Acinetobacter

an old friend, but a new enemy

Kevin Towner Nottingham University Hospitals NHS Trust

The genus Acinetobacter

Non-motile Gram-negative coccobacilli Catalase-positive Oxidase-negative Non-fermentative Non-fastidious strict aerobes

Habitats
Environment
soil, water, sewage

Foodstuffs (as spoilage organisms)

milk products, meat, poultry, fish

Human skin (25-70% of individuals) Infections in hospitalised patients

Members of the genus Acinetobacter are now recognised as significant nosocomial pathogens Critically-ill patients, particularly those requiring mechanical ventilation in ICUs Wound infections (trauma patients) Community-acquired infections (usually in patients with co-morbidities, with most reports from tropical or sub-tropical areas)

Which Acinetobacter?
Modern molecular-based taxonomy recognises at least 33 different genomic groups 18 of these have species names A further 28 groups have been identified that contain multiple strains, and there are at least 21 ungrouped single strains

Three major overlapping populations

Hospitals and hospitalised patients multiresistant isolates A. baumannii, sp.3, sp.13TU (the A. baumannii complex) particularly adapted to this environment? Skin (humans and animals) / foodstuffs sensitive isolates A. johnsonii, A. lwoffii, A. radioresistens Soil / environment / wastewaters sensitive isolates A. calcoaceticus, A. johnsonii Natural habitats of other species still poorly defined

Acinetobacter baumannii common misconceptions

A. baumannii is an aerobic, Gram-negative coccobacillus that is highly prevalent in nature. These organisms are usually commensal, but they are emerging as important opportunistic pathogens. (Villers et al., Ann Intern Med 1998) A. baumannii is a non-fermenting, Gram-negative, aerobic coccobacillus found extensively in natural environments that has assumed an increasing importance in nosocomial infections. (Garnacho-Montero et al., Clin Infect Dis 2003) A. baumannii, an aerobic Gram-negative coccobacillus, is ubiquitous in fresh water and soil. It is a frequent skin and oropharyngeal commensal. (Chen et al., Chest 2005) A. baumannii is a species of non-fermentative Gram-negative bacteria commonly found in water and soil. This organism was susceptible to most antibiotics in the 1970s. (Fournier et al., PLoSGenetics 2006) A. baumannii is ubiquitous in nature and has been recovered from soil, water, animals, and humans. Acinetobacter species are normal inhabitants of human skin. For this reason, it has been suggested that human skin could be the source of severe infections. (Fournier and Richet, Clin Infect Dis 2006)
slide courtesy of H. Seifert

Epidemiology of Acinetobacter - the truth (?)

A. non-baumannii: water, soil, plants, vegetables, human skin

A. baumannii is not a ubiquitous organism

Hospital environmental sources during outbreaks equipment,

beds, respiratory tubing, computer keyboards, cellphones

Patients Natural habitat (if any) remains to be defined
slide courtesy of H. Seifert

Problems in the hospital setting caused by A. baumannii

Persistence resistant to drying and disinfectants Antibiotic resistance increasing proportion of isolates are multiresistant (including carbapenems 24% in 2007 in the UK, compared with <0.5% in 1990) remarkable ability to acquire resistance genes Causes outbreaks

Survival strategies of A. baumannii long-term survival on dry surfaces

S. aureus A. baumannii Acinetobacter spp. Enterococcus E. coli A. baumanii BSA Water

29 days

10

15

20

25

30

35

40
[days]

45

Jawad et al. JCM 1996; 34:2881-87; Jawad et al. JCM 1998; 36:1938-41

Where is the reservoir for nosocomial infection with Acinetobacter baumannii ?

Patients admitted from the community? Patients admitted from other hospitals? Within the hospital itself?

Potential hospital sources

Hands of staff Ventilators Humidifiers Oxygen analysers Respirometers Bronchoscopes Lotion dispensers Bed frames Rubbish bins Sinks Air supply Jugs Bowls Soap Hand cream Plastic screens Bed linen Service ducts /dust Bedside charts Patients

Common source outbreaks of A. baumannii examples

Patients mattresses (Sherertz et al., JID 1985) Humidifiers (Gervich & Grout, AJIC 1985) Resuscitation bags (Hartstein et. al., AJM 1988) Ventilator tubing (Cefai et al., JHI 1990) Gloves (Patterson et al., AJM 1991) Pillows (Weernink et al., JHI 1995) Computer keyboards (Neely et al., CID 1999) Blood pressure cuffs (Bureau-Chalot et al., JHI 2004) Cell phones (Borer et al., EID 2005) Parenteral nutrition solution (De Vegas et al., ICHE 2006)

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

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 A. baumannii

Enhanced measures to eliminate A. baumannii from an ICU in London, UK (1)

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 in London, UK (2)

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 from an ICU when an uncompromising approach is taken to infection control

Factors facilitating the spread of A. baumannii

Increased length of hospital stay Prior antibiotics Once endemic, A. baumannii Mechanical ventilation difficult Exposure toto patients colonised with A. eradicate
baumannii

is

Environmental contamination Understaffing Poor adherence of staff to hand hygiene

Ward closure to combat A. baumannii outbreaks

Idzenga et al., J Hosp Infect 2006, NL Kraniotaki et al, IJAA 2006, GR, 2 weeks Longo et al., J Hosp Infect 2006, IT, 3 weeks Carbonne et al., J Hosp Infect 2005, FR, 4 weeks Pimentel et al., J Hosp Infect 2005, AUS 4 days Bernards et al., ICHE 2004, NL De Jong et al., J Hosp Infect 2004, SA Denton et al. J Hosp Infect. 2004, UK, 8 days Maragakis et al., JAMA 2004, USA, 4 weeks

In a potential outbreak situation: Most important source is already colonised or infected patients In a non-outbreak (sporadic) situation: Survives or is introduced?

Global epidemiology of individual A. baumannii strains

Multiple hospital outbreak within a city

New York (Landman et al., ArchIM 2002) London (Turton et al., JHI 2004) Johannesburg (Marais et al., AJIC 2004)

Multiple city outbreaks within a country

Czech Republic (Nemec et al., JMM 2004) Southeast England (Coelho et al., JCM 2004) France (Naas et al., EID 2006)

Outbreaks from hospitals in several countries in Europe

van Dessel et al., Res Microbiol 2004 Seifert et al., JCM 2005

Developing epidemiology of A. baumannii in the UK

A survey in 1999-2001 identified 34 different genotypes in 46 UK hospitals These were shown to belong to 10 different clusters In general, particular strains were characteristic of particular hospitals
(J Clin Microbiol 42: 832-834)

 Between 2003 and 2006, two carbapenemresistant A. baumannii lineages (SE clone and OXA-23 clone) became prevalent in over 40 hospitals each; susceptible only to colistin and tigecycline (J Clin Microbiol 44: 3623-3627) More recently, a further lineage (the Northwest strain) has become prevalent in several hospitals in the northern/midlands of the UK

Are specific carbapenem-resistant clones spreading in European hospitals?

As part of the EU ARPAC project, 169 hospitals in 32 countries provided data concerning multiresistant isolates of Acinetobacter spp. 130 reported encountering carbapenem-resistant isolates of Acinetobacter, ranging from rare sporadic isolates to an endemic/epidemic situation (Clin Microbiol Infect 2008; 14: 161-167)

 Diverse clusters identified by RAPD, PFGE and PCR-based sequence typing in European hospitals Three major European lineages As in the UK, multiple isolates from a single hospital generally belong to the same clone (some exceptions)

Acinetobacter baumannii has become a major cause of hospital-acquired infections because of its remarkable ability to survive and spread in the hospital environment and to rapidly acquire resistance determinants to a wide range of antibacterial agents Are we seeing worldwide spread of multiresistant lineages selected primarily on the basis of the resistance genes that they carry? Or is there something special about certain lineages that confers epidemic potential?

What treatment options remain for multidrug-resistant strains?

Polymyxin (colistin) (possibly in combinations) Sulbactam combinations Rifampicin/amikacin combinations Tigecycline (possibly in combinations) New siderophore monobactam (BAL30072) Synthetic peptides (in development) Phage therapy
(may be useful in individual patients, but resistance has already appeared to these options)

Whats the problem with Acinetobacter?

Epidemic spread of multidrug-resistant strains among patients in hospitals, particularly in ICUs Patients disseminate large numbers of organisms into their environment Survival on numerous surfaces and inanimate objects Resistant to drying, disinfectants and antibiotics Difficult to eradicate

Control is still possible!

1. Do you have a problem ?
Determine the base line Compare with other hospitals

2. If the answer is yes

Identify and type isolates Trace and isolate patients Re-emphasise and enhance hygiene and infection control procedures Review antibiotic policy Clean the Unit

More detailed guidance 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

So what else is special about Acinetobacter?

Perhaps by accident, it has evolved a range of its own special resistance genes (particularly carbapenemases) and the capacity to over-express them in response to antibiotic challenge It has evolved molecular mechanisms to capture resistance genes from other organisms A range of expression mechanisms (provision of promoters on insertion sequences) enables foreign resistance genes to be expressed

Acinetobacter the Gram-negative MRSA? it infects the ill it is multi-drug resistant it prolongs hospitalisation it causes outbreaks it persists its an EXPENSIVE pathogen!

Coming soon to a hospital near you!