Postantibiotic Effects of ABT-773 and Amoxicillin-Clavulanate against Streptococcus pneumoniae and Haemophilus influenzae

Abstract

This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae. The PAEs of ABT-773 and amoxicillin-clavulanate ranged from 2.3 to 6.0 h and 0 to 2.2 h against S. pneumoniae and from 2.7 to 9.1 h and 0 to 0.8 h against H. influenzae, respectively.The ketolides represent a novel subclass of agents within the macrolide-lincosamide-streptogramin group. ABT-773, the newest member of the ketolide group, demonstrates good in vitro activity against Streptococcus pneumoniae, Haemophilus influenzae, and other community-acquired respiratory tract pathogens (2, 6, 9). Due to enhanced accumulation into cells and tighter ribosomal binding, this new ketolide maintains in vitro activity against mef-and/or ermB-containing S. pneumoniae (3). The purpose of this study was to determine the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against S. pneumoniae and H. influenzae.(This work was presented in part of the poster session of the 22nd International Congress of Chemotherapy, Amsterdam, The Netherlands, 2001.) Clinical isolates of S. pneumoniae (n ϭ 4) and H. influenzae (n ϭ 4) were obtained from the microbiology laboratories at the University of Illinois at Chicago Medical Center (Chicago, Ill.) and Loyola University Medical Center (Maywood, Ill.). Two of the S. pneumoniae strains were resistant to penicillin and erythromycin (mefE gene), while the other two strains were susceptible to both agents. Half of the H. influenzae strains were beta-lactamase positive, while the other half were beta-lactamase negative. The isolates were stored at Ϫ70°C in skim milk and underwent three subcultures prior to MIC and PAE studies. Control strains (S. pneumoniae ATCC 49619 and H. influenzae ATCC 49247) were used to validate MIC results.ABT-773 (Abbott Laboratories, Abbott Park, Ill.) and amoxicillin-clavulanate (United States Pharmacopeia, Rockville, Md.) powders were prepared according to NCCLS guidelines or per the manufacturer's recommendations (8). The media for MIC and PAE studies were cation-supplemented Mueller-Hinton broth with 3% lysed horse blood (Remel, Lenexa, Kans.) and Haemophilus test medium (Remel) for S. pneumoniae and H. influenzae isolates, respectively.MIC studies were performed in duplicate per NCCLS guidelines using the microbroth dilution method (8). The organisms were freshly subcultured and incubated overnight in a 35°C incubator with 5% CO 2 . The inoculum was prepared by direct suspension and adjusted with sterile saline until the turbidity matched a 0.5 McFarland standard using a spectrophotometer at 625 nm. Each suspension was further diluted in broth media to obtain a final inoculum of approximately 5 ϫ 10 5 CFU/ml. The exact inoculum size was determined via colony counts. The microtiter plate contents were incubated at 35°C (humidified air) and read at 20 h. The MIC was defined as the lowest concentration at which there was no visible growth.The PAEs were ...

Activities of Two Novel Macrolides, GW 773546 and GW 708408, Compared with Those of Telithromycin, Erythromycin, Azithromycin, and Clarithromycin against Haemophilus influenzae

“…The PAEs produced by the novel macrolides, telithromycin, and azithromycin were longer than those produced by erythromycin. These results are consistent with those from previous studies (3,15). The PAE would be important only for organisms for which the MICs are high and in cases in which the levels in serum would fall below the MIC.…”