Preservation of Colonization Resistance Parameters During Empiric Therapy with Aztreonam in the Febrile Neutropenic Patient

Abstract

The role of the anaerobic intestinal flora in maintaining colonization resistance was examined in a study of empiric therapy in febrile neutropenic patients who received aztreonam plus tobramycin, aztreonam plus cloxacillin, or moxalactam plus tobramycin, regimens with differential effects on the anaerobic intestinal flora. Surveillancecultures showed that all regimens eradicated fecal carriage of enteric gram-negative bacilli but that fecal acquisition of fungi occurred in 4 (27%) of 15 aztreonam/tobramycin, 6 (43%) of 14 aztreonam/cloxacillin, and 13 (81%) of 16 moxalactam/tobramycin recipients. Fungi were acquired at 11 (22%) of 49 sites in aztreonam/tobramycin, 15(31%) of 48 sites in aztreonam/ cloxacillin, and 28 (54%) of 52 sites in moxalactam/tobramycin recipients. Aztreonam/tobramycin reduced fecal anaerobe counts by 10; aztreonam/cloxacillin, by a mean of 2.5 log₁₀ ; and moxalactam/tobramycin, by 5.l log₁₀ colony-forming units (cfu)/g of feces by day 10 ± 3 of therapy. Elimination of the anaerobes was reflected by a reduction in concentrations of short-chain fatty acids (SCFAs)in fecal supernatants. Fecal specimens containing ⩾10⁶ cfu of Bacteroides fragitis group organisms/g (dry weight) contained significantly higher concentrations of succinic, propionic, and isobutyric acids. Flat SCFAchromatograms wereobserved in 90% of fecal samples from which no anaerobes were recovered. Preservation of the anaerobic flora appears critical in the prevention of fungal acquisition in neutropenic patients.