Browsing by Author "Jhaveri, R"

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    Pediatric-specific antimicrobial susceptibility data and empiric antibiotic selection.
    (Pediatrics, 2012-09) Boggan, JC; Navar-Boggan, AM; Jhaveri, R
    OBJECTIVE: Duke University Health System (DUHS) generates annual antibiograms combining adult and pediatric data. We hypothesized significant susceptibility differences exist for pediatric isolates and that distributing these results would alter antibiotic choices. METHODS: Susceptibility rates for Escherichia coli isolates from patients aged ≤12 years between July 2009 and September 2010 were compared with the 2009 DUHS antibiogram. Pediatric attending and resident physicians answered case-based vignettes about children aged 3 months and 12 years with urinary tract infections. Each vignette contained 3 identical scenarios with no antibiogram, the 2009 DUHS antibiogram, and a pediatric-specific antibiogram provided. Effective antibiotics exhibited >80% in vitro susceptibility. Frequency of antibiotic selection was analyzed by using descriptive statistics. RESULTS: Three hundred seventy-five pediatric isolates were identified. Pediatric isolates were more resistant to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX) and less resistant to amoxicillin-clavulanate and ciprofloxacin (P < .0005 for all). Seventy-five resident and attending physicians completed surveys. In infant vignettes, physicians selected amoxicillin-clavulanate (P < .05) and nitrofurantoin (P < .01) more often and TMP-SMX (P < .01) less often with pediatric-specific data. Effective antibiotic choices increased from 68.6% to 82.2% (P = .06) to 92.5% (P < .01) across scenarios. In adolescent vignettes, providers reduced TMP-SMX use from 66.2% to 42.6% to 19.0% (P < .01 for both). Effective antibiotic choices increased from 32.4% to 57.4% to 79.4% (P < .01 and P = .01). CONCLUSIONS: Pediatric E. coli isolates differ significantly in antimicrobial susceptibility at our institution, particularly to frequently administered oral antibiotics. Knowledge of pediatric-specific data altered empirical antibiotic choices in case vignettes. Care of pediatric patients could be improved with use of a pediatric-specific antibiogram.
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    Viral factors induce Hedgehog pathway activation in humans with viral hepatitis, cirrhosis, and hepatocellular carcinoma.
    (Lab Invest, 2010-12) Pereira, Tde A; Witek, RP; Syn, WK; Choi, SS; Bradrick, S; Karaca, GF; Agboola, KM; Jung, Y; Omenetti, A; Moylan, CA; Yang, L; Fernandez-Zapico, ME; Jhaveri, R; Shah, VH; Pereira, FE; Diehl, AM
    Hedgehog (Hh) pathway activation promotes many processes that occur during fibrogenic liver repair. Whether the Hh pathway modulates the outcomes of virally mediated liver injury has never been examined. Gene-profiling studies of human hepatocellular carcinomas (HCCs) demonstrate Hh pathway activation in HCCs related to chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Because most HCCs develop in cirrhotic livers, we hypothesized that Hh pathway activation occurs during fibrogenic repair of liver damage due to chronic viral hepatitis, and that Hh-responsive cells mediate disease progression and hepatocarciongenesis in chronic viral hepatitis. Immunohistochemistry and qRT-PCR analysis were used to analyze Hh pathway activation and identify Hh-responsive cell types in liver biopsies from 45 patients with chronic HBV or HCV. Hh signaling was then manipulated in cultured liver cells to directly assess the impact of Hh activity in relevant cell types. We found increased hepatic expression of Hh ligands in all patients with chronic viral hepatitis, and demonstrated that infection with HCV stimulated cultured hepatocytes to produce Hh ligands. The major cell populations that expanded during cirrhosis and HCC (ie, liver myofibroblasts, activated endothelial cells, and progenitors expressing markers of tumor stem/initiating cells) were Hh responsive, and higher levels of Hh pathway activity associated with cirrhosis and HCC. Inhibiting pathway activity in Hh-responsive target cells reduced fibrogenesis, angiogenesis, and growth. In conclusion, HBV/HCV infection increases hepatocyte production of Hh ligands and expands the types of Hh-responsive cells that promote liver fibrosis and cancer.