Mortality and morbidity of nosocomial respiratory syncytial virus (RSV) infection in ventilated children--a ten year perspective.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the most common pathogens involved in nosocomial infection in children. The aim of the study was to determine the impact of nosocomial RSV infection on mortality and pediatric intensive care unit (PICU) morbidity of ventilated children. METHODS: This is a prospective observational cohort study of all children ventilated with RSV infection in a tertiary-referral PICU over a 10-year period. Determinants of the relationship of nosocomial (PICU-acquired and hospital ward-acquired) RSV infection to mortality and PICU morbidity were adjusted for by performing multiple regression analysis. RESULTS: Of 525 RSV-positive children ventilated on PICU during the ten-year study period, 38 (7.2%) acquired their RSV infection following PICU admission and 38 (7.2%) had acquired RSV in hospital. Ten (26%) children that acquired RSV on PICU died (RR 6.4, 95%CI 3.2-12.9) and 11 (29%) with hospital ward-acquired infection died (RR 9.8, 95%CI 5.1-18.9), compared to 18 (4%) with community-acquired RSV infection. Nosocomial RSV infection was significantly and independently associated with death which was more strongly predicted by immunodeficiency and congenital heart disease (P<0.01). Nosocomial RSV infection was the strongest predictor for morbidity as reflected in duration of ventilation and length of stay on PICU (P<0.01). CONCLUSION: Nosocomial RSV infection was independently associated with increased mortality and was the strongest predictor of duration of ventilation and length of stay in children on PICU. Decreasing nosocomial RSV infection would reduce deaths in ventilated children.

Right ventricular function in children with severe respiratory syncytial virus (RSV) bronchiolitis.

BACKGROUND: Previous studies have demonstrated the development of myocardial damage and hepatitis in children with severe respiratory syncytial virus (RSV) infection. The aim of this study was to assess right ventricular function in children with severe RSV disease and to investigate an association with disease severity, myocardial damage, and hepatitis. METHODS: This was a prospective observational study performed at a 20-bed regional multidisciplinary tertiary pediatric intensive care unit (PICU) in a university-affiliated children's hospital. Pulse wave Doppler echocardiographic assessments with a calculation of the right ventricular function (Tei index), left ventricular ejection fraction and diameters, cardiac troponin T levels, transaminase and C-reactive protein levels were performed at admission on consecutive children who were ventilated and diagnosed with a severe RSV infection and without congenital heart disease. RESULTS: Thirty-four ventilated children with confirmed RSV bronchiolitis were enrolled. The median age was 1.4 months (range 0.4-11.7), and the median length of ventilation was 5 days (range 2-10). Seven (20%) infants had an elevated right ventricular Tei index indicating reduced right ventricular function. Left ventricular function as well as C-reactive protein and transaminase levels were not different between patients with and without an elevated right ventricular Tei index. Cardiac troponin T was elevated in 14 patients (41%): 3/7 with an elevated and 11/27 with a normal Tei index (P=1). Ventilation and oxygenation indices and the duration of mechanical ventilation were not different between the two groups. CONCLUSION: A raised right ventricular Tei index, consistent with reduced right ventricular function, was observed in severe RSV disease, but the degree of dysfunction was not related to the level of biochemical myocardial or hepatic damage or level of respiratory support.

Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection.

BACKGROUND: 600,000 deaths worldwide are estimated to be directly or indirectly attributable to respiratory syncytial virus (RSV). OBJECTIVES: To determine: (1) the mortality rate; and (2) risk factors for death in children with severe RSV infection. SETTING: 20-bed, regional, multidisciplinary, tertiary, paediatric intensive care unit (PICU) in a university-affiliated children's hospital. METHODS: Cohort study of all children with severe RSV infection covering eight consecutive RSV seasons (1999-2007), using PICU admission as a marker of severity. RESULTS: Of the 406 RSV-positive patients that were admitted to PICU: 98.5% required mechanical ventilation; 35 children died--median age 5.1 months (interquartile range (IQR) 2.4-13.6), length of PICU stay 16 days (IQR 8-31) and 371 survived--median age 2.5 months (IQR 1.2-9), length of PICU stay 5 days (IQR 4-9). The overall PICU RSV mortality was 8.6% with a standardised mortality ratio of 0.76. During the study period 2009 RSV-positive patients were admitted to the children's hospital, giving a hospital RSV mortality rate of 1.7%. Of the deaths, 18 were directly RSV related (RSV bronchiolitis-related mortality PICU 4.4% and hospital 0.9%) as the patients were still RSV positive when they died and 17 children died from non-pneumonitis causes after becoming RSV negative. All of the RSV deaths had pre-existing medical conditions--chromosomal abnormalities 29%, cardiac lesions 27%, neuromuscular 15%, chronic lung disease 12%, large airway abnormality 9%, and immunodeficiency 9%. Nineteen children (56%) had pre-existing disease in two or more organ systems (relative risk (RR) 4.38). Predisposing risk factors for death were pre-existing disease (RR 2.36), cardiac anomaly (RR 2.98) and nosocomial/hospital-acquired RSV infection (RR 2.89). There is an interaction effect between pre-existing disease, nosocomial/hospital-acquired RSV infection and mortality (p<0.001). CONCLUSIONS: Pre-existing disease/comorbidity, in particular multiple pre-existing diseases and cardiac anomaly, is associated with a significantly higher risk of death from severe RSV infection. Nosocomial/hospital-acquired RSV infection is an additional major risk factor for death in children with severe RSV infection.

High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTI). Viral LRTI is a risk factor for bacterial superinfection, having an escalating incidence with increasing severity of respiratory illness. A study was undertaken to determine the incidence of pulmonary bacterial co-infection in infants and children with severe RSV bronchiolitis, using paediatric intensive care unit (PICU) admission as a surrogate marker of severity, and to study the impact of the co-infection on morbidity and mortality. METHODS: A prospective microbiological analysis was made of lower airways secretions on all RSV positive bronchiolitis patients on admission to the PICU during three consecutive RSV seasons. RESULTS: One hundred and sixty five children (median age 1.6 months, IQR 0.5-4.6) admitted to the PICU with RSV bronchiolitis were enrolled in the study. Seventy (42.4%) had lower airway secretions positive for bacteria: 36 (21.8%) were co-infected and 34 (20.6%) had low bacterial growth/possible co-infection. All were mechanically ventilated (median 5.0 days, IQR 3.0-7.3). Those with bacterial co-infection required ventilatory support for longer than those with only RSV (p<0.01). White cell count, neutrophil count, and C-reactive protein did not differentiate between the groups. Seventy four children (45%) received antibiotics prior to intubation. Sex, co-morbidity, origin, prior antibiotics, time on preceding antibiotics, admission oxygen, and ventilation index were not predictive of positive bacterial cultures. There were 12 deaths (6.6%), five of which were related to RSV. CONCLUSIONS: Up to 40% of children with severe RSV bronchiolitis requiring admission to the PICU were infected with bacteria in their lower airways and were at increased risk for bacterial pneumonia.

Use of surveillance cultures and enteral vancomycin to control methicillin-resistant Staphylococcus aureus in a paediatric intensive care unit.

This study assessed the effects of throat and gut surveillance, combined with enteral vancomycin, on gut overgrowth, transmission of methicillin-resistant Staphylococcus aureus (MRSA), infections and mortality in patients admitted to a paediatric intensive care unit (PICU). A 4-year prospective observational study was undertaken with 1241 children who required ventilation for >or=4 days. Patients identified as MRSA carriers following surveillance cultures of throat and rectum received enteral vancomycin. Twenty-nine (2.4%) children carried MRSA, 19 on admission and nine during treatment in the PICU; one patient was not able to be evaluated. Overgrowth was present in 22 (75%) of the carriers. Ten (0.8%) children developed 21 MRSA infections (15 exogenous infections in eight children at a median of 8 days (IQR 3-10.5); five primary endogenous infections at a median of 3 days (IQR 1-25) in three children when they were in overgrowth status; one child developed both types of infection). Enteral vancomycin reduced gut overgrowth significantly, completely preventing secondary endogenous infections. Transmission occurred on nine occasions over a period of 4 years. Four patients died, two (5.9%) with MRSA infection, giving a mortality (11.8%) similar to the study population (9.8%). No emergence of vancomycin-resistant enterococci or S. aureus with intermediate susceptibility to vancomycin was detected. A policy based on throat and gut surveillance, combined with enteral vancomycin, for critically-ill children who were MRSA carriers was found to be effective and safe, and challenges the recommended guidelines of nasal swabbing followed by topical mupirocin.

Cardiac Troponin T levels and myocardial involvement in children with severe respiratory syncytial virus lung disease.

AIMS: To determine the prevalence of myocardial damage in severe respiratory syncytial virus (RSV) disease as evident from elevated cardiac Troponin T (cTnT) levels. To assess the nature of the myocardial involvement as manifested in electro- and echocardiographic abnormalities. To compare severity of disease with and without myocardial involvement as evident from duration of ventilation, inotrope requirements and death. METHODS: This was a prospective observational cohort study of children with RSV infection admitted to the paediatric intensive care unit at the Royal Liverpool Children's Hospital during the winter season 2002/2003. cTnT concentrations were measured using a third generation monoclonal sandwich immunoassay (Roche Diagnostics). RESULTS: 34 children were included in our study. 12 (35%) had elevated cTnT levels. The levels measured after admission had a median [interquartile range (IQR)] of 50 pg/ml (37.5-67.5). There was no significant difference (p > 0.05) between patients with and without elevated cTnT levels with regards to gender, gestational age at birth, history of neonatal intensive care, presence of congenital heart disease, chronic lung disease, inotrope requirements, duration of ventilation, death, fractional shortening on echocardiogram or arrhythmias. Children with elevated cTnT levels were significantly younger [median (IQR): 1.4 months (0.8-2.0)] than children without [median (IQR): 4.0 months (1.7-6.6)] (p = 0.04). The systolic blood pressure on admission was lower in children with increased cTnT compared to those with undetectable cTnT (p = 0.01). CONCLUSIONS: Myocardial involvement is common in infants with severe RSV lung disease without congenital heart disease. cTnT level elevation was associated with hypotension.

RSV outbreak in a paediatric intensive care unit.

The Royal Liverpool Children's Hospital-Alder Hey paediatric intensive care unit (PICU) usually has a low rate of nosocomial respiratory syncytial virus (RSV) infection. We report and analyse a major outbreak of nosocomial (acquired) RSV infection on the PICU during a RSV season. All children admitted to the PICU were studied during the six-month winter period 1 October 2002 to 31 March 2002. Nasopharyngeal aspirates were tested using an in vitro enzyme-linked immunoassay (ELISA) membrane test for RSV antigen. PICU-acquired RSV infection was considered to have occurred when a child admitted to the PICU was RSV negative, or from whom no samples were taken as they did not exhibit signs of bronchiolitis, but was RSV positive five or more days after the admission. Fifty-four patients tested RSV positive using the ELISA on the PICU. All the patients were ventilated. Thirty-nine children were RSV positive using the ELISA on admission to the PICU ('imported' cases) and 15 became RSV positive whilst on the PICU ('acquired' cases). The source of the acquired RSV infection accounting for the first peak/outbreak in nosocomial cases were RSV-positive children in isolation cubicles. Acquired cases of RSV infection subsided with reinforcement of traditional methods of barrier precautions. The source of the second peak in nosocomial cases were persistent shedders of RSV. Seventy-three percent (11/15) of the acquired RSV cases had one or more of the following co-morbidities: congenital heart disease, chronic lung disease, airways abnormalities or immunosuppression. Droplet precautions (strict handwashing, use of gloves if handling body fluids, single-use aprons, education) rather than the physical barrier of the cubicle itself played a more important role in curtailing nosocomial spread. Persistent shedders of RSV are an important potential source of nosocomial RSV infection within a PICU. Patients with co-morbidities are at increased risk of nosocomial RSV infection.

Mortality in severe meningococcal disease.

AIM: To evaluate mortality of critically ill children admitted with meningococcal disease. METHODS: Prospective study of all children admitted to a regional paediatric intensive care unit (PICU) between January 1995 and March 1998 with meningococcal disease. Outcome measures were actual overall mortality, predicted mortality (by PRISM), and standardised mortality ratio. RESULTS: A total of 123 children were admitted with meningococcal disease. There was an overall PICU mortality of 11 children (8.9%). The total mortality predicted by PRISM was 24.9. The standardised mortality ratio (SMR) was 0.44. Results were compared with those from four previously published meningococcal PICU studies (USA, Australia, UK, Netherlands) in which PRISM scores were calculated. The overall PICU mortality and SMR were lower than those in the previously published studies. CONCLUSION: Compared with older studies and calibrating for disease severity, this study found a decrease in the mortality of critically ill children with meningococcal disease.

Immunization strategies to control a community-wide hepatitis A epidemic.

One fifth of 527 cases of hepatitis A occurred in self-identified injection drug users during a community-wide epidemic in Spokane County (Washington) in 1997-8. We hypothesized that an immunization campaign targeted at illicit drug users could control the epidemic. Starting in May 1998, hepatitis A vaccine was provided to individuals in jails and other sites frequented by illicit drug users. Volunteers at vaccination sites were surveyed about risk. Serial convenience samples of jail inmates who denied previous vaccination were anonymously tested for hepatitis A virus (HAV) immunoglobulin G (IgG). From May to December 1998, 2765 high-risk individuals were vaccinated against hepatitis A. The proportion of HAV IgG seropositive inmates increased from 30% to more than 50%. Our findings suggest that vaccination along with naturally occurring infection increased the rate of hepatitis A immunity among illicit drug users during the final months of the epidemic. This supports the hypothesis that targeted immunization of high risk groups may shorten the natural history of a community-wide epidemic.

Evaluation of the 5-French saline paediatric gastric tonometer.

OBJECTIVE: To evaluate the paediatric 5-French (Fr) saline-filled gastric tonometer. DESIGN: (a) In vitro comparison of saline bath reference pCO2 with tonometric pCO2 measured by normal saline-filled and phosphate-buffered saline-filled 5-Fr tonometers, and by a recirculating gas tonometer. ( b) In vivo comparison of gastric intramucosal pCO2i, measured by normal saline-filled 5-Fr tonometer (NST) and simultaneously by recirculating gas tonometer (RGT) in ten paediatric intensive care patients. (c) In vivo comparison of pCO2i measured simultaneously by 2 NST 5-Fr tonometers, before and after enteral feeding, in ten paediatric intensive care patients. MEASUREMENTS AND MAIN RESULTS: (a) Twenty consecutive measurements of pCO2 were made at constant reference pCO2 of 19, 38, 56, and 75 mmHg (2.5, 5.0, 7.5, and 10.0 kPa), respectively. The NST tonometer underestimated reference pCO2 by mean bias (limits of agreement) of 58% (20%), and the phosphate-buffered saline-filled tonometer by 6% (26%). The RGT showed mean bias 5.7% with narrow limits of agreement (1.5%). (b) In 50 paired (NST vs. RGT) in vivo measurements over pCO2i range 23-73 mmHg (3.0-9.7 kPa), the NST underestimated RGT pCO2i by a mean bias of 10 mmHg (1.3 kPa), with limits of agreement +/-10 mmHg (1.5 kPa). This resulted in NST consistently overestimating pHi and underestimating pCO2 gap (both P < 0.001). (c) One hundred simultaneous paired NST measurements were assessed (50 without, and 50 with enteral feeding). The mean biases (limits of agreement) were identical in the fasted and fed states 0.4+/-6 mmHg, with no difference between the fed and fasting states (P = 0.7). CONCLUSIONS: There are inherent problems in the methodology of saline tonometry, which adversely affect the accuracy and reliability of the 5-Fr paediatric gastric tonometer in comparison to recirculating gas tonometry.