Association Between Procalcitonin and Antibiotics in Children With Community-Acquired Pneumonia.

OBJECTIVE: To determine whether empirical antibiotic initiation and selection for children with pneumonia was associated with procalcitonin (PCT) levels when results were blinded to clinicians. METHODS: We enrolled children <18 years with radiographically confirmed pneumonia at 2 children's hospitals from 2014 to 2019. Blood for PCT was collected at enrollment (blinded to clinicians). We modeled associations between PCT and (1) antibiotic initiation and (2) antibiotic selection (narrow versus broad-spectrum) using multivariable logistic regression models. To quantify potential stewardship opportunities, we calculated proportions of noncritically ill children receiving antibiotics who also had a low likelihood of bacterial etiology (PCT <0.25 ng/mL) and those receiving broad-spectrum therapy, regardless of PCT level. RESULTS: We enrolled 488 children (median PCT, 0.37 ng/mL; interquartile range [IQR], 0.11-2.38); 85 (17%) received no antibiotics (median PCT, 0.32; IQR, 0.09-1.33). Among the 403 children receiving antibiotics, 95 (24%) received narrow-spectrum therapy (median PCT, 0.24; IQR, 0.08-2.52) and 308 (76%) received broad-spectrum (median PCT, 0.46; IQR, 0.12-2.83). In adjusted analyses, PCT values were not associated with antibiotic initiation (odds ratio [OR], 1.02, 95% confidence interval [CI], 0.97%-1.06%) or empirical antibiotic selection (OR 1.07; 95% CI, 0.97%-1.17%). Of those with noncritical illness, 246 (69%) were identified as potential targets for antibiotic stewardship interventions. CONCLUSION: Neither antibiotic initiation nor empirical antibiotic selection were associated with PCT values. Whereas other factors may inform antibiotic treatment decisions, the observed discordance between objective likelihood of bacterial etiology and antibiotic use suggests important opportunities for stewardship.

Pneumonia Severity in Children: Utility of Procalcitonin in Risk Stratification.

OBJECTIVES: To determine if serum procalcitonin, an indicator of bacterial etiology in pneumonia in all ages and a predictor of severe pneumonia in adults, is associated with disease severity in children with community-acquired pneumonia. METHODS: We prospectively enrolled children 2 months to <18 years with clinical and radiographic pneumonia at 2 children's hospitals (2014-2019). Procalcitonin samples were obtained at presentation. An ordinal outcome scale of pneumonia severity was defined: very severe (intubation, shock, or death), severe (intensive care admission without very severe features and/or high-flow nasal cannula), moderate (hospitalization without severe or very severe features), and mild (discharge). Hospital length of stay (LOS) was also examined. Ordinal logistic regression was used to model associations between procalcitonin and outcomes. We estimated adjusted odds ratios (aORs) for a variety of cut points of procalcitonin ranging from 0.25 to 3.5 ng/mL. RESULTS: The study included 488 children with pneumonia; 30 (6%) were classified as very severe, 106 (22%) as severe, 327 (67%) as moderate, and 25 (5%) as mild. Median procalcitonin in the very severe group was 5.06 (interquartile range [IQR] 0.90-16.83), 0.38 (IQR 0.11-2.11) in the severe group, 0.29 (IQR 0.09-1.90) in the moderate group, and 0.21 (IQR 0.12-1.2) in the mild group. Increasing procalcitonin was associated with increasing severity (range of aORs: 1.03-1.25) and increased LOS (range of aORs: 1.04-1.36). All comparisons were statistically significant. CONCLUSIONS: Higher procalcitonin was associated with increased severity and LOS. Procalcitonin may be useful in helping clinicians evaluate pneumonia severity.

Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer.

BACKGROUND: Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline. METHODS: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014). RESULTS: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period. CONCLUSIONS: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.

Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia.

BACKGROUND: Real-time polymerase chain reaction (PCR) on respiratory specimens and serology on paired blood specimens are used to determine the etiology of respiratory illnesses for research studies. However, convalescent serology is often not collected. We used multiple imputation to assign values for missing serology results to estimate virus-specific prevalence among pediatric and adult community-acquired pneumonia hospitalizations using data from an active population-based surveillance study. METHODS: Presence of adenoviruses, human metapneumovirus, influenza viruses, parainfluenza virus types 1-3, and respiratory syncytial virus was defined by positive PCR on nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We performed multiple imputation by developing a multivariable regression model for each virus using data from patients with available serology results. We calculated absolute and relative differences in the proportion of each virus detected comparing the imputed to observed (nonimputed) results. RESULTS: Among 2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed results increased viral etiology assignments by an absolute difference of 1.6%-4.4% and 0.8%-2.8% in children and adults, respectively; relative differences were 1.1-3.0 times higher. CONCLUSIONS: Multiple imputation can be used when serology results are missing, to refine virus-specific prevalence estimates, and these will likely increase estimates.

Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia.

Background: The role of human bocavirus (HBoV) in respiratory illness is uncertain. HBoV genomic DNA is frequently detected in both ill and healthy children. We hypothesized that spliced viral capsid messenger RNA (mRNA) produced during active replication might be a better marker for acute infection. Methods: As part of the Etiology of Pneumonia in the Community (EPIC) study, children aged <18 years who were hospitalized with community-acquired pneumonia (CAP) and children asymptomatic at the time of elective outpatient surgery (controls) were enrolled. Nasopharyngeal/oropharyngeal specimens were tested for HBoV mRNA and genomic DNA by quantitative polymerase chain reaction. Results: HBoV DNA was detected in 10.4% of 1295 patients with CAP and 7.5% of 721 controls (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.0-2.0]); HBoV mRNA was detected in 2.1% and 0.4%, respectively (OR, 5.1 [95% CI, 1.6-26]). When adjusted for age, enrollment month, and detection of other respiratory viruses, HBoV mRNA detection (adjusted OR, 7.6 [95% CI, 1.5-38.4]) but not DNA (adjusted OR, 1.2 [95% CI, .6-2.4]) was associated with CAP. Among children with no other pathogens detected, HBoV mRNA (OR, 9.6 [95% CI, 1.9-82]) was strongly associated with CAP. Conclusions: Detection of HBoV mRNA but not DNA was associated with CAP, supporting a pathogenic role for HBoV in CAP. HBoV mRNA could be a useful target for diagnostic testing.

Relationship Between Body Mass Index and Outcomes Among Hospitalized Patients With Community-Acquired Pneumonia.

Background: The effect of body mass index (BMI) on community-acquired pneumonia (CAP) severity is unclear. Methods: We investigated the relationship between BMI and CAP outcomes (hospital length of stay [LOS], intensive care unit [ICU] admission, and invasive mechanical ventilation) in hospitalized CAP patients from the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, adjusting for age, demographics, underlying conditions, and smoking status (adults only). Results: Compared with normal-weight children, odds of ICU admission were higher in children who were overweight (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.1-2.8) or obese (aOR, 2.1; 95% CI, 1.4-3.2), and odds of mechanical ventilation were higher in children with obesity (aOR, 2.7; 95% CI, 1.3-5.6). When stratified by asthma (presence/absence), these findings remained significant only in children with asthma. Compared with normal-weight adults, odds of LOS >3 days were higher in adults who were underweight (aOR, 1.6; 95% CI, 1.1-2.4), and odds of mechanical ventilation were lowest in adults who were overweight (aOR, 0.5; 95% CI, .3-.9). Conclusions: Children who were overweight or obese, particularly those with asthma, had higher odds of ICU admission or mechanical ventilation. In contrast, adults who were underweight had longer LOS. These results underscore the complex relationship between BMI and CAP outcomes.

Reducing Pediatric Sternal Wound Infections: A Quality Improvement Project.

OBJECTIVES: To evaluate whether a quality improvement intervention reduces sternal wound infection rates in children after cardiac surgery. DESIGN: This is a pre- and postintervention quality improvement study. SETTING: A 16-bed cardiac ICU in a university-affiliated pediatric tertiary care children's hospital. PATIENTS: All patients undergoing cardiac surgery via median sternotomy from January 2010 to December 2014 are included. The sternal wound infection rates for primary closure and delayed sternal closure are reported per 100 sternotomies. The hospital-acquired infection records were used to identify preintervention cases, while postintervention cases were collected prospectively. INTERVENTION: Implementation of a sternal wound prevention bundle during the preoperative, intraoperative, and postoperative periods for cardiac surgical cases. MEASUREMENTS AND MAIN RESULTS: During the preintervention period, 32 patients (3.8%) developed sternal wound infection, whereas only 19 (2.1%) developed sternal wound infection during the postintervention period (p = 0.04). The rates of sternal wound infection following primary closure were not significantly different pre- and postintervention (2.4% vs 1.6%; p = 0.35). However, patients with delayed sternal closure had significantly lower postintervention infection rates (10.6% vs 3.9%; p = 0.02). CONCLUSIONS: Implementation of a sternal wound prevention bundle during the perioperative period was associated with lower sternal wound infection rates in surgeries with delayed sternal closure.

Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia.

Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the extent to which these methods are correlated and the added diagnostic value of serology for respiratory viruses other than influenza virus have not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention (CDC) Etiology of Pneumonia in the Community (EPIC) study, we compared real-time reverse transcription-PCR (RT-PCR) and serology for the diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus 1 to 3 (PIV1, PIV2, and PIV3), and adenovirus (AdV) infections. Of 5,126 patients enrolled, RT-PCR and serology test results were available for 2,023, including 1,087 children below the age of 18 years and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; for HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; for the PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and for AdV, 111 (5.5%) tested positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the highest number of positive detections overall, but serology increased diagnostic yield for RSV (by 11.8%), HMPV (by 25.0%), AdV (by 32.4%), and PIV (by 48.9%). The method concordance estimated by Cohen's kappa coefficient (κ) ranged from good (for RSV; κ = 0.73) to fair (for AdV; κ = 0.27). Heterotypic seroresponses observed between PIVs and persistent low-level AdV shedding may account for the higher method discordance observed with each of these viruses. Serology can be a helpful adjunct to RT-PCR for research-based assessment of the etiologic contribution of respiratory viruses other than influenza virus to CAP.

Detection of 23 Gastrointestinal Pathogens Among Children Who Present With Diarrhea.

BACKGROUND: Diarrheal diseases are a major cause of ambulatory care visits and hospitalizations among children. Because of overlapping signs and symptoms and expensive and inefficient testing methods, the etiology of pediatric diarrhea is rarely established. METHODS: We identified children <18 years of age who were evaluated for diarrhea at Primary Children's Hospital in Salt Lake City, Utah, between October 2010 and September 2012. Stool specimens submitted for testing were evaluated by using the FilmArray gastrointestinal diagnostic system, which is a rapid multiplex polymerase chain reaction platform that can simultaneously detect 23 bacterial, viral, and protozoal agents. RESULTS: A pathogen was detected in 561 (52%) of 1089 diarrheal episodes. The most commonly detected pathogens included toxigenic Clostridium difficile (16%), diarrheagenic Escherichia coli (15%), norovirus GI/GII (11%), and adenovirus F 40/41 (7%). Shiga toxin-producing E coli were detected in 43 (4%) specimens. Multiple pathogens were identified in 160 (15%) specimens. Viral pathogens (norovirus, adenovirus, rotavirus, and sapovirus) were more common among children <5 years old than among those 5 to 17 years old (38% vs 16%, respectively; P < .001). Bacterial pathogens were identified most commonly in children 2 to 4 years of age. Children with 1 or more underlying chronic medical conditions were less likely to have a pathogen identified than those without a chronic medical condition (45% vs 60%, respectively; P < .01). Viral pathogens were detected more commonly in the winter, whereas bacterial pathogens were detected more commonly in the summer. CONCLUSIONS: Toxigenic C difficile, diarrheagenic E coli, and norovirus were the leading organisms detected among these children with diarrhea. Viral pathogens are identified frequently among young children with acute gastroenteritis.

Risk Factors for Recurrent Clostridium difficile Infection in Pediatric Inpatients.

OBJECTIVE: The purpose of this study was to identify the risk factors during the incident Clostridium difficile infection (CDI) episode, associated with developing recurrent CDI within 60 days, among hospitalized children that may be amenable to intervention. METHODS: This was a retrospective cohort study of pediatric patients hospitalized at a freestanding children's hospital from January 1, 2003, to December 31, 2010. Patients were eligible if they were <18 years of age at admission and had a new diagnosis of CDI. Patients <1 year of age and those with a history of CDI in the previous 60 days were excluded. Age, gender, race, complex chronic conditions, and other information were collected. Multivariable logistic regression was used to evaluate predictors of recurrent CDI. RESULTS: During the study period, there were 612 unique patients with an incident CDI episode; 65 (10.6%) experienced at least 1 recurrence. Patients with any complex chronic condition were 4.0 (95% confidence interval [CI]: 1.2-13.9) times more likely to experience recurrence. Patients with a malignancy and those who received non-CDI antibiotics at any time during CDI treatment were 2.3 (95% CI: 1.3-4.0) and 2.8 (95% CI: 1.2-6.9) times more likely to experience recurrence, respectively. CONCLUSIONS: The presence of underlying comorbidities, malignancies, and treatment with non-CDI antibiotics during CDI treatment were the most important risk factors for recurrence. Efforts to reduce unnecessary courses of non-CDI antibiotics could lower the risk of CDI recurrence.

Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia.

BACKGROUND: The clinical significance of viruses detected in patients with community-acquired pneumonia (CAP) is often unclear. METHODS: We conducted a prospective study to identify the prevalence of 13 viruses in the upper respiratory tract of patients with CAP and concurrently enrolled asymptomatic controls with real-time reverse-transcriptase polymerase chain reaction. We compared age-stratified prevalence of each virus between patients with CAP and controls and used multivariable logistic regression to calculate attributable fractions (AFs). RESULTS: We enrolled 1024 patients with CAP and 759 controls. Detections of influenza, respiratory syncytial virus, and human metapneumovirus were substantially more common in patients with CAP of all ages than in controls (AFs near 1.0). Parainfluenza and coronaviruses were also more common among patients with CAP (AF, 0.5-0.75). Rhinovirus was associated with CAP among adults (AF, 0.93) but not children (AF, 0.02). Adenovirus was associated with CAP only among children <2 years old (AF, 0.77). CONCLUSIONS: The probability that a virus detected with real-time reverse-transcriptase polymerase chain reaction in patients with CAP contributed to symptomatic disease varied by age group and specific virus. Detections of influenza, respiratory syncytial virus, and human metapneumovirus among patients with CAP of all ages probably indicate an etiologic role, whereas detections of parainfluenza, coronaviruses, rhinovirus, and adenovirus, especially in children, require further scrutiny.

Secondhand Smoke Exposure and Illness Severity among Children Hospitalized with Pneumonia.

OBJECTIVE: To assess the relationship between secondhand smoke (SHS) exposure and disease severity among children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN: Children hospitalized with clinical and radiographic CAP were enrolled between January 1, 2010, and June 30, 2012 at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community study. Household SHS exposure was defined based on the number of smokers in the child's home. Outcomes included hospital length of stay, intensive care unit admission, and mechanical ventilation. Proportional hazards and logistic regression models were used to assess associations between SHS exposure and outcomes. All models were adjusted for age, sex, race/ethnicity, household education level, government insurance, comorbidities, enrollment site, year, and season. RESULTS: Of the 2219 children included in the study, SHS exposure was reported in 785 (35.4%), including 325 (14.8%) with ≥2 smokers in the home. Compared with nonexposed children, the children exposed to ≥2 smokers had longer length of stay (median, 70.4 hours vs 64.4 hours; adjusted hazard ratio, 0.85; 95% CI, 0.75-0.97) and were more likely to receive intensive care (25.2% vs 20.9%; aOR, 1.44; 95% CI, 1.05-1.96), but not mechanical ventilation. Outcomes in children exposed to only 1 household smoker were similar to those in nonexposed children. CONCLUSION: Children hospitalized with CAP from households with ≥2 smokers had a longer length of stay and were more likely to require intensive care compared with children from households with no smokers, suggesting that they experienced greater pneumonia severity.

Community-acquired pneumonia requiring hospitalization among U.S. children.

BACKGROUND: Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. RESULTS: From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). CONCLUSIONS: The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).

Seasonality of acute otitis media and the role of respiratory viral activity in children.

BACKGROUND: Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infections in young children. AOM and respiratory viruses both display seasonal variation. Our objective was to examine the temporal association between circulating respiratory viruses and the occurrence of pediatric ambulatory care visits for AOM. METHODS: This retrospective study included 9 seasons of respiratory viral activity (2002 to 2010) in Utah. We used Intermountain Healthcare electronic medical records to assess community respiratory viral activity via laboratory-based active surveillance and to identify children <18 years with outpatient visits and International Classification of Diseases, Ninth Revision codes for AOM. We assessed the strength of the association between AOM and individual respiratory viruses using interrupted time series analyses. RESULTS: During the study period, 96,418 respiratory viral tests were performed; 46,460 (48%) were positive. The most commonly identified viruses were respiratory syncytial virus (22%), rhinovirus (8%), influenza (8%), parainfluenza (4%), human metapneumovirus (3%) and adenovirus (3%). AOM was diagnosed during 271,268 ambulatory visits. There were significant associations between peak activity of respiratory syncytial virus, human metapneumovirus, influenza A and office visits for AOM. Adenovirus, parainfluenza and rhinovirus were not associated with visits for AOM. CONCLUSIONS: Seasonal respiratory syncytial virus, human metapneumovirus and influenza activity were temporally associated with increased diagnoses of AOM among children. These findings support the role of individual respiratory viruses in the development AOM. These data also underscore the potential for respiratory viral vaccines to reduce the burden of AOM.

Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis.

Viral infections of the lower respiratory tract cause an enormous disease burden in children, and the role of respiratory viruses in serious lower respiratory tract infections (LRTIs) in older adults is increasingly appreciated. Although viruses are responsible for a large proportion LRTIs, antibiotics are often prescribed. New diagnostic platforms have the potential to detect a wider range of established and newly discovered viruses with greater sensitivity. This will create additional challenges. Although it is clear that influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus are important causes of pneumonia, the role of rhinoviruses and some of the newly described viruses, including human coronaviruses and bocavirus, is harder to determine. Better diagnostic tests that establish the cause of LRTIs in children have the potential to both reduce overall antibiotic use and to improve the targeted use of antibiotics. In addition, rapid identification of viral infections can help control nosocomial transmission.

Oseltamivir-resistant influenza A 2009 H1N1 virus in immunocompromised patients.

BACKGROUND: First-line treatment of influenza A 2009 H1N1 relies on neuraminidase inhibitors such as oseltamivir. Resistance conferred by the H275Y neuraminidase gene mutation is concerning and likely to increase. OBJECTIVES: To characterize oseltamivir resistance in a hospital-based patient population. PATIENTS AND METHODS: All available respiratory specimens positive for influenza A by direct fluorescent antibody, RT-PCR, or culture from patients at the University of Utah 5/09-12/09 were collected. Specimens were confirmed as 2009 H1N1 by the Utah Department of Health. RT-PCR and pyrosequencing were used to test for the H275Y mutation (CDC protocol). PyroMark Q24 AQ software (Qiagen, Valencia, CA, USA) was used to allow for quantitative H275Y mutation analysis. Medical records of patients with resistant virus were reviewed. RESULTS: We tested 191 influenza A virus-positive samples from 187 unique patients. Fifty (27%) patients were hospitalized. Four patient specimens (2.1%) were found to carry the H275Y mutation. Three patients were hospitalized, representing 6% of inpatient samples tested. Three patients had undergone hematopoietic stem cell transplant in the past year. Two patients died. Their influenza viruses were confirmed to be oseltamivir-resistant at an independent reference laboratory and through the Center for Disease Control and Prevention (CDC). One patient reported no history of prior oseltamivir exposure. CONCLUSIONS: Widespread oseltamivir resistance among 2009 H1N1 remains a potential threat. Rapid techniques, such as pyrosequencing, which has the additional benefit of identifying mixed mutant populations of virus, may play a key role in identifying at-risk individuals and potentially unsuspected cases. Targeted surveillance of immunocompromised patients will be critical toward improving future influenza planning and therapy.

Family clusters of variant X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency disorder. The clinical presentation is varied depending on the degree of involvement of the NADPH oxidase system responsible for the oxidative burst of neutrophils. We present 3 cases of variant X-linked CGD in an effort to introduce the disease and highlight the importance and limitations of CGD screening. The variant X-linked form of CGD results in a less severe phenotype and frequently presents later in life. Variant X-linked CGD is difficult to diagnose, but is becoming more readily recognized based on improved testing methods. A high index of suspicion in the setting of unusual infections such as Burkholderia cepacia pneumonia is essential to make the diagnosis. Family screening can lead to early intervention, prophylaxis, and appropriate genetic counseling.