Frequent Undetected Ward-Based Methicillin-Resistant Staphylococcus aureus Transmission Linked to Patient Sharing Between Hospitals.

Background: Recent evidence suggests that hospital transmission of methicillin-resistant Staphylococcus aureus (MRSA) is uncommon in UK centers that have implemented sustained infection control programs. We investigated whether a healthcare-network analysis could shed light on transmission paths currently sustaining MRSA levels in UK hospitals. Methods: A cross-sectional observational study was performed in 2 National Health Service hospital groups and a general district hospital in Southeast London. All MRSA patients identified at inpatient, outpatient, and community settings between 1 November 2011 and 29 February 2012 were included. We identified genetically defined MRSA transmission clusters in individual hospitals and across the healthcare network, and examined genetic differentiation of sequence type (ST) 22 MRSA isolates within and between hospitals and inpatient or outpatient and community settings, as informed by average and median pairwise single-nucleotide polymorphisms (SNPs) and SNP-based proportions of nearly identical isolates. Results: Two hundred forty-eight of 610 (40.7%) MRSA patients were linked in 90 transmission clusters, of which 27 spanned multiple hospitals. Analysis of a large 32 patient ST22-MRSA cluster showed that 26 of 32 patients (81.3%) had multiple contacts with one another during ward stays at any hospital. No residential, outpatient, or significant community healthcare contacts were identified. Genetic differentiation between ST22 MRSA inpatient isolates from different hospitals was less than between inpatient isolates from the same hospitals (P ≤ .01). Conclusions: There is evidence of frequent ward-based transmission of MRSA brought about by frequent patient admissions to multiple hospitals. Limiting in-ward transmission requires sharing of MRSA status data between hospitals.

Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data.

BACKGROUND: Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. METHODS AND FINDINGS: This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03-2.94]; HA-MRSA RR: 1.57 [1.06-2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01-1.19]) and residence in communal care homes (RR: 1.24 [1.12-1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04-2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16-2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19-2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level. CONCLUSIONS: There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes.

Universal hospital admission screening for carbapenemase-producing organisms in a low-prevalence setting.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat for healthcare providers worldwide. OBJECTIVES: To determine CPE carriage rates and risk factors in an unselected hospital cohort at the time of admission. METHODS: We approached 4567 patients within 72 h of admission to provide a rectal swab and answer a questionnaire on risk factors for carriage. Rectal swabs were cultured for carbapenem-resistant organisms on chromogenic and non-chromogenic agar, and tested for carbapenemase production by PCR (Check-Direct CPE). The study was approved by the NHS Research Ethics Committee. RESULTS: Only 6 CPE were cultured from 5 (0.1%) of 4006 patients who provided a rectal swab; only 1 was cultured using non-chromogenic media. An additional 76 culture-negative rectal swabs were initially PCR positive, but none grew a carbapenem-resistant organism despite enrichment culture and only two were positive when retested several months later by Check-Direct and a second PCR assay (Cepheid GeneXpert® Carba-R). A modified Ct cut-off of <35 would have resolved these apparent false-positives. 40% of patients had a risk factor that should prompt screening and pre-emptive isolation as defined by UK CPE guidelines but only 8.1% and 20.2% of these patients had been screened and pre-emptively isolated by clinical teams, respectively. Overseas hospitalization was the only significant risk factor for CPE carriage (P < 0.001, OR 64.3, 95% CI 7.3-488.5). CONCLUSIONS: This study highlights a very low carriage rate of CPE. Hospitalization abroad is the most important risk factor to guide admission screening in this low-prevalence setting.

Impact of mupirocin resistance on the transmission and control of healthcare-associated MRSA.

OBJECTIVES: The objectives of this study were to estimate the relative transmissibility of mupirocin-resistant (MupR) and mupirocin-susceptible (MupS) MRSA strains and evaluate the long-term impact of MupR on MRSA control policies. METHODS: Parameters describing MupR and MupS strains were estimated using Markov chain Monte Carlo methods applied to data from two London teaching hospitals. These estimates parameterized a model used to evaluate the long-term impact of MupR on three mupirocin usage policies: 'clinical cases', 'screen and treat' and 'universal'. Strategies were assessed in terms of colonized and infected patient days and scenario and sensitivity analyses were performed. RESULTS: The transmission probability of a MupS strain was 2.16 (95% CI 1.38-2.94) times that of a MupR strain in the absence of mupirocin usage. The total prevalence of MupR in colonized and infected MRSA patients after 5 years of simulation was 9.1% (95% CI 8.7%-9.6%) with the 'screen and treat' mupirocin policy, increasing to 21.3% (95% CI 20.9%-21.7%) with 'universal' mupirocin use. The prevalence of MupR increased in 50%-75% of simulations with 'universal' usage and >10% of simulations with 'screen and treat' usage in scenarios where MupS had a higher transmission probability than MupR. CONCLUSIONS: Our results provide evidence from a clinical setting of a fitness cost associated with MupR in MRSA strains. This provides a plausible explanation for the low levels of mupirocin resistance seen following 'screen and treat' mupirocin usage. From our simulations, even under conservative estimates of relative transmissibility, we see long-term increases in the prevalence of MupR given 'universal' use.

Clonal variation in high- and low-level phenotypic and genotypic mupirocin resistance of MRSA isolates in south-east London.

OBJECTIVES: Both low-level mupirocin resistance (LMR) and high-level mupirocin resistance (HMR) have been identified. The aim of this study was to determine the epidemiology of LMR and HMR in MRSA isolates at five hospitals that have used mupirocin for targeted decolonization as part of successful institutional control programmes. METHODS: All MRSA identified in three microbiology laboratories serving five central and south-east London hospitals and surrounding communities between November 2011 and February 2012 were included. HMR and LMR were determined by disc diffusion testing. WGS was used to derive multilocus sequence types (MLSTs) and the presence of HMR and LMR resistance determinants. RESULTS: Prevalence of either HMR or LMR amongst first healthcare episode isolates from 795 identified patients was 9.69% (95% CI 7.72-11.96); LMR was 6.29% (95% CI 4.70-8.21) and HMR was 3.40% (95% CI 2.25-4.90). Mupirocin resistance was not significantly different in isolates identified from inpatients at each microbiology laboratory, but was more common in genotypically defined 'hospital' rather than 'community' isolates (OR 3.17, 95% CI 1.36-9.30, P = 0.002). LMR was associated with inpatient stay, previous history of MRSA and age ≥65 years; HMR was associated with age ≥65 years and residential postcode outside London. LMR and HMR varied by clone, with both being low in the dominant UK MRSA clone ST22 compared with ST8, ST36 and ST239/241 for LMR and with ST8 and ST36 for HMR. V588F mutation and mupA carriage had high specificity (>97%) and area under the curve (>83%) to discriminate phenotypic mupirocin resistance, but uncertainty around the sensitivity point estimate was large (95% CI 52.50%-94.44%). Mutations in or near the mupA gene were found in eight isolates that carried mupA but were not HMR. CONCLUSIONS: Mupirocin resistance was identified in <10% of patients and varied significantly by clone, implying that changes in clonal epidemiology may have an important role in determining the prevalence of resistance in conjunction with selection due to mupirocin use.

25 years of surveillance of drug-resistant tuberculosis: achievements, challenges, and way forward.

Tuberculosis is second only to COVID-19 as a cause of death from a single infectious agent. In 2020, almost 10 million people were estimated to have developed tuberculosis and it caused 1·5 million deaths. Around a quarter of deaths caused by antimicrobial resistance are due to rifampicin-resistant tuberculosis. Antimicrobial resistance surveillance systems for many bacterial pathogens are still in the early stages of implementation in many countries, and do not yet allow for the estimation of disease burden at the national level. In this Personal View, we present the achievements, challenges, and way forward for the oldest and largest global antimicrobial resistance surveillance system. Hosted by WHO since 1994, the Global Project on Anti-Tuberculosis Drug Resistance Surveillance has served as a platform for the evaluation of the trends in anti-tuberculosis drug resistance for over 25 years at country, regional, and global levels. With an estimated 465 000 incident cases of multidrug-resistant and rifampicin-resistant tuberculosis in 2019, drug-resistant tuberculosis remains a public health crisis. The COVID-19 pandemic has reversed years of progress in providing essential tuberculosis services and reducing disease burden. The number of people diagnosed with drug-resistant tuberculosis has dropped by 22% since before the pandemic, and the number of patients provided with treatment for drug-resistant tuberculosis has dropped by 15%. Now more than ever, closing gaps in the detection of drug-resistant tuberculosis requires investment in research and development of new diagnostic tools and their rollout, expansion of sample transport systems, and the implementation of data connectivity solutions.

Infection prevention and control during the COVID-19 pandemic: challenges and opportunities for Kenyan public hospitals.

Background: Infection prevention and control, and water sanitation and hygiene have an essential role in ensuring the quality of care and patient outcomes in hospitals. Using a modification of the World Health Organization's water sanitation and hygiene facility improvement tool, we undertook assessments in 14 public hospitals in Kenya in 2018. The hospitals received written feedback on areas where they could make improvements. Following the first confirmed cases of COVID-19 in Kenya, we were drawn to ask whether the results of our pre-pandemic survey had led to action, and whether or not the threat of COVID-19 had focused more attention on infection prevention and control and water sanitation and hygiene. Methods: Using a semi-structured interview guide, we carried out phone interviews with key hospital leaders in 11 of the 14 hospitals. The data were transcribed and coded into thematic areas. We draw on these interviews to describe the status and awareness of infection prevention and control. Results: The infection prevention and control committee members are training health workers on infection prevention and control procedures and proper use of personal protective equipment and in addition, providing technical support to hospital managers. While some hospitals have also accessed additional funds to improve infection prevention and control, they tended to be small amounts of money.  Long-standing challenges with supplies of infection prevention and control materials and low staff morale persist.  Crucially, the reduced supply of personal protective equipment has led to fear and anxiety among health care personnel. Conclusions: As funds are mobilised to support care for COVID-19, we ask that funds prioritise infection prevention and control measures. This would have a profoundly positive effect on within hospital virus transmission, patient and staff safety but also lasting benefits beyond the COVID-19 pandemic.

Antibiotic use in Kenyan public hospitals: Prevalence, appropriateness and link to guideline availability.

OBJECTIVE: To examine prescription patterns and explore to what extent guidelines are available and how they might influence treatment appropriateness among hospitalised patients in Kenyan hospitals. METHODS: Data on antimicrobial usage were collected from hospitalised patients across 14 Kenyan public hospitals. For each prescription, appropriateness of treatment was defined using available local and international treatment guidelines and through consensus with local medical specialists. Association between appropriate treatment, guideline availability and other possible explanatory factors was explored using univariate and multiple regression analysis. RESULTS: There were 1675 (46.7%) of the 3590 hospitalised patients on antimicrobials with 3145(94%) of the 3363 antimicrobial prescriptions being antibiotics. Two patients (0.1%), had treatment based on available antibiotic susceptibility tests. Appropriate treatment was assessed in 1502 patients who had a single diagnosis. Of these, 805 (53.6%) received appropriate treatment. Physical availability of treatment guidelines increased the odds of receiving appropriate treatment Odds Ratio 6.44[95% CI 4.81-8.64]. CONCLUSION: Appropriate antibiotic prescription remains a challenge in Kenyan public hospitals. This may be improved by the availability of context-specific, up-to-date, and readily accessible treatment guidelines across all the departments, and by providing better diagnostic support.

Evaluating the foundations that help avert antimicrobial resistance: Performance of essential water sanitation and hygiene functions in hospitals and requirements for action in Kenya.

BACKGROUND: Water Sanitation and Hygiene (WASH) in healthcare facilities is critical in the provision of safe and quality care. Poor WASH increases hospital-associated infections and contributes to the rise of antimicrobial resistance (AMR). It is therefore essential for governments and hospital managers to know the state of WASH in these facilities to set priorities and allocate resources. METHODS: Using a recently developed survey tool and scoring approach, we assessed WASH across four domains in 14 public hospitals in Kenya (65 indicators) with specific assessments of individual wards (34 indicators). Aggregate scores were generated for whole facilities and individual wards and used to illustrate performance variation and link findings to specific levels of health system accountability. To help interpret and contextualise these scores, we used data from key informant interviews with hospital managers and health workers. RESULTS: Aggregate hospital performance ranged between 47 and 71% with five of the 14 hospitals scoring below 60%. A total of 116 wards were assessed within these facilities. Linked to specific domains, ward scores varied within and across hospitals and ranged between 20% and 80%. At ward level, some critical indicators, which affect AMR like proper waste segregation and hand hygiene compliance activities had pooled aggregate scores of 45 and 35% respectively. From 31 interviews conducted, the main themes that explained this heterogenous performance across facilities and wards included differences in the built environment, resource availability, leadership and the degree to which local managers used innovative approaches to cope with shortages. CONCLUSION: Significant differences and challenges exist in the state of WASH within and across hospitals. Whereas the senior hospital management can make some improvements, input and support from the national and regional governments are essential to improve WASH as a basic foundation for averting nosocomial infections and the spread of AMR as part of safe, quality hospital care in Kenya.

Evaluating hospital performance in antibiotic stewardship to guide action at national and local levels in a lower-middle income setting.

BACKGROUND: Inappropriate use of antibiotics can lead to the development of resistant pathogens. Ensuring proper use of these important drugs in all healthcare facilities is essential. Unfortunately, however, very little is known about how antibiotics are used in LMIC clinical settings, nor to what degree antibiotic stewardship programmes are in place and effective. OBJECTIVE: We aimed to record all Antibiotic Stewardship policies and structures in place in 16 Kenyan hospitals. We also wanted to examine the context of antibiotic-related practices in these hospitals. METHODS: We generated a set of questions intended to assess the knowledge and application of antibiotic stewardship policies and practices in Kenya. Using a set of 17 indicators grouped into four categories, we surveyed 16 public hospitals across the country. Additionally, we conducted 31semi-structured interviews with frontline healthcare workers and hospital managers to explore the context of, and reasons for, the results. RESULTS: Only one hospital had a resourced ABS policy in place. In all other hospitals, our survey teams commonly identified structures, resources and processes that in some way demonstrated partial or full control of antibiotic usage. This was verified by the qualitative interviews that identified common underlying issues. Most positively, we find evidence discipline-specific clinical guidelines have been well accepted and have conditioned and restricted antibiotic use. CONCLUSION: Only one hospital had an official ABS programme, but many facilities had existing structures and resources that could be used to improve antibiotic use. Thus, ABS Strategies should be built upon existing practices with national ABS policies taking maximum advantage of existing structures to manage the supply and prescription of antimicrobials. We conclude that ABS interventions that build on established responsibilities, methods and practices would be more efficient than interventions that presume a need to establish new ABS apparatus.

Extending the use of the World Health Organisations' water sanitation and hygiene assessment tool for surveys in hospitals - from WASH-FIT to WASH-FAST.

BACKGROUND: Poor water sanitation and hygiene (WASH) in health care facilities increases hospital-associated infections, and the resulting greater use of second-line antibiotics drives antimicrobial resistance. Recognising the existing gaps, the World Health Organisations' Water and Sanitation for Health Facility Improvement Tool (WASH-FIT) was designed for self-assessment. The tool was designed for small primary care facilities mainly providing outpatient and limited inpatient care and was not designed to compare hospital performance. Together with technical experts, we worked to adapt the tool for use in larger facilities with multiple inpatient units (wards), allowing for comparison between facilities and prompt action at different levels of the health system. METHODS: We adapted the existing facility improvement tool (WASH-FIT) to create a simple numeric scoring approach. This is to illustrate the variation across hospitals and to facilitate monitoring of progress over time and to group indicators that can be used to identify this variation. Working with stakeholders, we identified those responsible for action to improve WASH at different levels of the health system and used piloting, analysis of interview data to establish the feasibility and potential value of the WASH Facility Survey Tool (WASH-FAST) to demonstrate such variability. RESULTS: We present an aggregate percentage score based on 65 indicators at the facility level to summarise hospitals' overall WASH status and how this varies. Thirty-four of the 65 indicators spanning four WASH domains can be assessed at ward level enabling within hospital variations to be highlighted. Three levels of responsibility for WASH service monitoring and improvement were identified with stakeholders: the county/regional level, senior hospital management and hospital infection prevention and control committees. CONCLUSION: We propose WASH-FAST can be used as a survey tool to assess, measure and monitor the progress of WASH in hospitals in resource-limited settings, providing useful data for decision making and tracking improvements over time.

Using a common data platform to facilitate audit and feedback on the quality of hospital care provided to sick newborns in Kenya.

Essential interventions to reduce neonatal deaths that can be effectively delivered in hospitals have been identified. Improving information systems may support routine monitoring of the delivery of these interventions and outcomes at scale. We used cycles of audit and feedback (A&F) coupled with the use of a standardised newborn admission record (NAR) form to explore the potential for creating a common inpatient neonatal data platform and illustrate its potential for monitoring prescribing accuracy. Revised NARs were introduced in a high volume, neonatal unit in Kenya together with 13 A&F meetings over a period of 3 years from January 2014 to November 2016. Data were abstracted from medical records for 15 months before introduction of the revised NAR and A&F and during the 3 years of A&F. We calculated, for each patient, the percentage of documented items from among the total recommended for documentation and trends calculated over time. Gentamicin prescribing accuracy was also tracked over time. Records were examined for 827 and 7336 patients in the pre-A&F and post-A&F periods, respectively. Documentation scores improved overall. Documentation of gestational age improved from <15% in 2014 to >75% in 2016. For five recommended items, including temperature, documentation remained <50%. 16.7% (n=1367; 95% CI 15.9 to 17.6) of the admitted babies had a diagnosis of neonatal sepsis needing antibiotic treatment. In this group, dosing accuracy of gentamicin improved over time for those under 2 kg from 60% (95%36.1 to 80.1) in 2013 to 83% (95% CI 69.2 to 92.3) in 2016. We report that it is possible to improve routine data collection in neonatal units using a standardised neonatal record linked to relatively basic electronic data collection tools and cycles of A&F. This can be useful in identifying potential gaps in care and tracking outcomes with an aim of improving the quality of care.

Implications of targeted versus universal admission screening for meticillin-resistant Staphylococcus aureus carriage in a London hospital.

Universal admission screening for meticillin-resistant Staphylococcus aureus (MRSA) has been performed in England since 2010. We evaluated the predictive performance of a regression model derived from the first year of universal screening for detecting MRSA at hospital admission. If we had used our previous targeted screening policy, 75% fewer patients (21,699 per year) would have been screened. However, this would have identified only ~55% of all MRSA carriers, 65% of healthcare-associated MRSA strains, and 40% of community-associated strains. Failing to identify ~45% of patients (262 per year) carrying MRSA at hospital admission may have implications for MRSA control.