Pitfalls in dosing vancomycin.

BACKGROUND: Vancomycin is a frequently used antibiotic for the treatment of methicillin-resistant gram-positive bacteria. Newer guidelines suggest dosing vancomycin to achieve a trough concentration between 15 and 20 mg/L. Achieving this higher concentration requires greater doses of the antibiotic. Even when using a nomogram, these higher doses often result in excessively elevated trough levels and increase the risk for vancomycin-associated acute kidney injury. We undertook this quality improvement project to better understand the reasons contributing to a toxic vancomycin trough level. METHODS: Over a 9-month period, we examined all vancomycin trough concentrations greater than 25 mg/L to determine their cause. RESULTS: Fifty-four elevated levels were identified in 38 patients. In 47 instances, adequate data were available for analysis. We could classify the etiology of the excessive levels into 4 groups: (1) incorrect timing of the blood collection, (2) improper dosing, (3) changing renal function and (4) abnormal pharmacokinetics/pharmacodynamics. CONCLUSIONS: Educational programs could correct the first 3 problems. However, only more frequent therapeutic drug monitoring or use of another, less toxic, antibiotic would remedy the last one.

Successful conversion to belatacept after thrombotic microangiopathy in kidney transplant patients.

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation. TMA may occur de novo or as recurrent disease post-transplant. De novo disease is usually associated with immunosuppressive drugs or can be seen as a part of endothelial damage that accompanies antibody-mediated rejection. Treatment for de novo TMA is limited to plasma exchange and change in immunosuppression. We report two cases of de novo TMA post-transplant that were successfully treated by converting to belatacept for maintenance immunosuppression.

Brain tumors in individuals with familial adenomatous polyposis: a cancer registry experience and pooled case report analysis.

BACKGROUND: Most individuals with Familial Adenomatous Polyposis (FAP) harbor mutations in the APC gene on chromosome 5q21. They are at an increased risk of brain tumors, including cerebellar medulloblastoma, when compared with the general population (Brain Tumor Polyposis-BTP Type 2). Genotype-phenotype correlations between APC gene mutations and central nervous system (CNS) tumors have, thus far not been successful. Herein the authors have pooled their registry experience in BTP type 2 with the published reports. METHODS: The authors analyzed their established hereditary CRC Registry for brain tumors in FAP pedigrees (56 families, 213 individuals), pooled their patients with BTP and known APC mutations with those reported thus far elsewhere, and compared the resulting mutation distribution of FAP-BTP with the mutation distribution for APC mutations in the US. RESULTS: Twenty-eight patients from 24 families were accrued, the most common brain tumor in BTP was medulloblastoma (60%) predominantly in females (12:5) under the age of 20 (mean age 14.7 SD 9.2). Other histologic subtypes included astrocytoma and ependymoma. Analysis of the pooled APC mutation data by Chi-square test of association shows an odds ratio of 3.7 (P < .005) for all brain tumor subtypes and 13.1 (P < .001) for medulloblastoma in patients harboring segment 2 APC mutation (codons 679-1224) compared to nonsegment 2 mutation. CONCLUSIONS: In patients with FAP and identifiable APC gene mutation, CNS tumors, especially medulloblastoma which developed in most cases during childhood, are more common in females with FAP and APC gene mutation in codons 686-1217. Further studies are necessary to determine if this observation and the natural history of medulloblastoma in children justifies novel, aggressive, targeted screening of at-risk individuals.