No abstract

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 betalactam 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 Pseadomonas aeruginosa. LY-127935

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.

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.

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 i 8.7 tsg/ml for cephacetrile and cephalothin, respectively; 6 h after the dose, the respective levels were 12.4 i 4.3 and 3.7 + 0.9 ,ug/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 cephhlothin in antimicrobial treatment and overall side reactions.