Search PubMed⌕ Search

Biomedical subjects

R J Fass

Publications and source records attributed to R J Fass.

At least 109 records · Page 6Linked to original sources

In vitro activity of LY127935.

LY127935 is a unique new beta-lactam antibiotic. Its activity against 536 clinical isolates was studied by using microdilution methods of susceptibility testing and compared with the activities of cefamandole, cefoxitin, and cephalothin. The lowest concentrations required to inhibit at least 90% of strains tested (MIC(90)s) of LY127935 for Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae ranged from 2 to 8 mug/ml. The MIC(90)s for other staphylococci and streptococci were higher. The MIC(90)s for Enterobacteriaceae and Pseudomonas species ranged from 0.12 to 8 mug/ml and 8 to >32 mug/ml, respectively. The MIC(90)s for anaerobes ranged from 2 to >32 mug/ml. As determined by MIC(90)s, LY127935 was consistently the least active antibiotic against facultatively anaerobic gram-positive cocci and the most active against aerobic and facultatively anaerobic gram-negative bacilli. Its position with respect to activity against anaerobes varied from being the most active against Bacteroides fragilis and Clostridium perfringens to the least active against anaerobic cocci. In a population of multidrug-resistant isolates, concentrations of 8 mug or less of LY127935 per ml inhibited 82% of Enterobacteriaceae; concentrations of 32 mug or less per ml inhibited 100% of Enterobacteriaceae and 40% of P. aeruginosa. Increasing the inoculum size by 100-fold did not increase the minimal inhibitory concentrations of LY127935 or cefoxitin but did increase minimal inhibitory concentrations of cefamandole and cephalothin for some Enterobacteriaceae. All four drugs were bactericidal; minimal bactericidal concentrations were the same or one concentration higher than minimal inhibitory concentrations for 91 to 96% of strains tested. The broad spectrum and marked in vitro activity of LY127935 make it a promising new antibiotic.

Aerobiosis↗

Minimal inhibitory concentrations of 34 antimicrobial agents for control strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853.

The use of control strains of bacteria is important to monitor the accuracy and precision of antimicrobial susceptibility testing. Knowledge of the minimal inhibitory concentrations of commonly used organisms would be useful to achieve a degree of inter- as well as intra-laboratory reproducibility. The minimal inhibitory concentrations of 34 antimicrobial agents for control strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853, as determined by a microdilution method in cation-supplemented Mueller-Hinton broth, are reported.

Anti-Bacterial Agents↗

St Louis encephalitis in Ohio, September 1975: clinical and EEG studies in 16 cases.

In 1975, during the largest epidemic of St Louis encephalitis (SLE) in the United States, 416 cases were diagnosed in Ohio. Persons who were admitted to two Columbus (Ohio) hospitals with suspected acute viral CNS infection were prospectively studied to define the virologic and clinical aspects of SLE. Sixteen cases of SLE were diagnosed serologically. Fifteen patients had signs of encephalitis and one had aseptic meningitis. Six patients had the syndrome of inappropriate antidiuretic hormone secretion. Other frequent findings included moderate peripheral leukocytosis and CSF pleocytosis, with mild elevation of CSF protein levels but normal glucose levels. Severe neurologic sequelae were infrequent. The EEG proved valuable in diagnosis and prognosis. Results of brain scans were normal. Virus in CSF or urine was not demonstrated, nor was viral antigen in CSF or urine sediments. Specific antibody was found in the sera and CSF of all patients who were tested, but interferon was not detected.

Adult↗

Campylobacter fetus sepsis with mycotic aortic aneurysm.

Campylobacter fetus is a fastidious, curved, Gram-negative bacillus that has been increasingly associated with human disease. To our knowledge, we are reporting the first documented case of C fetus sepsis associated with an aortic mycotic aneurysm. Typical of previously reported cases of infections caused by this organism, this case involved a debilitated patient who was seen initially with a subacute febrile illness associated with bacteremia, but who died suddenly when the unsuspected aneurysm ruptured. The isolate was presumptively identified by its growth characteristics, motility, curved shape, and the presence of a single polar flagellum.

Aneurysm, Infected↗

Reduced level of non-esterified fatty acids in sera from patients with infectious respiratory disease.

Sera from 103 fasting individuals 3 to 76 years of age and free of clinical infectious disease and sera from 183 patients with infectious disease were assayed for serum total non-esterfied fatty acids (tNEFA) and compared. Data were also separated into five groups according to age of donor: 3--7, 8--19, 20--35, 36--60, and 61--76 years. The mean group serum levels of tNEFA increased with age. Among patients with infectious diseases sixty-five were diagnosed as having hepatitis, 41 with infectious mononucleosis, 18 with cellulitis, 12 with pulmonary tuberculosis, 11 with non-pneumococcal pneumonia, 9 with pneumococcal pneumonia, 8 with pharyngitis, 6 with pyelonephritis, 6 with aseptic meningitis, 4 with Gram-negative sepsis, and 3 with encephalitis. The sera from 23 non-fasting patients with gonorrhea were also tested. The serum tNEFA levels were found to be altered, in fact depressed from normal group values, only in patients with pneumonia or tuberculosis. This depression may be related to aberrant pulmonary metabolism during pneumonia.

Adolescent↗

Comparison of ticarcillin and carbenicillin activity against random and select populations Pseudomonas aeruginosa.

The in vitro activities of ticarcillin (T) and carbenicillin (C) against 253 strains of Pseudomonas aeruginosa (108 randomly selected clinical isolates and 145 isolates determined to be C resistant by 10 referring hospitals) were evaluated using both broth microdilution and disk diffusion techniques. T activity was usually twofold or greater than C activity for individual strains in both sample populations. The minimal inhibitory concentration (MIC) values of T and C were </=0.4 to >400 (median, 25) and 0.8 to >400 (median, 50) mug/ml, respectively, for the random sample and 1.6 to >400 (median, 50) and 12.5 to >400 (median, 200) mug/ml, respectively, for the select sample. For predicting susceptibility (MIC, </=50 mug of T and </=100 mug of C per ml), 75-mug T and 100-mug C disks were equivalent in accuracy for the random sample (T/T = 92.6%, T/C = 92.0%, C/T = 91.7%, C/C = 89.8%). Regression-line analyses of zones of inhibition versus MIC values for the four combinations showed coefficients of correlation to be -0.81, -0.76, -0.77, and -0.75, respectively. With the sample selected as being resistant to C, T was better than C for predicting T susceptibility (P < 0.05), and T was equivalent to C for predicting C susceptibility (T/T = 84.3%, T/C = 81.0%, C/T = 73.6%, C/C = 80.4%). Coefficients of correlation were -0.70, -0.74, -0.55, and -0.61, respectively. T and C disks were, therefore, equivalent for determining T and C susceptibilities, but the T disk was more reliable for determining T susceptibility in a population skewed with C-resistant strains.

Carbenicillin↗

Treatment of osteomyelitis and septic arthritis with cefazolin.

Sixteen cases of severe osteomyelitis and septic arthritis caused by staphylococci, streptococci, gonococci, and a variety of gram-negative bacilli were treated with 4 to 8 g of parenteral cefazolin per day; nine received subsequent therapy with oral cephalexin or ampicillin. Of 16 infections, 15 were apparently cured. Cefazolin concentrations in those patients were: serum (peak), 25 to 216 micrograms/ml; synovial fluid, 24 to 46 micrograms/ml; and bone, 3.2 to 10.6 micrograms/g. Bacterial pathogens had minimal inhibitory concentrations of cefazolin of 2 micrograms or less per ml and seemed to be eradicated from foci of infection during therapy. One infection in a diabetic patient did not respond; despite high concentrations of cefazolin in serum, no detectable antibiotic was present in her infected metatarsal, and the infecting Escherichia coli (minimal inhibitory concentration, 16 micrograms/ml) was not eradicated during therapy. Concentrations of cefazolin in bone in 10 uninfected patients who received 1-g intramuscular doses prophylactically before surgery were also measured. Concentrations in bones from those who had normal renal function ranged from less than 0.6 to 2.8 micrograms/g.

Adolescent↗

Treatment of mixed bacterial infections with clindamycin and gentamicin.

Thirty-eight patients with severe mixed bacterial infections were treated with clindamycin and gentamicin. In vitro, all staphylococci and streptococci (other than enterococci) and 96% of anaerobes were susceptible to clindamycin; all staphylococci and 92% of Enterobacteriaceae and Pseudomonas aeruginosa were susceptible to gentamicin. Enterococci were usually resistant to both antibiotics. Significant synergy was only occasionally observed with this combination of antibiotics; there were no instances of antagonism. Among the patients treated with both drugs, there were four patients with pneumonia and empyema, 15 with infections of the skin, soft tissue, and/or bone, and 19 with intraabdominal infection. Nine patients had bacteremia, and 29 had failed to respond or had developed infections during previous antibiotic therapy. The results of treatment with clindamycin and gentamicin were considered to be excellent: 30 patients were cured, four improved, and four failed to respond. Concentrations of clindamycin in serum greatly surpassed minimal inhibitory concentrations (MICs) of clindamycin-susceptible pathogens; these organisms were eradicated from foci of infection. Concentrations of gentamicin in serum did not consistently surpass MICs for gentamicin-susceptible pathogens; these organisms and enterococci often persisted in foci of infection. In patients with complicated infections that required prolonged courses of treatment, Enterobacteriaceae, Pseudomonas aeruginosa, and enterococci occasionally emerged as predominant pathogens. Adverse reactions frequently occurred but were mild and reversible; treatment was discontinued in only two patients who developed rashes.

Adult↗

Pharmacokinetics and tolerance of a single twelve-tablet dose of trimethoprim (960 mg)-sulfamethoxazole (4,800 mg).

To evaluate the potential usefulness of a single large oral dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of uncomplicated genitourinary gonorrhea, the pharmacokinetics of a 12-tablet dose containing 960 mg of TMP and 4,800 mg of SMZ were studied in 15 male volunteers, and the tolerance of this regimen was compared to that of a placebo in a double-blind crossover study. Both TMP and SMZ were rapidly absorbed. Peak mean serum concentrations (+/- standard deviation) of TMP, total SMZ, and free SMZ were 9.2 +/- 2.2, 259.4 +/- 40.9, and 233.7 +/- 33.6 mug/ml, respectively. Elimination half-lives were 16.7, 14.6, and 12.9 h, respectively. When results were compared to data from similar studies after smaller doses, peak mean serum concentrations were proportional to dose, but elimination half-lives were longer after larger doses. Urinary concentrations of TMP, total SMZ, and free SMZ were many-fold higher than serum concentrations. Percents recovery (+/- standard deviation) in urine were 60.6 +/- 10.6, 80.2 +/- 7.8, and 37.4 +/- 6.5%, respectively, during the 48 h after administration. The incidence of severe headache and of objective transient oliguria was significantly higher after TMP-SMZ than after placebo. Although the observed serum concentrations of TMP and SMZ surpassed concentrations necessary to inhibit clinical isolates of Neisseria gonorrhoeae in vitro for longer than 24 h, the adverse reactions associated with a 12-tablet dose of TMP-SMZ would preclude the clinical usefulness of such a therapeutic regimen.

Adolescent↗

In vitro activity of spectinomycin against recent urinary tract isolates.

The susceptibilities to spectinomycin of 303 recent urinary tract isolates were determined and compared to the susceptibilities of those strains to ampicillin, tetracycline, and gentamicin. Based on minimal inhibitory concentrations, 84% of Escherichia coli, Klebsiella, and Enterobacter, 31% of other Enterobacteriaceae, 7% of Staphylococcus aureus and Streptococcus (including enterococci), and 0% of Pseudomonas aeruginosa were susceptible to concentrations of spectinomycin that are easily surpassed in serum (</=32 mug/ml); 90% of all organisms tested other than P. aeruginosa were susceptible to concentrations that are easily surpassed in urine (</=128 mug/ml). Spectinomycin was active against more isolates than either ampicillin or tetracycline but against fewer isolates than gentamicin. Disk diffusion susceptibility tests did not reliably distinguish susceptible from resistant isolates with any of the four antibiotics studied.

Anti-Bacterial Agents↗

Clindamycin and gentamicin for aerobic and anaerobic sepsis.

Thirty-eight adult patients with serious pleuropulmonary, soft-tissue, bone, and intra-abdominal infections caused by combinations of aerobic, facultative, and anaerobic bacteria were treated with parenterally given clindamycin phosphate and gentamicin sulfate and surgery when appropriate. Nine had associated bacteremia. In 29, infections failed to respond to other therapeutic regimens, which included penicillins, cephalosporins, aminoglycosides, and chloramphenicol. Results with clindamycin and gentamicin were excellent and were attributed primarily to the activity of clindamycin against anaerobes, particularly Bacteroides fragilis. Serum concentrations of clindamycin surpassed by manyfold the minimal inhibitory concentrations (MICs) for anaerobes. Serum concentrations of gentamicin did not consistently surpass the MICs for Enterobacteriaceae and Pseudomonas aeruginosa, although those organisms were consistently gentamicinsusceptible by disk diffusion susceptibility tests. Persistent colonization with Enterobacteriaceae, P aeruginosa, enterococci, or Candida were common, and occasionally they were significant in prolonging the clinical courses of patients with extensive infections.

Adolescent↗

Regression-line analysis of trimethoprim-sulfamethoxazole activity against Neisseria gonorrhoeae.

A standardized disk diffusion test was developed and used to test the susceptibility of 102 strains of Neisseria gonorrhoeae to combinations of trimethoprim and sulfamethoxazole (TMP/SMX) by relating zone diameters of inhibition to minimal inhibitory concentrations (MIC's). MIC's for TMP/SMX in ratios of 1:20 ranged from 0.08/1.52 to 2.5/47.5 mug/ml and zones of inhibition ranged from 34 to 10 mm. The coefficient of correlation (r) was -0.75. For comparison, a regression line was similarly calculated for ampicillin. MIC's ranged from 0.02 to 0.32 mug/ml and zones of inhibition ranged from 50 to 31 mm; r was -0.71. With establishment of MIC breakpoints to define the categories, susceptible, intermediate, and resistant, the disk duffusion test would be as reliable for estimating susceptibility of gonococci to TMP/SMX as for estimating susceptiblity to ampicillin.

Drug Combinations↗

In vitro activity of gentamicin and minocycline alone and in combination against bacteria associated with intra-abdominal sepsis.

The minimal inhibitory concentrations of gentamicin and minocycline alone and in combination were determined by a broth microdilution method for 100 aerobic, facultative, and anaerobic isolates representative of pathogens recovered from patients with intra-abdominal sepsis. Gentamicin inhibited all strains of Klebsiella, Enterobacter, and Pseudomonas aeruginosa in concentrations of 0.4 to 3.1 mug/ml and all strains of Escherichia coli and Proteus mirabilis in concentrations of 0.8 to 12.5 mug/ml. Whereas minocycline did not consistently inhibit these organisms in concentrations of 1.6 mug or less/ml, it did act synergistically with gentamicin against 43% of the Enterobacteriaceae tested in clinically achievable concentrations; significant synergy was most common with E. coli (60%). Minocycline inhibited 62% of Bacteroides fragilis, 71% of Clostridium, 40% of anaerobic cocci, and 40% of enterococci tested in concentrations of 1.6 mug or less/ml. Whereas gentamicin rarely inhibited these organisms in concentrations of 6.2 mug or less/ml, it did act synergistically with minocycline against 20% of B. fragilis, 67% of Clostridium, 22% of anaerobic cocci, and 22% of enterococci (which had minimal inhibitory concentrations of minocycline within the range tested) at clinically achievable concentrations. Although only four (13%) of the 30 isolates resistant to both gentamicin and minocycline alone were inhibited by clinically achievable concentrations of the combination, the observed synergy, particularly against strains of E. coli, was considered to be of potential clinical usefulness. Antagonism between gentamicin and minocycline was not observed at the concentrations tested.

Abdomen↗

Microdilution technique for antimicrobial susceptibility testing of anaerobic bacteria.

A microdilution technique using commercially available media and materials was developed and used to determine the minimal inhibitory concentrations (MICs) of clindamycin, chloramphenicol, tetracycline, minocycline, ampicillin, carbenicillin, cephalothin, and gentamicin for 101 anaerobic isolates. Representative strains of Bacteroides, Clostridium, Fusobacterium, Peptococcus, and Peptostreptococcus were tested. The use of Schaedler broth at pH 7.2, an inoculum of 10(5) to 10(7) colony-forming units per ml, and incubation at 35 C in an anaerobic glove box with an atmosphere of 80% nitrogen, 10% hydrogen, and 10% carbon dioxide resulted in good growth and easily interpretable results. After 48 h of incubation, 97% of strains tested were inhibited by 3.1 mug or less of clindamycin per ml and 98% were inhibited by 12.5 mug or less of chloramphenicol per ml. Tetracycline and minocycline inhibited 81 and 88% of strains tested in concentrations of 1.6 mug or less per ml and 1.6 mug or less per ml, respectively. Ampicillin inhibited all strains other than B. fragilis in concentrations of 3.1 mug or less per ml. Excluding certain strains of Bacteroides and Clostridium, carbenicillin in concentrations of 12.5 mug or less per ml and cephalothin in concentrations of 6.2 mug or less per ml inhibited all strains tested. Gentamicin was inactive although some strains of anaerobic cocci and Bacteroides were inhibited by 3.1 mug or less per ml. After 18 to 24 h of incubation, eight of the 101 strains had not grown sufficiently for MICs to be determined; for the 93 strains which had grown sufficiently, 93% of 744 MICs were the same or one concentration lower than the 48-h MICs.

Anaerobiosis↗