Faculty Bibliography

The incidence of amikacin resistance among gram-negative bacilli isolated at the New York V.A. Medical Center increased from 2.0% to greater than 7% during an 18-month period from January 1980 to July 1981. This increase coincided with a threefold increase in amikacin use at this institution. The amikacin-resistant (AKR) isolates most frequently recovered in 1981 were species of Klebsiella, Serratia, and Pseudomonas. These organisms were recovered from multiple sites, including urine, sputum, wounds, blood, peritoneal fluid, and pleural fluid. The amikacin-modifying enzyme 6'-N-acetyltransferase was detected in 27 (67.5%) of 40 randomly selected AKR isolates. These data indicate that resistance to amikacin in this hospital is enzymatically mediated in most strains of AKR Klebsiella and Serratia and in about one-third of AKR strains of P. aeruginosa. This finding supports the conclusion that amikacin resistance is enhanced by the pressure of increased amikacin use

Sixteen patients with serious Gram-negative bacillary infections were treated with intravenous ceftazidime, 2 g every 8 h. The majority of patients had bacteraemia or pneumonitis or both. Ten patients were cured and six improved. Seven of ten patients infected with Pseudomonas aeruginosa were cured, and three improved. No adverse reactions occurred. Four strains of Ps. aeruginosa became resistant to ceftazidime in patients who were cured or improved clinically. Ceftazidime is effective as single drug therapy for serious Gram-negative infections, including those due to Ps. aeruginosa

Studies to date have indicated that nutritionally-variant streptococci (NVS) causing bacterial endocarditis are frequently inhibited but not killed by low concentrations of penicillin. We report a patient with endocarditis due to a NVS strain which was killed in vitro by penicillin at a concentration of 0.09 microgram/ml. Despite therapy with intravenous penicillin for four weeks, the infection relapsed and was then cured by combined penicillin-gentamicin in therapy. In vitro studies demonstrated a synergistic effect of these two antibiotics. This experience suggests that combination therapy with penicillin and an aminoglycoside may be required for cure of all cases of nutritionally-variant streptococcal endocarditis regardless of in vitro susceptibility to penicillin

The multiple-dose pharmacokinetics and tolerance of intravenous ceftriaxone were investigated in 44 adults with normal renal function. Doses of 0.5, 1.0, and 2.0 g every 12 h and 2 g every 24 h were administered intravenously at a constant rate over 30 min. Plasma and urine samples were collected after the first (day 1) and last (day 4) dose and assayed for ceftriaxone by high-pressure liquid chromatography. Considering all four doses, mean peak plasma concentrations ranged from 79 to 255 micrograms/ml on day 1 and from 101 to 280 micrograms/ml on day 4. Trough concentrations at 12 h on day 1 were 15 to 45 micrograms/ml and 20 to 59 micrograms/ml on day 4. After a dose regimen of 2 g every 24 h, trough levels were still in the clinically therapeutic range (13 to 15 microgram/ml). The mean beta-phase t1/2 was markedly long (6.3 to 6.9 h) and was independent of dose. The fraction of dose excreted unchanged in the urine (0.33 to 0.44) indicated a substantial nonrenal mechanism of elimination. The plasma clearance ranged between 1,002 and 1,449 ml/h, and renal clearance ranged from 353 to 529 ml/h. The apparent volume of distribution varied from 9.2 to 13.5 liters. The dose-related increases in calculated Vd and Clp could be attributed to concentration-dependent plasma protein binding because of a larger free fraction of drug at higher concentrations. The drug was well tolerated, and no significant clinical or laboratory abnormalities were noted

Five men developed disseminated infection with Mycobacterium avium-intracellulare. These patients all lived in the New York City area and presented with their illnesses between January 1981 and September 1981; four were homosexual and one was an intravenous drug abuser. Four patients died. All five patients had defects in the cell-mediated immune response. The infections were characterized histopathologically by poor or absent granulomatous tissue reaction. Clinical isolates of M. avium-intracellulare from all five patients agglutinated commonly used antimycobacterial drugs. The spectrum of opportunistic infections among populations of homosexuals and drug abusers should be expanded to include disseminated disease due to M. avium-intracellulare.

Eighteen patients with 21 serious infections were treated with ceftriaxone, 1 g intravenously every 12 h, for a mean duration of 8 days. Eighteen gram-negative and two gram-positive organisms were isolated. Sites of infection included blood (three patients), urinary tract (six patients), respiratory tract (seven patients), biliary tract (three patients), ascitic fluid (one patient), and skin (one patient). Serum, bile, and ascitic fluid concentrations of ceftriaxone were in excess of the minimal bactericidal concentration required for the infecting organism in all cases. A bacteriological response was demonstrated in 94% of the infections. A clinical response occurred in four infections from which no pathogens were recovered. In one patient, ceftriaxone failed to eradicate a peritoneal infection due to Bacteroides fragilis. In two patients, superinfection with enterococci developed both during and after therapy. Systemic tolerance to ceftriaxone was excellent