Therapy of Pseudomonas aeruginosa Infections with Tobramycin

Abstract

The efficacy of tobramycin in doses of 2.7 to 5.6 mg/kg per day in 29 courses of therapy in 25 hospitalized patients with serious Pseudomonas aeruginosa infections was studied. Eighty-three percent of the P. aeruginosa strains showed zones of inhibition of 16 mm or more around a 10-μg tobramycin disk in the Bauer-Kirby disk method. Tobramycin minimal inhibitory concentration ranged from <0.05 to 1.5 μg/ml (microtiter twofold dilution method); for gentamicin they ranged from 0.05 to 6.2 μg/ml; corresponding geometric means were 0.19 and 0.49 μg/ml. Therapy was given for a median of 10 days (mean 19, range 1 to 83). The clinically satisfactory response rate for the 29 courses of therapy was 52%: critically ill, 44%; seriously ill, 50%; moderately ill, 80%. The response rates for various sites of infection were bone and cartilage, 100%; urinary tract infection, 56%; wound, 50%; respiratory tract, 67%; septicemia, 40%; abscess, 0%; burns, 44%. No adverse reactions were seen. Serum concentration (μg/ml ± standard deviation) of tobramycin determined by an agar-well plate method, were 4.81 ± 2.17 (1 h); 3.24 ± 1.43 (2 h); 2.35 ± 1.30 (4 h); and 1.40 ± 1.09 (8 h). Tobramycin appears to be as effacacious as gentamicin in the treatment of serious P. aeruginosa infections and has a theoretical advantage of lower minimal inhibitory concentration for P. aeruginosa . The data suggest that, for life-threatening infections, dosages of tobramycin may need to be increased over those used in this study.

The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms

“…To address this question we tested if the loss of Psl would also affect sensitivity toward another cationic antimicrobial peptide, polymyxin B. In addition, we tested sensitivity toward the aminoglycoside tobramycin, a vital first-round treatment of Pseudomonal associated infections [52], [53], and the fluoroquinolone ciprofloxacin, an antibiotic used commonly in P. aeruginosa infections due to the ease of oral dosing and limited toxicity. As with colistin, we observed an increase in sensitivity (as determined by the MBC-B) of ΔpslAB biofilms relative to WT biofilms for polymyxin B (Figure 1B 32 µg/ml WT PAO1, 16 µg/ml ΔpslAB ), tobramycin (Figure 1C; 785 µg/ml WT PAO1, 285 µg/ml ΔpslAB ), and ciprofloxacin (Figure 1D; 90 µg/ml WT PAO1, 54 µg/ml ΔpslAB ).…”

Progressive Necrotizing External Otitis: Treatment with Ticarcillin and Tobramycin

“…It is similar to gentamicin but has a threefold greater activity in vitro against Pseudomonas; however, specific sensitivity testing must be performed. 18 Tobramycin is bactericidal and appears to act synergistically with carbenicillin against Pseudomonas. 19 The dose is 3 rng./kg.…”

Antibiotic blood concentrations in patients successfully treated with tobramycin

“…It has greater in vitro activity than gentamicin against Pseudomonas aeruginosa (Britt et al, 1972;Burger, Sanford and Zweighaft, 1973;Hyams, Sinberkoff and Rahal, 1973;Yourassowsky, Schuntens and Vanderlinden, 1973) and possibly in vivo (Burch et al, 1973). The pharmacology of tobramycin (Bechtol and Black 1975;Christopher et al, 1974;Jaffe, Meyers and Hirschman, 1974a;Regamey, Gordon and Kirby, 1973), the in vitro susceptibilities of Gram-negative organisms (Geddes et al, 1974;Waterworth, 1972) and its clinical effectiveness (Blair et al, 1975;Carmalt, Cortez and Rosenblatt 1976;Jaffe et al, 1974b;Klastersky, et al, 1974;Schoutens, Vanderlinden and Yourassowsky, 1973) are well documented. The authors have evaluated the results of tobramycin therapy with respect to each patient's underlying illness, type of infection, and a ratio of peak serum concentration and the minimal inhibitory concentration (MIC) of tobramycin against the patient's own pathogen (so-called therapeutic ratio).…”