Louis M. Bell

Outpatient management without antibiotics of fever in selected infants

Background In many academic centers it is standard practice to hospitalize all febrile infants younger than two months of age, whereas in community settings such infants are often cared for as outpatients. Methods We conducted a controlled study of 747 consecutive infants 29 through 56 days of age who had temperatures of at least 38.2 °C. After a complete history taking, physical examination, and sepsis workup, the 460 infants with laboratory or clinical findings suggestive of serious bacterial illness were hospitalized and treated with antibiotics. The screening criteria for serious bacterial illness included a white-cell count of at least 15,000 per cubic millimeter, a spun urine specimen that had 10 or more white cells per high-power field or that was positive on bright-field microscopy, cerebrospinal fluid with a white-cell count of 8 or more per cubic millimeter or a positive Grams stain, or a chest film showing an infiltrate. The 287 infants who had unremarkable examinations and normal laboratory r...

Patient density, nurse-to-patient ratio and nosocomial infection risk in a pediatric cardiac intensive care unit.

BACKGROUND An investigation of a Serratia marcescens outbreak in a pediatric cardiac intensive care unit (CICU) suggested that understaffing or overcrowding might have been underlying risk factors. OBJECTIVE To assess the effect of fluctuations in CICU nurse staffing levels and patient census on CICU nosocomial infection rate (NIR). METHODS The monthly CICU nursing hours, patient days and nosocomial infections were obtained from retrospective review of administrative, patient and microbiology records during December, 1994, through December, 1995 (study period). The NIR and nursing hours:patient day ratio were then calculated. The correlations between NIR vs. nursing hours, patient days and nursing hours:patient day ratio were determined. RESULTS The median monthly CICU NIR was 6.9 (range, 0 to 15.2) infections per 1000 patient days; the median number of hours worked per month by CICU registered nurses was 7754 (range, 7133 to 8452) hours; the median number of patient days treated per month was 507 (range, 381 to 590) patient days; and the median monthly nursing hours:patient day ratio was 15.2:1 (range, 13.2:1 to 19.9:1). The strongest linear correlation was observed between the monthly NIR and patient days (r = 0.89, P = 0.0001). There was an inverse correlation between the monthly NIR and nursing hours:patient day ratio (r = -0.77, P = 0.003). CONCLUSIONS The NIR was most strongly correlated with patient census but also was strongly associated with the nursing hours:patient day ratio. These factors may influence the infection rate because of breaks in health care worker aseptic technique or decreased hand washing. Increased patient census alone may increase the risk of cross-transmission of nosocomial infections. As hospitals proceed with cost containment efforts the effect of fluctuations in patient census and nurse staffing on patient outcomes needs evaluation.

Protective Effect of WC3 Vaccine Against Rotavirus Diarrhea in Infants During a Predominantly Serotype 1 Rotavirus Season

Abstract We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P < .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of theWC3vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.

Human parvovirus B19 infection among hospital staff members after contact with infected patients

In the spring and summer of 1988, two separate outbreaks of an illness with a rash resembling erythema infectiosum occurred among members of the nursing staff of the Childrens Hospital of Philadelphia. The sources were two adolescent patients with sickle cell disease and aplastic crisis who had unsuspected parvovirus infection. Tests for IgM and IgG antibodies to parvovirus B19 were positive in both patients, and electron microscopical examination showed parvovirus-like particles in the early serum samples. Of 40 health care workers exposed to infected patients, 12 (30 percent) were infected, 2 (5 percent) were possibly infected, 8 (20 percent) had evidence of a past infection with B19, and 18 (45 percent) remained seronegative. Attack rates among the susceptible contacts were 36 percent in the first outbreak and at least 38 percent in the second. Clinical symptoms began a mean of 12.6 days after exposure and included malaise, rash, and joint pain. We conclude that hospital workers are at risk of contracting nosocomial erythema infectiosum from patients with parvovirus-associated aplastic crisis. We recommend that all patients with hereditary hemolytic anemias who are admitted with a febrile illness be evaluated for aplasia and promptly placed in respiratory and contact isolation if aplastic crisis is suspected.

Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial.

IMPORTANCE Antimicrobial stewardship programs have been effective for inpatients, often through prescribing audit and feedback. However, most antimicrobial use occurs in outpatients with acute respiratory tract infections (ARTIs). OBJECTIVE To evaluate the effect of an antimicrobial stewardship intervention on antibiotic prescribing for pediatric outpatients. DESIGN Cluster randomized trial of outpatient antimicrobial stewardship comparing prescribing between intervention and control practices using a common electronic health record. After excluding children with chronic medical conditions, antibiotic allergies, and prior antibiotic use, we estimated prescribing rates for targeted ARTIs standardized for age, sex, race, and insurance from 20 months before the intervention to 12 months afterward (October 2008-June 2011). SETTING AND PARTICIPANTS A network of 25 pediatric primary care practices in Pennsylvania and New Jersey; 18 practices (162 clinicians) participated. INTERVENTIONS One 1-hour on-site clinician education session (June 2010) followed by 1 year of personalized, quarterly audit and feedback of prescribing for bacterial and viral ARTIs or usual practice. MAIN OUTCOMES AND MEASURES Rates of broad-spectrum (off-guideline) antibiotic prescribing for bacterial ARTIs and antibiotics for viral ARTIs for 1 year after the intervention. RESULTS Broad-spectrum antibiotic prescribing decreased from 26.8% to 14.3% (absolute difference, 12.5%) among intervention practices vs from 28.4% to 22.6% (absolute difference, 5.8%) in controls (difference of differences [DOD], 6.7%; P = .01 for differences in trajectories). Off-guideline prescribing for children with pneumonia decreased from 15.7% to 4.2% among intervention practices compared with 17.1% to 16.3% in controls (DOD, 10.7%; P < .001) and for acute sinusitis from 38.9% to 18.8% in intervention practices and from 40.0% to 33.9% in controls (DOD, 14.0%; P = .12). Off-guideline prescribing was uncommon at baseline and changed little for streptococcal pharyngitis (intervention, from 4.4% to 3.4%; control, from 5.6% to 3.5%; DOD, -1.1%; P = .82) and for viral infections (intervention, from 7.9% to 7.7%; control, from 6.4% to 4.5%; DOD, -1.7%; P = .93). CONCLUSIONS AND RELEVANCE In this large pediatric primary care network, clinician education coupled with audit and feedback, compared with usual practice, improved adherence to prescribing guidelines for common bacterial ARTIs, and the intervention did not affect antibiotic prescribing for viral infections. Future studies should examine the drivers of these effects, as well as the generalizability, sustainability, and clinical outcomes of outpatient antimicrobial stewardship. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01806103.

Risk Factors for and Outcomes of Bloodstream Infection Caused by Extended-Spectrum β-Lactamase–Producing Escherichia coli and Klebsiella Species in Children

Objective. The increasing prevalence of infections caused by extended-spectrum β-lactamase–producing Escherichia coli and Klebsiella species (ESBL-EK) has become a growing concern in the hospitalized patient population. Previous studies on risk factors for infection with ESBL-EK have mainly focused on adult populations, and these findings may not be relevant among the pediatric population that experiences a unique set of health care exposures and underlying conditions. The objective of this study was to define the risk factors and outcomes associated with ESBL-EK bloodstream infections in children. Methods. We conducted a nested case-control study using data from the Childrens Hospital of Philadelphia from May 1, 1999, to September 30, 2003. Eligible patients were identified from the hospital database of microbiology laboratory records. All patients with ESBL-EK bloodstream infections were compared to a random sample of patients with non–ESBL-EK bloodstream infections. Risk factors analyzed included prior antimicrobial use, comorbid conditions, and demographic characteristics. Pulsed-field gel electrophoresis was performed to determine genetic relatedness of the ESBL-EK isolates. Results. Thirty-five cases and 105 control subjects were included in the study. The median age among the cases was 2 years (interquartile range: 0–11), compared with 1 year (interquartile range: 0–8) among control subjects. Patients with ESBL-EK infections were 5.8 times (95% confidence interval: 1.9–17.7) more likely to have had exposure to an extended-spectrum cephalosporin in the 30 days before infection than those with non–ESBL-EK infections. Other independent predictors of ESBL-EK infection were being female, infection with a Klebsiella species, and steroid use in the 30 days before infection. All ESBL-EK isolates were susceptible to carbapenem antibiotics. Pulsed-field gel electrophoresis analysis revealed that the ESBL-EK isolates were polyclonal. Although a substantially higher proportion of children with ESBL-EK died (in-hospital mortality: 36% vs 13%), this difference was not statistically significant. Conclusions. Receipt of extended-spectrum cephalosporins in the 30 days before infection by an Escherichia coli or Klebsiella species is significantly associated with having an ESBL-EK infection in hospitalized children. Curtailed use of cephalosporins among high-risk groups may reduce the occurrence of ESBL-EK infections. Future studies on identifying high-risk children and investigating the impact of curtailed third-generation cephalosporin use to limit additional emergence of ESBL-EK infections should be undertaken.

Risk Factors and Predictors for Candidemia in Pediatric Intensive Care Unit Patients: Implications for Prevention

BACKGROUND Candida species are the leading cause of invasive fungal infections in hospitalized children and are the third most common isolates recovered from patients with healthcare-associated bloodstream infection in the United States. Few data exist on risk factors for candidemia in pediatric intensive care unit (PICU) patients. METHODS We conducted a population-based case-control study of PICU patients at Childrens Hospital of Philadelphia during the period from 1997 through 2004. Case patients were identified using laboratory records, and control patients were selected from PICU rosters. Control patients were matched to case patients by incidence density sampling, adjusting for time at risk. Following conditional multivariate analysis, we performed weighted multivariate analysis to determine predicted probabilities for candidemia given certain risk factor combinations. RESULTS We identified 101 case patients with candidemia (incidence, 3.5 cases per 1000 PICU admissions). Factors independently associated with candidemia included presence of a central venous catheter (odds ratio [OR], 30.4; 95% confidence interval [CI], 7.7-119.5), malignancy (OR, 4.0; 95% CI, 1.23-13.1), use of vancomycin for >3 days in the prior 2 weeks (OR, 6.2; 95% CI, 2.4-16), and receipt of agents with activity against anaerobic organisms for >3 days in the prior 2 weeks (OR, 3.5; 95% CI, 1.5-8.4). Predicted probability of having various combinations of the aforementioned factors ranged from 10.7% to 46%. The 30-day mortality rate was 44% among case patients and 14% among control patients (OR, 4.22; 95% CI, 2.35-7.60). CONCLUSIONS To our knowledge, this is the first study to evaluate independent risk factors and to determine a population of children in PICUs at high risk for developing candidemia. Future efforts should focus on validation of these risk factors identified in a different PICU population and development of interventions for prevention of candidemia in critically ill children.

A randomized, controlled trial of the efficacy of a heparin and vancomycin solution in preventing central venous catheter infections in children

OBJECTIVE To determine whether adding vancomycin to central venous catheter (CVC) flush solution would significantly reduce the incidence of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms. STUDY DESIGN Fifty-five children with cancer and eight children given total parenteral nutrition by the surgery or nutrition support services were randomly assigned to receive a heparin CVC flush solution (n = 31) or a heparin-vancomycin CVC flush solution (n = 32). RESULTS During 9158 catheter days, 6.5% of the patients in the heparin group and 15.6% of the patients in the heparin-vancomycin group had bacteremia attributable to luminal colonization with vancomycin-susceptible organisms (p = 0.43). The mean rates of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms were 0.6/1000 catheter days in the heparin group and 1.4/1000 catheter days in the heparin-vancomycin group (p = 0.25). There was no significant difference between the groups when the time to the first episode of bacteremia attributable to luminal colonization with a vancomycin-susceptible organism was compared by means of Kaplan-Meier survival estimates. Streptococcus viridans infection was not attributable to luminal colonization. CONCLUSION The addition of vancomycin to heparin CVC flush solution did not reduce bacteremia with vancomycin-susceptible organisms. Bacteremia with Streptococcus viridans was not related to the use of a CVC.

Media coverage of the measles-mumps-rubella vaccine and autism controversy and its relationship to MMR immunization rates in the United States.

OBJECTIVE. The purpose of this work was to assess the association between media coverage of the MMR-autism controversy and MMR immunization in the United States. METHODS. The public-use files of the National Immunization Survey were used to estimate annual MMR coverage from 1995 to 2004. The primary outcome was selective measles-mumps-rubella nonreceipt, that is, those children who received all childhood immunizations except MMR. Media coverage was measured by using LexisNexis, a comprehensive database of national and local news media. Factors associated with MMR nonreceipt were identified by using a logistic regression model. RESULTS. Selective MMR nonreceipt, occurring in as few as 0.77% of children in the 1995 cohort, rose to 2.1% in the 2000 National Immunization Survey. Children included in the 2000 National Immunization Survey were born when the putative link between MMR and autism surfaced in the medical literature but before any significant media attention occurred. Selective nonreceipt was more prevalent in private practices and unrelated to family characteristics. MMR nonreceipt returned to baseline before sustained media coverage of the MMR-autism story began. CONCLUSIONS. There was a significant increase in selective MMR nonreceipt that was temporally associated with the publication of the original scientific literature, suggesting a link between MMR and autism, which preceded media coverage of the MMR-autism controversy. This finding suggests a limited influence of mainstream media on MMR immunization in the United States.

Effectiveness of Decision Support for Families, Clinicians, or Both on HPV Vaccine Receipt

OBJECTIVE: To improve human papillomavirus (HPV) vaccination rates, we studied the effectiveness of targeting automated decision support to families, clinicians, or both. METHODS: Twenty-two primary care practices were cluster-randomized to receive a 3-part clinician-focused intervention (education, electronic health record-based alerts, and audit and feedback) or none. Overall, 22 486 girls aged 11 to 17 years due for HPV vaccine dose 1, 2, or 3 were randomly assigned within each practice to receive family-focused decision support with educational telephone calls. Randomization established 4 groups: family-focused, clinician-focused, combined, and no intervention. We measured decision support effectiveness by final vaccination rates and time to vaccine receipt, standardized for covariates and limited to those having received the previous dose for HPV #2 and 3. The 1-year study began in May 2010. RESULTS: Final vaccination rates for HPV #1, 2, and 3 were 16%, 65%, and 63% among controls. The combined intervention increased vaccination rates by 9, 8, and 13 percentage points, respectively. The control group achieved 15% vaccination for HPV #1 and 50% vaccination for HPV #2 and 3 after 318, 178, and 215 days. The combined intervention significantly accelerated vaccination by 151, 68, and 93 days. The clinician-focused intervention was more effective than the family-focused intervention for HPV #1, but less effective for HPV #2 and 3. CONCLUSIONS: A clinician-focused intervention was most effective for initiating the HPV vaccination series, whereas a family-focused intervention promoted completion. Decision support directed at both clinicians and families most effectively promotes HPV vaccine series receipt.