key: cord-019964-9leljj8j
authors: nan
title: Recent research in infectious disease
date: 2005-01-22
journal: J Infect
DOI: 10.1016/j.jinf.2004.11.005
sha: 
doc_id: 19964
cord_uid: 9leljj8j

nan

value was 83.8%, and negative predictive value was 98.6%.

The sensitivity of the assay was significantly higher than that of antepartum culture (54%). Furthermore, many clinicians use a risk-based approach to GBS colonization by treating high-risk women with empiric antibiotics without waiting for culture results. The assay was also significantly more sensitive than the risk-factor approach (94% versus 42%) with regard to predicting intrapartum status.

The quick and accurate results obtained with the IDI-Strep B assay during labor suggest that its use would lead to reduced rates of neonatal GBS colonization and the more judicious use of antibiotics. 2004;39:1129-35. How positive blood culture results are reported has an impact on outcomes of BSI ST. LOUIS (MD Consult)-Many patients with bloodstream infection (BSI) do not receive adequate therapy, even after the final microbiologic report is available. The method of reporting microbiologic information to the physician has a significant impact on whether and how this information is used, according to the October 15 Clinical Infectious Diseases.

Dr. Emilio Bouza and colleagues of Hospital General Universitario 'Gregorio Marañón' in Madrid evaluated data from 197 BSIs. Microbiologic results were reported in 3 different ways.

In 109 cases (group A), the physician was informed by telephone of the results and given a written report after the definitive results were known. In 99 cases (group B), physicians also received a written report at the bedside, along with written therapeutic recommendations. In 89 cases (group C), physicians also received clinical advice orally.

During empiric treatment, 27.7% of patients received inappropriate treatment, and 13.7% received no treatment. These patients had significantly longer hospital stays (mean, 27.2 versus 19.4 days) and a higher risk of having Clostridium difficile-associated diarrhoea (8.3% versus 1.9%), infection-related death (23.3% versus 13.6%), and all-cause mortality (30.8% versus 19.4%) than patients whose empiric therapy was appropriate.

After the reports were received, therapy was changed for 52.3% of patients in group B and 53.1% in group C but for none of the patients in group A. Consequently, the proportion of days during which patients received adequate treatment was significantly smaller in group A than in groups B and C (66.3% versus 92.1% and 91.2%, respectively).

Group A also received significantly fewer defined daily doses of appropriate antibiotics (16.4 versus 22.2 and 20.7 days) .

The duration of hospitalization, mortality rates after reports were received, and costs also tended to be lower in groups B and C.

These results suggest that written and/or oralalert reports providing clinical advice in addition to standard reports will improve the management of patients with BSI. Dr. Lynda Anne Szczech and colleagues of the Women's Interagency HIV Study recruited 2,038 HIV-positive from October 1994 through November 1995. Differences in the development of a new acquired immunodeficiency virus-defining illness (ADI) or death were compared according to renal status and HAART status.

At baseline, 287 patients (14.1%) had proteinuria. These patients had significantly lower CD4C lymphocyte counts and higher viral loads than patients without proteinuria, both at baseline and before starting HAART.

Before HAART was widespread, proteinuria was associated with a significantly increased risk of developing a new ADI (hazard ratio [HR], 1.37) and death (HR, 1.35). An elevated creatinine level was also a significant independent risk factor for mortality (HR, 1.72 per decrease in the inverse creatinine level).

However, even after HAART was initiated, proteinuria was a significant independent predictor of mortality (HR, 2.07). An elevated creatinine level was also a significant predictor of new-onset ADI and death (HRs, 1.54 and 1.96 per decrease in the inverse creatinine level, respectively.

Whether the kidney modulates HIV disease or whether these findings merely reflect the impact of greater comorbidity is not known. What is clear, however, is that HIV-positive women with these findings need improved monitoring and more aggressive treatment. Genetic and transmission analysis of Helicobacter pylori strains within a family Raymond J, Thiberge J-M, Chevalier C, Kalach N, Bergeret M, Labigne A, et al.

To look for evidence of intrafamilial infection, we isolated 107 Helicobacter pylori clones from biopsied specimens taken from both parents and four children. We compared the sequences of two housekeeping genes (hspA and glmM) from these clones with those of 131 unrelated strains from patients living in different geographic regions. Strain relationships within the family were determined by analyzing allelic variation at both loci and building phylogenetic trees and by using multilocus sequence typing. Both hspA-and glmM-based phylogenetic trees showed East Asian and African branches. All samples from family members showed natural mixed infection. Identical alleles found in some strains isolated from the children and parents, but not in the strains isolated from unrelated patients, demonstrated that strains have circulated within the family. Several mechanisms, such as point mutations, intragenic recombination, and introduction of foreign (African) alleles, were shown to enhance strain diversity within the family. Increasing reports of the appearance of novel nonmultiresistant methicillin-resistant Staphylococcus aureus MRSA (MRSA) strains in the community and of the spread of hospital MRSA strains into the community are cause for public health concern. We conducted two national surveys of unique isolates of S. aureus from clinical specimens collected from nonhospitalized patients commencing in 2000 and 2002, respectively. A total of 11.7% of 2,498 isolates from 2000 and 15.4% of 2,486 isolates from 2002 were MRSA. Approximately 54% of the MRSA isolates were nonmultiresistant (resistant to less than three of nine antibiotics) in both surveys. The majority of multiresistant MRSA isolates in both surveys belonged to two strains (strains AUS-2 and AUS-3), as determined by pulsed-field gel electrophoresis (PFGE) and resistogram typing. The 3 AUS-2 isolates and 10 of the 11 AUS-3 isolates selected for multilocus sequence typing (MLST) and staphylococcal chromosomal cassette mec (SCCmec) analysis were ST239-MRSA-III (where ST is the sequence type) and thus belonged to the same clone as the eastern Australian MRSA strain of the 1980s, which spread internationally. Four predominant clones of novel nonmultiresistant MRSA were identified by PFGE, MLST, and SCCmec analysis: ST22-MRSA-IV (strain EMRSA-15), ST1-MRSA-IV (strain WA-1), ST30-MRSA-IV (strain SWP), and ST93-MRSA-IV (strain Queensland). The last three clones are associated with community acquisition. A total of 14 STs were identified in the surveys, including six unique clones of novel nonmultiresistant MRSA, namely, STs 73, 93, 129, 75, and 80slv and a new ST. SCCmec types IV and V were present in diverse genetic backgrounds. These findings provide support for the acquisition of SCCmec by multiple lineages of S. aureus. They also confirm that both hospital and community strains of MRSA are now common in nonhospitalized patients throughout Australia. Use of multiple nucleic acid amplification tests to define the infected-patient 'gold standard' in clinical trials of new diagnostic tests for Chlamydia trachomatis infections Martin DH, Nsuami M, Schachter J, Hook EW 3rd, Ferrero D, Quinn TC, Gaydos C Nucleic acid amplification tests (NAATs) can be used to define the infected-patient 'gold standard' for the purpose of designing studies of the performance of Chlamydia trachomatis diagnostic tests. It is unclear how many test results run by different NAATs and what combinations of specimens comprise the best infected-patient gold standard. We approached this question with data from a large study of the performance of a new NAAT. Data were available from three endocervical swabs and a urine specimen collected from each of 1,412 women and tested by three different NAATs. Results from all three assays were used equally in a rotating fashion to define the infected-patient gold standard. Multiple different infectedpatient gold standards for estimating swab and urine specimen sensitivity and specificity for one NAAT method were created by varying the number and combinations of swab and urine comparator results with two different NAATs, The effect of changing the infected-patient gold standard definition was determined by constructing receiver-operator-like curves with calculated sensitivities and specificities for each test. The one-positive-of-two-results or two-positive-oftwo-results (same or two different assays) infected-patient gold standard definitions produced low sensitivity and low specificity estimates, respectively. If four comparator NAAT results were used, the any-three-positive-offour-results definition or the at-least-one-specimen-positive-by-each-of-two-comparator-assays definition appeared to provide better combinations of sensitivity and specificity estimates. The any-two-positive-out-of-three-results definition resulted in estimates that were as good as produced with the former two definitions. This analytic approach provides a means of clearly visualizing the effects of changing NAAT-based infected-patient gold standards and should be helpful in designing future studies of new C. trachomatis diagnostic tests. Prospective study of human metapneumovirus infection in children less than 3 years of age Konig B, Konig W, Arnold R, Werchau H, Ihorst G, Forster J Most lower respiratory tract infections (LRTIs) in children under the age of 3 years are due to respiratory syncytial virus (RSV). Epidemiological, host, and viral factors eventually account for the severity of LRTIs, but they do not completely explain it. Human metapneumovirus (hMPV) was recently identified in children with LRTIs. In a population-based prospective multicenter study (the PRI.DE study, conducted in Germany over 2 years), we tested 3,369 nasopharyngeal secretions from children younger than 3 years of age with LRTIs for RSV A and B, influenza viruses (IVs) A and B, and parainfluenza viruses (PIVs) 1 to 3. Of the children requiring intensive care (nZ85), 18% had hMPV infections, and 60% of these children were infected with hMPV in combination with RSV. We did not detect hMPV in a randomly selected subset of RSV-positive nasopharyngeal secretions (nZ120) from children not requiring intensive care support. hMPV was detected in !1% of virus-negative samples from patients without intensive care support (nZ620). Our data support the hypothesis that coinfections with RSV and hMPV are more severe than infections with either RSV or hMPV alone, at least in children younger than 3 years of age. Candida parapsilosis is an important cause of bloodstream infections in the health care setting. We investigated a large C. parapsilosis outbreak occurring in a community hospital and conducted a case-control study to determine the risk factors for infection. We identified 22 cases of bloodstream infection with C. parapsilosis: 15 confirmed and 7 possible. The factors associated with an increased risk of infection included hospitalization in the intensive care unit (adjusted odds ratio, 16.4; 95% confidence interval, 1.8 to 148.1) and receipt of total parenteral nutrition (adjusted odds ratio, 9.2; 95% confidence interval, 0.9 to 98.1). Samples for surveillance cultures were obtained from health care worker hands, central venous catheter insertion sites, and medical devices. Twenty-six percent of the health care workers surveyed demonstrated hand colonization with C. parapsilosis, and one hand isolate was highly related to all case-patient isolates by tests with the DNA probe Cp3-13. Outbreak strain isolates also demonstrated reduced susceptibilities to fluconazole and voriconazole. This largest known reported outbreak of C. parapsilosis bloodstream infections in adults resulted from an interplay of host, environment, and pathogen factors. Recommendations for control measures focused on improving hand hygiene compliance. 

Heikkinen T, Silvennoinen H, Peltola V, Ziegler T, Vainionpaa R, Vuorinen T, Kainulainen L, Puhakka T, Jartti T, Toikka P, Lehtinen P, Routi T, Juven T Background: Influenza vaccination of healthy children is encouraged because children are frequently hospitalized for influenza-attributable illnesses. However, most children with influenza are treated as outpatients, and scarce data are available on the burden of influenza in these children.

Methods:

We performed a prospective study of respiratory infections in preenrolled cohorts of children %13 years old during 2 consecutive respiratory seasons (2231 child-seasons of follow-up). At any sign of respiratory infection, we examined the children and obtained a nasal swab for the detection of influenza. The parents filled out daily symptom diaries. Of all the enrollees, 94% remained active participants in the study.

Results:

The average annual rate of influenza was highest (179 cases/1000 children) among children !3 years old. Acute otitis media developed as a complication of influenza in 39.7% of children !3 years old. For every 100 influenza-infected children !3 years old, there were 195 days of parental work loss (mean duration, 3.2 days).

Influenza causes a substantial burden of illness on outpatient children and their families. Vaccination of children !3 years old might be beneficial for reducing the direct and indirect costs of influenza in children. 

Moscicki AB, Ellenberg JH, Crowley-Nowick P, Darragh TM, Xu J, Fahrat S Background:

The risk of developing the human papillomavirus (HPV)-associated precancer high-grade squamous intraepithelial lesion (HSIL) in human immunodeficiency virus (HIV)-infected adolescents is unknown. We examined the risk of developing HSIL among adolescents with and without HIV infection.

Methods:

HIV-infected (nZ172) and-uninfected (nZ84) girls aged 13-18 years who were participating in a multicenter study of primarily horizontally acquired HIV infections in adolescents (Reaching for Excellence in Adolescent Health Care) and who did not have HSIL on cytologic examination at study entry or at the first follow-up visit were followed at 6-month intervals. HIV-uninfected girls were recruited for comparison in a 2:1 ratio (HIV infected: HIV uninfected). The primary outcome was cytologic diagnosis of HSIL confirmed by expert review.

Results: Incidence of HSIL by the end of follow-up was higher for HIV-infected girls than for HIV-uninfected girls (21.5% vs. 4.8%, respectively). In multivariate analysis, use of hormonal (either estrogen/progesterone oral combination or medroxyprogesterone acetate intramuscular) contraceptives, high cervical mucous concentrations of interleukin (IL)-12, a positive HPV test, and persistent low-grade squamous intraepithelial lesion (LSIL) were significantly associated with the development of HSIL.

Conclusions:

The incidence of HSIL was alarmingly high in HIVinfected adolescent girls. However, when other predictors were considered in multivariate analysis, HIV status was not retained in the model. The heightened risk for HSIL associated with persistent LSIL underscores the need to closely monitor HIV-infected adolescents with LSIL. The risk for HSIL associated with high concentrations of IL-12 may be suggestive of a local immune dysregulation. The role of hormonal contraception as a risk factor deserves further investigation. Little is known about the epidemiologic profile of trichomoniasis in men and its relationship to human immunodeficiency virus (HIV) infection. Among men presenting for care for symptomatic sexually transmitted infections (STIs) in Malawi, trichomoniasis is not considered for first-line treatment.

Methods: We conducted a cross-sectional survey of 1187 men attending either a dermatology or STI outpatient clinic in the capital of Malawi. Men were interviewed, and the etiologies of the STIs were determined.

Results: At the STI clinic (nZ756 men), we identified 150 men (20%) with Trichomonas vaginalis infection, 358 men (47%) with HIV infection, and 335 men (44%) with Neisseria gonorrhoeae infection. At the dermatology clinic (nZ431 men), we identified 54 (13%), 118 (27%), and 2 (0.5%) men, respectively. At both clinics, a lower education level and reporting never having used a condom were predictive of T. vaginalis infection. Only at the dermatology clinic was older age associated with infection, and only at the STI clinic were marital, genital ulcer disease, and HIV-infection status associated with T. vaginalis infection. At the STI clinic, urethral symptoms attributable to trichomoniasis were more severe among HIV-positive men than among HIV-negative men.

Conclusions: Given its high prevalence and the increased risk for HIV transmission, T. vaginalis infection should be reconsidered for inclusion in the Malawi STItreatment regimen for men. 2004; 190(8):1448-55. PMID: 15378437 [PubMed-in process] Role of human neutrophil peptide-1 as a possible adjunct to antituberculosis chemotherapy Kalita A, Verma I, Khuller GK We report the role of human neutrophil peptide (HNP)-1 as an adjunct to antituberculosis (anti-TB) drugs. The combination of HNP-1, isoniazid, and rifampicin was evaluated against Mycobacterium tuberculosis H(37)Rv in vitro, ex vivo, and in vivo, and synergism was observed on the basis of reductions in minimum inhibitory concentrations (MICs) of these agents. In vitro results revealed O1log unit reductions even when HNP-1 and anti-TB drugs were used at 1/16 MICs. This combination was also found to be bactericidal against intracellular mycobacteria even at 1/8 MICs of HNP-1 and drugs. HNP-1 used in conjunction with anti-TB drugs resulted in significant clearance of bacterial load from lungs, liver, and spleen of infected, compared with control animals. The effective therapeutic dosage of drugs could be reduced to half by supplementing HNP-1 in the therapeutic schedule. These results clearly suggest that HNP-1 can be used as adjunct chemotherapy with conventional drugs against TB. In this Phase III trial, Dr. Jo-Anne H. van Burik and the National Institute of Allergy and Infectious Diseases Mycoses Study Group studied 882 children and adults undergoing HSCT. About half were randomized to receive micafungin (50 mg; 1 mg/kg for patients !50 kg), whereas the others received fluconazole (400 mg; 8 mg/kg for patients !50 kg).

Drugs were administered once a day via infusion during the neutropenic phase of HSCT (i.e., before engraftment), and they were continued until neutropenia resolved or day 42 after HSCT, whichever came earlier, or until fungal infection developed. Time to treatment success was also significantly shorter with micafungin.

No excess toxicity occurred with micafungin as compared with fluconazole, and fewer patients receiving micafungin dropped out of the study due to drug-related adverse events (4.2% versus 7.2%, PZ0.058).

These results suggest that micafungin is an effective alternative to fluconazole for antifungal prophylaxis in neutropenic patients during HSCT. The authors obtained baseline blood samples from 174 girls 12 to 15 years old (76% African-American; 24% white). Seropositivity for HSV-1, HSV-2, and CMV was also assessed 3 years later.

At baseline, 41% of subjects (71 girls) had a history of sexual activity; this proportion increased to 73% (127 girls) by the 3-year follow-up.

Overall, seropositivity for CMV increased from 71% to 81%, seropositivity for HSV-1 increased from 44% to 49%, and seropositivity for HSV-2 doubled, from 7% to 14%. Among sexually experienced girls, HSV-2 seropositivity increased from 15% to 19%.

These increases correspond with attack rates of 13.8 cases of CMV per 100 person-years and 3.2 cases of HSV-1 per 100 person-years in the entire cohort. Among sexually experienced girls, HSV-2 attack rates were 4.4 cases per 100 person-years of sexual activity.

At follow-up, generalized estimating equation modeling identified 4 factors significantly associated with HIV-2 seropositivity: 

it also saves money, according to a new study.

Dr. Kent K. Hu and colleagues of Veterans Affairs Puget Sound Health Care System in Seattle, Wash, and other institutions discuss their findings in the November 15 Clinical Infectious Diseases.

The authors developed a decision analysis model based on hospitalized patients most likely to require a CVC for 2 to 10 days (i.e., those in intensive care units, with immunosuppression, or receiving total parenteral nutrition).

CVCs were inserted according to either MSB techniques (person inserting the catheter must wear a head cap, face mask, sterile body gown, and sterile gloves and use a full-size sterile drape around the site) or in accordance with lessstringent measures (only sterile gloves and a small regional sterile drape).

In the base-case analysis, the use of MSBs actually lowered costs by $252 as compared with less-stringent infection control measures ($369 versus $621 per catheter inserted).

The incidences of catheter-related BSI (2.8% versus 5.3%), catheter colonization (2.9% versus 5.5%), and death (0.4% versus 0.8%) were also lower with MSBs.

During sensitivity analyses-even over a wide range of clinical and economic assumptions-the use of MSBs resulted in improved patient safety.

These data suggest that the improved management of infection with the use of MSBs also pays off by lowering medical costs. Thus, even though MSBs are sometime cumbersome and time consuming, the authors suggest that they should be routinely used during CVC insertion. 2004;39:1441-5. Hypogonadism is a risk factor for gynecomastia in HIV-positive men ST. LOUIS (MD Consult)-Some studies suggest antiretroviral therapy is a risk factor for gynecomastia in men with human immunodeficiency virus (HIV) infection. However, no association has ever been found between the duration of exposure to any antiretroviral drug and the development of gynecomastia.

Instead, it appears hypogonadism is a predisposing factor to gynecomastia in HIV-infected men, according to the November 15 Clinical Infectious Diseases.

Dr. Alejandra Biglia and colleagues of the University of Barcelona in Spain and other institutions studied 2,275 men with HIV infection. Clinical examination with confirmatory sonography showed 40 men, or 1.8%, had gynecomastia. This is similar to the prevalence of gynecomastia in the general population.

These 40 cases were matched with 44 men with HIV but not gynecomastia, and clinical, demographic, and laboratory features were extensively compared between the 2 groups.

The mean free testosterone index was significantly lower in the cases than in the controls (42.6% vs. 58.0%). Hypogonadism was the strongest independent predictor of gynecomastia (adjusted odds ratio [OR] 7.6). Other factors increasing the risk of gynecomastia included hepatitis C virus infection (adjusted OR 6.1) and lipoatrophy (adjusted OR 5.6).

Furthermore, gynecomastia resolved in many patients with persistent gynecomastia after transdermal or intramuscular testosterone administration, and in fact improved without any intervention in a substantial proportion of men.

The authors also compared antiretroviral drug use between the cases and controls. Significantly more cases were taking stavudine (73% vs. 41%) or efavirenz (33% vs. 14%), but significantly more controls were taking zidovudine (34% vs. 10%).

However, the duration of exposure to each drug did not differ significantly between cases and controls, which further argues against antiretroviral therapy as the cause of gynecomastia in HIVpositive men.

The authors conclude gynecomastia in HIVinfected men appears to be related more to hypogonadism than to adverse effects of antiretroviral therapy. If gynecomastia proves to be related to hypogonadism, then hormone treatments may be able to reverse this lipodystrophy, and further study is warranted.

Clin Infect Dis 2004;39:1514-9.

Taira AV, Neukermans CP, Sanders GD Human papillomavirus (HPV) has been implicated as the primary etiologic agent of cervical cancer. Potential vaccines against high-risk HPV types are in clinical trials. We evaluated vaccination programs with a vaccine against HPV-16 and HPV-18. We developed disease transmission models that estimated HPV prevalence and infection rates for the population overall, by age group, by level of sexual activity within each age group, and by sex. Data were based on clinical trials and published and unpublished sources. An HPV-16/18 vaccine for 12year-old girls would reduce cohort cervical cancer cases by 61.8%, with a cost-effectiveness ratio of $14,583 per quality-adjusted life year (QALY). Including male participants in a vaccine rollout would further reduce cervical cancer cases by 2.2% at an incremental cost-effectiveness ratio of $442,039/QALY compared to female-only vaccination. Vaccination against HPV-16 and HPV-18 can be cost-effective, although including male participants in a vaccination program is generally not costeffective, compared to female-only vaccination. 

Yokoe DS, Noskin GA, Cunningham SM, Zuccotti G, Plaskett T, Fraser VJ, et al.

We evaluated antimicrobial exposure, discharge diagnoses, or both to identify surgical site infections (SSI). This retrospective cohort study in 13 hospitals involved weighted, random samples of records from 8,739 coronary artery bypass graft (CABG) procedures, 7,399 cesarean deliveries, and 6,175 breast procedures. We compared routine surveillance to detection through inpatient antimicrobial exposure (S9 days for CABG, S2 days for cesareans, and S6 days for breast procedures), discharge diagnoses, or both. Together, all methods identified SSI after 7.4% of CABG, 5.0% of cesareans, and 2.0% of breast procedures. Antimicrobial exposure had the highest sensitivity, 88% to 91%, compared with routine surveillance, 38% to 64%. Diagnosis codes improved sensitivity of detection of antimicrobial exposure after cesareans. Record review confirmed SSI after 31% to 38% of procedures that met antimicrobial surveillance criteria. Sufficient antimicrobial exposure days, together with diagnosis codes for cesareans, identified more postoperative SSI than routine surveillance methods. This screening method was efficient, readily standardized, and suitable for most hospitals. 

Miner AL, Sands KE, Yokoe DS, Freedman J, Thompson K, Livingston JM, et al.

We investigated using administrative claims data to identify surgical site infections (SSI) after breast surgery and cesarean section. Postoperative diagnosis codes, procedure codes, and pharmacy information were automatically scanned and used to identify claims suggestive of SSI ('indicators') among 426 (22%) of 1,943 breast procedures and 474 (10%) of 4,859 cesarean sections. For 104 breast procedures with indicators explained in available medical records, SSI were confirmed for 37%, and some infection criteria were present for another 27%. Among 204 cesarean sections, SSI were confirmed for 40%, and some criteria were met for 27%. The extrapolated infection rates of 2.8% for breast procedures and 3.1% for cesarean section were similar to those reported by the National Nosocomial Infection Surveillance program but differ in representing predominantly outpatient infections. Claims data may complement other data sources for identification of surgical site infections following breast surgery and cesarean section. Several studies have shown that nasopharyngeal sampling is more sensitive than oropharyngeal sampling for the detection of pneumococcal carriage in children. The data for adults are limited and conflicting. This study was part of a larger study of pneumococcal carriage on the Navajo and White Mountain Apache Reservation following a clinical trial of a seven-valent pneumococcal conjugate vaccine. Persons aged 18 years and older living in households with children enrolled in the vaccine trial were eligible. We collected both nasopharyngeal and oropharyngeal specimens by passing a flexible calcium alginate wire swab either nasally to the posterior nasopharynx or orally to the posterior oropharynx. Swabs were placed in skim milktryptone-glucose-glycerin medium and frozen at K708C. Pneumococcal isolation was performed by standard techniques. Analyses were based on specimens collected from 1,994 adults living in 1,054 households. Nasopharyngeal specimens (11.1%; 95% confidence interval [CI], 9.8 and 12.6%) were significantly more likely to grow pneumococci than were oropharyngeal specimens (5.8%; 95% CI, 4.8 to 6.9%) (P!0.0001). Few persons had pneumococcal growth from both specimens (1.7%). Therefore, both tests together were more likely to identify pneumococcal carriage (15.2%; 95% CI, 13.7 to 16.9%) than either test alone. Although we found that nasopharyngeal sampling was more sensitive than oropharyngeal sampling, nasopharyngeal sampling alone would have underestimated the prevalence of pneumococcal carriage in this adult population. Sampling both sites may give more accurate results than sampling either site alone in studies of pneumococcal carriage in adults. Microbiol 2004; 42(11):4974-6. PMID: 15528682 [PubMed-in process] Effects of intrapartum penicillin prophylaxis on intestinal bacterial colonization in infants Jaureguy F, Carton M, Panel P, Foucaud P, Butel MJ, Doucet-Populaire F Early-onset group B streptococcal (GBS) infections remain a leading cause of morbidity and mortality in infants. To prevent the vertical transmission of GBS and neonatal GBS infection, guidelines recommend intrapartum penicillin or amoxicillin prophylaxis. This intrapartum antibiotic prophylaxis (IAP) is suspected to favor colonization by antibiotic-resistant bacteria. However, the effects of this prophylaxis on the patterns of acquisition of gastrointestinal bacterial flora in infants have never been studied. We collected stool samples from 3-day-old infants born to mothers who received intrapartum amoxicillin (antibiotic-exposed group; nZ25) and to untreated mothers (non-antibiotic-exposed group; nZ25). The groups were matched for factors known to affect intestinal microbial colonization: gestational age, type of delivery, and type of feeding. Qualitative and quantitative differential analyses of the bacterial flora in stool samples were performed. Similar numbers of infants in the nonantibiotic-exposed and antibiotic-exposed groups were colonized by aerobic bacteria and amoxicillinresistant enterobacteria (75 and 77%, respectively) (PZ0.79). In contrast, significantly fewer infants in the antibiotic-exposed group than in the nonantibiotic-exposed group were colonized by anaerobic bacteria, especially Clostridium (12 and 40%, respectively) (P!0.05). Regarding intestinal bacterial colonization, the differences between antibiotic-exposed and non-antibiotic-exposed infants were remarkably few. The only statistically significant effect was the reduced initial bacterial colonization by Clostridium in the antibioticexposed group. In our study, the use of IAP did not favor colonization by beta-lactam-resistant bacteria. However, further evaluations are required to highlight the potential risks of the widespread use of antibiotics to prevent early-onset GBS infection. Microbiol 2004; 42(11):5184-8. PMID: 15528713 [PubMed-in process] Usefulness of routine epicardial pacing wire culture for early prediction of poststernotomy mediastinitis Mekontso-Dessap A, Honore S, Kirsch M, Houel R, Loisance D, Brun-Buisson C Poststernotomy mediastinitis (PSM) is one of the most serious complications of cardiac surgery, and its associated morbidity and mortality demand early recognition for emergency therapy. In this study, we investigated the usefulness of epicardial pacing wire (EPW) cultures for the prediction of PSM. Among 2,200 patients who underwent a cardiac surgical procedure at our hospital between 1 January 1999 and 31 December 2001, 82 (3.7%) had PSM; Staphylococcus aureus was the organism (45.1%) most frequently isolated at the time of surgical debridement. EPWs from 1,607 (73.0%) patients, 73 (4.5%) of whom developed PSM, were cultured. EPW cultures from 466 (29.0%) were positive, most often (74.9%) for coagulase-negative Staphylococci. EPW cultures were truly positive in 26 cases, truly negative in 1,106 cases, falsely positive in 428 cases, and falsely negative in 47 cases (with sterile cultures in 35 cases and a culture positive for an organism different from that isolated at the time of debridement in 12 cases). EPW culture had a positive predictive value of only 5.7% and a high negative predictive value (95.9%) for the diagnosis of PSM, with an accuracy of 70.4%. However, the likelihood ratio of positive (1.27) and negative (0.89) tests indicated only small changes in pretest-to-posttest probability. Therefore, a strategy of routine culture of EPWs to predict PSM seems questionable. Dual-probe assay for rapid detection of drug-resistant Mycobacterium tuberculosis by real-time PCR Wada T, Maeda S, Tamaru A, Imai S, Hase A, Kobayashi K Mutations in particular nucleotides of genes coding for drug targets or drug-converting enzymes lead to drug resistance in Mycobacterium tuberculosis. For rapid detection of drug-resistant M. tuberculosis in clinical specimens, a simple and applicable method is needed. Eight TaqMan minor groove binder (MGB) probes, which discriminate one-base mismatches, were designed (dual-probe assay with four reaction tubes). The target of six MGB probes was the rpoB gene, which is involved in rifampin resistance; five probes were designed to detect for mutation sites within an 81-bp hot spot of the rpoB gene, and one probe was designed as a tuberculosis (TB) control outside the rpoB gene hot-spot. We also designed probes to examine codon 315 of katG and codon 306 of embB for mutations associated with resistance to isoniazid and ethambutol, respectively. Our system was M. tuberculosis complex specific, because neither nontuberculous mycobacteria nor bacteria other than mycobacteria reacted with the system. Detection limits in direct and preamplified analyses were 250 and 10 fg of genomic DNA, respectively. The system could detect mutations of the rpoB, katG, and embB genes in DNAs extracted from 45 laboratory strains and from sputum samples of 27 patients with pulmonary TB. This system was much faster (3 h from DNA preparation) than conventional drug susceptibility testing (3 weeks). Results from the dual-MGBprobe assay were consistent with DNA sequencing. Because the dual-probe assay system is simple, rapid, and accurate, it can be applied to detect drugresistant M. tuberculosis in clinical laboratories. To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the community and their population dynamics, we studied the molecular epidemiology of a random sample (nZ490) from a collection of 2154 inpatient and outpatient MRSA isolates during a 7-year period in San Francisco. We noted a progressive replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing isolates with type IV SCCmec-bearing isolates, which coincided with O4-fold increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing isolates involved in the increase in methicillin resistance belonged to 4 molecular genotypes. These 4 genotypes were associated predominantly with community-onset disease, rather than hospital-or long-term-care facilityonset disease (76.9% vs. 19.4% vs. 3.7%; PZ0.0005), suggesting that they are not feral descendants of hospital isolates. The longitudinal results linked the dramatic increase in MRSA infections to an expanding community reservoir of MRSA genotypes with intrinsic community survival advantage. The outbreak of monkeypox in the midwestern United States during June 2003 marks the first documented human infection in the Western Hemisphere. Consistent with those in outbreaks in Africa, most cases in this outbreak were associated with febrile rash illness. We describe a cluster of monkeypox in a family with a spectrum of clinical illness, including encephalitis, and outline the laboratory confirmation of monkeypox.

Methods: Standardized patient information was collected by questionnaire and medical chart review; all cases described were laboratory confirmed. Laboratory methods included nucleic acid detection, viral culture, serologic testing, histopathologic evaluation, and immunohistochemical testing.

Results: Of 3 family members with monkeypox, 2 had rash illness only, and 1 required hospitalization for severe encephalitis. The family member with the mildest clinical course had previously received smallpox vaccination. Diagnostic testing by both polymerase chain reaction and culture revealed infectious monkeypox virus in skin lesions of all 3 patients; 2 patients had orthopoxvirus detected by immunohistochemistry in skin lesions. The patient with encephalitis had orthopoxvirus-reactive immunoglobulin M (IgM) in cerebrospinal fluid. All patients had detectable IgM responses to orthopoxvirus antigens.

Conclusions: These 3 patients illustrate a spectrum of clinical illness with monkeypox despite a common source of exposure; manifestation and severity of illness may be affected by age and prior smallpox vaccination. We report that monkeypox, in addition to causing febrile rash illness, causes severe neurologic infection, and we discuss the use of novel laboratory tests for its diagnosis.

The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1-infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk

Previous studies demonstrated that the concentration of BMCs varies throughout lactation, and we used these data to transform infected BMCs per million cells to infected BMCs per milliliter. The estimated concentration of infected BMCs per milliliter was higher in colostrum or early milk than in mature milk (P!0.001)

Factors influencing increases in CD4 cell counts of HIV-positive persons receiving long-term highly active antiretroviral therapy Smith CJ, Sabin CA, Youle MS, Kinloch-de Loes S, Lampe FC, Madge S, Cropley I, Johnson MA, Phillips AN Background: Highly active antiretroviral therapy (HAART) results in an improvement in immunologic function. We sought to investigate the factors associated with increases in CD4 cell count among human immunodeficiency virus (HIV)-positive antiretroviral-naive patients starting HAART.Methods: Five hundred ninety-six subjects were followed for a median of 2.5 years (interquartile range, 1.0-4.0 years). Factors associated with changes in CD4 cell counts in the first 3 months of HAART and from 3 months onwards were analyzed.Results: After 6, 12, and 24 months of HAART, the median increases in CD4 cell counts were 114, 181, and 248 cells/mm(3), respectively; 84%, 84%, and 80% of subjects had a virus load of !400 copies/mL during the same periods. White ethnicity, higher pre-HAART virus load, and lower pre-HAART CD4 and CD8 cell counts were associated with greater increases in CD4 cell counts during the first 3 months of HAART. From 3 months onward, a greater cumulative proportion of time spent with virus load !400 copies/mL was associated with a more favorable change in CD4 cell count (an average increase of 5.2 cells/mm(3)/year [95% confidence interval [CI], 3.8-6.7 cells/mm (3)/year] for each extra 10% cumulative time spent with a virus load !400 copies/mL) (P!0.0001). For every 100 cells/mm(3) higher in baseline CD4 cell count, the increase was 6 cells/mm(3)/year less (95% CI, 2-11 cells/mm(3)/year) (PZ0.02). Sex, risk group, age, and HAART regimen were not associated with increases in CD4 cell counts.Conclusions: These findings emphasize the importance of maintaining virological suppression and suggest other factors that influence long-term CD4 cell response. 2004; 190(10):1860-8. PMID: 15499544 [PubMed-in process] Association of levels of HIV-1-infected breast milk cells and risk of mother-tochild transmission Rousseau CM, Nduati RW, Richardson BA, John-Stewart GC, Mbori-Ngacha DA, Kreiss JK, Overbaugh J Understanding how the level of human immunodeficiency virus type 1 (HIV-1)-infected breast milk cells (BMCs) affects HIV transmission via breastfeeding can shed light on the mechanism of
