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Acinetobacteran old friend, but a new enemy

Kevin Towner

Nottingham University Hospitals NHS Trust

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The genusAcinetobacter

Non-motile Gram-negative coccobacilli Catalase-positive

Oxidase-negative Non-fermentative

Non-fastidious strict aerobes

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Habitats

Environmentsoil, water, sewage

Foodstuffs (as spoilage organisms)milk products, meat, poultry, fish

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

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Members of the genusAcinetobacterare nowrecognised 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)

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WhichAcinetobacter?

Modern molecular-based taxonomyrecognises 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 atleast 21 ungrouped single strains

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Three major overlapping populations

Hospitals and hospitalised patientsmultiresistant isolates

A. baumannii, sp.3, sp.13TU

(theA. baumannii complex)particularly adapted to this environment?

Skin (humans and animals) / foodstuffs

sensitive isolatesA. johnsonii, A. lwoffii, A. radioresistens

Soil / environment / wastewaters

sensitive isolatesA. calcoaceticus, A. johnsonii

Natural habitats of other species still poorly defined

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Acinetobacter baumannii common misconceptions

A. baumannii is an aerobic, Gram-negative coccobacillus that is highly prevalent innature. These organisms are usually commensal, but they are emerging as importantopportunistic pathogens. (Villers et al., Ann Intern Med1998)

A. baumannii is a non-fermenting, Gram-negative, aerobic coccobacillus foundextensively in natural environments that has assumed an increasing importance innosocomial infections. (Garnacho-Montero et al., Clin Infect Dis 2003)

A. baumannii, an aerobic Gram-negative coccobacillus, is ubiquitous in fresh waterand 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 the1970s. (Fournieret al., PLoSGenetics 2006)

A. baumannii is ubiquitous in nature and has been recovered from soil, water,animals, and humans.Acinetobacterspecies are normal inhabitants of human skin.For this reason, it has been suggested that human skin could be the source of severeinfections. (Fournier and Richet, Clin Infect Dis 2006)

slide courtesy of H. Seifert

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Epidemiology ofAcinetobacter - 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

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Problems in the hospital setting caused

byA. baumannii Persistence

resistant to drying and disinfectants Antibiotic resistance

increasing proportion of isolates aremultiresistant (including carbapenems

24% in 2007 in the UK, compared

with

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0 5 10 15 20 25 30 35 40 45

A. baumani i

E. col i

Enterococcus

Acinetobacter spp.

A. baumannii

S. aureus

BSA

Water[days]

Survival strategies ofA. baumannii

long-term survival on dry surfaces

29 days

J awad et al. J CM 1996; 34:2881-87; J awad et al. J CM 1998; 36:1938-41

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Where is the reservoir for nosocomial

infection withAcinetobacter baumannii ?

Patients admitted from the community?

Patients admitted from other hospitals?

Within the hospital itself?

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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

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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)

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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

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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 ofA. baumannii

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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 eliminateA. baumannii

from an ICU in London, UK (1)

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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

Enhanced measures to eliminateA. baumannii

from an ICU in London, UK (2)

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Factors facilitating the spread of A.baumannii

Increased length of hospital stay

Prior antibiotics

Mechanical ventilation

Exposure to patients colonised withA.baumannii

Environmental contamination

Understaffing

Poor adherence of staff to hand hygiene

Once endemic,A. baumannii is

difficult to eradicate

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Ward closure to combatA. baumanniioutbreaks

Idzenga et al., J Hosp Infect 2006, NL

Kraniotaki et al, IJ AA 2006, GR, 2 weeks Longo et al., J Hosp Infect 2006, IT, 3 weeks

Carbonneet 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 J ong et al., J Hosp Infect 2004, SA

Denton et al. J Hosp Infect. 2004, UK, 8 days

Maragakis et al., J AMA 2004, USA, 4 weeks

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In a potential outbreak situation:-

Most important source is already colonisedor infected patients

In a non-outbreak (sporadic) situation:-

Survives or is introduced?

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Global epidemiology of individualA. baumannii

strains Multiple hospital outbreak within a city

New York (Landmanet al

., ArchIM 2002)

London (Turton et al., J HI 2004)

J ohannesburg (Marais et al., AJ IC 2004)

Multiple city outbreaks within a country

Czech Republic (Nemec et al., J MM 2004)

Southeast England (Coelho et al., J CM 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., J CM 2005

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Developing epidemiology ofA.

baumannii in the UK

A survey in 1999-2001 identified 34 different genotypes in46 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)

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Between 2003 and 2006, two carbapenem-

resistantA. baumannii lineages (SE cloneand OXA-23 clone) became prevalent inover 40 hospitals each; susceptible only tocolistin and tigecycline (J Clin Microbiol44: 3623-3627)

More recently, a further lineage (theNorthwest strain) has become prevalent inseveral hospitals in the northern/midlands ofthe UK

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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 ofAcinetobacterspp. 130 reported encountering carbapenem-resistant

isolates ofAcinetobacter, ranging from rare

sporadic isolates to an endemic/epidemic situation(Clin Microbiol Infect2008; 14: 161-167)

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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 asingle hospital generally belong to the

same clone (some exceptions)

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Acinetobacter baumannii has become a major cause

of hospital-acquired infections because of itsremarkable ability to survive and spread in the

hospital environment and to rapidly acquire

resistance determinants to a wide range ofantibacterial agents

Are we seeing worldwide spread of multiresistantlineages selected primarily on the basis of theresistance genes that they carry?

Or is there something special about certainlineages that confers epidemic potential?

Wh i i

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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 tothese options)

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Whats the problem with

Acinetobacter?

Epidemic spread of multidrug-resistant strainsamong 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

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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 andenhance hygieneand infection control procedures

Review antibiotic policy

Clean the Unit

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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

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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

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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!

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Coming soon to a

hospital near you!