In vitro comparison of three new cephalosporins: LY-127935, cefotaxime and cefoperazone.

The comparative in vitro activity of three new cephalosporin antibiotics Ly-127935 (LY), cefotaxime (CTX) and cefoperazone (CFP) was examined. LY, CTX and CFP had similar activity against Staphylococcus aureus, Escherichia coli and Proteus mirabilis while CFP was less inhibitory than LY or CTX against Klebsiella spp.; indole + Proteus and gentamicin (GM)-susceptible Serratia. LY and CTX were effective while CFP was inactive against Enterobacter spp. and GM-resistant Serratia. CFP was more active than LY or CTX against GM-susceptible Pseudomonas aeruginosa but was the least active agent against GM-resistant isolates. Bacteroides fragilis were more susceptible to LY than CTX or CFP. Combination studies against P. aeruginosa with cephalosporin-GM pairs demonstrated synergy.

LY-127935: a novel beta-lactam antibiotic with unusual antibacterial activity.

The in vitro activity of LY-127935, a new beta-lactam antibiotic, was examined by using 370 clinical bacterial strains. In comparison with several other beta-lactam agents, LY-127935 was the most inhibitory against the Enterobacteriaceae. It was remarkably active against multi-drug-resistant strains of Enterobacter spp., Serratia spp., and Pseudomonas aeruginosa. LY-127935 had four- to eightfold greater activity than did cefoxitin against Bacteroides fragilis. Production of beta-lactamase by Enterobacteriaceae did not influence the minimal inhibitory concentration of LY-127935. However, the beta-lactamase-producing strains of B. fragilis and Haemophilus influenzae had generally higher minimal inhibitory concentrations. LY-127935 was the least active agent tested against gram-positive aerobic cocci. Variations in pH, salt content, protein content, or inocula size had little influence on susceptibility to LY-127935. Although combination studies with LY-127935 and gentamicin demonstrated synergy for P. aeruginosa, the rates of killing for the combination and for gentamicin alone were similar.

Comparative in vitro activity of azlocillin, ampicillin, mezlocillin, piperacillin, and ticarcillin, alone and in combination with an aminoglycoside.

The in vitro activities of the newer semisynthetic penicillins azlocillin, mezlocillin, and piperacillin were compared with those of ampicillin and ticarcillin by using 290 clinical laboratory isolates. Piperacillin and mezlocillin were the most active against Escherichia coli, Proteus mirabilis, Klebsiella spp., and Enterobacter spp. When Pseudomonas aeruginosa was tested, piperacillin and azlocillin were more active than either mezlocillin or ticarcillin. Streptococcus pneumoniae and Haemophilus influenzae species were highly susceptible to all of the penicillins tested. Ticarcillin had relatively poor activity against enterococci. The rate of bacterial killing with multiples of the minimal inhibitory concentration of azlocillin, ampicillin, or ticarcillin was tested for E. coli, P. mirabilis, P. aeruginosa, and Klebsiella spp. Increasing concentrations increased the bactericidal effect. The effect of combining azlocillin, ampicillin, or ticarcillin with an aminoglycoside was studied by using both killing curves and checkerboards. The isobolograms constructed from the checkerboards showed a synergistic pattern for the organisms tested, which included E. coli, P. aeruginosa, Klebsiella spp., P. mirabilis, and enterococci. However, the rate of killing was increased by the combination only for P. aeruginosa and enterococci.

Netilmicin: clinical efficacy, tolerance, and toxicity.

Netilmicin, a new aminoglycoside antibiotic, has increased in vitro bactericidal activity against many strains of Enterobacteriaceae as compared to other aminoglycosides. It is a poor substrate for some of the common gentamicin-inactivating enzymes, and it has minimal toxicity in experimental animals. In 27 hospitalized patients, clinical cure was achieved in all, and the initial infecting organism persisted in only one. Therapeutic serum and urine levels were easily obtained in most patients. No ototoxicity was observed in two patients whose treatment required inordinately high serum levels and in whom other risk factors were present. Ototoxicity in 1 of 21 patients studied was unilateral, partially reversible, and not associated with high serum levels. Although nephrotoxicity occurred in 4 of 25 patients (16%), other host factors could have accounted for the toxicity in two patients. A new observation, not noted with other aminoglycoside antibiotics, was the elevation of serum alkaline phosphatase in 43% of the patients studied.

Assay of aminoglycoside antibiotics in clinical specimens.

Optimal therapeutic use of aminoglycoside antibiotics requires monitoring of levels in serum. Three methods have been developed for clinical use; one yields a specific 14C-labeled product, and two are microbiologic methods in which different indicator strains are used to measure the diffusion of drug into agar. These methods were compared in assays with 200 sera from patients receiving gentamicin or sisomicin. Some specimens also contained either a beta-lactam antibiotic or clindamycin. In the presence of penicillin or cephalosporin, the level of aminoglycoside measured was accurate if the specimens were treated with beta-lactamase. The presence of clindamycin invalidated the results when Bacillus subtilis was used as the indicator strain, but not with the other microbiologic method or the enzymatic method. Under proper circumstances, the results obtained by the various methods were comparable, according to statistical analysis. The enzymatic procedure is the most specific and rapid method, but materials for agar well diffusion methods are more readily available and more economical. The procedures are practical, and their use is recommended in patients being treated with aminoglycoside antibiotics.

Double-blind comparison of cephacetrile with cephalothin-cephaloridine.

Under double-blind protocol, a controlled comparison was made between a new cephalosporin, cephacetrile, and cephalothin or cephaloridine. The patient's primary physician determined the indications for treatment, and the dosage was uniform for each route of administration. Infecting strains of staphylococci and Proteus mirabilis had a lower median inhibitory concentration for cephalothin than cephacetrile; the opposite was true for Escherichia coli and Klebsiella species. The average peak serum level 1 h after a dose of 2 g intravenously was 74.9 +/- 21 and 21.5 +/- 8.7 mug/ml for cephacetrile and cephalothin, respectively; 6 h after the dose, the respective levels were 12.4 +/- 4.3 and 3.7 +/- 0.9 mug/ml. Renal clearances were similar and the plasma clearance was proportional to the serum levels. In the urine, the concentration of cephacetrile was three times higher than that of cephalothin. Based on a percentage of therapeutic potential, success in the treatment of infections with susceptible organisms was 42 and 44% for the two different drug regimens. Initial bacterial resistance was found in about one-fifth of infections, and concomitant therapy with other drugs was practiced in one-half of the treatment courses. Intravenous use of cephacetrile was discontinued prematurely more often than was use of cephalothin, suggesting less tolerance. Although there was no overt toxicity, more than 75% of patients on either regimen had some form of unwanted response to treatment, the most common being superinfection. From this limited but controlled experience, cephacetrile can be considered comparable to cephalothin in antimicrobial treatment and overall side reactions.