Efectividad del aislamiento de contacto frente a las precauciones estándar en el control de la transmisión hospitalaria de enterobacterias productoras de beta-lactamasas de espectro extendido

Abstract

The emergence and dissemination of antimicrobial resistant microorganisms is one of the main Public Health concerns worldwide. Extended-spectrum beta-lactamases (ESBL) are one of the most prevalent mechanisms of antimicrobial resistance (AMR). These enzymes confer the ability to hydrolyze penicillins, cephalosporins and aztreonam. Its acquisition is mostly plasmid-mediated, which facilitates its dissemination, and its prevalence has grown dramatically in the community, with a high number of intestinal carriers throughout the world. Carbapenemases (CP) are another group of plasmid-mediated enzymes. They are able to hydrolyze carbapenems and nearly all beta-lactam antibiotics reducing therapeutic options in case of infection. They have spread throughout the world and currently they are more frequently isolated in healthcare centers. The fight against these microorganisms in healthcare settings include several interventions, including standard precautions (SP) and contact precautions, also known as contact isolation (CI). Contact precautions are intended to prevent transmission of microorganisms which are transmitted by direct or indirect contact with the patient or the patient’s environment. CI requires preferably a single-patient room, the use of patient-dedicated or single-use disposable non-critical equipment, restriction of visits and wearing gloves and gowns for all interactions with both the patient and the patient’s direct environment. However, placing patients colonized by ESBL-E under CI is controversial and there is a high variability in practices and the strictness of implementation between countries, even between centres in the same country or region. Recommendations are based on inconclusive evidence and CI is associated with undesirable effects and may be a contributing factor for the development of incidents related to patient safety. It also increases healthcare costs and results in the interruption of new patients’ admissions. The aim of this research was to establish the benefits of adding CI to SP for preventing hospital transmission of ESBL-producing Enterobacteriaceae (ESBL-E) in adult wards outside of intensive care units (ICU), via culture-based surveillance during the European Project RGNOSIS. A two-armed, cluster-randomised, crossover trial of two infection control strategies (SP and CI) was performed. Between March 3, 2014 and April 3, 2016, rectal swabs for ESBL-E surveillance cultures were obtained from all patients upon admission or as soon as possible, always within the first 3 days. Cultures were repeated weekly while the patient was hospitalized and on the day of discharge if possible, or within the previous 48 hours. The difference in the incidence density of ESBL-E acquisition between the two arms of the study was analyzed at unit and hospital level. The first article describes the prevalence of ESBL-E faecal carriers at admission at the Ramón y Cajal University Hospital in Madrid. The pneumology, gastroenterology, urology and neurosurgery wards took part in the study. During the research period 12,590 admissions of 9,706 patients took place in the participating wards; in 84.5% a rectal swab could be obtained within the first 3 days of admission. The prevalence of ESBL-E carriers was 7.69% (95% CI 7.18 – 8.19); 33.99% of the cases were known carriers. A total of 843 multiresistant Enterobacteriaceae were isolated in 818 patients, as 25 patients were colonised by more than one micro-organism at the time of admission (0.23%). 10.44% of the isolated Enterobacteriaceae were simultaneous ESBL and CP producers. Only 0.43% of the patients had an active ESBL-E infection at the time of admission (69.09% urinary tract infections). The most frequently isolated ESBL-producing microorganisms at admission were E. coli (77.70%), followed by K. pneumoniae (20.71%). The typing of 24.67% of total ESBL was posible; 83.17% belonged to the CTX-M group (52.88% CTX-M-15; 12.50% CTX-M14). Of the CP typed (73.86%), 90.77% were OXA-48. In the second paper, the benefits of adding CI to SP for preventing hospital transmission of ESBL-E in adult wards outside of ICU is evaluated. Hospitals from four European countries took part in the study (Hospital Universitario Ramón y Cajal, Madrid, Spain; Hôpitaux Universitaires de Genève, Switzerland; University Medical Centre Utrecht, The Netherlands; Charité – Universitätsmedizin Berlin, Germany). During the study period, 38,357 patients were admitted to the participating services. Of the 15,184 patients with a length of stay of more than 1 week, 75% (11,368 patients) had at least two cultures collected. Only these patients were included since at least two samples were required, the first being negative, to qualify an ESBL-E as hospital acquired. Adherence to hand hygiene and the use of gowns and gloves, as well as antimicrobials consumption were monitored, being similar in the different study periods. The incidence density of hospital acquired ESBL-E was 6‰ risk days (95% CI 5.4 -6.7) during the CI period, and 6.1‰ (95% CI 5.5 - 6.7) during the SP period (p=0.9710). Both the prevalence of ESBL-E at admission and the ESBL-E incidence density were similar between the CI and SP periods, despite substantial variation between the different units. At the patient-level, an adjusted multivariable model accounting for patients’ length of stay, including potential confounders (ward, ward type, and country), showed no evidence of an effect of CI on the risk of ESBL-E-acquisition over time (for care under CI, adjusted hazard ratio 1 [95% CI 0,86–1,5]). In the third article, the diversity of species and the distribution of the ESBL-E and CP-E populations were analyzed throughout the study period at the Ramón y Cajal University Hospital. ESBL-E incidence showed a decrease during the study period (p=0.003) and there were no significant differences between the two strategies, CI and SP (IRR = 1.04, 95% CI = 0.86–1.25, p = 0.07). Although CPE carrier prevalence remained unchanged during the study (IRR = 1.01, 95% CI = 0.98–1.02; p = 0.41) one of the units showed a statistically significant increase during the SP period. This increase could be attributable to an outbreak of NDM-1-producing K. pneumoniae probably started by a patient who had recently travelled to Pakistan. E. coli (78.5%) was the most frequent ESBL-producing microorganism followed by K. pneumoniae (17%). Species diversity among ESBL-E remained stable over time with E. coli being the predominant ESBL-E throughout the study. K. pneumoniae (53.5%) was the most frequent E-PC followed by E. coli (19.2%) and Enterobacter cloacae complex (11.1%). Species diversity decreased among the CPE population over time mainly due to K. pneumoniae dominance and increased E. coli prevalence in the last part of the study. In conclusion, contact isolation was not effective in reducing the ESBL-E transmission in the absence of an outbreak in conventional hospitalization units (not ICU). Therefore, it can be considered an unnecessary and not recommended practice due to its lack of effectiveness in reducing AMR transmission and its risks to patient safety. Efforts to contain the spread of ESBL-E within the hospital should focus on improving healthcare workers compliance with SP especially with hand hygiene, measures that have shown to be cost-effective and that do not impose restrictions on the patients.