Literature Review

Dr Lyn-li Lim joined VICNISS in early 2019. She is an infectious diseases physician with post-graduate training in epidemiology, public health and medical administration, and holds a co-appointment as a physician and antimicrobial stewardship lead at a public health service in Melbourne.
See below for her latest literature review:

Lessons from a Candida auris outbreak in England
(Literature review October 2019)

O’Connor et al. (J Hosp Infect 2019: 103; 106-111) describe their experience of an eight-week Candida auris outbreak on a vascular ward. Key learnings form their experience include the importance of early activation of a local incident management team supported by public health in screening and contact tracing. Of significance, isolates from two of the four cases demonstrated reduced susceptibility to echinocandins (first-line treatment for C. auris). As well, one bay contact with negative initial screening was positive when re-screened three-weeks later after transfer to another hospital.

Since its discovery in 2009, C. auris has been identified in more than 30 countries including Australia. In contrast to other Candida species, C. auris spreads easily in healthcare settings and has been associated with nosocomial outbreaks. The ability to persist in human hosts and inanimate surfaces, as well as the fact that this yeast is resistant to antifungal agents (resistance to fluconazole, variable susceptibility to other azoles, amphotericin and echinocandins), highlights the significance of this organism as a new nosocomial threat requiring enhanced infection control measures.

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Are ‘single room only’ hospitals effective in reducing healthcare-associated infections? 
(Literature review October 2019)

A proposed strategy to reduce transmission of multi-drug resistant organisms is to accommodate patients in single rooms to reduce chance of transmission from other patients and improve compliance with infection control measures. Evidence to date linking hospital architectural design and prevention of healthcare-associated infection (HAI) is conflicting. McDonald et al. (JAMA Int Med August 2019) report a reduction in infections (VRE) and colonisations (VRE and MRSA) when a Canadian hospital moved to a new 350-bed facility in which all patients had single rooms. However, no differences were observed in Clostridioides difficile infections (CDI) or MRSA infections.

In this time-series analysis, the move was associated with immediate and sustained reductions over 3-years in the incidence of nosocomial VRE colonisation (from 766 to 209 colonisations, incident rate ratio 0.25; 95% CI 0.19-0.34). There was also a fall in MRSA colonisation (from 129 to 112 colonisations, IRR 0.57; 95% CI 0.33-0.96) and VRE infection (from 55 to 14 infections, IRR 0.30; 95% CI 0.12-0.75). However, no change in nosocomial CDI (236 to 223 infections, IRR 1.00; 95% CI 0.98-1.02) or MRSA infections (27 to 37 infections; IRR 1.02, 95% CI 0.97-1.07) was observed. The IRR estimates adjusted rates pre- and post-hospital move. For VRE colonisation (IRR = 0.25), the colonisation rate reduced by 75% post-move. For MRSA colonisation (IRR 0.57), colonisation rate reduced by 43% post-move.

Limitations of the study include being unable to control for other contemporaneous interventions in infection control and antimicrobial stewardship and no data on MDR Gram-negative organisms. As well, MRSA colonisation may have been acquired pre-admission. While reasons for no change in CDI rate were not clear, it is possible that CDI disease burden may be associated with additional factors, including antibiotic prescribing patterns prior to hospitalisation.   

This study adds observational evidence to support recommendations for single-room design in healthcare facility construction, in order to decrease risks of transmission of specific multidrug resistant organisms and healthcare–associated infections. However, there is on-going need to also optimise practices around use of antimicrobials, hand hygiene and facility cleaning.

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Prevalence of healthcare associated infections in Australian hospitals 
(Literature Review August 2019)

Russo and colleagues (Antimic Res & Inf Control 2019:8;114) undertook a point prevalence study in a sample of large acute care hospitals. The primary objectives were (1) to estimate the total prevalence of HAIs among adult inpatients in public acute care hospitals in Australia and (2) to describe the HAIs by site, patient factors, medical specialty and geographical location.

Hospitals were recruited by seeking an expression of interest. To maximise representation of large acute care public facilities, inclusion criteria included being in the AIHW Principal Referral or Group A hospitals peer grouping (i.e. hospitals with 24-hour emergency departments, ICU and specialised units including, but not limited to, oncology and coronary care). Exclusions included specialist and private hospitals. Patients were systemically sampled according to random allocation of each ward to odd or even bed numbers. Patients were excluded if <18 years, in emergency or admitted for same-day procedure. European Centre for Disease Prevention and Control HAI definitions were used. 

2,767 patients from 19 hospitals were included. The median age of patients was 67 years, and 52.9% of the sample were male. Presence of multi-drug resistant organisms was documented for 10.3% of the patients. There were 363 HAIs present in 273 patients. The prevalence of patients with a HAI was 9.9% (95%CI: 8.8–11.0) with individual hospital prevalence rates ranging from 5.7% (95%CI:2.9–11.0) to 17.0% (95%CI:10.7–26.1). The most common HAIs were surgical site infection, pneumonia and urinary tract infection, comprising 64% of all HAIs identified.  A peripheral intravascular device was present in 55.2% and an IDC in 20.7%.  Of 38 patients with a BSI, 35 (92.1%) had a vascular device in-situ. The most common organisms isolated were S. aureus (18.9%), E.coli or Klebsiella (24.3%), Enterococcus spp (13.5%), Candida spp (10.8%).  Of 66 of patients with a UTI, 33 (50%) an IDC in-situ. Risk adjustment was not undertaken and severity of illness was not reported. The authors note selection bias in this study to ensure jurisdictional representation and inclusion limited to large public hospitals.

Russo et al have undertaken the first HAI point prevalence survey to be conducted in Australia in 34 years concluding that regular, large-scale HAI surveys should be undertaken to generate national HAI data to inform and drive national interventions. These study results complement state-level and regional healthcare-associated infection surveillance program activities which incorporate continuous surveillance, point-prevalence surveys and periodic monitoring  to provide hospitals with ward-level data, risk adjustment, measures of severity of illness to assist with immediate responses and tailoring of prevention strategies.

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Effectiveness of peripheral intravenous catheter-related insertion and maintenance bundles 
(Literature Review August 2019)

Bundles improve staff compliance with best practice by simplifying guidelines into a short point-of-care reminders. CVAD insertion and maintenance bundles have been widely implemented and are recognised to reduce infection rates.  The success of the CVAD bundle in ICU patients can be attributed to standardisation of the bundle components and consistency in their application. Ray-Barruel and colleagues (Inf, Dis & Health 2019: 24; 152e168) have undertaken the first systematic review to examine the effects of bundles on PIVC insertion and maintenance on PIVC complications (pain, infiltration, extravasation, blockage, premature dislodgement, thrombosis, phlebitis) and PIVC-related BSI.

13 studies were included in this review where an insertion or maintenance bundle was defined a priori as including at least two evidence-based practices for insertion respectively.  All included studies reported implementing a PIVC care bundle for insertion (n= 9) or maintenance (n =10), or both (n =8) in an acute care hospital inpatient setting. Twenty-one different insertion bundle components were detailed in 10 studies. Each insertion bundle comprised two to seven items: the most often reported items were 2% chlorhexidine gluconate (CHG) skin prep, hand hygiene, vessel assessment/ site selection, aseptic technique, integrated closed catheter, and transparent film dressing.  Twenty-two different maintenance bundle components were identified in 11 studies. Each maintenance bundle comprised two to seven items: the most common maintenance bundle items included daily review of need for PIVC (n=7) and poster reminders of the bundle intervention (n=7).

There are fewer published RCTs in PIVCs than CVADs, and while CVAD bundles are generally based on components supported by RCT evidence, this is not the case for PIVC bundles.  The effect of PIVC care bundles on PIVC-related bloodstream infection rates appears promising but further research is needed to identify which bundle components are effective to support standardisation of bundle components. 


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Infection Control Literature Review 
(Literature Review June 2019)

Healthcare-associated, hospital-onset (HO) Clostridioides difficile infection is associated with both antibiotics and prolonged hospital stays.  C. difficile spores can survive on surfaces for up to five months, suggesting that hospital environments may play an important role in the spread of HO-CDI. There is little data on the role of intra-hospital transfers on transmission dynamics of HO-CDI.  

McHaney-Lindstorm (Jour Hosp Infect 2019; 102 (2): 168-169) and colleagues examined whether a higher number of intra-hospital patient transfers increases the risk of HO-CDI infection. This was a case-control study where the control group was selected by performing a 1:3 match based antibiotic use during hospitalization and age. 
In all, 386 cases of HO-CDI were identified during the 2-year study period. The case and control groups were well balanced for age, antibiotic usage and Charlson Comorbidity Index scores. Multivariate logistic regression analysis suggested a significant relationship between CDI risk and the number of transfers, where for each additional transfer, the odds of HO-CDI infection increased by ∼7% (OR: 1.07; 95% CI: 1.02–1.13). 
These results suggest that intra-hospital transfers expose patients to more environments that may harbour the C. difficile spores, putting patients who experience more intra-hospital transfers at greater risk of CDI. This supports the practice of reducing unnecessary patient movement within hospitals. 

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Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope 
(Literature Review June 2019)

Infection control in endoscopy presents increasingly complex challenges. Since 2010, there have been several overseas outbreaks of CPE linked to the use of flexible endoscopes.  The Gastroenterological Society of Australia (GESA) and Gastroenterological Nurses College of Australia (GENCA) published the Infection Control in Endoscopy Guidelines (3rd edition, 2010) which are being updated this year.  In 2017, GESA, GENCA, ACIPC and Australasian Society of Infectious Diseases (ASID) developed consensus statements addressing this issue (J of Gastro and Hepatol 2019: 34:650-658). 
In this recent report (CID 2019: 68 (8); 1327–1334), transmission of mobile colistin resistance gene (mcr-1) was identified in two patients with highly-related K. pneumoniae clinical isolates.   An extensive field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organism, identified that a duodenoscope was the only common epidemiological link.  There were no identifiable breaches in reprocessing or infection control practices however evaluation of the scope identified intrusion of biomaterial under the sealed distal cap which was recalled.
Polymyxins such as colistin are used as a last-line antimicrobial treatment option for multi-drug resistant gram-negative infections. The spread of plasmid-mediated, mobile colistin resistance genes into carbapenamese-producing Enterobacteriacae raises the concern of potentially untreatable infections with significant transmission risks.   Instruments with complex tips (e.g. duodenoscopes and linear echoendoscopes) may transmit multidrug-resistant organisms persist despite recent initiatives to improve device safety. 

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Researching Effective Approaches to Cleaning in Hospitals (REACH) 
(Literature Review April 2019)

ACIPC 2018 delegates had the opportunity to hear investigators present interim findings from the REACH study which has now been published in Lancet Infectious Diseases (Mitchell B et al. Lancet Inf Dis 2019; epub 8/3/19). This is the first randomised controlled trial to investigate the effectiveness of a systematic bundle of interventions to improve environmental hygiene, targeting routine daily cleaning and terminal cleaning and disinfection in reducing health-care associated infections (HCAI) in hospitals.

The study was a stepped-wedge randomised controlled design, performed in 11 Australian hospitals between May 2016 and 2017. The intervention involved a review of the environmental hygiene approach in each hospital, and a structured, tailored set of recommendations to improve product choice, technique, audit, training, and communication of performance. The primary outcomes were incidences of health-care-associated S.aureus bacteraemia (SAB), C. difficile infection (CDI), and VRE infection. The secondary outcome was the thoroughness of cleaning of frequent touch points, assessed by a fluorescent marking gel. A unique aspect of the intervention was to raise the profile and importance of cleaning, support a culture shift in the perception and profile of environmental hygiene staff, and to encourage daily contact between environmental hygiene staff and ward leaders or managers. This is separately published (Mitchell B et al. Am J Inf Control 2018; 46(9):980-985).

Overall, there was a 37% reduction in VRE infections (from 0.35 to 0.22 per 10,000 occupied bed days (RR 0.63, 95% CI 0.41–0.97, p=0.0340), but no significant changes in the incidence of S. aureus bacteraemia (0.97 to 0.80/10,000 occupied bed days; RR 0.82, 95% CI 0.60–1.12, p=0.2180) or C. difficle infection (2.34 to 2.52/10,000 occupied bed days; RR 1.07, 95% CI 0.88–1.30, p=0.4655). The intervention increased the percentage of frequent touch points cleaned in bathrooms from 55% to 76% (odds ratio 2·07, 1·83–2·34, p<0·0001) and bedrooms from 64% to 86% (1·87, 1·68–2·09, p<0·0001). There were no noticeable changes in hand hygiene compliance or antimicrobial use during the study period.

This study underlines both the importance of environmental hygiene in preventing HCAI and also highlights our knowledge gaps around how what an effective environmental hygiene intervention looks like. The intervention was a mixture of training, education, organisational policy changes as required to increase the status of environmental hygiene and environmental hygiene staff. Any or all of these changes could have resulted in the reduction of VRE. It is unclear why there were no significant reductions in SAB and CDI: this could be further explored in the future by evaluating acquisition of colonisation rather than infection and looking also at the impact of appropriate use of a sporicidal disinfectant for C.difficile.

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Investigating Clostridium difficile Transmission Patterns between Infected and Colonised Patients Using Whole Genome Sequencing (Literature Review April 2019)

Clostridium difficile is a leading cause of health-care associated infections, rivalling MRSA, accounting for $3.2 billion in excess costs annually globally. A recently updated ASID/ACIPC position statement on infection control for patients with CDI in Australian healthcare facilities was published (IDH 2019:24:32-43). Infection control recommendations for hospitals focus on preventing transmission from symptomatic CDI patients. Kong et al (CID 2019; 68 (1):204-209) undertook to investigate the relative roles of carrier and cases as a source of transmission to patients with CDI.

Investigators analysed patient movement data and performed whole genome sequencing (WGS) on 554 C. difficile isolates originally obtained during a NAP1 strain outbreak. Samples were collected from 353 colonised patients and 201 CDI cases for genetic testing.

Of CDI cases, 105 (52%) were genetically linked with 81 (77%) also having a plausible ward link. Of those with a likely source, 34/81 (42%) of linked cases were associated exclusively with a previous CDI case and 19/81 (23%) associated exclusively with an asymptomatic carrier.

This is the largest study to date investigating the roles of carriers and cases as sources of transmission. The use of WGS is currently considered the most discriminating typing/fingerprinting method and being increasingly adopted over other techniques such as pulsed-field gel electrophoresis (PFGE) or PCR ribotyping. This study confirms that colonised patients may be a source of onward transmission to incident CDI cases, but that spread from infected donors with diarrhoea is likely more frequent.

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