The inhibitory and bactericidal activities of carbenicillin, ticarcillin, moxalactam, cefoperazone, azlocillin, piperacillin, ceftazidime, and three aminoglycosides, alone and in various combinations, were determined against 60 isolates of Pseudomonas aeruginosa from the sputum of patients with cystic fibrosis. Ceftazidime was the most active ,B-lactam, with minimum inhibitory and bactericidal concentrations for 90o of isolates of 4 ,ug/ml. Moxalactam was the least active of the new -lactams, with activity equivalent to that of carbenicillin; each had a minimum inhibitory concentration for 90% of isolates of 64 ,ug/ml and a minimum bactericidal concentration for 90% of isolates of 128 p.g/ml. Of the recently introduced 3-lactam derivatives, azlocillin, cefoperazone, ceftazidime, moxalactam, and piperacillin have a higher order of activity than their predecessors against not only the Enterobacteriaceae but also against Pseudomonas aeruginosa (2,10,13,15,18). Thus, they might be useful in the treatment ofP. aeruginosa pulmonary infections which are currently difficult to manage in patients with cystic fibrosis (CF). This possibility led to the current study of the activities of these new 3-lactams, alone and in combination with each other or gentamicin, tobramycin, and amikacin, against 60 isolates of P. aeruginosa from the sputum of patients with CF. MATERIALS AND METHODSA total of 60 isolates of P. aeruginosa, including mucoid and nonmucoid strains, was identified by standard microbiological methods. The organisms were then stored on tryptic soy agar slants and were checked for purity and subcultured monthly.Moxalactam (Eli Lilly & Co.), piperacillin (Lederle Laboratories), carbenicillin (Roerig-Pfizer Co.), azlocillin (Delbay Research Corp.), ticarcillin (Beecham Laboratories), cefoperazone (Pfizer Inc.), ceftazidime (Glaxo Research Group), gentamicin (Schering Corp.), tobramycin (Eli Lilly), and amikacin (Bristol Laboratories) were furnished as dry powders. Stock solutions were prepared from these powders and were used immediately or stored at -70°C for no longer than 2 weeks.Minimum inhibitory concentrations (MICs) were determined by microbroth dilution, and combination studies were done by microbroth checkerboard methods. Mueller-Hinton broth was used for all determinations. Mueller-Hinton broth was adjusted to optimal calcium and magnesium concentrations and a pH of 7.2 to 7.4 (6). The preparation and inoculation of microbroth plates were accomplished with the MIC-2000 system (Dynatech Corp.). Plates were used immediately or stored at -70°C for no longer than 2 weeks. Microbroth plates received an inoculum consisting of a 10' dilution of a log-phase culture adjusted to the density of a 0.
We tested CI-919 (AT-2266), a nalidixic acid analog, against 555 gram-positive and gram-negative bacteria, using microbroth or agar dilution methods. Current therapy of Pseudomonas aeruginosa infections requires parenteral administration of aminoglycosides, semisynthetic peniciliins, or one of the newer broad-spectrum cephalosporins. The development of a drug that is effective after oral administration would represent a major therapeutic advance.CI-919 (AT-2266; 1-ethyl-6-fluoro-1,4-dihydro -4 -oxo -7 -(1 -piperazinyl) -1,8 -naphthyridine-3-carboxylic acid) is a new antimicrobial agent structurally related to nalidixic acid and pipemidic acid (Fig. 1). Preliminary reports have indicated that CI-919 is active against both grampositive and gram-negative bacteria, including P. aeruginosa and aminoglycoside-resistant organisms (4,5,8). We previously showed that CI-919 was more active than tobramycin against systemic P. aeruginosa infections in mice
Minimum inhibitory concentrations of seven new β-lactam derivatives were determined against 35 isolates of Yersinia enterocolitica . Ceftizoxime and ceftriaxone were the most active of the antimicrobial agents tested.
The antibacterial activity of BMY-28142, a new aminothiazole cephalosporin, was measured by standardized broth microdilution and agar dilution methods against 450 gram-positive and gram-negative bacteria isolated from pediatric infections, including acute pulmonary exacerbations of cystic fibrosis. BMY-28142 activity was compared with that of aminoglycosides, 13-lactams, chloramphenicol, trimethoprim-sulfamethoxazole, vancomycin, and clindamycin. The activity of BMY-28142 in combination with other antimicrobial agents against Pseudomonas aeruginosa was also determined. Furthermore, the effects of inoculum and pH on BMY-28142 activity were evaluated. BMY-21842 was active against most of the gram-positive and gram-negative isolates, with the exception of methicillin-resistant Staphylococcus aureus and Pseudomonas cepacia. The combination of BMY-28142 with tobramycin was often synergistic, and combinations of BMY-28142 with either polymyxin B or imipenem were usually antagonistic. BMY-28142 antibacterial activity could be adversely affected at extremes of medium pH and by high inoculum densities.
We tested ciprofloxacin, a new quinoline derivative, against 783 gram-positive and gram-negative bacteria utilizing either standardized microbroth or agar dilution methods. Ciprofloxacin activity was compared to that of cephalosporins, enoxacin, norfloxacin, ampicillin, chloramphenicol, tobramycin, ticarcillin, erythromycin and trimethoprim/sulfamethoxazole. MIC90 values (range) in μg/ml were: Pseudomonas aeruginosa = 1 ( < 0.015–8); Staphylococcus spp. = 0.12( < 0.015–1); Enterobacteriaceae = 0.03 ( < 0.015–1); Haemophilus influenzae = 0.015 (0.004–0.03); < Streptococcus faeca-lis = 2 (0.5–4). The MIC90 of ciprofloxacin for 98 tobramycin-resistant isolates was 2.0 iig/ml. Ciprofloxacin was stable at temperatures of 35,22,4, -20 and -70 °C for up to 15 weeks. Varying the inoculum from 103 to 107 colony forming units per ml or the pH from 6–9 resulted in no increase in the MIC. Of the new quinoline derivatives tested, ciprofloxacin demonstrated consistently superior antibacterial activity. Ciprofloxacin may be particularly effective for oral administration in infections requiring prolonged antibiotic therapy, such as bone, joint, and complicated soft tissue infections, and in pulmonary infections in patients with cystic fibrosis.
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