Epidemiology of extended-spectrum beta-lactamase-producing Enterobacteriaceae amongst old persons in the healthcare setting

Abstract

Antimicrobial resistance is a major health concern in human medicine both in the healthcare setting and in the community. While the epidemiology of multidrug-resistant gram-positive bacteria has been extensively described in the medical literature, clinical data for multidrug-resistant gram-negative bacteria (MDR-GNB) have less frequently been reported. Since the eighties, extended-spectrum beta-lactamase production has been recognized as one of the most important mechanism of antibiotic resistance among Enterobacteriaceae (ESBLE). This work aimed to improve our understanding of the epidemiology of ESBLE with a special focus among older adults in the healthcare setting. Because asymptomatic colonization has been recognized as the first step before infection and as a potential reservoir for cross-transmission, our major aims were to define prevalence and clinical characteristics of patients colonized in the intestinal flora by ESBLE in three different settings: the hospital, nursing homes (NH) and the community. In certain parts of this work, we did also extend our focus to two other bacteria of interest, namely: methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enteroccci (VRE) in order to assess the risks of co-colonization and compare risk factors. The introduction (chapter 1) will define ESBLE and give some insights in the global trends of MDR-GNB. The second chapter reports data of a 20-month retrospective study performed at a Belgian University hospital between January 2008 and Augustus 2009. The global proportion of ESBLE recovered from clinical samples was 4.5%. Data from 114 consecutive patients colonized or infected by ESBLE were analysed. Among the 68 patients (65%) with a presumed healthcare-associated acquired infection, the four main diagnoses were urinary tract infection, lower respiratory tract infection, bloodstream infection and intra-abdominal infection. This study highlighted that ESBLE carriers (whether colonized or infected) had a high number of co-morbidities (for examples, diabetes and chronic renal insufficiency), bladder catheter, antibiotic exposure or previous hospitalization. We also reported an increase length of hospital stay and a higher intra-hospital mortality among this group of patients. Interestingly, two-thirds of the patients were aged over 65 years and were referred from a nursing home. The retrospective design and the lack of a control group were limiting factors, reasons why a prospective observational study was designed in a specific unit admitting old frail patients. The third chapter presents the results of a one year prospective cohort study performed amongst patients admitted to a geriatric evaluation and management unit between January 2010 and January 2011. The primary aim of that study was to determine the prevalence and potential predictors of ESBLE asymptomatic carriage amongst 337 consecutive patients admitted to the acute geriatric unit. The overall prevalence of ESBLE colonization was 11.6% (95% CI: 8.2-15.0), versus 7.5% for MRSA (95%CI: 4.6-10.4). The three main predictors of ESBLE carriage were: a low functional status, prior multiple contacts with the hospital within the previous year and the presence of a chronic catheter. Using a second set of screening samples at discharge, we reported an incidence density of 1.77 new cases of ESBLE colonization per 1000 patient-days. The rate of co-colonization was low, less than 1% and only 2 cases of VRE were observed. No increase of in-hospital mortality or of ESBLE-related nosocomial infection rate was observed but the study was probably underpowered. Low functional status was a common risk factor for ESBLE and MRSA colonization, highlighting the need to reinforce infection control measures and to reduce antibiotic selection pressure among this old frail population. In that study, patients referred from NH were four times more at risk to be colonized by MRSA while the risk to be ESBLE carriers was similar compared to patients admitted from the community. Nevertheless recent reports have suggested that NHs may account as a large reservoir of multi-drug resistant microorganisms (MDRO), although large variations in prevalence have been reported in the literature. The fourth chapter addresses the epidemiology of ESBLE among residents from a random sample of 60 Belgian NH. A point-prevalence survey was carried out between June 2011 and October 2011 in order to assess the prevalence and determinants of asymptomatic colonization by ESBLE, MRSA and VRE amongst 2791 NH residents. The weighted prevalence of ESBLE and MRSA carriage were 6.2% (95%CI: 5.6-6.9) and 12.2% (95%CI: 11.3-13.1), respectively. No cases of VRE were found. The best predictors of colonization by ESBLE were male gender, antibiotic exposure in the past 3 months and a low level of mobility. Risk factors for MRSA carriage included: male gender, a low functional status, pressure sores, antacid use and bladder catheter. The proportion of MRSA carriers decreased by 6.8% in comparison to a similar survey carried out in 2005. Furthermore, both MRSA and ESBLE carriage trends in NH were very similar to those observed in Belgian acute care hospitals over the same period in the setting of a national surveillance programme. These results emphasized the need for a global coordination of the surveillance of MDRO within and between chronic and acute care medical sectors. The fifth chapter reports the results from a point-prevalence survey in a sample of community-dwelling old persons aged over 80 years and recruited from the population-based BelFrail cohort study. During two study periods (2010 and 2011), 378 (67%) urinary samples were obtained from the 567 initially recruited participants in 2008. A total of 357 bacteria were isolated (212 samples), mainly Enterococcus spp., Escherichia coli (E. coli) and Staphylococcus spp. Among the 212 samples (56%) that grew with at least one bacteria, only 3 patients harboured an ESBL-producing E. coli (crude prevalence: 0.79% [95%CI: 0.16-2.30]). Due to the small number of patients carrying ESBLE, analysis with individual risk factors could not be performed. Results from published studies including patients from the community are reported at the end of this chapter. Chapter 6 summarizes the results of a one year prospective observational study, performed after hospital admission in a geriatric ward, with as primary goal to assess among MDRO colonized patients four geriatric outcomes: functional decline rate, nursing home admission rate, readmission to hospital and all-cause mortality. Among 320 followed patients through phone-calls, no increased risk for each individual selected outcome was noticed. Several limits when interpreting data are mentioned: the small sample size, the lack of repeated screening swabs during follow-up and the selected “high-risk” profile of included patients. Chapter 7 describes the use of a clinical score including five items aimed to identify, at admission to hospital, patients at risk of colonization by MRSA. The study was undertaken during a one year period (2006-2007) and included 221 patients admitted to a geriatric department. A crude prevalence of 10% (95%CI: 6-14%) was observed. The 5 criteria were: being aged over 87 years, known antecedents of previous MRSA carriage, multiple hospital stay(s) in the past year, chronic wounds, previous antibiotic exposure and long-term catheter use. Overall, the high negative predictive value (97%) of this simple clinical score was found as useful tool to avoid ordering laboratory test for screening MRSA colonization in patients with none of those 5 criteria upon admission to hospital. Similar data are reported for the prospective cohort study designed to detect ESBLE at admission in chapter 3. Chapter 8 reports that in a non-outbreak period, the prevalence of Clostridium difficile (CD) among asymptomatic patients was extremely low. The diagnostic method (rectal swabs in place of stool samples) that was used and pre-analytic problems may also explain in part this low rate. For these reasons, screening of CD carriage among the residents was finally not considered in the NH survey. The last chapter discusses and compares the results of our different surveys with those reported in other studies and by national or European surveillance networks. It critically describes the limitations of all studies and it aims to provide the reader with some practical clinical applications. Finally, a short perspective addresses the opportunities for further studies in the future.(MED 3) -- UCL, 201