Human immunodeficiency virus (HIV) protease inhibitors are associated with several metabolic abnormalities including hypercholesterolemia and hypertriglyceridemia. Fenofibrate is a new lipid-lowering agent for adults with very high triglyceride levels that was administered to two HIV-positive patients who were taking protease inhibitors and developed hypertriglyceridemia. Starting dosages were 134 and 201 mg/day, and were increased to 268 mg/day in both patients. Triglyceride levels decreased from 1450 to 337 mg/dl (76.8%) and from 1985 to 322 mg/dl (83.8%), respectively, after 10 months of therapy. High-density lipoprotein levels increased in both patients.

N-Formimidoyl thienamycin (N-F-thienamycin) and moxalactam were compared with other currently available and investigational antibiotics against 100 clinical isolates of Bacteroides fragilis by an agar dilution method. N-F-thienamycin was the most active among the beta-lactam agents tested, with a minimal inhibitory concentration for 90% of isolates (MIC90) of 0.25 micrograms/ml. Moxalactam was next in activity, with an MIC90 of 4 micrograms/ml. N-F-thienamycin was somewhat more active, and moxalactam was slightly less active, than metronidazole and clindamycin. An increase in inoculum size caused an increase in the MIC of N-F-thienamycin, cefoperazone, and cefotaxime. This inoculum effect could influence the usefulness of these drugs in certain clinical conditions. The minimal bactericidal concentration was less than two times the MIC for most agents and less than four times the MIC for all beta-lactam agents at each inoculum size tested. Investigation of the mechanism of resistance to beta-lactam agents demonstrated a correlation between the level of resistance and beta-lactamase activity in each strain tested. N-F-thienamycin and cefoxitin were not hydrolyzed, and moxalactam was less susceptible to hydrolysis than the other beta-lactam antibiotics. Moxalactam and N-F-thienamycin may prove to be useful against infections with B. fragilis.

A diverse group of anaerobic bacteria representing a spectrum of resistance to β-lactam antibiotics was studied to characterize their β-lactamase activity and relate it to resistance. The Bacteroides fragilis organisms had moderate resistance and produced a cephalosporinase with low activity. The Clostridium ramosum was intermediate in resistance and had intermediate, inducible β-lactamase activity. The B. clostridiiformis organism was highly resistant, produced a potent inducible penicillinase, and had a barrier to the penicillin substrates. Only the β-lactamase of C. ramosum fit Richmond's classification (class IV). Although there was a rough correlation between β-lactamase activity and antibiotic resistance, other mechanisms are undoubtedly involved in determining resistance levels.

The in vitro activity of the aminoglycoside antibiotic tobramycin was demonstrated by broth dilution and single-disc methods on 50 isolates each of Staphylococcus aureus, Klebsiella or Enterobacter, indole-positive and -negative Proteus, Escherichia coli, and Pseudomonas aeruginosa. All organisms were inhibited by 6.25 Mug or less of the drug/ml. Pseudomonas strains resistant to kanamycin or gentamicin or both were susceptible to tobramycin. Those strains which were inhibited by 6.25 MAg of tobramycin/ml by the broth dilution method had zone diameters of 16 mm or more by the single-disc method. Of 313 organisms tested by the disc method, 3 strains were found to be resistant to tobramycin, 73 were resistant to kanamycin, and 18 were resistant to gentamicin. Tobramycin was found to have satisfactory in vitro activity against many clinically important organisms, including strains resistant to gentamicin and kanamycin.Nebramycin is an antibiotic compound derived from the soil saprophyte Streptomyces tenebrarius. This compound is an aminoglycoside similar in structure to kanamycin, gentamicin, and neomycin and can be separated into eight active factors. After preliminary testing of each, factor 6, tobramycin, was found to have the highest specific activity and broadest spectrum.This study was undertaken to determine the susceptibility of clinically important species of gram-negative bacilli and Staphylococcus aureus to tobramycin in vitro, using both broth dilution and single-disc techniques.MATERIALS AND METHODS Organisms. The strains tested (from the Clinical Bacteriology Laboratory, Grady Memorial Hospital, Atlanta, Ga.) were obtained from specimens of pus, urine, and blood. Included were 50 strains each of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella or Enterobacter, indole-positive Proteus, and indole-negative Proteus, a total of 300.Thirteen gentamicin-resistant strains of P. aeruginosa (provided by J. A. Shulman) were also studied. These were isolated from burned patients.Standard strains S. aureus ATCC 25923 and E. co/i ATCC 25922 (provided by R. S. Griffith, Lilly Laboratories) were used as controls.Tube dilutions. Overnight cultures in Trypticase soy broth (BBL) were diluted 1:10,000, and 0.5 ml was added to serial twofold dilutions of the drug being tested in Mueller-Hinton broth (BBL). For each organism, a growth control was included. The total volume in each tube was 1 ml, and the final concentrations of drug ranged from 50 ug/ml to 0.1 ,Ag/ml. The results were read after 18 hr of incubation at 37 C. The minimal inhibitory concentration (MIC) was the lowest concentration of drug in which there was no visible turbidity.Disc susceptibility tests. Disc susceptibility tests were done as described by Bauer et al. (1) with the modifications proposed in the Federal Register (3). RESULTSSusceptibility to tobramycin. All fifty of the coagulase-positive strains of staphylococci tested were susceptible to 0.39 ,Ag or less of the drug/ml, the mode of the MIC values being .0.1 Ag/ml (Ta...

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