Candida auris part III. Are you prepared?

Schermafbeelding 2017-05-20 om 13.28.23

MMWR just published on the ongoing transmission of Candida auris in the US, while at the same time PLOS Pathogens came with an excellent review on the topic.

By now I had the debatable pleasure to be around for the birth of a few “superbugs”, but this one is clearly putting a lot of effort into reaching the top of the list. I believe (classical pessimist) that many institutions still ignore this new adversary (or are even unaware), and most certainly have no game-plan to prevent its introduction and consequent spread.  In the MMWR publication the current recommendations for C. auris–colonized or infected patients were repeated, with only one change from previous recommendations, namely that a more effective (sporicidal) disinfectant is needed, but I seriously wonder who follows this guidance.

Thus, here it comes, another 30-seconds-questionaire.  Why?  Because I hope that you will prove me wrong and that we – the infection control people at the frontline – act on threat, instead of re-act once we are overrun.

Link to questions  https://www.surveymonkey.com/r/QCK9RWS

References

Notes from the Field: Ongoing Transmission of Candida auris in Health Care Facilities — United States, June 2016–May 2017. Weekly / May 19, 2017 / 66(19);514–515 https://www.cdc.gov/mmwr/volumes/66/wr/mm6619a7.htm?s_cid=mm6619a7_e

Chowdhary A, Sharma C, Meis J. Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLOS Pathogens  https://doi.org/10.1371/journal.ppat.1006290 May 18, 2017

Do single rooms reduce HCAI?

An interesting review article examines the relationship between three related variables: the proportion of single rooms, the size of the patient room and patient proximity, and the availability of antiseptic hand rub, with various HCAI indicators. The bottom line is that both a move towards a higher proportion of single rooms and larger patient rooms are associated with reduced HCAI, and making hand gels more available improves compliance with their use (unsurprisingly).

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Spread the word, not the MDROs!

xdro registry

Guest blogger, Rita Bos (bio below) writes:

This month, while randomly searching Pubmed with the subject MDRO (I know, a rather bizarre hobby), I came across a French study on MDRO information in patient transfer letters. In this paper, which was published in the French journal “Médecine et maladies infectieuses” Lefebvre et al (of the Infection Control Unit of the Dijon University Hospital, Dijon, France) investigated the proportion of transfer letters that contained information of infection or colonization with MDR bacteria.

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What works to control antibiotic-resistant bacteria in the ICU? A two-for-the-price-of-one study

Not content with a single well-planned study to provide information on what works to control multidrug-resistant organisms (MDROs) in the ICU, the MOSAR study group published an interrupted time series and a cluster randomized trial of various interventions in the Lancet ID. This makes the study rather complex to read and follow, but there are a number of important findings.

Interrupted time series – ‘hygiene’ intervention (chlorhexidine and hand hygiene)

Following a 6-month pre-intervention period, a 6-month interrupted time series of a ‘hygiene’ intervention (universal chlorhexidine bathing combined with hand-hygiene improvement) was performed. The key outcomes were twofold: whether there was a change in trend during each phase, and whether there was a step-change between the phases. The hygiene intervention effected a trend change reduction in all MDROs combined and MRSA individually, but not in VRE or ESBLs (Table). However, there was no step-change compared with the baseline period.

Table: Summary of reduced acquisition of all MDROs combined, or MRSA, VRE and ESBLs individually.

Derde table

Cluster RCT – screening and isolation

In the 12-month cluster RCT of screening and isolation, the 13 ICUs in 8 European countries were randomized to either rapid screening (PCR for MRSA and VRE plus chromogenic media for ESBL-Enterobacteriaceae) or conventional screening (chromogenic media for MRSA and VRE only). When analysed together, the introduction of rapid or conventional screening was not associated with a trend or step-change reduction in the acquisition of MDROs (Table).  In fact, there was an increase in the trend of MRSA acquisition. When comparing rapid with conventional screening, rapid screening was associated with a step-change increase in all MDROs and ESBLs.

Discussion

  • The study suggests, prima facie, not to bother with screening and isolation. Indeed, the authors conclude: “In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathing, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing”. However, the major limitation here is that many of the ICUs were already doing screening and isolation during the baseline and hygiene intervention phases! I checked the manuscript carefully (including the supplemental material) to determine exactly how many units were, but it is not disclosed. To make this conclusion, surely the cluster RCT should have been ‘no screening and isolation’ vs. ‘screening and isolation’.
  • The increasing trend of MRSA associated with screening and isolation by either method, and step-change increases in all MDROs and ESBLs associated with rapid screening are difficult to interpret. Is an increase in acquisition due to screening and isolation plausible? Can more rapid detection of carriers really increase transmission (the turnaround time was 24 hours for rapid screening, and 48 hours for chromogenic screening)? The rapid screening arm also included chromogenic screening for ESBLs, whereas the conventional screening arm did not, so perhaps this apparent increase in acquisition is due to improved case ascertainment somehow?
  • Looking at the supplemental material, a single hospital seemed to contribute the majority of MRSA, with an increasing trend in the baseline period, and a sharp decrease during the hygiene intervention. There’s a suspicion, therefore, that an outbreak in a single ICU influenced the whole study in terms of MRSA. Similarly, a single hospital had a sharp increase in the ESBL rate throughout the screening intervention period, which may explain, to a degree, the increasing trend of ESBL in the rapid screening arm.
  • There was an evaluation of length of stay throughout the study phases, with a significant decrease during the hygiene intervention (26%), a significant increase during the rapid screening intervention, and no significant change during the conventional screening intervention. It seems likely that improved sensitivity of rapid screening identified more colonized patients who are more difficult to step down, resulting in an overall increase in length of stay.
  • The carriage of qacA and qacB was compared in the baseline and hygiene intervention phase, finding no difference in carriage rate (around 10% for both). This does not match our experience in London, where carriage rates of qacA increased when we introduced universal chlorhexidine bathing. However, this was restricted to a single clone; the acquisition of genes associated with reduced susceptibility to chlorhexidine seems to be clone-specific.
  • ICUs varied from open plan to 100% single rooms. Whilst the average proportion of patients in single rooms (15-22%) exceeded the average requirement of patients requiring isolation (around 10%), there was no measure of unit-level variation of single room usage. Since the study was analysed by cluster, the lack of single rooms on some units could have been more important than would appear from looking at the overall average. Put another way, a 100% open plan unit would have been forced to isolate all carriers on the open bay, and vice versa for a 100% single room unit.
  • The impact of the various interventions was moderate, even though a ‘high’ MRDO rate was necessary for enrollment (MRSA bacteraemia rate >10%, VRE bacteraemia rate >5%, or ESBL bacteraemia rate >10%). Would the impact of screening and isolation be different on a unit with a lower rate of MDROs? It’s difficult to tell.
  • Some of the microbiology is quite interesting: 8% of MRSA were not MRSA and 49% of VRE were not VRE! Also, 29% of the ESBLs were resistant to carbapenems (although it’s not clear how many of these were carbapenemase producers).

In summary, this is an excellent and ambitious study. The lack of impact on ESBL transmission in particular is disappointing, and may lead towards more frequent endogenous transmission for this group. The results do indicate screening and isolation did little to control MDRO transmission in units with improved hand hygiene combined with universal chlorhexidine. However, we need a ‘no screening and isolation’ vs. ‘screening and isolation’ cluster RCT before we ditch screening and isolation.

Article citation: Derde LP, Cooper BS, Goossens H et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31-39.

ICHE special edition on CRE and MDROs

CRE medium

Infection Control and Hospital Epidemiology have once again excelled themselves in putting together a fine special edition on CRE and MDROs. Around this time last year I posted an article on the ICHE special edition on the role of the environment, and this special edition is equally important. I strongly recommend that you read the special edition from cover to cover, but I’ve picked out a few of my personal highlights below:

  • A thoughtful editorial by Drs Lautenbach and Perencevich sets the scene. They reflect on our ‘woeful unpreparedness’ to address both current and future MDROs.
  • A number of articles provide updates on surveillance and prevalence. Brennan et al. report findings from a 6-month CRE point-prevalence survey based on voluntary reporting in the state of Michigan, finding a crude rate of 1.07 cases per 10,000 patient days. Interestingly, this rate was almost 3 cases per 10,000 patient days in long-term acute care facilities. Isolates were not collected and analyzed, so carbapenemase genes were not confirmed; the fact that close to 10% of isolates were susceptible to meropenem suggests that a good number of the CRE were not carbapenemase producers. Indeed, another state-level point-prevalence survey (Pfeiffer et al., from Oregon) found that only 3 of the 60 CRE isolates reported were carbapenemase producers. Another state-level survey of CRE (Johnson et al., from Michigan) identified regional clustering of CRE colonization of mechanically ventilated patients in the central region of the state.
  • Analysis through the SHEA Research Network found that contact isolation policies for multidrug-resistant Gram-negative rods (MDR-GNR) are surprisingly variable. Worryingly, almost 20% of facilities surveyed did not isolate patients infected or colonized with MDR Pseudomonas or Acinetobacter, and 6% do not isolate patients with CRE. Policies for de-escalation of contact precautions were equally variable. Contact isolation policies seem to be even more lax in long-term care facilities based on data from Pfeiffer et al., reporting that only half of patients colonized with MDROs are placed on contact precautions.
  • A number of studies evaluated risk factors for CRE. For example, Bhargava et al. identified high acute morbidity score, immunosuppression, presence of indwelling medical devices and prior antimicrobial exposures to be consistent risk factors for CRE in the various patient populations they evaluated.
  • A survey of the kitchen in a Swiss hospital identified ESBL-producing Enterobacteriaceae in 92% of raw chicken and 6% of rectal samples from food handlers.
  • The efficacy of chlorhexidine bathing for MDR-GNR has been questioned, so data from Lin et al. on this issue are particularly welcomed. In a study of 62 patients in a long-term acute care facility, daily chlorhexidine gluconate (CHG) bathing halved the chances of culturing CRE from the body sites analyzed. However, it’s worth noting that the measured CHG skin concentration (15-312 mg/L before the daily bath and 78-1250 mg/L after the daily bath) was much lower than the applied CHG concentration (10,000 mg/L). This potentially brings the subtly reduced susceptibility to CHG reported in MRSA into play.
  • Several studies evaluated the potential for environmental contamination with MDR-GNR. Rosa et al. found that exposure to surfaces contaminated with MDR A. baumannii increased the risk of acquisition by almost 3-fold. Although the design of the study was fundamentally different, it is interesting to note that the increased risk from admission to a room previously occupied by a patient with MDR A. baumannii was also around 3-fold in a previous study. Havill et al. reported that the survival time for CRE (including K. pneumoniae) on dry surfaces is measured in weeks not days. Rock et al. carefully observed 220 unique interactions between healthcare workers (HCW) and patients with KPC or non-KPC producing K. pneumoniae, finding that HCW gloves or gowns became contaminated during 14% of the 220 interactions, and 26% of 43 environmental samples were positive. There was no significant difference between HCW or environmental contamination rates for KPC vs. non-KPC producing K. pneumoniae.
  • There was not much on therapy for CRE – perhaps because there is little to say for pan-drug resistant CRE! An article discussing the challenges of managing CRE infections by Drekonja et al. through surveying the CDC funded Emerging Infections Network highlighted the common problems due to toxicity from using “last-line” antimicrobials colistin and tigecycline.

It seems that the prevalence of CRE is patchy in the USA at present, and that long-term care, and long-term acute facilities are an integral part of the story. Given the limited evidence base, interventions need to cover all bases: active surveillance, rapid and accurate diagnostics, environmental (and perhaps food) hygiene, contact isolation and perhaps antiseptic decolonization, all combined with facility-wide education and communication initiatives. The most effective – and cost-effective – interventions to prevent and control the spread of CRE and other MDR-GNR are controversial so to this end I am looking forward to the SHEA ‘From MRSA to CRE: Controversies in MDROs’ and joint HIS / IPS ‘What’s that coming over the hill: rising to the challenge of resistant Gram-negative rods’ Spring meetings next month!

Photo credit: Enterobacter cloacae NDM-1 growing on Oxoid Brilliance CRE Agar by Nathan Reading.

Mitigating the increased risk from the prior room occupant through HPV room disinfection

The role of surface contamination is increasingly recognised in the transmission of certain nosocomial pathogens1. The most compelling evidence comes from the finding that admission to a room previously occupied by a patient infected or colonised with some multidrug-resistant organisms (MDROs) increases the risk of acquiring that MDRO for the subsequent room occupant by a factor of two or more1-3. Conventional cleaning and disinfection does not reliably remove all environmental MDROs4,5. Hence, it seems that inadequate terminal disinfection of hospital rooms explains the association with the increased risk of acquisition from the prior room occupant. It follows, then, that improvements in terminal disinfection should reduce the levels of residual contamination and the transmission of pathogens through this route. A recent study from Johns Hopkins Hospital tested this hypothesis through the introduction of hydrogen peroxide vapour (HPV) terminal disinfection of selected patient rooms6.

A 30-month prospective cohort intervention study was performed on 6 high-risk units (5 ICUs). HPV was implemented on 3 of the units following a 12-month pre-intervention phase. Clinical impact was assessed by a cohort study. Each patient admitted to any study unit during both phases was included in one of three cohorts:

  • ‘MDRO-standard’ Patients admitted to a room where the prior room occupant had an MDRO and the room was disinfected using standard methods.
  • ‘MDRO-HPV’Patients admitted to a room where the prior room occupant had an MDRO and the room was decontaminated using HPV
  • ‘No MDRO-standard’ Patients admitted to a room where the prior room occupant was not known to have an MDRO and the room was disinfected using standard methods.

The key finding was that patients admitted to rooms decontaminated using HPV were 64% less likely to acquire any MDRO (incidence rate ratio [IRR] of the MDRO-HPV vs. MDRO-standard cohorts = 0.36, confidence interval CI=0.19-0.70, p<0.001) (see chart below).


Chart showing the MRDO acquisition rate in the three patient cohorts.

MRDO acquisition rates

‘MDRO-standard’ = Patients admitted to a room where the prior room occupant had an MDRO and the room was disinfected using standard methods. ‘MDRO-HPV’ = Patients admitted to a room where the prior room occupant had an MDRO and the room was decontaminated using HPV.

‘No MDRO-standard’ = Patients admitted to a room where the prior room occupant was not known to have an MDRO and the room was disinfected using standard methods.


The difference between cohorts was adjusted for patient level variables such as length of stay, morbidities and other variables that could explain the difference. This means that the difference between cohorts is attributable to HPV alone. When broken down into individual MDROs, the largest reduction was shown for VRE (a 75% reduction, p<0.0001). HPV provided a protective effect for the other MDROs assessed (C. difficile, MRSA and MDR-Gram-negative rods), but differences for these individual pathogens were not statistically significant.

Surprisingly, even when the prior room occupant was not known to have an MDRO, HPV reduced the risk of acquisition by 51% (comparing the MDRO-HPV with the No MDRO-standard cohort). You’d expect the acquisition rate in the ‘MDRO-HPV’ cohort to match the ‘No MDRO-standard cohort’. In fact, it is lower. This is likely due to survival of contamination from previous occupants, unrecognised colonisation or introduction by healthcare workers.

Environmental impact was assessed by sampling each patient room on all units monthly for the last 3 months of the pre-intervention phase and the first 6 months of the intervention phase. Swabs were collected from all patient rooms, occupied or unoccupied, regardless of patient status. The overall percentage of rooms contaminated with one or more MDRO was reduced significantly when HPV was in operation. Further, rooms contaminated with multiple MDROs, occasions when the MDRO from room differed from the room occupant’s known MDRO and MDROs cultured from empty rooms were less likely when HPV was in operation.These changes are due to improved terminal disinfection using HPV.

Whilst this study is one of the few to evaluate patient outcomes in addition to environmental impact of a no-touch automated room disinfection system7. it does have several limitations, some of which are highlight in an accompanying editorial8. Firstly, the rooms or units were not randomized to an intervention arm, which could have introduced bias. Secondly, whilst the conventional disinfection methods were optimized prior to the introduction of HPV, more could have been done to improve the efficacy of conventional methods which may have over-estimated the impact of HPV. Thirdly, the low prevalence of acquisition (especially for MDROs besides VRE) made detecting changes in incidence difficult. Fourthly, whilst the infection rates in the three cohorts did not change significantly with study phase and the clinical impact on an individual patient level was impressive, overall unit level changes in rates of infection were not reported.

The study has important implications for the proportion of transmission that is likely to involve contaminated surfaces. Extrapolating unadjusted data from the study indicates that 16.7% of the acquisitions that occurred during the study were attributable directly to the prior room occupant. This figure most likely underestimates the total contribution of contaminated surface to nosocomial transmission because contaminated surfaces are likely to be involved indirectly in transmission during the stay of affected patients1.

In summary, HPV disinfection significantly reduced the risk of patients acquiring MDROs from previous room occupants in high-risk settings. Furthermore, HPV also provides a protective effect even when the prior room occupant was not known to be infected or colonised with an MDRO. These clinical findings are supported by environmental data showing that HPV disinfection improves the efficacy of terminal disinfection, thus reducing environmental contamination. Whilst the study is not without its limitations, it takes the question of how to tackle hospital environmental contamination forward a pace or two.

Article citation: Passaretti CL, Otter JA, Reich NG et al. An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms. Clin Infect Dis 2013; 56: 27-35.

References:

1.  Otter JA, Yezli S, French GL. The role played by contaminated surfaces in the transmission of nosocomial pathogens. Infect Control Hosp Epidemiol 2011; 32: 687-699.

2.  Drees M, Snydman D, Schmid Cet al. Prior environmental contamination increases the risk of acquisition of vancomycin-resistant enterococci. Clin Infect Dis 2008; 46: 678-685.

3.  Huang SS, Datta R, Platt R. Risk of acquiring antibiotic-resistant bacteria from prior room occupants.Arch Intern Med 2006; 166: 1945-1951.

4.  Manian FA, Griesenauer S, Senkel Det al. Isolation of Acinetobacter baumannii complex and methicillin-resistant Staphylococcus aureus from hospital rooms following terminal cleaning and disinfection: can we do better? Infect Control Hosp Epidemiol 2011; 32: 667-672.

5.  French GL, Otter JA, Shannon KP, Adams NM, Watling D, Parks MJ. Tackling contamination of the hospital environment by methicillin-resistant Staphylococcus aureus (MRSA): a comparison between conventional terminal cleaning and hydrogen peroxide vapour decontamination. J Hosp Infect 2004; 57: 31-37.

6.  Passaretti CL, Otter JA, Reich NGet al. An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms. Clin Infect Dis2013; 56: 27-35.

7.  Otter JA, Yezli S, Perl TM, Barbut F, French GL. Is there a role for “no-touch” automated room disinfection systems in infection prevention and control? Submitted. J Hosp Infect 2013; 83: 1-13.

8.  McDonald LC, Arduino M. Climbing the evidentiary hierarchy for environmental infection control. Clin Infect Dis 2013; 56: 36-9.