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Intravenous inoculation of 6.2 × 10 10 to 6.7 × 10 10 Pseudomonas aeruginosa organisms into rhesus monkeys 5 days after intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in 8 of 10 untreated monkeys. When similarly infected monkeys were treated intramuscularly with 2.5 mg of colistin or 50 mg of carbenicillin per kg per day, all three monkeys in each treatment group survived; one of three monkeys receiving both antibiotics at the above doses died. Six of seven monkeys treated with 1.25 mg of colistin per kg per day and three of seven treated with 25 mg of carbenicillin per kg per day died; four of nine monkeys receiving both antibiotics at these doses died. A combination of the data obtained at both dose levels tested shows that 6 of 10, 3 of 10, and 5 of 12 monkeys, respectively, died after treatment with colistin, carbenicillin, and the colistin-carbenicillin combination. Antibacterial activity of serum from both infected and normal monkeys was not appreciably different when the two antibiotics were given singly or in combination. Under the conditions of this study and with the doses employed, the response of monkeys treated with the antibiotic combination did not differ significantly from that of monkeys treated with a single agent.

Intravenous inoculation of 3.4 X 1010 to 7.4 X 101°Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in eight of nine monkeys. After intramuscular administration, in two equal doses, of 5 MATERIALS AND METHODSEighty fully conditioned, young-adult monkeys (Macaca mulatta) weighing 3.2 to 4.6 kg were used. Physical examinations, hematological and bacteriological studies, and tests for C-reactive protein (CRP) were conducted over a period of at least 2 weeks to establish normalcy of the monkeys before use in experiments. VCR (Eli Lilly & Co.; 8) was used in these studies. Each ampoule contained 5.0 mg of VCR and 50 mg of lactose; the accompanying diluent was 0.9% sodium chloride containing 0.9% benzyl alcohol. Concentrations of 2.5 or 2.0 mg of VCR in 1.0 ml were prepared immediately before use. Monkeys inoculated intratracheally with VCR were anesthetized with sodium pentobarbital. Intravenous inoculations were made into the saphenous vein of unanesthetized monkeys.A pyocine type 6 strain of P. aeruginosa (Bricker) used to challenge monkeys was isolated repeatedly from urine from a patient with chronic infection. Six-hour Trypticase Soy Broth (TSB; BBL) cultures, incubated over magnetic stirrers in a water bath at 37 C, were centrifuged to a soft pellet in an International PR-2 refrigerated centrifuge. The cells were dispersed in 0.9% sodium chloride with the aid of glass beads and gentle mixing with a glass rod. The resulting smooth suspension was adjusted nephelometrically to the desired concentration by using a predetermined curve relating viable count to percent light transmission at 550 nm in a Leitz Rouy Photrometer. Surface plate counts were carried out by diluting the suspension in TSB and spreading 0.01-ml portions of the appropriate dilution over the surface of blood plates with a calibrated platinum loop. Plates were prepared from blood agar base (Difco) containing 5% ovine blood and were dried ovemight at room temperature to prevent excessive spreading of the individual Pseudomonas colonies.Monkeys were challenged intravenously with 3.4 X 1010 to 8.7 X 1010 Pseudomonas cells 4 days after intravenous or intratracheal inoculation of 2.0 or 2.5 mg of VCR. Therapy with tobramycin, gentamicin, colistin, and carbenicillin was instituted 16 hr after challenge and continued for 10 days. The daily dose was divided equally and given intramuscularly at 8:00 AM and 5:00 PM. Untreated control monkeys given VCR followed by Pseudomonas challenge received 0.9% sodium chloride intramuscularly.Monkeys were examined at least twice daily for 3 weeks after challenge and daily thereafter for at least 3 months. Laboratory studies included com-164 on May 12, 2018 by guest http://aac.asm.org/ Downloaded from

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