Joan Robinson

Early discontinuation of intravenous antimicrobial therapy in pediatric oncology patients with febrile neutropenia

BackgroundThere are no standard criteria for when to discontinue intravenous antimicrobial therapy (IVAMT) in children with febrile neutropenia (FN), but it is now common to discontinue IVAMT and discharge patients with an absolute neutrophil count (ANC) ≤ 500 /mm3. The purpose of this study was to evaluate the outcome of a large cohort of children with FN who had IVAMT discontinued with an ANC ≤ 500 /mm3MethodsA retrospective chart review was completed of patients in the Northern Alberta Childrens Cancer Program with FN and no apparent clinical source of fever from June 1, 1997 to July 1, 2002.ResultsOut of a total of 275 patients, 127 (46%) had at least one episode of FN, with FN occurring in patients with sarcomas more commonly than in those with leukemia/ lymphoma and least in those with other solid tumors. In 59 of 276 episodes of FN (21%) patients had a microbiologically defined infection at admission. Of the 217 remaining episodes, 112 of 199 patients (56%) with known neutrophil counts had IVAMT discontinued before their absolute neutrophil count (ANC) reached 500 /mm3 at the discretion of the clinician. Fever recurred in only two of these patients after discharge, and there were no bacterial infections diagnosed after parenteral antibiotics were discontinued.ConclusionEven without use of standard criteria for early discharge, clinicians appear to be skilled at selecting children with FN who can safely have IVAMT discontinued with an ANC ≤ 500 /mm3.

Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study

BackgroundThere is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU).MethodsThis was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled.ResultsThirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented.ConclusionCandidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, Candida infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.

Invasive candidiasis in low birth weight preterm infants: risk factors, clinical course and outcome in a prospective multicenter study of cases and their matched controls.

BackgroundThis multicenter prospective study of invasive candidiasis (IC) was carried out to determine the risk factors for, incidence of, clinical and laboratory features, treatment and outcome of IC in infants of birth weight <1250xa0g.MethodsNeonates <1250xa0g with IC and their matched controls (2:1) were followed longitudinally and descriptive analysis was performed. Survivors underwent neurodevelopmental assessment at 18 to 24xa0months corrected age. Neurodevelopmental impairment (NDI) was defined as blindness, deafness, moderate to severe cerebral palsy, or a score <70 on the Bayley Scales of Infant Development 2nd edition. Multivariable analyses were performed to determine risk factors for IC and predictors of mortality and NDI.ResultsCumulative incidence rates of IC were 4.2%, 2.2% and 1.5% for birth-weight categories <750xa0g, <1000xa0g, <1500xa0g, respectively. Forty nine infants with IC and 90 controls were enrolled. Necrotizing enterocolitis (NEC) was the only independent risk factor for IC (pu2009=u20090.03). CNS candidiasis occurred in 50% of evaluated infants, while congenital candidiasis occurred in 31%. Infants with CNS candidiasis had a higher mortality rate (57%) and incidence of deafness (50%) than the overall cohort of infants with IC. NDI (56% vs. 33%; pu2009=u20090.017) and death (45% vs. 7%; pu2009=u20090.0001) were more likely in cases than in controls, respectively. IC survivors were more likely to be deaf (28% vs. 7%; pu2009=u20090.01). IC independently predicted mortality (pu2009=u20090.0004) and NDI (pu2009=u20090.018).ConclusionIC occurred in 1.5% of VLBW infants. Preceding NEC increased the risk of developing IC. CNS candidiasis is under-investigated and difficult to diagnose, but portends a very poor outcome. Mortality, deafness and NDI were independently significantly increased in infants with IC compared to matched controls.

Accuracy of parents in measuring body temperature with a tympanic thermometer

BackgroundIt is now common for parents to measure tympanic temperatures in children. The objective of this study was to assess the diagnostic accuracy of these measurements.MethodsParents and then nurses measured the temperature of 60 children with a tympanic thermometer designed for home use (home thermometer). The reference standard was a temperature measured by a nurse with a model of tympanic thermometer commonly used in hospitals (hospital thermometer). A difference of ≥ 0.5 °C was considered clinically significant. A fever was defined as a temperature ≥ 38.5 °C.ResultsThe mean absolute difference between the readings done by the parent and the nurse with the home thermometer was 0.44 ± 0.61 °C, and 33% of the readings differed by ≥ 0.5 °C. The mean absolute difference between the readings done by the parent with the home thermometer and the nurse with the hospital thermometer was 0.51 ± 0.63 °C, and 72 % of the readings differed by ≥ 0.5 °C. Using the home thermometer, parents detected fever with a sensitivity of 76% (95% CI 50–93%), a specificity of 95% (95% CI 84–99%), a positive predictive value of 87% (95% CI 60–98%), and a negative predictive value of 91% (95% CI 79–98 %). In comparing the readings the nurse obtained from the two different tympanic thermometers, the mean absolute difference was 0.24 ± 0.22 °C. Nurses detected fever with a sensitivity of 94% (95 % CI 71–100 %), a specificity of 88% (95% CI 75–96 %), a positive predictive value of 76% (95% CI 53–92%), and a negative predictive value of 97% (95%CI 87–100 %) using the home thermometer. The intraclass correlation coefficient for the three sets of readings was 0.80, and the consistency of readings was not affected by the body temperature.ConclusionsThe readings done by parents with a tympanic thermometer designed for home use differed a clinically significant amount from the reference standard (readings done by nurses with a model of tympanic thermometer commonly used in hospitals) the majority of the time, and parents failed to detect fever about one-quarter of the time. Tympanic readings reported by parents should be interpreted with great caution.

Sustainability of humoral responses to varicella vaccine in pediatric transplant recipients following a pretransplantation immunization strategy

Abstract:u2002 Varicella infections pose serious challenges for organ transplant recipients. To determine the safety and immunogenicity of the OMVV and determine the maintenance of OMVV responses in transplanted subjects at varying periods of immunosuppression within the first twou2003yr following transplantation. Eligible subjects given a two‐dose OMVV pretransplantation were monitored for AE. Antibody levels were assessed at baseline, sixu2003wk post‐OMVV, pretransplantation and up to 24u2003months post‐transplantation. Seroprotection was defined as ≥5u2003gpEU. Twenty‐one seronegative children were vaccinated. Following 42 doses, no vaccine‐related serious AE occurred. Mab_titer were 17.8 (5.7–910.2) and 183.5u2003EU (18.8–8116.4) at six and 12u2003wk, respectively (pu2003<u20030.0001). Fourteen (66.7%) participants were transplanted at a median of 16u2003months (1.5–56) following OMVV and had Mab_titer of 27.2u2003EU (9.0–236.2) just prior to transplantation. Of 11 who had post‐transplantation serology, seroprotection was sustained at three, six and 12u2003months post‐transplantation in 10/11, 12/12 and 8/10 subjects. In five of six subjects with two‐yr follow‐up, antibody levels remained seroprotective. No breakthrough varicella infections occurred. The receipt of OMVV prior to transplantation induced humoral responses which persisted in the early months following transplantation and up to twou2003yr post‐transplantation and was not associated with any serious adverse consequences.

Pediatric malignancies presenting as a possible infectious disease

BackgroundThe 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.MethodsThe database of patients diagnosed with a malignancy in the Northern Alberta Childrens 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 Childrens Hospital and charts were reviewed on all patients referred to the infectious diseases consult service prior to the diagnosis of malignancy.ResultsAn 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), Langerhans 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.ConclusionIt 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.

Infections in Children Receiving Extracorporeal Life Support

OBJECTIVEnTo describe risk factors for and the outcome of infections in children receiving extracorporeal life support (ECLS) and to determine the need for removal of foreign bodies with bloodstream infections (BSIs) in children receiving ECLS.nnnDESIGNnRetrospective cohort study.nnnSETTINGnTertiary care childrens hospital.nnnPATIENTSnChildren receiving ECLS from May 1997 through May 2007.nnnMETHODSnFor patients with documented infections, medical records were examined for demographic, clinical, and laboratory details. Patients with and without documented infections were compared with regard to demographic characteristics and ECLS course.nnnRESULTSnOne hundred seventeen patients underwent ECLS for a total of 878 days (median, 5.12 days). Thirty-five patients (29.9%) developed 55 infections, including 21 BSIs (38.2%), 20 urinary tract infections (36.4%), 6 ventilator-associated pneumonia episodes (10.9%), 2 viral infections (3.6%), and 6 miscellaneous infections (10.9%). The rates (in cases per 1,000 ECLS-days) were 23.9 for BSI, 22.8 for urinary tract infection, and 6.8 for ventilator-associated pneumonia. There were no significant differences in the demographic characteristics, indications for ECLS, or ECLS course between infected and uninfected patients, except for the median duration of ECLS (10.1 vs 3.8 days; P < .001). One death was attributed to infection. Resolution of BSI occurred without removal of foreign bodies in 18 (85.7%) of 21 children.nnnCONCLUSIONSnLonger duration of ECLS was the only identified risk factor for infection. Mortality was not statistically significantly different between infected and uninfected patients. Most BSIs that occurred during ECLS cleared without removal of foreign bodies.

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.

Pediatric Investigators Collaborative Network on Infections in Canada Study of Respiratory Syncytial Virus–associated Deaths in Pediatric Patients in Canada, 2003–2013

Respiratory syncytial virus (RSV)–associated deaths in Canadian children during 2003–2013 were predominantly associated with chronic medical conditions and immunocompromised states among infants. One in 5 deaths occurred among patients with no known risk factors for severe RSV.

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

BackgroundHuman 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.MethodsA 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.ResultsIn 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.ConclusionsThe 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.