Description of demographic and clinical characteristics of extrapulmonary tuberculosis in Shandong, China.

BACKGROUND: According to the clinical manifestation, tuberculosis (TB) is divided into pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). The incidence rate of EPTB has increased in many countries. The demographic and clinical characteristics of EPTB in China remain still unclear. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 5,624 hospitalized patients with positive M. tuberculosis culture between January 2008 and June 2013 in Shandong province. We investigated the epidemiological, demographic, and clinical characteristics of patients with EPTB. RESULTS: Among 5,624 hospitalized TB patients with positive M. tuberculosis culture, 4,277 (76.05 %) had PTB, 618 (10.99 %) had EPTB, and 729 (12.96 %) had both PTB and EPTB. The proportion of EPTB increased significantly from 6.97 % in 2008 to 19.98 % in 2012 (p <0.001).  The most frequent sites or foci of EPTB were pleura (63.27 %), followed by bone/joint (13.75 %), and lymph nodes (8.9 %). The mean duration of treatment for pleural TB was eight months and for EPTB in the other foci was more than 15 months. CONCLUSION: The proportion of EPTB in Shandong province has significantly increased. Clinicians need to be aware of the trend and remain vigilant against EPTB. EPTB requires prolonged treatment, and clinical supervision should be strengthened to prevent drug resistance. HIPPOKRATIA 2020, 24(1): 27-32.

Trends in mortality following Clostridium difficile infection in Scotland, 2010-2016: a retrospective cohort and case-control study.

BACKGROUND: National surveillance of Clostridium difficile infection (CDI) in Scotland enables the monitoring of trends in incidence rates but not mortality. AIM: To assess factors associated with mortality for all CDI cases aged ≥15 years in Scotland between 2010 and 2016. METHODS: All CDI cases aged ≥15 years in Scotland between 2010 and 2016 were linked to hospital admission and mortality datasets. Logistic regression was used to assess factors associated with mortality (30-day all-cause). A case-control study of a hospitalized subset of cases and matched hospitalized controls assessed the impact of CDI on mortality and length of stay. FINDINGS: Thirty-day all-cause mortality decreased over the seven-year period (from 20.5% to 15.6%; P < 0.001), mainly among healthcare-associated CDI (HA-CDI). Increased age, higher Charlson score, HA-CDI, as well as liver, heart and malignancy comorbidities were associated with higher mortality. No association was observed between polymerase chain reaction ribotype and higher mortality, though 015 and 078 were associated with lower mortality. Adjusted odds ratio (OR) for 30-day mortality in hospitalized CDI cases compared to controls was 2.67 (95% confidence interval (CI): 2.42-2.94; P < 0.001). Whereas mortality declined over time in cases and controls, the trend in ORs remained relatively stable. Having CDI increased additional mean length of stay beyond infection by 22.3% (95% CI: 18.0-26.8%; P < 0.001). CONCLUSION: CDI is associated with an almost three-fold increase in 30-day mortality and places an increased burden on hospital resources by increasing mean LOS beyond the infection date by 22.3%. The decreasing CDI mortality trends may be due to overall improvements in mortality among the general and hospital population of Scotland. Therefore, despite large declines in incidence rates, CDI remains a serious healthcare problem.

Guidance document for prevention of Clostridium difficile infection in acute healthcare settings.

SCOPE: Clostridium difficile infection (CDI) is the most important infective cause of healthcare-associated diarrhoea in high income countries and one of the most important healthcare-associated pathogens in both Europe and the United States. It is associated with high morbidity and mortality resulting in both societal and financial burden. A significant proportion of this burden is potentially preventable by a combination of targeted infection prevention and control measures and antimicrobial stewardship. The aim of this guidance document is to provide an update on recommendations for prevention of CDI in acute care settings to provide guidance to those responsible for institutional infection prevention and control programmes. METHODS: An expert group was set up by the European society of clinical microbiology and infectious diseases (ESCMID) Study Group for C. difficile (ESGCD), which performed a systematic review of the literature on prevention of CDI in adults hospitalized in acute care settings and derived respective recommendations according to the GRADE approach. Recommendations are stratified for both outbreak and endemic settings. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: This guidance document provides thirty-six statements on strategies to prevent CDI in acute care settings, including 18 strong recommendations. No recommendation was provided for three questions.

How to: diagnose infection caused by Clostridium difficile.

BACKGROUND: Clostridium difficile is recognized as the major agent responsible for nosocomial diarrhoea. In the context of recent increase in the incidence and severity of C. difficile infections (CDI), an accurate diagnosis is essential for optimal treatment and prevention, but continues to be challenging. AIMS: The present article reviews each key step of CDI diagnosis including stool selection, methods and strategies used, and interpretation of the results. SOURCES: The most recent guidelines for CDI diagnosis published by scientific societies were reviewed. CONTENT: CDI diagnosis is based on clinical presentation and laboratory tests confirming the presence of toxigenic strain or toxins in stools. Stool selection is crucial and can be improved by implementing rejection criteria and a strict policy for appropriate testing. Multiple laboratory tests detecting different targets (free toxin or presence of a potentially toxigenic strain) are commercially available. However, none of these tests combine high sensitivity and specificity to diagnose CDI, low hands-on time and low cost. An optimized diagnosis can be achieved by implementing a two- or three-step algorithm. Algorithms currently recommended by the ESCMID comprise a screening test with high sensitivity followed by a more specific test to detect free toxins. Presence of free toxins in stools has been shown to better correlate with severe outcome whereas nucleic acid amplification tests may lead to an over-diagnosis by detecting asymptomatic carriers of a toxigenic strain. IMPLICATION: To date, no single test can accurately diagnose CDI. Guidelines from the ESCMID recommend a two- or three-step algorithm for optimal CDI detection.

First outbreak of colonization by linezolid- and glycopeptide-resistant Enterococcus faecium harbouring the cfr gene in a UK nephrology unit.

AIM: To describe an outbreak of colonization by linezolid- and glycopeptide-resistant Enterococcus faecium harbouring the cfr gene in a UK nephrology unit. METHODS: Isolates of linezolid-resistant E. faecium were typed by pulsed-field gel electrophoresis (PFGE), and examined by polymerase chain reaction (PCR) and sequencing for the transmissible cfr gene that confers resistance to linezolid. Enhanced environmental cleaning, initial and weekly screening of all patients, and monitoring of adherence to standard infection control precautions were implemented. FINDINGS: Five patients with pre-existing renal disease were found to have rectal colonization with linezolid-resistant E. faecium over a two-week period. The index case was a 57-year-old male from India who had travelled to the UK. One patient also had a linezolid-resistant E. faecium of a different PFGE profile isolated from a heel wound. All isolates were confirmed to harbour the cfr gene by PCR and Sanger sequencing, and all were resistant to glycopeptides (VanA phenotype). CONCLUSIONS: This article describes the first UK outbreak with a single strain of linezolid- and glycopeptide-resistant E. faecium harbouring the cfr gene, affecting five patients in a nephrology unit. Following the implementation of aggressive infection control measures, no further cases were detected beyond a two-week period.

Investigation of outbreaks of Pneumocystis jirovecii pneumonia in two Scottish renal units.

Pneumocystis jirovecii is recognized as an opportunistic pathogen. In recent years, human-to-human transmission of P. jirovecii has been demonstrated. However, outbreaks of P. jirovecii infections are not well defined because the epidemiological setting that facilitates transmission is not fully understood. This article describes two outbreaks of P. jirovecii pneumonia (PCP) in renal transplant patients in the West of Scotland. In total, 25 patients in two geographically contiguous locations were affected. Allele B was identified as the dominant type, along with allele A3. It was not possible to determine the exact reason for clustering of cases, although the outpatient clinic setting featured in one of the outbreaks. The outbreaks ceased with the use of trimethoprim-sulphamethoxazole prophylaxis; the target populations that received prophylaxis were different in the two outbreaks. Infection control teams should be alert to the possibility of outbreaks of PCP.

Prospective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis.

Since April 2015, whole genome sequencing (WGS) has been the routine test for Salmonella identification, surveillance and outbreak investigation at the national reference laboratory in England and Wales. In May 2015, an outbreak of Salmonella Enteritidis cases was detected using WGS data and investigated. UK cases were interviewed to obtain a food history and links between suppliers were mapped to produce a food chain network for chicken eggs. The association between the food chain network and the phylogeny was explored using a network comparison approach. Food and environmental samples were taken from premises linked to cases and tested for Salmonella. Within the outbreak single nucleotide polymorphism defined cluster, 136 cases were identified in the UK and 18 in Spain. One isolate from a food containing chicken eggs was within the outbreak cluster. There was a significant association between the chicken egg food chain of UK cases and phylogeny of outbreak isolates. This is the first published Salmonella outbreak to be prospectively detected using WGS. This outbreak in the UK was linked with contemporaneous cases in Spain by WGS. We conclude that UK and Spanish cases were exposed to a common source of Salmonella-contaminated chicken eggs.

Development of a sporicidal test method for Clostridium difficile.

BACKGROUND: Disinfectants with claimed activity against Clostridium difficile must be evaluated to ensure efficacy against the spores that comprise an environmental source of patient infection. Unfortunately there is, at present, no generally accepted method for evaluating these disinfectants. In the absence of such a method, laboratories have to adapt protocols that were not designed for products used in medical environments and consequently may use inappropriate test organisms, exposure times, and pass criteria. AIM: To develop and evaluate a method for testing the activity of disinfectants against C. difficile spores using exposure times and pass criteria which are relevant to clinical application. METHODS: A Joint Working Party of the Healthcare Infection Society (HIS) and the Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infections (ARHAI) of the Department of Health in England was assembled. The Working Party adapted a previously described enzyme-based method for spore purification (the Clospore method) using an exposure time of 5 min and a 5 log10 kill as a pass criterion. FINDINGS: Evaluation of the method by three laboratories demonstrated that the method is simple to follow and that the results are repeatable and reproducible. CONCLUSION: The method described by the Working Party produces a clean suspension with a high titre of spores. It is recommended that, for a disinfectant used in the environment, the product should demonstrate a 5 log10 reduction in 5 min under clean or dirty conditions to fulfil the requirements of the test.

Serovars, bacteriophage types and antimicrobial sensitivities associated with salmonellosis in dogs in the UK (1954-2012).

Serovars and bacteriophage (phage) types were determined for 442 isolates of Salmonella enterica from dogs in the UK submitted to the Scottish Salmonella Reference Laboratory from 1954 to 2012. The most frequent serovars were Salmonella Typhimurium (196 isolates; 44.3 per cent), Dublin (40 isolates; 9.0 per cent), Enteritidis (28 isolates; 6.3 per cent), Montevideo (19 isolates; 4.3 per cent), Virchow (10 isolates; 2.3 per cent), Heidelberg (8 isolates; 1.8 per cent) and Derby (8 isolates; 1.8 per cent), along with 55 other recognised serovars among 127 other isolates, and six incompletely classified isolates. Serovars were frequently represented by strains commonly associated with poultry, cattle or pigs and their products. Among 196 Salmonella Typhimurium isolates from dogs, the most frequent phage types (definitive types) were the multiple antimicrobial-resistant strains DT104 (62 isolates), DT204c (18 isolates) and DT193 (8 isolates), along with antimicrobial sensitive wild finch strains DT40 (13 isolates) and DT56 variant (8 isolates). Eleven of 28 isolates of Salmonella Enteritidis were phage type 4. S enterica was frequently recovered from faecal or intestinal samples of dogs with diarrhoea, although many dogs had concurrent infection with other enteric pathogens. Salmonella Dublin was recovered from the brain and/or cerebrospinal fluid of two dogs with meningoencephalitis. Salmonella Kedougou was isolated from the joint fluid of a dog with septic arthritis. Salmonella Typhimurium and Salmonella Dublin were each recovered from the vaginas of bitches that had aborted. Isolates of Salmonella Enteritidis phage types 1, 4 and 8, Salmonella Typhimurium DT104, Salmonella Dublin and Salmonella Indiana were isolated from clinically healthy dogs in households where the same strains were recovered from human beings with diarrhoea. The pattern ampicillin-chloramphenicol-spectinomycin-streptomycin-sulfamethoxazole-tetracycline (ACSpSSuT) was the most frequent resistance phenotype and was observed in 44 (13.3 per cent) of 330 isolates. Dogs in the UK are exposed to a wide variety of serovars of S enterica, sometimes associated with clinical disease, and represent a zoonotic risk.

Economic evaluation of treatment for MRSA complicated skin and soft tissue infections in Glasgow hospitals.

In the UK, methicillin-resistant Staphylococcus aureus (MRSA)-associated skin and soft tissue infections (SSTIs) are predominantly managed in the hospital using intravenous (IV) glycopeptides. We set out to explore the potential for and relative healthcare costs of earlier hospital discharge through switch to oral antibiotic therapy (linezolid or rifampicin and doxycycline) or continuation of IV therapy (teicoplanin) via an outpatient parenteral antimicrobial therapy (OPAT) service. Over 16 months, 173 patients were retrospectively identified with MRSA SSTI, of whom 82.8 % were treated with IV therapy. Thirty-seven patients were potentially suitable for earlier discharge with outpatient therapy. The model assumed 3 days of inpatient management and a maximum of 14 days of outpatient therapy. For the status quo, where patients received only inpatient care with IV therapy, hospital costs were calculated at £12,316 per patient, with 97 % of costs accounted for by direct bed day costs. The mean total cost savings achievable through OPAT or oral therapy was estimated to be £6,136 and £6,159 per patient treated, respectively. A significant proportion of patients with MRSA SSTI may be suitable for outpatient management with either oral therapy or via OPAT, with the potential for significant reduction in healthcare costs.

Investigating the link between the presence of enteroaggregative Escherichia coli and infectious intestinal disease in the United Kingdom, 1993 to 1996 and 2008 to 2009.

There are an estimated 17 million human diarrhoea cases annually in the United Kingdom. In 2008 and 2009, enteroaggregative E. coli (EAEC) were identified in 1.9% of stools. However, it remains unclear whether there is a causal link between presence of EAEC and disease. This study used bacterial load, the presence of co-infections and demographic data to assess if EAEC was independently associated with intestinal infectious disease. Quantitative real-time PCR data (Ct values) generated directly from stool specimens for several pathogen targets were analysed to identify multiple pathogens, including EAEC, in the stools of cases and healthy controls. Sensitivity and specificity using Ct value (60% and 60%) was not useful for identifying cases or controls, but an independent association between disease and EAEC presence was demonstrated: multivariate logistic regression for EAEC presence (odds ratio: 2.41; 95% confidence interval: 1.78­3.26; p<0.001). The population-attributable fraction was 3.3%. The group of bacteria known as EAEC are associated with gastrointestinal disease in at least half of the cases with EAEC positive stools. We conclude that the current definition of EAEC, by plasmid gene detection, includes true pathogens as well as non-pathogenic variants.

Guidance on the use of respiratory and facial protection equipment.

Infectious micro-organisms may be transmitted by a variety of routes, and some may be spread by more than one route. Respiratory and facial protection is required for those organisms that are usually transmitted via the droplet/airborne route, or when airborne particles have been artificially created, such as during 'aerosol-generating procedures'. A range of personal protective equipment that provides different degrees of facial and respiratory protection is available. It is apparent from the recent experiences with severe acute respiratory syndrome and pandemic (H1N1) 2009 influenza that healthcare workers may have difficulty in choosing the correct type of facial and respiratory protection in any given clinical situation. To address this issue, the Scientific Development Committee of the Healthcare Infection Society established a short-life working group to develop guidance. The guidance is based upon a review of the literature, which is published separately, and expert consensus.

Respiratory and facial protection: a critical review of recent literature.

Infectious micro-organisms may be transmitted by a variety of routes. This is dependent on the particular pathogen and includes bloodborne, droplet, airborne, and contact transmission. Some micro-organisms are spread by more than one route. Respiratory and facial protection is required for those organisms which are usually transmitted via the droplet and/or airborne routes or when airborne particles have been created during 'aerosol-generating procedures'. This article presents a critical review of the recently published literature in this area that was undertaken by Health Protection Scotland and the Healthcare Infection Society and which informed the development of guidance on the use of respiratory and facial protection equipment by healthcare workers.

Distinguishable epidemics of multidrug-resistant Salmonella Typhimurium DT104 in different hosts.

The global epidemic of multidrug-resistant Salmonella Typhimurium DT104 provides an important example, both in terms of the agent and its resistance, of a widely disseminated zoonotic pathogen. Here, with an unprecedented national collection of isolates collected contemporaneously from humans and animals and including a sample of internationally derived isolates, we have used whole-genome sequencing to dissect the phylogenetic associations of the bacterium and its antimicrobial resistance genes through the course of an epidemic. Contrary to current tenets supporting a single homogeneous epidemic, we demonstrate that the bacterium and its resistance genes were largely maintained within animal and human populations separately and that there was limited transmission, in either direction. We also show considerable variation in the resistance profiles, in contrast to the largely stable bacterial core genome, which emphasizes the critical importance of integrated genotypic data sets in understanding the ecology of bacterial zoonoses and antimicrobial resistance.

Antibiotic stewardship and early discharge from hospital: impact of a structured approach to antimicrobial management.

OBJECTIVES: To assess the impact of an infection team review of patients receiving antibiotics in six hospitals across the UK and to establish the suitability of these patients for continued care in the community. METHODS: An evaluation audit tool was used to assess all patients on antibiotic treatment on acute wards on a given day. Clinical and antibiotic use data were collected by an infection team (doctor, nurse and antibiotic pharmacist). Assessments were made of the requirement for continuing antibiotic treatment, route and duration [including intravenous (iv)/oral switch] and of the suitability of the patients for discharge from hospital and their requirement for community support. RESULTS: Of 1356 patients reviewed, 429 (32%) were on systemic antibiotics, comprising 165 (38%) on iv ±â€Šoral antibiotics and 264 (62%) on oral antibiotics alone. Ninety-nine (23%) patients (including 26 on iv antibiotics) had their antibiotics stopped immediately on clinical grounds. The other 330 (77%) patients (including 139 on iv antibiotics) needed to continue antibiotics, although 47 (34%) could be switched to oral. Eighty-nine (21%) patients were considered eligible for discharge, comprising 10 who would have required outpatient parenteral antibiotic therapy (OPAT), 55 who were suitable for oral outpatient treatment and 24 who had their antibiotics stopped. CONCLUSIONS: Infection team review had a significant impact on antimicrobial use, facilitating iv to oral switch and a reduction in the volume of antibiotic use, possibly reducing the risk of healthcare-associated complications and infections. It identified many patients who could potentially have been managed in the community with appropriate resources, saving 481 bed-days. The health economics are reported in a companion paper.