X-Linked Agammaglobulinemia: Infection Frequency and Infection-Related Mortality in the USIDNET Registry.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. A potential benefit of earlier diagnosis and treatment initiation on morbidity and mortality in XLA is incompletely understood. In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. Among the 231 XLA patients enrolled in the Registry, respiratory infections (N = 203, 88%) were the most commonly reported. Among those deceased (N = 20) where cause of death was known (N = 17), mortality was attributed to infection in most (N = 12, 71%). Chronic lung disease, often a consequence of repeated lower respiratory tract infection (LRTI), was also a frequent complication associated with mortality (N = 9, 53%). Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.5-3.3] vs. median 3.0 [IQR 1.0-5.0], p = 0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.5-5.0] vs. median 2.7 [IQR 1.6-6.0], p = 0.04). Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.4-2.4] vs. median 2.8 [IQR 1.0-5.4], p = 0.0006). For every year increase in age at start of therapy, the odds of experiencing a LRTI was 1.216 (OR 1.216, 95% CI 1.048-1.411, p = 0.01). Given the expected finding of reduced LRTIs and mortality among those with earlier age at diagnosis, our study findings support inclusion of XLA in newborn screening programs.

Improving case finding of invasive aspergillosis in children using string searches.

Surveillance for invasive Aspergillus (IA) in children is complex. We performed a retrospective study (2004-2013) using string searches of relevant terms within histopathology and radiology reports in efforts to improve detection of IA. Overall, 22 children met IA criteria, of whom 5 (23%) were only identified by string searches.

Utility of surveillance cultures for antimicrobial resistant organisms in infants transferred to the neonatal intensive care unit.

BACKGROUND: Infections with antibiotic resistant organisms (AROs) are an important source of morbidity and mortality among infants hospitalized in the neonatal intensive care unit (NICU). To identify potential reservoirs of AROs in the NICU, active surveillance strategies have been adopted by many NICUs to detect infants colonized with AROs. However, the yield, risks, benefits and costs of different strategies have not been fully evaluated. METHODS: We conducted a retrospective study in 2 level III NICUs from 2004 to 2010 to investigate the yield of surveillance cultures obtained from infants transferred to the NICU from other hospitals. Cultures were processed for methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and antibiotic-resistant gram-negative rods. Risk factors, selected outcomes and laboratory costs associated with ARO colonization were assessed. RESULTS: Among 1751 infants studied, the rate of colonization for methicillin-resistant S. aureus, vancomycin-resistant enterococci and antibiotic-resistant gram-negative rods was 3%, 1.7% and 1%, respectively. Age at transfer was the strongest predictor of ARO colonization; infants transferred at ≥ 7 days of life had 5.8 increased odds of ARO colonization compared with infants <7 days of age. Transferred infants who were colonized had similar rates of mortality, ARO infection and duration of hospitalization compared with those who were not colonized. The laboratory cost of surveillance cultures during the study period was $58,425. CONCLUSIONS: The rate of colonization with AROs at transfer was low particularly in infants <7 days old. Future studies should examine the safety of targeted surveillance strategies focused on older infants.

A new metric of antibiotic class resistance in gram-negative bacilli isolated from hospitalized children.

OBJECTIVE: The purpose of this study was to describe patterns of infection or colonization with antibiotic-resistant gram-negative bacilli (GNB) in hospitalized children utilizing an electronic health record. SETTING: Tertiary care facility. PARTICIPANTS: Pediatric patients 18 years of age or younger hospitalized from January 1, 2006, to December 31, 2008. METHODS: Children were identified who had (1) at least 1 positive culture for a multidrug-resistant (MDR) GNB, defined as a GNB with resistance to 3 or more antibiotic classes; or (2) additive drug resistance, defined as isolation of more than 1 GNB that collectively as a group demonstrated resistance to 3 or more antibiotic classes over the study period. Differences in clinical characteristics between the 2 groups were ascertained, including history of admissions and transfers, comorbid conditions, receipt of procedures, and antibiotic exposure. RESULTS: Of 56,235 pediatric patients, 46 children were infected or colonized with an MDR GNB, of which 16 were resistant to 3 classes and 30 were resistant to 4 classes. Another 39 patients had positive cultures for GNB that exhibited additive drug resistance. Patients with additive drug resistance were more likely than patients with MDR GNB to have had previous admissions to a long-term facility (8 vs 2; P = .04) and had more mean admissions (7 vs 3; P < .01) and more mean antibiotic-days (P < .01 to P = .02). Six patients with additive drug resistance later had a positive culture with an MDR GNB. CONCLUSIONS: An electronic health record can be used to track antibiotic class resistance in GNB isolated from hospitalized children over multiple cultures and hospitalizations.