16/09/2019

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Evolution of MDROs

Dr Deirdre O’BrienConsultant Microbiologist

Mercy University Hospital and South Infirmary Victoria University Hospital

@SafePatientCar1

# bugsndrugs

Talk outline

•What is a multidrug resistant organism (MDRO)?

•How do bacteria become resistant to antibiotics?

• Focus on resistance in Gram negative bacteria (ESBLs and CPE)

•What can be done?

Causes of death in Ireland 1926 - 2006

Data source: Society of Actuaries in Ireland 2011

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2

Antimicrobial Resistance

Antibiotic Options

MDROs and Antimicrobial Resistance: Key Facts 1-4

1. Antimicrobial resistance (AMR) threatens the effective prevention and treatment infections

2. Without effective antibiotics, the success of major surgery and cancer chemotherapy will be compromised

3. The cost of health care for patients with resistant infections is higher than care for patients with non-resistant infections due to longer duration of illness, additional tests and use of more expensive drugs

4. AMR is an increasingly serious threat to global public health that requires action across all government sectors and society

Multi-drug resistant bacteria (MDRO)

• MRSA

• VRE (Vancomycin Resistant Enterococci)

• Streptococcus pneumoniae

• Neisseria gonorrhoeae

• TB

• ESBL (Extended spectrum beta lactamaseproducing Gram negative bacteria)

• CPE (Carbapenemase producing Enterobacterales)

How do bacteria become resistant to antibiotics?

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Intrinsic v Acquired Resistance

Intrinsic resistance

”Born this way”

Acquired Resistance

when a microorganism obtains the ability to resist the activity of a particular antimicrobial agent to which it was previously susceptible

Can arise as a result of:

Genetic mutation

Acquisition of foreign resistance genes

Combination of these two mechanisms.

Acquired resistance can be passed from one bacterium to another

Key Fact 5

5. While antimicrobial use exerts ecological pressure on bacteria and contributes to the emergence and selection of AMR, poor infection prevention and control practices favour the further spread of these bacteria

Evolution of Resistance in Staphylococcus aureus

C. difficile and Antibiotics

•Hypervirulentstrain emerged in 2000s

•More resistant to fluoroquinolones(e.g. ciprofloxacin)

•More virulent, higher mortality rates

• Increased toxin A and B production

• Increased sporulation

ESBLs and CPE

Enterobacteriaceae- now known as Enterobacterales

• Enterobactererales : E coli, Klebsiella spp, Enterobacterspp.

• Normal gut flora

• Common cause UTI in community

• Hospital acquired infections: UTI, pneumonia, intra-abdominal infections, wound infections, bloodstream infections

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Resistance mechanisms associated with Enterobacterales spp.

• ESBL (Extended Spectrum Beta Lactamase)

• MDRKP (Multi-Drug Resistant Klebsiellapneumoniae)

• CPE (Carbapenemase Producing Enterobacterales)

• CRE (Carbapenem Resistant Enterobacterales)

Different carbapenemases…

• KPC

• OXA-48

• VIM

• NDM

• IMP

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Trends in K. pneumoniae and E. coli invasive infections with percentage 3GC-resistance and ESBL-positivity

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ESBL E.coli at highest level to date

Spread of CPE in Europe 2009-2016

Ireland and CPE

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Irish Hospitals with CPE Outbreaks Where do ESBLs and CPE

come from?

• Frequently plasmid encoded

• Plasmid= small DNA fragment that is capable of self replication and can be passed from one bacteria to another

• Plasmids containing enzymes for ESBL frequently carry genes encoding resistance to other antibiotics eg. aminoglycosides, quinolones

• May live harmlessly in gut but can cause infection when enter urinary tract, bloodstream etc.

Who is at risk of infections caused by ESBL and CPE producing bacteria?

•Gut colonization

•Length of ICU stay

•Presence of central venous or arterial catheters

•Emergency abdominal surgery

•Presence of a gastrostomy or jejunostomy tube

•Low birth weight

•Prior administration of any antibiotic

•Prior residence in a long-term care facility (eg. nursing home)

•Severity of illness

•Presence of a urinary catheter

•Ventilatoryassistance

•Undergoing haemodialysis

What kind of infections do ESBLs and CPE cause?

• Same range of infections as “regular” E.coli, Klebsiella spp. Proteus spp.

• Urinary tract infections

• Intra-abdominal infections

• Healthcare associated pneumonia

• Catheter related bloodstream infections

• Skin/ soft tissue (more unusual, these organisms tend to colonize rather than infect skin)

DO NOT TREAT ASYMPTOMATIC BACTERIURIA*

*This recommendation is for over 16 non-pregnant adults

• Increased risk of treatment failures• 50-70% ICU mortality with carbapenem-

resistant Klebsiella pneumoniae bloodstream infections vs. 41% for susceptible K. pneumoniae BSI

• 9.9-fold increase in 30 day mortality for carbapenem-resistant Pseudomonas aeruginosabloodstream infection

• Threatens the ongoing delivery of many areas of modern medical practice• e.g. organ transplantation, immunosuppressive

therapies, cancer chemotherapy, intensive care

DO NOT TREAT ASYMPTOMATIC BACTERIURIA

OXA-48 CPE from a patient in an Irish hospital

• Susceptible to:• ceftazidime-avibactam• gentamicin• chloramphenicol• colistin

• Resistant to:• ertapenem/meropenem/imipenem• ciprofloxacin• tigecycline• fosfomycin• cotrimoxazole• tobramycin• cefotaxime, ceftriaxone, ceftazidime• intermediate to amikacin

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Real life case….

•81 year old female

• Fell on holidays in Portugal, broke hip, IM nail

• Transferred back to Cork for rehabilitation

• This isolate in her urine on admission…..

Can patients be cleared of ESBL or CPE carriage?

• Probably not

• No decolonisation regimen

• Likely that patients will carry the ESBL producing organism for some time

• Persists in gut (will become part of normal flora)

• Sometimes strain lost naturally

• Use of antibiotics will not help

How are ESBLs, MDRKP and CPE transmitted?

•Most important mode of transmission via transient carriage on the hands of healthcare workers

•Environmental spread

•Antimicrobial use

What do I tell patients/relatives?

• Depends on whether colonized or infected-or they may be a CPE contact

• Explain that patient has an infection (correlate results with clinical findings) which is resistant to many commonly used antibiotics

• Spread can be prevented through correct hand hygiene procedures

Patient Impact

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Why do I need to worry about ESBLs- should I not focus on CPE?

• Absolutely not!!!

• More ESBLs = more need to use meropenem= more CPE

• Infection caused by ESBL= more likely to have increased mortality, longer hospital stays and greater hospital costs

•DO NOT TREAT ASYMPTOMATIC BACTERIURIA!!!!

What can be done about this?

• Nationwide spread of CRE in Israel 2006-failure to contain a local levels

• Acquisition rate of 55.5 cases per 100,000 patient days

• National intervention for CRE containment

Acquisition rate reduced to 4.8 cases per 100,000 patient days..

What worked?

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One health

• Farm animals account for 70% of global antibiotic use

• 80% of all antibiotics in the US given to farm animals

• Control and prevention of antimicrobial resistance (AMR) requires a holistic One Health approach

• Multi-disciplinary approach involving public health, human and veterinary medicine, livestock production, food safety, environmental sciences

Take home messages

•MDRO rates a major concern in Irish healthcare and globally

•Antimicrobial resistance a public health threat

•Stewardship and adherence to infection prevention and control practices our best (only) means to limit the spread