Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection.

BACKGROUND: Viral loads (VLs) frequently are followed during treatment of symptomatic congenital cytomegalovirus disease, but their predictive value is unclear. METHODS: Post hoc analysis of 2 antiviral studies was performed. Seventy-three subjects were treated for 6 weeks and 47 subjects were treated for 6 months. Whole blood VL was determined by real-time polymerase chain reaction before and during therapy. RESULTS: Higher baseline VL was associated with central nervous system involvement (3.82 log, range 1-5.65 vs 3.32 log, range 1-5.36; P = .001), thrombocytopenia (3.68 log, range 1-5.65 vs 3.43 log, range 1-5.36; P = .03), and transaminitis at presentation (3.73 log, range 1-5.60 vs 3.39 log, range 1-5.65; P = .009), but with overlap in the amount of virus detected between groups. In subjects treated for 6 months, lower VL at presentation correlated with better hearing outcomes at 12 months, but VL breakpoints predictive of hearing loss were not identified. Sustained viral suppression during 6 months of therapy correlated with better hearing outcomes at 6, 12, and 24 months (P = .01, P = .0007, P = .04), but a majority without viral suppression still had improved hearing. CONCLUSIONS: In infants with symptomatic congenital cytomegalovirus disease, higher whole blood VL before initiation of antiviral therapy has no clinically meaningful predictive value for long-term outcomes.

Bioavailability testing of a newly developed clindamycin oral suspension in a pediatric porcine model.

Background: Clindamycin's bitter taste and odor is known to affect treatment adherence in children. Recently, a formulation of clindamycin HCl complexed with ion exchange resin IRP 69 was shown to mask the bitter taste. Because of the potential benefit of this formulation for children, a pilot study using a porcine model was conducted to evaluate its relative bioavailability. Methods: A randomized two-way crossover study design using six (n = 6) healthy male piglets 10-12 kg was used to evaluate the absorption profiles and pharmacokinetic parameters of clindamycin from the resinate complex formulation (Test) compared to a commercialized reference suspension. A dose of 15 mg/kg was administered orally by gastric gavage to each piglet followed by repeated blood sampling over 12 h. A wash-out period of 48 h occurred between treatments. Plasma concentration vs. time data was analyzed by non-compartmental analysis. Results: The mean relative bioavailability of clindamycin from the resinate formulation was 78.8%. A two-tailed, paired Student t test yielded a p < 0.05 for AUC∞ and Tmax parameters. A two one-sided test (TOST) suggested a difference in AUC∞ and Cmax for the Test formulation compared to the reference formulation according to the FDA's criteria for bioequivalence. Conclusion: The bioavailability of clindamycin from this novel oral formulation supports continued evaluation of the drug in humans for potential pediatric applications.

Valganciclovir for symptomatic congenital cytomegalovirus disease.

BACKGROUND: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS: We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS: A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64). CONCLUSIONS: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

Oral acyclovir suppression and neurodevelopment after neonatal herpes.

BACKGROUND: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS: A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09). CONCLUSIONS: Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Pharmacokinetics and safety of extemporaneously compounded valacyclovir oral suspension in pediatric patients from 1 month through 11 years of age.

BACKGROUND: Valacyclovir provides enhanced acyclovir bioavailability in adults, but limited data are available in children. METHODS: Children 1 month through 5 years of age with or at risk for herpesvirus infection received a single 25 mg/kg dose of extemporaneously compounded valacyclovir oral suspension (n = 57), whereas children 1 through 11 years of age received 10 mg/kg valacyclovir oral suspension twice daily for 3-5 days (herpes simplex virus infection) (n = 28) or 20 mg/kg 3 times daily for 5 days (varicella-zoster virus infection) (n = 27). Blood samples for pharmacokinetic analysis were collected during the 6 h after the first dose. Safety was monitored throughout the studies. RESULTS: Dose proportionality in the maximum observed concentration (C(max)) of acyclovir and the area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) existed across the 10 to 20 mg/kg valacyclovir dose range. For children 2 through 5 years of age, an increase in dose from 20 to 25 mg/kg resulted in near doubling of the C(max) and AUC(0-infinity). Among infants 1 through 2 months of age receiving 25 mg/kg, the mean AUC(0-infinity) and C(max) were higher ( approximately 60% and 30%, respectively) than those among older infants and children receiving the same dose. Valacyclovir oral suspension was well tolerated. No clinically significant trends were noted in clinical chemical, hematologic, or urinalysis values from screening to follow-up. CONCLUSIONS: Among children 3 months through 11 years of age, the 20 mg/kg dose of this formulation of valacyclovir oral suspension produces favorable acyclovir blood concentrations and is well tolerated. A dosing recommendation cannot be made for infants <3 months of age because of decreased clearance in this age group. Trial registration. ClinicalTrials.gov identifier: NCT00297206 .

Single-dose pharmacokinetics of daptomycin in children with suspected or proved gram-positive infections.

BACKGROUND: New antimicrobials such as daptomycin fill a void in the growing need for antibiotics effective against resistant Gram-positive pathogens. Although the pharmacokinetics of daptomycin have been well characterized in adults, no studies have evaluated the pharmacokinetics and tolerability in a pediatric population. METHODS: Twenty-five children (12-17 years, n = 8; 7-11 years, n = 8; 2-6 years, n = 9) were enrolled in this multicenter, open-label study. Daptomycin was administered as a single 4-mg/kg intravenous dose followed by repeated blood sampling for 24 hours. Daptomycin was quantitated from plasma using a validated high performance liquid chromatography method and pharmacokinetic variables determined using a model-dependent approach. RESULTS: Daptomycin systemic exposure decreased with decreasing age, reflecting more rapid rates of clearance in younger children. Total body exposure estimates in adolescents were approximately 1.7x those observed in children <6 years of age (374.4 versus 215.3 microg*h/L), they were comparable to those observed in adult historic controls. Estimates of apparent elimination half-life averaged 6.7 hours in adolescents, 5.6 hours in children 7-11 years of age, and 5.3 hours in children <6 years of age. One child had an adverse event (infusion site reaction) considered to be related to study drug. CONCLUSIONS: Systemic drug exposure after a single weight-adjusted daptomycin dose is reduced in younger children compared with adolescents and adults consequent to an apparent age-associated change in total plasma clearance.

An Adaptable Pediatrics Faculty Mentoring Model.

An effective faculty mentoring program (FMP) is 1 approach that academic departments can use to promote professional fulfillment, faculty retention, and mitigate the risks of faculty burnout. Mentoring has both direct benefits for junior faculty mentees as they navigate the academic promotion process with their mentors, in addition to broader departmental and institutional benefits, with regard to recruitment, retention, and academic productivity. We describe a successful FMP model that has been adapted for use in 6 other pediatrics departments, summarizing the key personnel, mentoring process, and program evaluation methods. Important lessons learned and a generalizable mentoring "model" are provided. Program evaluation indicates a positive effect for the FMP on enhanced faculty self-efficacy, job satisfaction, and career development. The importance of communication, oversight, feedback, accountability, and valuing all faculty members is emphasized. Strategies to promote faculty engagement and the critical role of departmental leadership in prioritizing mentorship are discussed. The success of academic medical departments is inextricably linked to its commitment to the career development of individual faculty members at all levels and in all academic pathways. With our findings, we support the positive impact of a formal FMP in promoting enhanced self-efficacy and career satisfaction, which directly benefits the department and institution through enhanced productivity, retention, successful promotion, and overall professional fulfillment.

Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children.

OBJECTIVES: To describe the clinical characteristics and course of children with laboratory-diagnosed Rocky Mountain spotted fever (RMSF) and to identify clinical findings independently associated with adverse outcomes of death or discharge with neurologic deficits. STUDY DESIGN: Retrospective chart review of 92 patients at six institutions in the southeastern and southcentral United States from 1990 to 2002. Statistical analyses used descriptive statistics and multiple logistic regression. RESULTS: Children with RMSF presented to study institutions after a median of 6 days of symptoms, which most commonly included fever (98%), rash (97%), nausea and/or vomiting (73%), and headache (61%); no other symptom or sign was present in >50% of children. Only 49% reported antecedent tick bites. Platelet counts were <150,000/mm3 in 59% of children, and serum sodium concentrations were <135 mEq/dL in 52%. Although 86% sought medical care before admission, only 4 patients received anti-rickettsial therapy during this time. Three patients died, and 13 survivors had neurologic deficits at discharge. Coma and need for inotropic support and intravenous fluid boluses were independently associated with adverse outcomes. CONCLUSIONS: Children with RMSF generally present with fever and rash. Delays in diagnosis and initiation of appropriate therapy are unacceptably common. Prognosis is guarded in those with hemodynamic instability or neurologic compromise at initiation of therapy.

Human monocytic ehrlichiosis in children.

BACKGROUND: Human monocytic ehrlichiosis (HME) is a tick-borne illness caused by Ehrlichia chaffeensis. Data about disease in children have been largely derived from case reports or small case series. METHODS: A retrospective review of all medical and laboratory records from 6 sites located in the "tick belt" of the Southeastern United States was carried out. Demographic, history and laboratory data were abstracted from the identified medical records of patients. Bivariate statistical comparisons were performed using Fisher exact test or Wilcoxon rank sum tests. RESULTS: Common clinical signs and symptoms of patients with HME (n = 32) included fever (100%), headache (69%), myalgia (69%), rash (66%), nausea/vomiting (56%), altered mental status (50%) and lymphadenopathy (47%). Only 48% had a complaint of fever, headache and rash. Common laboratory abnormalities included thrombocytopenia (94%), elevated aspartate aminotransferase (90%), elevated alanine aminotransferase (74%), hypoalbuminemia (65%), lymphopenia (57%), leukopenia (56%) and hyponatremia (55%). The median number of days of illness before the initiation of antirickettsial therapy was 6. Patients who received sulfonamides before starting doxycycline therapy developed a rash, were admitted to the hospital, and started doxycycline at a later date. Twenty-two percent of patients were admitted to the intensive care unit with 12.5% of patients requiring ventilatory and blood pressure support. CONCLUSIONS: Although HME has been recognized among children for almost 20 years, there is only a limited knowledge about its clinical course. Even among physicians practicing in endemic regions, few cases are diagnosed each year. More work is needed to understand the true burden of disease and the natural history among asymptomatically and symptomatically infected children.

Impact of addition of philosophical exemptions on childhood immunization rates.

BACKGROUND: Although incidence of vaccine-preventable diseases has decreased, states' school immunization requirements are increasingly challenged. Subsequent to a federal court ruling affecting religious immunization exemptions to school requirements, new legislation made philosophical immunization exemptions available in Arkansas in 2003-2004. This retrospective study conducted in 2006 describes the impact of philosophical exemption legislation in Arkansas. METHODS: Arkansas Division of Health data on immunization exemptions granted were linked to Department of Education data for all school attendees (grades K through 12) during 2 school years before the legislation (2001-2002 and 2002-2003 [Years 1 and 2, respectively]) and 2 years after philosophical exemptions were available (2003-2004 and 2004-2005 [Years 3 and 4, respectively]). Changes in numbers, types, and geographic distribution of exemptions granted are described. RESULTS: The total number of exemptions granted increased by 23% (529 to 651) from Year 1 to 2; by 17% (total 764) from Year 2 to 3 after philosophical exemptions were allowed; and by another 50% from Year 3 to 4 (total 1145). Nonmedical exemptions accounted for 79% of exemptions granted in Years 1 and 2, 92% in Year 3, and 95% in Year 4. Importantly, nonmedical exemptions clustered geographically, suggesting concentrated risks for vaccine-preventable diseases in Arkansas communities. CONCLUSIONS: Legislation allowing philosophical exemptions from school immunization requirements was linked to increased numbers of parents claiming nonmedical exemptions, potentially causing an increase in risk for vaccine-preventable diseases. Continued education and dialogue are needed to explore the balance between individual rights and the public's health.

Variation in Tularemia Clinical Manifestations-Arkansas, 2009-2013.

BACKGROUND: Francisella tularensis, although naturally occurring in Arkansas, is also a Tier 1 select agent and potential bioterrorism threat. As such, tularemia is nationally notifiable and mandatorily reported to the Arkansas Department of Health. We examined demographic and clinical characteristics among reported cases and outcomes to improve understanding of the epidemiology of tularemia in Arkansas. METHODS: Surveillance records on all tularemia cases investigated during 2009-2013 were reviewed. RESULTS: The analytic dataset was assembled from 284 tularemia reports, yielding 138 probable and confirmed tularemia cases during 2009-2013. Arthropod bite was identified in 77% of cases. Of 7 recognized tularemia manifestations, the typhoidal form was reported in 47% of cases, approximately double the proportion of the more classic manifestation, lymphadenopathy. Overall, 41% of patients were hospitalized; 3% died. The typhoidal form appeared to be more severe, accounting for the majority of sepsis and meningitis cases, hospitalizations, and deaths. Among patients with available antibiotic data, 88% received doxycycline and 12% received gentamicin. CONCLUSIONS: Contrary to expectation, lymphadenopathy was not the most common manifestation observed in our registry. Instead, our patients were more likely to report only generalized typhoidal symptoms. Using lymphadenopathy as a primary symptom to initiate tularemia testing may be an insensitive diagnostic strategy and result in unrecognized cases. In endemic areas such as Arkansas, suspicion of tularemia should be high, especially during tick season. Outreach to clinicians describing the full range of presenting symptoms may help address misperceptions about tularemia.

Pharmacokinetics of rifapentine in children.

BACKGROUND: Rifapentine is a rifamycin antibiotic approved for the treatment of pulmonary infections caused by Mycobacterium tuberculosis. Although the pharmacokinetics of rifapentine has been investigated in adolescents and adults, no studies have assessed the pharmacokinetics of this drug in children or infants. METHODS: Twenty-four children (7.1 +/- 3.3 years; mean +/- 1 SD, 27.9 +/- 11.9 kg) were enrolled in this open label study. Children received a single oral dose (10 to <30 kg body weight received 150 mg; 30 to <60 kg body weight received 300 mg), followed by repeated blood sampling (n = 11) for 32 hours. Rifapentine and 25-desacetyl rifapentine were quantitated by a validated high-pressure liquid chromatography method. Pharmacokinetic parameters were determined using a model-independent approach. RESULTS: A significant difference in dose-normalized area under the curves (AUC0-n and AUC0-infinity) was observed between children receiving the 150 and 300 mg doses, which was accounted for by differences in age between the dosing arms. In separate analyses, including data from adults, further age-dependence in total body exposure (reflected by AUC) and elimination was observed. Adverse events associated with rifapentine were mild and included gastric distress (n = 1) and vomiting (n = 2). CONCLUSIONS: Given a comparable weight-normalized dose, rifapentine exposure estimates are lower in children than those reported in adults, suggesting that a larger weight-normalized (ie, mg/kg) dose of rifapentine is needed in children.

Association of Medical School Pediatric Department Chairs Principles of Lifelong Learning in Pediatric Medicine.

Pediatric general and subspecialty care requires continuous effort to maintain knowledge and competencies in clinical practice. Equally important are efforts by investigators and educators to maintain knowledge and competencies in the conduct of research and training. The Association of Medical School Pediatric Department Chairs initiated a survey in July 2015 to define principles of lifelong learning in pediatric medicine and determine the approaches and strategies used by chairs to assess knowledge and competence across the care, research, and teaching missions. A total of 101 of 142 chairs (71%) completed the survey. Six of 7 proposed principles were endorsed by 84% to 96% of Association of Medical School Pediatric Department Chairs members. The focus areas included individual accountability, individually relevant activities, use of evidence-based guidelines/national standards, gaining cognitive expertise, learning as a continuous effort, affordability, and focus on individual understanding. The chairs endorsed a requirement for evidence of lifelong learning, competence, and compliance by all faculty members in clinical (n = 89 [88%]), research (n = 63 [62%]), and educational (n = 85 [84%]) practice. The survey identified the strategies to assess lifelong learning and faculty competence and compliance in clinical, research, and educational roles. Across missions, chairs endorsed an expectation for individual responsibility supplemented by formal evaluation practices and institutional and regulatory office oversight. While chairs endorsed an important role for the American Board of Pediatrics in assessing and verifying lifelong learning, knowledge, and competence in general and specialty certification, most (n = 91 [90%]) endorsed a need to revise current board requirements to better emphasize closing gaps in knowledge and using approaches that are evidence-based. This study provides the perspectives of pediatric department chairs on principles for lifelong learning and strategies and approaches used to assess faculty competence and commitment to lifelong learning across missions.

A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis.

BACKGROUND: Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. METHODS: Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. RESULTS: Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)-positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. CONCLUSIONS: Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation.

Pharmacokinetics of intravenously administered azithromycin in pediatric patients.

BACKGROUND: The objective of this study was to characterize the pharmacokinetics and tolerance of a single intravenous (IV) azithromycin dose in children. METHODS: Subjects were stratified into 4 age groups: 0.5-2 years; >2-<6 years; 6-<12 years; and 12-<16 years. Each subject received a single 10 mg/kg dose (500 mg maximum) infused in 1 hour. Serial venous blood samples were obtained for a 168-hour period, and laboratory safety evaluations were performed immediately preceding azithromycin administration and at the conclusion of the study. Serum azithromycin concentrations were quantified with a validated high performance liquid chromatography method with mass spectrometric detection. Pharmacokinetic indices were calculated for each subject by noncompartmental techniques. RESULTS: Thirty-two subjects (6.7 +/- 5.0 years, 11 boys) participated. Mean serum concentration-time data were comparable for the 4 age groups. For all subjects with evaluable data, the mean area under the curve from 0 to 72 hours (AUC0-72) was 8.2 microg . h/mL (n = 26), the maximum concentration (Cmax) was 2.4 microg/mL and the elimination half-life (t1/2) was 65.2 hours (n = 25). The AUC0-72 and Cmax were not associated with age. The dose was well-tolerated with no serious adverse events. CONCLUSION: The disposition of azithromycin after a single 10-mg/kg IV dose (maximum labeled adult dose of 500 mg) is comparable in pediatric patients between 0.5 and 16 years of age. These pharmacokinetic data can be used to guide dose selection for future therapeutic trials of IV azithromycin in pediatric patients.

Intravenous voriconazole therapy in a preterm infant.

A preterm infant younger than 3 months developed a disseminated fluconazole-resistant Candida albicans infection that was treated with liposomal amphotericin B for 52 days, followed by the combination of intravenous voriconazole and liposomal amphotericin B for an additional 19 days. The infant received concomitant phenobarbital throughout the hospital stay. The infection resolved after addition of voriconazole to the treatment regimen. Intravenous voriconazole was begun at a high dosage, 6 mg/kg every 12 hours, for anticipated developmental and drug-induced changes in volume of distribution and clearance. On day 4 of therapy, serum concentrations of voriconazole were 3.27 microg/ml immediately after infusion and 0.33 microg/ml 6 hours after infusion. These levels were significantly lower than those achieved in adult pharmacokinetic and safety studies. After the infant's dosage was increased to 6 mg/kg every 8 hours, serum concentrations were 5.33 microg/ml 30 minutes after infusion and 2.67 microg/ml 6 hours after infusion. These levels were similar to those observed in adults. Intravenous voriconazole 6 mg/kg every 8 hours was administered safely, with concomitant phenobarbital therapy, in this preterm infant with developmentally diminished renal function.

Use of DNA fingerprinting in decision making for considering closure of neonatal intensive care units because of Pseudomonas aeruginosa bloodstream infections.

BACKGROUND: Bloodstream infections with Pseudomonas aeruginosa have been well-described in neonatal intensive care units (NICU) and have resulted in the temporary closure of some nurseries to new admissions. Nosocomial transmission of these infections has been verified by fingerprint analysis of the isolates. We utilized molecular fingerprinting to identify the source of bloodstream infections in an NICU and used this information to apply infection control measures that allowed the nursery to stay open and continue to accept referrals. METHODS: In June 1998 three premature infants transferred to our hospital (Hospital A) from Hospitals B and C had bloodstream infections with P. aeruginosa. Subsequently one additional neonate transferred from Hospital B was colonized with P. aeruginosa. Random amplification of polymorphic deoxyribonucleic acid (RAPD) was performed on the four isolates. All transfers from Hospital B were cultured, and surveillance programs were instituted in Hospitals A and B. Targeted infection control measures for all transfers were implemented. RESULTS: The four isolates were the same clone by RAPD. Investigation of the environment in Hospital A did not identify any source of the organism. Surveillance cultures on 49 neonates at Hospital A revealed only one patient colonized at an endotracheal tube. This patient was also a transfer from Hospital B. Results from Hospital B identified 4 of 40 (10%) neonates colonized. All isolates were clones identical with the bloodstream isolates from the neonates with bloodstream infections. Infection control measures for all babies transferred from Hospital B resulted in no new cases of P. aeruginosa bacteremia during the next 5 years. CONCLUSIONS: The use of molecular fingerprinting of isolates of P. aeruginosa allowed for a prompt and directed infection control plan to be implemented in Hospitals A and B. It also allowed the NICU in Hospital A to continue to accept referrals from other hospitals and to implement a targeted infection control plan for patients transferred from Hospital B.

Antibodies reactive to Rickettsia rickettsii among children living in the southeast and south central regions of the United States.

BACKGROUND: The reported annual incidence of Rocky Mountain spotted fever in the United States is 2.2 per million, but studies have suggested that human infection with Rickettsia rickettsii may be more common. This study estimated the prevalence of antibodies reactive to R rickettsii among children living in the southeastern and south central United States. STUDY DESIGN: Approximately 300 specimens were obtained from children at each of 7 pediatric referral centers (N = 1999). Serum was tested for R rickettsii antibodies by means of indirect immunofluorescence antibody assay. Three different cutoff titers (>or=64, >or=128, and >or=256) represented increasing levels of stringency to define positive specimens. RESULTS: Overall, 12.0% of children had R rickettsii antibody titers of at least 64; 7.3%, at least 128; and 4.3%, at least 256. Strong relationships were seen between increasing age and seroprevalence at each cutoff titer. Remarkably, 6.4% of children aged 13 to 17 years had titers of at least 256. Age-adjusted seroprevalence rates at titers of at least 64 varied from 21.9% in Little Rock, Ark, to 3.5% in Louisville, Ky. At titers of at least 256, seroprevalence ranged from 7.7% in Nashville, Tenn, to 1.8% in Winston-Salem, NC. Only site and age group were strong predictors of seropositivity; a weak association was seen with nonurban residence. CONCLUSIONS: To our knowledge, this is the largest serosurvey of rickettsial infection in children in the United States. Within the limitations of the immunofluorescence antibody assay, these data suggest that infections with R rickettsii or antigenically related spotted-fever group rickettsiae may be common and subclinical. The results also have implications for the interpretation of single immunofluorescence antibody assay titers in children with suspected Rocky Mountain spotted fever.