Whole Genome Sequencing Detects Minimal Clustering Among Escherichia coli Sequence Type 131-H30 Isolates Collected From United States Children's Hospitals.

We applied whole genome sequencing to identify putative transmission clusters among clinical multidrug-resistant Escherichia coli sequence type 131-H30 isolates from 4 United States children's hospitals. Of 126 isolates, 17 were involved in 8 putative transmission clusters; 4 clusters showed evidence of healthcare-associated epidemiologic linkages. Geographic clustering analyses showed weak geographic clustering.

Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double-blinded randomized controlled trial from the Children's Oncology Group.

BACKGROUND: To the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line-associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited. METHODS: In the current multicenter, randomized, double-blind, placebo-controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once-daily bathing with 2% CHG-impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI. Secondary endpoints included total positive blood cultures, acquisition of resistant organisms, and acquisition of cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration. RESULTS: The study was stopped early because of poor accrual. Among the 177 enrolled patients, 174 were considered as evaluable (88 were randomized to the CHG group and 86 were randomized to the control group). The rate of CLABSI per 1000 central line days in the CHG group was 5.44 versus 3.10 in the control group (risk difference, 2.37; 95% confidence interval, 0.05-4.69 [P = .049]). Post hoc conditional power analysis demonstrated a 0.2% chance that the results would have favored CHG had the study fully enrolled. The rate of total positive blood cultures did not differ between groups (risk difference, 2.37; 95% confidence interval, -0.41 to 5.14 [P = .078]). The number of patients demonstrating the new acquisition of resistant organisms did not differ between groups (P = .54). Patients in the CHG group were found to be more likely to acquire cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration (P = .032). CONCLUSIONS: The data from the current study do not support the use of routine CHG bathing in children with cancer or those undergoing allogeneic HCT.

Prospective, Real-time Metagenomic Sequencing During Norovirus Outbreak Reveals Discrete Transmission Clusters.

BACKGROUND: Norovirus outbreaks in hospital settings are a common challenge for infection prevention teams. Given the high burden of norovirus in most communities, it can be difficult to distinguish between ongoing in-hospital transmission of the virus and new introductions from the community, and it is challenging to understand the long-term impacts of outbreak-associated viruses within medical systems using traditional epidemiological approaches alone. METHODS: Real-time metagenomic sequencing during an ongoing norovirus outbreak associated with a retrospective cohort study. RESULTS: We describe a hospital-associated norovirus outbreak that affected 13 patients over a 27-day period in a large, tertiary, pediatric hospital. The outbreak was chronologically associated with a spike in self-reported gastrointestinal symptoms among staff. Real-time metagenomic next-generation sequencing (mNGS) of norovirus genomes demonstrated that 10 chronologically overlapping, hospital-acquired norovirus cases were partitioned into 3 discrete transmission clusters. Sequencing data also revealed close genetic relationships between some hospital-acquired and some community-acquired cases. Finally, this data was used to demonstrate chronic viral shedding by an immunocompromised, hospital-acquired case patient. An analysis of serial samples from this patient provided novel insights into the evolution of norovirus within an immunocompromised host. CONCLUSIONS: This study documents one of the first applications of real-time mNGS during a hospital-associated viral outbreak. Given its demonstrated ability to detect transmission patterns within outbreaks and elucidate the long-term impacts of outbreak-associated viral strains on patients and medical systems, mNGS constitutes a powerful resource to help infection control teams understand, prevent, and respond to viral outbreaks.

Epidemiology and Antimicrobial Resistance Characteristics of the Sequence Type 131-H30 Subclone Among Extraintestinal Escherichia coli Collected From US Children.

Background: Escherichia coli sequence type (ST) 131-H30 is a globally important pathogen implicated in rising rates of multidrug resistance among E. coli causing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology of H30 among children undefined. Methods: We used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistant E. coli conducted at 4 US children's hospitals to estimate the burden and identify host correlates of infection with H30. H30 isolates were identified using 2-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status. Results: A total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available for analyses. The estimated period prevalence of H30 was 5.3% among all extraintestinal E. coli isolates (95% confidence interval [CI], 4.6%-7.1%); H30 made up 43.3% (81/187) of extended-spectrum ß-lactamase (ESBL)-producing isolates in this study. Host correlates of infection with H30 differed by extended-spectrum cephalosporin resistance status: Among resistant isolates, age ≤5 years was positively associated with H30 infection (relative risk [RR], 1.83 [95% CI, 1.19-2.83]); among susceptible isolates, age ≤5 years was negatively associated with H30 (RR, 0.48 [95% CI, .27-.87]), while presence of an underlying medical condition was positively associated (RR, 4.49 [95% CI, 2.43-8.31]). Conclusions: ST131-H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. The H30 subclone appears to disproportionately affect young children relative to other extended-spectrum cephalosporin-resistant E. coli.

The Molecular and Clinical Epidemiology of Extended-Spectrum Cephalosporin- and Carbapenem-Resistant Enterobacteriaceae at 4 US Pediatric Hospitals.

OBJECTIVE: In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. METHODS: ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged <22 years from 4 freestanding pediatric medical centers were collected along with the associated clinical data. RESULTS: The overall frequencies of ESC-R and CR isolates according to hospital over the 4-year study period ranged from 0.7% to 2.8%. Rates of ESC-R or CR Escherichia coli and Klebsiella pneumoniae varied according to hospital and ranged from 0.75 to 3.41 resistant isolates per 100 isolates (P < .001 for any differences). E coli accounted for 272 (77%) of the resistant isolates; however, a higher rate of resistance was observed in K pneumoniae isolates (1.78 vs 1.27 resistant isolates per 100 same-species isolates, respectively; P = .005). One-third of the infections caused by ESC-R or CR E coli were community-associated. In contrast, infections caused by ESC-R or CR K pneumoniae were more likely than those caused by resistant E coli to be healthcare- or hospital-associated and to occur in patients with an indwelling device (P ≤ .003 for any differences, multivariable logistic regression). Nonsusceptibility to 3 common non-ß-lactam agents (ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole) occurred in 23% of the ESC-R isolates. The sequence type 131-associated fumC/fimH-type 40-30 was the most prevalent sequence type among all resistant E coli isolates (30%), and the clonal group 258-associated allele tonB79 was the most prevalent allele among all resistant K pneumoniae isolates (10%). CONCLUSIONS: The epidemiology of ESC-R and CR Enterobacteriaceae varied according to hospital and species (E coli vs K pneumoniae). Both community and hospital settings should be considered in future research addressing pediatric ESC-R Enterobacteriaceae infection.

Antibiotic Prophylaxis Is Associated with Subsequent Resistant Infections in Children with an Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection.

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged <22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH (E. coli) or tonB (Klebsiella pneumoniae) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.

Rapid Metagenomic Next-Generation Sequencing during an Investigation of Hospital-Acquired Human Parainfluenza Virus 3 Infections.

Metagenomic next-generation sequencing (mNGS) is increasingly used for the unbiased detection of viruses, bacteria, fungi, and eukaryotic parasites in clinical samples. Whole-genome sequencing (WGS) of clinical bacterial isolates has been shown to inform hospital infection prevention practices, but this technology has not been utilized during potential respiratory virus outbreaks. Here, we report on the use of mNGS to inform the real-time infection prevention response to a cluster of hospital-acquired human parainfluenza 3 virus (HPIV3) infections at a children's hospital. Samples from 3 patients with hospital-acquired HPIV3 identified over a 12-day period on a general medical unit and 10 temporally associated samples from patients with community-acquired HPIV3 were analyzed. Our sample-to-sequencer time was <24 h, while our sample-to-answer turnaround time was <60 h with a hands-on time of approximately 6 h. Eight (2 cases and 6 controls) of 13 samples had sufficient sequencing coverage to yield the whole genome for HPIV3, while 10 (2 cases and 8 controls) of 13 samples gave partial genomes and all 13 samples had >1 read for HPIV3. Phylogenetic clustering revealed the presence of identical HPIV3 genomic sequence in the two of the cases with hospital-acquired infection, consistent with the concern for recent transmission within the medical unit. Adequate sequence coverage was not recovered for the third case. This work demonstrates the promise of mNGS for providing rapid information for infection prevention in addition to microbial detection.

Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-ß-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients.

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Use of Antibiotics Reserved for Resistant Gram-Negative Infections at Freestanding U.S. Children's Hospitals from 2004 to 2014.

We used the Pediatric Health Information System database to assess the use of antibiotics reserved for the treatment of resistant Gram-negative infections in children from 2004 to 2014. Overall, use of these agents increased in children from 2004 to 2007 and subsequently decreased. Infect Control Hosp Epidemiol 2016:37:967-970.

Fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients.

Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.

Intestinal decontamination of multidrug-resistant Klebsiella pneumoniae after recurrent infections in an immunocompromised host.

Multidrug-resistant (MDR) Enterobacteriaceae infections are associated with increased morbidity. We describe a 20-year-old hematopoietic cell transplantation recipient with recurrent MDR Klebsiella pneumoniae infection, prolonged intestinal colonization, and subsequent intestinal decontamination. Further study should evaluate stool surveillance, molecular typing, and fecal microbiota transplantation for patients with intestinal MDR Enterobacteriaceae carriage.

Significance of positive mediastinal cultures in pediatric cardiovascular surgical procedure patients undergoing delayed sternal closure.

BACKGROUND: Many pediatric cardiac surgery centers obtain mediastinal cultures at the time of delayed sternal closure (DSC). There are no recommendations regarding how to treat patients with positive cultures. We explored the clinical significance of positive mediastinal cultures with regard to surgical site infections (SSI). METHODS: A retrospective study was performed on all patients who underwent DSC at our institution between December 2006 and December 2011. National Healthcare Safety Network criteria were used to prospectively identify SSIs. Univariate and multivariate logistic regression analyses were performed to evaluate potential risk factors for SSI and predictors for positive mediastinal cultures obtained at DSC. RESULTS: A total of 178 patients underwent DSC during the study period; 155 patients met the eligibility criteria for the study and were included in the analysis. Of the 155 included patients, 11 patients (7.1%) experienced SSI. Patients with a positive mediastinal culture obtained at DSC were more likely to experience SSI than were patients with a negative culture (p=0.003). In univariate analysis, a positive mediastinal culture was the only factor associated with SSI (odds ratio [OR], 7.4; 95% confidence interval [CI], 2.1 to 26.7). In multivariate analysis, age at operation≥2 weeks (adjusted OR [aOR], 4.9; 95% CI, 1.84 to 12.8), receipt of stress-dosed hydrocortisone while the chest was open (aOR, 2.9; 95% CI, 1.1 to 7.6), and gestational age≤37 weeks (aOR, 2.7; 95% CI, 1.01 to 7.27) were independent predictors for a positive mediastinal culture. CONCLUSIONS: Patients with positive mediastinal cultures obtained at DSC had a significantly higher rate of subsequent SSI, and a positive mediastinal culture was the only statistically significant predictor of SSI.

Pediatric infection and intestinal carriage due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae.

The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae, but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred.

C-reactive protein, APOE genotype and longitudinal cognitive change in an older population.

BACKGROUND: circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally. METHODS: logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years. RESULTS: increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation. CONCLUSIONS: this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population.

HHV-6 reactivation and associated sequelae after hematopoietic cell transplantation.

Human herpesvirus 6 (HHV-6) reactivation has been associated with acute graft-versus-host-disease (aGVHD), cytomegalovirus reactivation, and mortality after allogeneic hematopoietic cell transplantation (HCT), but previous studies have yielded inconsistent results. We performed a large prospective study of allogeneic HCT recipients in order to more definitively define the relationships between HHV-6 and these important outcomes. Plasma specimens were collected prospectively from 315 allogeneic HCT recipients and tested for HHV-6 DNA at baseline and twice weekly for 12 weeks. Cox proportional hazards models were used to evaluate the time-dependent associations between HHV-6 reactivation and the targeted outcomes. HHV-6 was detected in 111 of 315 patients (35%) at a median of 20 days after HCT. HHV-6 reactivation was associated with subsequent cytomegalovirus reactivation (adjusted hazard ratio [aHR], 1.9; 95% confidence interval [CI], 1.3-2.8; P = .002). High-level HHV-6 (>1,000 HHV-6 DNA copies/mL) was associated with subsequent grades II to IV aGVHD (aHR, 2.4; 95% CI, 1.60-3.6; P < .001). High-level HHV-6 reactivation was also associated with nonrelapse mortality (aHR, 2.7; 95% CI, 1.2-6.3; P = .02). HHV-6 reactivation was independently and quantitatively associated with increased risk of subsequent cytomegalovirus reactivation, aGVHD, and mortality after HCT. A randomized antiviral trial is warranted to establish causality between HHV-6 and these endpoints and to determine if reducing HHV-6 reactivation will improve outcome after HCT.

A Comprehensive Intervention Associated With Reduced Surgical Site Infections Among Pediatric Cardiovascular Surgery Patients, Including Those With Delayed Closure.

BACKGROUND: Surgical site infections (SSIs) cause significant morbidity and mortality in patients undergoing cardiovascular (CV) surgery. Following an increase in SSIs in this population, driven by a high rate in those with delayed closure, we implemented an intervention to reduce these infections and assessed the intervention using both population- and patient-level analyses. METHODS: An intervention drawing from existing guidelines and targeting preoperative preparation of the patient, prophylactic antibiotics, and postoperative incision care was implemented. Special attention was paid to standardizing the care of the incision of patients with delayed closure. National Healthcare Safety Network criteria were used to prospectively identify SSIs. Population-level intervention effect was assessed using interrupted time series. To assess intervention adherence and effect in our patient population, retrospective chart review was performed on a cohort of patients undergoing cardiac procedures pre- and postintervention. Multivariate analysis was used to assess risk of SSI at the patient level. RESULTS: Timely preoperative prophylactic antibiotic dosing increased from 60% preintervention to 92% postintervention, and redosing during prolonged surgeries increased from 5% to 79% (both, P < .001). At the population-level, a decrease of 6.7 infections per 100 surgeries per 6 months was observed directly following the intervention (P = .002). The SSI rate decreased from 40% to 0.8% (P < .001) in patients with delayed closure and from 4.3% to 1.8% (P = .02) in patients with immediate closure. In multivariate analyses, surgery prior to the intervention was the strongest predictor for SSI (incidence rate ratio, 3.98; 95% confidence interval, 1.59 to 9.97). CONCLUSIONS: Our intervention decreased SSIs in pediatric CV surgery patients, particularly those with delayed closures.

Variation in Antibiotic Use for Children Hospitalized With Inflammatory Bowel Disease Exacerbation: A Multicenter Validation Study.

BACKGROUND: Antibiotics are often given for inflammatory bowel disease (IBD) exacerbations, but their use among pediatric inpatients has not been assessed. We aimed to validate administrative data for identifying hospitalizations for IBD exacerbation and to characterize antibiotic use for IBD exacerbations across children's hospitals. METHODS: To validate administrative data for identifying IBD exacerbation, we reviewed charts of 409 patients with IBD at 3 US tertiary care children's hospitals. Using the case definition with optimal test characteristics, we identified 3450 children with 5063 hospitalizations for IBD exacerbation at 36 children's hospitals between January 1, 2007 and December 31, 2009, excluding those with diagnosis codes for specific bacterial infections. We estimated predicted and expected hospital-specific antibiotic utilization rates using mixed-effects logistic regression, adjusting for patient- and hospital-level factors. RESULTS: Administrative codes for receipt of intravenous steroids or endoscopy provided 79% positive predictive value and 71% sensitivity for identifying hospitalizations for IBD exacerbation. Antibiotics were administered for ≥2 of the first 3 hospital days during 40.7% of IBD exacerbations in US children's hospitals; however, the proportion of patients receiving antibiotics varied significantly across hospitals from 27% to 71% (P < .001), despite adjustment for several patient- and hospital-level variables. Among those given antibiotics, the 3 most common regimens were metronidazole alone (26.9%), metronidazole with ciprofloxacin (10.3%), and ampicillin with gentamicin and metronidazole (7.0%). CONCLUSIONS: Significant variability exists in antibiotic use for children hospitalized with IBD exacerbation, which is unexplained by disease severity or hospital volume. Further study should determine the optimal antibiotic therapy for this condition.

HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients.

Human herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective study aimed to evaluate associations between HHV-6 reactivation and central nervous system dysfunction after allogeneic HCT. Patients were enrolled before HCT. Plasma samples were tested for HHV-6 at baseline and twice weekly after transplantation until day 84. Delirium was assessed at baseline, 3 times weekly until day 56, and weekly on days 56 to 84 using a validated instrument. Neurocognitive testing was performed at baseline and at approximately day 84. HHV-6 was detected in 111 (35%) of the 315 included patients. Patients with HHV-6 were more likely to develop delirium (adjusted odds ratio = 2.5; 95% confidence interval, 1.2-5.3) and demonstrate neurocognitive decline (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-6.2) in the first 84 days after HCT. Cord blood and unrelated transplantation increased risk of HHV-6 reactivation. These data provide the basis to conduct a randomized clinical trial to determine whether prevention of HHV-6 reactivation will reduce neurocognitive morbidity in HCT recipients.

An outbreak of varicella with likely breakthrough disease in a population of pediatric cancer patients.

BACKGROUND: Varicella is highly contagious, and immunocompromised patients are at increased risk of severe illness, including disseminated disease, pneumonia, and encephalitis. We describe an outbreak of varicella with likely breakthrough disease in a population of pediatric cancer patients in October 2004. SETTING: A 250-bed tertiary care pediatric facility with a 33-bed oncology unit, outpatient clinics, and affiliated group housing and schoolroom spaces. METHODS: We defined varicella as an acute illness with a maculopapulovesicular rash, without other apparent cause. We defined breakthrough disease as varicella with onset more than 42 days after vaccination. Cancer patients were considered to be nonimmune if serologic test results were negative for varicella-zoster virus. Family members were considered to be nonimmune if they had no history of infection with wild-type varicella-zoster virus or of varicella vaccination. RESULTS: In a period of approximately 16 days, varicella was detected in 7 children (the index case, 5 secondary cases, and 1 tertiary case). Of the 7 identified cases, 4 appeared to be cases of breakthrough disease in previously vaccinated children. The outbreak resulted in the exposure of 82 families at a pediatric group housing facility; 28 children at the schoolroom; and 77 patients, 150 family members, and 9 staff members at 3 outpatient clinics. CONCLUSIONS: This outbreak highlights the important role that breakthrough varicella can play in healthcare centers with affiliated group housing. Formal recommendations on the management of exposed individuals who have been vaccinated should be made in such settings, especially if immunocompromised hosts are present.