Epidemiology and Outcomes of Patients With Healthcare Facility-Onset Clostridioides difficile Infection.

BACKGROUND: Clostridioides difficile infection (CDI) has become a rising public health threat. Our study aims to characterize the epidemiology and measure the attributable cost, length of stay, and in-hospital mortality of healthcare facility-onset Clostridioides difficile infection (HO-CDI) among patients in the U.S. Military Health System (MHS). METHODS: We performed a case-control and cross-sectional inpatient study of HO-CDI using MHS database billing records. Cases included those who were at least 18 years of age admitted to a military treatment facility with a stool sample positive for C. difficile obtained >3 days after admission. Risk factors in the preceding year were identified. Patient case-mix adjusted outcomes including in-hospital mortality, length of stay, and hospitalization cost were evaluated by high-dimensional propensity score adjusted logistic regression. RESULTS: Among 474,518 admissions within the MHS from 2008 to 2015, we identified 591 (0.12%) patients with HO-CDI and found a significant increase in the trend of HO-CDI over the 7-year study period (P < .001). Patients with HO-CDI had significantly higher hospitalization cost (attributable difference $66,044, P < .001), prolonged hospital stay (attributable difference 12.4 days, P < 0.001), and increased odds of in-hospital mortality (case-mix adjusted odds ratio 1.98; 95% CI, 1.43-2.74). CONCLUSIONS: Healthcare facility-onset Clostridioides difficile infection is rising in patients within the MHS and is associated with increased length of stay, hospital costs, and in-hospital mortality. We identified a significantly increased burden of hospitalization among patients admitted with HO-CDI, highlighting the importance of infection control and antimicrobial stewardship initiatives aimed at decreasing the spread of this pathogen.

Tele-TB: Using TeleMedicine to Increase Access to Directly Observed Therapy for Latent Tuberculosis Infection.

INTRODUCTION: Treatment of latent tuberculosis infection (LTBI) decreases risk of progression to active tuberculosis. Traditional treatment regimens required either daily isoniazid for 9 months, with historically poor compliance, or 12-week directly observed therapy (DOT) with isoniazid and rifapentine, with improved compliance but additional challenges of coordinating weekly clinic visits, further complicated if patients must travel a great distance for care. MATERIALS AND METHODS: Our referral area is complicated by congested traffic often resulting in one-way commutes, which can exceed 2 hours. These travel times would be prohibitive for conducting weekly in-clinic DOT. In an effort to improve access to DOT, we implemented TeleMedicine LTBI DOT (vDOT) within a military pediatric infectious diseases clinic. Patients aged 24 months or older diagnosed with LTBI were referred for possible enrollment into our vDOT clinic. All patients without contraindications for receiving isoniazid and/or rifapentine were offered LTBI treatment via weekly vDOT or daily treatment with isoniazid or rifampin. The first visit for vDOT patients was performed in person to discuss treatment options, demonstrate use of TeleMedicine software, and ensure the patient was able to take the medications. Baseline information about patients and travel time to our facility was determined. RESULTS: To date, 16 patients have completed LTBI therapy using vDOT. Average one-way travel time to our facility for patients was 51 minutes. Actual time spent in most vDOT encounters was less than 10 minutes. Appointments were arranged to take place outside usual school and work hours so patients could complete vDOT with minimal interruptions to daily life, resulting in 100% treatment compliance and completion. DISCUSSION: Conducting LTBI DOT using TeleMedicine is a viable and time-saving measure that still allows for high levels of patient compliance and treatment completion while minimizing interruptions to academic and work schedules.

Self-resolving superficial primary cutaneous mucormycosis in a 7-week-old infant.

A 7-week-old girl, born at 30 weeks' gestational age, presented to clinic for evaluation of a crop of vesicular lesions that were noted after removal of a bandage that had been in place for 4 days. A punch biopsy of the lesion revealed fungal elements that were later identified as Rhizopus spp. The lesion began to self-resolve, and no further treatment was needed, with full resolution of the lesion by 1 month after presentation. Clinicians should be aware of the variable presentations of mucormycosis and consider fungal infection in the differential diagnosis when evaluating vulnerable patients with skin eruptions.

Risk Factors for Community-Associated Clostridium difficile Infection in Children.

OBJECTIVE: To characterize the medication and other exposures associated with pediatric community-associated Clostridium difficile infections (CA-CDIs). STUDY DESIGN: We performed a case-control study using billing records from the US military health system database. CA-CDI cases included children 1-18 years of age with an outpatient International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code for Clostridium difficile infection (CDI) from 2001 to 2013. Each case was matched to 3 controls without CDI by age and sex. Children hospitalized at any time before their CDI were excluded. Outpatient pharmacy records were used to identify medication exposures in the preceding 12 weeks. In addition, we evaluated recent outpatient healthcare exposure, exposure to a sibling younger than 1 year of age, or to a family member with CDI. RESULTS: A total of 1331 children with CA-CDI were identified and 3993 controls were matched successfully. Recent exposure to fluoroquinolones, clindamycin (OR 73.00; 95% CI 13.85-384.68), third-generation cephalosporins (OR 16.32; 95% CI 9.11-29.26), proton pump inhibitors (OR 8.17; 95% CI 2.35-28.38), and to multiple classes of antibiotics, each was associated strongly the subsequent diagnosis of CA-CDI. Recent exposure to outpatient healthcare clinics (OR 1.35; 95% CI 1.31-1.39) or to a family member with CDI also was associated with CA-CDI. CONCLUSIONS: CA-CDI is associated with medications regularly prescribed in pediatric practice, along with exposure to outpatient healthcare clinics and family members with CDI. Our findings provide additional support for the judicious use of these medications and for efforts to limit spread of CDI in ambulatory healthcare settings and households.

Rising Vancomycin-Resistant Enterococcus Infections in Hospitalized Children in the United States.

OBJECTIVE: Vancomycin-resistant Enterococcus (VRE) is an emerging drug-resistant organism responsible for increasing numbers of nosocomial infections in adults. Few data are available on the epidemiology and impact of VRE infections in children. We hypothesized a significant increase in VRE infections among hospitalized children. Additionally, we predicted that VRE infection would be associated with certain comorbid conditions and increased duration and cost of hospitalization. METHODS: A retrospective study of inpatient pediatric patients was performed using data on hospitalizations for VRE from the Healthcare Cost and Utilization Project Kids' Inpatient Database from 1997 to 2012. We used a multivariable logistic regression model to establish factors associated with VRE infection and a high-dimensional propensity score match to evaluate death, length of stay, and cost of hospitalization. RESULTS: Hospitalizations for VRE infection showed an increasing trend, from 53 hospitalizations per million in 1997 to 120 in 2012 (P < .001). Conditions associated with VRE included Clostridium difficile infection and other diagnoses involving immunosuppression and significant antibiotic and health care exposure. Patients with VRE infection had a significantly longer length of stay (attributable difference [AD] 2.1 days, P < .001) and higher hospitalization costs (AD $8233, P = .004). VRE infection was not associated with an increased risk of death (odds ratio 1.03; 95% confidence interval 0.73-1.47). CONCLUSIONS: VRE infections among hospitalized children are increasing at a substantial rate. This study demonstrates the significant impact of VRE on the health of pediatric patients and highlights the importance of strict adherence to existing infection control policies and VRE surveillance in certain high-risk pediatric populations.

Healthy Late-preterm infants born 33-36+6 weeks gestational age have higher risk for respiratory syncytial virus hospitalization.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of hospitalization for children <1year old and is more severe in premature infants. OBJECTIVE: To assess whether late preterm (LPT) birth is an independent risk factor for RSV hospitalization and more severe RSV disease in children less than 24months old. METHODS: We conducted a retrospective cohort study of children enrolled in the military health system. LPT birth was defined as 33+0 through 36+6weeks gestation. Patients who received palivizumab or had known risk factors for RSV were excluded. Adjusted hazard ratios (HR) for LPT birth were calculated using a Cox proportional hazard model, while controlling for sex and RSV season. Severity of illness was assessed by comparing the need for respiratory support, length of stay, and age at RSV hospitalization between LPT and term children. RESULTS: A total of 599,535 children for 1,216,382 person-years were studied, of which 7597 children were admitted for RSV infection. LPT infants accounted for 643 (8.5%) of these RSV hospitalizations. The incidence density for RSV hospitalization of LPT infants was higher than term children (12.1 vs 7.8 per 1000 person-years). LPT infants had an increased adjusted risk for RSV hospitalization; specifically, those born 33+0 through 34+6weeks (HR 2.45; 95% confidence interval (CI) 1.96-3.07), and 35+0 through 36+6weeks (HR, 1.92; 95% CI, 1.66-2.22). LPT infants had longer hospital stays and required more respiratory support than term children. CONCLUSIONS: LPT birth is an independent risk factor for severe RSV disease and need for hospitalization.

Association of prematurity with the development of infantile hypertrophic pyloric stenosis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) has several known risk factors. The association between prematurity and IHPS and the timeline of presentation are poorly defined. Our aim was to evaluate the associations between IHPS and prematurity. METHODS: We performed a retrospective cohort study of 1,074,236 children born between June 2001 and April 2012 in the US Military Health System. IHPS cases and gestational ages (GA) were identified using billing codes. Additional risk factors for IHPS were controlled for in a multivariable logistic regression model. RESULTS: The incidence of IHPS was 2.99 per 1,000 in preterm infants and 2.25 per 1,000 in full term (relative risk (RR) = 1.33, 95% confidence interval (CI) 1.16-1.54). The adjusted odds ratio for prematurity was 1.26 (95% CI 1.08-1.46). The median (interquartile range (IQR)) chronological age at presentation was 40 d (30-56) in preterm infants vs. 33 d (26-45) in full term (P < 0.001). Median postmenstrual age at presentation was 42 wk in preterm infants (40-42) vs. 45 wk (44-46) in full term (P < 0.001). CONCLUSION: Prematurity is associated with IHPS. Premature infants develop IHPS at a later chronological age, but earlier postmenstrual age, than term infants. Providers should have an increased concern for IHPS development in premature infants.

Azithromycin in early infancy and pyloric stenosis.

BACKGROUND AND OBJECTIVE: Use of oral erythromycin in infants is associated with infantile hypertrophic pyloric stenosis (IHPS). The risk with azithromycin remains unknown. We evaluated the association between exposure to oral azithromycin and erythromycin and subsequent development of IHPS. METHODS: A retrospective cohort study of children born between 2001 and 2012 was performed utilizing the military health system database. Infants prescribed either oral erythromycin or azithromycin as outpatients in the first 90 days of life were evaluated for development of IHPS. Specific diagnostic and procedural codes were used to identify cases of IHPS. RESULTS: A total of 2466 of 1 074 236 children in the study period developed IHPS. Azithromycin exposure in the first 14 days of life demonstrated an increased risk of IHPS (adjusted odds ratio [aOR], 8.26; 95% confidence interval [CI], 2.62-26.0); exposure between 15 and 42 days had an aOR of 2.98 (95% CI, 1.24-7.20). An association between erythromycin and IHPS was also confirmed. Exposure to erythromycin in the first 14 days of life had an aOR of 13.3 (95% CI, 6.80-25.9), and 15 to 42 days of life, aOR 4.10 (95% CI, 1.69-9.91). There was no association with either macrolide between 43 and 90 days of life. CONCLUSIONS: Ingestion of oral azithromycin and erythromycin places young infants at increased risk of developing IHPS. This association is strongest if the exposure occurred in the first 2 weeks of life, but persists although to a lesser degree in children between 2 and 6 weeks of age.

Children with Down syndrome are high-risk for severe respiratory syncytial virus disease.

OBJECTIVE: To assess Down syndrome as an independent risk factor for respiratory syncytial virus (RSV) hospitalization in children younger than 3 years of age and to evaluate illness severity. STUDY DESIGN: A retrospective cohort study of children enrolled in the military health system database was conducted. The effect of Down syndrome on RSV hospitalization was assessed by Cox proportional hazards model, while we controlled for risk factors. Disease severity was assessed by length of hospital stay, need for respiratory support, and age at hospitalization. RESULTS: The study included 633 200 children and 3 209 378 person-years. Children with Down syndrome had a hospitalization rate of 9.6% vs 2.8% in children without Down syndrome. Down syndrome had a greater adjusted hazard ratio (HR) for RSV hospitalization than most risk factors, 3.46 (95% CI 2.75-4.37). A sensitivity analysis demonstrated HR 3.21 (95% CI 2.51-4.10) for patients with Down syndrome ages 0-23 months and HR 5.07 (95% CI 2.21-11.59) ages 24-36 months. The median (IQR) length of stay of children with and without Down syndrome was 4 days (2-7) and 2 days (1-4) (P < .001). Patients with Down syndrome had a greater risk of requiring respiratory support (relative risk 5.5; 95% CI, 2.5-12.3). The median (IQR) ages at admission for children with and without Down syndrome were 9.8 months (5.5-17.7) and 3.5 months (1.7-8.7) (P < .001). CONCLUSIONS: Down syndrome is independently associated with an increased risk for RSV hospitalization. Children with Down syndrome are older at time of RSV hospitalization and have more severe RSV illness than children without Down syndrome. This increased risk for hospitalization continues beyond 24 months.

A catheter-related bloodstream infection with Mycobacterium frederiksbergense in an immunocompromised child.

We report a case of a catheter-related bloodstream infection with Mycobacterium frederiksbergense in an immunocompromised child with acute lymphoblastic leukemia. Nontuberculous mycobacteria have been implicated in central venous catheter infections in immunosuppressed individuals, however, to our knowledge this is the first reported case of invasive infection with this organism.

Development of pyloric stenosis after a 4-day course of oral erythromycin.

Early exposure to oral erythromycin in young infants, particularly in the first 2 weeks of life, has previously been associated with the development of hypertrophic pyloric stenosis. We report a case of an infant who received an abbreviated 4-day course of oral erythromycin for suspected Chlamydia conjunctivitis at 5 days of life then underwent pyloromyotomy for pyloric stenosis less than 2 weeks later. Health care providers should use erythromycin judiciously in neonates because only a few days of exposure to this medication may lead to the development of a surgical condition of gastric outlet obstruction.

Development of pneumococcal mastoiditis due to multidrug-resistant serotype 19A despite three doses of 13-valent pneumococcal vaccine.

Acute mastoiditis is a potential complication of acute otitis media (AOM), with Streptococcus pneumoniae historically the most common pathogen isolated. Following the release of the 7-valent pneumococcal conjugate vaccine in 2000, a marked decline in invasive pneumococcal disease and a smaller reduction in pneumococcal AOM were observed, but data regarding its impact on acute mastoiditis are limited. With the recent introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), it is anticipated that pneumococcal AOM and invasive disease will further diminish. We report a case of acute mastoiditis from a multidrug-resistant serotype 19A S. pneumoniae in an immunocompetent child who had received three PCV13 vaccinations.

The effect of rotavirus immunization on rotavirus gastroenteritis hospitalization rates in military dependents.

We conducted a retrospective review of all U.S. military dependents less than 5 years old hospitalized with rotavirus-associated gastroenteritis from July 2003 to June 2009. The two post-vaccine seasons showed a significant reduction of 62.4% (95% CI, 58.6-65.8, P<0.001) in rotavirus gastroenteritis hospitalization rate compared to the three pre-vaccine seasons. Infants less than 12 months old showed the greatest reduction in incidence at 75.3%. A substantial decrease was also seen in unvaccinated children as well. Vaccine efficacy against hospitalization was 86.0% (95% CI, 77.7-91.3) after just a single dose. The overwhelming majority of children hospitalized for rotavirus since the introduction of the vaccine (ranging from 91.8 to 100% per season) had not received any of the rotavirus vaccine series.

Infant Botulism and Raised Intraocular Pressure.

Infant botulism is an exceedingly rare disease. Because confirmatory laboratory testing is not available for several days after time of presentation, infant botulism remains a clinical diagnosis. The authors demonstrate how raised intraocular pressure may provide an additional clinical clue to making the diagnosis.

Increased IL-15 production is associated with higher susceptibility of memory CD4 T cells to simian immunodeficiency virus during acute infection.

Acute SIV infection is characterized by explosive infection of memory CD4 T cells in peripheral and mucosal tissues. Interestingly, relatively few memory CD4 T cells are infected until as late as days 7-8 after challenge. However, by day 10 postinfection, most of the memory CD4 T cells are infected and carry viral DNA. The rapidity with which infection expands within 2-3 days to encompass virtually the entire memory CD4 T cell compartment suggests significant alterations in the susceptibility of memory CD4 T cells to infection during this period. The mechanism(s) underlying this increased permissiveness to infection is not known. In this study, we show that IL-15 secretion significantly correlates with the up-regulated expression of CD4 on memory CD4 T cells that is associated with increased permissiveness to SIV infection. Activation and proliferation of memory CD8, but not memory CD4 T cells, preceded the amplification of viral infection. Although memory CD4 T cells did not express normal activation markers, they displayed a significant up-regulation in the density of CD4 but not CCR5 expression between days 7 and 10 postinfection that correlated with increased plasma IL-15 levels and infection in these cells. Culture of purified CD4 T cells with IL-15 and/or SIV was associated with a significant increase in the expression of CD4 and infection of these sorted cells. Our results demonstrate that IL-15 contributes to the increased susceptibility of memory CD4 T cells to SIV during the early phase of acute SIV infection.

The effect of universal maternal screening on the incidence of neonatal early-onset group B streptococcal disease.

OBJECTIVE: To determine the effect of the revised guidelines on incidence of neonatal early-onset group B streptococcal disease (EoGBS) via retrospective analysis of births in a military population. METHODS: Information from records of all live births within military hospitals from 1993 to 2007 was obtained. The data were divided into three time frames, representing the evolution of identifying and managing at-risk deliveries for GBS transmission. Incidence of EoGBS decreased from 1.95 to 0.72 per 1000 live births following institution of the 1996 Centers for Disease Control and Prevention recommendations and continued to fall to 0.47 per 1000 since the adoption of universal screening in 2002. CONCLUSIONS: Universal culture-based screening is more effective than risk-based screening in preventing EoGBS in term infants. Cases of EoGBS continue to occur, however, at a baseline rate of nearly 0.5 per 1000 births, thus emphasizing the need for rapid diagnostics and ultimately a vaccine.

Isolated cardiac cysticercosis in an adolescent.

Cardiac cysticercosis is a rare and typically asymptomatic infection. We report a case of a young man from Cameroon with a left ventricular cyst discovered during a screening echocardiogram. Computed tomography and plain films did not reveal additional cysts. Serology was negative. The patient had the cyst surgically removed for suspected echinococcosis. Sectioning demonstrated a cysticercus. The literature on cardiac cysticercosis is reviewed.