In vitro activity of sparfloxacin (AT-4140), a new quinolone agent, against invasive isolates from pediatric patients

Abstract

Sparfloxacin is a new oral fluoroquinolone agent with putative activity against common pediatric pathogens. Using the broth microdilution method, we evaluated sparfloxacin activity in comparison with those of other antimicrobial agents against 383 pediatric isolates derived from cultures of blood and other normally sterile body fluids. MICs were assessed in Mueller-Hinton broth, serum, and urine, as well as at inoculum sizes of 10(4) to 10(8) CFU/ml. The emergence and stability of resistance and cross-resistance of Pseudomonas aeruginosa (mucoid and nonmucoid) and Staphylococcus aureus to sparfloxacin and ciprofloxacin were evaluated. Inhibitory activity of sparfloxacin against most test organisms was within achievable serum levels. Sparfloxacin was greater than or equal to 2- to 4-fold more active than other quinolones against gram-positive pathogens and 2- to 4-fold less active than ciprofloxacin against P. aeruginosa. Sparfloxacin activity was unaffected by urine and was enhanced by two- to eightfold in human serum. Its potency was not affected by inocula of less than or equal to 10(7) CFU/ml. The frequency of development of spontaneous resistance was similar to that found for other new quinolone agents, and stable resistance emerged only in P. aeruginosa. Sparfloxacin merits additional study against invasive pediatric pathogens.