Kentigern Thorburn

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.

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

Summary Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries. Funding Bill & Melinda Gates Foundation.

Antibiotic-resistant bacteria and infection in children with cerebral palsy requiring mechanical ventilation.

Introduction: Severe and chronic illness can alter the bacterial flora carried in the oropharynx and gut. There are little data on the bacterial flora of children with chronic neurologic impairment. Objectives: To assess carriage of abnormal bacterial flora, antibiotic-resistant bacteria, infection, and mortality in children with cerebral palsy (CP) admitted for pediatric intensive care. Design: Prospective observational single center cohort study. Setting: Twenty-bed regional pediatric intensive care unit (PICU) in a university-affiliated tertiary referral children’s hospital. Patients: All children with an established diagnosis of CP admitted to PICU and ventilated for four or more days during a 6-yr period. Measurements: Surveillance samples of throat and rectum were taken at admission to PICU and twice a week thereafter. Diagnostic samples were obtained on clinical indication. Main Results: Fifty-three children with a total of 77 admissions were included. Most (90%) of the children with CP had moderate to severe functional limitations. Eighty-nine percent of the children with CP (47/53) carried abnormal bacterial flora/potential pathogens, most frequently Pseudomonas and Klebsiella species. Forty-seven percent (22/47) had antibiotic-resistant bacteria. Thirty-five children (66%) developed 86 infections during their PICU admission. Lower airways and blood were the two most commonly infected sites—Pseudomonas aeruginosa and coagulase-negative Staphylococci, the predominant infecting microorganisms. Sixty-five percent (56/86) of infections were primary endogenous infections, 21% (18/86) exogenous, and 9% (8/86) secondary endogenous. Carriage of abnormal bacterial flora, antibiotic-resistant bacteria, and infection rate was significantly higher than that of children of comparative age without CP ventilated for four or more days on PICU. Nine (17%) of the children with CP died in PICU and 4 of the deaths were infection related. Conclusions: In children with moderate to severe chronic neurologic impairment admitted to PICU, there is a high rate of carriage of abnormal bacteria/potential pathogens, antibiotic-resistant bacteria, and infection.

Pulmonary bacterial co-infection in children ventilated for severe respiratory syncytial virus bronchiolitis is common

Sir, In a retrospective study on concurrent bacterial infection in infants ventilated for respiratory syncytial virus (RSV), bronchiolitis Kneyber et al. concluded that the “improvement in the diagnosis of a pulmonary concurrent bacterial infection is warranted to reduce the overuse of antimicrobial drugs” in this patient group [1]. This issue was highlighted by Andrews et al. in “Intensive Care Medicine’s Year in Review” 2005 article [2] as “Only a minority had evidence of bacterial infection”. Our view differs and we question this opinion/interpretation. A prospective study of 165 consecutive children in whom an admission broncho-alveolar lavage (BAL) sample was obtained found that up to 40% of patients admitted with severe RSV bronchiolitis were infected with bacteria in their lower airways [3]. This is in keeping with Kneyber et al. who found that 33% of children (9 of 24) in whom admission endotracheal aspirates were performed had a positive bacterial culture [1]. Duttweiler et al. retrospectively studied 127 infants admitted to intensive care for RSV bronchiolitis and found that 44% of those ventilated and endotracheally sampled had “concomitant bacteria pneumonia” [4]. Likewise, Randolph et al. retrospectively examined 165 previously healthy infants admitted to the intensive care unit with laboratoryconfirmed RSV infection and found that up to 38% of the intubated infants had “probable” or “possible” bacterial pneumonia [5]. Pulmonary bacterial co-infection is common in children ventilated for severe RSV bronchiolitis. The statement, “Only a minority had evidence of bacterial infection” [2] underscores the incidence in this patient group. Kneyber et al. [1] and Thorburn et al. [3] acknowledged that their studies may even have underestimated the actual number of concurrent bacterial infections. All the patients in both these studies [1, 3] received concomitant antibiotics, which limits any interpretation on the influence of antibiotics on outcome. This also limits comment on the “overuse of antimicrobials” [1, 2]. The only way to prove a definite impact of antimicrobials in this study population would be to carry out a randomized control trial. In the interim, one could argue that a bacterial co-infection rate of up to 40% in ventilated RSV patients is sufficient to warrant prophylactic/empirical antibiotics on admission to the paediatric intensive care unit (PICU). These critically ill children run a serious risk of developing bacterial pneumonia [6]. While awaiting further studies, we think that empirical antibiotic therapy appears to be justified in children with severe RSV bronchiolitis, pending the results of definitive cultures. “Improvement in the diagnosis of a pulmonary concurrent bacterial infection” can be achieved by obtaining lower airways secretions on admission to PICU in all patients. In the absence of finding bacteria in the lower airways, antibiotics can subsequently be stopped. References

Aluminum accumulation in critically ill children on sucralfate therapy.

Background Sucralfate, used in stress ulcer prophylaxis, contains aluminum, which can be absorbed from the gut. Objective To determine whether toxic serum aluminum levels can develop after short-term sucralfate therapy in critically ill children. Design Retrospective clinical study. Setting Pediatric intensive care unit of a pediatric university hospital. Patients Nineteen patients receiving mechanical ventilatory support (median age, 5 yrs [range, 0.25–16 yrs]; median weight, 17 kg [range, 3.5–60 kg]). Interventions All patients received sucralfate suspension nasogastrically. Measurements and Results Serum aluminum concentrations were measured after a short period on sucralfate therapy (median time, 7 days [range, 3–14 days]). There was no correlation between total sucralfate dose received (p = .35) or dose of sucralfate per unit of body weight (p = .55) and serum aluminum. Nine patients received peritoneal dialysis. Serum aluminum levels were higher in the nine patients who received peritoneal dialysis (median aluminum concentration, 2.86 &mgr;mol/L [range, 0.19–12.3 &mgr;mol/L]) than the ten patients not dialyzed (median aluminum concentration, 0.55 &mgr;mol/L [range, 0.18–0.94 &mgr;mol/L]) (p = .001). The peak serum creatinine levels were higher in the dialyzed patients (median creatinine level, 500 &mgr;mol/L [range, 163–910 &mgr;mol/L]) than those not dialyzed (median creatinine level, 98 &mgr;mol/L [range, 36–415 &mgr;mol/L]) (p = .006). There was a trend toward correlation between peak serum creatinine and serum aluminum (p = .06). Conclusion Aluminum accumulation occurs in children with acute renal failure on sucralfate, especially those receiving dialysis. If sucralfate is used in children in renal failure, serum aluminum concentrations should be monitored regularly.

Effects of feeding on gastric tonometric measurements in critically ill children

ObjectiveTo determine the effect of gastric feeding on the measurement of gastric intramucosal Pco2 (Pico2) and its derived gastric intramucosal Pco2-arterial Pco2 difference (Pico2-Paco2 difference) and gastric intramucosal pH (pHi) in a group of critically ill children using recirculating gas tonometry. DesignProspective clinical pilot study. SettingSixteen bed pediatric intensive care unit. PatientsTen mechanically ventilated and hemodynamically stable children (median age, 20.1 months [interquartile range (IQR), 9.7–47.6 months] and median weight, 10.2 kg [IQR, 10–16.5 kg]). InterventionsA 7-French recirculating gas tonometer was placed in the stomach via the orogastric route. MeasurementsIn each patient, baseline fasted/unfed Pico2, Pico2-Paco2 difference, and pHi were determined hourly over a 5-hr period. Gastric feeding was then reestablished (3 mL/kg/hr) within a median time of 3 hrs and a further 5 hourly measurements were determined. Concurrent arterial blood gas and lactate measurements were taken. Blood pressure and heart rate was monitored throughout. Main ResultsHemodynamic parameters remained stable throughout the study period. When compared with the unfed/fasting state, Pico2 measurements and Pico2-Paco2 difference were consistently lower and pHi values higher than when the patients were fed (two-way analysis of variance for repeated measures: all p < .001 between groups). Measurements did not vary over time. ConclusionsIn our patient group, gastric feeding decreased the Pico2 and Pico2-Paco2 difference and increased pHi compared with the unfed state. These findings are in contrast to those found in adult studies.

Prevention of Bloodstream Infections

Bloodstream infections occur from various sources. Certain microorganisms thrive in different parts of the body or colonize exogenous prosthetic pieces of equipment. Hence the source of a bloodstream infection can almost be predicted according to the microorganism detected. Coagulase-negative staphylococci (CNS) are in general associated with catheter-related bloodstream infections, whereas aerobic Gram-negative bacilli (AGNB) cause bloodstream infections following lymph drainage from the respiratory tract, intraabdominal space and urinary tract. Most bloodstream infections of unknown origin are gut-derived, e.g., fungemia following translocation of Candida albicans present as overgrowth in the gut. Table 6.1 shows that the contaminated catheter and the lower airways are leading causes of bloodstream infections [1–4].

Gut Mucosal Protection in the Critically Ill Patient: Toward an Integrated Clinical Strategy

Over the past 30 years, clinical strategies for the control of SURB have shifted from interventions to neutralize intragastric acid (antacids) and to inhibit acid synthesis (H2 receptor antagonists) towards maneuvers that aim to maintain and improve microcirculatory perfusion (aggressive circulatory support, including vasodilators). The use of anti-inflammatory drugs for the prevention of microcirculatory sludging is important to maintain adequate microcirculation. Prevention of infection is achieved by selective decontamination of the digestive tract. This therapy also suppresses H. pylori gastritis, which plays a role in the pathogenesis of SURB. The implementation of this strategy guarantees a consistently low incidence of <1% of SURB in patients requiring a minimum of 2 days of mechanical ventilation.