Mechanism of Protective Effect of Fosfomycin Against Aminoglycoside Ototoxicity

Ohtani, Iwao; Ohtsuki, Kohsei; Aikawa, Tohru; Sato, Yoichi; Anzai, Tomohiro

doi:10.1016/s0385-8146(84)80019-x

Cited by 8 publications

(7 citation statements)

References 10 publications

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“…Fosfomycin has been found in vivo to mitigate the toxicity of various co-administered antibiotics, for example nephrotoxicity related to aminoglycosides [96], glycopeptides [97] or amphotericin B [98] as well as ototoxicity related to aminoglycosides [99] or polymyxin B [100].…”

Section: Use Of Fosfomycin In Combination Drug Regimensmentioning

confidence: 99%

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

Roussos

Karageorgopoulos

Samonis

et al. 2009

International Journal of Antimicrobial Agents

163

151

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Section: Use Of Fosfomycin In Combination Drug Regimensmentioning

confidence: 99%

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

Roussos

Karageorgopoulos

Samonis

et al. 2009

International Journal of Antimicrobial Agents

163

151

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“…Experimental evidence. Rats treated with 50 mg/kg dibekacin combined with 500 mg/kg fosfomycin show markedly lower levels of kidney and serum AG than animals receiving dibekacin alone (39).…”

Section: Drug/compound: Fosfomycinmentioning

confidence: 85%

Prevention and modulation of aminoglycoside ototoxicity (Review)

Perletti¹,

Vral²,

Patrosso³

et al. 2008

Mol Med Report

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Abstract. More than 60 years after their isolation and characterization, aminoglycoside (AG) antibiotics remain powerful agents in the treatment of severe gram-negative, enterococcal or mycobacterial infections. However, the clinical use of AGs is hampered by nephrotoxicity and ototoxicity, which often develop as a consequence of prolonged courses of therapy, or of administration of increased doses of these drugs. The discovery of non-ototoxic antibacterial agents, showing a wider spectrum of activity, has gradually decreased the use of AGs as first line antibiotics for many systemic infections. However, AGs are now undergoing an unexpected revival, being increasingly indicated for the treatment of severe emerging infections caused by organisms showing resistance to most first-line agents (e.g., multidrug-resistant tuberculosis, complicated nosocomially-acquired acute urinary tract infections). Increasing adoption of aminoglycosides poses again to scientists and physicians the problem of toxicity directed to the kidneys and to the inner ear. In particular, aminoglycoside-induced deafness can be profound and irreversible, especially in genetically predisposed patients. For this reason, an impressive amount of molecular strategies have been developed in the last decade to counteract the ototoxic effect of aminoglycosides. The present article overviews: i) the molecular mechanisms by which aminoglycosides exert their bactericidal activity, ii) the mechanisms whereby AGs exert their ototoxic activity in genetically-predisposed patients, iii) the drugs and compounds that have so far proven to prevent or modulate AG ototoxicity at the preclinical and/or clinical level, and iv) the dosage regimens that have so far been suggested to decrease the incidence of episodes of AG-induced ototoxicity. Aminoglycoside antibiotics: a revival?Aminoglycoside (AG) antibiotics have been extensively used for the prophylaxis and the treatment of a wide variety of systemic infections, for the outstanding features displayed by these antibacterial agents, i.e., the concentration-dependent bactericidal activity, the post-antibiotic effect, the favorable pharmacokinetic profile, and the strong synergism with other antibiotics such as vancomycin and ß-lactams (1). More than 60 years after their isolation and characterization, these drugs remain powerful tools for treatment of severe gram-negative, enterococcal or mycobacterial infections. AGs are usually administered in combination with ß-lactam antibiotics for a variety of systemic infections (e.g., bacterial endocarditis or various pseudomonal infections), but are also used as monotherapy for infections of the urinary tract. Streptomycin, the first AG isolated and adopted for human therapy (Fig. 1), MOLECULAR MEDICINE REPORTS 1: 3-13, 2008 3 Prevention and modulation of aminoglycoside ototoxicity (Review) GIANPAOLO

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“…some drugs, including cyclosporine, cisplatinum, and certain antibiotics, eg, the aminoglycosides, 71,72 vancomycin, polymyxin B, and amphotericin B. This efficacy has also been observed in clinical practice.…”

Section: Drug Interactionsmentioning

confidence: 86%

“…[73][74][75] Detailed reviews have been published elsewhere. 30,61 Several hypotheses have been made to explain this protective effect with aminoglycosides, including competition for entry that would prevent accumulation and toxicity 71,72 and stabilization of lysosomal membranes. 76 …”

Section: Drug Interactionsmentioning

confidence: 99%

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

2011

Clinical Medicine Reviews in Therapeutics

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Abstract:The use of fosfomycin has been limited in therapeutics in recent years. Because it has shown good antibacterial activity in vitro and clinical efficacy in some domains, it has been proposed as an alternative to current antimicrobial agents, which are subject to increasing resistance. This paper reviews the main properties of fosfomycin and the latest publications concerning multidrugresistant Enterobacteriaceae infections. In uncomplicated urinary tract infections, a single oral dose was found to be safe and effective. In complicated urinary tract infections, the same results were observed with several doses. In both cases, by using fosfomycin to treat infections, the use of carbapenems could be reduced, leading to lower costs and better microbial ecology. In severe infections, combinations with intravenous fosfomycin need to be explored further because its future activity may depend on choosing a good partner drug. Because of the fast evolution of microbial resistance, more studies are urgently needed.

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Mechanism of Protective Effect of Fosfomycin Against Aminoglycoside Ototoxicity

Cited by 8 publications

References 10 publications

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

Prevention and modulation of aminoglycoside ototoxicity (Review)

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

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