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Acinetobacter baumanniian update

Dr.T.V.Rao MD

Dr.T.V.Rao MD 1

Acinetobacter baumannii

• Acinetobacter baumannii is a Gram negative bacteria. It is typically a short, almost round, rod-shape (coccobacillus). It can be an opportunistic pathogen in humans, affecting people with compromised immune systems and is becoming increasingly important as a hospital derived infection (nosocomial). It has also been isolated from soil and water samples in the environment.

Dr.T.V.Rao MD 2

New designation of the Genus

• It was not until 1968 that this genus designation became more widely accepted . Baumann et al. published a comprehensive survey and concluded that the different species listed above belonged to a single genus, for which the name Acinetobacter was proposed, and that further sub classification of different species based on phenotypic characteristics was not possible

Dr.T.V.Rao MD 3

Current taxonomy

• The genus Acinetobacter, as currently defined, comprises gram-negative, strictly aerobic, Nonfermenting, nonfastidious, nonmotile, catalase-positive, oxidase-negative bacteria with a DNA G+C content of 39% to 47%. Based on more recent taxonomic data, it was proposed that members of the genus Acinetobacter should be classified in the new family Moraxellaceae within the order

Dr.T.V.Rao MD 4

Acinetobacter - Motionless

• The name, Acinetobacter, comes from the Latin word for "motionless," because they lack cilia or flagella with which to move. Most species are not significant sources of infection. However, one opportunistic species, Acinetobacter baumannii , is found primarily in hospitals and poses a risk to people who have supressed immunity:

Dr.T.V.Rao MD 5

Global pockets of Acinetobacter baumannii infections

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Successful pathogen in Afghanistan war

• A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts

Dr.T.V.Rao MD 7

Acinetobacter a Emerging Multidrug Resistant Bacteria

• Since the 1970s, the spread of multidrug-resistant (MDR) Acinetobacter strains among critically ill, hospitalized patients, and subsequent epidemics, have become an increasing cause of concern. Reports of community-acquired Acinetobacter infections have also increased over the past decade. A recent manifestation of MDR Acinetobacter that has attracted public attention is its association with infections in severely injured soldiers.

Dr.T.V.Rao MD 8

Acinetobacter a threat to our patients

• The genus known as Acinetobacter has undergone significant taxonomic modification over the last 30 years. Its most important representative, Acinetobacter baumannii, has emerged as one of the most troublesome pathogens for health care institutions globally. Its clinical significance, especially over the last 15 years, has been propelled by its remarkable ability to up regulate or acquire resistance determinants, making it one of the organisms threatening the current antibiotic era.

Dr.T.V.Rao MD 9

Microbiology• Oxidase negative• Nitrate negative• Catalase positive• Nonfermentative• Nonmotile• Strictly aerobic • Gram negative

coccobacillus– Sometimes difficult to

decolorize• Frequently arranged in

pairs

Dr.T.V.Rao MD 10Bergogne-Bérézin E, Towner KJ. Clin Microbiol Rev 1996;9:148-165.

Morphology is distinctive

• Rod shaped during rapid growth and Coccobacillary in the stationary phase.

• Encapsulated (generally). • Nonmotile (although they

may exhibit twitching motility).

• Gram-negative organisms. Retention of crystal violet may result in incorrect identification as gram-positive cocci.

Dr.T.V.Rao MD 11

Microbiology• Ubiquitous:

– Widely distributed in nature (soil, water, food, sewage) & the hospital environment

• Survive on moist & dry surfaces• 32 species

– >2/3 of Acinetobacter infections are due to A. baumannii

• Highly antibiotic resistant– Numerous mechanisms of resistance to β-lactams described in

A. baumannii– 15 aminoglycoside-modifying enzymes described– Quinolone resistance due to mutations in DNA gyrase

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Biochemical Reactions

• Oxidase negative(opposite to Neisseria spp.or Moraxella spp.)

• Haemolytic• Indole negative. • Catalase positive.

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Biochemical Reactions

Acidify glucose (may enhance its ability to invade devitalized tissue).

• Grow at 44° C.• Aerobic. • Acinetobacter spp have the ability to use various

sources of nutrition which accounts for its growth on routine laboratory media. This also explains its survival as an environmental pathogen.

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Appearance in Microscope and Petri dish

Dr.T.V.Rao MD 15

Colony Characters

• Colonies are 1 to 2 mm, nonpigmented, domed, and muciod, with smooth to pitted surfaces.

• They can't reduce nitrate or to grow anaerobically (different from Enterobacteriaceae).

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Newer methods of Identification of different species

• Methods include high resolution fingerprinting with AFLP, PCR-RFLP with digestion of PCR amplified sequences, and analysis of various DNA sequences. Of these, AFLP analysis and amplified 16SrRNA ribosomal DNA restriction analysis have been validated with large numbers of strains of all described species. Nucleotide sequence based methods are expected to be the standard for identification in the near future.

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Common species identified using

• Acinetobacter calcoaceticus-baumanii complex: glucose-oxidising nonhemolytic, (A.baumannii can be identified by OXA-51 typing)

• Acinetobacter lwoffii: glucose-negative nonhemolytic

• Acinetobacter haemolyticus: haemolytic on blood agar.

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Respiratory route is prominent route of entry

• The respiratory system is the most common site for Acinetobacter infection because of its transient pharyngeal colonization of healthy persons and a high rate of tracheotomy colonization. Acinetobacter has been reported to cause community-acquired bronchiolitis and tracheobronchitis in healthy children.

Dr.T.V.Rao MD 19

Immune system and Acinetobacter Infections

• Acinetobacter baumannii is a bacterium in the Acinetobacter genus which can be dangerous for human beings who have compromised immune systems, causing opportunistic infections which can lead to death if the patient does not receive aggressive treatment.

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Survives in the natural environments with minimal needs

• The organism can survive for months on clothing and bedclothes, bed rails, ventilators and other surfaces in the environment, including sinks and doorknobs, making Nosocomial transmission extremely difficult to control.

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Transmission of: Acinetobacter

• Transmission: Acinetobacter can be spread from person to person (infected or colonized patients), contact with contaminated surfaces of exposure to the environment.

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Documented mechanisms of resistance in Acinetobacter baumannii

• Aminoglycosides-modifying enzymes

• Broad-spectrum β-lactamases

• Carbapenemases • Quantitative and/or

qualitative changes in outer membrane porins

• Altered penicillin-binding proteins.

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Mechanisms for resistance to Carbapenems:

• Metallo-β-lactamase (VIM, IMP): gene transfer, gene activation my insertion of an activation sequence (this is inserted upstream and switches on enzyme production) & mutation.

• OXA Carbapenemases (class D) -difficult to detect.

• Cell permeability changes. • Target (PBPs) change.

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Metallo-β-lactamases:

• Common in the Far East, rare in Europe.

• Various VIM & IMP types (plasmid mediated).

• Extracts have been shown to hydrolyse imipenem.

• High incidence in Pseudomonas aeruginosareferred to the HPA.

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Emerging Mechanisms in Pathogenicity

• A well-characterized porin of A. baumannii, the 38-kDa outer membrane protein A, has been shown to induce apoptosis of eukaryotic cells and to activate dendritic cells, leading to the differentiation of CD4+ T cells toward a Th1 phenotype Dr.T.V.Rao MD 26

Biofilms enhance the Pathogenicity

A. baumannii forms biofilms with enhanced antibiotic resistance and, more recently, that a chaperone-usher secretion system involved in Pilus assembly affects biofilm formation

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Iraqnobacter among US soldiers

• Some nurses, soldiers, and microbiologists infected with Iraqnobacter (Acinetobacter baumannii) due to its spread throughout the military hospitals. Many times soldiers have survived hellacious trauma on the battlefield only to succumb to even more damage by an organism that has picked up antimicrobial resistance factors to the drugs primarily associated with treating them almost impossible.

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Why it is important in critical care patients

• Acinetobacter commonly colonizes patients in the intensive care setting. Acinetobactercolonization is particularly common in patients who are intubated and in those who have multiple intravenous lines or monitoring devices, surgical drains, or indwelling urinary catheters..

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Diagnosis of Acinetobacter Infections

• Infection or colonization with Acinetobacter is usually diagnosed by clinical culture of blood, sputum, urine, wound, sterile body fluid, etc. Microbiologic cultures can be processed by standard methods on routine media.

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Microbiological Investigation

• Acinetobacter baumanniiisolates were presumptively identified by using morphology of the colonies, Gram staining, Oxidase and Catalase reactions, growth at 44°C, and the API-20 NE System (Bio-Merieux, Lyon, France) Identification as A. baumanniiwas verified by restriction analysis of the 16S-23S ribosomal RNA intergenic-spacer sequences, (described by Dolzani and colleagues)

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Collect the following Data before decisions on Treatment

• The following information will be collected: age, sex, occupation, hospital location at the time of positive culture (ER, medical ward, ICU etc), date of positive culture, prior hospitalization, receipt of outpatient dialysis, home care or other regular medical care (eg, outpatient chemotherapy), presence of invasive devices, receipt of antibiotics,

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ICU’s – A potential source of Acinetobacter Infections

• The elucidation of potential risk factors for resistant strains of Acinetobacter is therefore an important task, and the use of alternative antibiotics should be considered in ICUs where these strains are endemic .

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Acinetobacter outbreaks

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Detection of Acinetobacter Infections

Consider: organ site, genetic typing, hospital location

Common source

outbreak with respiratory site predominance

Common source

outbreak without

respiratory site predominance

Respiratory site outbreaks

without an identified common source

Non- respiratory site outbreaks

without an identified

common source

Villegas M, Hartstein A. Infect Control Hosp Epidemiol. 2003;24:284-295

Current trends in Antibiograms

• Most A. baumannii are now resistant tampicillin, Carbenicillin, Cefotaxime and Chloramphenicol.

• Resistance to Gentamycin, tobramycin and amikacin is increasing. Fluoroquinolones, ceftazidime,

• Trimethoprim-Sulphmethoxazole, Doxycycline, Polymyxin B, colistin, imipenem and meropenem may retain activity against Nosocomial Acinetobacter

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Treatment• Carbapenems (Imipenem and Meropenem) are

the mainstay of treatment for antimicrobial-resistant gram-negative infections, though Carbapenems-resistant Acinetobacter is increasingly reported.

• Resistance to the Carbapenems class of antibiotics makes multidrug-resistant Acinetobacter infections difficult, if not impossible, to treat.

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Multidrug Resistant strains a Global Concern

• Multidrug-resistant A. baumannii is a common problem in many hospitals in the US and Europe. First line treatment is with a Carbapenems antibiotic such as imipenem, but carbapenem resistance is increasingly common. Other treatment options include Polymyxin, Tigecycline and Aminoglycosides.

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Treating the Resistant Infections

• Colistin and Polymyxin B have been used to treat highly resistant Acinetobacter infections. The choice of appropriate therapy is further complicated by the toxicity of colistin which is mainly renal. Acinetobacter isolates resistant to colistin and Polymyxin B have also been reported. Dr.T.V.Rao MD 38

Medical interventions increasing the Acinetobacter Infections

• Underlying diseases and severity of illness, presence of urinary or intravascular devices, recent immunomodulative therapies or radiation therapy, physical exam findings, laboratory and radiographical data, antimicrobial usage within 30 days of onset of the infection,

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From Vietnam to Iraq

• Recently A. baumannii has also been seen in a number of wound infections in soldiers returning from the middle east. Wound infections in soldiers is not a new phenomenon for A. baumannii as it was the most common gram negative bacillus to contaminate wounds during the Vietnam waras well.

Dr.T.V.Rao MD 40

Acinetobacter baumannii Infections in Iraq war

• Since Operation Iraqi Freedom began in 2003, more than 700 US soldiers have been infected or colonized with Acinetobacter baumannii. A significant number of additional cases have been found in the Canadian and British armed forces, and among wounded Iraqi civilians.

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Origin of Iraqibacter• Where the Iraqibacter came from remains

something of a mystery. Soil samples taken by researchers in Iraq and Kuwait came back negative. However, it was found thriving in the hospitals. When Iraqibacter was compared to MDRAB samples taken in Europe before the war, they were found to be identical (Silberman, 2007). Thus, scientists believe that the current outbreak originated from European sources.

( So MDRAB did exist before the Iraq War.)

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Major infections due to Acinetobacter

• Ventilator-associated pneumonia • Urinary tract• Bloodstream infection • Secondary meningitis• Skin/wound infections• Endocarditis• CAPD-associated peritonitis• Ventriculitis

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Acinetobacter Bloodstream Infection

• Most common source is respiratory tract infection• Predisposing factors:

– Malignancy– Trauma– Burns– Surgical wound infections– Neonates

• Low birth weight• Need for mechanical ventilation

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Source of A. baumanii Nosocomial Bloodstream Infection

Respiratory tract71%

Central venous line 8%

Abdominal infection

19%

N=37

Garcia-Garmendia J-L et al. Clin Infect Dis 2001;33:939-946.

The respiratory tract is an important reservoir for Acinetobacter bloodstream infections

Acinetobacter Meningitis

• Most cases are hospital-acquired

• Often associated with neurosurgical procedures

• Risk factors:– Ventriculostomy– Heavy use of

antibiotics in the neurosurgical ICU

Dr.T.V.Rao MD 46

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Dr.T.V.Rao MD 47

Environmental Contamination with Acinetobacter

• Bed rails• Bedside tables• Ventilators• Infusion pumps• Mattresses• Pillows• Air humidifiers• Patient monitors

• X-ray view boxes• Curtain rails• Curtains• Equipment carts• Sinks• Ventilator circuits• Floor mops

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Factors Promoting Transmission of Acinetobacter in the ICU

• Long survival time on inanimate surfaces– In vitro survival time 329 days

(Wagenvoort JHT, Joosten EJAJ. J Hosp Infect 2002;52:226-229)

– 11 days survival on Formica, 12 days on stainless steel(Webster C et al. Infect Control Hosp Epidemiol 2000;21:246)

– Up to 4 months on dry surfaces(Wendt C et al. J Clin Microbiol 1997;35:1394-1397)

• Extensive environmental contamination• Highly antibiotic resistant• High proportion of colonized patients • Frequent contamination of the hands of healthcare workers

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Acinetobacter Transmission in the Hospital Setting

• Direct or indirect contact– Contaminated hands

of healthcare workers• Airborne transmission

via aerosol production (e.g., hydrotherapy) may occur

Dr.T.V.Rao MD 50Simor AE et al. Infect Control Hosp Epidemiol 2002;23:261-267.

Acinetobacter spp Skin Colonization

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Body siteHospitalized

patients (n=40)Healthy

controls (n=40)Forehead 33% 13%

Ear 35% 7%

Nose 33% 8%

Throat 15% 0%

Axilla 33% 3%

Hand 33% 20%

Groin 38% 13%

Perineum 20% 3%

Toe web 40% 8%

Any site 75% 42.5%Seifert H et al. J Clin Microbiol 1997;35:2819-2825.A. baumanii isolated from 2 patients & 1 control only

Acinetobacter Transmission in the Hospital SettingColonization of Healthcare Workers

• Outbreak of multidrug resistant A. baumannii in a Dutch ICU involving 66 patients with an epidemic strain

• Nursing staff were cultured (nares & axilla, same swab)– 15 nurses found to harbor epidemic strain– All were culture negative when re-cultured

(nose, throat, axilla, perineum)

Dr.T.V.Rao MD 52Wagenvoort JHT et al. Eur J Clin Microbiol Infect Dis 2002;21:326-327.

Hand Contamination in HCWs

18

36

29

18

05

10152025303540

Gram-negative rods S. aureus

PhysiciansNurses

Bauer TM et al. J Hosp Infect 1990;15:301-309.

% of HCWs (n=328) with hand contamination

Limiting the cross transmission of Acinetobacter

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Preventing Acinetobacter Transmission in the ICUGeneral Measures

• Hand hygiene– Use of alcohol-based hand sanitizers

• Contact precautions – Gowns/gloves– Dedicate non-critical devices to patient room

• Environmental decontamination• Prudent use of antibiotics• Avoidance of transfer of patients to Burn Unit from other

ICUs

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Preventing Acinetobacter Transmission in the ICUOutbreak Interventions

• Hand cultures• Surveillance cultures• Environmental cultures following terminal

disinfection to document cleaning efficacy• Cohorting• Ask laboratory to save all isolates for molecular

typing• Healthcare worker education• If transmission continues despite above interventions,

closure of unit to new admissions

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Efficacy of Hand washing Agents against Acinetobacter

• Experimental study to access removal of A. baumannii from the hands of volunteers– Fingertips inoculated

with either 103 CFU (light contamination) or 106 CFU (heavy contamination)

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Agent

Removal Rate

Light contamination Heavy contaminationPlain soap 99.97% 92.40%

70% Ethyl alcohol 99.98% 98.94%

10% Povidone-iodine 99.98% 98.48%

4% Chlorhexidine 99.81% 91.39%

Cardoso CL et al. Am J Infect Control 1999;27:327-331.

Efficacy of Hand washing Agents against Acinetobacter

• Experimental study to access removal of A. baumannii from the hands of volunteers– Fingertips inoculated with either 103 CFU (light contamination) or 106

CFU (heavy contamination)

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Agent

Removal Rate

Light contamination Heavy contaminationPlain soap 99.97% 92.40%

70% Ethyl alcohol 99.98% 98.94%

10% Povidone-iodine 99.98% 98.48%

4% Chlorhexidine 99.81% 91.39%

Cardoso CL et al. Am J Infect Control 1999;27:327-331.

Chlorhexidine Resistance in Acinetobacter

• Biocide resistance in gram-negative organisms is mainly intrinsic & chromosomal (plasmid mediated in gram-positive organism)

• 10 strains of A. baumannii tested for chlorhexidine susceptibility– Median MIC 32 mg/L– Median MBC 32 mg/mL– Chlorhexidine resistance increased with increased

antibiotic resistance

Dr.T.V.Rao MD 59Kõljalg S et al. J Hosp Infect 2002;51:106-113.

Can Acinetobacter Infect Health care Workers ?

• Acinetobacter rarely causes serious infection in otherwise healthy people and therefore poses minimal threat to healthcare workers or patients’ family members.

• Pregnant healthcare workers are not at increased risk from this organism and can therefore care for patients infected or colonized with the organism.

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Why Dealing with A.baumannii infections is problematic.

• A. baumannii important cause of nosocomial infections, in ICUs (Clin Infect 2004;10:684—704)

• Treatment difficult because multi-resistant• Colonized, infected patients point- sources of A.

baumannii infections in healthcare settings• Prolonged organism survival on environmental

surfaces in hospitals contributes to protracted outbreaks

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Active surveillance of cultures

• -Ventilator dependent /tracheotomy patients

• -Patients admitted from long term care facilities with endemic Acinetobacter

• -Patients with previous history of Acinetobacter infection

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CHROMagar Acinetobacter agar is the latest addition to the clinical range of chromogenic media developed by Dr.Alain

Rambach.

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Standard precautions in caring Patients

• Should be followed at all times. As with prevention of any healthcare-associated organism, careful hand hygiene should be performed at all appropriate times– either hand washing at the sink or using an alcohol based hand sanitizer. Contact precautions are indicated. They should be maintained for the duration of hospitalization or until negative cultures are obtained.

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Hand Hygiene is an Important Preventive option

• Acinetobacter can live on the skin and may survive in the environment for several days. Careful attention to infection control procedures such as hand hygiene and environmental cleaning can reduce the risk of transmission.

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Simple and Scientific Hand Washing can reduce infections with A.baumannii too ..

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Continues to be a important Pathogen

• Although commonly found on the skin of healthy humans, Acinetobacter plays the role of an opportunistic pathogen in the critically ill patient

• High level of antibiotic resistance makes it well suited as a pathogen in areas with high use of antibiotics (e.g., ICU setting)

• Control requires good hand hygiene, barrier precautions & environmental decontamination– Alcohol-based products containing chlorhexidine should be

considered the hand hygiene agents of choice

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• Programme Created by Dr.T.V.Rao MD for Medial and Health care

Workers in the Developing World • Email

• doctortvrao@gmail.com

Dr.T.V.Rao MD 68