PARENTERAL SPARFLOXACIN COMPARED WITH CEFTRIAXONE IN TREATMENT OF EXPERIMENTAL ENDOCARDITIS DUE TO PENICILLIN-SUSCEPTIBLE AND PENICILLIN-RESISTANT STREPTOCOCCI

A new, investigational, parenteral form of sparfloxacin was compared w ith ceftriaxone in the treatment of experimental endocarditis caused b y either of three penicillin-susceptible streptococci or one penicilli n-resistant streptococcus. Both drugs have prolonged half-lives in ser um, allowing single daily administration to humans. Sparfloxacin had r elatively low MICs (0.25 to 0.5 mg/liter) for all four organisms and w as also greater than or equal to eight times more effective than the o ther quinolones against 21 additional streptococcal isolates recovered from patients with bacteremia. Ceftriaxone MICs were 0.032 to 0.064 m g/liter for the penicillin-susceptible strains and 2 mg/liter for the resistant isolate. Both antibiotics resulted in moderate bacterial kil ling in vitro. Rats with catheter-induced aortic vegetations were inoc ulated with 10(7) CFU of the test organisms. Antibiotic treatment was started 48 h later and lasted either 3 or 5 days. The drugs were injec ted at doses which mimicked the kinetics in human serum produced by on e intravenous injection of 400 mg of sparfloxacin (i.e., the daily dos e expected to be given to human adults) and 2 g of ceftriaxone. Both a ntibiotics significantly decreased the bacterial densities in the vege tations. However, sparfloxacin was slower than ceftriaxone in its abil ity to eradicate valvular infection caused by penicillin-susceptible b acteria. While this difference was quite marked after 3 days of therap y, it tended to vanish when treatment was prolonged to 5 days. In cont rast, sparfloxacin was very effective against the penicillin-resistant isolate, an organism against which ceftriaxone therapy failed in vivo . No sparfloxacin-resistant mutant was selected during therapy. Thus, in the present experimental setting, this new, investigational, parent eral form of sparfloxacin was effective against severe infections caus ed by both penicillin-susceptible and penicillin-resistant streptococc i.