Synergistic Activity of Colistin and Rifampin Combination against Multidrug-Resistant Acinetobacter baumannii in an In Vitro Pharmacokinetic/Pharmacodynamic Model (original) (raw)
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The open microbiology journal, 2017
The existence of infections caused by multidrug resistant (MDR) Acinetobacter baumannii is a growing problem because of the difficulty to treat them. We examined the published literature and focused our analysis on the investigation of the synergism of colistin and rifampin against MDR A. baumannii isolates via systematic review and meta-analysis. A systematic literature search was performed using the following 4 databases (PubMed, Scopus, EMBASE and ISI Web of Sciences). The related articles were evaluated during the period from December 2014 to January 2015. Information based on resistance and sensitivity to antibiotics, the minimum inhibitory concentration and the effects of two antibiotics on each other including synergism, antagonism, relative synergism and additive antagonism were extracted. A meta-analysis of 17 studies including 448 samples was brought into process and 2% (95% CI 0-4%) and 72% (95% CI 56-89%) resistance to colistin and rifampin were observed, respectively. 4...
Infection and Drug Resistance
Purpose: Colistin is a drug of last resort for treating multidrug-resistant Acinetobacter baumannii infections. Unfortunately, colistin-resistant A. baumannii (CoR-AB) has been reported. Here, we examined the in vitro effect of mono-and combined antimicrobials against CoR-AB strains and their resistance mechanism, and evaluated the clinical outcomes of CoR-AB-infected patients. Patients and methods: Seventeen clinical CoR-AB strains were isolated from patients at Phramongkutklao hospital, 2011-2015. The mono-and synergistic activities of colistin, tigecycline, sulbactam, imipenem, meropenem, amikacin, fosfomycin, and cotrimoxazole were examined by minimum inhibitory concentration (MIC) and fractional inhibitory concentration index. Clonal relationship and resistance genes were determined by repetitive extragenic palindromic polymerase chain reaction with specific primers. The effect of carbonyl cyanide 3-chlorophenylhydrazone combined with colistin was used to test efflux pump involvement. Patient treatment outcomes were also reported. Results: The most prevalent infection in CoR-AB patients was pneumonia (35.3%), and all patients were administered colistin combined with another agent. The 30-day mortality was 70.6%, and the colistin MIC range and MIC50 was 16-512 µg/mL and 64 µg/mL, respectively. All CoR-AB strains were sensitive to tigecycline. Sporadic isolates were susceptible to sulbactam, imipenem, meropenem, and cotrimoxazole. A synergistic or additive effect was observed for colistin plus imipenem or meropenem (16.7%), sulbactam (66.7%), or tigecycline (66.7%). The CoR-AB isolates could be divided into four different clones (A-D) with a high prevalence of group B (47.1%). Eight isolates harbored blaOXA23, blaIMP, blaKPC, and blaNDM, and one contained blaOXA23, blaIMP, and blaKPC, while the eight remaining isolates carried only blaOXA23. The MIC values of all strains were greatly reduced for colistin plus carbonyl cyanide 3-chlorophenylhydrazone. Conclusion: CoR-AB clinical isolates exhibited very high colistin resistance and a high frequency of resistance genes. The mechanism of colistin resistance appears to be mediated via an efflux pump. Thus, certain antimicrobials could be used as salvage therapy for CoR-AB infection.
Disease and Molecular Medicine, 2016
Acinetobacter baumannii has emerged as one of the most important nosocomial pathogens and multi-drug resistant (MDR) isolates are of great concern worldwide. The aim of the present study was to investigate the in vitro synergistic activity of colistin in combination with other antibiotics against MDR A. baumannii blood stream isolates. A total of 54 non-duplicate, MDR A. baumannii isolates from blood culture specimens obtained between June 2011 and July 2012 were included in the study. In vitro synergistic activity of colistin in combination with imipenem, tigecycline or cefoperazone-sulbactam against study isolates was investigated by Etest superimposing method and the fractional inhibitory concentration (FIC) index was calculated for each antibiotic combination. The most frequent synergistic effect of colistin was found in combination with tigecycline in only 7 isolates (13.0%). All three antibiotics were found to have synergistic effect with colistin in four isolates (7.4%). Of isolates, 46 (85.2%) showed additive effect of colistin in combination with cefoperazone-sulbactam or tigecycline, 45 (83.3%) with imipenem. We found synergistic activity of colistin with other antibiotics in only a small number of isolates. Although Etest method is a practical method to investigate the synergistic activity, in case of choosing empirical treatment, colistin in combination with another antibiotic may be preferred.
Antimicrobial agents and chemotherapy, 2016
Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii. Nine clinical isolates (8 from bacteremia cases and 1 from pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, Korea, between Jan 2010 and Dec 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of ...
Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections
J Antimicrob Chemother, 2007
Objectives: The increased incidence of nosocomial infections by multidrug-resistant organisms has motivated the re-introduction of colistin in combination with other antimicrobials in the treatment of infections. We describe the clinical and microbiological outcomes of patients infected with multidrugresistant Acinetobacter baumannii who were treated with a combination of colistin and rifampicin.
Clinical Infectious Diseases, 2013
Background. Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. Methods. This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. Results. Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. Conclusions. In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. Clinical Trials Registration. NCT01577862.
Antimicrobial Agents and Chemotherapy, 2012
ABSTRACTColistin resistance, although uncommon, is increasingly being reported among Gram-negative clinical pathogens, and an understanding of its impact on the activity of antimicrobials is now evolving. We evaluated the potential for synergy of colistin plus trimethoprim, trimethoprim-sulfamethoxazole (1/19 ratio), or vancomycin against 12 isolates ofAcinetobacter baumannii(n= 4),Pseudomonas aeruginosa(n= 4), andKlebsiella pneumoniae(n= 4). The strains included six multidrug-resistant clinical isolates,K. pneumoniaeATCC 700603,A. baumanniiATCC 19606,P. aeruginosaATCC 27853, and their colistin-resistant derivatives (KPm1, ABm1, and PAm1, respectively). Antimicrobial susceptibilities were assessed by broth microdilution and population analysis profiles. The potential for synergy of colistin combinations was evaluated using a checkerboard assay, as well as static time-kill experiments at 0.5× and 0.25× MIC. The MIC ranges of vancomycin, trimethoprim, and trimethoprim-sulfamethoxazole...
International Journal of Arts Humanities and Social Sciences Studies, 2021
The general objective of this study was to determine the bacteriological effect of drug combinations with colistin to Extensive Drug resistant Acinetonacter baumanii strains (XDRAB). The antimicrobial combinations tested for Acinetobacter baumanii were colistin and teicoplanin, colistin and tigecycline, colistin and minocycline, colistin and trimethoprim/sulfa, colistin and rifampicin (n = 57). The methods used in this study are pairs of E-test strips which is easy and inexpensive to perform and using the determined MICs of single antimicroabial and the in combination with colistin. The degree of agreement between FIC results calculated by E-test method varies in the literature depending on the type of bacteria tested. For example, 86% agreement was found between the results of the two tests when used with Acineto baumanii. A limitation of the E-test method is that it does not provide information about the bactericidal activity of the combination. We have shown that this method particularly useful in screening a large number of isolates against several combinations of antimicrobials. The results revealed that The combination of colistin and teicoplanin although shows synergy but in the lowest mean 10.5% while combinations of colistin with trimethoprim/sulfa gave the highest percentage of 86% followed by colistin and tigecycline 80.7% and colistin and rifampicin with 61% which means that if you combined this antimicrobial agents it gives greater results than using them separately effects against XDRAB. The other antimicrobial agent gives less than 50% demonstrating either an additive affect or synergy. Other combinations tested were predominantly indifferent. We did not find a combination of antimicrobials that was consistently antagonistic when used against Acinetobacter baumanii. There are significant differences in the effect of single utilization of antibiotic (colistin) and combined drugs such as colistin and teicoplanin although it shows synergy but in lowest percentage of 10.5%, while 86% gives the highest percentage of combination with colistin and trimethoprim/sulfa then followed by colistin and tigecycline 80.7% and colistin and rifampicin with 61% which means that if you combined this antimicrobial agents it gives greater results than monotherapy against Extensive Drug resistant Acinetonacter baumanii. In conclusion, although the in vitro activity of an antimicrobial does not necessarily compare with the in vivo biological activity, results in previous work suggest a relationship between the MIC of an antimicrobial and clinical outcome of Acinetobacter baumanii against a single antimicrobial. In particular, a lower MIC was associated with a faster healing response. It is reasonable to assume that the lower the MIC of an antimicrobial for a given isolate, the more likely it is that the infection will respond to treatment and that the MIC of the antimicrobial can be used to evaluate the potential efficacy of a given agent for the treatment. It is not known whether the distributions of antimicrobial sensitivities of bacterial isolates tested in this study were affected by prior antimicrobial treatment before isolation of the bacteria. However, the isolates were selected from a national collection with a distribution of isolates similar to that in previous studies, and we think they are therefore representative of the bacteria. Based on IN VITRO analysis antimicrobial combination that demonstrates a synergistic or additive effect as determined by MIC, this combination may prove more effective than monotherapy with the individual agent. It should be noted that the definitions of effect, from synergy through to indifferent, are definitions that relate to interaction in vitro, and it is unknown whether they translate into an improved outcome for topical combination therapy. If the extrapolation to an in vivo effect is valid, a synergistic or additive antimicrobial combination offers a broader spectrum of activity that may reduce selective pressures and the emergence of resistance.