Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO(2). Macrolide-azalide-ketolide MICs were 0.004 to 32.0 microg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC = 2.0 microg/ml) against all anaerobes except Peptostreptococcus magnus and Bacteroides thetaiotaomicron, while pristinamycin MICs were 0.06 to 4.0 microg/ml. Amoxicillin-clavulanate had MICs of =1.0 microg/ml, while metronidazole was active (MICs, 0.03 to 2.0 microg/ml) against all except Propionibacterium acnes. After 48 h at twice the MIC, telithromycin was bactericidal (>/=99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred.
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Many drugs have been found to increase or decrease the clearance of theophylline. Some of new quinolone antimicrobial agents (ciprofloxacin, enoxacin, pefloxacin and tosufloxacin) and macrolide antibiotics (erythromycin, troleandomycin, roxithromycin and clarithromycin), are potent inhibitors of the metabolism of theophylline. Concomitant administration of these drugs may, thus, prolong the half-life of theophylline, elevate serum theophylline concentrations, and increase the risk of theophylline-related adverse events. Therefore, these data indicate that careful clinical and pharmacokinetic monitoring of patients receiving both theophylline and some of antimicrobial agents should be carried out.
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Mycobacterium avium and M. intracellulare were isolated from the sputum of patients infected with atypical mycobacteria using 1% Ogawa medium and identified by the DNA probe test. Then the MICs of various kinds of drugs against these mycobacterial species were determined on Dubos agar medium, and the drug susceptibilities were also determined on 1% Ogawa medium in parallel. The drugs tested were new macrolides, such as clarithromycin (CAM) and roxithromycin (RXM), new quinolones, such as ofloxacin (OFLX) and ciprofloxacin (CPFX), and antituberculous drugs, such as isoniazid (INH), rifampicin (PFP), streptomycin (SM), and ethambutol (EB). The MICs of the drugs tested, especially those of CAM, OFLX, and RFP, when determined on Dubos agar medium, were generally lower against M. intracellulare than against M. avium. The susceptibilities of the mycobacterial isolates tested to RFP and SM determined on Dubos agar medium were markedly different from those determined on 1% Ogawa medium. Such discrepancies may be accounted for by absorption of these drugs to the egg medium and instability of RFP in the egg medium. Overall, our results indicate that the new macrolides and new quinolones are effective against atypical mycobacteria.