publications

Acinetobacter baumannii : A Brief Account of Mechanisms of Multidrug Resistance and Current and Future Therapeutic Management

Acinetobacter baumannii : A Brief Account of Mechanisms of Multidrug Resistance and Current and Future Therapeutic Management

Clinical Experience of Colistin-Glycopeptide Combination in Critically Ill Patients Infected with Gram-Negative Bacteria

In Vitro Pharmacodynamics of Polymyxin B and Tigecycline Alone and in Combination against Carbapenem-Resistant Acinetobacter baumannii

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