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A total of 98 isolates of group A streptococci of T1M1 serotype isolated in Finland during 19881995 from bacteremic, pharyngeal, and pyogenic infections were studied by molecular means. The typing techniques used included restriction endonuclease analysis, ribotyping, and random amplified polymorphic DNA analysis. Representatives of each observed genotype were also examined for carriage of the speA gene encoding for pyrogenic exotoxin A. All of the serotype T1M1 isolates studied were considered to be of a single clonal origin, and 66% were identical by all three genotyping techniques used. Among the remaining 34% of closely related isolates, 13 different genotypes were detected. All isolates studied carried the speA gene. No evidence was found of correlation of the genomic type to the severity of the infection or the time of isolation. [ABSTRACT FROM PUBLISHER]

Ninety-nine penicillin-sensitive Streptococcus pneumoniae strains of common pediatric serogroups/types (6, 7, 14, 19, and 23) cultured from the blood of children with invasive disease (n = 49) or asymptomatic oropharyngeal carriage (n = 50) were analyzed by multilocus enzyme electrophoresis and ribotyping; 53 distinctive multilocus enzyme genotypes (ETs) and 53 ribotypes were identified. Multilocus enzyme electrophoresis showed good correlation with ribotying. ETs and ribotypes among invasive and carriage isolates were similar. Within different S. pneumoniae serogroups/types, both clonal (7 and 14) and heterogenous (6, 19, and 23) ET and rRNA hybridization patterns were observed. Greatest diversity was observed among serotypes 6A, 6B, and 19F. Use of 12 additional restriction enzymes besides PvuII and BglII did not increase ribotype discrimination within serotype 7 and 14 isolates. Serotype 7 and 14 strains, which appear clonal by subtyping, are rare among carriers but common causes of invasive disease. Characteristics associated with their clonality may represent an advantage for invasiveness. [ABSTRACT FROM AUTHOR]

The in-vitro activities of ten antibiotics against 83 toxigenic strains of Corynebacterium diphtheriae recently isolated in northwestern Russia and surrounding areas were determined by an agar dilution method. All of the strains were susceptible to erythromycin, penicillin, ampicillin, cefuroxime, chloramphenicol, ciprofloxacin, gentamicin and tetracycline. Trimethoprim and rifampicin were each active against 81 isolates, the two strains resistant to the latter agent having been isolated from two members of the same family. [ABSTRACT FROM AUTHOR]

A cluster of cases of Staphylococcus epidermidis bacteremia in a neonatal intensive-care unit (NICU) during 1991 raised the question of whether these infections were caused by a single strain. Sixty-seven isolates of S. epidermidis from blood cultures of 56 neonates treated in the NICU between 1986 and 1992 and 54 control strains from other patients with bacteremia were characterized by three typing methods: antibiogram, plasmid profile, and ribotype. Plasmid profiles and ribotype patterns indicated that 11 (16%) of the 67 episodes of S. epidermidis bacteremia in the NICU were caused by a single strain. Although this epidemic strain did not account entirely for the increase in the incidence of bacteremia in the NICU, it did persist for 4 years during the study period. Other clones responsible for smaller outbreaks were also found. These results suggest that S. epidermidis cross-infections are very common in the NICU setting. [ABSTRACT FROM PUBLISHER]

Maifan stone is a kind of mineral medicine in Chinese medicine, which has good adsorption, dissolution, mineralization and biological activity. It has an excellent therapeutic effect on livestock, poultry and aquatic animals suffering from intestinal diseases. This study explored the effect of Maifan stone on the growth ability of Lacticaseibacillus rhamnosus GG (L. rhamnosus GG) and the effect of Maifan stone‐L. rhamnosus GG‐fermented product on the intestinal inflammation and gut microbiota. We find that Maifan stone can adsorb L. rhamnosus GG to form a carrier bacteria. Maifan stone has the characteristics of acid tolerance and bile salt tolerance and can also improve the activity of L. rhamnosus GG in artificial gastrointestinal juice. The fermented product can reduce the degree of diarrhoea and colon pathology in rats to a certain extent and significantly improve intestinal inflammatory factors and gut microbiota. This study improves the application effect of L. rhamnosus GG in the prevention and treatment of diarrhoea animals and provides a scientific basis for the rational development of Maifan stone resources. [ABSTRACT FROM AUTHOR]

Antimicrobial-resistant Neisseria gonorrhoeae infections are a threat to public health. Novel strategies for combating such resistance include the development of molecular assays to facilitate real-time prediction of antimicrobial susceptibility. Resistance to ciprofloxacin is determined by the presence of a single mutation at codon 91 of the gyrase A gene; molecular assays to guide therapy are commercially available. Resistance to cefixime is conferred via 1 of 6 critical mutations in either the mosaic pen A gene or specific loci in the nonmosaic region. Resistance to ceftriaxone is conferred through mutations in 1 of 4 genes: pen A, pon A, pen B, and mtr ; however, the ability to predict reduced susceptibility based on those genes varies by geographic region. Here, we highlight the work done toward the development of 3 such assays for ciprofloxacin, cefixime, and ceftriaxone, discuss the status of our current understanding and ongoing challenges, and suggest future directions. [ABSTRACT FROM AUTHOR]

Trade-offs of antibiotic resistance evolution, such as fitness cost and collateral sensitivity (CS), could be exploited to drive evolution toward antibiotic susceptibility. Decline of resistance may occur when resistance to other drug leads to CS to the first one and when compensatory mutations, or genetic reversion of the original ones, reduce fitness cost. Here we describe the impact of antibiotic-free and sublethal environments on declining ceftazidime resistance in different Pseudomonas aeruginosa resistant mutants. We determined that decline of ceftazidime resistance occurs within 450 generations, which is caused by newly acquired mutations and not by reversion of the original ones, and that the original CS of these mutants is preserved. In addition, we observed that the frequency and degree of this decline is contingent on genetic background. Our results are relevant to implement evolution-based therapeutic approaches, as well as to redefine global policies of antibiotic use, such as drug cycling. [ABSTRACT FROM AUTHOR]

Summary: Alterations in the composition and reduced diversity of the infant microbiome are associated with allergic disease in children. Further, an altered microbiota is linked to immune dysregulation, including skewing of different T helper (Th) subsets, which is also seen in atopic individuals. The aim of this study was, therefore, to investigate the associations between gut lactobacilli and Th‐related plasma factors in allergy development during childhood. A total of 194 children with known allergy status at 1 year of age were followed to 10 years of age. We used real‐time polymerase chain reaction (PCR) to investigate the presence of three lactobacilli species (Lactobacillus casei, L. paracasei, L. rhamnosus) in infant fecal samples (collected between 1 week and 2 months of age) from a subgroup of children. Plasma chemokines and cytokines were quantified at 6 months and at 1, 2, 5 and 10 years of age with Luminex or enzyme‐linked immunosorbent assay (ELISA). Fractional exhaled nitrogen oxide (FeNO) was measured and spirometry performed at 10 years of age. The data were analysed by non‐parametric testing and a logistic regression model adjusted for parental allergy. An absence of these lactobacilli and higher levels of the chemokines BCA‐1/CXCL13, CCL17/TARC, MIP‐3α/CCL20 and MDC/CCL22 in plasma at 6 months of age preceded allergy development. The presence of lactobacilli associated with lower levels of atopy‐related chemokines during infancy, together with higher levels of interferon (IFN)‐γ and lower FeNO during later childhood. The results indicate that the presence of certain lactobacilli species in the infant gut may influence allergy‐related parameters in the peripheral immune system, and thereby contribute to allergy protection. [ABSTRACT FROM AUTHOR]

Aims: Antibiotic adjuvants can give a second life to the antibiotics to which bacteria are highly resistant. We evaluated the antimicrobial effects of extracts from Pithecellobium clypearia against methicillin‐resistant Staphylococcus aureus (MRSA) and also the potential for synergy with several antibiotics. Methods and Results: For this study, four extracts from P. clypearia were tested on MRSA using the broth microdilution method for activity assessment. The ethyl acetate fraction (S20b) had the strongest antibacterial activity against MRSA among the fractions tested. In all, 14 compounds such as gallic acid and luteolin in S20b were analysed by UFLC‐Q‐TOF‐MS/MS. S20b combined with erythromycin showed synergy effects against MRSA and combined with ceftriaxone sodium and levofloxacin showed additive effects against MRSA. Electron microscopy showed that extract S20b damaged the MRSA cell wall and K+ efflux measurements indicated that extract S20b increased cell membrane permeability. Moreover, S20b suppression of PBP2a expression was assessed by Western blot. Furthermore, an in vivo study was used to investigate the therapeutic potential of S20b based on a mouse pneumonia model. Conclusions: The in vitro study results have shown that S20b not only inhibits MRSA growth directly but also reduces the resistance of MRSA to the evaluated antibacterial agents. Based on the in vivo study, it can be concluded that S20b can treat pneumonia in the mouse model. Significance and Impact of the Study: This study is the first research to demonstrate that S20b can inhibit MRSA growth and reduce drug resistance of clinical isolates to antibiotics. S20b has the potential to be used as a therapeutic agent against MRSA and treatment for MRSA pneumonia. [ABSTRACT FROM AUTHOR]

In this point-prevalence study of 32 US children's hospitals, we determined that 1.7% of hospitalized children received at least 1 antimicrobial agent for a non–infection-related reason; macrolides were used most commonly. Antimicrobial stewardship efforts to understand and affect use for these reasons is an unmet need; additional research considering the individual and societal effects of these antimicrobial-prescribing practices should be undertaken. [ABSTRACT FROM AUTHOR]

Objectives There are substantial variations between different populations in the susceptibility of Neisseria gonorrhoeae to antimicrobials, and the reasons for this are largely unexplored. We aimed to assess whether the population-level consumption of antimicrobials is a contributory factor. Methods Using antimicrobial susceptibility data from 24 countries in the European Gonococcal Antimicrobial Surveillance Programme and antimicrobial consumption data from the IQVIA MIDAS database, we built mixed-effects linear/logistic regression models with country-level cephalosporin, fluoroquinolone, and macrolide consumption (standard doses/1000 population/year) as the explanatory variables (from 2009 to 2015) and 1-year-lagged ceftriaxone, cefixime, azithromycin, and ciprofloxacin geometric mean minimum inhibitory concentrations (MICs) as the outcome variables (from 2010 to 2016). Results Positive correlations were found between the consumption of cephalosporins and the geometric mean MICs of ceftriaxone and cefixime (P <.05 for both comparisons). Fluoroquinolone consumption was positively associated with the prevalence of resistance to ciprofloxacin (P <.05). Conclusions Differences in the population-level consumption of particular antimicrobials may contribute to variations in the level of antimicrobial resistance in N. gonorrhoeae in different settings. Further interventions to reduce misuse and overuse of antimicrobials in high-consumption populations and core groups are required. [ABSTRACT FROM AUTHOR]

Aim: To study the prophylactic effect of recombinant Lactococcus lactis (rLl) harbouring Ara h 2.02 peanut allergen, in sensitized and challenged mice. Methods and Results: Ara h 2.02 cDNA was cloned into pNZ8048 for heterologous expression in L. lactis. The purified recombinant allergen showed IgE binding comparable with native Ara h 2. Balb/c mice were fed with either recombinant (rLl), nonrecombinant L. lactis (Ll) or NaHCO3 (Sham) prior to sensitization and challenged with rAra h 2.02, whereas the baseline group was only fed with Ll. Allergen‐specific immunoglobulin and splenocyte cytokines responses were determined for each mouse. Mice fed with either Ll or rLl showed significant alleviation of IgE and IgG1 compared to the Sham group. Despite no significant decrease in Th2 (IL‐4, IL‐13, IL‐6) or increase in Th1 (IFN‐γ) cytokines, both groups showed lower IL‐10 level, while the IL‐4 : IFN‐γ ratio was significantly lower for rLl compared to Ll group. Conclusions: Oral administration of rLl harbouring Ara h 2.02 demonstrated alleviation of Th2‐associated responses in allergen‐challenged mice and a possible added allergen‐specific prophylactic effect. Significance and Impact of the Study: Ara h 2.02 coupled with the intrinsic properties of probiotic L. lactis as a delivery vehicle can be explored for the development of a commercially scalable vaccine. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown an association between body mass index (BMI) and infections, but the literature on type-specific community acquired infections is still limited.Methods: We included 39 163 Swedish adults who completed a questionnaire in September 1997 and were followed through record-linkages until December 2016. Information on BMI was self-reported and infections were identified from the Swedish National Patient Register using International Classification of Diseases (ICD), Tenth Revision (ICD-10) codes. We fitted multivariable Cox proportional hazards models for time-to-first-event analysis, and we used extensions of the standard Cox model when repeated events were included.Results: During a 19-year follow-up 32% of the subjects had at least one infection requiring health care contact, leading to a total of 27 675 events. We found an increased incidence of any infection in obese women [hazard ratio (HR) = 1.22; 95% confidence interval (CI) = 1.12; 1.33] and obese men (HR = 1.25; 95% CI = 1.09; 1.43) compared with normal weight subjects. For specific infections, higher incidences were observed for skin infections in both genders (HR = 1.76; 95% CI = 1.47; 2.12 for obese females and HR = 1.74; 95% CI = 1.33; 2.28 for obese males) and gastrointestinal tract infections (HR = 1.44; 95% CI = 1.19; 1.75), urinary tract infections (HR = 1.30; 95% CI = 1.08; 1.55) and sepsis (HR = 2.09; 95% CI = 1.46; 2.99) in obese females. When accounting for repeated events, estimates similar to the aforementioned ones were found.Conclusions: Obesity was associated with an increased risk of infections in both genders. Results from multiple-failure survival analysis were consistent with those from classic Cox models. [ABSTRACT FROM AUTHOR]

Background Infective endocarditis (IE) is a potentially life-threatening infection of the heart's endocardial surface. Despite advances in the diagnosis and management of IE, morbidity and mortality remain high. Aim To characterize the demographics, bacteriology and outcomes of IE cases presenting to an Irish tertiary referral centre. Design Retrospective cohort study. Methods Patients were identified using Hospital Inpatient Enquiry and Clinical Microbiology inpatient consult data, from January 2005 to January 2014. Patients were diagnosed with IE using Modified Duke Criteria. Standard Bayesian statistics were employed for analysis and cases were compared to contemporary international registries. Results Two hundred and two patients were diagnosed with IE during this period. Mean age 54 years. Of these, 136 (67%) were native valve endocarditis (NVE), 50 (25%) were prosthetic valve endocarditis (PVE) and 22 (11%) were cardiovascular implantable electronic device-associated endocarditis. Culprit organism was identified in 176 (87.1%) cases and Staphylococcal species were the most common (57.5%). Fifty-nine per cent of NVE required surgery compared to 66% of PVE. Mean mortality rate was 17.3%, with NVE being the lowest (12.5%) and PVE the highest (32%). Increasing age was also associated with increased mortality. Fifty-three (26.2%) patients had embolic complications. Conclusions This Irish cohort exhibited first-world demographic patterns comparable to those published in contemporary international literature. PVE required surgery more often and was associated with higher rates of mortality than NVE. Embolic complications were relatively common and represent important sequelae, especially in the intravenous drug user population. It is also pertinent to aggressively treat older cohorts as they were associated with increased mortality. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship (AS) programs promote the optimal use of antimicrobials and safe patient care. With most antimicrobials prescribed in the ambulatory setting, establishing benchmark data is imperative to gauge the impact of future AS initiatives.Objectives: To determine the frequency of potentially inappropriate antimicrobial prescribing in primary care practices in Manitoba, Canada and to assess the association between potentially inappropriate antimicrobial prescribing and patient, prescriber and practice-related factors.Methods: A retrospective cohort study using the Manitoba Primary Care Research Network repository of de-identified Electronic Medical Records from consenting primary care practices. Descriptive statistics and logistic regressions detailed patients with bacterial or viral infections of interest and antimicrobial prescriptions.Results: Eighteen percent (n = 35 574) of primary care visits for common infections were associated with a potentially inappropriate antimicrobial prescription. Among antimicrobials prescribed to patients diagnosed with bacterial infections, 37.8% (n = 2168) had a potentially inappropriate antimicrobial prescribed and 19.6% (n = 1126) had an antimicrobial prescribed for a duration outside of guideline-based ranges. Female patients, younger age and less office visits were associated with potentially inappropriate antimicrobial prescribing for bacterial infections. Among physician visits for viral infection, 15.9% (n = 29 833) were associated with an antimicrobial prescription. Older patients, those with more comorbidity, more office visits and those who were seen in larger or rural practices, were associated with potentially inappropriate antimicrobial prescribing for viral infections.Conclusions: High frequency of potentially inappropriate antimicrobial prescribing, especially in certain patient populations, suggests the need for coordinated community-based AS programs to optimize prescribing and improve patient care. [ABSTRACT FROM AUTHOR]

Over the last three decades, successful implementation of the diphtheria vaccination in the developed and developing countries has reduced the infections caused by the toxigenic strains of Corynebacterium diphtheriae, but a concomitant increase in the invasive infections due to the nontoxigenic strains was seen. In addition, the recent reports on the emergence of nontoxigenic toxin gene-bearing strains, having the potential to revert back to toxigenic form poses a significant threat to human beings. Besides infections caused by C. diphtheriae, the emergence of the respiratory, cutaneous and invasive infections by related pathogenic Corynebacterium species like C. ulcerans and C. pseudotuberculosis, complicate the diagnosis and management of infection. These observations together with the widespread prevalence of diphtheria in the vaccine era, necessitates the strengthening of the epidemiological surveillance and laboratory diagnosis of the pathogen. This review provides the overview of the advantages and limitations of different molecular methods and the role of MALDI- TOF in the laboratory diagnosis of Diphtheria. The contribution of next generation sequencing technology and different genotyping techniques in understanding the pathogenicity, transmission dynamics and epidemiology of the C. diphtheriae is discussed. [ABSTRACT FROM AUTHOR]

Background. The incidence of cellulitis is highly seasonal and this seasonality may be explained by changes in the weather, specifically, temperature. Methods. Using data from the Nationwide Inpatient Sample (years 1998 to 2011), we identified the geographic location for 773 719 admissions with the primary diagnosis (ICD-9-CM code) of cellulitis and abscess of finger and toe (681.XX) and other cellulitis and abscess (682.XX). Next, we used data from the National Climatic Data Center to estimate the monthly average temperature for each of these different locations. We modeled the odds of an admission having a primary diagnosis of cellulitis as a function of demographics, payer, location, patient severity, admission month, year, and the average temperature in the month of admission. Results. We found that the odds of an admission with a primary diagnosis of cellulitis increase with higher temperatures in a dose-response fashion. For example, relative to a cold February with average temperatures under 40° F, an admission in a hot July with an average temperature exceeding 90°F has 66.63% higher odds of being diagnosed with cellulitis (95% confidence interval [CI]: [61.2, 72.3]). After controlling for temperature, the estimated amplitude of seasonality of cellulitis decreased by approximately 71%. Conclusion. At a population level, admissions to the hospital for cellulitis risk are strongly associated with warmer weather. [ABSTRACT FROM AUTHOR]

Gram-positive, nonpathogenic lactic acid bacteria ( LAB) are considered to be promising candidates for the development of novel, safe production and delivery systems of heterologous proteins. Recombinant LAB strains were shown to elicit specific systemic and mucosal immune responses against selected antigens. For this reason, this group of bacteria is considered as a potential replacement of classical, often pathogenic, attenuated microbial carriers. Mucosal administration of recombinant LAB, especially via the best explored and universal oral route, offers many advantages in comparison to systemic inoculation, and is attractive from the immunological and practical point of view. Research aimed at designing efficient, mucosally applied vaccines in combination with improved immunization efficiency, monitoring of in vivo antigen production , determination of optimal dose for vaccination, strain selection and characterization is a priority in modern vaccinology. This paper summarizes and organizes the available knowledge on the application of LAB as live oral vaccine vectors. It constitutes a valuable source of general information for researchers interested in mucosal vaccine development and constructing LAB strains with vaccine potential. [ABSTRACT FROM AUTHOR]

Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The objectives of this systematic review and meta-analysis were to identify and appraise all controlled observational studies that have examined risk factors for the development of nonpurulent cellulitis of the leg ( NPLC). A systematic literature search of electronic databases and grey literature sources was performed in July 2015. The Newcastle-Ottawa Scale ( NOS) was used to assess methodological quality of included studies. Of 3059 potentially eligible studies retrieved and screened, six case-control studies were included. An increased risk of developing NPLC was associated with previous cellulitis [odds ratio ( OR) 40·3, 95% confidence interval ( CI) 22·6-72·0], wound ( OR 19·1, 95% CI 9·1-40·0), current leg ulcers ( OR 13·7, 95% CI 7·9-23·6), lymphoedema/chronic leg oedema ( OR 6·8, 95% CI 3·5-13·3), excoriating skin diseases ( OR 4·4, 95% CI 2·7-7·1), tinea pedis ( OR 3·2, 95% CI 1·9-5·3) and body mass index > 30 kg m−2 ( OR 2·4, 95% CI 1·4-4·0). Diabetes, smoking and alcohol consumption were not associated with NPLC. Although diabetics may have been underrepresented in the included studies, local risk factors appear to play a more significant role in the development of NPLC than do systemic risk factors. Clinicians should consider the treatment of modifiable risk factors including leg oedema, wounds, ulcers, areas of skin breakdown and toe-web intertrigo while administering antibiotic treatment for NPLC. [ABSTRACT FROM AUTHOR]

Summary: Accurate diagnosis and recognition of predisposing factors has been shown to be challenging in lower limb cellulitis (LLC). Assessment of 1746 consecutive patients with cellulitis presenting to a UK university hospital showed increasing overdiagnosis, with only 31.9% of patients referred during the period 2015–2018 having the diagnosis of LLC confirmed. Recognition of at least one predisposing factor increased from 61% to 89% following introduction of more specific screening questions. This identified a need for better primary care dermatology education and the benefit of a proforma with specific screening questions for reversible predisposing factors for LLC. [ABSTRACT FROM AUTHOR]

Background. Skin and soft tissue infections are common reasons for medical care. Use of broad-spectrum therapy and costs have increased. Assessment of early treatment response has been given a central role both in clinical trials and everyday practice. However, there is a paucity of data on the dynamics of response, causes of early nonresponse, and how early nonresponse affects resource use and predicts outcome. Methods. We prospectively enrolled 216 patients hospitalized with cellulitis. Clinical and biochemical response data during the first 3 days of treatment were analyzed in relation to baseline factors, antibiotic use, surgery, and outcome. Multivariable analysis included logistic lasso regression. Results. Clinical or biochemical response was observed in the majority of patients the day after treatment initiation. Concordance between clinical and biochemical response was strongest at days 2 and 3. Female sex, cardiovascular disease, higher body mass index, shorter duration of symptoms, and cellulitis other than typical erysipelas were predictors of nonresponse at day 3. In contrast, baseline factors were not predictive of clinical failure assessed posttreatment. Among cases with antibiotic treatment escalation by day 2, 90% (37/41) had nonresponse at day 1, but only 5% (2/40) had inappropriate initial therapy. Nonresponse at day 3 was a predictor of treatment duration >14 days, but not of clinical failure. Conclusions. Nonpharmacological factors had a major impact on early response dynamics. Delayed response was rarely related to inappropriate therapy but strongly predictive of early treatment escalation, suggesting that broadening antibiotic treatment may often be premature. [ABSTRACT FROM AUTHOR]

We investigated the possible association between body mass index (BMI; weight (kg)/height (m)2) and hospitalization or treatment for acute infection in a prospective cohort study. We linked 75,001 women enrolled in the Danish National Birth Cohort from 1996 to 2002, who had information on BMI and a broad range of confounders, to data on infectious diseases and use of antimicrobial agents from the National Patient Register and the Danish Prescription Register. Associations were tested using Cox proportional hazards models. During 12 years of follow-up, we observed a U-shaped association between baseline BMI and later hospitalization for 1) any infectious disease and 2) infections of the respiratory tract, whereas a dose-response relationship was seen for skin infections. The most pronounced associations were seen for acute upper respiratory infections at multiple and unspecified sites (underweight (BMI <18.5): hazard ratio (HR) = 4.26, 95% confidence interval (CI): 1.69, 10.7; obesity (BMI >30): HR = 3.64, 95% CI: 1.62, 8.18), erysipelas (obesity: HR = 5.19, 95% CI: 3.38, 7.95), and fungal infections (underweight: HR = 3.19, 95% CI: 1.53, 6.66). Slightly greater use of antimicrobials was observed among overweight (BMI 25-<30; HR = 1.08,95% CI: 1.06,1.10) and obese (HR= 1.21, 95% CI: 1.17, 1.24) women. Among Danish women, underweight and obesity were associated with increased risk of community-acquired infectious diseases, especially infections of the upper respiratory tract and skin. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is a major cause of life-threatening infections. Complement activation plays a vital role in opsonophagocytic killing of pneumococci in blood. Initial complement activation via the classical and lectin pathways is amplified through the alternative pathway amplification loop. Alternative pathway activity is inhibited by complement factor H (FH). Our study demonstrates the functional consequences of the variability in human serum FH levels on host defense. Using an in vivo mouse model combined with human in vitro assays, we show that the level of serum FH correlates with the efficacy of opsonophagocytic killing of pneumococci. In summary, we found that FH levels determine a delicate balance of alternative pathway activity, thus affecting the resistance to invasive pneumococcal disease. Our results suggest that variation in FH expression levels, naturally occurring in the human population, plays a thus far unrecognized role in the resistance to invasive pneumococcal disease. [ABSTRACT FROM AUTHOR]

Background. Invasive group A Streptococcus (iGAS) infections cause significant morbidity and mortality worldwide. We analyzed whether obesity and diabetes were associated with iGAS infections and worse outcomes among an adult US population. Methods. We determined the incidence of iGAS infections using 2010-2012 cases in adults aged ≥18 years from Active Bacterial Core surveillance (ABCs), a population-based surveillance system, as the numerator. For the denominator, we used ABCs catchment area population estimates from the 2011 to 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. The relative risk (RR) of iGAS was determined by obesity and diabetes status after adjusting for age group, gender, race, and other underlying conditions through binomial logistic regression. Multivariable logistic regression was used to determine whether obesity or diabetes was associated with increased odds of death due to iGAS compared to normal weight and nondiabetic patients, respectively. Results. Between 2010 and 2012, 2927 iGAS cases were identified. Diabetes was associated with an increased risk of iGAS in all racial groups (adjusted risk ratio [aRR] ranged from 2.71 to 5.08). Grade 3 obesity (body mass index [BMI] ≥40) was associated with an increased risk of iGAS for whites (aRR = 3.47; 95% confidence interval [CI], 3.00-4.01). Grades 1-2 (BMI = 30.0-<40.0) and grade 3 obesity were associated with an increased odds of death (odds ratio [OR] = 1.55, [95% CI, 1.05, 2.29] and OR = 1.62 [95% CI, 1.01, 2.61], respectively) when compared to normal weight patients. Conclusions. These results may help target vaccines against GAS that are currently under development. Efforts to develop enhanced treatment regimens for iGAS may improve prognoses for obese patients. [ABSTRACT FROM AUTHOR]

Previous studies on Candida species in a clinical setting in Ghana have shown a prevalence of Candida albicans. Despite this, very little is known about the various strain types and their population genetic structure. In this study three microsatellite loci, CAI, CAIII and CAVI, were used to investigate the population genetic structure of C. albicans from clinical isolates in Ghana. In all, 240 clinically unrelated C. albicans isolates were recovered from patients reporting at three teaching hospitals. All the isolates were heterozygous for at least one of the three loci, except for one isolate, which was homozygous for all three loci. Sixty-seven unique alleles and 240 different genotypes were generated by the three polymorphic microsatellite loci, resulting in a very high discriminatory potential of approximately 0.98. There was no significant difference in allele frequencies from the small number of anatomical sites sampled, regardless of the host conditions although high genotypic diversities were observed among the isolates. There was evidence for clonal reproduction, including over-expression of observed heterozygotes across the populations. The populations deviated significantly from Hardy-Weinberg equilibrium and pair-wise genotypic linkage disequilibria comparisons across the three loci were significant, also suggesting a clonal population. The overall Wright FIS for the three loci was negative, and the overall FST value was not significantly different from zero for the three loci analyzed, indicating a clonal and homogeneous population across the three sampling locations from Ghana. [ABSTRACT FROM AUTHOR]

Objectives: Macrolide resistance among Streptococcus pyogenes [group A streptococci (GAS)] in Portugal decreased between 1999 and 2006 and this decrease was accompanied by alterations in the prevalence of macrolide resistance phenotypes and clonal composition of the population. The aims of this study were to determine the macrolide resistance rate, resistance phenotypes and clones of GAS recovered from pharyngitis in 2007-13 in Portugal.Methods: Antimicrobial susceptibility was tested by disc diffusion. Macrolide-resistant isolates were characterized by emm typing, T typing, PFGE profiling and MLST, and the presence of macrolide resistance determinants was determined by PCR.Results: We found continuing changes in macrolide resistance phenotypes and a persistent decline in overall erythromycin resistance, from 10% in 2007 to 1% in 2013. During this period there was a marked increase in emm11-ST403 cMLSB isolates, the disappearance of the emm3-ST315 M lineage and changes in the prevalence of previously identified GAS clones. Unexpectedly, the decline in erythromycin resistance and the decreasing prevalence of the MLSB phenotype were accompanied by a high consumption of long-acting and intermediate-acting macrolides, known to select for resistance and particularly for the erm(B) gene.Conclusions: The continuous decline in macrolide resistance detected since 2000, accompanied by a high clonal instability, emphasizes the importance of considering factors other than antibiotic consumption in explaining the prevalence of macrolide-resistant GAS. [ABSTRACT FROM AUTHOR]

Objectives: Evidence indicates a relationship between obesity and infection. We assessed the prevalence of obesity in hospitalized patients and evaluated its impact on antimicrobial management.Methods: Three National Health Service hospitals in London in 2011-12 were included in a cross-sectional study. Data from all adult admissions units and medical and surgical wards were collected. Patient data were collected from the medication charts and nursing and medical notes. Antimicrobial therapy was defined as 'complicated' if the patient's therapy met two or more of the following criteria: (i) second- or third-line therapy according to local policy; (ii) intravenous therapy where an alternative oral therapy was appropriate; (iii) longer than the recommended duration of therapy as per local policy recommendations; (iv) repeated courses of therapy to treat the same infection; and (v) specialist advice on antimicrobial therapy provided by the medical microbiology or infectious diseases teams.Results: Of the 1014 patients included in this study, 22% (225) were obese, 69% (696) were normal/overweight and 9% (93) were underweight. Obese patients were significantly more likely to have more complicated antimicrobial therapy than normal/overweight and underweight patients (36% versus 19% and 23%, respectively, P = 0.002). After adjustment for hospital, age group, comorbidities and the type of infection, obese patients remained at significantly increased odds of receiving complicated antimicrobial therapy compared with normal/overweight patients (OR = 2.01, 95% CI 1.75-3.45).Conclusions: One in five hospitalized patients is obese. Compared with the underweight and normal/overweight, the antimicrobial management in the obese is significantly more complicated. [ABSTRACT FROM AUTHOR]

Background: People with severe obesity (body mass index [BMI] > 40 kg/m2) have an 85% higher mortality than people with a healthy BMI. Poor physical function may contribute to this excess mortality. Lymphoedema-like swelling can affect the legs of severely obese people with normal lymphoscintigraphy.Aim: We sought to determine the relationship between the presence of lymphoedema-like swelling and physical function in the severely obese.Design and Methods: In people with severe obesity, we ascertained whether lower leg lymphoedema-like swelling was present and determined the circumference of the lower leg, time taken to ascend and descend a 17-cm step 50 times and time taken to walk 500 m.Results: The 330 participants, 33% of whom were male, were aged 43.4 ± 12.7 years (mean ± standard deviation) and had a BMI of 51.7 ± 8.4 kg/m2. Lymphoedema-like swelling was present in approximately one-third (n = 108) in whom a prior history of cellulitis and venous thromboembolism was more common (relative risks 6.16 and 3.86, respectively) than in those without lymphoedema-like swelling. Participants with lymphoedema-like swelling, compared with non-affected counterparts, had a higher lower leg circumference (35.0 ± 7.1 vs. 32.4 ± 4.8 cm), a slower step speed (0.40 ± 0.12 vs. 0.43 ± 0.10 steps/s) and a slower walking speed (0.97 ± 0.37 vs. 1.08 ± 0.30 m/s, P < 0.05 for all comparisons).Conclusions: In this cross-sectional study, 33% of our severely obese participants had lymphoedema-like swelling. Participants with lymphoedema-like swelling had worse physical function than those without. This association was independent of BMI. The presence of obesity-related chronic lymphoedema-like swelling should lead to interventions that improve physical function. [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate the potential of Bacillus methylotrophicus as a probiotic. Methods and Results A Bacillus isolate designated strain C14 was isolated from Korean traditional fermented soybean paste (doenjang). The strain was identified, and its physiological and biochemical properties were characterized. The gastrointestinal tolerance and immunomodulatory function of strain C14 were also investigated. Strain C14 was identified as B. methylotrophicus by analysis of its biochemical properties using the API 50 CHB system and by phylogenetic analysis of the 16S rDNA sequence. Strain C14 showed >80% and >75% of survival for artificial gastric juices (pH 2·5 and 1% pepsin) and 0·5% (w/v) bile salt, respectively. Heat-killed B. methylotrophicus C14 inhibited the adhesion of various pathogens and enhanced the adhesion of probiotic bacteria to Caco-2 cells. The heat-killed cells also induced high levels of immune cell proliferation compared with the control and stimulated interleukin-6 and tumour necrosis factor- α production in mouse macrophages. Conclusions Bacillus methylotrophicus C14 could be used as a probiotic. Significance and Impact of the Study Recently identified B. methylotrophicus is a new potential probiotic with high gastrointestinal tolerance. [ABSTRACT FROM AUTHOR]

Drug-resistant Neisseria gonorrhoeae poses a significant public health challenge. In recent years, gonococci resistant to first- and second-line antibiotics have spread worldwide and new strains have developed that are increasingly resistant to third-generation cephalosporins, which are currently our last line of available treatments. Given the timeline required to develop new drugs or an effective vaccine for N. gonorrhoeae, a top priority is to use the drugs that are available as effectively as possible. Currently, clinical management of gonorrhoea is based upon treatment guidelines informed by international gonococcal antimicrobial susceptibility surveillance programmes. This approach, although currently the most practical, is subject to a number of limitations since surveillance data inherently provide population-level information. As a result, basing treatment guidelines on these data can result in the prescription of more aggressive or broader treatment than is needed by individual patients and hence inadvertently contribute to the development and spread of resistance to important drugs. Clearly, methods are needed that provide patient-specific drug susceptibility information in a time frame that would allow clinicians to prescribe individualized treatment regimens for gonorrhoea. Fortunately, in recent years, there have been a number of advances in the development of rapid methods for characterizing both the genotype and the drug resistance phenotype of N. gonorrhoeae strains. Here, we review these advances and propose additional studies that would help facilitate a transition towards an individualized treatment approach for gonorrhoea. [ABSTRACT FROM PUBLISHER]

In the present study, we have analysed the ability of Streptococcus pyogenes [ Group A streptococcus ( GAS)] to activate the NACHT-domain-, leucine-rich repeat- and PYD-containing protein 3 ( NALP3) inflammasome complex in human monocyte-derived macrophages and the molecules and signalling pathways involved in GAS-induced inflammatory responses. We focused upon analysing the impact of dynamin-dependent endocytosis and the role of major streptococcal virulence factors streptolysin O ( SLO) and streptolysin S ( SLS) in the immune responses induced by GAS. These virulence factors are involved in immune evasion by forming pores in host cell membranes, and aid the bacteria to escape from the endosome-lysosome pathway. We analysed cytokine gene expression in human primary macrophages after stimulation with live or inactivated wild-type GAS as well as with live SLO and SLS defective bacteria. Interleukin ( IL)-1β, IL-10, tumour necrosis factor ( TNF)-α and chemokine (C-X-C motif) ligand ( CXCL)-10 cytokines were produced after bacterial stimulation in a dose-dependent manner and no differences in cytokine levels were seen between live, inactivated or mutant bacteria. These data suggest that streptolysins or other secreted bacterial products are not required for the inflammatory responses induced by GAS. Our data indicate that inhibition of dynamin-dependent endocytosis in macrophages attenuates the induction of IL-1β, TNF-α, interferon ( IFN)-β and CXCL-10 mRNAs. We also observed that pro- IL-1β protein was expressed and efficiently cleaved into mature- IL-1β via inflammasome activation after bacterial stimulation. Furthermore, we demonstrate that multiple signalling pathways are involved in GAS-stimulated inflammatory responses in human macrophages. [ABSTRACT FROM AUTHOR]

Selection of appropriate typing method depends on a number of factors, including the scale of the investigation, the rapidity required of the results and the financial and technical resources available. Several typing methods have been applied to Corynebacterium diphtheriae genotyping, but most are laborious and time-consuming or require expensive equipment. We report an evaluation of the utility of the PCR melting profile technique for simple and easy-to-perform genotyping of C. diphtheriae. We compared the method with ribotyping-the 'gold standard' for C. diphtheriae typing-and PFGE, MLST, AFLP, RAPD and spoligotyping. Significance and Impact of the Study Occurrence of Corynebacterium diphtheriae infections-in the form of diphtheria in endemic countries and in the form of invasive infections in countries with high antidiphtheria vaccination coverage-indicates the need for maintenance of ability to genotype this pathogen by laboratories. Application of an appropriate typing method is essential not only in outbreak investigations for understanding and predicting epidemics but also in monitoring of the evolution and spread of epidemic clones of C. diphtheriae. The PCR melting profile method presented in the study is a good alternative for C. diphtheriae typing. [ABSTRACT FROM AUTHOR]

Objectives To determine patterns of ambulatory antibiotic prescribing in US adults, including the use of broad-spectrum versus narrow-spectrum agents, to provide a description of the diagnoses for which antibiotics are prescribed and to identify patient and physician factors associated with broad-spectrum antibiotic prescribing. Methods We used data for patients aged ≥18 years from the National Ambulatory and National Hospital Ambulatory Medical Care Surveys (2007–09). These are nationally representative surveys of patient visits to offices, hospital outpatient departments and emergency departments (EDs) in the USA, collectively referred to as ambulatory visits. We determined the types of antibiotics prescribed, including the use of broad-spectrum versus narrow-spectrum antibiotics, and examined prescribing patterns by diagnoses. We used multivariable logistic regression to identify factors associated with broad-spectrum antibiotic prescribing. Results Antibiotics were prescribed during 101 million (95% CI: 91–111 million) ambulatory visits annually, representing 10% of all visits. Broad-spectrum agents were prescribed during 61% of visits in which antibiotics were prescribed. The most commonly prescribed antibiotics were quinolones (25% of antibiotics), macrolides (20%) and aminopenicillins (12%). Antibiotics were most commonly prescribed for respiratory conditions (41% of antibiotics), skin/mucosal conditions (18%) and urinary tract infections (9%). In multivariable analysis, among patients prescribed antibiotics, broad-spectrum agents were more likely to be prescribed than narrow-spectrum antibiotics for respiratory infections for which antibiotics are rarely indicated (e.g. bronchitis), during visits to EDs and for patients ≥60 years. Conclusions Broad-spectrum agents constitute the majority of antibiotics in ambulatory care. More than 25% of prescriptions are for conditions for which antibiotics are rarely indicated. Antibiotic stewardship interventions targeting respiratory and non-respiratory conditions are needed in ambulatory care. [ABSTRACT FROM PUBLISHER]

Objectives Reliable data about antibiotic utilization in the large pharmaceutical market of the world's most populous country, the People's Republic of China, are in short supply. Although many primary studies have investigated the use of antibiotics in China, most of the relevant studies were published in the Chinese language. This systematic review aims to summarize reported percentages of outpatient encounters resulting in the prescription of antibiotics in China. Methods We systematically searched and reviewed studies of antibiotic prescribing patterns in China, published in Chinese or English between 2000 and August 2012. The study quality was assessed and the overall percentage of outpatient encounters resulting in the prescription of antibiotics was calculated using random-effects meta-analysis. Subgroup analyses were conducted to investigate heterogeneity across studies. Results We included 57 eligible studies (with a total of 556 435 outpatient encounters). The overall percentage of outpatients prescribed antibiotics was 50.3% (95% CI: 47.4%–53.1%). Of the outpatients prescribed antibiotics, 74.0% (95% CI: 71.3%–76.6%) were prescribed one antibiotic, 23.3% (95% CI: 21.1%–25.7%) were prescribed two antibiotics and 2.0% (95% CI: 1.3%–2.8%) were prescribed three or more antibiotics. The proportion of antibiotic utilization differed greatly across hospital levels and geographical regions and fluctuated over time. Conclusions The percentage use of antibiotics is high in China. The excessive use of antibiotics is particularly more problematic in lower-level hospitals and in less developed western China. The implementation and impact of the national efforts to control the excessive use of antibiotics should be appropriately evaluated. [ABSTRACT FROM PUBLISHER]

Pseudomonas aeruginosa are known to have a wide physiological potential allowing them to constantly populate diverse environments leading to severe infections of humans such as septicemia, leg ulcers, and burn wounds. We set out to probe physiological characteristics of P. aeruginosa isolates from diabetic leg ulcers collected from Helsinki metropolitan area. A total of 61 clinical isolates were obtained. Detailed phenotypic (physiological) characteristics [outer membrane ( OM) permeability, membrane voltage, and activity of multidrug resistance pumps] were determined in several growth phases leading to the division of the analyzed set of P. aeruginosa strains into five distinct clusters including cells with similar physiological properties. In addition, their antibiotic resistance patterns and genetic heterogeneity were determined. Multiple isolates from the same patient were genetically very closely related and belonged to the same phenotypic cluster. However, genetically close isolates from different patients expressed very different phenotypic properties. The characteristics of infected patients seem to determine the growth environments for microorganisms that adapt by changing their physiological and/or genetic properties. [ABSTRACT FROM AUTHOR]

Candida albicans is one of the most medically important fungi because of its high frequency as a commensal and pathogenic microorganism causing superficial as well as invasive infections. Strain typing and delineation of the species are essential for understanding its biology, epidemiology and population structure. A wide range of molecular techniques have been used for this purpose including non- DNA-based methods (multi-locus enzyme electrophoresis), conventional DNA-based methods (electrophoretic karyotyping, random amplified polymorphic DNA, amplified fragment length polymorphism, restriction enzyme analysis with and without hybridization, rep- PCR) and DNA-based methods called exact typing methods because they generate unambiguous and highly reproducible typing data (including microsatellite length polymorphism and multi-locus sequence typing). In this review, the main molecular methods used for C. albicans strain typing are summarized, and their advantages and limitations are discussed with regard to their discriminatory power, reproducibility, cost and ease of performance. [ABSTRACT FROM AUTHOR]

Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasing in incidence and manifests as skin and soft tissue infections including furuncles. The majority of studies have focused on the epidemiology of single furuncles and not recurrent disease. There is a lack of data concerning the incidence of furunculosis outside the U.S.A. Objectives This report reviews the literature of recurrent furunculosis and the impact of CA-MRSA on the disease. Methods Article citations were searched within PubMed. Search terms used were 'furunculosis', 'recurrent furunculosis', 'skin abscess' and 'recurrent boils'. Articles were discarded if they did not refer to furunculosis secondary to S. aureus. Results A total of 1515 articles were initially retrieved with the term 'furunculosis', 77 with the term 'recurrent furunculosis', 2778 with the term 'skin abscess', and 1526 with the term 'recurrent boils'. After excluding articles not referring to S. aureus furunculosis, 86 articles were included for this review. Conclusions Furunculosis is increasing within the U.S.A. secondary to the CA-MRSA epidemic and the resistant organism's close association with the Panton-Valentine leucocidin (PVL) virulence factor. PVL is associated with follicular infections in general, having its strongest association with furunculosis and its recurrence. The majority of furuncles in the U.S.A. are caused by CA-MRSA, while elsewhere in the world they are caused by methicillin-sensitive S. aureus. Nasal carriage of S. aureus is the primary risk factor for recurrent furunculosis and occurs in 60% of individuals. [ABSTRACT FROM AUTHOR]

From 2002–2010, the epidemiology of invasive group A streptococcal disease changed dramatically in Utah. The incidence of invasive disease rose from 3.5 to 9.8 cases/100 000 persons, while the incidence of acute rheumatic fever decreased from 6.1 to 3.7 cases/100 000.Background. Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity and mortality. Recent national surveillance data report stable rates of invasive GAS disease, although these may not capture geographic variation.Methods We performed a population-based, retrospective laboratory surveillance study of invasive GAS disease among Utah residents from 2002–2010. We used Intermountain Healthcare's electronic medical records and data warehouse to identify patients from whom GAS was isolated by culture. We defined clinical syndromes of invasive GAS disease on the basis of International Classification of Diseases, Ninth Revision codes. We abstracted demographic information, comorbidities, and microbiologic and laboratory findings.Results. From 2002–2010, we identified 1514 cases of invasive GAS disease among Utah residents. The estimated mean annual incidence rate was 6.3 cases/100 000 persons, which was higher than the national rate of 3.6 cases/100 000 (P < .01). The incidence of invasive GAS disease in Utah rose from 3.5 cases/100 000 persons in 2002 to 9.8 cases/100 000 persons in 2010 (P = .01). Among children aged <18 years, the incidence of invasive GAS increased from 3.0 cases/100 000 children in 2002 to 14.1 cases/100 000 children in 2010 (P < .01). The increase in the pediatric population was due, in part, to an increase in GAS pneumonia (P = .047). The rate of invasive GAS disease in adults aged 18–64 years increased from 3.4 cases/100 000 persons in 2002 to 7.6 cases/100 000 persons in 2010 (P = .02). Rates among those aged ≥65 years were stable. The incidence of acute rheumatic fever declined from 6.1 to 3.7 cases/100 000 (P = .04).Conclusions The epidemiologic characteristics of invasive GAS disease in Utah has changed substantially over the past decade, including a significant increase in the overall incidence of invasive disease—driven primarily by increasing disease in younger persons—that coincided temporally with a decrease in the incidence of acute rheumatic fever. [ABSTRACT FROM AUTHOR]

Peanut allergy accounts for the majority of severe food-related allergic reactions and there is a need for new prevention and treatment strategies. Probiotics may be considered for treatment on the basis of their immunomodulating properties. Cytokine profiles of probiotic strains were determined by in vitro co-culture with human PBMCs. Three strains were selected to investigate their prophylactic potential in a peanut sensitization model by analysing peanut-specific antibodies, mast cell degranulation and ex vivo cytokine production by splenocytes. The probiotic strains induced highly variable cytokine profiles in PBMCs. L. salivarius HMI001 , L. casei Shirota ( LCS) and L. plantarum WCFS1 were selected for further investigation owing to their distinct cytokine patterns. Prophylactic treatment with both HMI001 and LCS attenuated the Th2 phenotype (reduced mast cell responses and ex vivo IL-4 and/or IL-5 production). In contrast, WCFS1 augmented the Th2 phenotype (increased mast cell and antibody responses and ex vivo IL-4 production). In vitro PBMC screening was useful in selecting strains with anti-inflammatory and Th1 skewing properties. In case of HMI001 (high IL-10/ IL-12 ratio) and LCS (high interferon-γ and IL-12), partial protection was seen in a mouse peanut allergy model. Strikingly, certain strains may worsen the allergic reaction as shown in the case of WCFS1. [ABSTRACT FROM AUTHOR]

We found that clinicians are treating for longer courses than necessary and using broad-spectrum agents even if microbiologic data support narrowing therapy. Antimicrobial stewardship teams can improve the treatment of patients with community-acquired pneumonia while safely decreasing unnecessary antibiotic use.Background. Initial management of community-acquired pneumonia (CAP) has been a Centers for Medicare and Medicaid Services performance measure for a decade. We hypothesized that an intervention directed at management of CAP that assesses areas not covered by the performance measures—treatment duration and antimicrobial selection after additional microbiology data are available—would further improve CAP management.Methods. We performed a single-center, prospective study to compare management of adult inpatients with presumed CAP before (from 1 January 2008 through 31 March 2008) and after (from 1 February 2010 through 10 May 2010) an intervention consisting of education and prospective feedback to teams regarding antibiotic choice and duration. The primary outcome measure was duration of antibiotic therapy in the 2 periods.Results. There were 62 patients in the preintervention period and 65 patients in the intervention period. The duration of antibiotic therapy decreased from a median of 10 to 7 days (P < .001), with 148 fewer days of antibiotic therapy. The median lengths of stay were similar in the 2 groups (4 vs 5 days). A causative pathogen was identified less frequently during the intervention period (14% vs 34%); however, antibiotics were more frequently narrowed or modified on the basis of susceptibility results during the intervention period (67% vs 19%). Fewer patients received duplicate therapy within 24 hours in the intervention period (90% vs 55%).Conclusions. The duration of therapy for CAP was excessive at our institution and was decreased with a stewardship intervention. Confirmatory studies at other institutions are needed; efforts to assess and reduce duration of therapy for CAP should be strongly considered. [ABSTRACT FROM AUTHOR]

Objectives High rates of methicillin-resistant Staphylococcus aureus (MRSA) and fluoroquinolone-resistant Pseudomonas aeruginosa may be related, in part, to the overuse of fluoroquinolones. The objective was to analyse and correlate long-term surveillance data on MRSA and fluoroquinolone-resistant P. aeruginosa rates and antibiotic consumption after implementation of an institution-wide programme to reduce fluoroquinolone use. Methods An interrupted time series/quasi-experimental study of monthly fluoroquinolone use and MRSA and fluoroquinolone-resistant P. aeruginosa isolation rates was carried out in a tertiary hospital during three periods: pre-intervention (January 2000–August 2005), intervention (September 2005–March 2006), and post-intervention (March 2006–March 2010). The effect of the intervention on the consumption of fluoroquinolones and bacterial resistance was assessed using segmented regression analyses. Results Mean monthly fluoroquinolone consumption dropped by 29.1 defined daily doses per 1000 patient-days (DDD/1000 PD) (95% CI 13.1–45.9; P = 0.0005) from a mean of 148.2 to 119.1 DDD/1000 PD during the intervention period. A sustained and significant decrease in fluoroquinolone consumption of −0.95 DDD/1000 PD/month was also observed during the post-intervention period (P = 0.0002). During the post-intervention period the rate of fluoroquinolone-resistant P. aeruginosa continuously decreased, from a mean of 42% to 26%, with a constant relative change rate of −13%/year (95% CI −19 to −5, P = 0.001). A decrease in the MRSA rate was observed during the intervention period, from a mean resistance rate of 27% to 21% (P < 0.0001). Conclusions We showed the sustained impact of a fluoroquinolone control programme on the reduction of fluoroquinolone use with a significant decrease in fluoroquinolone-resistant P. aeruginosa and MRSA rates over 4 years. [ABSTRACT FROM PUBLISHER]

Summary The immunomodulatory effects of probiotics were assessed following exposure of normal peripheral blood mononuclear cells (PBMC), cord blood cells and the spleen-derived monocyte/macrophage cell line CRL-9850 to Lactobacillus acidophilus LAVRI-A1, Lb. rhamnosus GG, exopolysaccharides (EPS)-producing Streptococcus thermophilus St1275, Bifidobacteriun longum BL536, B. lactis B94 and Escherichia coli TG1 strains. The production of a panel of pro- and anti-inflammatory cytokines by PBMC following bacterial stimulation was measured, using live, heat-killed or mock gastrointestinal tract (GIT)-exposed bacteria, and results show that (i) all bacterial strains investigated induced significant secretion of pro- and anti-inflammatory cytokines from PBMC-derived monocytes/macrophages; and (ii) cytokine levels increased relative to the expansion of bacterial cell numbers over time for cells exposed to live cultures. Bifidobacteria and S. thermophilus stimulated significant concentrations of transforming growth factor (TGF)-β, an interleukin necessary for the differentiation of regulatory T cells (Treg)/T helper type 17 (Th17) cells and, as such, the study further examined the induction of Th17 and Treg cells after PBMC exposure to selected bacteria for 96 h. Data show a significant increase in the numbers of both cell types in the exposed populations, measured by cell surface marker expression and by cytokine production. Probiotics have been shown to induce cytokines from a range of immune cells following ingestion of these organisms. These studies suggest that probiotics' interaction with immune-competent cells produces a cytokine milieu, exerting immunomodulatory effects on local effector cells, as well as potently inducing differentiation of Th17 and Treg cells. [ABSTRACT FROM AUTHOR]

Unfortunately for mankind, it is very likely that the antibiotic resistance problem we have generated during the last 60 years due to the extensive use and misuse of antibiotics is here to stay for the foreseeable future. This view is based on theoretical arguments, mathematical modeling, experiments and clinical interventions, suggesting that even if we could reduce antibiotic use, resistant clones would remain persistent and only slowly (if at all) be outcompeted by their susceptible relatives. In this review, we discuss the multitude of mechanisms and processes that are involved in causing the persistence of chromosomal and plasmid-borne resistance determinants and how we might use them to our advantage to increase the likelihood of reversing the problem. Of particular interest is the recent demonstration that a very low antibiotic concentration can be enriching for resistant bacteria and the implication that antibiotic release into the environment could contribute to the selection for resistance. Several mechanisms are contributing to the stability of antibiotic resistance in bacterial populations and even if antibiotic use is reduced it is likely that most resistance mechanisms will persist for considerable times. [ABSTRACT FROM AUTHOR]

Within a susceptible wild-type population, a small fraction of cells, even <10−9, is not affected when challenged by an antimicrobial agent. This subpopulation has mutations that impede antimicrobial action, allowing their selection during clinical treatment. Emergence of resistance occurs in the frame of a selective compartment termed a mutant selection window (MSW). The lower margin corresponds to the minimum inhibitory concentration of the susceptible cells, whereas the upper boundary, named the mutant prevention concentration (MPC), restricts the growth of the entire population, including that of the resistant mutants. By combining pharmacokinetic/pharmacodynamic concepts and an MPC strategy, the selection of resistant mutants can be limited. Early treatment avoiding an increase of the inoculum size as well as a regimen restricting the time within the MSW can reduce the probability of emergence of the resistant mutants. Physiological and, possibly, genetic adaptation in biofilms and a high proportion of mutator clones that may arise during chronic infections influence the emergence of resistant mutants. Moreover, a resistant population can emerge in a specific selective compartment after acquiring a resistance trait by horizontal gene transfer, but this may also be avoided to some extent when the MPC is reached. Known linkage between antimicrobial use and resistance should encourage actions for the design of antimicrobial treatment regimens that minimize the emergence of resistance. Emergence of a resistant bacterial subpopulation within a susceptible wild-type population can be restricted with a regimen using an antibiotic dose that is sufficiently high to inhibit both susceptible and resistant bacteria [ABSTRACT FROM AUTHOR]

Infections caused by multiresistant Gram-positive bacteria represent a major health burden in the community as well as in hospitalized patients. Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium are well-known pathogens of hospitalized patients, frequently linked with resistance against multiple antibiotics, compromising effective therapy. Streptococcus pneumoniae and Streptococcus pyogenes are important pathogens in the community and S. aureus has recently emerged as an important community-acquired pathogen. Population genetic studies reveal that recombination prevails as a driving force of genetic diversity in E. faecium, E. faecalis, S. pneumoniae and S. pyogenes, and thus, these species are weakly clonal. Although recombination has a relatively modest role driving the genetic variation of the core genome of S. aureus, the horizontal acquisition of resistance and virulence genes plays a key role in the emergence of new clinically relevant clones in this species. In this review, we discuss the population genetics of E. faecium, E. faecalis, S. pneumoniae, S. pyogenes and S. aureus. Knowledge of the population structure of these pathogens is not only highly relevant for (molecular) epidemiological research but also for identifying the genetic variation that underlies changes in clinical behaviour, to improve our understanding of the pathogenic behaviour of particular clones and to identify novel targets for vaccines or immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives Although antibiotic use in the community is a significant contributor to resistance, little is known about social patterns of use. This study aimed to explore the use of antibiotics by age, gender, ethnicity, socio-economic status and rurality. Methods Data were obtained on all medicines dispensed to ambulatory patients in one isolated town for a year, and data on antibiotics are presented in this paper. Demographic details were obtained from pharmacy records or by matching to a national patient dataset. Results During the study year, 51% of the population received a prescription for one or more antibiotics, and on average people in the region received 10.15 defined daily doses (DDDs). Prevalence of use was higher for females (ratio, 1.18), and for young people (under 25) and the elderly (75 and over), and the amount in DDDs/person/year broadly followed this pattern. Māori (indigenous New Zealanders) were less likely to receive a prescription (48% of the population) than non-Māori (55%) and received smaller quantities on average. Rural Māori, including rural Māori children, received few prescriptions and low quantities of antibiotics compared with other population groups. Conclusions The level of antibiotic use in the general population is high, despite campaigns to try to reduce unnecessary use. The prevalence of acute rheumatic fever is high amongst rural Māori, and consequently treatment guidelines recommend prophylactic use of antibiotics for sore throat in this population. This makes the comparatively very low level of use of antibiotics amongst rural Māori children very concerning. [ABSTRACT FROM PUBLISHER]