(DRAFT) RECOMMENDATIONS FOR THE CONTROL OF MULTI-DRUG RESISTANT GRAM-NEGATIVES: CARBAPENEM RESISTANT ENTEROBACTERIACEAE

(DRAFT) RECOMMENDATIONS FOR THE CONTROL OF MULTI-DRUG RESISTANT GRAM-NEGATIVES: CARBAPENEM RESISTANT ENTEROBACTERIACEAE John Ferguson (Hunter New England, NSW) on behalf of MRGN Task Force

Acknowledgement

Situation analysis Worldwide emergence of highly pathogenic CRE with high mortality Evidence of high transmissibility of some strains in healthcare and potentially in residential aged care Australian travellers, those exposed to healthcare or residential care overseas, including medical tourists at risk Local detection of most CRE determinants and ESBL in travellers Increasing sporadic cases and several recorded outbreaks/clusters of CRE (IMP-4, OXA48 )

CRE Guideline purposes 1. To alert healthcare professionals and the community to the emerging threat by CRE in Australia; 2. To provide recommendations in preventing, detecting and containing CRE; and 3. To provide informational resources for healthcare professionals and consumers.

Methods Sources Literature review Jurisdictional guidelines and factsheets WA CRE Policy Directive 2012 International guidelines and recommendations APIC/CDC Best practice statement CDC CRE Guidelines 2012 Israeli experience Process Teleconferences, multiple drafts. Grading of evidence for recommendations not determined

Horizontal strategies Vertical strategies Standard precautions including hand hygiene Aseptic practices (other) Targeted interventions based on risk analysis or outbreak setting Active screening- universal or targeted Environmental cleaning and disinfection Isolation under transmission-based contact precautions Sterilisation & disinfection of reused equipment Immunisation Antimicrobial stewardship Structural elements- hospital designproportion single to multiple rooms, toilet provision, ventilation controls (Universal application skin and/or mucosal disinfection) Surveillance and analysis of risk across healthcare system Selective decolonisation (MRSA) or bacterial load reduction Selective augmented cleaning and disinfection Surveillance pathogen or unit (patient) or procedure targeted

Horizontal strategies Vertical strategies Standard precautions including hand hygiene Aseptic practices (other) Targeted interventions based on risk analysis or outbreak setting Active screening- universal or targeted Environmental cleaning and disinfection Isolation under transmission-based contact precautions Sterilisation & disinfection of reused equipment Immunisation Antimicrobial stewardship Structural elements- hospital designproportion single to multiple rooms, toilet provision, ventilation controls (Universal application skin and/or mucosal disinfection) Surveillance and analysis of risk across healthcare system Selective decolonisation (MRSA) or bacterial load reduction Selective augmented cleaning and disinfection Surveillance pathogen or unit (patient) or procedure targeted

OVERVIEW Section 1: Reducing community and individual risk from CRE Section 2: Detection and surveillance for CRE Section 3: Additional control measures Section 4: Laboratory screening methods

1. Standard infection control precautions 2. Antimicrobial stewardship Hospitals Community (Animal practice and agricultural production not included) 3. Information resources

NHMRC 2010 Infection Prevention and Control Guidelines

The model predicts that: (i) without strict screening and decolonization of colonized individuals at admission, MRSA may persist; (ii) decolonization of colonized residents, improving hand hygiene in both residents and HCWs, reducing the duration of contamination of HCWs, and decreasing the resident:staff ratio are possible control strategies; (v) An introduction of a colonized individual into an MRSA-free nursing home has a much higher probability of leading to a major outbreak taking off than an introduction of a contaminated HCW.

http://www.theecologist.org/news/news_analysis/11338 10/common_infections_will_be_untreatable_if_antibiotic _misuse_continues.html

Antibiotic usage situation: Australia Community care- high overall usage rates relative to many European nations Residential aged care high levels of unnecessary & inappropriate usage Agricultural and veterinary use high though little data Hospitals: Large variation in total use High proportion is inappropriate in hospital point prevalence surveys Wide variation in broad spectrum Gram negative agent usage across tertiary facilities (NAUSP)

NAUSP data (37 hospitals): average use remains constant; marked changes with some classes

More than 3-fold difference in usage across these hospitals

Almost 6-fold difference in usage across these hospitals

Scottish 4 C s program Quinolones have fallen to 60/1,000 bed-days TGC have fallen to below 10/1,000 bed-days

Experience in Perth: effect of reducing cephalosporin use on C. difficile incidence. Reference: : Dr Claudia Thomas, PhD thesis 2003 Commun Dis Intell. 2003;27 Suppl:S28-31

a significant decrease in the proportion of patients prescribed carbapenems from 21.4 to 16.9 defined daily doses (DDDs)/100 bed days (39% reduction; P,0.04), third-generation cephalosporins from 35.4 to 26.6 DDDs/100 bed days (42% reduction; P,0.001) and vancomycin (33% reduction; P¼0.05) between two 6 month evaluation periods in 2001 and 2002. Gentamicin use was unchanged.

2 high acuity Australian intensive care units PLOS one June 2012 Volume 7 Issue 6 e38719

AMS and Gram negative resistance: unresolved questions Are the wide variations in Australian hospital antibiotic usage significantly associated with resistance levels? What are the differential ecological effects of different Gram negative agent classes on colonisation and infection? What usage thresholds if any exist for these effects and how does this differ in different resistance or care situations? Do multi-resistant Gram negative infections add to the existing infectious burden?

S&Q Standard 3.14 a great opportunity

And even greater resource/ opportunity Do we (ID folk) follow them, reference them and promote their validity? Are they restrictive enough?? Should quinolones and TGC be restricted further? Is there an increased role for cotrimoxazole and tetracyclines

Carriage & clearance Duration of carriage uncertain returned travellers, > 50% carrying resistant E. coli post-travel had no detectable resistant strains two months after return; 18% remained colonised at six months Some organism clones better adapted to prolonged carriage than others; antimicrobial use also associated with prolonged duration of carriage. No accepted criteria for clearance yet No decolonisation approaches of proven worth Rogers, B.A., Kennedy, K.J., Sidjabat, H.E., et al. Prolonged carriage of resistant E. coli by returned travellers: clonality, risk factors and bacterial characteristics. Eur J Clin Microbiol Infect Dis. Sep;31(9):2413-20. 2012 Kennedy, K., Collignon, P. Colonisation with Escherichia coli resistant to "critically important" antibiotics: a high risk for international travellers. European Journal of Clinical Microbiology and Infectious Diseases.2010;29(12):1501-6.

Screening: what samples? MRSA/ MSSA preoperative MRSA detection/ clearance VRE Minimum standard Nose Nose, throat, perianal, wounds, IDC urine Rectal (perianal) or faeces Optimal + wounds + Urine MRGN Rectal (perianal) or faeces + Urine + Inguinal + throat (Acinetobacter) http://hicsigwiki.asid.net.au/index.php?title=screening_and_clearance_proce ss-mrsa Widmer ICHE 2012 ESBL sites of carriage isolated urine positivity in 24%. Thurlow ICHE 2013- isolated inguinal positivity for KPC in 12%.

Other issues with screening Duration of carriage; can clearance ever be assured? Timing and frequency of screening False negative results may occur early after acquisition, in the presence of certain antimicrobial agents and when the organism is present in low numbers. Multiple screens performed over a period of time are likely to improve screening sensitivity, however no consensus recommendations can be made regarding the optimal timing and frequency of screening due to insufficient data. Suggested target groups for enhanced screening: Patients being admitted to haematology, ICU, burns and transplant units Patients with recent (previous 3 months) broad spectrum antibiotic therapy exposure (carbapenem, quinolones, or 3rd and 4th generation cephalosporins) Patients who have required a long duration of hospital stay (eg. > 1 month) due to severe illness Knowledge of endemicity at other hospital locations

Clinical Infectious Diseases 2012;55(11):1505 11

RESULTS Active screening for ESBL carriage could be performed in 133 consecutive contact patients. Transmission confirmed by PFGE occurred in 2 (1.5%) of 133 contact patients, after a mean exposure to the index HOWEVER. Patients screened early after exposure Very good level of standard precautions in place in this hospital ESBL community carriage and transmission predominates Clinical Infectious Diseases 2012;55(11):1505 11

RESULTS Two index cases carrying NDM1-Kp with different PFGE patterns were identified. Nosocomial transmission to 7 patients (4 roommates, 2 ward mates, and 1 environmental contact) was subsequently identified. Risk factors for acquisition of NDM1-Kp were a history of prior receipt of certain antibiotics (fluoroquinolones [odds ratio (OR), 16.8 (95% confidence interval [CI], 1.30 58.8); Pp.005], trimethoprim-sulfamethoxazole [OR, 11.3 (95% CI, 1.84 70.0); Pp.01], and carbapenems [OR, 16.8 (95% CI, 1.79 157.3); Pp.04]) and duration of exposure to NDM1-Kp-positive roommates (26.5 vs 6.7 days; P!.001).

ESBL situation Increasing community carriage; ie. reservoir large, unidentifiable without extensive screening In hospital transmission potential low with E. coli if good IC program in place Standard vs Contact precautions no studies Additional benefit of vertical effort not likely to be costeffective Antimicrobial stewardship ++ Need to watch for single strain infection outbreaks however

Cf. CRE (KPC) case identified in patient transferred from overseas to Australian hospital Low/rare community carriage in Australia Documented cross-transmission potential High morbidity Domestic reservoir small, risk factors for carriage identifiable making targeted screening feasible Vertical effort likely to be cost-effective Horizontal measures still very important,

Environment

Evidence for environmental contamination contributing to GNR spread Prospective French ICU cohort study showed that prior room occupancy by a patient colonized or infected with A. baumannii or P. aeruginosa was a significant risk factor for the acquisition of these pathogens (OR 4.2 and 2.3 respectively) Numerous outbreaks of A. baumannii associated with contaminated inanimate fomites, which resolve once the common source is identified and removed, replaced, or adequately disinfected Several outbreaks in which environmental surfaces were contaminated with clinical strain(s) but a common source was not identified Otter et al Infect Control Hosp Epidemiol 2011;32(7)

CarbaNP test (acknowledgement J Bell) Nordmann P., Poirel L, Dortet L. 2012. Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 18:1503-1507. Dortet L, Poirel L, Nordmann P. Rapid Identification of Carbapenemase Types in Enterobacteriaceae and Pseudomonas spp. by using a Biochemical Test. AAC 56:6437-6440.

National surveillance of AMR Yet another extensive scoping study completed 2013 (14 years post JETACAR ) Significant budgetary provision made in 2013 federal budget 3 years One Health approach strong support: recent Colloquium Passive and active surveillance systems envisaged across all sectors (human and animals) Usage Resistance Analysis

CRE Guidelines - from here Jurisdictional signoff completed (ACSQHC) DOHA review and final approval Distribution Implementation