Systematic Review of Antimicrobial Lock Solutions for Prevention of Bacteremia in Pediatric Patients With Intestinal Failure.

OBJECTIVES: The goal of this systematic review was to determine whether antimicrobial lock (AML) solutions prevent catheter-related bloodstream infections (CRBSI) in children with intestinal failure (IF). METHODS: Electronic databases were searched: Ovid MEDLINE (1946-), Ovid Embase (1974-), Wiley Cochrane Library (inception-), and Web of Science Core Collection via Clarivate Analytics (1900-). Randomized and nonrandomized trials, case or cohort studies that studied any AML solution, and used comparator groups were included if they studied children with IF. A meta-analysis compared the rates of CRBSI with AML solutions versus controls, and a Boucher analysis was used to indirectly compare AML solutions. RESULTS: Twenty-eight studies met eligibility criteria (1 open label and 27 observational studies). Quality was good (N = 13), fair (N = 9), and poor (N = 6). All but 4 studied ethanol and taurolidine. Of 15 ethanol studies, 11 reported a decrease and 3 reported a trend toward a decreased incidence of CRBSI compared to controls; 1 reported no difference. Of 9 taurolidine studies, 7 reported a decrease and 2 a trend toward decreased CRBSI rates. There was a decrease in CRBSI with ethanol versus control ( P = 0.008) and with taurolidine-citrate versus control ( P < 0.0005). Using Bucher indirect comparison of the pooled estimates from ethanol versus control to taurolidine versus control, the estimated difference was -0.99 (-4.125, 2.27; P = 0.55). CONCLUSIONS: There were no randomized trials and over half of the 28 included studies were fair or poor quality. All but 1 reported at least a trend toward reduction in CRBSI. AML solutions appear to prevent CRBSI.

Cerebrospinal fluid shunt infections in children.

Cerebrospinal fluid (CSF) shunts are commonly used for the long-term management of hydrocephalus in children. Shunt infection remains a common complication, occurring in about 5%-15% of CSF shunts. This narrative review summarises key evidence from recent literature on the epidemiology, pathogenesis, clinical presentation, diagnosis, management, outcomes and prevention of CSF shunt infections in children. The majority of shunt infections occur due to contamination at the time of surgery, with coagulase-negative staphylococci and Staphylococcus aureus being the most common infecting organisms. Clinical presentations of shunt infection can be varied and difficult to recognise. CSF cultures are the primary test used for diagnosis. Other CSF and blood parameters may aid in diagnosis but lack sensitivity and specificity. Core aspects of management of shunt infections include systemic antimicrobial therapy and surgical removal of the shunt. However, many specific treatment recommendations are limited by a lack of robust evidence from large studies or controlled trials. Shunt infections may result in long hospital stays, worsening hydrocephalus, neurological sequelae and other complications, as well as death. Therefore, reducing the incidence of infection and optimising management are high priorities. Antibiotic prophylaxis at the time of shunt placement, improved surgical protocols and antibiotic-impregnated shunts are key strategies to prevent shunt infections. Nevertheless, further work is needed to identify additional strategies to prevent complications and improve outcomes.

CMV-specific T-cells and CD27-CD28-CD4+ T-cells for assignment of cytomegalovirus (CMV) status in adults awaiting organ transplant.

BACKGROUND/OBJECTIVES: Determination of Cytomegalovirus (CMV) status in solid organ transplant (SOT) candidates is essential to stratify risk of post-transplant CMV disease. Passive transfusion-acquired antibodies can make serologic determination of CMV status unreliable. We evaluated 3 assays, not affected by passive antibodies (PA), in assignment of CMV status: quantification of CMV-specific CD4 + T-cells (CMV-TC) and exhausted CD27-CD28- CD4 + T-cells, and detection of CMV DNA with Nucleic Acid Amplification Testing (NAAT). STUDY DESIGN: We enrolled 50 adults awaiting SOT and 50 immunocompetent age-matched controls, and collected a throat swab, urine, saliva and blood sample on each. Using flow cytometry CD4 + T-cells were phenotypically analyzed for expression of CD27 and CD28 and CMV-specific CD4 + T-cells were identified by CD69 expression and intracellular IFN-γ quantification after stimulation with CMV-antigen lysate. CMV NAAT was performed on all specimens using real-time PCR. CMV serology (CMV IgG) was determined by enzyme immunoassay. Subjects were considered to have potential PA if they received blood products within 2 months of collection. RESULTS: The CMV-TC assay discriminated between CMV-seropositive and seronegative SOT candidates without PA well (sensitivity 79%, specificity 93%) while the CD27-CD28-CD4 + T-cell assay had good sensitivity (86%) but specificity of 74%. Detection of CMV DNA was uncommon in CMV-seropositive SOT candidates (2/21). CONCLUSIONS: Given its high specificity, the CMV-TC assay is valuable in confirming true-positive CMV status in seropositive SOT candidates with PA, while use of CD27-CD28-CD4 + T-cell analysis is limited by moderate specificity. Detection of CMV DNA is of limited value in assignment of CMV status in adults.

Assigning Cytomegalovirus Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T Cells, and CD27-CD28-CD4+ T Cells.

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pretransplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays unaffected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: (1) CMV nucleic acid amplification testing (NAAT), (2) quantification of CMV-specific CD4+ T cells, and (3) quantification of CD27-CD28-CD4+ T cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status. Detection of CMV-specific CD4+ T cells was sensitive and specific in children >18 months but was less sensitive in children <12 months. CD27-CD28-CD4+ T cells are not likely useful in CMV risk stratification in children.

Practices regarding human Papillomavirus counseling and vaccination in head and neck cancer: a Canadian physician questionnaire.

BACKGROUND: Human papillomavirus (HPV) has recently been implicated as a causative agent in a rapidly growing number of oropharyngeal cancers. Emerging literature supports the hypothesis that HPV vaccination may protect against HPV-related head and neck cancer (HNC) in addition to HPV-related cervical and anogenital disease. While the association between HPV infection and cervical cancer is widely understood, its relation to HNC is less well known. The purpose of this study was to better understand HPV counseling practices for infection and vaccination in relation to HNC of primary care physicians (PCPs), Obstetricians/Gynecologists (OBGYNs), and Otolaryngology - Head and Neck Surgeons (OHNSs) in Canada. METHODS: A Canada-wide electronic questionnaire regarding counseling practices on HPV infection, transmission, and vaccination was designed and distributed to PCPs, OBGYNs, and OHNSs across Canada through electronic and paper-based methods. Basic Descriptive statistics were used to analyze responses. RESULTS: In total, 337 physicians responded (239 family physicians, 51 OHNSs, 30 OBGYNs, and 17 pediatricians). Three out of four PCPs reported routine counseling of their patients regarding HPV infection, transmission, and vaccination. Among this group, 68% reported "never" or "rarely" counseling patients that HPV can cause HNC. The most commonly reported reason that PCPs cited for not counseling was a lack of knowledge. The majority of OHNSs (81%) and OBGYNs (97%) counseled patients regarding HPV infection, transmission, and vaccination. However, very few OHNSs (10%) regularly counseled patients with HPV-related HNC about HPV-related anogenital cancer. Similarly, very few OBGYNs (18%) regularly counseled patients with HPV related cervical/anogenital cancer about HPV related HNC. CONCLUSIONS: The rate of counseling on HPV infection, transmission, and vaccination in relation to HNC among PCPs is low. The most common reason is a lack of knowledge. Specialists rarely counsel patients with confirmed HPV-related cancer about other HPV-related malignancies. More research is needed on the relationship between different HPV-related cancers in order to better inform counseling practices.

The genetic diversity of Epstein-Barr virus in the setting of transplantation relative to non-transplant settings: A feasibility study.

This study examines EBV strains from transplant patients and patients with IM by sequencing major EBV genes. We also used NGS to detect EBV DNA within total genomic DNA, and to evaluate its genetic variation. Sanger sequencing of major EBV genes was used to compare SNVs from samples taken from transplant patients vs. patients with IM. We sequenced EBV DNA from a healthy EBV-seropositive individual on a HiSeq 2000 instrument. Data were mapped to the EBV reference genomes (AG876 and B95-8). The number of EBNA2 SNVs was higher than for EBNA1 and the other genes sequenced within comparable reference coordinates. For EBNA2, there was a median of 15 SNV among transplant samples compared with 10 among IM samples (p = 0.036). EBNA1 showed little variation between samples. For NGS, we identified 640 and 892 variants at an unadjusted p value of 5 × 10(-8) for AG876 and B95-8 genomes, respectively. We used complementary sequence strategies to examine EBV genetic diversity and its application to transplantation. The results provide the framework for further characterization of EBV strains and related outcomes after organ transplantation.

Respiratory syncytial virus infections in pediatric transplant recipients: A Canadian Paediatric Surveillance Program study.

The incidence and spectrum of severity of RSV infections in SOT or HSCT recipients is not known. From September 2010 through August 2013, pediatricians were surveyed monthly by the CPSP for SOT or HSCT recipients with RSV infection within two yr post-transplant. There were 24 completed case report forms that fit the inclusion criteria (10 HSCT and 14 SOT recipients). Six of 24 cases (25%) remained outpatients, and 11 (46%) were managed on an inpatient ward, while seven (29%) required intensive care of which five required mechanical ventilation and two died of RSV infection. Ten of 23 cases (43%) were nosocomial with these data not recorded for one case. Many transplant recipients recover uneventfully from RSV infection in the first two yr post-transplant. However, severe disease and death also occur. Larger studies are required to establish risk factors for poor outcomes. Prevention of nosocomial RSV should be a priority in transplant recipients.

Urinary tract infections in infants and children: Diagnosis and management.

Recent studies have resulted in major changes in the management of urinary tract infections (UTIs) in children. The present statement focuses on the diagnosis and management of infants and children >2 months of age with an acute UTI and no known underlying urinary tract pathology or risk factors for a neurogenic bladder. UTI should be ruled out in preverbal children with unexplained fever and in older children with symptoms suggestive of UTI (dysuria, urinary frequency, hematuria, abdominal pain, back pain or new daytime incontinence). A midstream urine sample should be collected for urinalysis and culture in toilet-trained children; others should have urine collected by catheter or by suprapubic aspirate. UTI is unlikely if the urinalysis is completely normal. A bagged urine sample may be used for urinalysis but should not be used for urine culture. Antibiotic treatment for seven to 10 days is recommended for febrile UTI. Oral antibiotics may be offered as initial treatment when the child is not seriously ill and is likely to receive and tolerate every dose. Children <2 years of age should be investigated after their first febrile UTI with a renal/bladder ultrasound to identify any significant renal abnormalities. A voiding cystourethrogram is not required for children with a first UTI unless the renal/bladder ultrasound reveals findings suggestive of vesicoureteral reflux, selected renal anomalies or obstructive uropathy.

De récentes études ont suscité des changements majeurs dans la prise en charge des infections urinaires chez les enfants. Le présent document de principes porte sur le diagnostic et la prise en charge des nourrissons et des enfants de plus de deux mois atteints d'une infection urinaire aiguë, sans affection sous-jacente connue des voies urinaires ou facteurs de risque de vessie neurogène. Il convient d'écarter la possibilité d'infection urinaire chez les enfants atteints d'une fièvre inexpliquée qui ne savent pas encore parler et chez les enfants plus âgés ayant des symptômes évocateurs de ce type d'infection (dysurie, urgences mictionnelles, hématurie, douleur abdominale, douleur lombaire ou nouvelle incontinence diurne). Chez les enfants qui sont propres, il faut faire un prélèvement d'urine à mi-jet pour analyse et culture. Chez les autres, le prélèvement par cathéter ou par ponction sus-pubienne est préconisé. L'infection urinaire est peu probable si l'analyse d'urine est complètement normale. La collecte d'urine dans un sac peut être utilisée pour analyse, mais pas pour culture. Une antibiothérapie de sept à dix jours est recommandée en cas d'infection urinaire fébrile. Si l'enfant n'est pas gravement malade et qu'il est susceptible de recevoir et de tolérer chaque dose, on peut lui donner un traitement initial d'antibiotiques par voie orale. Il faudrait soumettre les enfants de moins de deux ans à une échographie des reins et de la vessie après leur première infection urinaire fébrile, afin de déceler toute anomalie rénale d'importance. Lors d'une première infection urinaire, la cysto-urétrographie mictionnelle (CUGM) est inutile, à moins que l'échographie des reins et de la vessie ne donne des résultats évocateurs d'un reflux vésico-urétéral, de certaines anomalies rénales ou d'une uropathie obstructive.

Randomized trial of success of pediatric anesthesiologists learning to use two video laryngoscopes.

OBJECTIVES: The primary purpose of this study was to establish the ability of pediatric anesthesiologists to learn to use two video laryngoscopes - the GlideScope(®) system (GS) and the Karl Storz Direct Coupled Interface, DCI(®), (KS). BACKGROUND: The number of intubation attempts required to attain proficiency with a video laryngoscope is not known. METHODS: Baseline intubation times, using direct laryngoscopy, were determined for each anesthesiologist on 20 children. Anesthesiologists were then randomized to perform 20 intubations with the GS or KS before crossing over to the other device. RESULTS: There were 193 successful intubations and eight failed intubations (4.0%) with the GS. Median time-to-intubation with the GS for each anesthesiologist ranged from 24.5 to 32.8 s. There were 193 successful intubations and three failed intubations (1.5%) with the KS (P > 0.05 vs failed attempts with GS). Median time-to-intubation with the KS ranged from 21.9 to 31.1 s. For both the GS and KS, five of eight anesthesiologists met the study definition of 'Success'. There was no correlation between median time-to-intubation with all laryngoscopes combined and years since completion of training. The distribution of Cormack and Lehane scores was almost identical for the GS and KS; there were fewer grade III or IV scores than with direct laryngoscopy (P = 0.03; Fischer's exact test). Mean and median times on intubation no. 16-20 were shorter for the KS than for the GS. CONCLUSIONS: Although only 65% of anesthesiologists attained the stringent study definition of 'Success', all rapidly leaned to use both video laryngoscopes.

The natural history of hepatitis C virus infection acquired during childhood.

BACKGROUND: The outcome of patients with hepatitis C virus (HCV) infection acquired during childhood in the absence of antiviral therapy is not clear. AIMS: The purpose of this study was to review the outcome of untreated HCV acquired in childhood. Only population-based studies were included, as referred cases would be predicted to have more severe disease. METHODS: A systematic review of the literature was completed up to October 2010 to identify studies where a population was screened for HCV infection that was presumably acquired during childhood. Demographical and clinical data were collected on infected patients who had not been treated with an antiviral. Primary outcome was development of a severe adverse outcome (cirrhosis, hepatoma, need for a liver transplant or liver-related death). RESULTS: There were 25 studies reporting a total of 733 infected patients. Liver biopsy results were provided for 180 patients (25%), revealing cirrhosis in eight (1.0% of the total and 4.0% of those who had a biopsy). None of the other patients developed a severe adverse outcome. As a result of the small number of patients with a severe adverse outcome, risk factors for HCV progression could not be identified. CONCLUSION: Although HCV can lead to liver transplantation and death during childhood, the vast majority of patients with disease acquired during childhood have slowly progressive disease. There is no clear indication for antiviral therapy in the majority of children with HCV infection.

Fever of unknown origin in children: a systematic review.

BACKGROUND: there are no previous systematic reviews of published pediatric case series describing the etiology of fever of unknown origin (FUO). The purpose of collecting these data is to determine the etiologies for children with FUO in both developing and developed countries. METHODS: the database Ovid Medline R (1950 to August 2009 week 4) and Ovid Embase (1980 to 2010 week 2) were used to conduct the search. Studies in any language were included if they provided the diagnosis in a series of 10 or more children with FUO. The diagnosis of each child at the time of publication of the study was recorded. RESULTS: there were 18 studies that met the inclusion criteria, describing 1638 children. The diagnosis at the time of publication was malignancy for 93 children (6%), collagen vascular disease for 150 (9%), miscellaneous non-infectious conditions for 179 (11%), infection for 832 (51%), and no diagnosis for 384 (23%). There were 491 bacterial infections (59% of all infections) with common diagnoses being brucellosis, tuberculosis, and typhoid fever in developing countries, osteomyelitis, tuberculosis, and Bartonellosis in developed countries, and urinary tract infections in both. For children with no diagnosis after investigations, most had fever that ultimately resolved with no sequelae. CONCLUSIONS: about half of FUOs in published case series are ultimately shown to be due to infections with collagen vascular disease and malignancy also being common diagnoses. However, there is such a wide variety of possibilities that investigations should primarily be driven by the clinical story.

Empyema associated with community-acquired pneumonia: a Pediatric Investigator's Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: Although the incidence of serious morbidity with childhood pneumonia has decreased over time, empyema as a complication of community-acquired pneumonia continues to be an important clinical problem. We reviewed the epidemiology and clinical management of empyema at 8 pediatric hospitals in a period before the widespread implementation of universal infant heptavalent pneumococcal vaccine programs in Canada. METHODS: Health records for children<18 years admitted from 1/1/00-31/12/03 were searched for ICD-9 code 510 or ICD-10 code J869 (Empyema). Empyema was defined as at least one of: thoracentesis with microbial growth from pleural fluid, or no pleural fluid growth but compatible chemistry or cell count, or radiologist diagnosis, or diagnosis at surgery. Patients with empyemas secondary to chest trauma, thoracic surgery or esophageal rupture were excluded. Data was retrieved using a standard form with a data dictionary. RESULTS: 251 children met inclusion criteria; 51.4% were male. Most children were previously healthy and those

Use of throat swab or saliva specimens for detection of respiratory viruses in children.

BACKGROUND: Nasopharyngeal (NP) specimens are commonly used for the detection of respiratory viruses, but throat and saliva specimens are easier to obtain. The objective of this study was to compare the viral yield of direct fluorescent antigen detection of NP specimens and nucleic acid amplification tests (NAT) of direct fluorescent antigen-negative NP specimens with the viral yield of NAT of throat swab and saliva specimens. METHODS: NP, throat swab, and saliva specimens were obtained from children and adolescents aged

Chronic norovirus and adenovirus infection in a solid organ transplant recipient.

A 10-month-old boy developed chronic diarrhea 2 months after a combined liver, pancreas, and small bowel transplant. Norovirus and adenovirus were detected in multiple stool specimens during a 114-day period. Enteric viral infectious should be considered in solid organ transplant recipients with chronic diarrhea.

Pediatric infective endocarditis: Has Staphylococcus aureus overtaken viridans group streptococci as the predominant etiological agent?

BACKGROUND: Viridans group streptococci (VGS) have traditionally been the most common etiological agents of infective endocarditis (IE). Advances in cardiovascular surgery and the increasing use of long-term central venous catheters may have altered the epidemiology of pediatric IE. METHODS: A chart review of children younger than 17 years of age with IE was completed at the Stollery Children's Hospital (Edmonton, Alberta) between 1985 and 2004. The literature was reviewed to look for changes over time in the most common etiological agents of pediatric IE. RESULTS: There were 31 cases of definite IE and nine cases of possible IE at the Stollery Children's Hospital, 19 of which were nosocomial. Thirty cases (75%) had congenital heart disease. The etiological agents were Staphylocccus aureus (n=16), VGS (n=5), coagulase-negative staphylococci (n=3), enterococcus (n=3), other streptococci (n=8), Enterobacter cloacae (n=1) and Stenotrophomonas maltophilia (n=1), while three cases were culture negative. Two deaths were due to S aureus IE. Review of the literature identified an increasing number of case series in which S aureus was the predominant etiological agent, but VGS still predominated in some recent series. CONCLUSION: Congenital heart disease remains the primary risk factor for pediatric IE. Prospective population-based studies are required to determine whether S aureus has become the predominant pathogen.

Pediatric malignancies presenting as a possible infectious disease.

BACKGROUND: The clinical, laboratory, and radiological features of malignancy can overlap with those of infection. The purpose of this study was to determine the findings in children who were initially thought to have an infectious disease but ultimately proved to have a malignancy. METHODS: The database of patients diagnosed with a malignancy in the Northern Alberta Children's Cancer Program (NACCP) January 1, 1993 to December 31, 2003 was merged with the database of inpatients referred to the infectious diseases service at the Stollery Children's Hospital and charts were reviewed on all patients referred to the infectious diseases consult service prior to the diagnosis of malignancy. RESULTS: An infectious diseases consultation for diagnosis was requested in 21 of 561 patients prior to the confirmation of malignancy, and 3 of these 21 patients had both infection and malignancy (leukemia (N = 13), lymphoma (N = 3), rhabdomyosarcoma (N = 1), Langerhan's cell histiocytosis (N = 1), fibrous histicocytosis (N = 1), ependymoma (N = 1), and neuroblastoma (N = 1). The most common reason for infectious diseases consultation was suspected muskuloskeletal infection (N = 9). A palpable or radiographically enlarged spleen was noted in 11 patients (52%). All but 2 patients had abnormal hematologic parameters while an elevated lactate dehydrogenase (LDH) occurred in 10 patients (48%). Delay of diagnosis because of investigation or therapy for an infectious disease occurred in only 2 patients. CONCLUSION: It is not common for treatment of pediatric malignancies to be delayed because infection is thought to be the primary diagnosis. However, pediatric infectious diseases physicians should consider malignancy in the differential diagnosis when they see patients with fever and bone pain, unexplained splenomegaly or abnormal complete blood cell counts. Other clues may include hepatomegaly or elevated LDH.

Acute herpes simplex laryngotracheitis: Report of two pediatric cases and review of the literature.

Herpes simplex virus (HSV) is a rare cause of laryngotracheitis (LT) with only 22 previously reported and confirmed pediatric cases in the literature. It is often associated with immune deficiency states and presents with a severe acute upper airway obstruction commonly requiring intensive care management and artificial ventilation. We present two cases of atypical laryngotracheitis in which HSV was found to be the causative pathogen subsequent to laryngoscopy and microbiologic investigations. While the first case was a previously well 8-month-old girl, the second was a 22-month-old immunosuppressed boy. One-third of the total confirmed cases in the English literature required intensive care management eliciting the setting as a pointer to the diagnosis. Laryngoscopy is a readily available tool for rapid diagnosis and controlled securing of the airway. This step may avoid controversial and potential counter-productive use of systemic steroids in these cases.

Enhanced identification of viral and atypical bacterial pathogens in lower respiratory tract samples with nucleic acid amplification tests.

The advantages of nucleic acid amplification tests (NAT) over conventional methods for the detection of pathogens in lower respiratory tract samples have not been established. NAT for respiratory pathogens were performed on 439 endotracheal tube (ETT) and bronchoalveolar lavage (BAL) samples. A potential pathogen was detected in 87 samples. Of 22 samples that tested positive by conventional methods, 15 tested positive for the same pathogen by NAT, 1 tested positive for a different pathogen, 2 had co-infections identified only by NAT, and 4 tested negative by NAT. An additional 73 pathogens were detected by NAT in 65 samples including 30 pathogens that were missed by conventional methods (19 adenovirus, 6 respiratory syncytial virus, 3 parainfluenza virus 1-4, 2 influenza A), 41 pathogens not routinely identified by conventional methods in most laboratories (23 rhinovirus, 8 human coronavirus OC43, 5 human metapneumovirus (hMPV), 2 human coronavirus 229E, 2 human coronavirus NL63, 1 Chlamydophila pneumoniae) and 2 pathogens from samples where no respiratory virus testing was requested (1 influenza A, 1 parainfluenza virus). Four of 52 patients who had multiple BAL samples submitted on the same day had negative and positive results by NAT on different samples. NAT improves detection of potential pathogens from ETT and BAL samples.