Roland A. Ammann

Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course

Background: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. In contrast to other confirmed risk factors that predispose to a higher morbidity and mortality, the particular risk of a preexisting neuromuscular impairment (NMI) in hospitalized children with RSV infection has not been prospectively studied in a multicenter trial. Methods: The DMS RSV Paed database was designed for the prospective multicenter documentation and analysis of all clinically relevant aspects of the management of inpatients with RSV infection. Patients with clinically relevant NMI were identified according to the specific comments of the attending physicians and compared with those without NMI. Results: This study covers 6 consecutive seasons; the surveillance took place in 14 pediatric hospitals in Germany from 1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541 pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe course of the infection (multiple risk factors in some patients; prematurity in 30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually, the attributable mortality was significantly higher in the NMI group (5.5% vs. 0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was independently associated with pediatric intensive care unit (PICU) admission (OR, 4.94; 95% CI, 2.69–8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI, 1.28–10.22; P = 0.017). Conclusion: This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.

Predicting Adverse Events in Children With Fever and Chemotherapy-Induced Neutropenia: The Prospective Multicenter SPOG 2003 FN Study

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

Serum concentrations of lectin-pathway components in healthy neonates, children and adults: mannan-binding lectin (MBL), M-, L-, and H-ficolin, and MBL-associated serine protease-2 (MASP-2).

To cite this article: Sallenbach S, Thiel S, Aebi C, Otth M, Bigler S, Jensenius JC, Schlapbach LJ, Ammann RA. Serum concentrations of lectin‐pathway components in healthy neonates, childrens and adults: mannan‐binding lectin (MBL), M‐, L‐, and H‐ficolin, and MBL‐associated serine protease‐2 (MASP‐2).Pediatr Allergy Immunol 2011;: 424–430.

Real-Time Quantitative Broad-Range PCR Assay for Detection of the 16S rRNA Gene Followed by Sequencing for Species Identification

ABSTRACT Here we determined the analytical sensitivities of broad-range real-time PCR-based assays employing one of three different genomic DNA extraction protocols in combination with one of three different primer pairs targeting the 16S rRNA gene to detect a panel of 22 bacterial species. DNA extraction protocol III, using lysozyme, lysostaphin, and proteinase K, followed by PCR with the primer pair Bak11W/Bak2, giving amplicons of 796 bp in length, showed the best overall sensitivity, detecting DNA of 82% of the strains investigated at concentrations of ≤102 CFU in water per reaction. DNA extraction protocols I and II, using less enzyme treatment, combined with other primer pairs giving shorter amplicons of 466 bp and 342 or 346 bp, respectively, were slightly more sensitive for the detection of gram-negative but less sensitive for the detection of gram-positive bacteria. The obstacle of detecting background DNA in blood samples spiked with bacteria was circumvented by introducing a broad-range hybridization probe, and this preserved the minimal detection limits observed in samples devoid of blood. Finally, sequencing of the amplicons generated using the primer pair Bak11W/Bak2 allowed species identification of the detected bacterial DNA. Thus, broad-spectrum PCR targeting the 16S rRNA gene in the quantitative real-time format can achieve an analytical sensitivity of 1 to 10 CFU per reaction in water, avoid detection of background DNA with the introduction of a broad-range probe, and generate amplicons that allow species identification of the detected bacterial DNA by sequencing. These prerequisites are important for its application to blood-containing patient samples.

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland

BackgroundPediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic.MethodsProspective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods.Results7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis.ConclusionOur study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.

Predicting bacteremia in children with fever and chemotherapy-induced neutropenia.

Background. Fever and neutropenia are common clinical problems in pediatric oncology and frequently necessitate emergency hospitalization and immediate empiric broad spectrum antimicrobial therapy. Estimating the risk of bacteremia in fever and neutropenia is a challenge. The purpose of this study was to develop an algorithm predicting the risk of bacteremia and Gram-negative bacteremia in children and adolescents with fever and neutropenia, based on information accessible at presentation. Methods. We collected information available within 2 h of presentation of children with fever and neutropenia and, on outcome, from all pediatric cancer patients presenting with fever and neutropenia from 1993 through 2001 in a retrospective single center cohort study. After univariate analyses a multivariate decision tree was constructed, and its performance was evaluated by cross-validation. Results. Bacteremia was detected in 87 (24%) and Gram-negative bacteremia in 30 (8%) of 364 episodes of fever and neutropenia. At the predetermined sensitivity level, ≥95%, decision tree models reached cross-validated specificities of 37 and 43%, with negative predictive values of 96 and 99%, for bacteremia and Gram-negative bacteremia, respectively. Absence of a clinically or radiologically evident source of infection and previous episodes of fever and neutropenia were defined as two newly described factors associated with bacteremia. Conclusions. Based on this retrospective analysis, it appears that bacteremia can be predicted with clinically useful specificity at a high level of sensitivity, using clinical information available at presentation in pediatric cancer patients with fever and neutropenia.

Low incidence of respiratory syncytial virus hospitalisations in haemodynamically significant congenital heart disease

Background: Haemodynamically significant congenital heart disease (CHD) is a risk factor for severe respiratory syncytial virus (RSV) disease in young children. Population based data on the incidence of RSV hospitalisations in CHD patients are needed to estimate the potential usefulness of RSV immunoprophylaxis using palivizumab. Aims: (1) To obtain population based RSV hospitalisation rates in children <24 months of age with CHD. (2) To compare these rates with non-CHD patients and with previous studies. (3) To determine the number of patients needed to treat (NNT) with palivizumab to prevent one RSV hospitalisation. Methods: Six year, longitudinal, population based study at an institution, which is the sole provider of primary to tertiary in-patient care for a precisely defined paediatric population. Results: RSV hospitalisation rates (per 100 child-years) in CHD patients aged <6, <12, 12–24, and <24 months of age were 2.5 (95% CI 0.8 to 5.6), 2.0 (0.8 to 3.8), 0.5 (0.1 to 1.8), and 1.3 (0.6 to 2.3), respectively, and the relative risk (RR) in comparison with non-CHD patients was 1.4 (0.6 to 3.1), 1.6 (0.8 to 3.2), 2.7 (0.7 to 9.7), and 1.8 (1.0 to 3.3), respectively. NNT was between 80 (35 to 245) and 259 (72 to 2140) for various age groups. Conclusion: RSV hospitalisation rates in CHD patients were fourfold lower than reported from the USA. Based on these low rates and RR, unrestricted use of palivizumab does not appear to be justified in this study area.

Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients

Fever in neutropenia (FN) is a frequent complication in pediatric oncology. Deficiency of mannose‐binding lectin (MBL), an important component of innate immunity, is common due to genetic polymorphisms, but its impact on infections in oncologic patients is controversial. This study investigated whether MBL serum levels at cancer diagnosis are associated with the development of FN in pediatric cancer patients.

Obesity in long-term survivors of childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) with current cure rates reaching 80% emphasizes the necessity to determine treatment related long‐term effects. The present study examines the prevalence of and the risk factors for overweight and obesity in a cohort of ALL survivors treated and living in the French speaking part of Switzerland.

Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia : results of the prospective multicenter SPOG 2003 FN study

Study Aim: To develop a score predicting the risk of bacteremia in cancer patients with fever and neutropenia (FN), and to evaluate its performance. Methods: Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of bacteremia was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results: Bacteremia was reported in 67 (16%) of 423 FN episodes. In 34 episodes (8%), bacteremia became known only after reassessment after 8 to 24 hours of inpatient management. Predicting bacteremia at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The reassessment score predicting future bacteremia in 390 episodes without known bacteremia used the following 4 variables: hemoglobin ≥90 g/L at presentation (weight 3), platelet count <50 G/L (3), shaking chills (5), and other need for inpatient treatment or observation according to the treating physician (3). Applying a threshold ≥3, the score—simplified into a low-risk checklist—predicted bacteremia with 100% sensitivity, with 54 episodes (13%) classified as low-risk, and a specificity of 15%. Conclusions: This reassessment score, simplified into a low-risk checklist of 4 routinely accessible characteristics, identifies pediatric patients with FN at risk for bacteremia. It has the potential to contribute to the reduction of use of antimicrobials in, and to shorten the length of hospital stays of pediatric patients with cancer and FN.