Penelope A. Bryant

Sick and tired: Does sleep have a vital role in the immune system?

It is a common belief that we are more susceptible to infections when deprived of sleep. Consistent with this, there is increasing evidence that sleep deprivation has detrimental effects on the immune response, indicating that sleep should be considered a vital part of the immune system and that there is a reciprocal relationship between sleep and immunity. This relationship is important because, over recent decades, there has been a documented decrease in the mean duration and quality of sleep in the population. The concept that lack of sleep might be compromising immunity in the population has far-reaching public-health implications for both individuals and society.

Chips with everything: DNA microarrays in infectious diseases

Two developments are set to revolutionise research in and clinical management of infectious diseases. First, the completion of the human genome project together with the sequencing of many pathogen genomes, and second, the development of microarray technology. This review explains the principles underlying DNA microarrays and highlights the uses to which they are being put to investigate the molecular basis of infectious diseases. Pathogen studies enable identification of both known and novel organisms, understanding of genetic evolution, and investigation of determinants of pathogenicity. Host studies show the complexities of development and activation of both innate and adaptive immunity. Host-pathogen studies allow global analysis of gene expression during pathogenesis. Microarray technology will accelerate our understanding of the complex genetic processes underlying the interaction between microorganisms and the host, with consequent improvements in the diagnosis, treatment, and prevention of infectious diseases.

The Antibiotic Resistance and Prescribing in European Children Project: A Neonatal and Pediatric Antimicrobial Web-based Point Prevalence Survey in 73 Hospitals Worldwide

Background: The neonatal and pediatric antimicrobial point prevalence survey (PPS) of the Antibiotic Resistance and Prescribing in European Children project (http://www.arpecproject.eu/) aims to standardize a method for surveillance of antimicrobial use in children and neonates admitted to the hospital within Europe. This article describes the audit criteria used and reports overall country-specific proportions of antimicrobial use. An analytical review presents methodologies on antimicrobial use. Methods: A 1-day PPS on antimicrobial use in hospitalized children was organized in September 2011, using a previously validated and standardized method. The survey included all inpatient pediatric and neonatal beds and identified all children receiving an antimicrobial treatment on the day of survey. Mandatory data were age, gender, (birth) weight, underlying diagnosis, antimicrobial agent, dose and indication for treatment. Data were entered through a web-based system for data-entry and reporting, based on the WebPPS program developed for the European Surveillance of Antimicrobial Consumption project. Results: There were 2760 and 1565 pediatric versus 1154 and 589 neonatal inpatients reported among 50 European (n = 14 countries) and 23 non-European hospitals (n = 9 countries), respectively. Overall, antibiotic pediatric and neonatal use was significantly higher in non-European (43.8%; 95% confidence interval [CI]: 41.3–46.3% and 39.4%; 95% CI: 35.5–43.4%) compared with that in European hospitals (35.4; 95% CI: 33.6–37.2% and 21.8%; 95% CI: 19.4–24.2%). Proportions of antibiotic use were highest in hematology/oncology wards (61.3%; 95% CI: 56.2–66.4%) and pediatric intensive care units (55.8%; 95% CI: 50.3–61.3%). Conclusions: An Antibiotic Resistance and Prescribing in European Children standardized web-based method for a 1-day PPS was successfully developed and conducted in 73 hospitals worldwide. It offers a simple, feasible and sustainable way of data collection that can be used globally.

Cytomegalovirus transmission from breast milk in premature babies: does it matter?

There is evidence that CMV is commonly present in breast milk and is often transmitted to babies. CMV infection acquired postnatally can cause serious disease in very premature babies. Interventions to remove CMV from breast milk are possible but may damage other important constituents.

Prospective Study of a Real-Time PCR That Is Highly Sensitive, Specific, and Clinically Useful for Diagnosis of Meningococcal Disease in Children

ABSTRACT Due to the early administration of antibiotics, meningococcal disease is increasingly difficult to diagnose by culturing. Laboratory studies have shown PCR to be sensitive and specific, but there have been few clinical studies. The objectives of this study were to determine the diagnostic accuracy and clinical usefulness of meningococcal PCR through a prospective comparison of real-time PCR, nested PCR, and standard culturing of blood and cerebrospinal fluid (CSF). The setting was a tertiary-care pediatric hospital in Australia, and the participans were 118 children admitted with possible septicemia or meningitis. The main outcome measures—sensitivity, specificity, and positive and negative predictive values—were compared to a “gold standard ” fulfilling clinical and laboratory criteria. For 24 cases of meningococcal disease diagnosed by the gold standard, culturing of blood or CSF was positive for 15 (63%), nested PCR was positive for 21 (88%), and real-time PCR was positive for 23 (96%). The sensitivity, specificity, and positive and negative predictive values of real-time PCR (the most sensitive test) for all specimens were, respectively, 96% (95% confidence interval, 79 to 99%), 100% (95% confidence interval, 96 to100%), 100% (95% confidence interval, 85 to 100%), and 99% (95% confidence interval, 94 to 100%). Of 54 patients with suspected meningococcal disease at admission, 23 had positive PCR results. Only one PCR specimen was positive in a patient thought unlikely to have meningococcal disease at admission. Blood PCR remained positive for 33% of patients tested at up to 72 h. Real-time PCR has high positive and negative predictive values in this clinical setting, with better confirmation of cases than nested PCR. Targeting patients for PCR based on admission criteria appears to be practical, and the test may remain useful for several days after the start of antibiotic administration.

Indeterminate Interferon-γ Release Assay Results in Children

To the Editors: We read with interest the recent report by Haustein et al entitled “The likelihood of an indeterminate test result from a whole-blood interferonrelease assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status.” This report adds to recent publications that question the performance of current interferon(IFN) release assays (IGRA) for the diagnosis of tuberculosis (TB) in routine pediatric clinical practice. The retrospective study by Haustein et al in 237 children highlights the high proportion of indeterminate test results obtained with the QuantiFERON-TB (QFT) Gold In-Tube assay (35% of the study population). Notably, indeterminate test results were over-represented in children younger than 5 years of age, and those with immunodeficiencies or medical conditions associated with immunosuppression. Importantly, these groups represent children most at risk for disease progression after exposure to M. tuberculosis.

Antibiotic-resistant Gram-negative bacteremia in pediatric oncology patients--risk factors and outcomes.

Background: Infection with antibiotic-resistant (AR) Gram-negative (GN) bacteria is associated with increased morbidity and mortality. The aim of this study was to determine risk factors and outcomes associated with GN bacteremia with acquired resistance to antibiotics used in the empiric treatment of febrile neutropenia in pediatric oncology patients at our institution. Methods: All episodes of GN bacteremia in oncology patients at the Royal Children’s Hospital Melbourne, from 2003 to 2010 were retrospectively reviewed. Information regarding age, diagnosis, phase of treatment, inpatient status, previous AR GN infection, treatment with inotropes or ventilatory support, admission to intensive care unit, and hospital and intensive care unit length of stay were obtained from electronic records. Results: A total of 280 episodes of GN bacteremia in 210 patients were identified. Of these, 42 episodes in 35 patients were caused by an AR GN organism. Factors independently associated with AR GN bacteremia were high-intensity chemotherapy (odds ratio 3.7, 95% confidence interval: 1.2–11.4), hospital-acquired bacteremia (odds ratio 4.3, 95% confidence interval: 2.0–9.6) and isolation of AR GN bacteria from any site within the preceding 12 months (odds ratio 9.9, 95% confidence interval: 3.8–25.5). Episodes of AR GN bacteremia were associated with longer median hospital length of stay (23.5 days versus 14.0 days; P = 0.0007), longer median intensive care unit length of stay (3.8 days versus 1.6 days; P = 0.02) and a higher rate of invasive ventilation (15% versus 5.2%; P = 0.03). No significant difference in infection-related or all-cause mortality between the 2 groups was identified. Conclusions: In pediatric oncology patients, AR GN bacteremia is associated with an increased rate of adverse outcomes and is more likely in patients who have received high-intensity chemotherapy, have been in hospital beyond 48 hours and who have had previous AR GN infection or colonization.

Clinical and microbiologic features guiding treatment recommendations for brain abscesses in children.

Background: There are no guidelines for the management of brain abscesses in children, and there is a paucity of recent data describing clinical and microbiologic features. We aimed to identify factors affecting outcome to inform antibiotic recommendations. Methods: From 1999 to 2009, 118 children presented with brain abscesses to 4 neurosurgical centers in the United Kingdom. Clinical, microbiologic and treatment data were collected. Results: The commonest preceding infection was sinusitis, with 59% of all children receiving antibiotics before diagnosis. Nonspecific symptoms were common, with only 13% having the triad of fever, headache and focal neurological deficit. Time between symptom onset and diagnosis varied widely (median, 10 days; range, 0–44). Magnetic resonance imaging was more frequently diagnostic than computed tomography. The most frequent organisms were Streptococcus milleri (38%), except after penetrating head injury or neurosurgery, for which Staphylococcus aureus was most common. The commonest empiric antibiotics were ceftriaxone/cefotaxime and metronidazole, which offered effective antimicrobial therapy in up to 83% of cases. Metronidazole added benefit in a maximum of 7% of cases, with ceftriaxone/cefotaxime alone sufficient in at least 76% and in all cases with cyanotic congenital heart disease or meningitis. A carbapenem would have been effective in 90%. The case fatality rate was 6% (33% in the immunocompromised). Long-term neurological sequelae affected 35%. Age younger than 5 years and a Glasgow Coma Scale score ⩽8 were associated with poor outcome at 6 months. Conclusions: We recommend ceftriaxone/cefotaxime and metronidazole as empiric treatment, although metronidazole may be unnecessary in many cases, with antistaphylococcal cover in cases of head trauma. Meropenem potentially would be a better choice in the immunocompromised. A prospective study of intravenous and oral treatment guided by clinical improvement is required beause 1–2 weeks of intravenous antibiotics during a total of 6 weeks may be sufficient in children.

Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines

Few studies are available to inform duration of intravenous antibiotics for children and when it is safe and appropriate to switch to oral antibiotics. We have systematically reviewed antibiotic duration and timing of intravenous to oral switch for 36 paediatric infectious diseases and developed evidence-graded recommendations on the basis of the review, guidelines, and expert consensus. We searched databases and obtained information from references identified and relevant guidelines. All eligible studies were assessed for quality. 4090 articles were identified and 170 studies were included. Evidence relating antibiotic duration to outcomes in children for some infections was supported by meta-analyses or randomised controlled trials; in other infections data were from retrospective series only. Criteria for intravenous to oral switch commonly included defervescence and clinical improvement with or without improvement in laboratory markers. Evidence suggests that intravenous to oral switch can occur earlier than previously recommended for some infections. We have synthesised recommendations for antibiotic duration and intravenous to oral switch to support clinical decision making and prospective research.

Successful treatment of foscarnet-resistant herpes simplex stomatitis with intravenous cidofovir in a child.

A leukemic child developed recurrent herpes simplex virus lesions shortly after receiving a bone marrow transplant and while taking acyclovir. The isolate was resistant to acyclovir and foscarnet in vitro. The lesions responded to a course of cidofovir.