Comparative Activity of Netilmicin, Gentamicin, Amikacin, and Tobramycin Against
            <i>Pseudomonas aeruginosa</i>
            and
            <i>Enterobacteriaceae</i>

Netilmicin, a new aminoglycoside antibiotic, has increased in vitro bactericidal activity against many strains of Enterobacteriaceae as compared to other aminoglycosides. It is a poor substrate for some of the common gentamicin-inactivating enzymes, and it has minimal toxicity in experimental animals. In 27 hospitalized patients, clinical cure was achieved in all, and the initial infecting organism persisted in only one. Therapeutic serum and urine levels were easily obtained in most patients. No ototoxicity was observed in two patients whose treatment required inordinately high serum levels and in whom other risk factors were present. Ototoxicity in 1 of 21 patients studied was unilateral, partially reversible, and not associated with high serum levels. Although nephrotoxicity occurred in 4 of 25 patients (16%), other host factors could have accounted for the toxicity in two patients. A new observation, not noted with other aminoglycoside antibiotics, was the elevation of serum alkaline phosphatase in 43% of the patients studied.

Section: Materiais and Methods Thirty-one Patients On The Medical Andmentioning

confidence: 99%

Netilmicin: Clinical Efficacy, Tolerance, and Toxicity

Panwalker

Malow

Zimelis

et al. 1978

“…This study was undertaken as a result of our interest in determining whether there were any important differences between the aminoglycoside antibiotics gentamicin and tobramycin. A review of the literature indicated only minor differences in in vitro antibacterial activity (1,6,8,14,20,31). Gentamicin is slightly more active against Serratia species, and tobramycin is slightly more active against isolates of Pseudomonas aeruginosa.…”

mentioning

confidence: 99%

Comparative Nephrotoxicity of Gentamicin and Tobramycin in Rats

Gilbert

Plamp

Starr

et al. 1978

A rat model was utilized to compare the nephrotoxic potential of gentamicin and tobramycin. Gentamicin, 40 mg/kg per day, predictably produced renal failure and morphological evidence of proximal tubular necrosis over 14 days of treatment. An identical dosage of tobramycin was associated with only minimal morphological changes and normal concentrations of serum creatinine and blood urea nitrogen. Similar results were obtained even after the tobramycin dosage was tripled to 120 mg/kg per day. A decrease in urine osmolality, mechanism unknown, was observed in all aminoglycoside-treated rats, but the lowest osmolalities were found in the gentamicin-treated rats. According to both histological criteria and renal function measurements, gentamicin was more nephrotoxic than tobramycin in this animal model. This study was undertaken as a result of our interest in determining whether there were any important differences between the aminoglycoside antibiotics gentamicin and tobramycin. A review of the literature indicated only minor differences in in vitro antibacterial activity (1,6,8,14,20,31). Gentamicin is slightly more active against Serratia species, and tobramycin is slightly more active against isolates of Pseudomonas aeruginosa. In vivo animal studies of antibacterial activity again show similar degrees of activity, except that tobramycin is more active against P. aeruginosa infections (5,30). The pharmacokinetics of the two drugs in humans are felt to be virtually identical (9,12,22,28). Comparative toxicity studies of the effects of these two drugs in humans have not been reported.In a rat model, tobramycin was found to have a lower lethal dose than gentamicin (5). Tobramycin was found to have a lower lethal dose than gentamicin (5). Tobramycin was found to be less ototoxic than gentamicin in guinea pigs (2). Tobramycin was considered less nephrotoxic than gentamicin in rats on the basis of subtle but consistent histological changes and differences in drug-induced urinary lysosomal enzymes (12, 21). Since a clear difference in nephrotoxic potential would have clinical importance, studies were designed to more precisely detect any abnormalities in renal structure or function.Initially, a prospective randomized doubleblind study in humans was considered. A recent report describes such a study comparing gentamicin and amikacin (26). However, it appears virtually impossible to determine the incidence of aminoglycoside-induced nephrotoxicity in humans. There is no way for the investigator to separate disease-induced toxicity from drug-induced toxicity. Also, preillness measurements of renal structure and function are rarely available. Because of these concerns, we chose to use a rat model of aminoglycoside nephrotoxicity. Nephrotoxicity was quantitated by histological changes and alterations in renal fimction. The results demonstrate that, in this model, tobramycin is less nephrotoxic than gentamicin.MATERIALS AND METHODS Animals. Adult male Fischer 344 rats, weighing 175 to 275 g, were used. The rats were kept sing...

“…(6) Salmonella spp. (5) Vibrio parahaemolyticus (3) Gaffkya tetragena (1) Sarcina lutea (1) Edwardsiella tarda (1) Herellea vaginicola (1) Klebsiella oxytoca (1) Providencia spp. (2) Shigella dysenteriae (1 to assess the nephrotoxicity of the two compounds were urine volume, protein excretion, osmolality, microscopic characteristics, blood chemistry, and histopathology.…”

Section: Resultsmentioning

confidence: 99%

Antibacterial activities, nephrotoxicity, and ototoxicity of a new aminoglycoside, Win 42122-2

Came¹,

O'Connor²,

Dobson³

et al. 1979

Win 42122-2 is a new aminoglycoside antibiotic obtained from a mutant strain of Micromonospora purpurea. In vitro and in vivo comparisons of Win 42122-2 with gentamicin and amikacin revealed that Win 42122-2 generally was less active than gentamicin against Pseudomonas and many Enterobacteriacae, especially Klebsiella and indole-negative Proteus. Against most gentamicin-susceptible isolates, Win 42122-2 was more active than amikacin. Gentamicin-resistant clinical isolates were usually resistant to Win 42122-2, although it was active against certain gentamicin-resistant organisms, depending upon the aminoglycoside-modifying enzymes harbored by the organism. However, Win 42122-2 was markedly less toxic than gentamicin in subacute nephrotoxicity studies in rats, ototoxicity experiments in guinea pigs, and ataxia determinations in cats. This series of antibacterial determinations and toxicity evaluations indicated that the reduced toxicity of the antibiotic may be sufficient to provide an improved therapeutic ratio over gentamicin and other aminoglycosides, even though Win 42122-2 is less potent than gentamicin against some bacteria.