Voriconazole Therapeutic Drug Monitoring is Necessary for Children with Invasive Fungal Infection / 소아감염

PURPOSE: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. METHODS: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end. RESULTS: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1%) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P=0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P=0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P=0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. CONCLUSION: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.

Clinical and Epidemiological Characteristics of Human Metapneumovirus Infections, in Comparison with Respiratory Syncytial Virus A and B / 소아감염

PURPOSE: To identify the clinical and epidemiological characteristics of human metapneumovirus infections (hMPV) in children compared to respiratory syncytial virus A (RSV A) and B (RSV B). METHOD: A retrospective review of medical records was performed in 36 patients with hMPV infection, 106 with RSV A infection, and 51 with RSV B infection, from September 2007 to July 2012. RESULTS: The peak incidence of hMPV infection was observed in May, whereas for RSV infections in November and December. hMPV infection occurred in older patients compared to RSV A and B infection (29.9+/-32.5 months vs. 13.6+/-15.4 months, P<0.001; 29.9+/-32.5 months vs. 12.1+/-13.5 months, P<0.001, respectively). hMPV infection was more often associated with fever compared to RSV A (97.2% vs. 67.9%, P<0.001), while wheezing was less frequent compared to RSV A and B infection (16.7% vs. 47.2%, P=0.001; 16.7% vs. 37.3%, P=0.037, respectively). hMPV infection was more often diagnosed as pneumonia compared to RSV A infection (72.2% vs. 50.0%, P=0.047) while bronchiolitis was less frequent than in RSV A (5.6% vs. 34.9%, P=0.001) or RSV B infection (5.6% vs. 29.4%, P=0.006). In addition, intravenous antibiotic was more often prescribed for patients with hMPV infection than those with RSV A and B (69.4% vs. 39.6%, P=0.002; 69.4% vs. 43.1, P=0.015, respectively). CONCLUSION: This study identified characteristics of hMPV infection compared to RSV A and B infection. Seasonality in spring, higher age group, and higher proportion of pneumonia in hMPV infections may be a useful guide for management of respiratory viral infections in children.

Outcome of Antimicrobial Therapy of Pediatric Urinary Tract Infections Caused by Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae / 감염과화학요법

BACKGROUND: The purpose of this study was to compare the outcome of carbapenem versus non-carbapenem antimicrobial therapy for pediatric urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. MATERIALS AND METHODS: From 2006 to 2011, 42 episodes of UTI caused by ESBL-producing Enterobacteriaceae were diagnosed at Seoul National University Children's Hospital. Patients were grouped according to the antimicrobials they received into a carbapenem group and a non-carbapenem group. Medical records were retrospectively reviewed to assess treatment outcome, time to defervescence after initiation of treatment, and relapse rate. RESULTS: There were 36 children with 42 episodes of UTI caused by ESBL-producing Enterobacteriaceae. Twenty-seven cases (64%) had an underlying urologic disease, 28 (67%) cases were caused by Escherichia coli, and 14 (33%) cases were caused by Klebsiella pneumoniae. Four (10%) cases were treated with carbapenem, 23 cases (55%) were treated with non-carbapenem, and 15 (36%) cases were treated by switching from a carbapenem to a non-carbapenem and vice versa. There was no treatment failure at the time of antimicrobial discontinuation. Between the carbapenem and the non-carbapenem treatment groups, there were no significant differences in bacterial etiology (P = 0.59), time to defervescence after the initiation of antimicrobials (P = 0.28), and relapse rate (P = 0.50). In vitro susceptibility to non-carbapenem antimicrobials did not affect the time to defervescence after the initiation of antimicrobial treatment, and the relapse rate in the non-carbapenem group. CONCLUSIONS: This study found no significant difference in the treatment outcome between pediatric patients treated with carbapenem and those treated with non-carbapenem antimicrobials for UTI caused by ESBL-producing Enterobacteriaceae. Therefore, the initially administered non-carbapenem can be maintained in UTI patients showing clinical improvement.