Synergistic Interaction in Vitro with Use of Three Antibiotics Simultaneously against Pseudomonas maltophilia

Yu, Victor L.; Felegie, T P; Yee, Robert B.; Pasculle, A. William; Taylor, Floyd H.

doi:10.1093/infdis/142.4.602

Cited by 40 publications

(21 citation statements)

References 6 publications

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“…1). Synergy for three antibiotics has been defined by several investigators as a fractional sum of Ͻ1.0 (⌺FIC of Ͻ1.0) (3,27). Plotted values showing concave surface areas on the isobolograms correspond to synergy, and convex areas represent antagonism (3,27).…”

Section: Discussionmentioning

confidence: 99%

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In Vitro Double and Triple Synergistic Activities of Polymyxin B, Imipenem, and Rifampin against Multidrug-Resistant Acinetobacter baumannii

Yoon

Urban

Terzian

et al. 2004

Antimicrob Agents Chemother

158

105

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Eight unrelated clinical Acinetobacter baumannii isolates resistant to all commonly used antibiotics were subjected to three-dimensional checkerboard microtiter plate dilution and time-kill studies at one-fourth of their MICs of polymyxin B, imipenem, and rifampin. Synergy was demonstrated with combinations of polymyxin B and imipenem, polymyxin B and rifampin, and polymyxin B, imipenem, and rifampin. Double combinations of polymyxin B and imipenem and of polymyxin B and rifampin were bactericidal for seven of eight isolates, and triple combinations were bactericidal for all isolates within 24 h. Future clinical studies using double and triple therapy with these antibacterials may provide an effective option against potentially lethal infection due to multiresistant Acinetobacter baumannii.In recent years, Acinetobacter baumannii has emerged as one of the more ubiquitous antibiotic-resistant gram-negative nosocomial pathogens among critically ill patients (4, 23). Although the carbapenems, ampicillin-sulbactam, and amikacin have retained excellent in vitro and clinical activities against susceptible strains of A. baumannii, a growing number of reports have documented resistance to these antibacterials (1, 2, 10, 12-14, 16). As a result nontraditional agents, including polymyxin B and colistin, have been used to treat patients infected with multiresistant A. baumannii (6, 9, 15). However, pulmonary infections have not responded well to such monotherapy, and resistance has occurred among strains that have persisted during treatment (6,15,24).In this communication, we describe the in vitro double and triple interactions of polymyxin B, imipenem, and rifampin against eight unique strains of multidrug-resistant A. baumannii using checkerboard microdilution and time-kill methods. MATERIALS AND METHODSEight multidrug-resistant clinical strains of A. baumannii were obtained from the Clinical Microbiology Laboratory at New York Hospital Queens. All isolates had different pulsed-field gel electrophoresis patterns and were considered unrelated according to the criteria established by Tenover et al. (21). MICs of selected individual antibiotics were then determined using microdilution and E-test methods (AB Biodisk North America Inc., Piscataway, N.J.) by the Infectious Disease Research Laboratory. E-test metallo-beta-lactamase (E-test MBL) strips were used to detect the presence of molecular class B beta-lactamases (25). Rifampin and polymyxin B were obtained from Sigma (St. Louis, Mo.), and imipenem powder was supplied by Merck and Co. (Rahway, N.J.). MIC determinations were performed using checkerboard microdilution methods with Mueller-Hinton broth and a final inoculum of approximately 5 ϫ 10 5 CFU/ml. Microdilution plates for evaluation of triple drug combinations were performed in the following manner. The first microtiter plate contained no imipenem and increasing concentrations of rifampin ranging from 0 to 32 g/ml on the x axis and increasing concentrations of polymyxin B ranging from 0 to 32 g/ml on the y axis. Ea...

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Section: Discussionmentioning

confidence: 99%

“…A bactericidal effect was defined as Ն99.9% killing of the starting inoculum. FICs of Ͻ1.0, 1.0, and Ͼ1.0 were used to define synergy, addition, and antagonism, respectively, according to previously published methods (3,27). Time-kill studies were also performed according to earlier described techniques (7,17).…”

Section: Methodsmentioning

confidence: 99%

In Vitro Double and Triple Synergistic Activities of Polymyxin B, Imipenem, and Rifampin against Multidrug-Resistant Acinetobacter baumannii

Yoon

Urban

Terzian

et al. 2004

Antimicrob Agents Chemother

158

105

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“…All study isolates were susceptible to TMP-SMX. Yu et al (40) found that the addition of rifampin to TMP-SMX plus carbenicillin resulted in consistent synergy by the checkerboard method. Confirmation of these results by time-kill studies was performed with one isolate only and may not adequately reflect the behavior of all strains.…”

Section: Discussionmentioning

confidence: 99%

In vitro activities of antimicrobial combinations against Stenotrophomonas (Xanthomonas) maltophilia

Poulos

Matsumura

Willey

et al. 1995

Antimicrob Agents Chemother

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Stenotrophomonas (Xanthomonas) maltophilia is inherently resistant to multiple antimicrobial agents. In order to investigate the in vitro potential of combinations of antimicrobial agents, we obtained 230 epidemiologically unrelated clinical isolates from seven hospitals across Canada and from Northwestern Memorial Hospital in Chicago. Ticarcillin-clavulanate combined with ciprofloxacin or trimethoprim-sulfamethoxazole were assayed for synergy against 31 ticarcillin-resistant strains of S. maltophilia by using microtiter checkerboard panels and against 20 strains by using time-kill methodology. The combination of ciprofloxacin with ceftazidime was also evaluated by time-kill studies. Ticarcillin-clavulanate plus trimethoprim-sulfamethoxazole demonstrated synergy by checkerboard panels, with fractional inhibitory concentration indices ranging from 0.033 to 0.49, and by time-kill studies for all 20 strains tested. Synergy between ticarcillin-clavulanate plus ciprofloxacin was found by the checkerboard method for 24 of 31 strains (77%), with fractional inhibitory concentration indices ranging from 0.188 to 0.75. A correlation between synergy by the checkerboard method and the reference time-kill study method was not observed for ticarcillin-clavulanate plus ciprofloxacin, with results for 3 of 10 strains being nonconcordant. Synergy with both ticarcillin-clavulanate plus ciprofloxacin and ceftazidime plus ciprofloxacin by the time-kill method was found to correlate with ciprofloxacin MICs of <32 g/ml and zone diameters of >15 mm on Mueller-Hinton agar. Evaluation of these combinations in vivo may be warranted.Stenotrophomonas (Xanthomonas) maltophilia is an aerobic, gram-negative bacillus which has been isolated from humans, animals, food, pharmaceuticals, and various environmental sources. Because of the low level of pathogenicity and limited invasiveness of S. maltophilia, serious community-acquired infection is infrequent (12, 18). However, significant morbidity and mortality are widely recognized among neutropenic, immunocompromised, and debilitated patients, in whom this organism may become disseminated and result in life-threatening disease (12,18,23,27,37).The antimicrobial resistance of S. maltophilia is attributed to low outer membrane permeability (9,14,15,20,21,39) and the unusual production of multiple chromosomally mediated, broad-spectrum ␤-lactamases, among which are L1 and L2 (1,10,14,15,29,30,32,33). L1 and related ␤-lactamases are group 3 metallopenicillinases and carbapenemases (1,7,15,20,30,33), while L2 and related ␤-lactamases are group 2e cephalosporinases capable of hydrolyzing penicillins and monobactams (1,7,15,20,29,32). All ␤-lactamases are induced synchronously, indicating an apparent overlap of regulatory systems (1,22,30).In vitro susceptibility testing of S. maltophilia is problematic, and results obtained by such tests should be interpreted with caution (1,6,10,13,16,21,38). The National Committee for Clinical Laboratory Standards (NCCLS) (26) currently recommends broth or agar dilu...

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“…Furthermore, various antibiotic combinations yielded additive or synergistic effects against this microorganism, notably timentin + cotrimoxazole [49], fluoroquinolones + extended spectrum ß-lactams or ami- noglycosides [49,52], cotrimoxazole + polymyxin B [51], and ceftazidime + trovafloxacin [50]. Also, triple combinations of antibiotics (cotrimoxazole + carbenicillin + rifampin or gentamicin + carbenicillin + rifampin) were synergistically active against S. maltophilia [10,54].…”

Section: Introductionmentioning

confidence: 99%

Antibiotic Susceptibility of Stenotrophomonas (Xanthomonas) maltophilia: Comparative (NCCLS Criteria) Evaluation of Antimicrobial Drugs with the Agar Dilution and the Agar Disk Diffusion (Bauer-Kirby) Tests

Traub

Leonhard

Bauer³

1998

Chemotherapy

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Ninety-six clinical isolates of Stenotrophomonas maltophilia were examined with the agar dilution method for susceptibility to 19 antimicrobial drugs. Doxycycline, cotrimoxazole, timentin, ofloxacin, fosfomycin, and piperacillin + tazobactam, in that order, inhibited the majority of strains. All isolates were resistant to nitrofurantoin. Concurrent disk susceptibility (Bauer-Kirby method) testing, using currently valid NCCLS interpretative criteria for Pseudomonas aeruginosa, uncovered a significant incidence of very major (category I), major (category II), and minor (categories III and IV) discrepancies for aminoglycosides, cephalosporins, chloramphenicol, and piperacillin + tazobactam and ticarcillin + clavulanic acid. Therefore, new interpretative criteria indicative of intermediate (I) susceptibility of S. maltophilia to these various antibiotics were proposed. In addition, new intermediate susceptibility criteria were proposed for the two β-lactam-β-lactamase inhibitor combinations. It was recommended to exclude ciprofloxacin from test batteries against this microorganism due to the wide scatter of minimal inhibitory concentration values and diameters of inhibition zones; the same was true for polymyxin B. It is hoped that the proposed modified, species- specific criteria will improve the clinical utility of laboratory-generated disk antibiograms with respect to the inherently multiple antibiotic-resistant, opportunistic pathogen S. maltophilia.

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Synergistic Interaction in Vitro with Use of Three Antibiotics Simultaneously against Pseudomonas maltophilia

Cited by 40 publications

References 6 publications

In Vitro Double and Triple Synergistic Activities of Polymyxin B, Imipenem, and Rifampin against Multidrug-Resistant Acinetobacter baumannii

In Vitro Double and Triple Synergistic Activities of Polymyxin B, Imipenem, and Rifampin against Multidrug-Resistant Acinetobacter baumannii

In vitro activities of antimicrobial combinations against Stenotrophomonas (Xanthomonas) maltophilia

Antibiotic Susceptibility of Stenotrophomonas (Xanthomonas) maltophilia: Comparative (NCCLS Criteria) Evaluation of Antimicrobial Drugs with the Agar Dilution and the Agar Disk Diffusion (Bauer-Kirby) Tests

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