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

2. 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

3. 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

5. 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: )
[main changes:- advances in ICU infection prevention, care bundles, decontamination strategies, hand hygiene interventions]

6. 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

7. (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

8. Lots of Guidelines. (not much evidence. only expert opinion
Lots of Guidelines! (not much evidence? only expert opinion?) ARPAC Study - Clin Microbiol Infect 11:
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?

9. 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:
Saudi Med J 33:
Clin Microbiol Infect 19:
Ann Clin Microbiol Antimicrob 12:10

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

11. 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!

12. 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…

13. 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)

14. 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

15. 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

16. 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

17. 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

18. 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 (
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

19. 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

20. 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:
Is a universal decontamination strategy possible?

21. 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)

22. 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:

23. 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

24. 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: )

25. 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

26. 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!

27. 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 !!!

28. Key Recommendations (i)
(Clin Microbiol Infect 11: )
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

29. 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

30. (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