Prospective Assessment of Nephrotoxicity with Concomitant Aminoglycoside and Vancomycin Therapy

ABSTRACTThere is conflicting evidence about the nephrotoxic potential of vancomycin in combination with aminoglycosides. In a prospective fashion, we have attempted to address the issue of nephrotoxicity associated with aminoglycosides and vancomycin, while studying the risk of pharmacokinetic factors potentially associated with nephrotoxicity.At a university-affiliated 600-bed teaching hospital, 492 consecutive patients receiving aminoglycosides and/or vancomycin were monitored. The patients were divided into three groups: A) patients receiving an aminoglycoside, B) patients receiving vancomycin, and C) patients receiving aminoglycoside concurrently with vancomycin. In Groups A, B and C, nephrotoxicity, defined as a 50% reduction in creatinine clearance, developed in 4.5%, 0% and 25% of patients, respectively. Using univariate analysis, it was found that the variables predisposing patients in Groups A and C to toxicity included: underlying diseases (malignant vs. non-malignant disease); prolonged duration of therapy; elevated trough serum aminoglycoside concentration and the use of concomitant nephrotoxic medications. Multivariate analysis revealed that the most significant predisposing factor was the number of potentially nephrotoxic concomitant drugs administered with the aminoglycoside and vancomycin. The results of this study suggest that there is increased nephrotoxicity associated with concurrent administration of aminoglycosides and vancomycin particularly when two or more other potential nephrotoxic medications are given.RÉSUMÉLes preuves concernant la néphrotoxicité de la vancomycine en combinaison avec les aminoglycosides sont contradictoires. Dans le cadre d'une étude prospective, nous avons essayé de résoudre ce problème tout en étudiant le risque des facteurs pharmacocinétiques qui peuvent être associés à la néphrotoxicité.Dans un hôpital de 6QO lits affiliés à une université, on a surveillé 492 patients consécutifs qui ont reçu des aminoglycosides et (ou) de la vancomycine. Les patients ont été répartis en trois groupes: A) patients recevant un aminoglycoside; B) patients recevant la vancomycine et C) patients recevant les deux substances. On a ensuite déterminé la néphrotoxicité pour les groupes A, B et C, ce terme étant défini par une réduction de 5O% de la clairance de la créatinine. Les résultats étaient respectivement de 4,5%, 0% et 25%. Au moyen d'une analyse à une seule variable, on a constaté que les variables qui prédisposaient les patients des groupes A et C à la néphrotoxicité comprennent les maladies sous-jacentes (affection maligne ou non), un traitement prolongé, une concentration sérique élevée d'aminoglycosides associée au creux et l'administration d'autres médicaments néphrotoxiques. L'analyse multivariée révèle que le facteur prédisposant le plus significatif est le nombre de médicaments potentiellement néphrotoxiques administrés avec les aminoglycosides et la vancomycine. Les résultats de l'étude suggèrent qu'on assiste à une hausse de la néphrotoxicité en raison de l'administration concurrente d'aminoglycosides et de vancomycie, surtout lorsqu'on administre déjà deux ou plusieurs autres médicaments éventuellement néphrotoxiques

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN