Tara L. Greenhow

Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine.

Background: The introduction of routine vaccination with heptavalent conjugated pneumococcal vaccine has changed the overall incidence of bacteremia in children 3 months–3 years old. Objective: To describe the changing incidence and etiology of bacteremia in previously healthy toddlers presenting to outpatient clinical settings. Methods: Retrospective case series of all blood cultures obtained between September 1998 and August 2003 in Kaiser Permanente Northern California outpatient clinics and emergency departments from previously healthy children 3 months–3 years old. Results: Implementation of routine vaccination with the conjugated pneumococcal vaccine resulted in an 84% reduction of Streptococcus pneumoniae bacteremia (1.3–0.2%) and a 67% reduction in overall bacteremia (1.6–0.7%) in the study population. The rate of blood culture isolation of contaminating organisms remained unchanged at 1.8%; therefore, by the end of the study, >70% of organisms identified in blood cultures were contaminants. During the 5 study years, total blood cultures drawn decreased by 35% in outpatient pediatric clinics but remained unchanged in emergency departments. By 2003, one-third of all pathogenic organisms isolated from blood cultures were Escherichia coli, one-third were non-vaccine serotype S. pneumoniae, the majority of the remaining one-third were Staphylococcus aureus, Salmonella spp., Neisseria meningitidis and Streptococcus pyogenes. In our population of children routinely immunized with the conjugated pneumococcal vaccine, a white blood cell count >15,000 by itself is a poor predictor of bacteremia in the febrile toddler (sensitivity, 74.0%; specificity, 54.5%; positive predictive value, 1.5%; negative predictive value, 99.5%). Conclusion: In the United States, routine vaccinations with Haemophilus influenzae type b and S. pneumoniae vaccines have made bacteremia in the previously healthy toddler a rare event. As the incidence of pneumococcal bacteremia has decreased, E. coli, Salmonella spp. and Staphylococcus aureus have increased in relative importance. The use of the white blood cell count alone to guide the empiric use of antibiotics is not indicated. New guidelines are needed to approach the previously healthy febrile toddler in the outpatient setting.

Changing Epidemiology of Bacteremia in Infants Aged 1 Week to 3 Months

BACKGROUND Bacteremia in young infants has remained an important ongoing concern for decades. Despite changes in prenatal screening and infant immunizations, the current epidemiology of this problem has received little attention. METHODS: We conducted a retrospective analysis of all blood cultures collected at Kaiser Permanente Northern California on full-term, previously healthy infants presenting for care between 1 week to 3 months of age for whom a blood culture was drawn from January 1, 2005, through December 31, 2009. RESULTS: During the study period, 4255 blood cultures were collected from 160 818 full-term infants. Only 2% of all blood cultures were positive for pathogens (93/4255), whereas 247 positive cultures were due to contaminants. The incidence rate of true bacteremia was 0.57 in 1000 full-term births. The most common pathogen was Escherichia coli (56%). Ninety-eight percent of infants with E coli bacteremia had a urinary tract infection. Group B Streptococcus and Staphylococcus aureus were the second and third most common pathogens, respectively. There were no cases of Listeria monocytogenes bacteremia or meningococcemia and only 1 case of enterococcal bacteremia. Ampicillin resistant pathogens accounted for 36% of organisms. CONCLUSIONS: Our study indicates bacteremia in young infants occurs infrequently and in only 2.2% of those who had a blood culture drawn. On the basis of the epidemiology of pathogens found in this large cohort, these data suggest a change in currently recommended presumptive antibiotic coverage in 1-week to 3-month-old infants with suspected bacteremia.

The changing epidemiology of serious bacterial infections in young infants.

Background: Management of febrile young infants suspected of having serious bacterial infections has been a challenge for decades. The impact of changes in prenatal screening for Group B Streptococcus and of infant immunizations has received little attention in population-based studies. Methods: This study analyzed all cultures of blood, urine and cerebrospinal fluid obtained from full-term infants 1 week to 3 months of age, who presented for care at Kaiser Permanente Northern California during a 7-year period utilizing electronic medical records. Results: A total of 224,553 full-term infants were born during the study period. Of 5396 blood cultures, 129 bacteremic infants were identified (2%). Of 4599 urine cultures, 823 episodes of urinary tract infection (UTI) were documented in 778 infants (17%). Of 1796 CSF cultures, 16 infants had bacterial meningitis (0.9%). The incidence rate of serious bacterial infections (bacteremia, UTI and meningitis) and febrile serious bacterial infections was 3.75 and 3.1/1000 full-term births, respectively. Escherichia coli was the leading cause of bacteremia (78), UTI (719) and bacterial meningitis (7). There were 23 infants with Group B Streptococcus bacteremia including 6 cases of meningitis and no cases of Listeria infection. Nine percentage of infants had multiple sites of infection; 10% of UTIs were associated with bacteremia and 52% of bacteremia was associated with UTI. Conclusions: Compared with earlier studies, UTIs now are found significantly more often than bacteremia and meningitis with 92% of occult infections associated with UTIs. These data emphasize the importance of an urinalysis in febrile infants.

Utility of DNA Microarrays for Detection of Viruses in Acute Respiratory Tract Infections in Children

Objective To assess the utility of a panviral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections (RTIs). Study design The Virochip was compared with conventional direct fluorescent antibody (DFA)- and polymerase chain reaction (PCR)-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. Results The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity, 85% to 90%; specificity, ≥99%; positive predictive value, 94% to 96%; negative predictive value, 97% to 98%) in the detection of respiratory syncytial virus, influenza A, and rhinoviruses/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. Conclusions Given its favorable sensitivity and specificity profile and expanded spectrum for detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric RTIs.

Diagnostic Accuracy of the Urinalysis for Urinary Tract Infection in Infants <3 Months of Age

BACKGROUND: The 2011 American Academy of Pediatrics urinary tract infection (UTI) guideline suggests incorporation of a positive urinalysis (UA) into the definition of UTI. However, concerns linger over UA sensitivity in young infants. Infants with the same pathogenic organism in the blood and urine (bacteremic UTI) have true infections and represent a desirable population for examination of UA sensitivity. METHODS: We collected UA results on a cross-sectional sample of 276 infants <3 months of age with bacteremic UTI from 11 hospital systems. Sensitivity was calculated on infants who had at least a partial UA performed and had ≥50 000 colony-forming units per milliliter from the urine culture. Specificity was determined by using a random sample of infants from the central study site with negative urine cultures. RESULTS: The final sample included 245 infants with bacteremic UTI and 115 infants with negative urine cultures. The sensitivity of leukocyte esterase was 97.6% (95% confidence interval [CI] 94.5%–99.2%) and of pyuria (>3 white blood cells/high-power field) was 96% (95% CI 92.5%–98.1%). Only 1 infant with bacteremic UTI (Group B Streptococcus) and a complete UA had an entirely negative UA. In infants with negative urine cultures, leukocyte esterase specificity was 93.9% (95% CI 87.9 – 97.5) and of pyuria was 91.3% (84.6%–95.6%). CONCLUSIONS: In young infants with bacteremic UTI, UA sensitivity is higher than previous reports in infants with UTI in general. This finding can be explained by spectrum bias or by inclusion of faulty gold standards (contaminants or asymptomatic bacteriuria) in previous studies.

Bacteraemic urinary tract infection: Management and outcomes in young infants

Objectives To determine predictors of parenteral antibiotic duration and the association between parenteral treatment duration and relapses in infants <3 months with bacteraemic urinary tract infection (UTI). Design Multicentre retrospective cohort study. Setting Eleven healthcare institutions across the USA. Patients Infants <3 months of age with bacteraemic UTI, defined as the same pathogenic organism isolated from blood and urine. Main outcome measures Duration of parenteral antibiotic therapy, relapsed UTI within 30 days. Results The mean (±SD) duration of parenteral antibiotics for the 251 included infants was 7.8 days (±4 days), with considerable variability between institutions (mean range 5.5–12 days). Independent predictors of the duration of parenteral antibiotic therapy included (coefficient, 95% CI): age (−0.2 days, −0.3 days to −0.08 days, for each week older), year treated (−0.2 days, −0.4 to −0.03 days for each subsequent calendar year), male gender (0.9 days, 0.01 to 1.8 days), a positive repeat blood culture during acute treatment (3.5 days, 1.2–5.9 days) and a non-Escherichia coli organism (2.2 days, 0.8–3.6 days). No infants had a relapsed bacteraemic UTI. Six infants (2.4%) had a relapsed UTI (without bacteraemia). The duration of parenteral antibiotics did not differ between infants with and without a relapse (8.2 vs 7.8 days, p=0.81). Conclusions Parenteral antibiotic treatment duration in young infants with bacteraemic UTI was variable and only minimally explained by measurable patient factors. Relapses were rare and were not associated with treatment duration. Shorter parenteral courses may be appropriate in some infants.

Management and Outcomes of Previously Healthy, Full-Term, Febrile Infants Ages 7 to 90 Days.

BACKGROUND: There is considerable variation in the approach to infants presenting to the emergency department and outpatient clinics with fever without a source. We set out to describe the current clinical practice regarding culture acquisition on febrile young infants and review the outcomes of infants with and without cultures obtained. METHODS: This study analyzed Kaiser Permanente Northern California’s electronic medical record to identify all febrile, full term, previously healthy infants born between July 1, 2010, and June 30, 2013, presenting for care between 7 and 90 days of age. RESULTS: During this 3-year study, 96 156 full-term infants were born at Kaiser Permanente Northern California. A total of 1380 infants presented for care with a fever with an incidence rate of 14.4 (95% confidence interval: 13.6–15.1) per 1000 full term births. Fifty-nine percent of infants 7 to 28 days old had a full evaluation compared with 25% of infants 29 to 60 days old and 5% of infants 61 to 90 days old. Older infants with lower febrile temperatures presenting to an office setting were less likely to have a culture. In the 30 days after fevers, 1% of infants returned with a urinary tract infection. No infants returned with bacteremia or meningitis. CONCLUSIONS: Fever in a medical setting occurred in 1.4% of infants in this large cohort. Forty-one percent of febrile infants did not have any cultures including 24% less than 28 days. One percent returned in the following month with a urinary tract infection. There was no delayed identification of bacteremia or meningitis.

Preterm neonates with candidal brain microabscesses: a case series.

We present three cases ofVLBW infants with Candida albicans fungemia who had brainmicroabscesses (<3 mm) detected by head ultrasound (HUS) andmagnetic resonance imaging (MRI) who were successfully treatedwith prolonged therapy.Case no. 1A 26-week gestational age 790-gram female infant was born to a24-year-old woman. Blood cultures were negative; however, shereceived 7 days of ampicillin and gentamicin.On day of life (DOL) 19, she developed temperature instabilityand pustules on her legs and wrist; complete blood count revealeda white blood cell (WBC) of 42.7 10

Scapular mass in an adolescent.

1. Michaels MG, Greenberg DP, Sabo DL, Wald ER. Treatment of children with congenital cytomegalovirus infection with ganciclovir. Pediatr Infect Dis J 2003;22:504–8. 2. Whitley RJ, Cloud G, Grouber W, et al. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a Phase II study: National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis 1997;175:1080–6. 3. Kimberlin DW, Lin CY, Sanchez PJ, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 2003;143:16–25. 4. Frenkel LM, Capparelli EV, Danker WM, et al. Oral ganciclovir in children: pharmacokinetics, safety, tolerance and antiviral effects. J Infect Dis 2000;182:1616–24.

Bacteremia in Children 3 to 36 Months Old After Introduction of Conjugated Pneumococcal Vaccines

After the introduction of PCV13, Escherichia coli, Salmonella spp, and Staphylococcus aureus caused 77% of bacteremia, and 76% of bacteremia occurred with a source. BACKGROUND AND OBJECTIVES: In June 2010, Kaiser Permanente Northern California replaced all 7-valent pneumococcal conjugate vaccine (PCV7) vaccines with the 13-valent pneumococcal conjugate vaccine (PCV13). Our objectives were to compare the incidence of bacteremia in children 3 to 36 months old by 3 time periods: pre-PCV7, post-PCV7/pre-PCV13, and post-PCV13. METHODS: We designed a retrospective review of the electronic medical records of all blood cultures collected on children 3 to 36 months old at Kaiser Permanente Northern California from September 1, 1998 to August 31, 2014 in outpatient clinics, in emergency departments, and in the first 24 hours of hospitalization. RESULTS: During the study period, 57 733 blood cultures were collected in the population of children 3 to 36 months old. Implementation of routine immunization with the pneumococcal conjugate vaccine resulted in a 95.3% reduction of Streptococcus pneumoniae bacteremia, decreasing from 74.5 to 10 to 3.5 per 100 000 children per year by the post-PCV13 period. As pneumococcal rates decreased, Escherichia coli, Salmonella spp, and Staphylococcus aureus caused 77% of bacteremia. Seventy-six percent of all bacteremia in the post-PCV13 period occurred with a source. CONCLUSIONS: In the United States, routine immunizations have made bacteremia in the previously healthy toddler a rare event. As the incidence of pneumococcal bacteremia has decreased, E coli, Salmonella spp, and S aureus have increased in relative importance. New guidelines are needed to approach the previously healthy febrile toddler in the outpatient setting.