In-vitro and in-vivo studies of trimethoprim-sulphamethoxazole against multiple resistant Staphylococcus aureus.

Methicillin and gentamicin resistant strains of Staphylococcus aureus (MRSA) remains a cause of significant morbidity and mortality. Vancomycin is usually effective against these strains, but toxicity and expense are significant drawbacks. Resistance to the new quinolones has been demonstrated in vitro and during clinical therapeutic trials. Trimethoprim-sulphamethoxazole has proved to be effective in vitro against staphylococcal strains that are resistant to gentamicin, methicillin, and quinolones. As determined by time-kill kinetic studies, trimethoprim-sulphamethoxazole was rapidly bactericidal. Clinical evaluation of trimethoprim-sulphamethoxazole against MRSA in patients with osteomyelitis is under study. We believe that our data support the use of trimethoprim-sulphamethoxazole as a potentially economical and effective alternative for the treatment of infections caused by MRSA.

Comparison of in vitro activity of quinolone antibiotics and vancomycin against gentamicin- and methicillin-resistant Staphylococcus aureus by time-kill kinetic studies.

Quinolone antibiotics have been proposed as possible alternatives to vancomycin for methicillin-resistant Staphylococcus aureus infections. We investigated the activities of amifloxacin, ciprofloxacin, norfloxacin, and vancomycin by time-kill kinetic studies. Antibiotic concentrations of 0, 1.0, and 4.0 times the MIC were used against four strains of gentamicin- and methicillin-resistant S. aureus. Staphylococci were plated onto ciprofloxacin-containing agar at all time points, in repeat time-kill kinetic studies. Macrobroth dilution MICs and MBCs were determined. Ciprofloxacin levels were measured by bioassay. Replica plating was performed from the original susceptible inoculum (MIC, 0.125 micrograms/ml) onto ciprofloxacin-supplemented agar. At 4.0 times the MIC, only with ciprofloxacin was there regrowth at 24 and 48 h. All four strains of staphylococci grew on agar supplemented with 1 microgram of ciprofloxacin per ml; three of four grew on agar supplemented with 2 micrograms of ciprofloxacin per ml. MICs and MBCs for these resistant clones ranged from 8 to 32 micrograms/ml. No degradation in activity or amount of ciprofloxacin could be detected in the bioassay. Replica-plated staphylococci grew on agar containing 1 microgram/ml but not higher concentrations of ciprofloxacin at 48 h. Amifloxacin and norfloxacin sustained bactericidal activity comparable to that of vancomycin. We conclude that heteroresistant subpopulations of gentamicin- and methicillin-resistant S. aureus can emerge under antibiotic selection pressure. Such resistant clones may then mutate in the presence of subinhibitory concentrations of antibiotic to higher levels of ciprofloxacin resistance.