Aminoglycoside-resistant Isolates Research Articles

THE POTENTIAL FOR ORAL ANTIBIOTIC THERAPY FOR PSEUDOMONAS INFECTIONS IN CHILDREN

New, orally absorbed quinoline derivatives are highly active against a broad spectrum of bacteria, including Pseudomonas (Antimicrob Ag Chemother 23:658, 1983). Pseudomonas (n=145) were tested in vitro against enoxacin, norfloxacin, ciprofloxacin, and ofloxacin. All were active against P. aeruginosa (MIC90 ≤4 μg/ml), including aminoglycoside-resistant isolates. Enoxacin and ciprofloxacin were most active against other Pseudomonas species, including many strains of P. cepacia and P. maltophilia. The pharmacokinetics of these drugs were determined in mice and rats and therapeutic studies performed in two models: (1) Graded inocula of Pseudomonas species were injected IP into mice, followed by single dose therapy ½ hour later. Oral enoxacin was more active than norfloxacin or tobramycin in reducing bacteremia and mortality due to P. aeruginosa and P. cepacia (e.g. LD50 102 for saline v. 106.1 for enoxacin for P. aeruginosa); (2) Oral enoxacin was begun 3 days or 3 weeks after persistent Pseudomonas pulmonary infection in the agar-bead rat model. Bacterial concentrations in lung were reduced by 66% and 76%, respectively. These in vitro and in vivo data support the continued development of quinolines as oral antibiotics for Pseudomonas infections in children.

In-vitro activity of enoxacin against aminoglycoside-resistant gram-negative bacilli and other clinical isolates.

The in-vitro activity of enoxacin was tested against 500 clinical isolates of Gram-negative bacilli that were resistant to one or more of gentamicin, tobramycin and amikacin, and against 1060 recent consecutive clinical isolates of Gram-negative bacilli and Gram-positive cocci. Enoxacin was active against staphylococci (MICs less than or equal to 4 mg/l) but less active against Streptococcus faecalis (MICs mostly 8 mg/l). It was active against Pseudomonas aeruginosa (MICs 0.5-4 mg/l) and very active against Enterobacteriaceae. In the series of consecutive isolates 97% of Enterobacteriaceae had MICs less than or equal to 1 mg/l. The aminoglycoside-resistant series of Enterobacteriaceae included more strains with higher MICs (13% were 2-4 mg/l and 10% were greater than or equal to 8 mg/l); the majority of the isolates with MICs greater than or equal to 8 mg/l); the majority of the isolates with MICs greater than or equal to 8 mg/l were Serratia marcescens and Providencia spp. Among the non-fermenting species the least sensitive were Acinetobacter calcoaceticus and Ps. maltophilia. Enoxacin-resistant strains of Enterobacteriaceae were resistant to nalidixic acid, but nalidixic acid-resistant strains ranged from fully sensitive to highly resistant to enoxacin.

Control of aminoglycoside resistance by barrier precautions.

The efficacy of antibiotic resistance (barrier) precautions for control of aminoglycoside resistance was evaluated from 1978 to 1981. Despite increasing aminoglycoside use and a 13-fold increase in aminoglycoside-resistant isolates on a newly opened oncology unit, the hospital-wide frequency of aminoglycoside resistant Enterobacteriaceae remained low, supporting the continued value of barrier precautions which were initiated in our hospital in 1974. This control enabled us to focus on exceptions to the effectiveness of barrier precautions. These were traced to environmental reservoirs, very chronic and heavily infected patients, asymptomatic carriers of Serratia, and oncology patients receiving oral non-absorbable aminoglycosides. In addition, resistance in Pseudomonas aeruginosa paralleled aminoglycoside use and, as in our prior experience, continued to rise. With increasing adoption of barrier precautions by others such exceptions should be anticipated.