Emergence of tobramycin-resistant S. epidermidis possessing aminoglycoside modifying enzymes and bacteremic superinfection during empiric therapy of febrile neutropenic episodes.

During a randomized clinical trial comparing tobramycin plus ticarcillin to netilmicin plus ticarcillin as empiric therapy of febrile neutropenic patients, Staphylococcus epidermidis emerged as the predominate superinfecting pathogen in tobramycin recipients. Overall clinical response was 68% (44/65 responding) in tobramycin/ticarcillin recipients and 73% (45/62) in netilmicin/ticarcillin recipients. However, 5/65 tobramycin/ticarcillin treated episodes were complicated by bacteremic superinfection with Staphylococcus epidermidis, as compared to 0/62 netilmicin/ticarcillin treated episodes (p less than 0.05). Four of the five bacteremic strains produced aminoglycoside adenylating enzyme ANT 4', 4''. Prior colonization of patients with identical strains was demonstrated by plasmid profile analysis, antibiograms and biotyping with the API Staph-Ident system. During the trial, 36 consecutive patients were studied for colonization patterns with coagulase-negative staphylococci. S. epidermidis accounted for 566/831 (68%) isolates of coagulase-negative staphylococci recovered from surveillance cultures. Tobramycin-resistant strains were acquired in 2/17, 4/12 and 9/14 patients during trimethoprim/sulfamethoxazole, netilmicin/ticarcillin and tobramycin/ticarcillin therapy, respectively. Prior to aminoglycoside therapy, 77% of strains were susceptible to less than or equal to 8 micrograms/ml of tobramycin, but only 35% and 28% were susceptible to tobramycin after initiation of tobramycin/ticarcillin and netilmicin/ticarcillin therapy, respectively. In contrast, greater than or equal to 93% of isolates were susceptible to netilmicin before and after aminoglycoside therapy. Absence of several sites susceptible to modification by aminoglycoside inactivating enzymes produced by staphylococci may give netilmicin a therapeutic advantage in the therapy of febrile neutropenic patients.