Risk factors associated with laboratory-confirmed bloodstream infections in a tertiary neonatal intensive care unit.

BACKGROUND: Bloodstream infections (BSI) remain a leading cause of morbidity and mortality among infants admitted to neonatal intensive care units (NICUs). At the time of evaluation for suspected BSI, presenting signs may be nonspecific. We sought to determine the clinical signs and risk factors associated with laboratory-confirmed BSI among infants evaluated for late-onset sepsis in a tertiary NICU. METHODS: This prospective cohort study included infants >3 days of age admitted to a level 4 NICU from July 2006 to October 2009 for whom a blood culture was drawn for suspected sepsis. Clinicians documented presenting signs at the time of culture. Laboratory-confirmed BSI was defined as per the National Healthcare Safety Network. Multivariate analyses were performed using a logistic regression random effects model. RESULTS: Six-hundred and eighty eligible episodes of suspected BSI were recorded in 409 infants. Enteral contrast within the preceding 48 hours was the most significant risk factor for laboratory-confirmed BSI [Odds Ratio: 9.58 (95% confidence interval: 2.03-45.19)] followed by presence of a central venous catheter. Apnea and hypotension were the most strongly associated presenting signs. CONCLUSION: Among infants evaluated in a tertiary NICU, recent exposure to enteral contrast was associated with increased odds of developing BSI. Apnea and hypotension were the most strongly associated clinical signs of infection.

Antibiotic sensitivity and resistance patterns in pediatric staphylococcal scalded skin syndrome.

Historical resistance patterns often guide empiric antibiotic choices in staphylococcal scalded skin syndrome (SSSS), but little is known about the difference in susceptibility between SSSS and other childhood staphylococcal infections. A retrospective chart review of culture-confirmed cases of SSSS seen in the inpatient dermatology consultation service at the Children's Hospital of Philadelphia between 2005 and 2011 was performed. Most cases of SSSS at our institution are due to oxacillin-susceptible Staphylococcus aureus, and approximately half of the cases are due to clindamycin-resistant strains. Clindamycin and a penicillinase-resistant penicillin are suggested as empiric treatment for SSSS until culture susceptibility data are available to guide therapy.

Emergency department epidemiology of pneumococcal bacteremia in children since the institution of widespread PCV7 vaccination.

BACKGROUND: The heptavalent pneumococcal conjugate vaccine (PCV7) has produced a shift in the epidemiology of invasive infections from Streptoccoccus pneumoniae. OBJECTIVE: Our aim was to determine the temporal changes in pneumococcal bacteremia (Streptococcus pneumoniae bacteremia [SPB]) in the emergency department (ED) since the introduction of PCV7. METHODS: This was a retrospective cohort study of children 0-18 years with SPB evaluated from 1998-2009 in a tertiary-care pediatric ED. The primary outcome was annual proportion of children with SPB from PCV7 serotypes (ie, 4, 6B, 9V, 14, 18C, 19F, and 23F) and nonvaccine serotypes (NVT). Rates of SPB (per 10,000 ED visits) were calculated. SPB was analyzed by time period: before October 2000 was considered "pre-PCV7," November 2000 to October 2003 was considered "peri-PCV7," and after November 2003 was "post-PCV7." Febrile young children (FYC) were defined as children age <36 months and fever without source. RESULTS: A total of 201 episodes of SPB occurred during the study, with a median age of 20.3 months (interquartile range 10.7-49.5 months; range 1.6-215.4 months); 56.7% were male and 69.7% were African American. SPB from PCV7 serotypes decreased more than fourfold, from 82.2% pre-PCV7 to 19.5% peri- and post-PCV7. Most SPB was from NVT serotype 19A (31.3%) peri- and post-PCV7. Annual rates of SPB were 4.01/10,000 ED visits pre-PCV7, decreasing to 2.10 peri-PCV7, and 1.75 post-PCV7. Among the 56 (27.8%) FYC with SPB, NVT were responsible for 11.5% of SPB pre-PCV7, and increased to 80.0% peri- and post-PCV7 (p < 0.001). CONCLUSIONS: Rates of SPB have decreased since the introduction of PCV7, yet SPB still occurs among children in the ED. NVT are increasing in prevalence, and SPB from PCV7-serotypes have decreased.

Pediatric Risk Factors for Candidemia Secondary to Candida glabrata and Candida krusei Species.

This 13-year retrospective study investigated risk factors for candidemia secondary to Candida species with increased likelihood of fluconazole resistance. Of 344 candidemia cases, 23 were caused by C glabrata or C krusei (CGCK). Age >2 years, recent fluconazole exposure, and recent surgery were independent risk factors for CGCK.

Rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) using the KeyPath MRSA/MSSA blood culture test and the BacT/ALERT system in a pediatric population.

CONTEXT: Timely initiation of directed antimicrobial therapy for Staphylococcus aureus bacteremia is dependent on rapid identification of S. aureus to ascertain methicillin-susceptibility status. OBJECTIVES: To investigate the performance of the rapid KeyPath (MicroPhage, Inc, Longmont, Colorado) methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) blood culture test (MMBT). DESIGN: Positive BacT/ALERT Pediatric FAN (fastidious antibiotic neutralization) blood culture bottles (bioMérieux, Inc, Durham, North Carolina) were tested prospectively using MMBT and routine bacterial identification and antibiotic susceptibility testing procedures as the gold standard. The MMBT uses an S. aureus-specific bacteriophage cocktail that infects bacterial cells and replicates them, resulting in cellular lysis. Bacteriophage-specific antibodies detect the increase in bacteriophage concentration in an immunoassay device. Phage amplification, in both the presence and absence of cefoxitin, indicates the presence of MRSA. The sensitivity, specificity, positive predictive value, and negative predictive value of MMBT in detecting S. aureus, MSSA, and MRSA were calculated. RESULTS: Of 188 positive blood cultures tested, 199 (63%) had Gram-positive cocci in clusters, 46 (24%) grew S. aureus (26 MSSA [57%], 20 MRSA [43%]) with the MMBT detecting 40 of 46 (87%). The sensitivity, specificity, positive predictive value, and negative predictive value among blood cultures with Gram-positive cocci in clusters were 87%, 100%, 100%, and 92% for S. aureus; 81%, 100%, 100%, and 95% for MSSA; and 95%, 100%, 100%, and 99% for MRSA. All blood cultures without growth of S. aureus tested negative by MMBT. CONCLUSIONS: The MMBT detected MSSA and MRSA directly from positive BacT/ALERT PF bottles with positive predictive values of 100%, suggesting that positive results could be reported immediately, but the sensitivity of this assay limited immediate reporting of negative results.

Epidemiology of bloodstream infections in children with sickle cell disease.

The incidence of invasive Streptococcus pneumoniae and Haemophilus influenzae type b infections in the sickle cell disease population has declined. In this report, we determine the predominant organisms responsible for bloodstream infections in a pediatric sickle cell disease population during the postheptavalent conjugate vaccine era. Central venous access device associated infections are a new burden to efforts aimed at preventing bloodstream infections in this population.

Genotyping of Candida parapsilosis from three neonatal intensive care units (NICUs) using a panel of five multilocus microsatellite markers: broad genetic diversity and a cluster of related strains in one NICU.

Candida parapsilosis (CP) (n = 40) isolated from an unselected patient population in the neonatal intensive care units (NICUs) of three US hospitals were collected over periods of 3.5-9 years. Two previously published microsatellite markers and three additional trinucleotide markers were used to produce multiplex genotypes, which revealed broad strain diversity among the NICU isolates with a combined index of discrimination (D) = 0.997. A cluster of eight related CP strains from four infants in a single NICU was observed. An extended collection of 24 CP isolates from the general population of that hospital showed that the cluster of NICU isolates was related to three isolates from general hospital patients. This microsatellite marker set is suitable to investigate clusters of colonizing and infecting strains of CP.

Cerebrospinal fluid reference ranges in term and preterm infants in the neonatal intensive care unit.

OBJECTIVE: To determine reference ranges of cerebrospinal fluid (CSF) laboratory findings in term and preterm infants in the neonatal intensive care unit. STUDY DESIGN: Data were collected prospectively as part of a multisite study of infants aged <6 months undergoing lumbar puncture for evaluation of suspected sepsis. Infants with a red blood cell count >500 cells/µL or a known cause of CSF pleocytosis were excluded from the analysis. RESULTS: A total of 318 infants met the inclusion criteria. Of these, 148 infants (47%) were preterm, and 229 (72%) received antibiotics before undergoing lumbar puncture. The upper reference limit of the CSF white blood cell (WBC) count was 12 cells/µL in preterm infants and 14 cells/µL in term infants. CSF protein levels were significantly higher in preterm infants (upper reference limit, 209 mg/dL vs 159 mg/dL in term infants; P < .001), and declined with advancing postnatal age in both groups (preterm, P = .008; term, P < .001). CSF glucose levels did not differ in term and preterm infants. Antibiotic exposure did not significantly affect CSF WBC, protein, or glucose values. CONCLUSIONS: CSF WBC counts are not significantly different in preterm and term infants. CSF protein levels are higher and decline more slowly with postnatal age in preterm infants compared with term infants. This study provides CSF reference ranges for hospitalized preterm and term infants, particularly in the first month of life.

Cerebrospinal fluid enrichment broth cultures rarely contribute to the diagnosis of bacterial meningitis.

This study included children undergoing lumbar puncture in the emergency department. Bacteria were isolated from 34 (1.7%) of 1898 cerebrospinal fluid (CSF) enrichment broth cultures; 30 were contaminants. The primary CSF Gram stain was negative in all specimens with a positive enrichment broth culture. Enrichment broth cultures rarely contributed to the diagnosis of bacterial meningitis, and positive CSF enrichment broth cultures contributed to diagnostic uncertainty.

Pneumococcal bacteremia in a vaccinated pediatric sickle cell disease population.

The incidence of pneumococcal disease in sickle cell disease declined significantly with penicillin prophylaxis as well as with the pneumococcal polysaccharide and heptavalent conjugate vaccines. In this report, we describe our experience with pneumococcal bacteremia in pediatric patients with sickle cell disease in the post-heptavalent pneumococcal conjugate vaccine era. Despite established prophylactic strategies, pneumococcal bacteremia continues to occur in patients with sickle cell disease.

Influence of antibiotic susceptibility patterns on empiric antibiotic prescribing for children hospitalized with community-acquired pneumonia.

OBJECTIVE: The aim of this study was to determine the influence of pneumococcal penicillin-nonsusceptibility patterns on individual antibiotic prescription among 33 children's hospitals using a multilevel, random- intercept, logistic regression analysis. METHODS: It was a multilevel cross-sectional study. The participants were children, 1-18 years of age, with community-acquired pneumonia (CAP) who were discharged in 2006. Hospital antibiotic susceptibility data were collected from surveys, and patient data were obtained from an administrative database. The primary exposure was the proportion of penicillin-nonsusceptible pneumococcal isolates reported in 2005 by each hospital. A secondary exposure included using the proportion of penicillin-resistant pneumococcal isolates to determine whether a threshold of susceptibility existed. Receipt of broad-spectrum empiric antibiotic therapy in 2006 (ie, antibiotics other than penicillins or aminopenicillins) was the main outcome measure. RESULTS: Four thousand eight hundred eighty-eight children diagnosed with CAP were eligible. The proportion of penicillin-nonsusceptible isolates ranged from 9% to 70% across hospitals whereas the proportion of penicillin-resistant isolates ranged from 0% to 60%. Broad-spectrum antibiotics were prescribed to 93% of patients; 45% of patients received cephalosporin class antibiotics alone. There was no significant association between the proportion of pencillin-nonsusceptible pneumococcal isolates at individual hospitals and narrow-spectrum prescribing. However, every 10% increase in penicillin-resistant pneumococcal isolates was associated with a 39% increase in broad-spectrum antibiotic prescribing (adjusted odds ratio: 1.39; 95% confidence interval: 1.08-1.69). CONCLUSIONS: There was substantial variability in empiric antibiotic prescribing for CAP among children's hospitals in the United States. High-levels (ie, resistant) but not modest-levels (ie, intermediate susceptibility) of penicillin resistance were associated with broad-spectrum antibiotic prescribing.

Clostridium difficile testing algorithms using glutamate dehydrogenase antigen and C. difficile toxin enzyme immunoassays with C. difficile nucleic acid amplification testing increase diagnostic yield in a tertiary pediatric population.

We evaluated the performance of the rapid C. diff Quik Chek Complete's glutamate dehydrogenase antigen (GDH) and toxin A/B (CDT) tests in two algorithmic approaches for a tertiary pediatric population: algorithm 1 entailed initial testing with GDH/CDT followed by loop-mediated isothermal amplification (LAMP), and algorithm 2 entailed GDH/CDT followed by cytotoxicity neutralization assay (CCNA) for adjudication of discrepant GDH-positive/CDT-negative results. A true positive (TP) was defined as positivity by CCNA or positivity by LAMP plus another test (GDH, CDT, or the Premier C. difficile toxin A and B enzyme immunoassay [P-EIA]). A total of 141 specimens from 141 patients yielded 27 TPs and 19% prevalence. Sensitivity, specificity, positive predictive value, and negative predictive value were 56%, 100%, 100%, and 90% for P-EIA and 81%, 100%, 100%, and 96% for both algorithm 1 and algorithm 2. In summary, GDH-based algorithms detected C. difficile infections with superior sensitivity compared to P-EIA. The algorithms allowed immediate reporting of half of all TPs, but LAMP or CCNA was required to confirm the presence or absence of toxigenic C. difficile in GDH-positive/CDT-negative specimens.

Broad-range bacterial polymerase chain reaction in the microbiologic diagnosis of complicated pneumonia.

BACKGROUND: A bacterial cause is not frequently identified in children with pneumonia complicated by parapneumonic effusion (ie, complicated pneumonia). OBJECTIVES: To determine the frequency of positive blood and pleural fluid cultures in children with complicated pneumonia and to determine whether broad-range 16S rRNA polymerase chain reaction (PCR) improves identification of a microbiologic cause. METHODS: This prospective cohort study included children 1-18 years of age hospitalized with complicated pneumonia. RESULTS: Pleural fluid drainage was performed in 64 (51.6%) of 124 children with complicated pneumonia. A microbiologic cause was identified in 11 of 64 patients (17.2%; 95% confidence interval [CI]: 8.9%-28.7%). Bacteria were isolated from pleural fluid culture in 6 of 64 patients (9.4 %; 95% CI: 3.5%-19.3%) undergoing pleural drainage; the causative bacteria were Staphylococcus aureus (n = 5) and Streptococcus pneumoniae (n = 1). Blood culture identified a bacterial cause in 3 of 44 cases (6.8%; 95% CI: 1.4%-18.7%) undergoing pleural fluid drainage; S. pneumoniae (n = 1), Haemophilus influenzae (n = 1), and S. aureus (n = 1) were isolated. Only 3 of the 19 pleural fluid samples (15.8%; 95% CI: 3.4%-39.6%) analyzed with 16S rRNA PCR were positive. S. pneumoniae was the only organism detected in all three samples; two of these three had negative pleural fluid cultures and absence of bacteria on Gram stain. S. aureus was isolated from pleural fluid culture in one patient with a negative 16S rRNA PCR test. CONCLUSIONS: Causative bacteria were infrequently identified in children with complicated pneumonia. Broad-range 16S rRNA PCR only modestly improved the microbiologic yield over conventional culture methods.

Declining incidence of candidemia in a tertiary inpatient pediatric population.

We examined the incidence of candidemia, Candida species distribution, and antifungal susceptibility patterns in a pediatric institution. We identified 301 episodes of candidemia from 2001 to 2010 inclusive. Annual incidence decreased from 0.68 to 0.12 cases/1,000 patient days between 2004 and 2010. Candida albicans was the most common species, followed by C. parapsilosis. All isolates tested were susceptible to amphotericin B and caspofungin, but 11% were resistant or dose-dependently susceptible to fluconazole.

Diagnostic accuracy of cerebrospinal fluid gram stain in children with suspected bacterial meningitis.

This cross-sectional study included 1938 children undergoing lumbar puncture; 21 (1.1%) cases were classified as definite (n = 17) or probable (n = 4) bacterial meningitis. Gram stain sensitivity was 94.1% (95% confidence interval, 71.3%-99.9%) for those with definite meningitis; the positive predictive value was 47.1% (95% confidence interval, 29.8%-64.9%). The sensitivity was 95.2% for those with definite or probable meningitis. Antibiotic pretreatment did not affect results.

Comparison of the Idaho Technology FilmArray system to real-time PCR for detection of respiratory pathogens in children.

The FilmArray Respiratory Panel (RP) multiplexed nucleic acid amplification test (Idaho Technology, Inc., Salt Lake City, UT) was compared to laboratory-developed real-time PCR assays for the detection of various respiratory viruses and certain bacterial pathogens. A total of 215 frozen archived pediatric respiratory specimens previously characterized as either negative or positive for one or more pathogens by real-time PCR were examined using the FilmArray RP system. Overall agreement between the FilmArray RP and corresponding real-time PCR assays for shared analytes was 98.6% (kappa = 0.92 [95% confidence interval (CI), 0.89 to 0.94]). The combined positive percent agreement was 89.4% (95% CI, 85.4 to 92.6); the negative percent agreement was 99.6% (95% CI, 99.2 to 99.8). The mean real-time PCR threshold cycle (C(T)) value for specimens with discordant results was 36.46 ± 4.54. Detection of coinfections and correct identification of influenza A virus subtypes were comparable to those of real-time PCR when using the FilmArray RP. The greatest comparative difference in sensitivity was observed for adenovirus; only 11 of 24 (45.8%; 95% CI, 27.9 to 64.9) clinical specimens positive for adenovirus by real-time PCR were also positive by the FilmArray RP. In addition, upon testing 20 characterized adenovirus serotypes prepared at high and low viral loads, the FilmArray RP did not detect serotypes 6 and 41 at either level and failed to detect serotypes 2, 20, 35, and 37 when viral loads were low. The FilmArray RP system is rapid and extremely user-friendly, with results available in just over 1 h with almost no labor involved. Its low throughput is a significant drawback for laboratories receiving large numbers of specimens, as only a single sample can be processed at a time with one instrument.

Mycobacterium chelonae-abscessus complex associated with sinopulmonary disease, Northeastern USA.

Members of the Mycobacterium chelonae-abscessus complex represent Mycobacterium species that cause invasive infections in immunocompetent and immunocompromised hosts. We report the detection of a new pathogen that had been misidentified as M. chelonae with an atypical antimicrobial drug susceptibility profile. The discovery prompted a multicenter investigation of 26 patients. Almost all patients were from the northeastern United States, and most had underlying sinus or pulmonary disease. Infected patients had clinical features similar to those with M. abscessus infections. Taxonomically, the new pathogen shared molecular identity with members of the M. chelonae-abscessus complex. Multilocus DNA target sequencing, DNA-DNA hybridization, and deep multilocus sequencing (43 full-length genes) support a new taxon for these microorganisms. Because most isolates originated in Pennsylvania, we propose the name M. franklinii sp. nov. This investigation underscores the need for accurate identification of Mycobacterium spp. to detect new pathogens implicated in human disease.

Prevalence of Trichomonas vaginalis infection in symptomatic adolescent females presenting to a pediatric emergency department.

OBJECTIVES: Adolescent females are disproportionately affected by sexually transmitted infections (STIs). Although Trichomonas vaginalis (TV) has been declared the most common nonviral STI, TV testing is not routinely conducted in the emergency department (ED), and when it is performed, insensitive testing methods are often used. Therefore, this study sought to determine the prevalence of TV and factors associated with TV infection among symptomatic adolescent females presenting to a pediatric ED. METHODS: This was a prospective prevalence study of female patients ages 14 to 19 years presenting to a pediatric ED with lower abdominal pain and/or genitourinary (GU) complaints. Patients were tested for TV, Neisseria gonorrhoeae (GC), and Chlamydia trachomatis (CT). RESULTS: Of the 276 patients who met inclusion criteria, 203 underwent TV testing; prevalence was 9.9% (95% confidence interval [CI] = 5.7% to 14.0%). Assuming all eligible patients who did not have TV testing were not infected with TV, sensitivity analysis revealed a minimum TV prevalence of 7.2% (95% CI = 4.2% to 10.3%). The overall prevalence of any STI was 22.5% (95% CI = 17.5% to 27.4%), with CT being the most prevalent (19.7%; 95% CI = 14.5 to 24.9). Aside from vaginal discharge (odds ratio [OR] = 3.7; 95% CI = 1.1 to 11.3), there were no other factors significantly associated with TV infection. CONCLUSIONS: A substantial proportion of adolescent females presenting to a pediatric ED with lower abdominal or GU symptoms had TV infection. TV testing should be considered as part of the evaluation of adolescent females presenting to the ED with lower abdominal, urinary, or vaginal complaints.

Recurrence rate of clostridium difficile infection in hospitalized pediatric patients with inflammatory bowel disease.

BACKGROUND: The incidence and associated morbidity of Clostridium difficile (CD) infection has been increasing at an alarming rate in North America. Clostridium difficile-associated diarrhea (CDAD) is the leading cause of nosocomial diarrhea in the USA. Patients with CDAD have longer average hospital admissions and additional hospital costs. Evidence has demonstrated that patients with inflammatory bowel disease (IBD) have a higher incidence of CD in comparison to the general population. The aim of this study was to compare the rate of recurrence of CD in hospitalized pediatric patients with IBD compared to hospitalized controls. The secondary aim was to evaluate whether infection with CD resulted in a more severe disease course of IBD. METHODS: This was a nested case control retrospective study of hospitalized pediatric patients. Diagnosis of CD was confirmed with stool Toxin A and B analysis. The following data were obtained from the medical records: demographic information, classification of IBD including location of disease, IBD therapy, and prior surgeries. In addition, prior hospital admissions within 1 year and antibiotic exposure were recorded. The same information was recorded following CD infection. Cases were patients with IBD and CD; two control populations were also studied: patients with CD but without IBD, and patients with IBD but without CD. RESULTS: For aim 1, a total of 111 eligible patients with IBD and CD infection and 77 eligible control patients with CD infection were included. The rate of recurrence of CD in the IBD population was 34% compared to 7.5% in the control population (P < 0.0001). In evaluating the effect of CD infection on IBD disease severity, we compared the 111 IBD patients with CD to a second control population of 127 IBD patients without CD. 57% of IBD-CD patients were readmitted with an exacerbation of disease within 6 months of infection with CD and 67% required escalation of therapy following CD infection, compared to 30% of IBD patients without CD (P < 0.001). Of the patients with IBD and CD, 44% of the cases were new-onset IBD, 63% were on immunosuppression therapy, and 33% were on gastric acid suppression prior to infection. In comparing the IBD-CD and control CD populations, there was no significant difference in antibiotic exposure: 33% of IBD patients and 26% of control patients were on antibiotics (P < 0.2). With regard to prior hospitalization, 10% of patients with IBD were hospitalized in the 30 days prior to infection in comparison to 27% of the control CD patients (P < 0.002). CONCLUSIONS: CD infection in patients with IBD results in a higher rate of recurrence and is associated with higher morbidity than the general population. Patients with IBD often required hospitalization and escalation of therapy following infection with CD, suggesting that CD resulted in increased severity of IBD disease. In addition, IBD patients were more likely develop community-acquired CD, while the control patients developed nosocomial infections, indicating a higher susceptibility to CD infection in patients with IBD.