Kristina Bryant

Safety and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine

OBJECTIVE: Invasive pneumococcal disease rates have declined since immunization with 7-valent pneumococcal conjugate vaccine (PCV7) (Prevenar/Prevnar [Wyeth Pharmaceuticals, Philadelphia, PA]) became routine. Certain nonvaccine Streptococcus pneumoniae serotypes (1, 3, 5, 6A, 7F, and 19A) still cause significant morbidity and mortality. The safety and immunogenicity of PCV7 were compared with those of 13-valent PCV (PCV13), which contains saccharides from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F conjugated to CRM197. PATIENTS AND METHODS: Infants were randomly assigned to receive PCV13 or PCV7 at ages 2, 4, and 6 months with other vaccines. Post–third-dose antibodies to each pneumococcal polysaccharide were measured by immunoglobulin G enzyme-linked immunosorbent assay. Antibacterial functional antibodies were measured by opsonophagocytic assay (OPA). RESULTS: Subjects received PCV13 (n = 122) or PCV7 (n = 127). All PCV13 serotypes were immunogenic, with 88% to 98% of infants achieving antibody concentrations of ≥0.35 μg/mL to shared PCV7 serotypes. For the 6 additional serotypes, 97% to 100% of PCV13-vaccinated infants achieved antibody concentrations of ≥0.35 μg/mL. Geometric mean antibody concentration for PCV13 recipients ranged from 1.32 μg/mL (serotype 23F) to 4.26 μg/mL (serotype 14). The ratio of OPA geometric mean titers for the 7 shared serotypes (PCV13:PCV7) ranged from 0.6 to 1.4, suggesting no clinically meaningful differences. For PCV13-only serotypes, OPA geometric mean titers were significantly higher in the PCV13 group than in the PCV7 group. Local reactions and systemic events were similar between groups. CONCLUSIONS: PCV13 was well tolerated and immunogenic, with most infants developing antipolysaccharide antibody concentrations of ≥0.35 μg/mL, as well as OPA responses, to each of the 13 serotypes.

Clostridium difficile infections in children.

Clostridium difficile, a spore-forming Grampositive bacillus, is a frequent cause of antibiotic-associated diarrhea and a common nosocomial pathogen. Clinical manifestations of disease range from self-limited diarrhea to life-threatening colitis and death. Historically, C. difficile-associated infection (CDI) has been much less common in children than adults. Up to 70% of infants may be asymptomatically colonized with C. difficile, including toxigenic strains. Rates of colonization decrease with age, falling in the second year of age to 6%. Rates of colonization in children over age 2 are similar to those in adults ( 3%). Infants may acquire colonization early in the first week of life. Studies examining risk factors for C. difficile colonization have failed to show a consistent association between mode of delivery or receipt of formula versus breast milk. However, healthcareassociated acquisition of the organism is well described in neonatal intensive care units (NICUs), and C. difficile contamination of the NICU environment has been demonstrated. Most studies have failed to show an epidemiologic association between colonization and disease in infants 1 year of age. For example, in one Swedish study, C. difficile was isolated with equal frequency in healthy children between 1 week and 1 year of age (17%) and children 6 years of age with diarrhea (18%). In a study of outpatient children, C. difficile was isolated from 7% of patients with diarrhea and 14.8% of healthy controls. Children with C. difficile were younger than children without the organism (P 0.05); prior antibiotic exposure was noted in only 22%. In another study, toxin B was identified in 4.2% of 618 children with diarrhea and in an equivalent proportion of healthy controls. In contrast, Tullus et al observed all-cause diarrhea to be more frequent in children colonized with C. difficile after the age of 6 months. Similar findings have been noted in most controlled studies of NICU patients. C. difficile toxin was recovered from the stools of 55% of patients in one NICU but signs of enteric disease, including necrotizing enterocolitis, occurred with equal frequency in both toxin-positive and toxin-negative infants. Data from juvenile rabbits suggest that the lack of disease in colonized human infants may be related to the relative absence of receptors for toxin A on immature enterocytes. However, more recent data suggest the numbers of toxin A receptors present on the enterocytes of neonatal pigs are adequate to cause disease, suggesting that differences in the appearance of receptors with age may be a species-specific phenomenon. Sporadic case reports suggest that severe CDI occasionally occurs in infants, especially those with underlying intestinal pathology. For example, C. difficile pseudomembranous colitis has been identified at autopsy in infants with Hirshprung’s disease. Fatal C. difficile-associated pseudomembranous colitis has also been described in a premature infant with necrotizing enterocolitis. The accurate diagnosis of CDI in young children may be complicated by a lack of specificity of commonly used enzyme immunoassays in very young children. Most of these tests have not been validated for use in young children. Young children with asymptomatic C. difficile colonization nevertheless may represent a reservoir for transmission of disease to others. A 19-year-old woman developed CDI in the immediate postpartum period. Although her symptoms resolved with metronidazole treatment, she developed 3 recurrences. Her asymptomatic infant was a carrier of the identical strain of C. difficile, suggesting the infant was a potential source of the mother’s recurrent disease. The emergence of an epidemic strain of binary toxin-producing-C. difficile, B1/ NAP1/027, may be changing the epidemiology of CDI in children. B1/NAP1/027 has been associated with severe disease in both adult and pediatric patients without recent exposure to healthcare facilities and, in some cases, without recent antimicrobial use. In 2005, the Centers for Disease Control and Prevention reported cases of severe CDI in populations previously at low risk for disease, including healthy children with no recent antibiotic use. A 5-year retrospective study performed at a tertiary care children’s hospital revealed an increase in the number of patients seen in the emergency department with community-acquired CDI; 43% lacked From the *Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY; and ††Centers for Disease Control and Prevention, Atlanta, GA. Disclaimer: The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Copyright

Renal candidiasis in neonates with candiduria.

BACKGROUND Candida species commonly cause urinary tract infection in infants admitted to neonatal intensive care units. The purpose of this study was to describe the natural history of renal candidiasis as evidenced by sonography in infants with candiduria. METHODS The medical records of all infants who developed candiduria during their neonatal intensive care hospitalization between 1982 and 1993 were reviewed. Candiduria was defined as the isolation of Candida from (1) one or more specimens obtained by bladder catheterization or suprapubic aspiration, (2) one or more voided specimens and concurrent positive cultures from another sterile body site or (3) one or more voided specimens and changes on renal ultrasound consistent with renal candidiasis. Renal ultrasounds were retrospectively reviewed by one pediatric radiologist. Nonshadowing echogenic foci were considered evidence of renal fungus balls. RESULTS Forty-one infants with candiduria were identified. Thirty-six infants underwent 1 or more renal imaging studies (ultrasonography, 35; computerized tomography, 1). The incidence of renal candidiasis in neonates with candiduria, defined as renal fungus balls or renal fungal abscess, was 42%. Of the 13 patients who had sonographic abnormalities suggestive of renal fungus balls, 7 had abnormalities on the first ultrasound obtained after the discovery of candiduria, whereas 6 patients developed abnormalities between 8 and 39 days later. CONCLUSIONS Serial renal ultrasounds are required to reliably detect late appearing renal fungus balls in neonates with candiduria. Complications requiring surgical intervention, like urinary tract obstruction, were uncommon.

Improving influenza immunization rates among healthcare workers caring for high-risk pediatric patients

OBJECTIVE To assess influenza vaccination rates of healthcare workers (HCWs) in neonatal intensive care units (NICUs), pediatric intensive care units (PICUs), and oncology units in Pediatric Prevention Network (PPN) hospitals. PARTICIPANTS Infection control practitioners and HCWs in NICUs, PICUs, and oncology units. METHODS In November 2000, posters, electronic copies of a slide presentation, and an influenza fact sheet were distributed to 32 of 76 PPN hospitals. In January 2001, a survey was distributed to PPN hospital participants to obtain information about the immunization campaigns. On February 7, 2001, a survey of influenza immunization was conducted among HCWs in NICU, PICU, and oncology units at participating hospitals. RESULTS Infection control practitioners from 19 (25%) of the 76 PPN hospitals completed the surveys. The median influenza immunization rate was 43% (range, 12% to 63%), with 7 hospitals exceeding 50%. HCWs (n = 1123) at 15 PPN hospitals completed a survey; 53% of HCWs reported receiving influenza immunization. Immunization rates varied by work site: 52% in NICUs and PICUs compared with 60% in oncology units. Mobile carts and PPN educational fact cards were associated with higher rates among these subpopulations (P < .001) (361 [63%] of 575 vs 236 [44%] of 541 for mobile carts; 378 [60%] of 633 vs 219 [45%] of 483 for fact cards). CONCLUSION Despite delayed distribution of influenza vaccine during the 2000-2001 season, immunization rates at 7 hospitals and among HCWs in high-risk units exceeded the National Association of Childrens Hospitals and Related Institutions goal of 50%.

Epidemiology of methicillin-resistant Staphylococcus aureus at a children's hospital.

OBJECTIVE To describe the relative contribution of and risk factors for both community-acquired and nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections. DESIGN Retrospective cohort study. SETTING 270-bed, tertiary-care childrens hospital. PARTICIPANTS All MRSA-infected children from whom MRSA was recovered between October 1, 1999, and September 30, 2001. METHODS Demographic, clinical, and risk factor data were abstracted from medical records. Categorical variables were analyzed using the chi-square or Fishers exact test and continuous variables were analyzed using the Mann-Whitney test. RESULTS Of the 62 patients with new MRSA infection, 37 had community-acquired MRSA and 25 had nosocomial MRSA. Most community-acquired MRSA infections were of the skin and soft tissue, the middle ear, and the lower respiratory tract. Nosocomial MRSA infections occurred in the lower respiratory tract, the skin and soft tissue, and the blood. Risk factors for infection, including underlying medical illness, prior hospitalization, and prior surgery, were similar for patients with community-acquired MRSA and nosocomial MRSA. History of central venous catheterization and previous endotracheal intubation was more common in patients with nosocomial MRSA. Only 3 patients with community-acquired MRSA had no identifiable risk factor other than recent antibiotic use. Resistance for clindamycin, erythromycin, and levofloxacin was similar between strains of community-acquired MRSA and nosocomial MRSA. CONCLUSIONS Similarities in patient risk factors and resistance patterns of isolates of both community-acquired and nosocomial MRSA suggest healthcare acquisition of most MRSA. Thus, classifying MRSA as either community acquired or nosocomial underestimates the amount of healthcare-associated MRSA.

Healthcare Personnel Attire in Non-Operating-Room Settings

Healthcare personnel (HCP) attire is an aspect of the medical profession steeped in culture and tradition. The role of attire in cross-transmission remains poorly established, and until more definitive information exists priority should be placed on evidence-based measures to prevent healthcare-associated infections (HAIs). This article aims to provide general guidance to the medical community regarding HCP attire outside the operating room. In addition to the initial guidance statement, the article has 3 major components: (1) a review and interpretation of the medical literature regarding (a) perceptions of HCP attire (from both HCP and patients) and (b) evidence for contamination of attire and its potential contribution to cross-transmission; (2) a review of hospital policies related to HCP attire, as submitted by members of the Society for Healthcare Epidemiology of America (SHEA) Guidelines Committee; and (3) a survey of SHEA and SHEA Research Network members that assessed both institutional HCP attire policies and perceptions of HCP attire in the cross-transmission of pathogens. Recommendations for HCP attire should attempt to balance professional appearance, comfort, and practicality with the potential role of apparel in the cross-transmission of pathogens. Although the optimal choice of HCP attire for inpatient care remains undefined, we provide recommendations on the use of white coats, neckties, footwear, the bare-below-the-elbows strategy, and laundering. Institutions considering these optional measures should introduce them with a well-organized communication and education effort directed at both HCP and patients. Appropriately designed studies are needed to better define the relationship between HCP attire and HAIs.

Catheter Dwell Time and CLABSIs in Neonates With PICCs: A Multicenter Cohort Study

OBJECTIVE: To determine whether the daily risk of central line–associated bloodstream infections (CLABSIs) increases over the dwell time of peripherally inserted central catheters (PICCs) in high-risk neonates. METHODS: Multicenter retrospective cohort including NICU patients with a PICC inserted between January 2005 and June 2010. We calculated incidence rates and used Poisson regression models to assess the risk of developing CLABSI as a function of PICC dwell time. RESULTS: A total of 4797 PICCs placed in 3967 neonates were included; 149 CLABSIs occurred over 89 946 catheter-days (incidence rate 1.66 per 1000 catheter-days). In unadjusted analysis, PICCs with a dwell time of 8 to 13 days, 14 to 22 days, and ≥23 days each had an increased risk of infection compared with PICCs in place for ≤7 days (P < .05). In adjusted analysis, the average predicted daily risk of CLABSIs after PICC insertion increased during the first 2 weeks after PICC insertion and remained elevated for the dwell time of the catheter. There was an increased risk of CLABSIs in neonates with concurrent PICCs (adjusted incidence rate ratio 2.04, 1.12–3.71). The incidence of Gram-negative CLABSIs was greater in PICCs with dwell times >50 days (incidence rate ratio 5.26, 2.40–10.66). CONCLUSIONS: The risk of CLABSIs increased during the 2 weeks after PICC insertion and then remained elevated until PICC removal. Clinicians should review PICC necessity daily, optimize catheter maintenance practices, and investigate novel CLABSI prevention strategies in PICCs with prolonged dwell times.

Immunogenicity and Safety of H influenzae Type b–N meningitidis C/Y Conjugate Vaccine in Infants

BACKGROUND: Meningococcal disease incidence is highest in children younger than 2 years of age, yet there is no US-licensed vaccine for this age group. A phase III study evaluated the immunogenicity and safety of an investigational Haemophilus influenzae type b (Hib)–Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY). MATERIALS AND METHODS: A total of 4180 infants were randomly assigned to receive the HibMenCY at the ages of 2, 4, 6, and 12 to 15 months or the licensed Hib tetanus toxoid conjugate vaccine (ActHIB) at 2, 4, and 6 months and Hib conjugated to N meningitidis outer membrane protein (PedvaxHIB) at 12 to 15 months. Routinely scheduled vaccines were coadministered. Serum bactericidal activity using human complement and anti–polyribosylribitol phosphate antibodies were assessed in 991 subjects. Local and systemic adverse reactions were recorded for 4 days after each dose. RESULTS: The percentage of HibMenCY recipients with serum bactericidal assay using human complement titers of 1:8 or higher after dose 3 was 98.8% for N meningitidis serogroup C (MenC) and 95.8% for N meningitidis serogroup Y (MenY). After dose 4, the percentages were 98.5% and 98.8%, respectively. The percentage of HibMenCY recipients with postdose 3 anti-polyribosylribitol phosphate antibody levels of ≥1.0 μg/mL was noninferior to that of control (96.3% vs 91.2%). After dose 4, MenC and MenY serum bactericidal assay using human complement antibody titers increased 12-fold over pre–dose 4 levels. Incidence of pain, redness, and swelling at the HibMenCY injection sites tended to be lower than with Hib type b after the first 3 doses and after the fourth dose. Rates of systemic symptoms were similar across groups. CONCLUSIONS: The HibMenCY was immunogenic against MenC and MenY and induced anti–polyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine. The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine.

Animals in Healthcare Facilities: Recommendations to Minimize Potential Risks

Animals may be present in healthcare facilities for multiple reasons. Although specific laws regarding the use of service animals in public facilities were established in the United States in 1990, the widespread presence of animals in hospitals, including service animals to assist in patient therapy and research, has resulted in the increased presence of animals in acute care hospitals and ambulatory medical settings. The role of animals in the transmission of zoonotic pathogens and cross-transmission of human pathogens in these settings remains poorly studied. Until more definitive information is available, priority should be placed on patient and healthcare provider safety, and the use of standard infection prevention and control measures to prevent animal-to-human transmission in healthcare settings. This paper aims to provide general guidance to the medical community regarding the management of animals in healthcare (AHC). The manuscript has four major goals:

The past, present, and future of healthcare‐associated infection prevention in pediatrics: catheter‐associated bloodstream infections.

Central line–associated bloodstream infections cause morbidity and mortality in children. We explore the evidence for prevention of central line–associated bloodstream infections in children, assess current practices, and propose research topics to improve prevention strategies.