In Vitro Bactericidal Effectiveness of Four Aminoglycoside Antibiotics

Sisomicin and gentamicin (2 mg/kg) were administered in a random fashion to patients with bacteriuria superimposed on abnormalities of the urinary tract. Cure was achieved in a similar number of patients in both groups, but superinfection and reinfection with resistant microorganisms was more frequent in patients receiving gentamicin. Untoward side effects were not frequent in this series, especially if the serious underlying urological disease of most patients is taken into consideration. The susceptibility of the causative pathogens to the antibiotic administered and the severity of the underlying disease were the most important factors in the outcome.Sisomicin is a new aminoglycoside antibiotic produced by the growth of a species of Micromonospora, Micromonospora inyoensis. This antibiotic is produced substantially as a single component and resembles most closely gentamicin C,A, a component of the gentamicin complex. From in vitro data and from preliminary clinical studies (4,6,8), no major difference is to be expected between gentamicin and sisomicin; however, cross-resistance between gentamicin and sisomicin does not always exist, and no comparative study has yet been published from the clinical point of view.The present investigation was undertaken to compare the efficacy and the tolerance of gentamicin and sisomicin when used to eradicate bacteriuria in patients with underlying diseases of the urinary tract. An in vitro comparison of gentamicin and sisomicin performed on a large number of recently isolated microorganisms will be presented as well. MATERIALS AND METHODSBacteriological studies. The bacteria tested were isolated from patients hospitalized at the Institut Jules Bordet, which is the clinical center for cancer therapy of Brussels University. Bacteria studied comparatively with sisomicin and gentamicin were isolated during the first semester of 1974. They included 250 Escherichia coli, 183 Klebsiella, 40 Enterobacter, 85 Proteus mirabilis, 20 indole-negative Proteus, and 140 Pseudomonas aeruginosa. Only one isolate of the same bacterial species per patient has been considered here. These bacteria were identified according to Edwards and Ewings (3). Minimum inhibitory concentrations (MIC) of sisomicin and gentamicin were determined by the inocula-replicating method (7) using Mueller-Hinton agar (BBL) and an overnight bacterial suspension in Trypticase soy broth (BBL) diluted to a final concentration of approximately 105 viable microorganisms/ ml. For the evaluation of cross-resistance between sisomicin and gentamicin only differences greater than a single dilution were taken into consideration. A similar technique was used to determine the MIC of the bacteria isolated from the patients who were included in the clinical trial.To determine the bactericidal activity of the sera and urines of the patients against the offending pathogen, a standard twofold tube-dilution technique was employed. Trypticase soy broth and a final inoculum containing 106 viable bacteria/ml were used throughout.The level o...

Section: Bacteriological Results Are Indicated Insupporting

confidence: 80%

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confidence: 99%

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confidence: 99%

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Comparison of Sisomicin and Gentamicin in Bacteriuric Patients with Underlying Diseases of the Urinary Tract

Klastersky

Hensgens

Gerard

et al. 1975

“…The overall spectrum of antimicrobial activity in vitro ofthe new aminoglycoside antibiotic sisomicin (10) is similar to that of gentamicin, although sisomicin has been reported to show somewhat greater activity against Pseudomonas aeruginosa, Klebsiella sp., and indole-positive Proteus (2, 4,6,9,11). In this study we compared the activity of sisomicin and gentamicin in mouse protection tests against six clinical gram-negative isolates, including one strain each of Klebsiella sp., Escherichia coli, Enterobacter aerogenes, Serratia marscens, Proteus mirabilis, and Pseudomonas aeruginosa.…”

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confidence: 99%

Comparison of Activity of Sisomicin and Gentamicin in Mouse Protection Tests with Gram-Negative Bacilli

Meyers

Hirschman

1976

The efficacy of sisomicin and gentamicin was compared in mouse protection studies against strains of Escherichia coli, Klebsiella sp., Enterobacter aerogenes, Serratia marcescens, Proteus mirabilis , and Pseudomonas aeruginosa . There was no significant difference in mortality of the mice in any of the protocol groups when five different dosages of sisomicin and gentamicin given by three separate schedules were compared for each bacterial inoculum in each antibiotic protocol. The mean protective dose values of sisomicin were at least one-half those of gentamicin for each protocol against Pseudomonas aeruginosa .

“…Tube dilution assays were done in MuellerHinton broth as previously described (9). Grid studies were performed so that double dilutions of cephalothin, and cefazolin were combined with double dilutions of gentamicin or tobramycin.…”

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confidence: 99%

Synergy Between Cephalosporin and Aminoglycoside Antibiotics Against Providencia and Proteus

Hyams

Rahal

1974

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Clinical isolates of Providencia and Proteus with relative aminoglycoside resistance were tested for susceptibility to combinations of gentamicin or tobramycin with cephalothin or cefazolin. The minimal bactericidal concentration of aminoglycoside for one-third of the strains was reduced by fourfold or more in the presence of one-fourth of the minimal bactericidal concentration of either cephalosporin. This effect was achieved by clinically attainable concentrations of cephalothin or cefazolin.Although Providencia has been an uncommon cause of clinical infections, recent epidemics have been described in hospitalized patients, particularly in burn units (5,14,15). We have noted a gradually increasing incidence of clinical isolates of Providencia in our hospital, although serious infections have remained rare. In vitro studies on these strains have indicated relative resistance to all aminoglycoside antibiotics. Most strains have required minimal inhibitory and bactericidal concentrations of 12.5 to 50 gg of gentamicin per ml. A synergistic effect of penicillins or cephalosporins with aminoglycosides has previously been demonstrated against Enterobacteriaceae (3, 4, 10) and Pseudomonas (6,12,17). We have therefore studied nine strains of Providencia and seven strains of the related genus, Proteus, which were moderately or highly resistant to gentamicin. Our purpose was to evaluate two cephalosporins, cephalothin and cefazolin, in crossover combination with two aminoglycosides, gentamicin and tobramycin, for possible in vitro synergy against these organisms.MATERIALS AND METHODS Providencia and Proteus strains were collected from the clinical microbiology laboratory on the basis of gentamicin resistance by routine disk sensitivity testing. Tube dilution assays were done in MuellerHinton broth as previously described (9). Grid studies were performed so that double dilutions of cephalothin, and cefazolin were combined with double dilutions of gentamicin or tobramycin. This resulted in duplicate minimal inhibitory and bactericidal concentration values for each drug against each strain. Of the 144 such duplications, four differed by two tube dilutions and the remainder differed by one dilution or less. Synergy was defined as a fourfold decline in minimal inhibitory concentrations (MIC) or minimal bactericidal concentration (MBC) of gentamicin or tobramycin after the addition of one-fourth of the MIC or MBC of a cephalosporin antibiotic to each tube. RESULTSThe MIC and MBC values of each drug against the nine strains of Providencia and seven strains of Proteus tested are shown in Fig. 1