Coping with multiresistant bacteria in the ICU Kevin Towner Nottingham, UK

FACT: infections acquired in the ICU are associated with significant morbidity and mortality Wound infections (surgical, trauma or burns patients) Infections of critically-ill patients, particularly those requiring mechanical ventilation (ventilator-associated pneumonia) Skin and soft tissue infections Bloodstream infections Urinary tract infections Meningitis

Evolution of antimicrobial resistance in the ICU During the 1970s, most ICU infections could be treated successfully with (e.g.) methicillin, gentamicin, minocycline, nalidixic acid, trimethoprim, ampicillin or carbenicillin (alone or in combinations) During the 1980s, high proportions of strains causing infections became resistant to commonly used antimicrobials, including aminopenicillins, ureidopenicillins, 1st, 2nd and 3rd generation cephalosporins, cephamycins, most aminoglycosides, quinolones, chloramphenicol, trimethoprim and tetracyclines Emergence of carbapenem-resistant strains was first documented during the late 1980s/early1990s Pan-resistant strains appeared in the late 1990s

Problem Organisms MRSA VRE E.coli and K. pneumoniae resistant to ESBLs, carbapenems, quinolones Multiresistant A. baumannii Multiresistant P. aeruginosa In the last decade, MDR Gram-negative bacteria (e.g., Pseudomonas, Acinetobacter) have become more common, whereas resistant Gram-positive bacteria (e.g. S. aureus) have been reported less frequently (Semin Resp Crit Care Med 32:115-138) [main changes:- advances in ICU infection prevention, care bundles, decontamination strategies, hand hygiene interventions]

However, all is not yet lost! e.g., Depending on geographical location, a significant proportion of Gram-negative strains currently still retain susceptibility to carbapenems and/or at least some other antibiotics Every possible effort should be made to retain for as long as possible the effectiveness of antibiotics that still show some activity and restrict the spread of MDR strains

(a multifaceted, multiprofessional team approach) How to Cope? A bundle of bundles! (a multifaceted, multiprofessional team approach) Prevention of clinical infection Infection control – containment of resistance / decontamination measures Surveillance of organisms/resistance Antibiotic policies and audit Education

Lots of Guidelines. (not much evidence. only expert opinion Lots of Guidelines! (not much evidence? only expert opinion?) ARPAC Study - Clin Microbiol Infect 11:937-954 Many agreements, but also disagreements, in international guidance documents How to identify and tackle the challenges in local application? How to measure success in implementing guidelines?

How to Cope? Prevent clinical infection! Care intervention bundles, combining rigorous infection control and clinical care processes, are effective in preventing (e.g.) VAP, CLBSIs Curr Opin Infect Dis 22:159-166 Saudi Med J 33:278-283 Clin Microbiol Infect 19:363-369 Ann Clin Microbiol Antimicrob 12:10

How to Cope? Prevent clinical infection! ICU stay promotes enrichment and dissemination of MDR bacteria Prolonged ICU stay is significantly correlated with increased endogenous dissemination and cross-transmission

A Typical ICU 41% (77/189) carriage of a multi-resistant isolate amongst ICU patients 71% of these were colonised in the first week on ICU Of those colonised in the first week, 26% (vs. 5%) developed clinically significant infection Good infection control practice is essential!

Factors facilitating the spread of MDR bacteria in the ICU Increased length of hospital stay Prior antibiotics Mechanical ventilation Exposure to other patients colonised with MDR bacteria Environmental contamination Understaffing Poor adherence of staff to hand hygiene Once endemic, MDR bacteria are difficult to eradicate…

Normal infection control procedures Identify whether cross-infection or common-source infection Review policies and procedures related to patient care Epidemiological survey and surveillance cultures; epi typing Contact isolation, cohorting of patients (and nurses) Enforce strict hand disinfection Environmental disinfection of patient rooms and surfaces Restrict antibiotic use Conventional infection control measures are unable to halt transmission of certain organisms (e.g., A. baumannii)

Survival of Acinetobacter in the environment Survives in dry particles and dust for up to 10 days (7 days for S. aureus) Encapsulated strains survive for >4 months on PVC, ceramics, rubber, steel Survives exposure to chlorhexidine, gluconate and phenol-based disinfectants Survives exposure to radiation

Enhanced measures to eliminate A. baumannii from an ICU (i) Patients screened 3x/week 2x/week environmental screening  identified reservoirs such as phones and computers Full gown/gloves worn for all interaction with MRAB patients Isolation/cohorting of MRAB patients Repeated deep cleaning of whole ICU until environmental clearance Deep/internal cleaning of all equipment (e.g. ventilators, mattresses etc) Restricted access to ICU Daily Infection Control ward round Register of cases kept – previous patients isolated on readmission

Enhanced measures to eliminate A. baumannii from an ICU (ii) Major elective surgical cases delayed or transferred to other hospitals 6 beds closed; 2 beds closed long term Gown/gloves adopted for contact with any bed area or equipment Clear distinction between clean and dirty areas Results: No new case of MRAB in ICU since 6th June 2005. The cost of the first six months of this episode: 1.1 million Euro Conclusion: It is still possible to eradicate MRAB (and other MDR organisms) from an ICU when an uncompromising approach is taken to infection control

How to Cope? Infection control policies Adequate staff resources Hand hygiene! Other standard precautions, enhanced when necessary Sufficient isolation facilities Epidemiological typing of ‘outbreak’ strains Decontamination of patients Audit / feedback Education and reinforcement

Detailed guidance used in the UK is available on the HPA website (www Detailed guidance used in the UK is available on the HPA website (www.hpa.org.uk) Contact isolation precautions Risk factors for colonisation or infection Antibiotic prescribing policies Patient transfer procedures (internal and external) Use of dedicated equipment Screening strategies Cleaning and decontamination procedures Ward closure if necessary

Epidemiology of A. baumannii Transmission from a common source Airborne transmission Patient-to-patient transmission Hands of hospital personnel Contamination of environmental surfaces Contamination of medical equipment Colonised patient is the primary reservoir

How to Cope? Does patient decontamination work? Good evidence that chlorhexidine body washes may be effective in preventing carriage and (possibly) BSIs with MRSA and VRE in different ICU settings Evidence that chlorhexidine body washes reduce carriage or infections with MDR Gram-negative bacteria is lacking (insufficient data) Intensive Care Med 38:931-939 Is a universal decontamination strategy possible?

How to Cope? Surveillance of organisms/resistance List of local ALERT organisms for each hospital Standardised AST methods (comparisons with other hospitals!) External and internal quality assurance schemes Epidemiological typing of ‘outbreak’ strains Investigation of unusual resistance phenotypes (either locally or at a reference laboratory)

How to Cope? Appropriate use of antibiotics! Good evidence suggests that a strategy aimed at reducing the prolonged use of broad-spectrum antibiotics is the only means to reduce the emergence of MDR bacteria Curr Opin Crit Care 14:587-592

How to Cope? Appropriate use of antibiotics! Antibiotic stewardship programme with strategic goals Written ‘Antibiotic Formulary’ Clinicians must follow antibacterial prescribing policy of the hospital Culture-based therapy ‘De-escalating strategy’ – initial administration of empirical antibiotics active against MDR pathogens, followed by optimised treatment based on unequivocal susceptibility testing data

How to Cope? Education and Audit Implementation of audit and education programmes concerning antimicrobial prescribing and infection control for all healthcare workers (from undergraduates to experienced professionals) Specific multidimensional programmes to improve hand hygiene with reminders in the workplace and performance feedback – shown to be effective in limited resource countries (Infect Control Hosp Epidemiol 2013; 34:415-423)

What’s the challenge for hospitals? The need to detect epidemic spread of multi-resistant strains among patients in hospitals, particularly in ICUs The fact that patients disseminate large numbers of certain organisms into their environment The long-term survival of certain bacteria on numerous surfaces and inanimate objects The resistance of these organisms to drying, disinfectants and antibiotics The difficulty of eradicating these organisms from the hospital environment The need to institute proper hand hygiene and care bundles for the prevention of infection

Known Facts (i) Bacteria have developed a wide range of sophisticated resistance mechanisms to combat the challenge of exposure to antibiotics Use of antibiotics is important in selecting for the development and spread of resistance Antibiotic resistance in bacteria is increasing - both in the community and hospitals – and can severely limit the therapeutic options in ICUs Choice of empirical therapy should depend on the local susceptibility pattern – knowledge of this is essential!

Known facts (ii) Therapy should be culture-directed whenever possible and in accord with a hospital’s antibiotic prescribing policy Well-controlled clinical trials of existing and new therapies are required Continued (enhanced) emphasis on the prevention of cross-infection (particularly care bundles and hand hygiene) and the introduction of new resistant strains into a particular hospital ICU environment is essential !!!

Key Recommendations (i) (Clin Microbiol Infect 11:937-954) Surveillance of antimicrobial resistance standardised testing methods continual local surveillance for ALERT organisms feedback to prescribers Surveillance of antimicrobial consumption continual surveillance of antimicrobial use data investigations of changes in use clinical pharmacy services to support prescribing Antibiotic stewardship establish antibiotics formulary and stewardship policy reserve key antibiotics audit performance based on resistance and consumption data

Key Recommendations (ii) Infection Control Policy ensure sufficient resource (staff and facilities) implement standard precautions (especially hand hygiene) and audit compliance validate and implement rapid screening methods for ALERT organisms develop and evaluate local surveillance, outbreak detection (rapid molecular typing) and control measures Education implement education programmes on antimicrobial prescribing and infection control for all grades of HCWs make programmes multimedia and evidence-based with feedback on local compliance

(a multifaceted, multiprofessional team approach) How to Cope? A bundle of bundles! (a multifaceted, multiprofessional team approach) Prevention of clinical infection Infection control – containment of resistance / decontamination measures Surveillance of organisms/resistance Antibiotic policies and audit Education