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Biomedical subjects

R J Fass

Publications and source records attributed to R J Fass.

134 records · Page 8Linked to original sources

In vitro activity of DNA gyrase inhibitors, singly and in combination, against Mycobacterium avium complex.

The in vitro activities of the DNA gyrase inhibitors ciprofloxacin, coumermycin, and novobiocin against 31 clinical isolates of Mycobacterium avium complex were studied using a microdilution technique. Minimal inhibitory concentrations (MICs) were determined in 4 days using Middlebrook 7H9 broth, and minimal bactericidal concentrations (MBCs) were determined by subculturing to Middlebrook 7H10 agar. MICs were: ciprofloxacin, 0.5-greater than 16 (mean, 4.1) micrograms/ml; novobiocin, 4-greater than 128 (mean, 54.7) micrograms/ml; and coumermycin, 2-greater than 16 (mean, 17.5) micrograms/ml. MBCs were usually more than two dilution steps higher than MICs. Checkerboard studies failed to reveal synergistic or antagonistic inhibitory activity of DNA gyrase-A and DNA gyrase-B inhibitors in vitro.

Aminocoumarins↗

Therapy of skin, soft tissue, and bone infections with cefoxitin sodium.

Twenty-seven patients with skin and soft tissue infections, including three with contiguous osteomyelitis, were given cefoxitin intravenously or intramuscularly; the infections of 25 (93%) were resolved with cefoxitin therapy. Etiologic agents included staphylococci, streptococci, Enterobacteriaceae, and anaerobes. Susceptible pathogens were inhibited by less than or equal to 8 micrograms of cefoxitin/ml. This level of drug was surpassed by mean peak serum concentrations eight- to 12-fold after intravenous infusions and two- to threefold after intramuscular injections and resulted in eradication of susceptible organisms from lesions during treatment. Intravenously administered cefoxitin was well tolerated, although eosinophilia, phlebitis, elevation of levels of hepatic enzymes, and a positive direct Coombs' test were observed. Intramuscular injections of cefoxitin in 0.5% lidocaine caused pain and induration and thus were poorly tolerated.

Abscess↗

In vitro susceptibilities of nonfermentative gram-negative bacilli other than Pseudomonas aeruginosa to 32 antimicrobial agents.

The animal inhibitory concentrations of 32 antimicrobial agents for 322 strains of non-fermentative gram-negative bacilli, representing 30 species and unnamed groups other than Pseudomonas aeruginosa, were determined in cation-supplemented Mueller-Hinton broth with use of a microdilution method. The activities of beta-lactam antibiotics varied, but azlocillin, mezlocillin, piperacillin, cefotaxime, and moxalactam consistently were more active than were available penicillins and cephalosporins; the penicillin-like antibiotic mecillinam was less active. The activities of the aminoglycoside antibiotics were similar to each other although streptomycin and sometimes kanamycin were less active than the other aminoglycosides. Although minocycline and doxycycline usually were more active than tetracycline, the percentages of strains susceptible to the first two drugs at concentrations achievable in vivo were only occasionally higher than the percentage of strains susceptible to tetracycline. The activity of trimethoprim-sulfamethoxazole was variable. Chloramphenicol, erythromycin, clindamycin, and vancomycin were relatively inactive against most of the organisms tested, but the high degrees of activity of these drugs against specific species or strains, particularly those that were resistant to many drugs, indicated potential clinical usefulness of these agents.

Alcaligenes↗

Tobramycin: in vitro and clinical evaluation in 30 patients.

Clinical evaluation of intramuscular tobramycin was accomplished in 30 patients with respiratory, soft tissue, urinary tract, bone or septicemic infections due to gram negative bacilli. Median sensitivity to tobramycin of Pseudomonas aeruginosa isolates (19 strains) was 0.62 mug/ml and range 0.31-2.5 mug/ml; less activity was observed for Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and Enterobacter species isolates but median minimum inhibitory concentrations were less than or equal to 2.5 mug/ml. Therapy resulted in clinical and bacteriologic cures in 16 patients (53 per cent) including 13 of 16 (181 per cent) with urinary tract infections; 9 of the 14 patients who did not obtain bacteriologic cure had satisfactory clinical responses. Tobramycin was effective for selected gram negative bacillary infections and particularly for P. aeruginosa.

Adult↗

Pneumonia and empyema caused by Clostridium sordellii.

A case of pleuropulmonary infection caused by Clostridium sordellii is reported for the first time. The clinical presentation with acute onset resembling pulmonary infarction, the absence of toxicity, hemolysis and shock, and response to penicillin and drainage was similar to that of patients with pleuropulmonary infection caused by C. perfringens.

Clostridium Infections↗

Treatment of osteomyelitis and septic arthritis with cefamandole.

Fourteen patients with bone and joint infections caused by a variety of bacterial pathogens were treated with intravenous cefamandole, 4 to 12 g/day; ten received additional therapy with 2 g/day of cefaclor and one with 2 g/day of cephalexin. Ten of 14 patients were cured. Of those cured, infecting pathogens had minimal inhibitory concentrations of cefamandole of 4 micrograms or less/ml. Of those who were not cured, two had recurrent infections that had not responded to other previously administered antibiotics, one had a mixed infection with resistant strains, and one had positive bone cultures five months after a favorable clinical response. Peak and valley cefamandole serum concentrations were 48.0 to 173.0 micrograms/ml and 23.4 micrograms or less/ml, respectively. Synovial fluid concentrations were 11.1 to 16.7 micrograms/ml and bone concentrations were 0.2 to 20.4 micrograms/g. Adverse effects included leukopenia in one and hepatic enzyme elevations in four patients. Cefamandole, with and without cefaclor, was efficacious in therapy of bone and joint infections caused by susceptible organisms.

Arthritis, Infectious↗

A single large dose of trimethoprim-sulfamethoxazole fails to cure gonococcal urethritis in men.

In a single-blind study, 50 men who had acute gonococcal urethritis were treated with a single oral dose of either 720 mg trimethoprim (TMP) plus 3,600 mg sulfamethoxazole (SMZ) or 3.5 g ampicillin plus 1 g probenecid. Isolates of Neisseria gonorrhoeae were tested for in-vitro susceptibility to the chemotherapeutic agents administered by agar-dilution and disk-diffusion methods, and results were correlated with cure or failure to cure as determined bacteriologically. Among patients returning for follow up, the cure rate after TMP/SMZ was 69%. Cure was predictable when the isolates of N. gonorrhoeae were inhibited by < or = 0.63/11.87 micrograms/ml of TMP/SMZ (fixed ratio, 1:19) or when the zones of inhibition were > or = 23 mm; failure was predictable when > or = 1.25/23.75 micrograms/ml of TMP/SMZ was necessary for inhibition and when zones of inhibition were < or = 21 mm (P < 0.02). The cure rate after therapy with ampicillin was 100%, a rate significantly higher than that found after TMP/SMZ (P < 0.02); all isolates were inhibited by < or = 0.16 microgram/ml of ampicillin. Adverse reactions were not seen after either TMP/SMZ or ampicillin.

Adult↗

Detection of polysaccharide cell wall antigen of Neisseria gonorrhoeae in a rabbit model by counterimmunoelectrophoresis.

A rabbit chamber model was developed and inoculated with 10(9) colony-forming units (cfu) of viable Neisseria gonorrhoeae to determine whether the lipopolysaccharide-derived Gc2 polysaccharide cell wall antigens could be detected by counterimmunoelectrophoresis (CIE). Four hours after inoculation, a polymorphonuclear leukocyte response was noted in the chambers; this response was followed by progressive phagocytosis of the organisms and a fall in number of cfu/ml. All visible bacteria were intracellular, and chamber fluids were sterile 6 hr after inoculation. Use of sero specific antisera permitted detection by CIE of the Gc2 polysaccharide antigen in sera of all rabbits within 48 hr after inoculation of the chambers, whereas blood cultures remained sterile throughout the experiment. At 2-6 hr after inoculation, the Gc2 polysaccharide antigen was also detected as a single precipitin band in the chamber fluid of inoculated rabbits. At 24 hr the precipitin band was not observed; rather, a halo above the antigen well was noted. The halo was found to be a nonspecific complex containing the Gc2 polysaccharide antigen and no antibody. In the rabbit model studied, CIE was sufficiently sensitive to detect concentrations of the Gc2 polysaccharide antigen of greater than or equal to 0.97 microgram/ml in serum and chamber fluid.

Animals↗