A simple model of infective endocarditis was produced in rats. With the aid of a guide wire, polyethylene catheters were passed into the left ventricle through the right carotid artery of Sprague-Dawley rats weighing 300 to 350 g. A volume of 1 ml of an overnight culture of Streptococcus mitis, Staphylococcus aureus, or Streptococcus faecalis was intravenously injected 1 to 2 days after catheterization. Bacterial titers of Streptococcus mitis in vegetations were about 104-fold greater than in other tissues. Blood cultures were always positive after 6 h. Mortality was 19% at 1 week and 82% at 2 weeks. Catheters were pulled 24 h after infection, and vegetation titers of >7.0 logo colony-forming units per g were sustained at 5 days. In intravenously infected rats without catheters, blood and tissues were sterile after 3 to 5 days. With Staphylococcus aureus, vegetations had >9.0 logio colonyforming units and with Streptococcus faecalis 8.8 + 0.3 logo colony-forming units per g at 2 days. The rat model of infective endocarditis should prove to be suitable for further pathological and therapeutic studies.

Twenty-six patients, 20 to 77 years of age, were treated with netilmicin, mean dose 2 mg/kg every 8 h intramuscularly or in a 20-min intravenous infusion. The mean serum half-lives in patients with creatinine clearances of 290 ml/min and 60 to 90 ml/min were 3.2 and 3.4 h, respectively. In patients with serum creatinines of 51.4 mg/100 ml and creatinine clearances of 260 ml/min, mean serum levels were 9.0 and 1.2 ,ug/ml, respectively, 5 to 15 min and 7.5 h post-intravenous infusion, and 7.1 and 1.7 ,ig/ml, respectively, 1 and 8 h post-intramuscular injection. Twenty-five patients had acute pyelonephritis; 7 of the 25 had bacteremia. The infecting bacteria were Escherichia coli (15), Proteus mirabilis (5), Pseudomonas aeruginosa (2), Klebsiella pneumoniae (1), Enterobacter hafniae (1), and both Proteus rettgeri and Proteus morganii (1). All were inhibited by 6.3 ,ug of netilmicin per ml, except for the P. rettgeri, which required 25 ,ug/ml for inhibition. Of 23 patients who could be evaluated, 19 were bacteriologically and clinically cured at follow-up. Of the remaining four, one relapsed, two became reinfected, and one was lost to follow-up. Five patients developed nephrotoxicity; two of the five had previous renal insufficiency. Three patients, one with abnormal renal function, developed ototoxicity detected only with audiograms. These studies suggest that netilmicin is effective in serious gram-negative bacillary infections, but is nephrotoxic and ototoxic in humans.The aminoglycosides gentamicin, tobramycin, and amikacin have all proved to be useful agents in therapy of serious infections caused by gramnegative bacilli. These antibiotics are nephrotoxic and ototoxic. Netilmicin, a new aminoglycoside with broad-spectrum activity against gram-negative bacilli, has been shown to be less nephrotoxic and ototoxic than gentamicin in experimental animals (3,15,18).The purpose of this study was to investigate the pharmacology and efficacy of netilmicin in patients with suspected bacteremia caused by gram-negative bacilli.

Fewer than ten biopsy-proven case reports exist on vancomycin-associated interstitial nephritis (VAIN) and vancomycin-associated acute tubular necrosis (VAATN). Among these, several are confounded by the use of other potentially offending drugs. We report a case of isolated VAIN/VAATN in a patient on no other potentially nephrotoxic agents other than vancomycin. The patient received intravenous vancomycin for coagulase-negative staphylococcus bacteremia. Her baseline serum creatinine of 0.9 mg/dL increased to 9.6 mg/dL after 1 week of therapy during which vancomycin levels peaked at 141 μg/mL. Renal biopsy revealed acute interstitial nephritis with lymphocytic and eosinophilic infiltrate and acute tubular necrosis. Upon discontinuation of vancomycin and administration of prednisone complete renal recovery ensued over a period of 4 weeks.

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The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactaase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and oneeighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.Cefazolin (CZ) is much more susceptile to inactivation by Staphylococcus aureus betalactamase than cephalothin (CF) (7), raising doubts about the usefulness of CZ in staphylococcal endocarditis (2). This study compares the efficacy of CZ, CF, and methicillin (M) in the therapy of left-sided endocarditis in rabbits, caused by a highly penicillin-resistant, methicillin-susceptible strain of S. aureus, which rapidly inactivates CZ in vitro. MATERIALS AND METHODSOrganism. A strain of S. aureus obtained from the blood of a patient with endocarditis was used in all experiments. The minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of CZ, CF, M, and penicillin G were determined by using an antibiotic dilution method in both heart infusion broth (HIB; Difco Laboratories, Detroit, Mich.) and pooled rabbit serum (Microbiological Associates, Inc., Bethesda, Md.). The antibiotics were diluted in twofold steps in tubes containing 0.5 ml of HIB or serum. The bacterial inoculum for each tube was 0.5 ml of a 10-2 dilution in HIB or serum of an 18-h HIB culture. The MIC was considered to be the lowest concentration of antibiotic that prevented turbidity after 24 h of incubation at 370C. After the MIC was determined, 0.01 ml of each clear tube was streaked on the surface of a sheep blood agar plate with a sterile platinum loop. The minimal bactericidal concentration was the lowest concentration of antibiotic that resulted in no growth on the plate after 48 h at 370C. Stock cultures were made by incubating the organism in HIB at 37°C for 24 h and storing 1-ml portions at -20°C. For each experiment, a portion was subcultured into HIB, incubated at 37°C for 18 h, and diluted in HIB or serum.In vitro studies. The rate at which the S. aureus was killed was studied in flasks with HIB containing CZ, CF, or M. The inoculum in HIB was added to each flask and incubated at 370...