(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

Targeted interventions based on risk analysis or outbreak setting

Aseptic practices (other) Active screening- universal or targeted

Environmental cleaning and disinfection Isolation under transmission-based contact precautions

Sterilisation & disinfection of reused equipment

Selective decolonisation (MRSA) or bacterial load reduction

Immunisation Selective augmented cleaning and disinfection

Antimicrobial stewardship

Structural elements- hospital design- proportion single to multiple rooms, toilet provision, ventilation controls

(Universal application skin and/or mucosal disinfection)

Surveillance and analysis of risk across healthcare system

Surveillance – pathogen or unit (patient) or procedure targeted

Horizontal strategies Vertical strategies

Standard precautions including hand hygiene

Targeted interventions based on risk analysis or outbreak setting

Aseptic practices (other) Active screening- universal or targeted

Environmental cleaning and disinfection Isolation under transmission-based contact precautions

Sterilisation & disinfection of reused equipment

Selective decolonisation (MRSA) or bacterial load reduction

Immunisation Selective augmented cleaning and disinfection

Antimicrobial stewardship

Structural elements- hospital design- proportion single to multiple rooms, toilet provision, ventilation controls

(Universal application skin and/or mucosal disinfection)

Surveillance and analysis of risk across healthcare system

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/1133810/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? Minimum standard Optimal

MRSA/ MSSA preoperative

Nose

+ wounds

MRSA detection/ clearance

Nose, throat, perianal, wounds, IDC urine

VRE Rectal (perianal) or faeces

+ Urine

MRGN

Rectal (perianal) or faeces

+ Urine + Inguinal + throat (Acinetobacter)

http://hicsigwiki.asid.net.au/index.php?title=Screening_and_Clearance_Process-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 cost-

effective • 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…