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author:("oxman, Betsy")
2.  Efflux-mediated resistance identified among norfloxacin resistant clinical strains of group B Streptococcus from South Korea 
Epidemiology and Health  2014;36:e2014022.
Group B Streptococcus (GBS), a common bowel commensal, is a major cause of neonatal sepsis and an emerging cause of infection in immune-compromised adult populations. Fluoroquinolones are used to treat GBS infections in those allergic to beta-lactams, but GBS are increasingly resistant to fluoroquinolones. Fluoroquinolone resistance has been previously attributed to quinolone resistance determining regions (QRDRs) mutations. We demonstrate that some of fluoroquinolone resistance is due to efflux-mediated resistance.
We tested 20 GBS strains resistant only to norfloxacin with no mutations in the QRDRs, for the efflux phenotype using norfloxacin and ethidium bromide as substrates in the presence of the efflux inhibitor reserpine. Also tested were 68 GBS strains resistant only to norfloxacin not screened for QRDRs, and 58 GBS strains resistant to ciprofloxacin, levofloxacin or moxifloxacin. Isolates were randomly selected from 221 pregnant women (35-37 weeks of gestation) asymptomatically carrying GBS, and 838 patients with GBS infection identified in South Korea between 2006 and 2008. The VITEK II automatic system (Biomerieux, Durham, NC, USA) was used to determine fluoroquinolone resistance.
The reserpine associated efflux phenotype was found in more than half of GBS strains resistant only to norfloxacin with no QRDR mutations, and half where QRDR mutations were unknown. No evidence of the efflux phenotype was detected in GBS strains that were resistant to moxifloxacin or levofloxacin or both. The reserpine sensitive efflux phenotype resulted in moderate increases in norfloxacin minimum inhibitory concentration (average=3.6 fold, range=>1-16 fold).
A substantial portion of GBS strains resistant to norfloxacin have an efflux phenotype.
PMCID: PMC4258715  PMID: 25322878
Fluoroquinolones; Norfloxacin; Ciprofloxacin; Levofloxacin; Moxifloxacin; Mutations; Efflux; Minimum inhibitory concentration
3.  Identifying the interaction between influenza and pneumococcal pneumonia using incidence data 
Science translational medicine  2013;5(191):191ra84.
The association between influenza virus and the bacterium Streptococcus pneumoniae (pneumococcus) has been proposed as a polymicrobial system, whereby transmission and pathogenicity of one pathogen (bacterium) are affected by interactions with the other (virus). However, studies focusing on different scales of resolution have painted an inconsistent picture: individual-scale animal experiments have unequivocally demonstrated an association, while epidemiological support in human populations is, at best, inconclusive. Here, we integrate weekly incidence reports and a mechanistic transmission model within a likelihood-based inference framework to characterize the nature, timing and magnitude of this interaction. We find support for a strong but short-lived interaction, with influenza infection increasing susceptibility to pneumococcal pneumonia ~100-fold. We infer modest population-level impacts arising from strong processes at the level of an individual, thereby resolving the dichotomy in seemingly inconsistent observations across scales. An accurate characterization of the influenza-pneumococcal interaction can form a basis for more effective clinical care and public health measures for pneumococcal pneumonia.
PMCID: PMC4178309  PMID: 23803706
4.  Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza and Streptococcus pneumoniae 
A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immune-mediated model of the viral–bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4–6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness.
PMCID: PMC3730679  PMID: 23825111
influenza–pneumococcal interaction; within-host model; influenza; pneumococcus; mathematical model
5.  Vaginal and Oral Microbes, Host Genotype and Preterm Birth 
Medical hypotheses  2009;73(6):963-975.
Preterm birth (PTB) is a leading cause of infant mortality and morbidity in the U.S. and across the globe. Infection and associated inflammation are important initiators for PTB pathways; an estimated 40% of PTBs are attributed to amniochorionic-decidual or systemic inflammation. Historically, intrauterine infections have been implicated in PTB; recent evidence suggests that infections remote from the fetal site may also be causative. There is strong epidemiological evidence that bacterial vaginosis and periodontitis -- two syndromes characterized by perturbations in the normal vaginal and oral bacterial microflora respectively-- are linked to infection-associated PTB. Oral and vaginal environments are similar in their bacterial microbiology; identical bacterial species have been independently isolated in periodontitis and bacterial vaginosis. Periodontitis and bacterial vaginosis also share many behavioral and sociodemographic risk factors suggesting a possible common pathophysiology. Genetic polymorphisms in host inflammatory responses to infection are shared between bacterial vaginosis, periodontitis and PTB, suggesting common mechanisms through which host genotype modify the effect of abnormal bacterial colonization on preterm birth. We review the state of knowledge regarding the risk of PTB attributable to perturbations in bacterial flora in oral and vaginal sites and the role of host genetics in modifying the risk of infection-related PTB. We posit that bacterial species that are common in perturbed vaginal and oral sites are associated with PTB through their interaction with the host immune system.
PMCID: PMC4026093  PMID: 19942083
Prematurity; infection; genotype
6.  Alternative Approaches to Conventional Treatment of Acute Uncomplicated Urinary Tract Infection in Women 
The increasing resistance of uropathogens to antibiotics, and recognition of generally self-limiting nature of uncomplicated urinary tract infection (UTI) suggests that it is time to reconsider empirical treatment of UTI using antibiotics. Identifying new and effective strategies to prevent recurrences and alterative treatment strategies are a high priority. We review the recent literature regarding the effects of functional food products, probiotics, vaccines, and alternative treatments on treating and preventing UTI.
PMCID: PMC3622145  PMID: 23378124
functional foods; probiotics; vaccines; anti-inflammatories
7.  Healthcare Workers’ Hand Microbiome May Mediate Carriage of Hospital Pathogens 
Pathogens  2013;3(1):1-13.
One function of skin microbiota is to resist colonization and infection by external microorganisms. We sought to detect whether the structure of the hand microbiota of 34 healthcare workers (HCW) in a surgical intensive care unit mediates or modifies the relationship between demographic and behavioral factors and potential pathogen carriage on hands after accounting for pathogen exposure. We used a taxonomic screen (16S rRNA) to characterize the bacterial community, and qPCR to detect presence of Staphylococcus aureus, Enterococcus spp., methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans on their dominant hands. Hands were sampled weekly over a 3-week period. Age, hand hygiene, and work shift were significantly associated with potential pathogen carriage and the associations were pathogen dependent. Additionally, the overall hand microbiota structure was associated with the carriage of potential pathogens. Hand microbiota community structure may act as a biomarker of pathogen carriage, and modifying that structure may potentially limit pathogen carriage among HCW.
PMCID: PMC4235731  PMID: 25437604
skin; hand; microbiome; microbiota; hand hygiene; healthcare; pathogen
8.  Impact of Technical Sources of Variation on the Hand Microbiome Dynamics of Healthcare Workers 
PLoS ONE  2014;9(2):e88999.
We assessed the dynamics of hand microbial community structure of 34 healthcare workers from a single surgical intensive care unit over a short (3 week) time period, whilst taking into account the technical sources of variability introduced by specimen collection, DNA extraction, and sequencing. Sample collection took place at 3 different time points. Only the sampling collection method appeared to have a significant impact on the observed hand microbial community structure among the healthcare workers. Analysis of samples collected using glove-juice showed a slightly more similar microbial composition within individual hand samples over time than between the hands of different individuals over time. This was not true for samples collected using a swab, where samples from a single individual were no more similar to each other over time than those among other individuals over time, suggesting they were essentially independent. DNA extraction techniques (lysozyme only versus enzyme cocktail) and sequencing (replicate set 1 versus 2) using Ion Torrent Personal Genome Machine, were not influential to the microbial community structures. Glove-juice sample collection may likely be the method of choice in hand hygiene studies in the healthcare setting.
PMCID: PMC3925205  PMID: 24551205
9.  Implications of the Human Microbiome Project for Epidemiology 
American Journal of Epidemiology  2013;177(3):197-201.
The structure and function of microorganisms that live in and on us, the human microbiota, are a tremendous resource. Microbiota may help to explain individual variability in health outcomes and be a source of new biomarkers for environmental exposures and of novel prognostic and diagnostic indicators. The increase in availability of low-cost, high-throughput techniques makes it relatively straightforward to include microbiota assessments in epidemiologic studies. With the recent joint publications of the findings of the Human Microbiome Consortium and related studies, the consequent surge of interest in microbiome research, and remarkable media attention, the time is ripe for epidemiologists to contribute their expertise to and translate results of microbiota research for population health.
PMCID: PMC3626050  PMID: 23296358
Human Microbiome Project; microbiome; microbiota
10.  Risk Factors Associated with Group B Streptococcus Resistant to Clindamycin and Erythromycin in Pregnant Korean Women 
Infection & Chemotherapy  2013;45(3):299-307.
The prevalence of group B streptococcus (GBS) among pregnant women and neonates in the Republic of Korea has increased. In addition, rates of resistance to antibiotics recommended for pregnant women allergic to penicillin, such as clindamycin and erythromycin, have increased. The aim of this study was to evaluate subject characteristics associated with GBS resistance to clindamycin and erythromycin.
Materials and Methods
A total of 418 clinical isolates from pregnant women in Korea were screened for antibiotic resistance from January 2006 to December 2011. Sociodemographic information, medical and obstetric history, and details of events during the previous 2 weeks were recorded using a standardized questionnaire.
The resistance rates were 39.5% for clindamycin and 23.0% for erythromycin. In multiple logistic regression analysis, the subject characteristic significantly associated with resistance to both antibiotics was a history of symptomatic sore throat in the 2 weeks before obtaining the specimen (erythromycin: odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.10 to 4.13; clindamycin: OR: 2.31, 95% CI: 1.21, 4.42). Premature rupture of membranes (PROM) had an association of borderline significance.
In the urgent treatment of GBS-colonized pregnant women, the subject's history of previous sore throat and PROM should be considered when choosing appropriate antibiotics.
PMCID: PMC3848523  PMID: 24396631
Antibiotic resistance; Clindamycin; Erythromycin; Risk factors; Streptococcus agalactiae
12.  Why the Human Microbiome Project Should Motivate Epidemiologists to Learn Ecology 
Epidemiology (Cambridge, Mass.)  2010;21(6):757-759.
PMCID: PMC3715124  PMID: 20924228
13.  Epidemiology of neonatal sepsis in South Korea 
Neonatal sepsis is a severe clinical syndrome characterized by systemic signs of infection, shock and system organ failure; diagnosis is confirmed on positive culture from a normally sterile site(s). There are few reports comparing incidence, mortality, and risk factors between clinically diagnosed sepsis and that confirmed by culture.
All infants diagnosed with early- (within first 72 h after birth) or late-onset (72 h–4 weeks after birth) neonatal sepsis between 1997 and 1999 from four neonatal centers in South Korea, were investigated.
The estimated incidence rate of neonatal sepsis during the 3 years was 30.5 per 1000 live births for clinical sepsis and 6.1 per 1000 live births for sepsis with positive culture, with case-fatality rates of 4.7% and 2.2%, respectively. When only early-onset sepsis was considered, the incidence and fatality rates were 25.1 per 1000 live births and 6.1% for clinical sepsis, and 4.3 per 1000 live births and 2.5% for culture-confirmed sepsis, respectively. For the 179 patients (185 causative organisms) of proven sepsis, Staphylococcus spp. including S. aureus were the most frequent isolates. In early-onset clinical sepsis, having very low birthweight (≤1500 g), a low Apgar score at 5 min (≤7), and being male were related to higher rates of case-fatality (relative risk: 11.3, 6.8 and 2.5, respectively)
Clinical sepsis was more common than culture-confirmed sepsis and had a higher case-fatality rate. It seems prudent to take rapid and decisive steps toward better management of the high-risk group whether the sepsis is clinically diagnosed or culture confirmed.
PMCID: PMC3684947  PMID: 19405921
case fatality rate; epidemiology; newborns; sepsis; South Korea
14.  Both Host and Pathogen Factors Predispose to Escherichia coli Urinary-Source Bacteremia in Hospitalized Patients 
We determined host and pathogen risk factors for urinary-source bacteremia in a prospective study of patients with Escherichia coli bacteriuria. Both host (urinary retention; history of urogenital surgery) and pathogen factors (a capsule characteristic) were independent predictors of bacteremia.
Background. The urinary tract is the most common source for Escherichia coli bacteremia. Mortality from E. coli urinary-source bacteremia is higher than that from urinary tract infection. Predisposing factors for urinary-source E. coli bacteremia are poorly characterized.
Methods. In order to identify urinary-source bacteremia risk factors, we conducted a 12-month prospective cohort study of adult inpatients with E. coli bacteriuria that were tested for bacteremia within ±1 day of the bacteriuria. Patients with bacteremia were compared with those without bacteremia. Bacterial isolates from urine were screened for 16 putative virulence genes using high-throughput dot-blot hybridization.
Results. Twenty-four of 156 subjects (15%) had E. coli bacteremia. Bacteremic patients were more likely to have benign prostatic hyperplasia (56% vs 19%; P = .04), a history of urogenital surgery (63% vs 28%; P = .001), and presentation with hesitancy/retention (21% vs 4%; P = .002), fever (63% vs 38%; P = .02), and pyelonephritis (67% vs 41%; P = .02). The genes kpsMT (group II capsule) (17 [71%] vs 62 [47%]; P = .03) and prf (P-fimbriae family) (13 [54%] vs 40 [30%]; P = .02) were more frequent in the urinary strains from bacteremic patients. Symptoms of hesitancy/retention (odds ratio [OR], 7.8; 95% confidence interval [CI], 1.6–37), history of a urogenital procedure (OR, 5.4; 95% CI, 2–14.7), and presence of kpsMT (OR, 2.9; 95% CI, 1–8.2) independently predicted bacteremia.
Conclusions. Bacteremia secondary to E. coli bacteriuria was frequent (15%) in those tested for it. Urinary stasis, surgical disruption of urogenital tissues, and a bacterial capsule characteristic contribute to systemic invasion by uropathogenic E. coli.
PMCID: PMC3357479  PMID: 22431806
15.  Patient characteristics but not virulence factors discriminate between asymptomatic and symptomatic E. coli bacteriuria in the hospital 
BMC Infectious Diseases  2013;13:213.
Escherichia coli is a common cause of asymptomatic and symptomatic bacteriuria in hospitalized patients. Asymptomatic bacteriuria (ASB) is frequently treated with antibiotics without a clear indication. Our goal was to determine patient and pathogen factors suggestive of ASB.
We conducted a 12-month prospective cohort study of adult inpatients with E. coli bacteriuria seen at a tertiary care hospital in St. Louis, Missouri, USA. Urine cultures were taken at the discretion of treating physicians. Bacterial isolates were tested for 14 putative virulence genes using high-throughput dot-blot hybridization.
The median age of the 287 study patients was 65 (19–101) years; 78% were female. Seventy percent had community-acquired bacteriuria. One-hundred ten (38.3%) patients had ASB and 177 (61.7%) had symptomatic urinary tract infection (sUTI). Asymptomatic patients were more likely than symptomatic patients to have congestive heart failure (p = 0.03), a history of myocardial infarction (p = 0.01), chronic pulmonary disease (p = 0.045), peripheral vascular disease (p = 0.04), and dementia (p = 0.03). Patients with sUTI were more likely to be neutropenic at the time of bacteriuria (p = 0.046). Chronic pulmonary disease [OR 2.1 (95% CI 1.04, 4.1)] and dementia [OR 2.4 (95% CI 1.02, 5.8)] were independent predictors for asymptomatic bacteriuria. Absence of pyuria was not predictive of ASB. None of the individual virulence genes tested were associated with ASB nor was the total number of genes.
Asymptomatic E. coli bacteriuria in hospitalized patients was frequent and more common in patients with dementia and chronic pulmonary disease. Bacterial virulence factors could not discriminate symptomatic from asymptomatic bacteriurias. Asymptomatic E. coli bacteriuria cannot be predicted by virulence screening.
PMCID: PMC3658957  PMID: 23663267
Escherichia coli; Bacteriuria; Urinary tract infection; Asymptomatic; Virulence factors
16.  A Modeling Framework for the Evolution and Spread of Antibiotic Resistance: Literature Review and Model Categorization 
American Journal of Epidemiology  2013;178(4):508-520.
Antibiotic-resistant infections complicate treatment and increase morbidity and mortality. Mathematical modeling has played an integral role in improving our understanding of antibiotic resistance. In these models, parameter sensitivity is often assessed, while model structure sensitivity is not. To examine the implications of this, we first reviewed the literature on antibiotic-resistance modeling published between 1993 and 2011. We then classified each article's model structure into one or more of 6 categories based on the assumptions made in those articles regarding within-host and population-level competition between antibiotic-sensitive and antibiotic-resistant strains. Each model category has different dynamic implications with respect to how antibiotic use affects resistance prevalence, and therefore each may produce different conclusions about optimal treatment protocols that minimize resistance. Thus, even if all parameter values are correctly estimated, inferences may be incorrect because of the incorrect selection of model structure. Our framework provides insight into model selection.
PMCID: PMC3736756  PMID: 23660797
anti-bacterial agents; bacteria; bacterial infections; basic reproduction number; drug resistance; humans; models, theoretical
17.  A comparison of sexual behavior patterns among men who have sex with men and heterosexual men and women 
Men who have sex with men (MSM) have higher rates of HIV and other sexually transmitted infections (STI) than women and heterosexual men. This elevated risk persists across age groups and reflects biological and behavioral factors, yet there have been few direct comparisons of sexual behavior patterns between these populations.
We compared sexual behavior patterns of MSM and male and female heterosexuals aged 18–39 using 4 population-based random digit dialing surveys. A 1996–1998 survey in 4 U.S. cities and 2 Seattle surveys (2003, 2006) provided estimates for MSM; a 2003–2004 Seattle survey provided data about heterosexual men and women.
Sexual debut occurred earlier among MSM than heterosexuals. MSM reported longer cumulative lifetime periods of new partner acquisition than heterosexuals, and a more gradual decline in new partnership formation with age. Among MSM, 86% of 18–24 year olds and 72% of 35–39 year olds formed a new partnership during the prior year, compared to 56% of heterosexual men and 34% of women at ages 18–24, and 21% and 10%, respectively, at ages 35–39. MSM were also more likely to choose partners >5 years older and were 2–3 times as likely as heterosexuals to report recent concurrent partnerships. MSM reported more consistent condom use during anal sex than heterosexuals reported during vaginal sex.
MSM have longer periods of partnership acquisition, a higher prevalence of partnership concurrency, and more age-disassortative mixing than heterosexuals. These factors likely help explain higher HIV/STI rates among MSM, despite higher levels of condom use.
PMCID: PMC3334840  PMID: 22522237
men who have sex with men; heterosexuals; sexual behavior; HIV; STI
18.  Wounds, Functional Disability, and Indwelling Devices Are Associated With Cocolonization by Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci in Southeast Michigan 
Cocolonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) is a precursor to vancomycin-resistant S. aureus emergence. MRSA/VRE cocolonization incidence is higher among skilled nursing facility residents with functional disability and indwelling devices and occurs more frequently in wounds than other anatomical sites.
Background. Methicillin-resistant Staphylococcus aureus (MRSA) remains sensitive to vancomycin; when vancomycin-resistant S. aureus (VRSA) emerges, treatment becomes more complex. VRSA emergence is attributed to conjugative transfer of the vancomycin-resistance gene cluster from vancomycin-resistant enterococci (VRE) to MRSA. Because cocolonization with MRSA and VRE precedes VRSA development, this study investigates the epidemiology of cocolonization in skilled nursing facility (SNF) residents at high risk for MRSA or VRE colonization.
Methods. A prospective observational study conducted at 15 SNFs in southeast Michigan. Overall, 178 residents (90 with indwelling urinary catheters and/or feeding tubes and 88 device-free) were cultured monthly for MRSA and VRE, and clinical data were recorded.
Results. The incidence of MRSA/VRE cocolonization among residents with indwelling devices was 6.5 per 100 resident-months; 5.2 (95% confidence interval [CI]: 1.49–18.1) times that among those without devices. MRSA/VRE cocolonization in the device group occurred most frequently in wounds (4.1 per 100 resident-months). In a logistic regression analysis limited to residents with devices, functional disability (rate ratio [RR], 1.3; 95% CI: 1.1–1.4) and wound presence (RR, 3.4; 95% CI: 1.4–8.6) were independent risk factors of cocolonization.
Conclusions. In a population of SNF residents, individuals with indwelling devices who also had functional disability or wounds were at greatest risk of MRSA/VRE cocolonization. These individuals should be routinely monitored for the presence of VRSA colonization.
PMCID: PMC3214588  PMID: 22080118
19.  Gram Stains: A Resource for Retrospective Analysis of Bacterial Pathogens in Clinical Studies 
PLoS ONE  2012;7(10):e42898.
We demonstrate the feasibility of using qPCR on DNA extracted from vaginal Gram stain slides to estimate the presence and relative abundance of specific bacterial pathogens. We first tested Gram stained slides spiked with a mix of 108 cfu/ml of Escherichia coli and 105 cfu/ml of Lactobacillus acidophilus. Primers were designed for amplification of total and species-specific bacterial DNA based on 16S ribosomal gene regions. Sample DNA was pre-amplified with nearly full length 16S rDNA ribosomal gene fragment, followed by quantitative PCR with genera and species-specific 16S rDNA primers. Pre-amplification PCR increased the bacterial amounts; relative proportions of Escherichia coli and Lactobacillus recovered from spiked slides remained unchanged. We applied this method to forty two archived Gram stained slides available from a clinical trial of cerclage in pregnant women at high risk of preterm birth. We found a high correlation between Nugent scores based on bacterial morphology of Lactobacillus, Gardenerella and Mobiluncus and amounts of quantitative PCR estimated genus specific DNA (rrn copies) from Gram stained slides. Testing of a convenience sample of eight paired vaginal swabs and Gram stains freshly collected from healthy women found similar qPCR generated estimates of Lactobacillus proportions from Gram stained slides and vaginal swabs. Archived Gram stained slides collected from large scale epidemiologic and clinical studies represent a valuable, untapped resource for research on the composition of bacterial communities that colonize human mucosal surfaces.
PMCID: PMC3469605  PMID: 23071487
20.  Transmission probabilities and durations of immunity for three pathogenic group B Streptococcus serotypes 
Infection, Genetics and Evolution  2011;11(6):1407-1412.
Group B Streptococcus (GBS) remains a major cause of neonatal sepsis and is an emerging cause of invasive bacterial infections. The 9 known serotypes vary in virulence, and there is little cross-immunity. Key parameters for planning an effective vaccination strategy, such as average length of immunity and transmission probabilities by serotype, are unknown. We simulated GBS spread in a population using a computational model with parameters derived from studies of GBS sexual transmission in a college dormitory. Here we provide estimates of the duration of immunity relative to the transmission probabilities for the 3 GBS serotypes most associated with invasive disease: Ia, III, and V. We also place upper limits on the durations of immunity for serotype Ia (570 days), III (1125 days) and V (260 days). Better transmission estimates are required to establish the epidemiological parameters of GBS infection and determine the best vaccination strategies to prevent GBS disease.
PMCID: PMC3391980  PMID: 21605704
vaccines; modeling; Streptococcus agalactiae; group B Streptococcus
21.  Skin microbiota: Microbial community structure and its potential association with health and disease 
Skin, the largest human organ, is a complex and dynamic ecosystem inhabited by a multitude of microorganisms. Host demographics and genetics, human behavior, local and regional environmental characteristics, and transmission events may all potentially drive human skin microbiota variability, resulting in an alteration of microbial community structure. This alteration may have important consequences regarding health and disease outcomes among individuals. More specifically, certain diversity patterns of human microbiota may be predictive or diagnostic of disease. The purpose of this review is to briefly describe the skin microbiota, outline the potential determining factors driving its variability, posit the likelihood of an association between the resulting microbial community structure on the skin with disease outcomes among individuals, and finally, to present some challenges and implications for studying the skin microbiota.
PMCID: PMC3114449  PMID: 21463709
microbial ecology; epidemiology; diversity; transmission; skin
22.  Early development of bacterial community diversity in emergently placed urinary catheters 
BMC Research Notes  2012;5:332.
Approximately 25% of hospitalized patients have a urinary catheter, and catheter associated urinary tract infection is the most common nosocomial infection in the US, causing >1 million cases/year. However, the natural history of the biofilms that rapidly form on urinary catheters and lead to infection is not well described.
We characterized the dynamics of catheter colonization among catheters collected from 3 women and 5 men in a trauma burn unit with different indwelling times using TRFLP and culture. All patients received antibiotic therapy. Results: Colony-forming units increased along the extraluminal catheter surface from the catheter balloon to the urethra, but no trend was apparent for the intraluminal surface. This suggests extraluminal bacteria come from periurethral communities while intraluminal bacteria are introduced via the catheter or already inhabit the urine/bladder. Richness of operational taxonomic units (OTUs) increased over time on the intraluminal surface, but was constant extraluminally.
OTU community composition was explained best by time rather than axial location or surface. Our results suggest that catheter colonization can be very dynamic, and possibly have a predictable succession.
PMCID: PMC3500218  PMID: 22738659
Urinary tract infection; Microbial ecology; Biofilms; Urinary catheter
23.  Identification of a Novel Keyhole Phenotype in Double-Disk Diffusion Assays of Clindamycin-Resistant Erythromycin-Sensitive Strains of Streptococcus agalactiae 
Microbial Drug Resistance  2011;17(1):121-124.
Our objective was to characterize 46 unique, erythromycin-sensitive, and clindamycin-resistant Streptococcus agalactiae strains from S. Korea that displayed a novel phenotype in double-disk diffusion assay. We used polymerase chain reaction to determine presence of erythromycin and clindamycin resistance genes, disc diffusion assays to determine resistance phenotype, and microbroth dilution to determine minimal inhibitory concentration. We detected a novel phenotype in the double-disk diffusion assay for inducible resistance among 46 S. agalactiae strains that were both erythromycin sensitive and clindamycin resistant. Thirty-two strains with the novel phenotype tested positive for erm(B) by DNA–DNA hybridization; sequencing of the erm(B) gene revealed mutations in the ribosomal binding site region in the erm(B) open reading frame, which is consistent with a lack of erythromycin resistance phenotype. Although identified from patients at multiple hospitals, genotyping suggested that the strains are closely related. The new phenotype shows increased sensitivity to clindamycin in the presence of erythromycin.
PMCID: PMC3124752  PMID: 21166574
24.  Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection: Results From a Randomized Placebo-Controlled Trial 
Among otherwise healthy college women with a newly-diagnosed acute UTI, drinking 8 oz of 27% cranberry juice twice a day did not decrease the 6-month incidence of a second UTI compared to those drinking a placebo.
Background. A number of observational studies and a few small or open randomized clinical trials suggest that the American cranberry may decrease incidence of recurring urinary tract infection (UTI).
Methods. We conducted a double-blind, placebo-controlled trial of the effects of cranberry on risk of recurring UTI among 319 college women presenting with an acute UTI. Participants were followed up until a second UTI or for 6 months, whichever came first. A UTI was defined on the basis of the combination of symptoms and a urine culture positive for a known uropathogen. The study was designed to detect a 2-fold difference between treated and placebo groups, as was detected in unblinded trials. We assumed 30% of participants would experience a UTI during the follow-up period.
Results. Overall, the recurrence rate was 16.9% (95% confidence interval, 12.8%–21.0%), and the distribution of the recurrences was similar between study groups, with the active cranberry group presenting a slightly higher recurrence rate (20.0% vs 14.0%). The presence of urinary symptoms at 3 days, 1–2 weeks, and at ≥1 month was similar between study groups, with overall no marked differences.
Conclusions. Among otherwise healthy college women with an acute UTI, those drinking 8 oz of 27% cranberry juice twice daily did not experience a decrease in the 6-month incidence of a second UTI, compared with those drinking a placebo.
PMCID: PMC3060891  PMID: 21148516
25.  Risk Factors for Group B Streptococcus Colonization Among Pregnant Women in Korea 
Epidemiology and Health  2011;33:e2011010.
To identify obstetric and maternal factors related to Group B Streptococcus (GBS) colonization in pregnant women in Korea.
The study was conducted between the years 2006-2008 in four hospitals, Cheil and Eulji hospital in Seoul, and Motae and Eulji hospital in Daejeon. We recruited 2,644 pregnant women between 35 to 37 weeks of gestation who had visited for antenatal care. Participants completed a questionnaire, and urine, vaginal and rectal specimens were obtained and cultured using selective broth media. After delivery, medical records were reviewed.
GBS colonization was significantly associated with hospital, age group, education, frequency of pregnancy, and premature rupture of membranes (PROM, more than 18 hours). After adjustment for other variables, Cheil hospital (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.20-3.52), and the first pregnancy (OR, 2.32; 95% CI, 1.12-4.81) remained significant. History of vaginitis showed marginal significance (OR, 1.50; 95% CI, 0.98-2.29).
To prevent GBS infection of neonates, clinicians should be alert to the potentially higher risk of GBS colonization in pregnant women in their first pregnancy, and women with premature rupture of membranes (PROM) (18 hours+) or who have a history of vaginitis.
PMCID: PMC3221034  PMID: 22111030
Colonization; Pregnant women; Risk factors; Screening; Streptococcus agalactiae

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