IN-VIVO EFFICACY OF AZITHROMYCIN IN TREATMENT OF SYSTEMIC INFECTION AND SEPTIC ARTHRITIS INDUCED BY TYPE-IV GROUP-B STREPTOCOCCUS STRAINS IN MICE - COMPARATIVE-STUDY WITH ERYTHROMYCIN AND PENICILLIN-G

We compared the activities of azithromycin, erythromycin, and penicill in G in a mouse model of systemic infection and septic arthritis induc ed by type IV group B streptococci (GBS). The in vitro and in vivo eff icacy data for these drugs were analyzed relative to the pharmacokinet ics of the drugs in sera, joints, and kidneys. Adult CD-1 mice were in fected intravenously with 10(7) CFU of type IV GBS. Intraperitoneal dr ug administration was initiated with different dose regimens at differ ent times after infection, A single dose of azithromycin (100 mg/kg) s trongly reduced the incidence of articular lesions with respect to tha t with erythromycin or penicillin G, Treatment with azithromycin (thre e intraperitoneal administrations of 50 mg/kg at 12-h intervals) resul ted in the complete prevention of arthritis. In contrast, erythromycin was poorly effective and penicillin G was effective only if inoculate d 30 min after infection and at high doses (400,000 or 600,000 IU/kg), Furthermore, azithromycin was able to cure about 70% of the mice when administered 7, 8, and 9 days after GBS infection. Azithromycin was m uch more active than erythromycin and penicillin G with respect to bac terial killing in the joints and kidneys. In fact, cultures from these tissues were always negative no matter what treatment schedule was em ployed, The pharmacokinetics of azithromycin account for its superior in vivo efficacy against type TV GBS, A longer half-life and higher le vels of this drug in serum and tissues with respect to those for eryth romycin or penicillin G were achieved, The high affinity of azithromyc in for the joints strongly supports its potential value for therapy of septic arthritis, which is a severe and frequent clinical manifestati on of GBS infection.