A comparative study of gentamicin and netilmicin in the treatment of gram-negative infections.

Netilmicin is active in vitro against a wide variety of gram-negative bacteria, including certain gentamicin-resistant isolates, and Staphylococcus aureus. This study presents the results of a prospective, randomized, double-blinded protocol designed to determine the relative efficacy and toxicity of netilmicin and gentamicin in the therapy of gram-negative infections. The demographic make-up of both treatment groups was similar. Cure rates were 96.7 percent with netilmicin and 94.4 percent with gentamicin. Possible transient nephrotoxicity developed in nine patients receiving netilmicin and in eight patients receiving gentamicin.

Cefmenoxime. Clinical, bacteriologic, and pharmacologic studies.

Cefmenoxime, a new semisynthetic third-generation cephalosporin, was evaluated in 105 patients (45 men and 60 women) with the following infections: skin or skin structure (33), pulmonary (22), urinary tract (30), and septicemia (20). Forty-two infections were hospital-acquired, 85 patients had underlying diseases, 29 patients required concomitant surgery, and 32 patients had positive results of blood culture. Cefmenoxime dosages ranged from 4 to 12 g per day intravenously for one and a half to 51 days. Cultures revealed 183 organisms in the 105 patients. Minimal inhibitory concentrations were obtained for cefmenoxime, cefoperazone, cefotaxime, cefamandole, cefoxitin, and moxalactam. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against all organisms tested and were the most active agents tested against all aerobic and facultative organisms except Staphylococcus aureus. Mean serum peak and trough levels obtained after 2 g every six hours were 84.1 micrograms/ml (peak), 8.3 micrograms/ml (trough); and after 2 g every four hours, 106 micrograms/ml (peak) and 10.9 micrograms/ml (trough). Of 105 infections, 86 were clinically cured, three were not cured, and 16 were not evaluable. Safety studies revealed 24 transient reactions in 23 patients including eosinophilia, diarrhea, leukopenia, rash, elevated liver enzyme levels, Antabuse effect, and phlebitis. On the basis of these clinical and in vitro results, cefmenoxime is a safe drug for the treatment of infections caused by gram-negative and gram-positive aerobic organisms.

Amikacin levels in the human biliary tract.

The concentrations of amikacin in serum, gallbladder, and common duct bile, and gallbladder tissue in patients undergoing surgery of the biliary tract were investigated. Patients received 500 mg amikacin intravenously or intramuscularly from 1 to 11 hours before surgery. Another group had T-tubes inserted and blood and bile levels were studied serially postoperatively. One half hour after 500 mg amikacin, serum levels were high and bile levels were 30 per cent of the serum levels, with tissue levels less than 19 per cent of the serum levels. At 6 hours, serum levels were 37 per cent of the 1-hour levels; however, bile levels were 34 per cent of the simultaneous serum levels. At 11 hours, both postdose serum and bile amikacin levels were low. However, simultaneous bile levels were higher than serum levels. No patient suffered from any side effects from amikacin.

In vitro and clinical evaluation of ceforanide.

Ceforanide, a new cephalosporin antibiotic with a long half-life (three hours), was evaluated for its antimicrobial activity, pharmacology, and clinical efficacy. Fifty-two patients with 56 infections due to susceptible organisms received ceforanide, 0.5 g, 1 g, or 2 g, intramuscularly or intravenously every 12 hours for four to 60 days (average: 14.1 days). The in vitro studies of our clinical isolates showed that 12.0 micrograms/ml or less of ceforanide inhibited all Streptococcus pneumoniae, beta hemolytic streptococci group A, B, F, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Hemophilus influenzae. After a 1 gram intramuscular dose, the mean peak serum concentration at one hour was 44.0 micrograms/ml, and at 12 hours was 3.8 micrograms/ml. After a 1 gram intravenous dose, the mean peak serum concentration was 65.0 micrograms/ml, and the mean trough serum concentration at 12 hours was 9.6 micrograms/ml. The infections treated included ten pneumonias, ten urinary tract infections, seven bacteremias, two osteomyelitis, and 35 skin-soft tissue infections. Of the 56 evaluable infections treated, 52 had a clinical cure with only four failures. Ceforanide was well tolerated, with no patients developing thrombophlebitis, or liver or renal abnormalities. Three patients developed abnormal Coombs' reactions and one had diarrhea.

Cefmenoxime penetration into gallbladder bile and tissue.

Cefmenoxime concentrations in gallbladder bile and tissue were assessed in patients undergoing cholecystectomy. A 0.5-g intravenous dose produced mean concentrations in bile of 54.1 micrograms/ml at 62.9 min and 56.3 micrograms/ml at 194 min after the dose was given. A 1.0-g intravenous dose produced concentrations in bile of 117.9 micrograms/ml at 53 min and 169.7 micrograms/ml of 194 min after the dose was given. Mean concentrations in tissue ranged from 6.1 to 17.9 micrograms/g. Biliary tree penetration was dose and time dependent. Therapeutic concentrations were achieved.

Clinical experience with cefotaxime in the treatment of serious bone and joint infections.

Cefotaxime, a new parenteral cephalosporin that is beta-lactamase resistant, was evaluated for safety and efficacy in 55 patients (at 22 hospitals) with serious bone and joint infections. Septic arthritis and bursitis and acute and chronic osteomyelitis were treated with 2-16 g of parenteral cefotaxime per day (mean, 7.45 g) for 4-54 days (mean, 22.8 days). Thirty-seven patients had underlying diseases or conditions, 13 patients had infections that were hospital acquired, and 39 patients required surgery. Staphylococcus was the most frequently isolated pathogen. Overall, 39 of the 51 patients who met all criteria for evaluation had satisfactory responses to cefotaxime. The drug was well tolerated by all patients. Further investigation of cefotaxime for the treatment of bone and joint infections is warranted.

Cefoxitin therapy in aerobic, anaerobic, and mixed aerobic-anaerobic infections.

Cefoxitin, a new beta-lactamase-resistant cephamycin, was evaluated in 66 patients for clinical and bacteriological efficacy, serum levels, tolerance, and toxicity. Seventeen patients had soft tissue infections, 14 had pleuropulmonary infections, 14 had intraabdominal infections, 13 had pelvic infections, and 8 had urinary tract infections. Among the 66 patients, 62 were cured and 4 could not be evaluated. Twelve patients had hospital-acquired infections, 31 had underlying disease, and 45 required a surgical procedure. Isolates included 116 aerobic and 72 anaerobic bacteria. Cefoxitin was more active than cephalothin against facultative and obligate anaerobic gram-negative organisms isolated from these patients. Mean peak cefoxitin levels in sera were 52 micrograms/ml after a 2-g infusion and 30 micrograms/ml after a 1-g infusion. Phlebitis occurred in two patients, eosinophilia in one, rash in two, vasculitis in one, and transient rises in SGOT and SGPT in two. Cefoxitin appears to be a safe and effective drug for the treatment of many aerobic, anaerobic, and mixed aerobic-anaerobic infections.