Aminoglycoside-induced hearing loss in humans

Brummett, Robert E.; Fox, Kaye E.

doi:10.1128/aac.33.6.797

Cited by 160 publications

(80 citation statements)

References 77 publications

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“…The toxicity of netilmicin given qd observed in this study is, however, not greater than that reported in a retrospective study of netilmicin given according to conventional schedules (4.4% at low frequency; 10) or in global analysis of a large number of clinical trials conducted with netilmicin up to 1983 (15). In a study of netilmicin in the treatment of pelvic inflammatory disease in young women, Tulkens et al (29) observed no cochleotoxicity of netilmicin given qd in the low-frequency range and only 1 patient (of 19) with cochleotoxicity in the high-frequency range (3). By using the same criterion as Tulkens et al (29) (i.e., any decrease of .15 dB), the occurrence of cochleotoxicity in the present study was not significantly different in the two groups.…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection

Auwera

Meunier

Ibrahim

et al. 1991

Antimicrob Agents Chemother

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The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily (qd) or thrice daily (tid) for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients. The overall efficacy was 96%. Nephrotoxicity, assessed by the measure of urinary excretion of phospholipids, was lower for the patients receiving the qd regimen than for those receiving the tid regimen. Elevation of serum creatinine (20% over baseline) occurred in one patient receiving the qd regimen and in three receiving the tid regimen. Cochleotoxicity, assessed by pure-tone audiometry (250 to 18,000 Hz) occurred in one patient receiving the qd regimen and none receiving the tid regimen. Concentrations in sera were measured on days 1 and 5. No significant accumulation was observed in either group. Median serum bactericidal titers, expressed as reciprocal values (percentage of the sera with a titer .8), were measured against 25 test organisms in samples collected 6 h after the administration of netilmicin and were, for the qd group, 16 (82%) against members of the family Enterobacteriaceae and <2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and <2 (0%) against P. aeruginosa. The rate of killing in serum was rapid (2 to 3 log in 2 h against P. aeruginosa; 3 to 5 log in 2 h against members of the Enterobacteriaceae) and correlated with the sampling time and hence the concentration in serum of netilmicin. The duration of the postantibiotic effect in serum depended also on the strain and the sampling time of the serum.Gram-negative infections are a major cause of morbidity in cancer patients, especially when they are neutropenic. Treatment of these infections consists of the administration of a broad-spectrum P-lactam antibiotic often in combination with an aminoglycoside. The use of combination therapy is advocated for infections due to Pseudomonas aeruginosa and is particularly important when microorganisms resistant to the 3-lactam antibiotic are responsible for the infection. A favorable outcome in patients with gram-negative bacillary bacteremia or pneumonia treated with aminoglycosides is related directly to the initial peak concentration in serum (20, 21) and to achieving a ratio of initial peak serum concentration to the MIC for the offending pathogen of greater than 6:1 (19). These observations confirm previous studies on the predictive value of the serum bactericidal titer on the outcome of gram-negative bacillary bacteremia (26,33). In addition, a prolonged postantibiotic effect (PAE) has been observed with aminoglycosides in vitro and in experimental infections (31,32). The main side effects of aminoglycosides are ototoxicity and nephrotoxicity (4,8,17,28). Studies in animals (1,11,16,23,34) have suggested that both nephrotoxicity and ototoxicity are lower when the daily dose is given as a single administration rather than in two or three divided doses over 24 h. A prospective study comparing netilmicin given onc...

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Section: Discussionmentioning

confidence: 99%

Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection

Auwera

Meunier

Ibrahim

et al. 1991

Antimicrob Agents Chemother

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“…Aminoglycosides penetrate into the vestibular and cochlear tissue, damaging the sensory air cells in the cochlea and labyrinth (32,63). The relationship between aminoglycoside pharmacokinetic parameters and auditory toxicity is unclear.…”

Section: Ototoxicitymentioning

confidence: 99%

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

2012

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SUMMARY Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa , those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria.

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“…Fluoroquinolones are known to induce the formation of singlet oxygen ( 1 O 2 ) and superoxide anion (O 2 Ϫ ), which are responsible for the phototoxic effect of the fluoroquinolones (37). In addition, the two prominent side effects of aminoglycoside antibiotics, ototoxicity and nephrotoxicity, are also believed to involve ROS (9,26). A number of diverse cellular processes that lead to cell death are also mediated through ROS (8,11).…”

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confidence: 99%

Involvement of Reactive Oxygen Species in the Action of Ciprofloxacin againstEscherichia coli

Goswami

Mangoli

Jawali

2006

Antimicrob Agents Chemother

184

158

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Ciprofloxacin is an important and commonly used member of the fluoroquinolone group of antibiotics. Ciprofloxacin inhibits DNA topoisomerase II and DNA topoisomerase IV activities, eventually leading to bacterial cell death. In addition, an increase of reactive oxygen species in the bacterial cells in response to ciprofloxacin has been shown. We investigated the role of reactive oxygen species in the antibacterial action of ciprofloxacin by studying the effects of different antioxidant compounds on ciprofloxacin susceptibility of Escherichia coli. Among the antioxidants checked, glutathione and ascorbic acid provided substantial protection against ciprofloxacin. The involvement of superoxide anion (O 2 ؊ ) and hydrogen peroxide (H 2 O 2 ) in the antibacterial action of ciprofloxacin was analyzed using superoxide dismutase, catalase, and alkyl hydroperoxide reductase knockout strains of E. coli. The effects of multicopy sod genes on ciprofloxacin susceptibility of E. coli were also analyzed. On the basis of our results, we conclude that O 2 ؊ and H 2 O 2 may be involved in antibacterial action of ciprofloxacin. Our findings that glutathione gave protection against other fluoroquinolones and not against nonfluoroquinolone antibiotics imply that reactive oxygen species may have a similar role in the antibacterial action of all these fluoroquinolones and that glutathione-mediated protection is not a general phenomenon but specific to fluoroquinolones. These observations are of significance, as fluoroquinolones are important antibiotics with immense therapeutic value, and the effectiveness of treatment by these drugs may be affected by dietary intake and cellular levels of these antioxidants.The emergence of drug resistance against ␤-lactam and aminoglycoside antibiotics resulted in the discovery of newer classes of synthetic antibiotics, including quinolones. Since the discovery of the first quinolone, nalidixic acid, various structural and chemical modifications resulted in expanded-spectrum and broad-spectrum quinolones (reviewed in references 3 and 29). These drugs are well absorbed following oral administration, with moderate to excellent bioavailability, and they show rapid bactericidal effect against susceptible organisms and cover a broad antibacterial spectrum (29). Since these drugs consist of carboxyl and amine groups along with other chemical functionalities, their acid-base behavior is influenced by the physiochemical properties of the solvent and their antibacterial activity is pH dependent (30). The mechanism of antibacterial action of quinolones is not completely understood; however, it has been proposed that the initial event is the inhibition of DNA synthesis by interference with the nick sealing activity of DNA topoisomerase II (DNA gyrase) and DNA topoisomerase IV. In the presence of these antibiotics, the enzyme is trapped on the DNA, resulting in the formation of quinolone-enzyme-DNA complexes, and the subsequent release of DNA ends from this complex leads to

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Aminoglycoside-induced hearing loss in humans

Cited by 160 publications

References 77 publications

Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection

Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

Involvement of Reactive Oxygen Species in the Action of Ciprofloxacin againstEscherichia coli

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