Preventing infections caused by carbapenemase-producing bacteria in the intensive care unit - Think about the sink
Introduction
Healthcare-associated infection (HAI) represents the most common adverse event among hospitalized patients globally [1]. Data derived from Europe [2] and the USA [3] report a hospital-wide prevalence of HAI of 6.5% and 3.2%, respectively, with intensive care units (ICUs) specifically a setting in which HAIs are acquired at a higher rate and exhibit higher mortality [4]. A multicentre study in ICUs in Brazil showed that 60% of sepsis cases were from HAIs [5]. Importantly, recent data showed that up to 55% of all HAIs can be prevented by multifaceted infection prevention and control (IPC) interventions [6], ultimately resulting in a significant reduction in hospital-acquired sepsis.
Carbapenem antibiotics are commonly prescribed for critical care patients, and are integral elements of empiric treatment regimens [7]. In recent years, the prevalence of Gram-negative bacteria exhibiting resistance to carbapenems has increased, and this has been acknowledged by the World Health Organisation as a significant threat to human health and of the highest priority for research and development of novel therapies [8].
Carbapenem-resistance among Gram-negative bacteria is mediated by a number of mechanisms, with resistance to beta-lactams, including cephalosporins, and some carbapenem classes of antibiotics occuring via β-lactamase and extended β-lactamase production [9]. This can be mediated by upregulation and expression of chromosomally-encoded genes, such as blaAmpC [10], but significantly can also occur via β-lactamases encoded for on mobile genetic elements, such as plasmids, which are readily transferable and can disseminate both vertically and horizontally. In such cases, carbapenem-resistance is achieved via the acquired capacity for the production of carbapenemase enzymes, which are capable of hydrolysing carbapenem antibiotics [11]. Carbapenemase enzymes include: oxacillinase 48 (OXA-48), K. pneumoniae carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM) [12].
In critical care, the treatment of carbapenem-resistant infections is challenging as these organisms are often also resistant to many other antimicrobials such as flouroquinolones, and to emerging agents such as ceftazidim-avibactam [13,14]. Furthermore, while many patients may be colonised and not require an anti-infective agent, others develop serious infection. In a US study of 338 ICU patients, 28% became colonised with CPB, colonisation predicted systemic infection, and CPB colonisation was independently associated with 90-day mortality [15].
Livermore et al. [16] have recently highlighted an additional obstacle in the management of worsening carbapenem-resistance among Gram-negative bacteria- the lack of a clearly defined nomenclature or typing scheme. Carbapenemase-producing bacteria (CPB) are the focus of this review. In the literature, carbapenem-resistant Enterobacterales or Enterobacteriaceae (CRE) are terms often used interchangeably with carbapenemase-producing Enterobacterales (CPE) [16]. Many CPB and CPE are carbapenem-resistant, but others do not meet resistance thresholds [16,17]. However, the presence of a plasmid encoding a carbapenemase gene is significant among these organisms, and it is the capacity for horizontal acquisition of such plasmids, and the novel pathways that exist in hospitals to facilitate this, that challenge conventional IPC strategies. Some bacteria (i.e. Burkholderia spp. and Stenotrophomonas maltophilia) have chromosomally encoded carbapenemases, but these are not as readily transmissible as those harboured on plasmids [18]. Therefore, in this review, we will use the term CPB to refer to all bacteria known to carry carbapenemase-encoding plasmids, even if they exhibit breakpoints classifying them as susceptible to a carbapenem in-vitro.
Some nosocomial CPB infections may result from the trans-location of endogenous bacteria to usually sterile sites [19]. However, environmental pathways also facilitate dissemination within critical care units [20]. Gram-negative bacteria, such as A. baumannii, are readily transmitted from environmental surfaces to healthcare workers' hands [21]. Patients admitted to rooms previously occupied by individuals with A. baumannii [22] are at significant risk of acquiring these organisms from environmental sites contaminated by previous occupants. Novel transmission pathways available to and exploited by CPB have also resulted in outbreaks in critical care areas, and these pathways typically involve sinks and associated pipework [12].
Hospital sinks are breeding grounds and reservoirs for the transmission of nosocomial pathogens [12]. Campaigns over decades to promote hand hygiene have seen the instillation of numerous handwashing sinks. Hand hygiene is a vital IPC practice, however, each sink in critical care directly connects to a potential ecological niche for CPB. Retroactive contamination of the critical care environment via handwashing sinks has been linked to patient infections [12,23]. Sub-optimal room and sink designs can put patients at risk [23,24], increasing rates of CPB dispersal.
The concept of bacteria flourishing in ‘wet environments’ of hospitals is not new. Reports of Ps. aeruginosa and Legionella pneumophilia have, until now, represented the greater perceived threat from hospital water, and IPC strategies are embedded in most institutions to manage these. Reports of CPB, first published in the early 2000s, necessitate an urgent review of such policies, as existing strategies for their control (which include surveillance, flushing protocols, disinfectant regimens and oversight by maintenance personnel) are insufficient to control CPB [25].
Section snippets
Methods
We undertook to define and describe effective IPC measures to minimise the contamination of hospital sinks by CPB and to prevent transmission to vulnerable patients. We reviewed outbreaks related to contaminated hospital sinks, examining specific design features and healthcare provider behaviours that contribute to transmission with the aim of generating a narrative review for a critical care audience. We describe IPC measures that aimed to prevent CPB transmission through minimizing
Results
A total of 217 studies were returned based on the entered search teams. After removal of duplicates and inclusion of only English-language studies, 119 outbreak studies were screened for inclusion. Outbreaks of CPB that did not involve or mention investigations of sinks or drains were excluded. The narrative review was then synthesized based on outbreak reports that included the implementation of bundled interventions (n = 30), guidelines (n = 8), observational studies (n = 2), systematic
Conclusion
A growing body of evidence implicates handwashing sinks in outbreaks. There is no consensus of how to reliably mitigate or suppress these outbreaks, given that CPB outbreaks are often protracted and have grave consequences with potentially fatal infections. Collaboration between critical care physicians and nurses, infection prevention and control practitioners, architects, and engineers/estates management teams, is required to improve design and to implement measures to prevent acquisition of
Ethics approval and consent to participate
This review was drafted based on the literature and contains no patient or other confidential data. Hence, there are no ethical issues; not applicable.
Consent for publication
Not applicable.
Availability of data and materials
Not applicable.
Competing interests
HH has been in receipt of research funding from Pfizer and Astellas recently and he has received a consultancy payment from Pfizer within the last four years. GFC is in receipt of an Enterprise Ireland Award with CombiLift, and an Industry Seed Fund Award from RCSI and Cynata Therapeutics. All other authors have no potential conflicts of interest to declare.
Funding
Both AK and MB were funded through a research grant from the Health Research Board, Ireland (HRA-DI-2015-1141) while this was being drafted. GFC is funded through a Health Research Board Emerging Clinician Scientist Award.
Author contributions
AK developed the concept of the review. AK wrote the manuscript with assistance from MB. MB, HH and GFC revised and provided insights into the manuscript. HH supervised the project. All authors agreed the findings of the review and have endorsed the submission of this manuscript.
Acknowledgements
Not applicable.
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