Comparison of imipenem versus cefuroxime plus tobramycin as empirical therapy for febrile granulocytopenic patients and efficacy of vancomycin and aztreonam in case of failure.

143 aplastic episodes with fever in 91 haematological patients with granulocytopenia were treated empirically in a randomized prospective study using either imipenem (Imi) or a combination of tobramycin and cefuroxime (T/C). Response after 72 h was significantly better in patients receiving Imi (44/75 vs 27/68, p < 0.05). This was seen especially in patients with bacteriologically proven infections where the isolated staphylococci and streptococci were more susceptible to Imi. In both groups, patients who failed to respond to the initial antibiotic therapy were given vancomycin and aztreonam (V/A). The response rate after another 72 h, measured using the same criteria as after the first 72 h, did not differ statistically between the groups. One patient in each study group died from the bacterial infection, both from Gram-positive bacteraemia. Duration of fever was significantly shorter in the Imi group (4 days vs 7 days, p < 0.04). Serum peak and trough concentrations of the antibiotics were comparable. Both regimens were well tolerated. Our results show that monotherapy with imipenem is superior to the combination of tobramycin and cefuroxime during the first 72 h of therapy and can be safely administered to neutropenic patients with predominantly Gram-positive infections. A combination of vancomycin and aztreonam, given when initial imipenem treatment has failed, was effective in only a few patients. Adjuvant glycopeptide therapy from the outset in the treatment of febrile granulocytopenic patients did not seem worthwhile.

Antibiotic treatment, intestinal aerobic microflora and experimental sarcoma L-1 growth in Balb/c-mice.

The present paper deals with the influence of a 10 days treatment with mezlocillin, piperacillin, cefotaxime, clindamycin or gentamicin on the endogenous intestinal microflora of Balb/c-mice and on the local growth of sarcoma L-1 tumor. Clindamycin and gentamicin demonstrated no influence, whereas cefotaxime and piperacillin caused the eradication of gram-negative resp. gram-positive bacteria but these antibiotics didn't produce a growth inhibition of local L-1 sarcoma tumor. The oral or parenteral application of mezlocillin (a 3 days treatment was sufficient) eradicated the complete aerobic and anaerobic intestinal microflora. This effect was significantly correlated with an increase of the cecum weight and the inhibition of local tumor growth. Possible mechanisms of these effects are discussed.

The screening of four aminoglycosides in the selective decontamination of the digestive tract in mice.

The suppressive effect of amikacin, gentamicin, tobramycin and paromomycin on the aerobic endogenous flora and on the colonization resistance of the digestive tract was tested by administering one of the antibiotics orally at five different dose levels. At a certain dose level, all antibiotics suppressed the endogenous Enterobacteriaceae species. Amikacin was particularly effective in this respect. Low doses of amikacin rapidly destroyed the colonization resistance. This resistance only remained unaffected in animals treated with tobramycin in doses that were still adequate to completely suppress the endogenous Enterobacteriaceae species. We concluded that of all the antibiotics tested in this study, only tobramycin may have a future in (clinical) application for the selective decontamination of the digestive tract. Selective decontamination can be considered an effective method for infection prevention in leukopenic patients.

Selective elimination of Enterobacteriaceae species from the digestive tract in mice and monkeys.

In mice and in monkeys, ;selective' elimination of Enterobacteriaceae species from the digestive tract of animals with a sensitive flora was accomplished by oral treatment with nalidixic acid (1 mg./g. body weight in mice and 0.4 mg./g. body weight in monkeys). During treatment, the concentration of enterococci (and also of Candida albicans in the monkey) remained unaltered. This indicates that the fraction of the anaerobic microflora which is responsible for the colonization resistance of the digestive tract is not affected by the treatment. An important consequence seems to be, that elimination of yeast and fungi with fungistatic drugs can be started at the same time as elimination of Enterobacteriaceae is attempted.