Activity of ciprofloxacin against resistant clinical isolates

The susceptibility of 28 clinical isolates of Pseudomonas maltophilia to 16 antimicrobial agents was determined in vitro by a standard agar dilution method with inoculum sizes of 104 and 106 CFU. All isolates exhibited multiple drug resistance. Nine isolates were selected for studies of combinations of ciprofloxacin with seven antipseudomonal ,-lactams and three aminoglycosides by a checkerboard agar dilution technique. Synergistic or additive combinations of ciprofloxacin in clinically achievable concentrations were most frequent with meziocillin (89%), followed by cefoperazone (67%), piperacillin (56%), cefsulodin (56%), and ceftazidime (33%), and were infrequent with aztreonam (11%), the aminoglycosides (0 to 14%), or imipenem (0%). Antagonism was not observed in any combination. These data suggest that combinations of ciprofloxacin with these agents may be useful for some nosocomial multiply drug-resistant P. maltophilia infections.Pseudomonas maltophilia is an important nosocomial pathogen (12) which presents a unique therapeutic challenge because of its tendency to exhibit multiple resistance to aminoglycosides and P-lactams (3,6,9,13). Furthermore, synergistic activity of aminoglycoside-,-lactam combinations is infrequently observed (3, 9). We examined the in vitro susceptibility of 28 clinical isolates of P. maltophilia to ciprofloxacin and three other quinolones (norfloxacin, difloxacin, and A-56620), as well as to nine extended-spectrum 1-lactams (carbenicillin, ticarcillin, piperacillin, imipenem, SCH-34343, aztreonam, ceftazidime, cefoperazone, and cefsulodin) and three aminoglycosides (gentamicin, tobramycin, and amikacin), by an agar dilution method. Selected strains were used to test for synergy of ciprofloxacin in combination with other agents by a checkerboard agar dilution technique. Demonstration of synergistic activity in vitro with these antimicrobial combinations may suggest useful therapeutic regimens for these difficult infections in the clinical setting.A total of 28 P. maltophilia isolates obtained from patients in Vancouver General Hospital were available for study. Sources included sputum (7 isolates), wounds (7 isolates), urine (2 isolates), cerebro spinal fluid (1 isolate), and miscellaneous sites (11 isolates). In vitro susceptibility to each antibiotic was determined by the agar dilution method (1). A Steers replicator was used to deliver a 0.0025-ml inoculum onto the surface of Mueller-Hinton agar (BBL Microbiology Systems) supplemented with calcium (50 mg/liter) and magnesium (25 mg/liter) and containing twofold serial dilutions of the test antibiotics. Unsupplemented Mueller-Hinton agar contained 1.5 mM calcium and 0.7 mM magnesium, as determined by atomic absorption spectrophotometry. The final cation concentrations in the supplemented medium were 2.7 mM calcium and 1.7 mM magnesium. The effect of inoculum was assessed by testing both inoculum sizes, 104 and 106 CFU per spot, for each organism. Plates without antibiotics served as controls. All plates were incubated for 24 h a...

supporting

confidence: 92%

Synergistic interactions of ciprofloxacin and extended-spectrum beta-lactams or aminoglycosides against multiply drug-resistant Pseudomonas maltophilia

Chow

Wong

Bartlett

1988

“…Of the 21 patients with negative cultures at the end of therapy, 11 were evaluated with follow-up cultures 21 to 30 days after the completion of therapy. Bacteriologic relapses occurred in 7 of the 11 patients (64%) but were not accompanied by clinical deterioration.…”

mentioning

confidence: 92%

Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections

Piercy

Barbaro

Luby

et al. 1989

Thirty-seven patients with methicillin-resistant Staphylococcus aureus infections and/or colonization were treated with oral ciprofloxacin (750 mg twice a day). Clinical cure or improvement of infections occurred in 91% of the patients, and bacteriologic cure occurred in 60%. Ciprofloxacin therapy suppressed methicillin-resistant S. aureus colonization in 55% of the patients. Ciprofloxacin-resistant strains emerged in 6 of the 37 patients.

“…The 4-quinolone ciprofloxacin appeared to be a promising agent in the treatment of staphylococcal infections because of its activity against methicillin-resistant strains (9,11,16). However, reports of emerging resistance of the staphylococci to ciprofloxacin are increasing (4,7,(13)(14)(15).…”

mentioning

confidence: 99%

Activity of new quinolones against ciprofloxacin-resistant staphylococci

Forstall

Knapp

Washington

1991

Because of the development of newer fluoroquinolones with inproved activity against gram-positive organisms, we elected to compare the inhibitory properties of ofloxacin, temafloxacin, sparfloxacin, PD131628, PD127391, and WIN57273 against 105 ciprofloxacin-resistant staphylococci. Based on comparison of MICs for 90% of the organisms (MIC9s), WIN57273 was the most active agent against oxacillin-resistant Staphylococcus aureus; the MIC90 was 0.5 ,ig/ml. Against oxacilHin-resistant, coagulase-negative staphylococci, PD127391 and WIN57273 were the most active agents; the MIC9 was 0.5 ,ug/ml. Against isolates of staphylococci for which ciprofloxacin MICs were .32 jig/m, WVIN57273 and PD127391 still exhibited high activity, inhibiting 100 and 95% of the isolates, respectively, at 2 ,ug/ml. The spontaneous mutation rates for ciprofloxacin-susceptible staphylococci were lowest for ofloxacin. The frequency of spontaneous mutations of ciprofloxacin-resistant staphylococci was low; however, the MICs of PD127391 and WIN57273 for these mutant isolates were greater than 2 ,ug/mI. WIN57273 and PD127391 are two potent new quinolones with high levels of activity against highly ciprofloxacin-resistant staphylococci. There is, however, a major concern of selection of spontaneous mutants resistant to these newer agents.The 4-quinolone ciprofloxacin appeared to be a promising agent in the treatment of staphylococcal infections because of its activity against methicillin-resistant strains (9, 11, 16). However, reports of emerging resistance of the staphylococci to ciprofloxacin are increasing (4,7,(13)(14)(15). We observed in our 1990 clinical isolates of Staphylococcus aureus and coagulase-negative Staphylococcus spp. a 25 and 27% resistance to ciprofloxacin, respectively. Because of the development of newer fluoroquinolones with improved activity against gram-positive organisms, we elected to compare the inhibitory properties of these agents against 105 oxacillin-and ciprofloxacin-resistant staphylococci. The agents we compared were ofloxacin (2), temafloxacin (A-62254) (1), sparfloxacin (CI-978; AT-4140) (2), PD127391 Other antimicrobial agents were provided by the indicated pharmaceutical companies: ciprofloxacin, Miles Pharmaceuticals, West Haven, Conn.; temafloxacin, Abbott Laboratories, North Chicago, Ill.; ofloxacin, Ortho Pharmaceutical Corp., Raritan, N.J.The organisms used in this study were stored (-70°C) clinical isolates of oxacillin-and ciprofloxacin-resistant S. aureus and coagulase-negative Staphylococcus spp. from the Cleveland Clinic Foundation, Cleveland, Ohio. Sources of the isolates included wounds, sputum, blood, urine, and other sites. Organisms were thawed, subcultured on blood agar, and transferred on blood agar prior to testing. Organ-* Corresponding author.isms used for quality control included S. aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853.MICs were determined by microdilution according to standard procedures published by the N...