Whole-genome Sequencing to Track Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Nosocomial Outbreaks.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare institutions posed a significant problem. Due to limited evidence, guidance on appropriate infection prevention and control (IPC) measures such as the wearing of face masks varied. Here, we applied whole virus genome sequencing (WvGS) to analyze transmission routes of SARS-CoV-2 in hospital-acquired (HA) COVID-19. METHODS: An investigation was undertaken for all HA cases of COVID-19 from March to April 2020. Fifty SARS-CoV-2 samples were analysed by WvGS and their phylogenetic relationship established. RESULTS: WvGS identified transmission events previously undetected by epidemiological analysis and provided evidence for SARS-CoV-2 transmission between healthcare workers (HCW) and patients and among HCW themselves. The majority of HA COVID-19 cases occurred in patients highly dependent on nursing care, suggesting the likely route of transmission was by close contact or droplet, rather than aerosol, transmission. Mortality among HA COVID-19 infections was recorded as 33%. CONCLUSIONS: This study provides evidence that SARS-CoV-2 transmission occurs from symptomatic and asymptomatic HCWs to patients. Interventions including comprehensive screening of HCWs for COVID-19 symptoms, PCR testing of asymptomatic HCWs upon identification of HA cases and implementation of universal use of surgical masks for all clinical care is indicated to prevent viral transmission. Our study highlights the importance of close collaboration between guidance bodies and frontline IPC experts for developing control measures in an emergency pandemic situation caused by a virus with undefined transmission modus.

PCR-ribotype distribution of Clostridium difficile in Irish pigs.

Clostridium difficile is an important enteric pathogen in humans causing infections in the healthcare environment and the community. Carriage of C. difficile and C. difficile-related enterocolitis has been reported in piglets worldwide. The aim of this study was to investigate the rates of C. difficile isolation from pigs in Ireland. Faecal samples from piglet litters and sows were collected from six farms in 2015. The sows were non-diarrhoeal at the time of sampling. The diarrhoeal status of the piglets was unknown. C. difficile was isolated from 34/44 (77%) of piglet litter samples and from 33/156 (21%) of sow samples. The isolation rate in sows varied from 3 to 39% and in piglet litters from 72 to 86% depending on farm location. Toxin A and toxin B were present in 99% (66/67) of isolates; and binary toxin in 85% (57/67). Only PCR-ribotypes 078 (88%) and 193 (12%) were identified in piglets. Seven PCR-ribotypes were detected in sow C. difficile isolates: PCR-ribotypes 078 (67%), 050 (12%), 014/020 (6%), 015 (6%), 029 (3%), 035 (3%) and 193 (3%). This study shows that toxigenic C. difficile strains such as PCR-ribotype 078 can be commonly isolated from pigs at different geographical locations in Ireland. Since PCR-ribotype 078 is frequently found in humans in Ireland, this highlights the potential for interspecies transmission.

Interventions to improve antibiotic prescribing practices for hospital inpatients.

BACKGROUND: The first publication of this review in Issue 3, 2005 included studies up to November 2003. This update adds studies to December 2006 and focuses on application of a new method for meta-analysis of interrupted time series studies and application of new Cochrane Effective Practice and Organisation of Care (EPOC) Risk of Bias criteria to all studies in the review, including those studies in the previously published version. The aim of the review is to evaluate the impact of interventions from the perspective of antibiotic stewardship. The two objectives of antibiotic stewardship are first to ensure effective treatment for patients with bacterial infection and second support professionals and patients to reduce unnecessary use and minimize collateral damage. OBJECTIVES: To estimate the effectiveness of professional interventions that, alone or in combination, are effective in antibiotic stewardship for hospital inpatients, to evaluate the impact of these interventions on reducing the incidence of antimicrobial-resistant pathogens or Clostridium difficile infection and their impact on clinical outcome. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE from 1980 to December 2006 and the EPOC specialized register in July 2007 and February 2009 and bibliographies of retrieved articles. The main comparison is between interventions that had a restrictive element and those that were purely persuasive. Restrictive interventions were implemented through restriction of the freedom of prescribers to select some antibiotics. Persuasive interventions used one or more of the following methods for changing professional behaviour: dissemination of educational resources, reminders, audit and feedback, or educational outreach. Restrictive interventions could contain persuasive elements. SELECTION CRITERIA: We included randomized clinical trials (RCTs), controlled clinical trials (CCT), controlled before-after (CBA) and interrupted time series studies (ITS). Interventions included any professional or structural interventions as defined by EPOC. The intervention had to include a component that aimed to improve antibiotic prescribing to hospital inpatients, either by increasing effective treatment or by reducing unnecessary treatment. The results had to include interpretable data about the effect of the intervention on antibiotic prescribing or microbial outcomes or relevant clinical outcomes. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed quality. We performed meta-regression of ITS studies to compare the results of persuasive and restrictive interventions. Persuasive interventions advised physicians about how to prescribe or gave them feedback about how they prescribed. Restrictive interventions put a limit on how they prescribed; for example, physicians had to have approval from an infection specialist in order to prescribe an antibiotic. We standardized the results of some ITS studies so that they are on the same scale (percent change in outcome), thereby facilitating comparisons of different interventions. To do this, we used the change in level and change in slope to estimate the effect size with increasing time after the intervention (one month, six months, one year, etc) as the percent change in level at each time point. We did not extrapolate beyond the end of data collection after the intervention. The meta-regression was performed using standard weighted linear regression with the standard errors of the coefficients adjusted where necessary. MAIN RESULTS: For this update we included 89 studies that reported 95 interventions. Of the 89 studies, 56 were ITSs (of which 4 were controlled ITSs), 25 were RCT (of which 5 were cluster-RCTs), 5 were CBAs and 3 were CCTs (of which 1 was a cluster-CCT).Most (80/95, 84%) of the interventions targeted the antibiotic prescribed (choice of antibiotic, timing of first dose and route of administration). The remaining 15 interventions aimed to change exposure of patients to antibiotics by targeting the decision to treat or the duration of treatment. Reliable data about impact on antibiotic prescribing data were available for 76 interventions (44 persuasive, 24 restrictive and 8 structural). For the persuasive interventions, the median change in antibiotic prescribing was 42.3% for the ITSs, 31.6% for the controlled ITSs, 17.7% for the CBAs, 3.5% for the cluster-RCTs and 24.7% for the RCTs. The restrictive interventions had a median effect size of 34.7% for the ITSs, 17.1% for the CBAs and 40.5% for the RCTs. The structural interventions had a median effect of 13.3% for the RCTs and 23.6% for the cluster-RCTs. Data about impact on microbial outcomes were available for 21 interventions but only 6 of these also had reliable data about impact on antibiotic prescribing.Meta-analysis of 52 ITS studies was used to compare restrictive versus purely persuasive interventions. Restrictive interventions had significantly greater impact on prescribing outcomes at one month (32%, 95% confidence interval (CI) 2% to 61%, P = 0.03) and on microbial outcomes at 6 months (53%, 95% CI 31% to 75%, P = 0.001) but there were no significant differences at 12 or 24 months. Interventions intended to decrease excessive prescribing were associated with reduction in Clostridium difficile infections and colonization or infection with aminoglycoside- or cephalosporin-resistant gram-negative bacteria, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. Meta-analysis of clinical outcomes showed that four interventions intended to increase effective prescribing for pneumonia were associated with significant reduction in mortality (risk ratio 0.89, 95% CI 0.82 to 0.97), whereas nine interventions intended to decrease excessive prescribing were not associated with significant increase in mortality (risk ratio 0.92, 95% CI 0.81 to 1.06). AUTHORS' CONCLUSIONS: The results show that interventions to reduce excessive antibiotic prescribing to hospital inpatients can reduce antimicrobial resistance or hospital-acquired infections, and interventions to increase effective prescribing can improve clinical outcome. This update provides more evidence about unintended clinical consequences of interventions and about the effect of interventions to reduce exposure of patients to antibiotics. The meta-analysis supports the use of restrictive interventions when the need is urgent, but suggests that persuasive and restrictive interventions are equally effective after six months.

PCR ribotype prevalence and molecular basis of macrolide-lincosamide-streptogramin B (MLSB) and fluoroquinolone resistance in Irish clinical Clostridium difficile isolates.

BACKGROUND: Antimicrobial use is recognized as a risk factor for Clostridium difficile infection (CDI) and outbreaks. We studied the relationship between PCR ribotype, antimicrobial susceptibility and the genetic basis of resistance in response to exposure to antimicrobial agents. METHODS: C. difficile isolates were cultured from 133 CDI patients for whom recent antimicrobial drug exposure had been recorded. Isolates were ribotyped by PCR and assessed for their susceptibility to the macrolide-lincosamide-streptogramin B (MLS(B)) group of compounds (erythromycin and clindamycin) and fluoroquinolone antimicrobials (ciprofloxacin, levofloxacin and moxifloxacin). Where relevant, the genetic basis of resistance was determined. RESULTS: Prevalent ribotypes (including 027, 001 and 106) exhibited significantly greater antimicrobial resistance compared with ribotypes 078 and 014, among others. Clindamycin-resistant ribotype 078 was detected for the first time. Ribotypes 027 and 001 were more likely to exhibit MLS(B) resistance, a feature that was associated with the erm(B) gene. Exposure to MLS(B) or fluoroquinolone antimicrobial compounds in the 8 weeks prior to the onset of infection was not associated with specific genetic markers of resistance. Single amino acid substitutions in the A and B subunits of DNA gyrase were noted and were ribotype specific and linked to resistance to moxifloxacin. CONCLUSIONS: Resistance to MLS(B) and fluoroquinolone antimicrobial compounds is common among prevalent ribotypes of C. difficile. The genetic basis for antimicrobial resistance appears to be ribotype specific and conserved in the absence of recent antimicrobial selection pressure.

An Unusual Case of Brucella abortus Prosthetic Joint Infection.

Brucellosis is a systemic infection caused by brucella species. Prosthetic joint infection due to brucella species is rare. We report the case of a prosthetic joint infection presenting fourteen years post treatment for systemic brucellosis.

Unusual infections and novel therapy in the immunocompromised host.

New methods of identification have led to an ever-increasing number of unusual pathogens causing infection in the immunocompromised host. Reports of antimicrobial-resistant organisms in this group of patients are also increasing, with the result that new treatments must be sought urgently. New agents and new strategies for the development of antimicrobial agents are critical for future progress in the treatment of resistant organisms.

Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses.

Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome. The relationship between host immune and inflammatory responses during severe C. difficile infection (CDI) and the risk of mortality has yet to be defined. We aimed to investigate the host systemic IgG anti-toxin immune responses, the in vitro cytotoxicity of the infecting C. difficile ribotyped strain, and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality. Inflammatory markers, co-morbidities and CDI outcomes were recorded in a prospective cohort of 150 CDI cases. Serum anti-cytotoxin A (TcdA) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed. A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality (P<0.05). Ribotype 027 isolates were significantly more toxinogenic than other ribotypes (P<0.00001). High cytotoxin titres correlated with increased inflammatory markers but also higher anti-TcdA and -TcdB (P<0.05) IgG responses resulting in a lower risk of mortality. On multivariate analysis, predictors of mortality were peak white cell count >20 × 10(9) l(-1) [odds ratio (OR) 11.53; 95 % confidence interval (CI) 2.38-55.92], creatinine concentration >133 µmol l(-1) (OR 6.54; 95 % CI 1.47-29.07), Horn's index >3 (OR 4.09; 95 % CI 0.76-22.18) and low anti-TcdA IgG (OR 0.97; 95 % CI 0.95-0.99), but not ribotype, cytotoxin titre or anti-TcdB IgG. Thus, host pro-inflammatory and humoral responses correlate with the cytotoxin titre of the infecting strain and effective anti-toxin immune responses reduce the risk of mortality.

Do educational interventions improve management of patients with community-acquired pneumonia?

Community-acquired pneumonia (CAP) is the Leading cause of death from infection. In order to evaluate physicians' adherence to hospital guidelines for CAP, an observational prospective study during two consecutive winter periods at an Irish teaching hospital was performed. A series of educational sessions on management of CAP was provided for medical staff at the end of the first year. Comparison of results showed significant improvement in the rate of blood culture sampling (p < .01), sputum sampling (p < .05), and combined blood culture and sputum sampling (p < .01). Length of antibiotic treatment was more appropriate in the second study year. Results indicate that antibiotic audit and educational interventions improve physicians' adherence to hospital guidelines.

Systematic review of antimicrobial drug prescribing in hospitals.

Prudent prescribing of antimicrobial drugs to hospital inpatients may reduce incidences of antimicrobial drug resistance and healthcare-associated infection. We reviewed the literature from January 1980 to November 2003 to identify rigorous evaluations of interventions to improve hospital prescribing of antimicrobial drugs. We identified 66 studies with interpretable data, of which 16 reported 20 microbiologic outcomes: gram-negative resistant bacteria, 10 studies; Clostridium difficile-associated diarrhea, 5 studies; vancomycin-resistant enterococci, 3 studies; and methicillin-resistant Staphylococcus aureus, 2 studies. Four studies provided strong evidence that the intervention changed microbial outcomes with low risk for alternative explanations, 8 studies provided less convincing evidence, and 4 studies provided no evidence. The strongest and most consistent evidence was for C. difficile-associated diarrhea, but we were able to analyze only the immediate impact of interventions because of nonstandardized durations of follow-up. The ability to compare results of studies could be substantially improved by standardizing methods and reporting.