Antimicrobial susceptibilities of Bordetella species isolated in a Multicenter Pertussis Surveillance Project.Kurzynski, T A; Boehm, D M; Rott-Petri, J A; Schell, R F; Allison, P E
doi: 10.1128/AAC.pmid: 2894817
MICs for 90% (MIC90s) of 75 Bordetella pertussis strains for amoxicillin, erythromycin, rifampin, and sulfamethoxazole-trimethoprim were 1, less than or equal to 0.12, 1, and 4 micrograms/ml, respectively. Susceptibility rates were all greater than or equal to 93%. Only 17% of the strains were susceptible to tetracycline. The MIC90s of ciprofloxacin, enoxacin, norfloxacin, ofloxacin, and roxithromycin were less than or equal to 0.06, 0.5, 0.25, 0.12, and 0.5 micrograms/ml, respectively. For B. parapertussis, the MIC90s were 16-fold higher with amoxicillin and rifampin and 2- to 4-fold higher with the fluoroquinolones and roxithromycin. Antimicrob Agents Chemother. 1988 January; 32(1): 137-140
A-61827 (A-60969), a new fluoronaphthyridine with activity against both aerobic and anaerobic bacteria.Fernandes, P B; Chu, D T; Swanson, R N; Ramer, N R; Hanson, C W; Bower, R R; Stamm, J M; Hardy, D J
doi: 10.1128/AAC.pmid: 3348609
A-61827 (A-60969 is the hydrochloric salt of A-61827) is a new aryl-fluoronaphthyridine which is active against aerobic and anaerobic bacteria. The MICs of A-61827 for 90% of strains (MIC90) of staphylococci and streptococci were less than or equal to 1 microgram/ml and were generally 1 to 4 twofold dilutions less than those of ciprofloxacin for these bacteria. The MIC90S of A-61827 for members of the family Enterobacteriaceae and Pseudomonas aeruginosa were also less than or equal to 1 microgram/ml. Ciprofloxacin was 1 to 3 twofold dilutions more active than A-61827 against these gram-negative bacteria. Neisseria gonorrhoeae, Campylobacter jejuni, and Haemophilus influenzae were susceptible to less than 0.06 microgram of A-61827 per ml. The MIC90 of A-61827 for Legionella pneumophila was 0.25 microgram/ml. A-61827 was as potent or 1 to 2 twofold dilutions more potent than ciprofloxacin against these organisms. The MIC90 of A-61827 for all anaerobic bacteria was less than or equal to 4 micrograms/ml compared with less than or equal to 32 micrograms/ml for ciprofloxacin. In mouse protection tests, A-61827 was as active as ciprofloxacin against Escherichia coli, P. aeruginosa, and Salmonella typhimurium and 5 to 10 times more active than ciprofloxacin against Staphylococcus aureus and Streptococcus pyogenes. A-61827 was as active as ciprofloxacin against P. aeruginosa in a mouse pyelonephritis model and more active than ciprofloxacin and metronidazole in a mouse Bacteroides fragilis abscess model. After oral administration of 100 mg/kg to mice, the peak concentrations of A-61827 and ciprofloxacin in serum were 2.3 and 2.4 micrograms/ml and the half-lives in serum were 3.9 and 1.2 h, respectively. Antimicrob Agents Chemother. 1988 January; 32(1): 27-32
Pharmacokinetics and pharmacodynamics of cefoperazone-sulbactam in patients on continuous ambulatory peritoneal dialysis.Johnson, C A; Zimmerman, S W; Reitberg, D P; Whall, T J; Leggett, J E; Craig, W A
doi: 10.1128/AAC.pmid: 3348613
This study was conducted to determine the pharmacokinetics of the fixed combination antibiotic cefoperazone-sulbactam in patients receiving continuous ambulatory peritoneal dialysis (CAPD). In addition, the pharmacodynamic profile of this combination was determined by the use of mean bactericidal titers against selected bacterial strains. Six noninfected CAPD patients were given a fixed dose of cefoperazone (2 g) and sulbactam (1 g) either intravenously or intraperitoneally over 10 min in a randomized, two-way crossover fashion. The mean peak cefoperazone concentration in serum after intravenous administration was 280.9 micrograms/ml. The mean peak concentration in serum after intraperitoneal cefoperazone administration was 38.9 micrograms/ml and occurred 2 to 4 h postdose. The mean peak sulbactam concentration in serum after intravenous administration was 82.2 micrograms/ml. The mean peak concentration in serum after intraperitoneal sulbactam administration was 24.4 micrograms/ml and occurred at 6 h. The absolute bioavailability of the intraperitoneal dose was 61% for cefoperazone and 70% for sulbactam. Cefoperazone total body and renal clearances were unaffected by renal failure and dialysis. However, both clearance values for sulbactam were reduced markedly. Only intraperitoneal dosing provided peak inhibitory and bactericidal titers in dialysate for all organisms tested. Intravenous dosing provided satisfactory dialysate titers only for very susceptible bacterial strains. End-stage renal disease and CAPD do not alter cefoperazone pharmacokinetics; however, sulbactam dosing may need to be adjusted. Antimicrob Agents Chemother. 1988 January; 32(1): 51-56
Inhibitors of folic acid synthesis in the treatment of experimental Pneumocystis carinii pneumonia.Walzer, P D; Kim, C K; Foy, J M; Linke, M J; Cushion, M T
doi: 10.1128/AAC.pmid: 3258144
Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be demonstrated by the addition of an inhibitor of dihydrofolate reductase to the regimen. Dihydrofolate reductase inhibitors (trimethoprim, diaveridine, and pyrimethamine) used alone were ineffective against P. carinii. All drugs were well tolerated except pyrimethamine, which caused bone marrow depression; folinic acid ameliorated this adverse reaction but did not interfere with P. carinii treatment. These data have potential clinical implications but need to be interpreted with caution and in light of other systems of P. carinii drug evaluation. Antimicrob Agents Chemother. 1988 January; 32(1): 96-103
LY146032 compared with penicillin G in experimental aortic valve endocarditis caused by group G streptococci.Bayer, A S; Yih, J; Hirano, L
doi: 10.1128/AAC.pmid: 2831811
Rabbits with group G streptococcal aortic endocarditis received no therapy (controls); repeated doses of procaine penicillin G, 300 mg/kg (body weight) per day, administered intramuscularly; or LY146032, a new peptolide antibiotic, 20 mg/kg per day, administered intravenously. Penicillin G and LY146032 reduced mean intravegetation group G streptococcal densities significantly below those observed in controls at both day 3 and day 6 of therapy. Penicillin G effected a more rapid clearance of intravegetation streptococci than LY146032 by day 3, but not by day 6, of therapy. Antimicrob Agents Chemother. 1988 January; 32(1): 141-143
In vitro culture system to determine MICs and MBCs of antimicrobial agents against Treponema pallidum subsp. pallidum (Nichols strain).Norris, S J; Edmondson, D G
doi: 10.1128/AAC.pmid: 2964810
A new procedure for determining the susceptibility of Treponema pallidum subsp. pallidum to antimicrobial agents was developed, utilizing a tissue culture system which promotes the in vitro multiplication of this organism. In the absence of antibiotics, T. pallidum (Nichols virulent strain) multiplied an average of 10-fold when incubated for 7 days in the presence of Sf1Ep cottontail rabbit epithelial cell cultures. Varied concentrations of penicillin G, tetracycline, erythromycin, and spectinomycin were added to triplicate cultures to determine their effects on treponemal multiplication, motility, and virulence. The MIC of each antibiotic was defined as the lowest concentration which prevented treponemal multiplication, whereas the MBC was defined as the lowest concentration which abrogated the ability of the cultured treponemes to multiply and cause lesions in rabbits. The in vitro culture technique provided highly reproducible MICs and (in parentheses) MBCs of each of the antibiotics tested: aqueous penicillin G, 0.0005 (0.0025) microgram/ml; tetracycline, 0.2 (0.5) microgram/ml; erythromycin, 0.005 (0.005) microgram/ml; and spectinomycin, 0.5 (0.5) microgram/ml. The significance of these results in light of the in vivo activities and the previous in vitro evaluations of these antibiotics is discussed. The T. pallidum in vitro cultivation system shows promise as a method for studying the interaction between T. pallidum and antimicrobial agents and for screening new antibiotics for syphilis therapy. Antimicrob Agents Chemother. 1988 January; 32(1): 68-74
Demonstration of dose-response relationship in seasonal prophylaxis of respiratory infections with alpha-2b interferon.Monto, A S; Albrecht, J K; Schwartz, S A
doi: 10.1128/AAC.pmid: 2831814
Recombinant alpha-2b interferon was evaluated in two controlled trials, each lasting for 2 months or more, with different dose levels and schedules of administration. The first study was conducted during a period of transmission of type A (H1N1) and type B influenza. At 2.5 x 10(6) IU per day, no effect on influenza infection could be detected, but there appeared to be an effect on rhinovirus isolation. During the subsequent autumn 1.7 x 10(6) IU per day was found to have only a minimal effect on rhinovirus infection (efficacy from 22 to 27%). Under similar circumstances the preceding year, but with a daily dose of 3.0 x 10(6) IU, efficacy had been 76%. Since there was no evidence of change in rhinovirus strains circulating or their interferon susceptibility, this represented a dose-response relationship. It was possible to evaluate side effects in the 1,200 individuals involved. A lower dose was associated with lower frequency of symptoms of blood-tinged mucus. Persons using a placebo spray had a higher frequency of this side effect than an observed control. Using the spray 5 days a week was no less likely to produce symptoms than everyday use. Once-daily use was less likely to produce side effects than twice-daily use. There was no indication of sensitization when interferon was used for two separate periods of 4 weeks. Antimicrob Agents Chemother. 1988 January; 32(1): 47-50