Acinetobacter Acinetobacter baumanniibaumannii

an emerging infectionan emerging infection

Dr.T.V.Rao MDDr.T.V.Rao MD

Acinetobacter baumanniiAcinetobacter baumanniianan

Emerging Bacterial InfectionEmerging Bacterial Infection Acinetobacter baumanniiAcinetobacter baumannii is a ubiquitous is a ubiquitous

pathogen capable of causing both pathogen capable of causing both community and health care–associated community and health care–associated infections (HAIs), although infections (HAIs), although HAI’HAI’s are the s are the most common form. This organism has most common form. This organism has emerged recently as a major cause of HAI emerged recently as a major cause of HAI because of the extent of its antimicrobial because of the extent of its antimicrobial resistance and its propensity to cause large, resistance and its propensity to cause large, often multifacility, nosocomial outbreaks. often multifacility, nosocomial outbreaks.

Global pockets of Global pockets of Acinetobacter baumanii Acinetobacter baumanii

infectionsinfections

Acinetobacter a Emerging Acinetobacter a Emerging Multidrug Resistant BacteriaMultidrug Resistant Bacteria

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

Background:Background: Acinetobacter baumanniiAcinetobacter baumannii

Gram negative bacillus Gram negative bacillus Water and soilWater and soil Associated with biofilms, antibiotic Associated with biofilms, antibiotic

resistanceresistance Survives on inanimate surfaces for weeksSurvives on inanimate surfaces for weeks Not part of normal human floraNot part of normal human flora Infections and outbreaks Infections and outbreaks

– Intensive care unit and healthcare settings Intensive care unit and healthcare settings – Compromised immune systems and riskCompromised immune systems and risk– Colonized and infected patients as point Colonized and infected patients as point

sourcessources

Several species among the Several species among the AcinetobacterAcinetobacter

The genus The genus AcinetobacterAcinetobacter comprises 17 comprises 17 validly named and 14 unnamed (genomic) validly named and 14 unnamed (genomic) species. Some unrelated (genomic) species species. Some unrelated (genomic) species have common designations, while some have common designations, while some other species seem to be congruent but other species seem to be congruent but have different names. A phenotypic species have different names. A phenotypic species identification system has been described identification system has been described and a variety of genotypic methods has and a variety of genotypic methods has been explored and applied to investigate been explored and applied to investigate the diversity or phylogeny in the genus. the diversity or phylogeny in the genus.

AcinetobacterAcinetobacter - - MotionlessMotionless

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

According to the CDC, A. baumannii causes 80% According to the CDC, A. baumannii causes 80% of all Acinetobacter infectionsof all Acinetobacter infections

Acinetobacter baumanniiAcinetobacter baumanniiMorphologyMorphology

Acinetobacter Acinetobacter baumanniibaumannii is a is a pleomorphic pleomorphic aerobic gram-aerobic gram-negative bacillus, negative bacillus, commonly isolated commonly isolated from the hospital from the hospital environment and environment and hospitalized hospitalized patients. patients.

Genome Biology of Genome Biology of Acinetobacter sppAcinetobacter spp

Morphology is distinctiveMorphology is distinctive

Rod shaped during rapid growth and Rod shaped during rapid growth and coccobacillary in the stationary phase. coccobacillary in the stationary phase.

Encapsulated (generally). Encapsulated (generally). Nonmotile (although they may exhibit Nonmotile (although they may exhibit

twitching motility). twitching motility). Gram-negative organismsGram-negative organisms. .

Retention of crystal violet may result Retention of crystal violet may result in incorrect identification as gram-in incorrect identification as gram-positive cocci. positive cocci.

Other species are Other species are occasional pathogensoccasional pathogens

A. A. baumanniibaumannii is is the major species the major species of of AcinetobacterAcinetobacter.. Others occasional Others occasional human pathogens human pathogens include include A. A. calcoaceticus, A. calcoaceticus, A. lwoffi, A. junii, A. lwoffi, A. junii, A. johnsonii johnsonii and and A. A. baylyibaylyi. .

Current importance as Current importance as Emerging PathogenEmerging Pathogen

Emerging as important global, pan-Emerging as important global, pan-resistant GNB Nosocomial pathogen. resistant GNB Nosocomial pathogen.

Clearly pathogenic when Clearly pathogenic when recovered from blood and recovered from blood and normally sterile body sites.normally sterile body sites.

May cause Nosocomial epidemics May cause Nosocomial epidemics from contaminated common sources, from contaminated common sources, e.g., ventilation equipment, catheters, e.g., ventilation equipment, catheters, etc. etc.

Biochemical ReactionsBiochemical Reactions

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

HaemolyticHaemolytic Indole negativeIndole negative. . Catalase Catalase

positivepositive. .

Biochemical ReactionsBiochemical Reactions

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

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

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

Apperance in Microscope Apperance in Microscope and Petri dishand Petri dish

Colony CharactersColony Characters

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

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

Newer methods of Newer methods of Identification of different Identification of different

speciesspecies Methods include high resolution Methods include high resolution

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

Common species identified Common species identified usingusing

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

Acinetobacter lwoffiiAcinetobacter lwoffii: glucose-: glucose-negative nonhemolytic negative nonhemolytic

Acinetobacter haemolyticusAcinetobacter haemolyticus: : haemolytic on blood agar. haemolytic on blood agar.

Immune system and Immune system and Acinetobacter InfectionsAcinetobacter Infections

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

Survives in the natural Survives in the natural environments with minimal environments with minimal

needsneeds The organism can The organism can

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

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.

Drug Resistance Drug Resistance in in

AcinetobactersAcinetobacters

Complex mechanisms of Drug Complex mechanisms of Drug ResitanceResitance makes treatment makes treatment

options difficultoptions difficult

Documented mechanisms of Documented mechanisms of resistance in Acinetobacter resistance in Acinetobacter

baumanniibaumannii

Aminoglycosides-modifying enzymes Aminoglycosides-modifying enzymes Broad-spectrum β-lactamases Broad-spectrum β-lactamases Carbapenamases Carbapenamases Quantitative and/or qualitative Quantitative and/or qualitative

changes in outer membrane porins changes in outer membrane porins Altered penicillin-binding proteins. Altered penicillin-binding proteins.

Mechanisms for resistance Mechanisms for resistance to Carbapenemsto Carbapenems::

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

OXA Carbapenamases (class D) - OXA Carbapenamases (class D) - difficult to detect. difficult to detect.

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

Emerging Mechanisms in Emerging Mechanisms in PathogenictyPathogenicty

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

Biofilms enhance the Biofilms enhance the PathogenictyPathogenicty

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

what arewhat are Metallo-β-Metallo-β-lactamses:lactamses:

Common in the Far East, rare in Common in the Far East, rare in Europe. Europe.

Various VIM & IMP types (plasmid Various VIM & IMP types (plasmid mediated). mediated).

Extracts have been shown to Extracts have been shown to hydrolyse imipenem. hydrolyse imipenem.

High incidence in High incidence in Pseudomonas Pseudomonas aeruginosaaeruginosa referred to the HPA. referred to the HPA.

IraqnobacterIraqnobacter among US among US soldierssoldiers

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

Why it is important in critical Why it is important in critical care patientscare patients

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

Hospitalized patients are highly Hospitalized patients are highly venerable to Acinetobacter venerable to Acinetobacter

InfectionsInfections AcinetobacterAcinetobacter

infections infections are uncommon are uncommon and occur and occur almost almost exclusively in exclusively in hospitalized hospitalized patientspatients

Co-humans ( HCW ) are Co-humans ( HCW ) are great carriers of Infectiongreat carriers of Infection

Acinetobacter Acinetobacter causes causes colonization more often colonization more often than infection; this than infection; this means that it lives in or means that it lives in or on the body without on the body without causing illness (e.g., the causing illness (e.g., the skin of a healthcare skin of a healthcare worker). People who are worker). People who are colonized can become colonized can become carriers who spread the carriers who spread the bacteria to other bacteria to other people, usually without people, usually without realizing it.realizing it.

Risk factors includeRisk factors include:: hospitalization hospitalization significant co-significant co-

morbidity morbidity mechanical mechanical

ventilation ventilation cardio respiratory cardio respiratory

failure failure previous infection previous infection antimicrobial therapy antimicrobial therapy CVP lines CVP lines urinary catheters urinary catheters

Respiratory route is prominent Respiratory route is prominent route of entryroute 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.

Diagnosis of Acinetobacter Diagnosis of Acinetobacter InfectionsInfections

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

Microbiological Microbiological InvestigationInvestigation

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

Problems in treatingProblems in treating Acinetobacter baumanniiAcinetobacter baumannii

One of the biggest issues with One of the biggest issues with treating treating Acinetobacter baumanniiAcinetobacter baumannii is is that the bacterium is naturally that the bacterium is naturally resistant to a number of resistant to a number of antibiotics,antibiotics, making it challenging to find a drug making it challenging to find a drug regimen which will effectively attack regimen which will effectively attack it in an infected patien it in an infected patien

Collect the following Data Collect the following Data before decisions on before decisions on

TreatmentTreatment The following information will be The following information will be

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

ICU’sICU’s – – A potential source of A potential source of Acinetobacter InfectionsAcinetobacter Infections

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

Current trends in Current trends in AntibiogramsAntibiograms

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

Resistance to Gentamycin, tobramycin and amikacin is increasing. Flouroquinolones, ceftazidime,

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

TreatmentTreatment

Carbapenems (Imipenem and Meropenem) Carbapenems (Imipenem and Meropenem) are the mainstay of treatment for are the mainstay of treatment for antimicrobial-resistant gram-negative antimicrobial-resistant gram-negative infections, though Carbapenems-resistant infections, though Carbapenems-resistant Acinetobacter is increasingly reported.Acinetobacter is increasingly reported.

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

Multidrug Resistant strains Multidrug Resistant strains a Global Concerna Global Concern

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

Treating the Resistant Treating the Resistant InfectionsInfections

Colistin and Polymyxin Colistin and Polymyxin B have been used to B have been used to treat highly resistant treat highly resistant Acinetobacter Acinetobacter infections. The choice infections. The choice of appropriate therapy of appropriate therapy is further complicated is further complicated by the toxicity of by the toxicity of colistin which is mainly colistin which is mainly renal. renal. Acinetobacter Acinetobacter isolates resistant to isolates resistant to colistin and Polymyxin colistin and Polymyxin B have also been B have also been reportedreported. .

Medical interventions Medical interventions increasing the Acinetobacter increasing the Acinetobacter

InfectionsInfections Underlying diseases and severity of Underlying diseases and severity of

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

From Vietnam to IraqFrom 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 war as well.

Acinetobacter baumannii Acinetobacter baumannii Infections in Iraq warInfections in Iraq war

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

Origin of Origin of IraqibacterIraqibacter Where the Iraqibacter came from remains Where the Iraqibacter came from remains

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

( So MDRAB did exist before the Iraq War.)( So MDRAB did exist before the Iraq War.)

Can Acinetobacter Infect Can Acinetobacter Infect Health care WorkersHealth 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.

Why Dealing with A.baumani Why Dealing with A.baumani infections is problematic.infections is problematic.

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

Treatment difficult because multi-resistantTreatment difficult because multi-resistant Colonized, infected patients point- sources Colonized, infected patients point- sources

of of A. baumanniiA. baumannii infections in healthcare infections in healthcare settingssettings

Prolonged organism survival on Prolonged organism survival on environmental surfaces in hospitals environmental surfaces in hospitals contributes to protracted outbreakscontributes to protracted outbreaks

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

Standard precautionsStandard precautions in in caring Patientscaring 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.

Interventions Interventions recommended by military recommended by military

medical officialsmedical officials 1 Institution of active 1 Institution of active

surveillance of groin, surveillance of groin, axillary, and/or wound axillary, and/or wound cultures for cultures for A. A. baumanniibaumannii for all for all patients; 2) use patients; 2) use of contact precautions of contact precautions for colonized or for colonized or infected patients; and infected patients; and 3) increased availability 3) increased availability and use of alcohol-and use of alcohol-based hand rubs. based hand rubs.

Hand Hygiene is an Hand Hygiene is an Important Preventive Important Preventive

optionoption AcinetobacterAcinetobacter can live can live

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

Simple and Scientific Hand Washing Simple and Scientific Hand Washing can reduce infections with A.baumanican reduce infections with A.baumani

too too ....

Created by Dr.T.V.Rao Created by Dr.T.V.Rao MD for “ e” learningMD for “ e” learning

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