Vancomycin nephrotoxicity

Pharmacokinetics of vancomycin Renal transport of vancomycin Epidemiology of vancomycin nephrotoxicity Risk factors for nephrotoxicity Therapeutic drug monitoring of vancomycin Prevention of vancomycin nephrotoxicity Alternative gram positive antibiotics References ... 

Despite the known renal disposition and nephrotoxicity of vancomycin, elucidation of its renal transport pathway remains incompletely defined. Early research by Sokol in rabbits demonstrated that vancomycin enters the proximal tubule cell across the basal lateral membrane via the organic acid transport system [186]. In addition, Sokol showed that vancomycin remains sequestered and concentrates inside the PTC. Vancomycin was found to enter the tubular lumen only by the much slower transport pathway of simple diffusion a secretory pathway was not found. This data would suggest that this renal transport pathway is a potential mechanism of vancomycin nephrotoxicity. However, there is not yet data that associates the PTC sequestration of vancomycin with nephrotoxicity or... 

Itoh F, Sato K, Harauchi T, Hirata M, Mizushima Y. Modification of vancomycin nephrotoxicity by other antibiotics in rats. Jpn J Antibiot 1995 48(3) 380-388. 

Other predicted interactions of tacrolimus include additive neuro- or nephrotoxicity with aciclovir, aminoglycosides, co-trimoxazole, ganciclovir, gyrase inhibitors, NSAIDs (see NSAIDs , (p.1081)) or vancomycin (nephrotoxicity has been seen with amphotericin B and tacrolimus). ... 

In a review of vancomycin nephrotoxicity, vancomycin was stUl considered first-line therapy for MRSA infections, but with particular caution if the baseline creatinine is raised, if vasopressors are required, or if concomitant nephrotoxins are being used [56 ]. 

An additive nephrotoxicity develops when pentamidine isethionate is administered with other nephrotoxic drugs (eg, aminoglycosides, vancomycin, or amphotericin B). An additive bone marrow depression occurs when the drug is administered with antineoplastic drugs or when the patient lias received radiation therapy recently. 

Vancomycin Infusion related toxicity (phlebitis, red man syndrome) Potential for additive renal toxicity if being coadministered with a nephrotoxic agent (e.g., aminoglycoside) monitor renal function (BUN/SCr) weekly in stable patients Consider vancomycin troughs to ensure therapeutic concentrations ... 

Antibiotics with activity against urease-producing bacteria, such as neomycin [42], paromomycin [44] or metronidazole [45], also reduce the production of intestinal ammonia and have proved to be of value. Vancomycin has also been used in patients with lactulose-resistant chronic encephalopathy [46]. The efficacy of neomycin is similar to that of lactulose [42]. However, a small percentage of this drug is absorbed from the gastrointestinal tract and may cause ototoxic and nephrotoxic effects, especially with continuous use over several months [47]. This drug should be used with particular caution by patients with renal insufficiency. The efficacy of metronidazole for... 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

Other inhibitors of cell wall synthesis. Bacitracin and vancomycin interfere with the transport of pepti-doglycans through the cytoplasmic membrane and are active only against gram-positive bacteria. Bacitracin is a polypeptide mixture, markedly nephrotoxic and used only topically. Vancomycin is a glycopeptide and the drug of choice for the (oral) treatment of bowel inflammations occurring as a complication of antibiotic therapy (pseudomembranous enterocolitis caused by Clostridium difficile), it is not absorbed. 

Drugs that may interact with vancomycin include aminoglycosides, anesthetics, neurotoxic/nephrotoxic agents, and nondepolarizing muscle relaxants. 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

WARNING Renal impair is the major tox foUow administration instructions Uses CMV retinitis w/ HIV Action Selective inhibition of viral DNA synth Dose Rx 5 mg/kg IV over 1 h once/wk for 2 wk w/ probenecid Maint 5 mg/kg IV once/2 wk w/ probenecid (2 g PO 3 h prior to cidofovir, then 1 g PO at 2 h 8 h after cidofovir) X in renal impair Caution [C, -] Contra Probenecid or sulfa allergy Disp Inj SE Renal tox, chills, fever, HA, NA /D, thrombocytopenia, neutropenia Interactions t Nephrotox W/ aminoglycosides, amphot icin B, foscar-net, IV pentamidine, NSAIDs, vancomycin t effects W/zidovudine EMS Monitor ECG for hypocalcemia (t QT int val) and hypokalemia (flattened T waves) OD May cause renal failure hydration may be effective in reducing drug levels/effects Cilostazol (Pletal) TAntiplatelet, Arterial Vasodilator/ Phosphodiesterase Inhibitor] Uses Reduce Sxs of intermittent claudication Action Phosphodiesterase in inhibitor t s cAMP in pits blood vessels, vasodilation inhibit pit aggregation Dose 100 mg PO bid, 1/2 h before or 2 h after breakfast dinner Caution [C, +/-] Contra CHE, hemostatic disorders. 

Foscarnet (Foscavir) [Antiviral] Uses CMV retinitis acyclovir-resistant hCTpes Infxns Action -1- Viral DNA polym ase RT Dose CMV retinitis Induction 60 mg/kg IV qSh or 100 mg/kg ql2h X 14—21 d Meant 90-120 mg/kg/dIV (Moo.-Fiti ) Acyclovir-resistant HSV Induction 40 mg/kg IV q8-12h x 14—21 d use central line -1- w/ renal impair Caution [C, —] T Sz potential w/ fluoroquinolones avoid n hrotoxic Rx (cyclosporine, aminoglycosides, ampho B, protease inhibitors) Contra CrCl <0.4 mL/min/kg Disp Inj SE Nephrotox, electrolyte abnormalities Interactions T Risks of Sz W/ quinolones t risks of n hrotox W/ aminoglycosides, amphotCTicin B, didanosine, pentamidine, vancomycin EMS Known to cause electrolyte disturbances (extremity numbness paresthesia indicates electrol5rte unbalance) monitor ECG OD May cause extremity numbing, and Szs hydrate w/ IV fluids... 

Vancomycin can cause red-man syndrome consisting of diffuse flushing, presumably mediated by histamine-release. This problem can be prevented by limiting the infusion rate. The most serious adverse reactions are ototoxicity and nephrotoxicity. The toxicity for both organ systems is potentiated by aminoglycosides. Vancomycin will cross the placenta barrier and has the potential to cause fetal ototoxicity. 

The severity of aminoglycoside nephrotoxicity is additive with that of vancomycin, polymixin, gallium, furosemide, enflurane, cisplatin, and cephalosporins. Aminoglycoside nephrotoxicity is synergistic with that of amphotericin B and cyclosporine. 

The major adverse effect associated with vancomycin therapy is ototoxicity, which may result in tinnitus, high-tone hearing loss, and deafness in extreme instances. More commonly, the intravenous infusion of vancomycin can result in chills, fever, and a maculopapular skin rash often involving the head and upper thorax (red man syndrome). Red man syndrome is associated with increased levels of serum histamine. Vancomycin is rarely nephrotoxic when used alone. Teicoplanin rarely causes red man syndrome or nephrotoxicity. 

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