Susceptibilities of 123 Xanthomonas maltophilia strains to clinafloxacin, PD 131628, PD 138312, PD 140248, ciprofloxacin, and ofloxacin

Abstract

The susceptibilities of 123 clinically isolated strains of Xanthomonas maltophilia to six fluoroquinolones (clinafloxacin, PD 131628, PD 138312, PD 140248, ciprofloxacin, and ofloxacin) were examined by microdilution MIC methodology. Clinafloxacin and PD 131628 were the most active compounds tested (MICs for 50% of the strains tested [MIC50s] of 0.5 and 1.0 ,ug/ml and MIC90s of 2.0 and 4.0 ,ug/ml, respectively). PD 138312, PD 140248, ciprofloxacin, and ofloxacin were less active, with MIC50s ranging from 4.0 to 8.0 ,ug/ml and MIC90s of 16.0 ,ug/ml for all four compounds. Only clinafloxacin and PD 131628 were active against ciprofloxacinresistant strains, with MIC50s of 0.5 and 1.0 ,ug/ml and MIC90s of 2.0 and 4.0 ,ug/ml, respectively.Infections caused by Xanthomonas maltophilia are increasingly encountered, especially in patients with compromised host defense mechanisms (10,11,17). The problem is further complicated by the inherently resistant nature of this species, which is due to a combination of permeability defects and ,B-lactamase production (3,10,11,13,17). Of commonly used antimicrobial agents, only trimethoprim-sulfamethoxazole has been found to be consistently active in vitro against this organism (10,17). Available quinolones such as ciprofloxacin and ofloxacin are marginally active, with MICs for susceptible isolates clustering around the breakpoint (1,4,9,(12)(13)(14). Clinafloxacin (CI-960, PD 127391) and PD 131628 (the active component of the prodrug CI-990) are two new fluoroquinolones with improved activity against gram-positive cocci, gramnegative nonfermenters, and anaerobes (5,6,8,9,12,16). This study compared the activities of clinafloxacin, PD 131628, two other experimental broad-spectrum fluoroquinolones (PD 138312 and PD 140248) (2, 7), ciprofloxacin, and ofloxacin against 123 clinical isolates of X maltophilia.Most clinical isolates (85%) were from different patients at Hershey Medical Center and University Hospitals of Cleveland and were collected over a 3-year period. The remainder were obtained from sources listed in the Acknowledgments and were isolated over a 6-year period. All strains were reidentified and MIC studies performed at Hershey Medical Center. Strains were identified by standard methods (10) Suscep-tibility breakpoints for ciprofloxacin (2.0 ,ug/ml) and ofloxacin (4.0 ,ug/ml) were those recommended by the National Committee for Clinical Laboratory Standards for members of the family Enterobacteriaceae (15). Breakpoints for the other four compounds were all 2.0 pug/ml, on the basis of preliminary data for members of the family Enterobacteriaceae (2). It should be noted, however, that no definitive quinolone susceptibility breakpoints are available for X maltophilia.The results of MIC testing are presented in Tables 1 and 2. Clinafloxacin and PD 131628 were the most active agents against all X. maltophilia strains, with 94 and 80% of the strains susceptible to the respective compounds at the preliminary breakpoints. MIC ranges of 0.06 to 8.0 and 0.125 to 16.0 iig/ml, MI...

Clinical Importance of Stenotrophomonas maltophilia Nosocomial Pneumonia Due to its High Mortality in Hemodialysis Patients

“…On the other hand, newer quinolones such as clinafloxacin and sparfloxacin appear to be more active against the bacterium than the older agents in this class (14). It has been reported that 93% of 25 ciprofloxacin-resistant strains were susceptible to clinafloxacin (15). The present data have also shown that only 5% of S. maltophilia isolated from HD pneumonia patients were susceptible to ciprofloxacin, while 57% were susceptible to levofloxacin.There are scant reports on the effective use of the newer quinolones in clinical settings towards S. maltophilia-related infection and prospective studies are awaited in the future.…”

In Vitro Activities of Clinafloxacin against Contemporary Clinical Bacterial Isolates from 10 North American Centers

“…Clinafloxacin was more than 10 times more active than ciprofloxacin against 99 strains of Stenotrophomonas maltophilia, resulting in 95% of strains being susceptible to clinafloxacin and 43% of strains being susceptible to ciprofloxacin. These results are comparable to those of previous studies (4,12).…”

Stenotrophomonas (Xanthomonas) maltophilia: A Multidrug‐Resistant Nosocomial Pathogen

“…Clinafloxacin, sparfloxacin, and PD-13 1628 are investigational fluoroquinolgnes with in vitro activity superior to that of ciprofloxacin against S. r n a l t o p h i l i~.~~~~~~~ In one series of 123 isolates, 94% were susceptible to clinafloxacin and 80% to PD-131628. 49 Breakpoints were 2 pg/ml. It is important to note that 80% of strains were resistant to ciprofloxacin (MIC > 2 pg/ml), and although MICs increased among other quinolones when isolates were ciprofloxacin resistant, 93% and 74% of strains remained susceptible to clinafloxacin and PD-131628, respectively.…”