Anand P. Panwalker

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.

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.

Efficacy of Cinoxacin in Urinary Tract Infections

Cinoxacin, a new synthetic antibacterial agent with in vitro activity against all species of Enterobacteriaceae, was used in the treatment of urinary tract infections in 20 patients. The dose of cinoxacin was 250 mg orally every 6 h for 10 days. The etiological agents were Escherichia coli in fifteen, Klebsiella-Enterobacter in five, Proteus mirabilis in two, and Providencia in one. The minimal inhibitory concentration for these organisms ranged from 2 to 64 μg/ml. Eleven of the 20 patients had renal involvement by defined criteria, whereas the remaining nine were considered to have bladder bacilluria. The initial strain was eradicated during and immediately after treatment in 19 of 20 cases. At 6 weeks, 65% had sterile urine. Bactericidal urine levels of cinoxacin were obtained in all patients. No significant hematological, renal, hepatic, or gastroenterologic toxicity was noted. Cinoxacin appears to be a safe and useful drug in the treatment of urinary tract infections caused by Enterobacteriaceae. Images

Actinobacillus actinomycetemcomitans endocarditis in a patient with a prosthetic aortic valve

SummaryBacterial endocarditis caused by Actinobacillus actinomycetemcomitans is a rare disease. A 48-year-old man who had a Starr-Edwards aortic valve prosthesis inserted in 1972 was admitted for evaluation of confusion, headaches, anorexia, weight loss, diarrhea and weakness. Six blood cultures yielded gram-negative organisms which were subsequently identified as A. actinomycetemcomitans. Treatment with ampicillin and gentamicin resulted in cure which has been maintained after an observation period of eleven months. This represents the second report of A. actinomycetemcomitans endocarditis in a patient with a prosthetic valve.ZusammenfassungBakterielle Endokarditis durch Befall mit Actinobacillus actinomycetemcomitans ist eine seltene Erkrankung. Ein 48jähriger Mann, dem 1972 eine künstliche Aortenklappe vom Typ Starr-Edwards eingesetzt worden war, wurde zur klinischen Beurteilung eines aus Verwirrung, Kopfschmerzen, Anorexie, Gewichtsverlust, Diarrhoe und Schwäche bestehenden Syndroms stationär aufgenommen. Sechs Blutkulturen wiesen gramnegative Organismen aus, die nachfolgend als A. actinomycetemcomitans identifiziert wurden. Eine Behandlung mit Ampicillin und Gentamycin führte zur Heilung, die nach einer Beobachtungsdauer von elf Monaten anhielt. Dies ist der zweite Bericht über Endokarditis infolge A. actinomycetemcomitans bei einem Patienten mit Klappenersatz.

Clinical Efficacy of Moxalactam with Emphasis on Infections Due to Multidrug-Resistant Organisms in Patients with Renal Insufficiency

The efficacy of moxalactam, a new beta-lactam antibiotic with an expanded spectrum of in vitro activity, was evaluated in 22 patients with 27 sites of infection. The pathogens included six strains of multidrug-resistant Serratia marcescens and one of Pseudomonas aeruginosa. The minimal inhibitory concentration of moxalactam for the study isolates ranged from less thant 0.12 to 32 microgram/ml. Peak serum levels exceeded the minimal inhibitory concentration of the pathogen in every instance with mean peak serum levels of 43.0, 65.0 and 123 microgram/ml for doses of 0.5, 1.0 and 2.0 g, respectively. Pharmacokinetic data was obtained in patients with normal and abnormal renal function and during hemodialysis. Moxalactam was found to have excellent penetration into synovial, peritoneal, pleural and cerebrospinal fluids. 23 of the 27 infections were cured, There were six episodes of recurrent infections at the 4-week follow-up among the 12 patients treated for urinary tract infections. Drug toxicity was not a major problem. There were nine instances of superinfection noted (three each due to Candida spp., enterococci and P. aeruginosa), only of which was clinically significant.

Klebsiella species: antimicrobial susceptibilities, bactericidal kinetics, and in vitro inactivation of beta-lactam agents.

In vitro properties of 19 antimicrobial agents were tested with 56 isolates of Klebsiella spp. The aminoglycosides and the new beta-lactam compounds cefotaxime and moxalactam were the most inhibitory drugs tested. Chloramphenicol, tetracycline, trimethoprim, and trimethoprim-sulfamethoxazole were moderately active, whereas piperacillin, mezlocillin, and furazlocillin were ineffective against 25% of the isolates. Gentamicin was the only agent tested that was uniformly bactericidal in time-kill experiments with drug concentrations of four times the minimal inhibitory concentration. In combination studies with gentamicin, moxalactam and furazlocillin each increased the rate of bacterial killing for three of five isolates as compared with gentamicin alone, whereas chloramphenicol significantly retarded the rate of bacterial killing for the same number of strains. Furazlocillin was completely inactivated after 24 h of incubation with each of five selected strains. The inactivation of moxalactam, cefoxitin, and cephalothin was 36, 56, and 72%, respectively. In all instances in which these four agents were inactivated to levels below the minimal bactericidal concentration, there was accelerated growth after initial inhibition. However, regrowth also occurred in three instances in which drug levels were higher than the minimal bactericidal concentration. Retesting after drug exposure revealed a 4- to 32-fold rise in the minimal inhibitory concentration and minimal bactericidal concentration in two of these isolates.

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.