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...

identification revealed a lack of gelatin, esculin, and tyrosine hyVeterinary Medicine, University of Ghent, Ghent, and the Laboratorium drolysis, a lack of urease activity, and the presence of nitratevoor Dierenziektebestrijding, Torhout, Belgium; and the Laboratory for reductase activity. Glucose and maltose were acidified, whereas Bacteriology, Faculty of Medicine, Strasbourg, France sucrose, mannitol, lactose, and glycogen were not. Propionic acid was produced by anaerobic fermentation of glucose, as reported References previously [6].In retrospect, the acute symptoms of our patient can be attributed Combinationand time-kill studies for synergy, were done to help predict the clinical response to therapy. The incidence of infections due to vancomycin-resistant Entero-A 76-year-old man with ischemic heart disease and aortic stenococcus faecium (VREF) has continued to increase during the past sis, underwent gastrectomy for gastric adenocarcinoma. His post-10 years. These organisms are typically multidrug resistant, and operative course was complicated by pneumonia, respiratory failoptimal antimicrobial therapy for serious VREF infections is unure, and central venous catheter-associated bacteremia due to known. None of the agents tested demonstrated bactericidal activity when used alone. However, the combinations of quinupristin/dalfopristin with doxycycline, quinupristin/dalfopristin with rifampin, and doxycycline with rifampin, were each synergistic against the patient's VREF isolate (figure 1). Although VREF bacteremia is now a well-recognized clinical entity, there is still only limited experience in treating endocarditis due to this organism (only two previously reported cases) [4,5]. Successful treatment of bacterial endocarditis generally requires the use of an agent or combination of agents with bactericidal activity against the infecting organism. This is often difficult to achieve in the management of infections due to vancomycin- Figure 1. Time-kill studies displaying the interaction of quinuprisresistant enterococci, especially VREF, as these organisms are tin/dalfopristin, doxycycline, and rifampin. -ࡗ -Å growth contypically multidrug resistant [6]. Although teicoplanin has been trol; -l -Å quinupristin/dalfopristin (0.25 mg/mL); -᭡ -Å used to treat selected infections caused by vancomycin-resistant doxycycline (0.06 mg/mL); --Å rifampin (1.0 mg/mL); enterococci with the vanB resistance phenotype, emergence of rrr᭝rrr Å quinupristin/dalfopristin (0.25 mg/mL) and doxycycline resistance during therapy has occurred [6], and Vijayvargiya and (0.06 mg/mL); -rr-ᮀ-rr -Å quinupristin/dalfopristin (0.25 mg/mL) Veis [4] described a patient with VREF endocarditis who failed and rifampin (1.0 mg/mL); ---᭺---Å doxycycline (0.06 mg/mL) and to respond to treatment with teicoplanin and gentamicin. Moreover, rifampin (1.0 mg/mL).most North American strains of VREF possess the vanA phenotype that is resistant to teicoplanin [6]. The investigational drug quinupristin/dalfopristin has in vitro activity against many...

The probe-based Velogene Rapid MRSA Identification Assay (ID Biomedical Corp., Vancouver, British Columbia, Canada) and the latex agglutination MRSA-Screen (Denka Seiken Co., Tokyo, Japan) were evaluated for their ability to identify methicillin-resistant Staphylococcus aureus (MRSA) and to distinguish strains of MRSA from borderline oxacillin-resistant S. aureus (BORSA; mecA-negative, oxacillin MICs of 2 to 8 g/ml). The Velogene is a 90-min assay using a chimeric probe to detect the mecA gene. MRSA-Screen is a 15-min latex agglutination test with penicillin-binding protein 2a antibody-sensitized latex particles. We compared these assays with the BBL Crystal MRSA ID System (Becton Dickinson, Cockeysville, Md.) and with PCR for mecA gene detection. A total of 397 clinical isolates of S. aureus were tested, consisting of 164 methicillin-susceptible strains, 197 MRSA strains, and 37 BORSA strains. All assays performed well for the identification of MRSA with sensitivities and specificities for Velogene, MRSA-Screen, and BBL Crystal MRSA ID of 98.5 and 100%, 98.5 and 100%, and 98.5 and 98%, respectively. Three MRSA strains were not correctly identified by each of the Velogene and MRSA-Screen assays, but repeat testing with a larger inoculum resolved the discrepancies. The BBL Crystal MRSA ID test misclassified four BORSA strains as MRSA. Both the Velogene and the MRSA-Screen assays are easy to perform, can accurately differentiate BORSA isolates from MRSA isolates, and provide a rapid alternative for the detection of methicillin resistance in S. aureus in clinical laboratories, especially when mecA PCR gene detection is unavailable.