An outbreak of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 in a regional burns centre.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) outbreaks have been reported previously in burns centres with resulting mortality and morbidity. This article describes the first human-associated outbreak in the UK caused by a strain of mupirocin-resistant (MuR) livestock-associated MRSA clonal complex 398 (LA-MRSA CC398) in an adult burns centre. The centre historically had a very low prevalence of MRSA infections. AIM: To describe the clinical and epidemiological context of how the outbreak was identified and contained using a range of infection prevention and control (IPC) measures guided by both traditional and genetic methods. METHODS: A cluster of MuR-MRSA led to an outbreak investigation. Cases were detected via retrospective search and real-time laboratory surveillance. Isolates were sent continuously for whole-genome sequencing (WGS). A live timeline of cases and interventions was produced throughout the period. FINDINGS: The outbreak consisted of 12 cases (seven males and five females) aged between 22 and 70 years. Patients were identified between May and October 2020. All patients were colonized rather than infected. The strain acquired the plasmid bearing MupA while colonizing the index case before dissemination. The index case was found to be a chicken farmer. This outbreak was eventually controlled using IPC measures, audits, and blind staff decolonization guided by insight from WGS. CONCLUSION: It was not possible to determine how the strain entered the centre, or if a staff carrier was involved. The outbreak demonstrated the potential for continued transmissions for months despite active surveillance and stringent control measures.

Effects of fluoroquinolone restriction (from 2007 to 2012) on resistance in Enterobacteriaceae: interrupted time-series analysis.

BACKGROUND: Antibiotic stewardship is a key component in the effort to reduce healthcare-associated infections. AIM: To describe the implementation and analyse the impact of fluoroquinolone restriction on resistance in Enterobacteriaceae, focusing on urinary isolates of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli, which were historically almost universally resistant to fluoroquinolones. METHODS: ESBL-producing E. coli hospital and community isolates, obtained between April 2009 and March 2012 from consecutive non-duplicate urine samples, were included in an interrupted time-series analysis based on a Poisson distribution model. Periods before and after fluoroquinolone restriction were compared. The trend in fluoroquinolone resistance in all urinary isolates of Enterobacteriaceae (N ≈ 20,000 per year) and blood culture isolates of E. coli (N ≈ 350) between 2009 and 2013 were also analysed. FINDINGS: A large decline in the percentage of ciprofloxacin-resistant ESBL-producing urinary E. coli isolates was observed in both hospital (risk ratio: 0.473; 95% confidence interval: 0.315-0.712) and community settings (0.098; 0.062-0.157). The decline was also marked in all urinary isolates of Enterobacteriaceae and E. coli isolates from blood cultures. CONCLUSION: We conclude that reducing fluoroquinolone usage to a level of ≤2 defined daily doses per 100 occupied bed-days in hospital sufficiently removed selection pressure to allow resistant Enterobacteriaceae ­ specifically, the UK endemic strains of ESBL-producing E. coli ­ to revert back to fluoroquinolone susceptibility within a short span of four months. This was accompanied with a concomitant reduction in overall ESBL burden.

Effects of fluoroquinolone restriction (from 2007 to 2012) on Clostridium difficile infections: interrupted time-series analysis.

BACKGROUND: Antimicrobial stewardship is a key component in the reduction of healthcare-associated infections, particularly Clostridium difficile infection (CDI). We successfully restricted the use of cephalosporins and, subsequently, fluoroquinolones. From an endemically high level of >280 cases per year in 2007-08, the number of CDIs reduced to 72 cases in 2011-12. AIM: To describe the implementation and impact of fluoroquinolone restriction on CDI. METHODS: This was an interrupted time-series analysis pre and post fluoroquinolone restriction for 60 months based on a Poisson distribution model. FINDINGS: In June 2008, fluoroquinolone consumption halved to about 5 defined daily doses (DDD) per 100 occupied bed-days (OBD). This was followed by a significant fall in CDI number [rate ratio (RR): 0.332; 95% confidence interval (CI): 0.240-0.460] which remained low over the subsequent months. Subsequently, fluoroquinolone consumption was further reduced to about 2 DDD/100 OBD in June 2010 accompanied by further reduction in CDI rate (RR: 0.394; 95% CI: 0.199-0.781). In a univariate Poisson model the CDI rate was associated with fluoroquinolone usage (RR: 1.086; 95% CI: 1.077-1.094). CONCLUSION: We conclude that in an environment where cephalosporin usage is already low, the reduction in fluoroquinolone usage was associated with an immediate, large, and significant reduction in CDI cases.

Incidence of bla NDM-1 gene in Escherichia coli isolates at a tertiary care referral hospital in Northeast India.

PURPOSE: Increasing reports on New Delhi metallo-ß-lactamase-1 (NDM-1) producing Escherichia coli constitute a serious threat to global health since it is found to be highly resistant to most of the currently available antibiotics including carbapenems. This study has been performed to find out the incidence blaNDM-1 in E. coli isolates recovered from the various clinical samples at a tertiary care referral hospital in Northeast India. MATERIALS AND METHODS: A total of 270 non-duplicated E. coli isolates were recovered from the various clinical samples at a tertiary care referral hospital in Northeast India. All isolates with reduced susceptibility to meropenem or ertapenem (diameter of zones of inhibition, ≤ 21 mm) were further phenotypically confirmed for carbapenemase production by modified Hodge test. All screened isolates were also subjected to the polymerase chain reaction detection of blaNDM-1 gene and additional bla genes coding for transmission electron microscopy, SHV, CTX-M, and AmpC. RESULTS: Out of 270 E. coli isolates, 14 were screened for carbapenemase production on the basis of their reduced susceptibility to meropenem or ertapenem. All screened isolates were found to be positive for blaNDM-1 . Each of the blaNDM-1 possessing isolate was also positive for two or more additional bla genes, such as blaTEM , blaCTX-M and blaAmpC . Phylogenetic analysis showed very less variation in blaNDM-1 gene with respect to blaNDM-1 possessing E. coli isolates from other parts of India and abroad. CONCLUSIONS: Our findings highlight the incidence of blaNDM-1 in E. coli isolates with a reduced susceptibility to meropenem or ertapenem.

Co-morbidities as predictors of mortality in Clostridium difficile infection and derivation of the ARC predictive score.

Clostridium difficile associated diarrhoea (CDAD) has increased significantly in the last 15 years, but predictors of outcome are inadequately understood. This was a cohort study of 2761 patients in North East England between 2002 and 2009, with the end-point of mortality at 30 days. The role of age, gender and co-morbidities was examined by binary logistic regression. Rounded odds ratios were used to develop a predictive score. A predictive score based on age, renal disease and cancer (ARC score) differentiated groups with differing risk of 30-day mortality (risk for score of 0-3 was 9-21%, score of 4-7 was 31-48% and score of 8 was 66%). Co-morbidities were shown to be important predictors of outcome in CDAD, and can be combined with age in the ARC score to assess the likelihood of survival. This requires further validation in other populations, but has important implications for clinical and research practice.

Phylogenetic diversity of Escherichia coli strains producing NDM-type carbapenemases.

BACKGROUND: The global accumulation of Escherichia coli with CTX-M extended-spectrum ß-lactamases partly reflects the dissemination of clonal lineages, notably ST131 and ST405. More recently, E. coli have emerged that produce NDM carbapenemase. We sought to determine the clonal diversity of E. coli with this enzyme from English hospitals, and to compare them with isolates from Pakistan and India. METHODS: The 18 NDM-positive E. coli were from hospitals in England (n = 10), Pakistan (n = 7) and India (n = 1). Isolates were compared by phylogenetic grouping, multilocus sequence typing and PFGE of XbaI-digested DNA. Isolates were screened by PCR for acquired AmpC genes, bla(CTX-M), and the 16S rRNA methylase genes armA and rmtC. RESULTS: Most of the isolates belonged to phylogenetic groups B1 (n = 9) or D (n = 7); two were group A and none was group B2. Nine isolates from England and Pakistan belonged to the B1 lineage ST101, with seven of these clustering at >77% similarity by PFGE. Other lineages included ST405 (n = 3, group D), ST648 (n = 3, group D), the ST23 complex (one each of ST90 and ST410, both group A) and ST156 (n = 1, group D). Sixteen of 18 isolates had a group 1 CTX-M gene, 13 had a CIT-type acquired AmpC, and 16 had either or both of armA and rmtC. CONCLUSIONS: The E. coli isolates producing NDM-1 carbapenemase belonged to six sequence types and included diverse clonal lineages. Nevertheless, isolates of B1-ST101 accounted for half the collection, and included isolates from both England and Pakistan. None of the isolates belonged to ST131 or to phylogroup B2.

Multidrug-resistant Enterobacteriaceae including metallo-ß-lactamase producers are predominant pathogens of healthcare-associated infections in an Indian teaching hospital.

PURPOSE: A study was carried out in an Indian teaching hospital in 2009 to detect the rate of surgical site infections (SSI) and peripheral vascular access site infections. MATERIALS AND METHODS: The study was a point-prevalence study involving over 300 patients. The presence of infection was determined according to the CDC criteria. Swabs were taken from the infected sites and identification and sensitivity were carried out using VITEK® 2 automated system. Characterisation of ß-lactamase was carried out at ARRML, Colindale, London. RESULTS: The rate of SSI was 15% for the clean and clean-contaminated categories while that for the dirty contaminated category was 85% (NNIS risk index 0). Cultures yielded definite or probable pathogens from 64% (9/14) of the patients with SSI. In 1/3 rd of the cultures, Staphylococcus aureus was grown and the rest had Enterobacteriaceae, either extended-spectrum ß-lactamase (ESBL) producers or Amp-C hyperproducers and, alarmingly, three isolates were positive for newly recognised New Delhi metallo-ß-lactamase-1 (NDM-1). In medicine, 87% (n = 99) of the patients had a peripheral IV access device, 55% developed associated phlebitis/infection and, in seven, probable pathogens were isolated (Candida species and Escherichia coli producing ESBL and NDM-1, respectively, Staphylococcus aureus and Enterococcus faecium). All ESBL and metallo-ß-lactamase producers were resistant to multiple classes of antimicrobials, the latter being sensitive only to colistin and tigecycline. The study also found that all post-operative patients were on antibiotics, 92% on IV [213 defined daily doses (DDD)/100 post-op patients] limited mainly to the third-generation cephalosporins (26%) and aminoglycosides (24%) and imidazole derivatives (30%). In medicine, 83% (n = 82) were on IV antibiotics (123 DDD/100 bed-days), limited mainly to the third-generation cephalosporins (74%). CONCLUSION: Indiscriminate use of antibiotics is a major problem predisposing patients to harm by multi-resistant pathogens. Carbapenems were in little use in this hospital, but the selection pressure exerted by cephalosporins and other unrelated classes was sufficient to select NDM-1-producing strains due to co-selection, suggesting a role of single plasmid carrying resistance genes to multiple classes.

Thirty-day mortality of Clostridium difficile infection in a UK National Health Service Foundation Trust between 2002 and 2008.

Few standardised data are available on mortality rates in patients with Clostridium difficile infection (CDI). The literature often reports 'attributable' mortality or cannot be universally applied. We aimed to investigate the pattern and trends in all-cause mortality in a large unselected cohort of patients affected by CDI. This was done by means of a retrospective cohort study between 2002 and 2008 of all patients with positive stool toxin tests indicating CDI in one National Health Service (NHS) Trust, comprising three general hospitals and seven community hospitals. Vital status of the patients was determined from two sources. In total, 2571 patients with a first episode of CDI were identified (1638 females; median age 82.1 years). Cumulative mortality at 7 days, 14 days, 30 days and 1 year was 13.4%, 20.8%, 32.5% and 58.7%, respectively. There was no significant difference in mortality between sex, year of diagnosis or hospital site. Mortality at 30 days increased incrementally from 3.4% in those aged <40 years to 41% in those >90 years. Mortality rates were significantly higher than reported by previous studies but were remarkably consistent over the time period and between different hospitals within the Trust. Prognosis falls with increasing age, and the age of this cohort may explain the high 30-day absolute mortality. CDI infection is associated with high early mortality. To reduce mortality, new interventions need to be introduced soon after diagnosis. There is a need for standardised outcome data for CDI.

Prevalence and risk factors for colonisation with extended spectrum beta-lactamase producing enterobacteriacae vis-à-vis usage of antimicrobials.

PURPOSE: A point prevalence study was carried out in a teaching hospital in Assam to determine the prevalence, sensitivity profile and risk factors for acquisition of extended spectrum beta-lactamase (ESBL) producing enterobacteriacae vis-upsilon-vis amount and pattern of antibiotic use. MATERIALS AND METHODS: ESBL was detected by double disc synergy method. Defined daily dose and bed-days were calculated. RESULT: Colonisation rate of ESBL producing enterobacteriacae ranged from 14% (n=73) in medicine to the highest 41% (n=29) in orthopaedic with an intermediate 23% (n=80) in surgery. Presence of ESBL was found to be strongly associated with resistance to specific classes of antimicrobials. Exposure to cefotaxime and gentamicin, and surgery were risk factors for acquiring ESBL producing enterobacteriacae. Non-ESBL producing community isolates were found to be considerably more sensitive to different antibiotics with no resistance detected to trimethoprim, co-trimoxazole, ciprofloxacin and aminoglycosides. CONCLUSION: The study confirms the role of certain 'high risk' antimicrobials in acquisition of ESBL producing Enterobacteriaceae and shows that periodic cohort studies could be an effective strategy in surveillance of antimicrobial resistance in hospitals of resource poor countries to inform antibiotic policy and treatment guidelines.

Characterisation of methicillin resistant S. aureus strains and risk factors for acquisition in a teaching hospital in northeast India.

PURPOSE: A point prevalence study was carried out in a teaching hospital in Assam to characterise S. aureus strains, establish the rate of colonisation of methicillin resistant S. aureus (MRSA) and associated risk factors for its acquisition. MATERIALS AND METHODS: Antibiogram-Resistogram profile was done by BSAC standardized disc sensitivity method; Phage and RFLP typing were carried out by the PHLS, London. RESULTS: Single MRSA strain resistant to multiple classes of anti-staphylococcal antibiotics dominated the hospital. The MRSA colonisation rate was found to be 34% (n=29) and 18% (n=80) in orthopaedics and surgery, respectively and only approximately 1% (n=73) in the medical units. Exposure to ciprofloxacin and surgery were risk factors but duration of hospital stay was not. In contrast, methicillin sensitive S. aureus (MSSA) strains were usually distinct strains and sensitive to most of the anti-staphylococcal antibiotics including 18% to penicillin. CONCLUSIONS: The MRSA strain prevalent in the hospital phenotypically resembles the predominant Asian strain viz., Brazilian/Hungarian strains (CC8-MRSA-III). Duration was not a risk factor, which suggests that in absence of exposure to specific antimicrobials, even in a hospital with no or little infection control intervention, a vast majority remain free from MRSA. This underlines the importance of rational prescribing empirical antibiotics.

Infection control with limited resources: why and how to make it possible?

The risk of healthcare-associated infections (HCAIs) in developing countries can exceed 25% compared to developed countries. Lack of awareness and institutional framework to deal with patient safety in general and HCAI in particular perpetuates the culture of acceptance of avoidable risks as inevitable. Most HCAIs are avoidable and can be prevented by relatively simple means. It is no longer acceptable to put patients at risk of avoidable infections. The World Health Organization (WHO)-led World Alliance for Patient Safety launched a worldwide campaign on patient safety focusing on simple means like hand hygiene to combat HCAIs. To drive necessary changes to deliver sustainable improvement in clinical care requires strategic approach and clinical leadership. This article reviews the scale of the problem, the WHO recommended interventions and improvement strategies in institutional setup in developing and transitional countries.