Aminoglycoside antibiotics, used to treat bacterial infections by interfering with proofreading during protein synthesis, cause sensorineural hearing loss in genetically susceptible individuals. The only aminoglycoside-hypersensitivity mutations which have been described in humans are in the mitochondrial 125 rRNA gene, potentially allowing increased antibiotic binding to mitochondrial ribosome...

Coadministration of sodium ticarcillin with an aminoglycoside is known to reduce the nephrotoxicity of the aminoglycoside. However, it is not known whether the penicillin or the obligatory sodium load confers protection. To investigate this, gentamicin has been administered intraperitoneally in doses of 50, 60, or 80 mg/kg per day for 12 days in groups of rats receiving either a normal or a low...

Bacterial resistance to antibiotics is a serious public health problem. The emergence of “superbugs” — pathogenic bacteria that can survive the effects of most commonly used antibiotics – significantly compromises existing treatments against infectious diseases. The predominant mechanism of resistance to aminoglycosides, a class of bactericidal antibiotics that are widely used in hospitals, is ...

Aminoglycosides are antibiotics commonly used to treat life-threatening Gram-negative bacterial infections. However, their use is hampered by their severe nephrotoxicity due to accumulation in renal proximal tubules. Several pathways have been implicated in the renal uptake of aminoglycosides including megalin, an endocytic receptor in proximal tubular cells. Here, we have used mouse models wit...

We studied 21 strains of amikacin-resistant Serratia marcescens from three different U.S. cities, Twenty of the 21 strains contained conjugative R plasmids mediating gentamicin and tobramycin resistance. Amikacin-resistant S. marcescens from two cities predominated in protracted outbreaks. Conversely, the amikacin-resistant Charleston strain (serotype 02/03:nonmotile) was isolated from only fou...

Induction of a major outer membrane protein, H1, in Pseudomonas aeruginosa resulted in decreased susceptibility to gentamicin and streptomycin. Mutants which overproduce protein H1 and cells in which H1 is induced in response to growth conditions had altered kinetics of uptake and killing. It was further demonstrated that gentamicin and streptomycin interact with the outer membrane to permeabil...

To examine the nephrotoxicity of prolonged gentamicin administration compared to the effect obtained when a less toxic aminoglycoside is substituted during the course of treatment, we gave gentamicin (67.5 mg/kg per day) to rats for 21 days, gentamicin for 14 days followed by either netilmicin or tobramycin for 7 days, or gentamicin for 14 days followed by saline diluent. After initial tubular,...

Enterococcal endocarditis is usually treated with a combination of a penicillin and an aminoglycoside. Recent reports have documented the emergence of enterococci in France with high-level resistance to gentamicin, tobramycin, and kanamycin and the emergence of strains in Houston, Tex. with high-level resistance to all of these drugs and streptomycin. In this study, we examined strains from a g...

The use of higher-dose, extended interval (i.e., once-daily) aminoglycoside regimens to optimize bacterial killing is justified by a pharmacodynamic principle of aminoglycosides, namely concentration-dependent killing, and by the partial attribution of the toxicity of aminoglycosides to prolonged serum concentrations. Numerous in-vitro and animal studies have supported using once-daily aminogly...