Tobramycin: In Vitro Activity and Comparison with Kanamycin and Gentamicin

Abstract

The in vitro activity of the aminoglycoside antibiotic tobramycin was demonstrated by broth dilution and single-disc methods on 50 isolates each of Staphylococcus aureus, Klebsiella or Enterobacter, indole-positive and -negative Proteus, Escherichia coli, and Pseudomonas aeruginosa. All organisms were inhibited by 6.25 Mug or less of the drug/ml. Pseudomonas strains resistant to kanamycin or gentamicin or both were susceptible to tobramycin. Those strains which were inhibited by 6.25 MAg of tobramycin/ml by the broth dilution method had zone diameters of 16 mm or more by the single-disc method. Of 313 organisms tested by the disc method, 3 strains were found to be resistant to tobramycin, 73 were resistant to kanamycin, and 18 were resistant to gentamicin. Tobramycin was found to have satisfactory in vitro activity against many clinically important organisms, including strains resistant to gentamicin and kanamycin.Nebramycin is an antibiotic compound derived from the soil saprophyte Streptomyces tenebrarius. This compound is an aminoglycoside similar in structure to kanamycin, gentamicin, and neomycin and can be separated into eight active factors. After preliminary testing of each, factor 6, tobramycin, was found to have the highest specific activity and broadest spectrum.This study was undertaken to determine the susceptibility of clinically important species of gram-negative bacilli and Staphylococcus aureus to tobramycin in vitro, using both broth dilution and single-disc techniques.MATERIALS AND METHODS Organisms. The strains tested (from the Clinical Bacteriology Laboratory, Grady Memorial Hospital, Atlanta, Ga.) were obtained from specimens of pus, urine, and blood. Included were 50 strains each of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella or Enterobacter, indole-positive Proteus, and indole-negative Proteus, a total of 300.Thirteen gentamicin-resistant strains of P. aeruginosa (provided by J. A. Shulman) were also studied. These were isolated from burned patients.Standard strains S. aureus ATCC 25923 and E. co/i ATCC 25922 (provided by R. S. Griffith, Lilly Laboratories) were used as controls.Tube dilutions. Overnight cultures in Trypticase soy broth (BBL) were diluted 1:10,000, and 0.5 ml was added to serial twofold dilutions of the drug being tested in Mueller-Hinton broth (BBL). For each organism, a growth control was included. The total volume in each tube was 1 ml, and the final concentrations of drug ranged from 50 ug/ml to 0.1 ,Ag/ml. The results were read after 18 hr of incubation at 37 C. The minimal inhibitory concentration (MIC) was the lowest concentration of drug in which there was no visible turbidity.Disc susceptibility tests. Disc susceptibility tests were done as described by Bauer et al. (1) with the modifications proposed in the Federal Register (3). RESULTSSusceptibility to tobramycin. All fifty of the coagulase-positive strains of staphylococci tested were susceptible to 0.39 ,Ag or less of the drug/ml, the mode of the MIC values being .0.1 Ag/ml (Ta...

Clinical Study of the Use of the New Aminoglycoside Tobramycin for Therapy of Infections Due to Gram-Negative Bacteria

“…Tobramycin is more active in vitro against strains of Pseudomonas than gentamicin (5,6,19) but a clinical comparison of tobramycin and gentamicin in the treatment of Pseudomonas infections has not yet been reported. Dienstag and Neu (6) reported in vitro synergy of tobramycin and carbenicillin against strains of Pseudomonas.…”

“…Gentamicin, an aminoglycoside, hitherto has provided the most efficacious therapy for infections due to gramnegative bacilli (3,11,14,18). Tobramycin is a new aminoglycoside with an in vitro spectrum of activity against aerobic gram-negative bacilli similar to gentamicin (5,6,19). However, tobramycin appears to have greater activity than gentamicin against a significant number of pseudomonas strains (5,6,19 were obtained.…”

“…Tobramycin is a new aminoglycoside with an in vitro spectrum of activity against aerobic gram-negative bacilli similar to gentamicin (5,6,19). However, tobramycin appears to have greater activity than gentamicin against a significant number of pseudomonas strains (5,6,19 were obtained. Whenever possible, audiograms were monitored at similar intervals.…”

Transferrable Resistance to Tobramycin in Klebsiella pneumoniae and Enterobacter cloacae Associated with Enzymatic Acetylation of Tobramycin

“…Its effectiveness in vitro is comparable with that of gentamicin, a chemically related aminoglycoside, against Staphylococcus aureus and certain species of Enterobacteriaceae, but most susceptible strains of Pseudomonas aeruginosa are inhibited by a lower concentration of tobramycin than gentamicin. Although resistance both to gentamicin and to tobramycin occurs in some bacterial strains, other isolates are either resistant to gentamicin and susceptible to tobramycin or resistant to tobramycin and susceptible to gentamicin (5)(6)(7)(8)(9)15). Resistance to aminoglycoside antibiotics in clinical isolates of bacteria is generally determined by R factors, although other mechanisms of resistance have been described.…”

“…A number of recent studies have attested to the broad spectrum of antibacterial activity for tobramycin, a new aminoglycoside antibiotic (5,7,9). Its effectiveness in vitro is comparable with that of gentamicin, a chemically related aminoglycoside, against Staphylococcus aureus and certain species of Enterobacteriaceae, but most susceptible strains of Pseudomonas aeruginosa are inhibited by a lower concentration of tobramycin than gentamicin.…”