Charles R. Woods

Lactobacillus Sepsis Associated With Probiotic Therapy

Probiotic strains of lactobacilli are increasingly being used in clinical practice because of their many health benefits. Infections associated with probiotic strains of lactobacilli are extremely rare. We describe 2 patients who received probiotic lactobacilli and subsequently developed bacteremia and sepsis attributable to Lactobacillus species. Molecular DNA fingerprinting analysis showed that the Lactobacillus strain isolated from blood samples was indistinguishable from the probiotic strain ingested by the patients. This report indicates, for the first time, that invasive disease can be associated with probiotic lactobacilli. This report should not discourage the appropriate use of Lactobacillus or other probiotic agents but should serve as a reminder that these agents can cause invasive disease in certain populations.

Microbial DNA Typing by Automated Repetitive-Sequence-Based PCR

ABSTRACT Repetitive sequence-based PCR (rep-PCR) has been recognized as an effective method for bacterial strain typing. Recently, rep-PCR has been commercially adapted to an automated format known as the DiversiLab system to provide a reliable PCR-based typing system for clinical laboratories. We describe the adaptations made to automate rep-PCR and explore the performance and reproducibility of the system as a molecular genotyping tool for bacterial strain typing. The modifications for automation included changes in rep-PCR chemistry and thermal cycling parameters, incorporation of microfluidics-based DNA amplicon fractionation and detection, and Internet-based computer-assisted analysis, reporting, and data storage. The performance and reproducibility of the automated rep-PCR were examined by performing DNA typing and replicate testing with multiple laboratories, personnel, instruments, DNA template concentrations, and culture conditions prior to DNA isolation. Finally, we demonstrated the use of automated rep-PCR for clinical laboratory applications by using isolates from an outbreak of Neisseria meningitidis infections. N. meningitidis outbreak-related strains were distinguished from other isolates. The DiversiLab system is a highly integrated, convenient, and rapid testing platform that may allow clinical laboratories to realize the potential of microbial DNA typing.

Anogenital and respiratory tract human papillomavirus infections among children: age, gender, and potential transmission through sexual abuse.

Objectives. To evaluate human papillomavirus (HPV) presentation among children <13 years of age and its association with suspected child sexual abuse (CSA), and to assess sexual abuse consideration among different clinical services treating these children. Methods. Records of children <13 years of age from 1985 to 2003 were selected for review if the children had a HPV-related International Classification of Diseases, Ninth Revision, code or had been examined in the CSA clinic. Abstracted data included demographic features, clinical findings, clinical services involved, age at diagnosis, age when care was first sought, and age when symptoms were first noted. Results. HPV was identified by clinical examination and/or biopsy for 124 children, 40 with laryngeal lesions, 67 with anogenital lesions, 10 with oral lesions, and 7 with both anogenital and oral lesions. The mean age at HPV diagnosis was 4.0 ± 2.9 years, compared with 6.4 ± 3.0 years for 1565 HPV-negative children. Among 108 HPV cases with data for age when symptoms were first noted, the mean age was 3.3 ± 2.9 years (median: 2.2 years) for children with anogenital and oral HPV and 2.4 ± 2.3 years (median: 1.9 years) for children with laryngeal HPV. Among HPV-positive patients, 56% were female, compared with 82% of HPV-negative children. Fifty-five (73%) of 75 children with anogenital HPV infections were referred to the CSA clinic for evaluation, compared with none of 49 children with laryngeal or oral HPV infections treated by the otolaryngology service. Laryngeal cases presented earlier than anogenital and oral lesions. Abuse was considered at least possible for 17 of 55 children with any CSA evaluation. The mean age of likely abused, HPV-positive children was 6.5 ± 3.8 years (median: 5.3 years), compared with 3.6 ± 2.3 years (median: 2.6 years) for likely not abused, HPV-positive children. The likelihood of possible abuse as a source of HPV infection increased with age. The positive predictive value of HPV for possible sexual abuse was 36% (95% confidence interval: 13–65%) for children 4 to 8 years of age and 70% (95% confidence interval: 35–93%) for children >8 years of age. Conclusions. The data from this epidemiologic study of HPV suggest that many anogenital and laryngeal HPV infections among preadolescent children are a result of nonsexual horizontal transmission, acquired either perinatally or postnatally. It seems that many children >2 years of age acquire HPV infection from nonsexual contact. Different subspecialties vary greatly in their suspicion and evaluation of CSA. At this time, there remains no clear age below which sexual abuse is never a concern for children with anogenital HPV infections. Every case needs a medical evaluation to determine whether enough concern for abuse exists to pursue additional investigations.

Orbital cellulitis in children.

Background: To review the epidemiology and management of orbital cellulitis in children. Methods: The medical records of children ≤18 years old and hospitalized from June 1, 1992, through May 31, 2002, at the Brenner Childrens Hospital, with a discharge ICD-9 code indicating a diagnosis of orbital cellulitis and confirmed by computed tomography scan were reviewed. A literature search for additional studies for systematic review was also conducted. Results: Forty-one children with orbital cellulitis were identified. The mean age was 7.5 years (range, 10 months to 16 years), and 30 (73%) were male (male:female ratio = 2.7). All cases of orbital cellulitis were associated with sinusitis; ethmoid sinusitis was present in 40 (98%) patients. Proptosis and/or ophthalmoplegia was documented in 30 (73%), and 34 (83%) had subperiosteal and/or orbital abscesses. Twenty-nine (71%) had surgical drainage and 12 (29%) received antibiotic therapy only. The mean duration of hospitalization was 5.8 days. The mean duration of antibiotic therapy was 21 days. Conclusions: Orbital cellulitis occurs throughout childhood and in similar frequency among younger and older children. It is twice as common among males as females. Selected cases of orbital cellulitis, including many with subperiosteal abscess, can be treated successfully without surgical drainage.

Use of combination vaccines is associated with improved coverage rates.

Background: The number of shots represented by the routine childhood immunization schedule poses a logistical challenge for providers and a potential deterrent for parents. By reducing the number of injections, use of combination vaccines could lead to fewer deferred doses and improved coverage rates. Objective: To determine the effect of combination vaccines on coverage rates. Methods: This was a retrospective study of administrative claims data from the Georgia Department of Community Health Medicaid program conducted from January through September of 2003. Coverage rates were compared between children who received at least 1 dose of HepB/Hib (COMVAX) or DTaP/HepB/IPV (PEDIARIX) (the combination cohort) and children who received no doses of either combination (the reference cohort). Infants with fewer than 4 vaccination visits were excluded from the analysis. Multivariate logistic regression was performed on the whole study population to assess the effect of combination vaccines while controlling for potential confounders. Hepatitis B and pneumococcal conjugate vaccine coverage rates were not included as outcomes. Results: The study population consisted of 18,821 infants, 16,007 in the combination cohort and 2814 in the reference cohort. Unadjusted coverage rates for DTaP, IPV and the 4 DTaP:3 IPV:1 MMR, 4 DTaP: 3 IPV: 1 MMR: 3 Hib: 1 varicella, and 3 DTaP:3 IPV: 3 Hib series were higher in the combination cohort. Receipt of at least 1 dose of a combination vaccine was independently associated with increased coverage for each of these vaccines and vaccine series when controlling for gender, birth quarter, race, rural versus urban residence and historical provider immunization quality. Conclusions: Use of combination vaccines in this Medicaid population was associated with improved coverage rates. Additional studies are warranted, including those examining private sector populations and outcomes such as timeliness and cost.

Multicenter surveillance of invasive meningococcal infections in children

OBJECTIVES. Meningococcal disease continues to result in substantial morbidity and mortality in children, but there is limited recent surveillance information regarding serogroup distribution and outcome in children in the United States. The objective of this study was to collect demographic, clinical, laboratory, and outcome information for infants and children who had Neisseria meningitidis infections of various serogroups and were cared for in 10 pediatric hospitals. METHODS. Investigators at each of the participating hospitals identified children with meningococcal infections and collected demographic and clinical information using a standard data form. Meningococcal isolates were sent to a central laboratory for serogrouping by slide agglutination and penicillin susceptibility. RESULTS. From January 1, 2001, through March 15, 2005, 159 episodes of systemic meningococcal infections were detected. The greatest numbers of children were younger than 12 months (n = 41) or were 12 to 24 months of age (n = 22). Meningitis was the most common clinical manifestation of disease accounting for 112 (70%) cases; 43 (27%) children had bacteremia only. Children who were younger than 5 years (17 of 102) were significantly less likely to require mechanical ventilation than children who were 5 to 10 years of age (12 of 24) or children who were older than 10 years (13 of 33). Overall, 55 (44%) isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but 1 isolate (intermediate) were susceptible to penicillin. The overall mortality rate was 8% (13 of 159) but was greater for children who were ≥11 years of age (7 [21.2%] of 33) than for children who were younger than 11 years (6 [4.8%] of 126). Unilateral or bilateral hearing loss occurred in 14 (12.5%) of 112 children with meningitis. CONCLUSIONS. The morbidity and the mortality of meningococcal infections are substantial. With the recent licensure of meningococcal conjugate vaccines, our baseline trends in meningococcal disease can be compared with those seen after widespread vaccination to assess the success of routine immunization.

Susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, including serotype 19A, and Moraxella catarrhalis paediatric isolates from 2005 to 2007 to commonly used antibiotics

OBJECTIVES The aim of this study was to evaluate susceptibility to common paediatric antibiotics for Streptococcus pneumoniae, non-typeable Haemophilus influenzae and Moraxella catarrhalis isolated from 2005 through 2007. METHODS Microdilution MIC assays were performed using CLSI-approved methods. S. pneumoniae 19A strains were identified by quellung reaction. RESULTS Among 143 non-typeable H. influenzae, 42% produced beta-lactamase. By 2007 breakpoints (PK/PD:CLSI), percentage susceptibility for non-typeable H. influenzae was: ceftriaxone = cefixime = high-dose amoxicillin/clavulanate (all 100%:100%) > standard-dose amoxicillin/clavulanate (91.6%:100%) > cefuroxime axetil (88.1%:99.3%) > cefdinir (83.9%:100%) > trimethoprim/sulfamethoxazole (73.4%:73.4%) >high-dose amoxicillin (58%:58%) > standard-dose amoxicillin (55.2%:58%) > cefprozil (28.7%:83.2%) > cefaclor (3.5%:83.2%) > azithromycin (0%:87.4%). Of 208 S. pneumoniae (42 serotype 19A), 86 were penicillin-susceptible, 60 were penicillin-intermediate and 62 were penicillin-resistant by 2007 CLSI breakpoints. Percentage susceptibility for all S. pneumoniae/19A by PD breakpoints was: ceftriaxone (95.2%/86.1%) > high-dose amoxicillin (89.4%/58.3%) > clindamycin (85%/58.3%) > standard-dose amoxicillin (73.5%/33.3%) > cefuroxime axetil (69.2%/36.1%), cefprozil (67.3%/33.3%) > cefdinir (59.1%/33.3%) > cefixime (57.7%/33.3%) > azithromycin (56.7%/33.3%) > trimethoprim/sulfamethoxazole (50.5%/25%) > penicillin (41.3%/19.4%) > cefaclor (28.8%/8.3%). Percentage M. catarrhalis (n = 62) susceptibility by PK/PD breakpoints was: high-dose amoxicillin/clavulanate = cefixime (100%) > azithromycin (98.4%) > ceftriaxone (96.8%) > standard-dose amoxicillin/clavulanate (88.7%) > cefdinir (80.6%) > cefprozil = cefuroxime axetil (37.1%) > high-dose amoxicillin (11.2%) > cefaclor (6.5%) > standard-dose amoxicillin (4.8%). CONCLUSIONS Despite high rates of beta-lactamase production among non-typeable H. influenzae and M. catarrhalis, multiple oral treatment options exist for non-typeable H. influenzae and M. catarrhalis. Multidrug-resistant serotype 19A S. pneumoniae ( approximately 20%) limits treatment options for ambulatory S. pneumoniae respiratory disease.

Trends in Human Immunodeficiency Virus (HIV) Counseling, Testing, and Antiretroviral Treatment of HIV-Infected Women and Perinatal Transmission in North Carolina

Since 1993, trends in perinatal human immunodeficiency virus (HIV) transmission have been monitored by use of chart review of patients identified at a central diagnostic laboratory. In the population studied, either pre- or postnatal antiretroviral therapy to the infant increased from 21% in 1993 to 95% in 1997. Concurrently, the number of HIV-infected infants declined from 25 in 1993 to 4 in 1997. The complete Pediatric AIDS Clinical Trials Group Protocol 076 regimen was the most effective in reducing transmission (3.1%). Twenty-two of 35 infants who became infected in 1995-1997 had mothers who did not receive antiretroviral therapy, although counseling practices improved with time. In 1995, 87% of the mothers of HIV-seropositive infants were counseled, whereas in 1997, 96% were counseled (P<.005). None of 59 infants tested had high-level phenotypic zidovudine resistance, although 5 (8.8%) of 57 infants had virus isolates with at least one mutation in the reverse transcriptase gene associated with reduced phenotypic susceptibility to zidovudine.

Vertical Transmission of Multidrug-Resistant Human Immunodeficiency Virus Type 1 (HIV-1) and Continued Evolution of Drug Resistance in an HIV-1–Infected Infant

To confirm the vertical transmission of multidrug-resistant (MDR) human immunodeficiency virus type 1 (HIV-1) and to assess its impact on further evolution of drug-resistant virus in an infant, proviral DNA amplified from infected peripheral blood mononuclear cell cultures was sequenced to identify reverse transcriptase (RT) and protease (PR) mutations. The infant had proviral DNA with evidence of RT mutations (M41L, L74V, and T215Y) and 3 PR substitutions (K20R, M36I, and V82A). After delivery, the mothers proviral DNA had the same substitutions. Phylogenetic analyses of these HIV-1 RT and PR sequences indicated epidemiological linkage. Plasma drug susceptibility was determined by using a recombinant virus assay. Plasma HIV-1 obtained after the infants birth demonstrated reduced susceptibility to zidovudine and ritonavir. Thus, vertical transmission of MDR HIV-1 was demonstrated in the setting of detectable maternal plasma viremia. Further accumulation of broad MDR in the infants virus to 3 antiretroviral classes occurred, despite postnatal 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.