Theodore C. Eickhoff

Carbenicillin and gentamicin: Pharmacologic studies in patients with cystic fibrosis and pseudomonas pulmonary infections

Fourteen treatment courses with carbenicillin, 100 to 600 mg. per kilogram every 4 hours, gentamicin, 4–5 mg. per kilogram per day, or a combination of these drugs were given to patients with cystic fibrosis, who had extensive pulmonary disease and Pseudomonas aeruginosa colonization, to determine the penetration of these antibiotics into sputum, to attempt to eradicate pseudomonas organisms from sputum, and to observe the clinical effects of such intensive chemotherapy. The mean minimum inhibiting concentration (MIC) of carbenicillin for 27 pseudomonas strains was 85.6 μg per milliliter. The mean peak serum level of carbenicillin at 600 mg. per kilogram every 4 hours was 2,176 μg per milliliter at 15 minutes; the mean peak sputum level was 78 μg per milliliter at 60 minutes. Peak serum levels at 100 to 400 mg. per kilogram every 4 hours ranged from 248 to 464 μg per milliliter with sputum peaks of 0 to 18.4 μg per milliliter. Sputum concentrations of carbenicillin and gentamicin, alone or in combination, were inadequate to eradicate pseudomonas organisms. There was no objective evidence of improvement as a result of chemotherapy in this small group of patients.

In Vitro Comparison of Cefoxitin, Cefamandole, Cephalexin, and Cephalothin

The in vitro effect of cefoxitin, cefamandole, cephalexin, and cephalothin was tested against 645 strains of bacteria recently isolated from clinical sources. Against gram-positive organisms cephalothin and cefamandole were the most effective, generally being three- to fourfold more active than cephalexin or cefoxitin. Enterococci were not inhibited by less than 25 μg of any of the antibiotics per ml. Against Enterobacteriaceae, cefoxitin and cefamandole were the most active. An exception was the Enterobacter strains, against which cefoxitin was the least effective. None of the Pseudomonas aeruginosa strains were susceptible to 100 μg of any of the cephalosporins per ml. Cefamandole was the most active agent against Neisseria meningitidis and Neisseria gonorrhoeae. It was also the most effective agent against Haemophilus influenzae, even when taking into account a threefold inoculum effect.

Bacterial risk in staging splenectomy.

Excerpt To the editor: There is an increasing trend toward laparotomy and splenectomy in the staging of Hodgkins disease (1). Serious infections have been associated with asplenia (2, 3) but appar...

In Vitro Activity of Netilmicin Compared with Gentamicin, Tobramycin, Amikacin, and Kanamycin

The in vitro activity of netilmicin was compared with that of gentamicin, tobramycin, amikacin, and kanamycin against 636 strains of bacteria recently isolated from clinical sources. Gentamicin was the most active antibiotic, but netilmicin and tobramycin closely paralleled it. Netilmicin was generally four-to eightfold less active than gentamicin against Serratia and group A streptococci, and was twofold less active against Pseudomonas aeruginosa. When effects of inoculum size and concentration of divalent cations in the media were evaluated, netilmicin was shown to be similar to gentamicin in vitro. Minimum inhibitory concentrations for P. aeruginosa were increased as much as 18-fold when the Mg2+ and Ca2+ concentrations were increased to physiological levels in Mueller-Hinton broth.

Effects of Ampicillin-Amikacin and Ampicillin-Rifampin on Enterococci

Fifty-seven clinical isolates of enterococcus were tested for susceptibility to 10 antibiotics in a microtiter broth dilution system. Amoxicillin, ampicillin, vancomycin, and rifampin inhibited all strains at concentrations easily achievable in blood. Resistance to rifampin developed rapidly. Of the aminoglycosides, gentamicin was most active, followed in decreasing order by tobramycin, amikacin, kanamycin, and streptomycin. High-level resistance to streptomycin was present in 26% of the strains and to kanamycin in 23% of the strains. Growth curve studies of selected strains revealed synergy with ampicillin-amikacin and antagonism with ampicillin-rifampin. It is suggested that ampicillin-gentamicin constitutes adequate initial therapy for enterococcal infections until the results of tests for high-level resistance to kanamycin and streptomycin are known and that clinical trails of ampicillin-amikacin are warranted.

Comparative activity in vitro of ticarcillin, BL-P1654, and carbenicillin.

The activity of ticarcillin, BL-P1654, and carbenicillin was compared in vitro using a microtiter tube dilution test in Mueller-Hinton broth against 50 recent clinical isolates each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, and Pseudomonas aeruginosa. Bactericidal end points were determined using a modified Steers replicator. Ticarcillin was generally two to four times more active against all organisms tested except S. epidermidis against which BL-P1654 was most active. Median minimum inhibitory concentrations in micrograms per milliliter were for S. aureus: ticarcillin (6.2), carbenicillin (12.5), BL-P1654 (25); for S. epidermidis: BL-P1654 (1.6), ticarcillin (3.2), carbenicillin (3.2); for E. coli: ticarcillin (3.2), BL-P1654 (6.2), carbenicillin (6.2); for Klebsiella sp.: >100 for all three drugs; for Enterobacter sp.: ticarcillin (3.2), carbenicillin (6.2), BL-P1654 (12.5); for Proteus sp.: ticarcillin (1.6), carbenicillin (1.6), BL-P1654 (3.2); for P. aeruginosa: ticarcillin (31), BL-P1654 (62), carbenicillin (125). Bactericidal end points were dependent on both the drug and the species but were in general no more than twofold more than the minimum inhibitory concentration with the exception of BL-P1654 against P. aeruginosa. BL-P1654 was bactericidal for only 60% of the strains tested at a concentration of 500 μg/ml.

Adult Immunizations: How Are We Doing?

Physicians seldom ask adult patients about basic immunizations or seek to determine whether the patients occupation, lifestyle, or travel may warrant additional vaccine coverage. Yet more than 30,000 lives could be saved every year in the United States if adult immunization recommendations were implemented. Strategies for improving delivery are reviewed and information on specific vaccines is updated.

Characterization of an Ampicillin-Resistant Haemophilus influenzae Type B

A 28-year-old female in Denver was found in early 1974 to have frontal sinusitis, osteomyelitis, and bacteremia due to Haemophilus influenzae, type B. The minimal inhibitory concentration of ampicillin for this organism was 100 μg/ml and the minimal bactericidal concentration was >100 μg/ml. It was inhibited by chloramphenicol at 0.4 μg/ml. Further studies demonstrated that ampicillin and methicillin were synergistic against this organism. It was shown to produce a diffusible beta-lactamase. Transferase of resistance from this organism to a susceptible Haemophilus parainfluenzae and a reciprocal transfer were accomplished. A test for transformation was negative as was a test for reversal of resistance by ethylenediaminetetraacetic acid.

Combined Action of 6-Mercaptopurine and Antibiotics on Gram-Negative Bacteria in Vitro

Summary The antibacterial activity of a commonly used antimetabolite, 6-mercapto-purine (6-MP), was studied in vitro using chemically defined media. 6-Mercaptopurine (1-5 μg/ml) had weak bacteriostatic activity against Escherichia coli, klebsiella, enterobacter and pseudomonas. Synergism occurred between 6-MP and aminoglycoside antibiotics whereas 6-MP was weakly antagonistic to the action of penicillin and cephalosporin antibiotics. These combined actions were not reversed by fetal bovine serum (50%) but were readily reversed by an excess of hypoxanthine or adenine. No interactions occurred between 6-MP and tetracycline, chloramphenicol or polymyxin B. The authors are indebted to Mrs. Susan Knorr for excellent technical assistance.