In vitro inactivation of aminoglycosides by apalcillin

Abstract

Apalcillin, at concentrations of 75, 150, 300, and 600 ,ug/ml, was combined in vitro with amikacin, gentamicin, netilmicin, or tobramycin. Incubation at 37C resulted in an apalcillin concentration-dependent and time-dependent decrease of aminoglycoside activity of up to 60%. Amikacin was the most stable and tobramycin was the least stable aminoglycoside under the conditions tested.The in vitro inactivation of aminoglycoside antibiotics by beta-lactam antibiotics has often been reported (2-4, 9-15). The extent of such inactivation has been shown to vary as a function of various experimental parameters, such as time, temperature, solvent, method of assay, and antibiotic concentration (2,4,9,11,14). Of particular interest has been aminoglycoside inactivation by the newer broad-spectrum penicillin derivatives, such as carbenicillin, azlocillin, ticarcillin, etc. (9-15).Apalcillin is a relatively new semi-synthetic penicillin with activity against a broad spectrum of gram-negative bacteria (1,7,8). This naphthyridine derivative of ampicillin has particularly good activity against Pseudomonas aeruginosa (5) and will likely be used in combination with other broadspectrum antimicrobial agents, such as the aminoglycosides, in therapy against gram-negative infections. In view of the prospective combination of apalcillin use and the inactivation of aminoglycoside antibiotics by other beta-lactam antibiotics, we determined to measure the in vitro effect of apalcillin on aminoglycoside activity when these compounds are mixed together.The stability of the aminoglycosides amikacin (Bristol Laboratories, Syracuse, N.Y.), gentamicin and netilmicin (Schering Corp., Bloomfield, N.J.), and tobramycin (Eli Lilly & Co. Indianapolis, Ind.) was evaluated when they were mixed in combination with apalcillin (Wyeth Laboratories, Philadelphia, Pa). Each antibiotic solution was prepared from a standard reference powder and diluted in pooled, drug-free human serum. The final apalcillin concentrations in the reaction mixture were 0, 75, 150, 300, and 600 ,ug/ml. The concentration of gentamicin, netilmicin, and tobramycin used in combination with each apalcillin concentration was 10 ,ug/ml, and amikacin was prepared at 20 ,ug/ml.The antibiotic pairs were combined, mixed, and then placed at 37°C in a water bath shaker. Duplicate samples for assay were removed from each mixture at 0, 8, 24, and 36 h after mixing. These samples were immediately frozen. The aminoglycoside concentration in each sample was determined by thawing the samples and immediately measuring the aminoglycoside by fluorescence polarization immunoassay (TDX; Abbott Laboratories) according to the specifications of the manufacturer (6). Possible changes in apalcillin concentration during antibiotic interaction were not determined. Assays were done in duplicate on each sample. The data, analyzed by using a two-way analysis of variance, were * Corresponding author. significant to greater than the 95% confidence level, both as a function of time and of apalcillin concentration. Tabl...

Potential Drug-Drug Interactions and their Associated Factors at the University Children's Hospital in Syria: A Cross-Sectional Study

“…The combination of aminoglycosides and cephalosporins is synergistically nephrotoxic, necessitating careful monitoring for signs of nephrotoxicity [24,25]. Additionally, cephalosporins may inactivate aminoglycosides [26]. However, this is expected to be clinically significant only in patients with severely impaired renal function [27,28].…”

Improved efficacy with nonsimultaneous administration of first doses of gentamicin and ceftazidime in vitro

“…We could not demonstrate inactivation of either antibiotic when they were combined at the concentrations used in this experiment. There are other reports supporting the absence of an interaction between gentamicin and ceftazidime (18,19) and between ceftazidime and tobramycin (16). Secondly, when the antibiotics are given simultaneously, one antibiotic may be inhibiting a specific action of the other.…”