MDROs 101 Multidrug-Resistant Organisms By Dr. Sherif Ibrahim

Review epidemiology of MDROs Objectives Review epidemiology of MDROs Reservoir Mode of transmission Type of infection Role of environment Review specific MDROs Prevention strategies Contact Precautions Exercise

Multi-Drug Resistant Organisms (MDROs) Epidemiology Definition: microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents Importance: Limited options for treatment Increase the length of stay and cost of hospitalization Increase admission to and stay in ICU High mortality rates

MDROs - Epidemiology Transmission: Mainly person to person through hands of healthcare personnel (HCP) Contact with contaminated environmental surfaces Transmission depends on Availability of vulnerable patients Antimicrobial pressure Colonization pressure Adherence to infection control measures Frequent movement among healthcare facilities Colonization Pressure: It is defined as the proportion of patients colonized with a particular organism in a defined geographic area within a hospital/healthcare facility during a specified time period Antimicrobial Pressure: Increased antimicrobial use leads to selective pressure on normal flora resulting in emergence of MDROs

MDROs – Epidemiology Reservoirs Risk factors Infected and colonized patients Contaminated environmental surfaces & patient care equipment Risk factors Colonization, age > 65, ICU admission, long hospital stay, frequent hospitalizations, invasive procedures, indwelling devices, underlying diseases, enteral feeding, LTCFs, antimicrobial exposure

MDROs – Epidemiology Infected: a person who has culture-positive for an MDRO and displays signs or symptoms of infection Colonized: a person who has culture- positive for an MDRO but has no signs or symptoms of infection

Important MDROs ESCAPE Enterococcus faecium (VRE) Staphylococcus aureus (MRSA) Clostridium difficile (C. Diff) Acinetobacter baumannii Pseudomonas aeruginosa Enterobacteriaceae (CRKP/CRE)

Gram Positive MDROs Methicillin‐Resistant Staphylococcus aureus (MRSA) Vancomycin‐Resistant Enterococci (VRE)

MRSA – Epidemiology Staph aureus (SA) resistant to beta‐lactams. Nasal colonization  general population 25-30 % for SA < 2% for MRSA Other colonization sites: rectum, axilla, throat, wounds Higher carriage among HCP, dialysis patients, diabetics, IV drug users Reservoirs: ……. and……... Transmission…… and……… MRSA carriage varied substantially across 10 nursing homes. Overall point prevalence was 31% (range, 7%–52%) Versus 6% in hospitals and 9%–24% in intensive care units. Reservoirs: colonized and infected individuals (frequent contact with the healthcare system) Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services. Beta-Lactams: penicillins, cephalosporins, cephamycins, carbapenems, monobactams

MRSA – Epidemiology 49-65 % of HA-Staph infections NHSN 94,360 invasive MRSA infections annually/US 18,650 associated deaths 86% of all invasive MRSA are HAIs Staphylococcus aureus Intrinsic virulence Cause a wide range of life threatening infections Adapt to different environmental conditions Can survive in the environment 1-56 days Predominant pathogen in HAIs a survey of 463 hospitals in 2006-2007  565 of device-associated SA infections are MRSA MRSA can be carried in the nares for more than 1 year; in one study, subsequent MRSA infections occurred in 29% of patients within 18 months of a previous colonization or infection

Prevention and Control MRSA colonization generally precedes infection Risk of developing MRSA infection among colonized individuals is 29% in 18 months Rationale for prevention Prevent transmission from colonized to un-colonized individuals Prevent infection in colonized individuals MRSA-specific strategies (Decolonization) Non MRSA-specific strategies (reduce device- associated infections)

Vancomycin‐Resistant Enterococci (VRE) Epidemiology Aerobic Gram positive cocci that inhabitant of GI tract and female genital tract Endemic in most U.S. hospitals 25% all enterococcal isolates are VRE Resistance is commonly seen in isolates of E. faecium than E. faecalis Risk factors (Host, Healthcare facility, Antimicrobial exposure)

VRE Epidemiology Reservoirs: ….. and …….. Transmission: ……and …… Common sites of infection: urinary tract, surgical wound, blood stream Mortality rate is 2 times higher in VRE than VSE infections Survives on environment  days – weeks Reservoirs: colonized and infected individuals (frequent contact with the healthcare system) Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services. Resistance develops due to acquisition of van gene clusters on mobile genetic elements that are transferable between enterococcal strains Host Related Risk Factors: VRE colonization , Enterococcal stool density, Immunodeficiency, Transplant recipient, Clostridium difficile diarrhea , Renal insufficiency, Severity of underlying illness Healthcare facilities: ICU Admission, Proximity to a patient with VRE, Length of hospitalization, Multiple unit stays, Enteral feedings (Total perienteral nutrition) Medications: Number, type, and duration of antibiotic therapy, Vancomycin use, 3rd Generation Cephalosporin utilization, Anti-anaerobic antibiotics (such as Clindamycin), Flouroquinolones (such as Ciprofloxacin)

Gram Negative MDROs Glucose fermenter (Enterobacteriaceae) Foodborne (Salmonella, Shigella) Healthcare-associated Enterobacter species (E. cloacae) Community and Healthcare-associated Klebsiella species (K. pneumoniae) Escherichia coli Non–glucose fermenters Acinetobacter baumannii Pseudomonas aeruginosa

Enterobacteriaceae Epidemiology Normal human gut flora Environment (soil & water) Important cause of community and HA infections Wide range of infections (UTI, Bacteremia, pneumonia, wound infection) E. coli most common cause of outpatient UTIs E coli and Klebsiella accounted for 15% all HAIs reported to NHSN 2007 Risk of Enterobacteriaceae infections high among patients with a pathologic intra-abdominal condition /surgery. Urinary tract infection both catheterized and non catheterized patients because of the proximity of the urethral meatus to the anus. Recent Prolonged hospitalization, LTCF

Development of Antimicrobial-Resistant Enterobacteriaceae B lactamases  resistant to B-lactams for decades Extended spectrum B-lactamases (ESBL)  resistant to 3rd generation cephalosporins, monobactams Usually nosocomial however 34% from patients with no healthcare contact Carbapenems  the last line of defense for treatment

Development of Antimicrobial-Resistant Enterobacteriaceae Carbapenem-Resistant Enterobacteriaceae (CRE) Resistance  production of a carbapenemase also known as KP carbapenemase (KPC) Resides on transferable plasmids wide spread transmission Limits options for treatment (Polymyxins problems with nephrotoxicity) Reservoirs: ……..and ….. Transmission; …..and …… Resistance mainly occurs in KP, reported in other Enterobecteriacea, few reports in Pseudomonas Reservoirs: colonized and infected individuals (frequent contact with the healthcare system) Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services.

Geographical Distribution of KPC-Producers Sporadic isolate(s) 2001 Centers for Disease Control and Prevention. 18 18

Geographical Distribution of KPC-Producers Widespread Sporadic isolate(s) 2006 Centers for Disease Control and Prevention. 19 19

Geographical Distribution of KPC-Producers Sporadic and Widespread isolate(s) 2010 Centers for Disease Control and Prevention. 20 20

Susceptibility Profile of KPC-Producing KP Antimicrobial Interpretation Amikacin I Chloramphenicol R Amox/clav Ciprofloxacin Ampicillin Ertapenem Aztreonam Gentamicin Cefazolin Imipenem Cefpodoxime Meropenem Cefotaxime Pipercillin/Tazo Cetotetan Tobramycin Cefoxitin Trimeth/Sulfa Ceftazidime Polymyxin B MIC >4mg/ml Ceftriaxone Colistin Cefepime Tigecycline S

Mortality Associated with CRKP 48 20 38 12 OR 3.71 (1.97-7.01) OR 4.5 (2.16-9.35)

CRKP in Long-Term Care Facilities Few clinical cases  large reservoir of colonized patients in LTCFs. Colonization rate was as high as 49% in one outbreak Recipe for CRKP outbreaks: Infection control breaches (lack of compliance) Unrecognized colonized residents serving as reservoirs for transmission

MDR- Acinetobacter baumannii (Ab) Epidemiology Non-motile gram negative bacteria (32 species) Ubiquitous  widely distributed in nature (soil, water, food, sewage) & the hospital environment MDR-Ab is primarily a nosocomial pathogen Long survival time on inanimate surfaces extensive environmental contamination Transmission …. and…… Reservoirs: …… and ….. Reservoirs: colonized and infected individuals (frequent contact with the healthcare system) Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services. In vitro survival time 329 days 11 days survival on Formica, 12 days on stainless steel Up to 4 months on dry surfaces (Wagenvoort JHT, Joosten EJAJ. J Hosp Infect 2002;52:226-229) (Webster C et al. Infect Control Hosp Epidemiol 2000;21:246) (Wendt C et al. J Clin Microbiol 1997;35:1394-1397) 32 species >2/3 of Acinetobacter infections are due to A. baumanii The bacteria colonize the pharynx intermittently in 7% of the general population and in addition can be isolated from sputum, urine, stool, and vaginal discharges MDR-AB carriage and natural history have not been well studied Skin colonization are 25 to 40% among healthy individuals and up to 75% for hospitalized patients

MDR- Ab Epidemiology Widespread environmental contamination Respiratory care equipment Bed rails, Bedside tables, Mattresses, Pillows Curtains, door handles Keyboards Floor mops, sinks Air humidifiers Patient care items Wound care procedures Equipment carts, Infusion pumps Patient monitors and X-ray board The bacteria colonize the pharynx intermittently in 7% of the general population and in addition can be isolated from sputum, urine, stool, and vaginal discharges MDR-AB carriage and natural history have not been well studied Skin colonization are 25 to 40% among healthy individuals and up to 75% for hospitalized patients Most common gram negative carried by skin of HCP Frequently colonizes tracheostomy site Chlorohexidine resistance

MDR- Ab Epidemiology MDR- Acinetobacter mainly causes HAIs Pneumonia (Ventilator-associated pneumonia) Urinary tract Bacteremia Meningitis Skin/wound infections MDR- Acinetobacter infections Acute care (ICUs) traditionally, associated with outbreaks LTAC & LTCFs Injured military personnel Outbreaks  mortality rates up to 75%

MDR- Pseudomonas aeruginosa Epidemiology Aerobic gram-negative rods Ubiquitous in soil and water Moist environment (hydrophilic) (e.g. sink drains, vegetables, river water, etc.) P. aeruginosa is an opportunistic infection  rarely colonize healthy individuals At Risk individuals: Immuno-compromised Burn patients Patients on mechanical ventilation Cystic fibrosis patients

P. aeruginosa Epidemiology 10% of all hospital-acquired infections Often cause severe life threatening HAIs Can be found everywhere Can be community acquired In healthcare facilities: respiratory equipment, food, sinks, taps, toilets, weak disinfectants, showers and mops, uncooked vegetables, flower water Transmission …..and ………. Reservoirs ……. and ………… Colonization precedes infection in 50% of cases Reservoirs: colonized and infected individuals (frequent contact with the healthcare system) Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services. colonization  moist areas axilla, ears, perineum

Prevention Strategies (MDROs) Core Measures Administrative support Surveillance Patient placement Patient/staff cohorting Hand hygiene Contact precautions Protocol for lab notification Dedicated equipment Device use Environmental measures Monitor compliance Education Antimicrobial stewardship Supplemental Measures Preemptive isolation Active surveillance culture Chlorohexidine bathing

C. difficile : Epidemiology Gram positive spore forming bacillus (rods) Obligate anaerobe Part of the GI Flora in 1-3% of healthy adult 70% of children < 12 months Some strains produce toxins A & B Toxins-producing strains cause C. diff Infection (CDI) CDI ranges from mild, moderate, to severe and even fatal illness G positive means (Dark blue when use gram stain Obligate anaerobes does not require O2 to survive Toxins are required to cause disease. A is the major toxins B can also cause the same illness as A CDI used to be called CDAD

C. difficile Epidemiology Transmission Fecal – oral route Contaminated hands of healthcare workers Contaminated environmental surfaces. Person to person in hospitals and LTCFs Reservoir: Human: colonized or infected persons Contaminated environment C. diff spores can survive for up 5 months on environmental surfaces. surfaces, devices commodes, bathing tubs, and electronic rectal thermometers) Source of infection can be endogenous or exogenous

C. difficile: Epidemiology A common cause of nosocomial antibiotic- associated diarrhea (AAD) Most common infectious cause of acute diarrheal illness in LTCFs The only nosocomial organism that is anaerobic and forms spores Infective dose is < 10 spores

Number of annual deaths CDI: Impact Number of annual cases Cost Number of annual deaths Hospital-onset, hospital acquired (HO-HA) 165,000 $ 1.3 B 9000 Nursing home-onset 263.000 $ 2.2 B 16,500

Clinical Manifestations Illness caused by toxin-producing strains of C. difficile ranges from Asymptomatic carriers = Colonized Mild or moderate diarrhea Pseudo membranous colitis that can be fatal A median time between exposure to onset of CDI symptoms is of 2–3 days Risk of developing CDI after exposure ranges between 5-10 days to 10 weeks

Rationale for Preventive strategies Colonized no symptoms Antimicrobial stewardship Antimicrobials C Diff exposure & acquisition Patients acquire C diff at the HCF 1- contact with a healthcare worker with transient hand colonization, 2 contact with the contaminated environment, or (3) by direct contact with a patient with CDI. The rate of acquisition during hospitalization increases linearly with time and can be as high as 40% after 4 weeks of hospitalization Optimizing Environmental cleaning and Hand Hygiene Admitted to healthcare facility Infected Symptomatic

Preventive Strategies: C. Diff Core Measures Surveillance Contact Precautions (CP) for duration of diarrhea Hand hygiene (HH) Dedicated equipment Cleaning and disinfection of equipment and environment Laboratory-based alert system for immediate notification Educate HCP, housekeeping, admin staff, patients, families, visitors, about CDI Monitor compliance Supplemental Measures Extend (CP) beyond duration of diarrhea (48 hours) Presumptive isolation for symptomatic patients Implement soap and water for HH before exiting room of a patient with CDI Implement universal glove use on units with high CDI rates Use sodium hypochlorite (bleach) - containing agents for environmental cleaning Implement an antimicrobial stewardship program

Contact Precautions (CP) Patient placement (factors to consider) Hand hygiene (HH) Gloves Don gloves upon room entry Change gloves after contact with infectious materials Change gloves when moving from contaminated to non contaminated site Remove gloves and HH before leaving the room or caring for another patient Gowns Don gown upon room entry Remove and discard gloves before removing gown Discarding gown before exiting the room After gown and gloves removal HH make sure not to touch any potentially contaminated environmental surface in the room Dedicated equipment (BP cuff, stethoscope, thermometer, etc.)

Contact Precautions in LTCFs Challenges of implementing CP in LTCFs Contact Precautions should be used for the following residents with MDROs Dependent on HCP in their activities of daily life Ventilator-dependent Incontinent of stool Wound with difficult to contain discharge Contact Precautions can be relaxed for all others residents with MDROs (consider resident’s mental status and personal hygiene) Standard precautions should be observed all times Dedicated equipment Signage for HCP and visitors

Conclusion MDROs represent a major clinical and infection control challenge particularly in LTCFs You cannot do it alone  Regional approach Aggressive infection control approach works Appropriate antimicrobial use Training and education (HCP, Patients, Families) Communications (intrafacility and interfacilities)

Exercise During morning rounds you were assigned rooms 103 and 107 for the day Room 103 Under contact precautions Has 2 patients Patient #1 was recently treated for CRKP UTI, has a Foley catheter and is stool incontinent Patient # 2 is CRKP colonized and has a deep bedsore in the right buttock Room # 107 Has two residents admitted for short term rehabilitation S/P total knee replacement. One of them is stool incontinent

Questions What type of precautions would you use upon entering Room 103 and why? How is this type of organism transmitted? What type of precautions will you be using for room 107 and why? Do you think it is a good practice to provide care for these two rooms in the same day? Please explain why and what is the best practice in this situation? Patient # 2 in room 103 is ambulatory and he wants to go to the activity room. What would you do? In the schedule, all four patients are due for bathing. Specify who would go first.

Questions

Resources and References SHEA/APIC Guideline: Infection Prevention and Control in the Long- Term Care Facility http://www.dhhr.wv.gov/oeps/disease/AtoZ/Documents/SHEA%20Guide%20to%20LTCF%20Infec tion%20Control%20Jul08.pdf Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings http://www.cdc.gov/hicpac/pdf/isolation/Isolation2007.pdf Management of Multidrug-Resistant Organisms In Healthcare Settings, 2006 http://www.cdc.gov/hicpac/pdf/MDRO/MDROGuideline2006.pdf DIDE Website http://www.dhhr.wv.gov/oeps/disease/HAI/Pages/default.aspx CDC Healthcare-Associated Infections http://www.cdc.gov/hai/ CDC SHEA “Train the Trainer” May 2011 Epidemiology and Prevention of Common Emerging MDROs “Alex Kallen, MD, MPH” DHQP, CDC