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Nakamura, Tsutomu; Hashimoto, Yoshiaki; Kokuryo, Toshiyuki; Inui, Kentaro

doi:10.1023/a:1011971019868

Cited by 26 publications

(10 citation statements)

References 12 publications

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“…In fact, studies in rats have shown that fosfomycin protects against aminoglycoside nephrotoxicity by inhibiting aminoglycoside-induced histamine release following mast cell destruction (265). Similar findings regarding vancomycin, amphotericin B, and cisplatin nephrotoxicity have been published (266)(267)(268). Clinical data confirming these observations are not available.…”

Section: Adverse Eventsmentioning

confidence: 50%

Fosfomycin

et al. 2016

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SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

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Section: Adverse Eventsmentioning

confidence: 50%

Fosfomycin

et al. 2016

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“…Toyoguchi et al [ 25 ] showed that cilastatin may reduce VAN-induced nephrotoxicity in rabbits by decreasing serum BUN and creatinine levels. Nakamura et al [ 26 , 38 ] presented similar results in rats. Both authors conclude that the protection observed after treatment with cilastatin is associated with reduced accumulation of VAN in renal tubules [ 25 , 26 , 38 ].…”

Section: Discussionmentioning

confidence: 63%

“…Nakamura et al [ 26 , 38 ] presented similar results in rats. Both authors conclude that the protection observed after treatment with cilastatin is associated with reduced accumulation of VAN in renal tubules [ 25 , 26 , 38 ]. In fact, accumulation of VAN in renal cells has been proposed as a major cause of toxicity [ 2 , 35 , 37 ].…”

Section: Discussionmentioning

confidence: 63%

“…Some authors suggested that the mechanism behind VAN-induced renal damage was similar to that of gentamicin [ 10 , 26 , 39 ], which is induced by accumulation of the drug from the brush border membrane to the renal proximal tubules [ 40 , 41 ]. Gentamicin is transported inside the cell by endocytosis involving megalin, a brush border lipid raft ligand [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, cilastatin seems to be able to reduce luminal entry of drugs across the membranes (e.g., CsA, tacrolimus, and cisplatin) even if they are not substrates for DHP-I activity [ 18 , 19 ]. Although the exact mechanism of VAN accumulation in proximal cells has not been elucidated yet [ 36 ] and remains open to debate [ 26 , 43 , 44 ], Fujiwara et al [ 42 ] recently revealed that significant amounts of VAN were present in the apical pole, specifically in the S1 and S2 segments of the proximal tubules. The presence of VAN near the brush border could also suggest the presence of an unknown transporter(s) in this area [ 42 ], a hypothesis that was also reported by Nakamura et al [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity

Humanes

Jado

Camaño

et al. 2015

BioMed Research International

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Vancomycin is a very effective antibiotic for treatment of severe infections. However, its use in clinical practice is limited by nephrotoxicity. Cilastatin is a dehydropeptidase I inhibitor that acts on the brush border membrane of the proximal tubule to prevent accumulation of imipenem and toxicity. The aim of this study was to investigate the potential protective effect of cilastatin on vancomycin-induced apoptosis and toxicity in cultured renal proximal tubular epithelial cells (RPTECs). Porcine RPTECs were cultured in the presence of vancomycin with and without cilastatin. Vancomycin induced dose-dependent apoptosis in cultured RPTECs, with DNA fragmentation, cell detachment, and a significant decrease in mitochondrial activity. Cilastatin prevented apoptotic events and diminished the antiproliferative effect and severe morphological changes induced by vancomycin. Cilastatin also improved the long-term recovery and survival of RPTECs exposed to vancomycin and partially attenuated vancomycin uptake by RPTECs. On the other hand, cilastatin had no effects on vancomycin-induced necrosis or the bactericidal effect of the antibiotic. This study indicates that cilastatin protects against vancomycin-induced proximal tubule apoptosis and increases cell viability, without compromising the antimicrobial effect of vancomycin. The beneficial effect could be attributed, at least in part, to decreased accumulation of vancomycin in RPTECs.

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Underestimation of rat serum vancomycin concentrations measured by an enzyme‐multiplied immunoassay technique and the strategy for its avoidance

Konishi

Iga

Nagai

2013

Drug Testing and Analysis

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An enzyme-multiplied immunoassay technique (EMIT) has been widely adopted for the measurement of serum concentrations of vancomycin (VCM) in clinical practice. Because of the growing demand for its application to fundamental pharmacokinetic studies, we examined whether VCM concentrations in rat serum were accurately measured by EMIT. It was found that measured values of known amounts of VCM spiked to rat serum were markedly underestimated with a large analytical variance. When ultrafiltrated rat serum was used as the sample matrix, interference was significantly improved, and the degree of underestimation was attenuated also by diluting samples with physiological saline. These results suggest that endogenous substances of a high molecular weight in rat serum interfere with the analysis of VCM concentrations by EMIT. However, measured values of rat serum VCM concentrations by EMIT were restored to theoretical levels by exposing samples to 70°C for 3-7 min. A likely explanation for the avoidance of interference is that an appropriate thermal force eliminated the immunological function of endogenous substances falsely recognizing VCM without affecting the VCM molecule itself. Regarding serum samples collected from rats that were administered VCM, values measured by EMIT following the heat-treatment agreed well with those by the high performance liquid chromatography (HPLC) method. This is the first report showing interference by endogenous high-molecular substances in the measurement of drug concentrations in rat serum using EMIT. Our findings will contribute to the appropriate use of VCM based on evidence provided by clinical-oriented rat experiments requiring the measurement of serum VCM concentrations by EMIT.

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Cited by 26 publications

References 12 publications

Fosfomycin

Fosfomycin

Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity

Underestimation of rat serum vancomycin concentrations measured by an enzyme‐multiplied immunoassay technique and the strategy for its avoidance

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