Chlamydial and gonococcal testing during pregnancy in the United States.

OBJECTIVE: The objective of the study was to estimate the rates of testing, prevalence, and follow-up testing for chlamydial and gonococcal infection in a nationally based population that is comparable with the US pregnant population in terms of age and race. STUDY DESIGN: We extracted laboratory results for 1,293,423 pregnant women tested over a 3-year period. RESULTS: During pregnancy, 59% (761,315 of 1,293,423) and 57% (730,796 of 1,293,423) of women were tested at least once for Chlamydia trachomatis or for Neisseria gonorrhoeae, respectively. Of those women tested, 3.5% (26,437 of 761,315) and 0.6% (4605 of 730,796) tested positive for chlamydial and gonococcal infection, respectively, at least once during pregnancy. Of those women who were initially positive for the given infection, 78% (16,039 of 20,489) and 76% (2610 of 3435) were retested, of whom 6.0% (969 of 16,039) and 3.8% (100 of 2610) were positive on their last prenatal test for C trachomatis and N gonorrhoeae, respectively. CONCLUSION: Many pregnant women are not tested for C trachomatis and N gonorrhoeae despite recommendations to test. Follow-up testing to monitor the effectiveness of treatment is also not always performed.

North American zoonoses.

A variety of infectious agents can be transmitted from animals to humans, either directly or indirectly. Unfortunately, the diagnosis of a zoonosis may not be considered at presentation, which can lead to a delay in initiating appropriate therapy, or is never made because the symptoms are non-specific and no exposure history is obtained. The keys to making a diagnosis are to recognize the clinical manifestations of the diseases (eg, fever of unknown origin, arthritis, rash, or lymphadenopathy), to obtain an exposure history, and to understand the local epidemiology. When a child presents with an unexplained febrile illness or infectious disease, clinicians should ask about potential exposures to animals, including pets, ingestion of unusual foods, such as raw or unpasteurized milk, and a travel history.

Impact of empiric antibiotic use on development of infections caused by extended-spectrum beta-lactamase bacteria in a neonatal intensive care unit.

BACKGROUND: The neonatal intensive care unit at Miller Children's Hospital changed from empiric use of cefotaxime and vancomycin (CEF) to tobramycin and vancomycin (TOB) for hospital-acquired infections in November 1999 because of an increase in infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria. The objectives of this study were to evaluate the incidence and impact of this change on the development of ESBL infections. METHODS: We retrospectively reviewed medical records of infants who received CEF or TOB between January 1998 and December 2002. A standardized form was used to collect demographic data, information on antibiotic use, and culture results. RESULTS: The mean gestational age and birth weight of the 250 infants were 28.8 +/- 4.0 weeks and 1213.1 +/- 662 g, respectively. There were no differences between infants who received CEF (N = 130) or TOB (N = 120) in terms of gestational age, birth weight, device use, invasive procedures, or prior antibiotic use. There were 11 ESBL infections. Infants in the CEF group were more likely than those in the TOB group to develop ESBL infection (7.8% versus 0.8%, P = 0.008). There were 11 deaths, with none attributed to ESBL infection. In a multivariate analysis, duration of prior ampicillin and gentamicin use and exposure to CEF were associated with ESBL infection [odds ratio (OR): 3.1, 95% confidence interval (CI): 1.28-7.49, P = 0.012; and OR: 33.7; 95% CI: 1.02-1136, P = 0.05, respectively]. CONCLUSIONS: The change from empiric use of CEF to TOB was associated with a significant decrease in the incidence of ESBL infections.

Universal hepatitis A vaccination in the United States: a call for action.

Previous hepatitis A recommendations for the United States targeted vaccination of at-risk individuals and children living in states and communities with consistently elevated rates of hepatitis A. Recommendations now call for routine hepatitis A vaccination of all children in the United States beginning at age 1 year (12-23 months). Currently, vaccination coverage rates for hepatitis A remain below rates of other routine childhood vaccines. Achieving a national immunization rate greater than 90% for the recommended 2 doses of hepatitis A vaccine would lessen disease impact throughout society. Routine childhood immunization against hepatitis A can be a highly effective strategy to reduce infection in children and community transmission of the virus, and the elimination of indigenous transmission of hepatitis A is an attainable goal.

Update on adolescent immunization: pertussis, meningococcus, HPV, and the future.

Since January 2005, new vaccines against pertussis, meningococcal disease, and human papillomavirus (HPV) infection have been licensed. The target recipients are adolescents and preadolescents, who are at higher risk of these infections than other age groups. Routinely scheduled visits for 11- to 12-year-olds will allow for immunization against these and other diseases and give us an opportunity to provide anticipatory guidance against high-risk behaviors.

The safety and immunogenicity of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children: a study of manufacturing consistency and persistence of antibody.

BACKGROUND: This clinical trial was conducted to demonstrate that each of 3 consistency lots of a combined measles, mumps, rubella and varicella vaccine (MMRV) would be well tolerated, induce clinically acceptable and similar immune responses to each antigen and induce immune responses similar to measles, mumps and rubella vaccine (MMR) administered concomitantly with varicella vaccine (V). An additional objective was to evaluate the persistence of antibodies 1 year postvaccination. METHODS: Study participants 12 to 23 months of age received a single injection of either one of 3 consistency lots of MMRV or MMR + V administered at separate injection sites. RESULTS: A total of 3,928 healthy children were enrolled at study sites in the United States and Canada. Immune responses to measles, mumps, rubella and varicella in children immunized with each of 3 lots of MMRV were similar and the combined response to all 3 lots was comparable to that of the control group. The 1-year antibody persistence rates for measles, mumps, rubella and varicella viruses were each greater than 95% and comparable among the recipients of the 3 consistency lots of MMRV and the control group. All vaccines were generally well tolerated during the 42 days after vaccination and the overall incidence of adverse experiences was comparable between recipients of MMRV and MMR + V. Rates of fever (temperature >or=38.9 degrees C oral equivalent or tactile) were greater in recipients of MMRV than in recipients of MMR + V (39.1% versus 33.1%, P = 0.001). Fevers were transient and there was no difference in the incidence of febrile seizures. CONCLUSIONS: MMRV was generally well tolerated and had comparable immunogenicity and overall safety profiles to MMR + V administered concomitantly. Long-term persistence of antibodies after receipt of MMRV is expected based on similar antibody titers against all 4 antigens 1 year postvaccination compared with recipients of MMR and V.

Management of community-associated methicillin-resistant Staphylococcus aureus infections in children.

In recent years, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a pathogen in children without established risk factors, and its prevalence in the United States is increasing. Although many CA-MRSA infections are mild, primarily involving the skin and soft tissues, the organism can cause serious, invasive, and life-threatening infections. To provide a comprehensive review of the epidemiology, clinical features, therapy, and prevention of CA-MRSA infections in children, we performed MEDLINE (1966-January 2006) and Cochrane Library searches, and reviewed abstracts for relevance to S. aureus infections. Only articles pertaining to CA-MRSA infections in pediatrics were closely examined. As a genetically distinct pathogen, CA-MRSA is generally susceptible to multiple non-beta-lactam antimicrobials. The optimal treatment for CA-MRSA infections in pediatric patients has not been well studied. Common antibiotics used include clindamycin, trimethoprim-sulfamethoxazole, vancomycin, and rifampin. Rational empiric antimicrobial therapy for infections caused by S. aureus requires consideration of the possibility of methicillin resistance. The local prevalence and susceptibilities of CA-MRSA, severity of infection, and individual risk factors should be considered in selecting treatment.

Appropriate antibiotic use and why it is important: the challenges of bacterial resistance.

After the introduction of antibiotics in the mid-20th century, clinicians soon witnessed clinical failures secondary to bacterial resistance. Despite scientists' efforts to synthesize more potent antibiotics during the last five decades, bacterial resistance continues to evolve, in large part because of the overuse and misuse of antibiotics. The treatment of several pathogens, including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci, is problematic. New solutions are needed to preserve the activity of our current antibiotic armamentarium, to lower the overall risk of bacterial resistance and to successfully treat patients with resistant bacterial infections. Options include: development of new antibiotics to treat resistant organisms; vaccination to prevent infections; and improved use of antibiotics. Because bacteria will eventually develop means to avoid being killed by antibiotics, judicious use of antibiotics by all clinicians is imperative. Appropriate antibiotic use involves selection of a "targeted spectrum" antibiotic, as well as an appropriate dose and duration.

Fusobacterium osteomyelitis in a child with sickle cell disease.

Children who have sickle cell disease are at increased risk for osteomyelitis caused by Salmonella spp. and Staphylococcus aureus. We report a case of anaerobic osteomyelitis caused by Fusobacterium nucleatum in a child with sickle cell disease. The infection did not resolve with antibiotic therapy alone, but was cured after surgical debridement and hyperbaric oxygen therapy.

Aseptic meningitis in infants younger than six months of age hospitalized with urinary tract infections.

BACKGROUND: Aseptic meningitis associated with urinary tract infection (UTI) in young infants has not been described in detail in the literature. We performed a retrospective study to determine the incidence and clinical features of aseptic meningitis accompanying UTI. METHODS: We retrospectively reviewed the medical records of all infants younger than 6 months of age hospitalized with a UTI at Miller Children's Hospital from March 1995 through March 2000. UTI was defined as a urine culture growing > or =10,000 colony-forming units/ml of a single organism from a catheterized specimen or > or =100,000 colony-forming units/ml of a single organism from a bagged urine specimen. Meningitis was defined as a positive cerebrospinal fluid culture or cerebrospinal fluid with >35 white blood cells/mm3 in infants < or =30 days of age or with >10 white blood cells/mm3 in infants >30 days of age. RESULTS: Of 386 infants with UTI, a lumbar puncture was performed in 260, and 31 (11.9%) had aseptic meningitis. One infant had bacterial meningitis. None of the 26 infants with UTI and bacteremia had aseptic meningitis. Two infants with meningitis had confirmed enteroviral infections, but aseptic meningitis did not occur more frequently in any particular month or during times of peak enteroviral activity. CONCLUSIONS: A cerebrospinal fluid pleocytosis is relatively common in hospitalized infants <6 months of age who have a UTI and usually does not reflect bacterial meningitis. Knowledge of this may prevent unnecessary courses of antibiotics for presumed bacterial meningitis and lead to evaluation for other possible causes of aseptic meningitis including viral or congenital infections.

Kinetics of maternal hepatitis a antibody decay in infants: implications for vaccine use.

We conducted a seroepidemiologic study to evaluate the kinetics of maternal hepatitis A antibody decay in infants. Serum samples obtained from 200 infants at 2 and 4 months of age were tested for hepatitis A antibody. Seventy-six infants (38%) were hepatitis A antibody-positive with a geometric mean antibody titer of 2634 mIU/ml. Samples collected at 4, 6 and/or 12 months of age showed seropositivity rates of 100, 95 and 39%, respectively. These data indicate that maternal antibody levels remained high through the first 6 months of life but decayed significantly by 12 months of age.

Impact of the Yosemite hantavirus outbreak on hantavirus antibody testing at a national reference laboratory.

In conjunction with the 2012 Yosemite hantavirus outbreak, the number of sera our facility tested for hantavirus antibodies increased. We tracked test results and used the data set to determine if a more efficient testing algorithm was possible. Sera were screened using laboratory-developed pan-hantavirus IgG and IgM enzyme immunoassays (EIAs), with an index of >1.10 defined as positive. Sera that were IgM positive by screening (screen IgM(+)) were tested for Sin Nombre virus (SNV)-specific IgM using a laboratory-developed EIA; screen IgM(+) IgG(+) sera were also tested for SNV IgG using a laboratory-developed immunoblot assay. SNV antibody-positive samples were sent to state public health laboratories (PHL) or the CDC for confirmation. Of 3,946 sera tested from July through December 2012, 205 were screen IgM(+) IgG negative (IgG(-)); 7/205 were SNV IgM(+), but only 1/5 sent to PHL/CDC was confirmed as SNV IgM(+). Of 61 screen IgM(+) IgG(+) sera, 16 were SNV antibody positive; 13/16 sera (from 11 patients) went to PHL/CDC, where SNV infection was confirmed for all patients. Of 12 confirmed patients, 7 had been exposed at Yosemite. A modified algorithm defining screen indices of ≥2.00 as positive identified 11/12 confirmed cases while reducing the number of sera requiring SNV-specific antibody testing by 65%; the patient missed was not tested until 3 months after the onset of symptoms. Hantavirus antibody testing at our facility identified 12 SNV-infected patients, including 7 exposed at Yosemite. Some screen IgM(+) IgG(-) SNV IgM(+) results were false positives, emphasizing the value of PHL/CDC confirmatory testing. We identified a modified algorithm requiring analysis of fewer specimens for SNV-specific antibodies without loss of sensitivity.

Age-related differences in patterns of increased Bordetella pertussis antibodies.

During the period 2008 to 2010, we identified 11,386 serum samples with increased (positive) levels of antibodies recognizing Bordetella pertussis antigens. We sought to characterize the distribution of positive antibody result patterns in relation to patient age. IgG and IgA antibodies recognizing pertussis toxin (PT) and filamentous hemagglutinin (FHA) were quantified using a multianalyte immunodetection assay. Four mutually exclusive positive result patterns were observed: increased FHA antibodies only, increased PT IgA but not IgG, increased PT IgG but not IgA, and increased PT IgG and IgA. In patients < 21 years old, the predominant pattern was increased PT IgG but not IgA, whereas in patients ≥ 21 years old, it was increased FHA antibodies only. The proportion of positive serum samples exhibiting increased PT IgA but not IgG was < 20% in all age categories but showed a stepwise rise with age. The proportions of positive serum samples exhibiting increased PT IgG and IgA were similar (26 to 32%) in the age categories spanning 11 to 60 years of age but lower in the < 11- and > 60-year-old groups. In 3 of 5 age categories, a significant rise in the proportion of positive serum samples exhibiting increased FHA antibodies only occurred in 2010. Patterns of positive B. pertussis antibody results varied with age. The predominance of increased FHA antibodies only in patients > 20 years old suggests that many adults thought to have B. pertussis infections actually have other infections that induce FHA-reactive antibodies. Similarly, the 2010 rise in the frequency of increased FHA antibodies only in some age groups suggests an increase in non-B. pertussis infections.

Prevalence and Characteristics of Human Metapneumovirus Infection Among Hospitalized Children at High Risk for Severe Lower Respiratory Tract Infection.

BACKGROUND: Human metapneumovirus (HMPV) is a significant cause of respiratory tract infections. Little is known about HMPV in children who are at high risk for lower respiratory tract infection (LRTI). METHODS: To determine the prevalence of HMPV in high-risk children and to identify HMPV risk factors, children ≤24 months with prematurity, chronic lung disease, and/or congenital cardiac disease who were hospitalized with LRTI were prospectively enrolled. Nasopharyngeal aspirates were tested for HMPV, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza types 1-3. Demographics, medical history, and outcomes for those with HMPV and RSV were compared. A multivariate analysis was performed to determine HMPV risk factors. RESULTS: Over 4 years, 1126 eligible children were enrolled. Pathogens were identified in 61% of subjects. HMPV was identified in 9.0%, second to RSV (45%). Coinfection with HMPV and RSV occurred in <1% of subjects. Subjects infected with HMPV were older (8.2 vs 4.0 months, P < .001), were born more prematurely (27 vs 33 weeks, P < .001), and more commonly had chronic lung disease (59.3% vs 21.8%, P < .001) compared with subjects infected with RSV. In a multivariate analysis that compared children infected with HMPV to all others, increasing age and household exposure to children ages 6-12 were associated with an increased risk, whereas birth at older gestational age and exposure to children age >12 were associated with a decreased risk. CONCLUSIONS: HMPV was detected in 9% of high-risk children who were hospitalized with lower respiratory tract disease, representing the second most common virus in this population. Compared with all other subjects (including RSV-infected), subjects infected with HMPV were older but were born more prematurely.

Dengue virus immunoglobulin M detection in a reference laboratory setting during the 2010 dengue virus outbreak on Caribbean islands.

A large outbreak of dengue virus (DV) infections occurred on Caribbean islands during 2010, with cases peaking during the second half of the year. In conjunction with the outbreak, we observed an unprecedented spike in the number of sera submitted for DV antibody testing between June and December 2010, with a concomitant increase in the number of IgM-positive specimens, indicative of acute DV infection. Analysis of the place of residence of the IgM-positive patients identified from June to December of 2010 revealed that 58.1% were residents of Caribbean islands (Puerto Rico and the U.S. Virgin Islands), whereas 40.6% were residents of the U.S. mainland or Hawaii. The U.S. residents represented 42 states plus the District of Columbia, but most (53%) were from just 3 states (California, Florida, and New York). In comparison to the Caribbean IgM-positive patient group, the U.S. IgM-positive patient group contained proportionately more adults 21 to 60 years old and fewer individuals <21 years old. These findings indicate that the 2010 Caribbean DV outbreak affected many U.S. residents (mostly adults, presumably travelers) from diverse geographic areas and emphasize the potential for a viremic DV-infected returning traveler to spark a local DV outbreak by introducing DV into a community with competent mosquito vectors.

Nephrotoxicity associated with amphotericin B deoxycholate in neonates.

BACKGROUND: The prevalence of nephrotoxicity in neonates receiving amphotericin B deoxycholate (amphoB) is not well-defined. While some studies report a lack of toxicity, others claim a frequency as high as 85%. METHODS: We reviewed medical records of all infants < or = 90 days of age in the neonatal intensive care unit who received at least 3 doses of amphoB between January 1990 and December 2004. A standardized form was used to collect demographic, therapeutic, microbiologic, and laboratory data for each patient. Nephrotoxicity was defined as a rise in serum creatinine (SCr) of at least 0.4 mg/dL any time during amphoB therapy. RESULTS: A total of 92 infants met entry criteria. Median gestational age was 26 (range: 23-41) weeks and median birth weight was 863 (range: 546-4000) grams. Overall, 15 (16%) infants experienced nephrotoxicity, and 16 (17%) developed hypokalemia (<3.0 mmol/L). There were no differences between infants who did or did not develop nephrotoxicity in terms of gestational age, birth weight, gender, underlying medical conditions, or use of other potentially nephrotoxic medications. AmphoB exposure and duration of therapy were similar between infants who developed nephrotoxicity and those who did not, with a mean cumulative dose of 13.5 +/- 9.6 mg/kg and duration of 16.3 +/- 10.4 days. With the exception of 1 infant, the elevated SCr values resolved in all infants by the end of amphoB therapy. CONCLUSION: AmphoB administration does not appear to be associated with lasting measurable nephrotoxicity in neonates. Because of changes in serum creatinine and potassium, renal function and potassium levels should be monitored closely in infants receiving amphoB.

A prospective, multicenter study of caspofungin for the treatment of documented Candida or Aspergillus infections in pediatric patients.

OBJECTIVE: We evaluated the safety, tolerability, and efficacy of caspofungin in pediatric patients with invasive aspergillosis, invasive candidiasis, or esophageal candidiasis. METHODS: This was a multicenter, prospective, open-label study in children 3 months to 17 years of age with proven or probable invasive aspergillosis, proven invasive candidiasis, or proven esophageal candidiasis. All of the patients received caspofungin 70 mg/m(2) on day 1, followed by 50 mg/m(2) per day (maximum: 70 mg/day), as primary or salvage monotherapy. Favorable response was defined as complete resolution of clinical findings and microbiologic (or radiographic/endoscopic) eradication (complete response) or significant improvement in these parameters (partial response). Efficacy was assessed at the end of caspofungin therapy in patients with a confirmed diagnosis who received >/=1 dose of caspofungin. The primary safety evaluation was the proportion of patients with clinical or laboratory drug-related adverse events. RESULTS: Of the 49 patients enrolled, 3 were <2 years of age, 30 were 2 to 11 years of age, and 16 were 12 to 17 years of age. Forty-eight patients had confirmed disease: invasive aspergillosis (10), invasive candidiasis (37), and esophageal candidiasis (1). Eight of 10 patients with invasive aspergillosis had pulmonary involvement; 34 of 37 patients with invasive candidiasis had candidemia. Caspofungin was given for 2 to 87 days. Success at end of therapy was achieved in 5 of 10 patients with invasive aspergillosis, 30 of 37 with invasive candidiasis, and 1 of 1 with esophageal candidiasis. One patient (invasive candidiasis) relapsed during the 28-day follow-up period. Drug-related clinical or laboratory adverse events occurred in 27% and 35% of patients, respectively. There were no serious drug-related adverse events or discontinuations of caspofungin because of toxicity. CONCLUSIONS: Caspofungin was generally well tolerated in pediatric patients aged 6 months through 17 years. Efficacy outcomes in patients with invasive aspergillosis or invasive candidiasis were consistent with previous adult studies in these indications.

Population pharmacokinetics of amphotericin B lipid complex in neonates.

The pharmacokinetics of amphotericin B lipid complex (ABLC) were investigated in neonates with invasive candidiasis enrolled in a phase II multicenter trial. Sparse blood (153 samples; 1 to 9 per patient, 1 to 254 h after the dose) and random urine and cerebrospinal fluid (CSF) samples of 28 neonates (median weight [WT], 1.06 kg; range, 0.48 to 4.9 kg; median gestational age, 27 weeks; range, 24 to 41 weeks) were analyzed. Patients received intravenous ABLC at 2.5 (n = 15) or 5 (n = 13) mg/kg of body weight once a day over 1 or 2 h, respectively, for a median of 21 days (range, 4 to 47 days). Concentrations of amphotericin B were quantified as total drug by high-performance liquid chromatography. Blood data for time after dose (TAD) of <24 h fitted best to a one-compartment model with an additive-error model for residual variability, WT0.75 (where 0.75 is an exponent) as a covariate of clearance (CL), and WT as a covariate of volume of distribution (V). Prior amphotericin B, postnatal age, and gestational age did not further improve the model. The final model equations were CL (liters/h) = 0.399 x WT(0.75) (interindividual variability, 35%) and V (liters) = 10.5 x WT (interindividual variability, 43%). Noncompartmental analysis of pooled data with a TAD of >24 h revealed a terminal half-life of 395 h. Mean concentrations in the urine after 1, 2, and 3 weeks ranged from 0.082 to 0.430 microg/ml, and those in CSF ranged from undetectable to 0.074 microg/ml. The disposition of ABLC in neonates was similar to that observed in other age groups: weight was the only factor that influenced clearance. Based on these results and previously published safety and efficacy data, we recommend a daily dosage between 2.5 and 5.0 mg/kg for treatment of invasive Candida infections in neonates.