Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>The accessory gene regulator (<it>agr</it>) is a quorum sensing cluster of genes which control colonization and virulence in <it>Staphylococcus aureus</it>. We evaluated <it>agr </it>function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against <it>agr </it>functional and dysfunctional HA-MRSA and CA-MRSA.</p> <p>Methods</p> <p>40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of <it>agr </it>function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10⁶and 10⁸cfu/ml of <it>agr </it>functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model.</p> <p>Results</p> <p>15% isolates were <it>agr </it>dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10⁶cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among <it>agr </it>functional and dysfunctional strains. However, against a high initial inoculum of 10⁸cfu/ml, killing activity was notably attenuated against <it>agr </it>dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log₁₀CFU/ml for <it>agr </it>functional vs. 2.41 log₁₀CFU/ml for <it>agr </it>dysfunctional MRSA (p = 0.0007).</p> <p>Conclusions</p> <p>Dysfunction in <it>agr </it>was less common among CA-MRSA vs. HA-MRSA. <it>agr </it>dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.</p

Objective and Subjective Components of the First-Night Effect in Young Nightmare Sufferers and Healthy Participants

The first-night effect—marked differences between the first- and the second-night sleep spent in a laboratory—is a widely known phenomenon that accounts for the common practice of excluding the first-night sleep from any polysomnographic analysis. The extent to which the first-night effect is present in a participant, as well as its duration (1 or more nights), might have diagnostic value and should account for different protocols used for distinct patient groups. This study investigated the first-night effect on nightmare sufferers (NM; N D 12) and healthy controls .N D 15/ using both objective (2-night-long polysomnography) and subjective (Groningen Sleep Quality Scale for the 2 nights spent in the laboratory and 1 regular night spent at home) methods. Differences were found in both the objective (sleep efficiency, wakefulness after sleep onset, sleep latency, Stage-1 duration, Stage-2 duration, slow-wave sleep duration, and REM duration) and subjective (self-rating) variables between the 2 nights and the 2 groups, with a more pronounced first-night effect in the case of the NM group. Furthermore, subjective sleep quality was strongly related to polysomnographic variables and did not differ among 1 regular night spent at home and the second night spent in the laboratory. The importance of these results is discussed from a diagnostic point of view

Q fever epidemic in Hungary, April to July 2013

We investigated a Q fever outbreak with human patients showing high fever, respiratory tract symptoms, headache and retrosternal pain in southern Hungary in the spring and summer of 2013. Seventy human cases were confirmed by analysing their serum and blood samples with micro-immunofluorescence test and real-time PCR. The source of infection was a merino sheep flock of 450 ewes, in which 44.6% (25/56) seropositivity was detected by enzyme-linked immunosorbent assay. Coxiella burnetii DNA was detected by real-time PCR in the milk of four of 20 individuals and in two thirds (41/65) of the manure samples. The multispacer sequence typing examination of C. burnetii DNA revealed sequence type 18 in one human sample and two manure samples from the sheep flock. The multilocus variable-number tandem repeat analysis pattern of the sheep and human strains were also almost identical, 4/5-9-3-3-0-5 (Ms23-Ms24-Ms27- Ms28-Ms33-Ms34). It is hypothesised that dried manure and maternal fluid contaminated with C. burnetii was dispersed by the wind from the sheep farm towards the local inhabitants. The manure was eliminated in June and the farm was disinfected in July. The outbreak ended at the end of July 2013

Q fever epidemic in Hungary, April to July 2013

We investigated a Q fever outbreak with human patients showing high fever, respiratory tract symptoms, headache and retrosternal pain in southern Hungary in the spring and summer of 2013. Seventy human cases were confirmed by analysing their serum and blood samples with micro-immunofluorescence test and real-time PCR. The source of infection was a merino sheep flock of 450 ewes, in which 44.6% (25/56) seropositivity was detected by enzyme-linked immunosorbent assay. Coxiella burnetii DNA was detected by real-time PCR in the milk of four of 20 individuals and in two thirds (41/65) of the manure samples. The multispacer sequence typing examination of C. burnetii DNA revealed sequence type 18 in one human sample and two manure samples from the sheep flock. The multilocus variable-number tandem repeat analysis pattern of the sheep and human strains were also almost identical, 4/5-9-3-3-0-5 (Ms23-Ms24-Ms27-Ms28-Ms33-Ms34). It is hypothesised that dried manure and maternal fluid contaminated with C. burnetii was dispersed by the wind from the sheep farm towards the local inhabitants. The manure was eliminated in June and the farm was disinfected in July. The outbreak ended at the end of July 2013

Evaluation of pulse wave velocity for predicting major adverse cardiovascular events in post-infarcted patients: comparison of oscillometric and MRI methods

Increased aortic pulse wave velocity (PWV) has been proved as a strong predictor of major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI). Due to the various technical approaches the level of high PWV values show significant differences. We evaluated the cut-off PWV values for MACE prediction using cardiac magnetic resonance imaging (CMR) and oscillometric methods for validating the prognostic value of high PWV in post-infarcted patients. Phase contrast imaging (PCI) and oscillometric based Arteriograph (AG) were compared in this 6 years fol lowup study, including 75 consecutive patients of whom 49 suffered previous ST-elevation myocardial infarction (STEM I). Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization. An acceptable agreement and significant correlation (rho: 0.332, p 6.47 m/s, AG: >9.625 m/s, p < 0.001, respectively). Multivariate Cox regression revealed PWV as a predictor of MACE (PWV CMR hazard ratio (HR):1.31 (CI: 1.1-1.7) PWV AG HR:1.24 (CI:1.0-1.5), p < 0.05, respectively). Increased PWV derived by AG and CMR methods are feasible for MACE prediction in post-infarcted patients. However, adjusted cut-off values of PWV are recommended for different techniques to improve individual risk stratification.Cardiovascular Aspects of Radiolog

Characterisation and Carriage Ratio of Clostridium difficile Strains Isolated from a Community-Dwelling Elderly Population in the United Kingdom

Background Community-associated Clostridium difficile infection (CDI) appears to be an increasing problem. Reported carriage rates by C.difficile are debatable with suggestions that primary asymptomatic carriage is associated with decreased risk of subsequent diarrhoea. However, knowledge of potential reservoirs and intestinal carriage rates in the community, particularly in the elderly, the most susceptible group, is limited. We have determined the presence of C.difficile in the faeces of a healthy elderly cohort living outside of long-term care facilities (LCFs) in the United Kingdom. Methods Faecal samples from 149 community-based healthy elderly volunteers (median age 81 years) were screened for C.difficile using direct (Brazier's CCEY) and enrichment (Cooked Meat broth) culture methods and a glutamate dehydrogenase (GDH) immunoassay. Isolates were PCR-ribotyped and analysed for toxin production and the presence of toxin genes. Results Of 149 faecal samples submitted, six (4%) were found to contain C.difficile. One particular sample was positive by both the GDH immunoassay and direct culture, and concurrently produced two distinct strain types: one toxigenic and the other non-toxigenic. The other five samples were only positive by enrichment culture method. Overall, four C.difficile isolates were non-toxigenic (PCR-ribotypes 009, 026 (n = 2) and 039), while three were toxigenic (PCR-ribotypes 003, 005 and 106). All individuals who had a positive culture were symptom-free and none of them had a history of CDI and/or antibiotics use in the 3 month period preceding recruitment. Conclusions To our knowledge, this is the first study of the presence of C.difficile in healthy elderly community-dwelling individuals residing outside of LCFs. The observed carriage rate is lower than that reported for individuals in LCFs and interestingly no individual carried the common epidemic strain PCR-ribotype 027 (NAP1/BI). Further follow-up of asymptomatic carriers in the community, is required to evaluate host susceptibility to CDI and identify dynamic changes in the host and microbial environment that are associated with pathogenicity

Epidemiology of influenza-associated hospitalization in adults, Toronto, 2007/8

The purpose of this investigation was to identify when diagnostic testing and empirical antiviral therapy should be considered for adult patients requiring hospitalization during influenza seasons. During the 2007/8 influenza season, six acute care hospitals in the Greater Toronto Area participated in active surveillance for laboratory-confirmed influenza requiring hospitalization. Nasopharyngeal (NP) swabs were obtained from patients presenting with acute respiratory or cardiac illness, or with febrile illness without clear non-respiratory etiology. Predictors of influenza were analyzed by multivariable logistic regression analysis and likelihoods of influenza infection in various patient groups were calculated. Two hundred and eighty of 3,917 patients were found to have influenza. Thirty-five percent of patients with influenza presented with a triage temperature ≥38.0°C, 80% had respiratory symptoms in the emergency department, and 76% were ≥65 years old. Multivariable analysis revealed a triage temperature ≥38.0°C (odds ratio [OR] 3.1; 95% confidence interval [CI] 2.3–4.1), the presence of respiratory symptoms (OR 1.7; 95% CI 1.2–2.4), admission diagnosis of respiratory infection (OR 1.8; 95% CI 1.3–2.4), admission diagnosis of exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or respiratory failure (OR 2.3; 95% CI 1.6–3.4), and admission in peak influenza weeks (OR 4.2; 95% CI 3.1–5.7) as independent predictors of influenza. The likelihood of influenza exceeded 15% in patients with respiratory infection or exacerbation of COPD/asthma if the triage temperature was ≥38.0°C or if they were admitted in the peak weeks during the influenza season. During influenza season, diagnostic testing and empiric antiviral therapy should be considered in patients requiring hospitalization if respiratory infection or exacerbation of COPD/asthma are suspected and if either the triage temperature is ≥38.0°C or admission is during the weeks of peak influenza activity

Positive nasal culture of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for surgical site infection in orthopedics

Background Although nasal carriage of MRSA has been identified as one of the risk factors for surgical site infection (SSI) with MRSA, there have been no reports of this in the orthopedics field

Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada

In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission.A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission. ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients.Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients