Nephrotoxicity due to Combination Antibiotic Therapy with Vancomycin and Aminoglycosides in Septic Critically Ill Patients

Abstract

The aim of this prospective observational study was to evaluate the incidence of nephrotoxicity due to combination therapy with vancomycin and aminoglycosides in septic critically ill patients admitted to the intensive care unit. Methods: Thirty consecutive critically ill patients were treated with vancomycin concurrent with aminoglycosides for sepsis. Inclusion criteria were: the need for mechanical ventilation and the presence of severe infection due to bacteria susceptible to vancomycin and aminoglycosides. Exclusion criteria were: age <18 years, impaired renal function (24-hour creatinine clearance <90 ml/min) or previous adverse reaction to either drug. Serum creatinine and urea concentrations, creatinine clearance, 24-hour urinary excretion of proteins, β₂-microglobulin and enzymes were measured immediately before starting therapy and at different times thereafter. Results: Eleven of the 30 patients had a transient and modest increase in serum urea, 15 patients presented with urinary excretion of β₂-microglobulin and tubular enzymes, and 14 patients had urinary proteins.In the only patient with severe acute renal failure (serum creatinine 8.2 mg/dl), the clinical course was complicated by prolonged hypotension. Conclusion: Concurrent administration of vancomycin and aminoglycosides to critically ill septic patients with normal renal function at baseline induced mainly slight and transient toxic tubular effects. The only clinically significant nephrotoxic event occurred in a patient with septic shock.

Vancomycin‐Associated Nephrotoxicity in Adult Medicine Patients: Incidence, Outcomes, and Risk Factors

“…These elevated trough values (>15 mg/l) have been previously associated with increased nephrotoxicity . Patient weight exceeding 101.4 kg, daily vancomycin dose over 4 g, use of concomitant nephrotoxic agents, severity of illness, duration of therapy more than 7 days, and history of kidney disease have also been identified as risk factors for VAN …”

Vancomycin Nephrotoxicity

“…Traditional definitions of AKI have been less stringent, with a common definition being that of an increase in SCr of ≥0.5 mg/dL or 50% above baseline or a decrease in creatinine clearance (CrCl) of ≥50% from baseline without an alternative cause. 17 The majority of studies published have used the more traditional definitions of nephrotoxicity, 7,13,18 –26 although a few employed the RIFLE criteria. 15,17,19 Prediction of VAN has been demonstrated with the use of the 2007 Acute Kidney Injury Network (AKIN) criteria, a slightly modified version of the RIFLE criteria (Table 1).…”

“…Aminoglycosides are among the most widely studied nephrotoxic drugs given concurrently with vancomycin, 7,23,25 but the results are conflicting. Other agents commonly associated with nephrotoxicity include amphotericin B, tacrolimus, diuretics, vasopressors, and contrast media.…”

“…33 A small (n = 30) prospective study also failed to provide evidence for additive nephrotoxic effects of vancomycin and aminoglycosides in critically ill patients with normal baseline renal function. 23…”

Pediatric acute kidney injury: A syndrome under paradigm shift

“…[64] Concomitant use of vancomycin and aminoglycosides and other drugs such as cyclosporine, amphotericin B, cephalosporins, and loop diuretics along with their prolonged treatment (>21 days) enhanced the nephrotoxic potential of vancomycin. [65] Frequent courses of aminoglycoside treatment and persistently high trough or peak levels expose kidneys to high concentrations of the drug, resulting in accumulation of aminoglycosides in the renal cortex and predisposing the patient to AKI. General preventive measures for drug-induced nephrotoxicity include, addressing all the modifiable risk factors.…”