Acinetobacter infection : Epidemiology & clinical

manifestations

CONTENTS

• Historical aspects• Classification• Epidemiology• Risk factors and clinical manifestations• Laboratory diagnosis• Prevention• Treatment• Future therapeutic strategies

HISTORICAL ASPECTS

• In 1911,Beijerinck described an organism named Micrococcus calcoaceticus, isolated from soil by enrichment in a calcium-acetate containing minimal medium

• In the following decades, similar organisms were described and assigned to at least 15 different genera and species

• In 1954, Brisou and Prevot proposed the current genus, Acinetobacter

Acinetobacter

• Akinetos, Greek adjective, unable to move• Bakterion, Greek noun, rod• Non-motile rod

Scientific ClassificationKingdom Bacteria

Phylum Proteobacteria

Class Gammaproteobacteria

Order Pseudomonadales

Family Moraxellaceae

Genus Acinetobacter

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

– Sometimes difficult to decolorize• Frequently arranged in pairs

Bergogne-Bérézin E, Towner KJ. Clin Microbiol Rev 1996;9:148-165.

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

– Sometimes difficult to decolorize• Frequently arranged in pairs

Species of clinical significance• A.baumannii – most common species associated with

nosocomial infections• A.lwoffii – more commonly associated with secondary

meningitis • A.ursingii – associated with blood stream infections• A.junii – rare cause of ocular infection & bacteremia,

esp. in pediatric patients• A.radioresistens, A.johnsonii and A.lwoffii – natural

inhabitants of human skin and commensals in oropharynx and vagina

VIRULENCE FACTORS

• Lipopolysaccharide component of cell wall • Exopolysaccharide production

– Biofilm formation – Protect bacteria from host defenses

• Lipid A• Endotoxins • OMP for the induction of apoptosis• Fimbriae • Enzyme production to damage tissue lipids• Siderophore mediated iron acquisition systems

EPIDEMIOLOGY

Natural habitats

• Ubiquitous: Widely distributed in nature – soil– water– food– sewage– hospital environment

• Survive for weeks on dry surfaces

• In humans, Acinetobacter sp. can colonize skin, wounds, respiratory tract & GIT, with some species as commensals in oropharynx and vagina

Hospital acquired Acinetobacter infection

82.9%

Community acquired Acinetobacter infection

17.1%

Col K K Lahiri et al.,AFMC, Pune 2004

Continued….

• Most common nosocomial infections a/w Acinetobacter baumannii – Ventilator associated pneumonia and blood stream infections

• Acinetobacter was isolated from various types of nosocomial infections such as respiratory tract infections (48.8%), BSI’s (16.27%), secondary meningitis (14%), UTI (9.3%) etc.( Prashanth K et al, JIPMER 2005)

• Nosocomial infections caused by other Acinetobacter sp., such as A. johnsonii, A. junii, A. parvus, A. radioresistens, A. schindleri and A. ursingii, are rare and are mainly restricted to catheter-related bloodstream infections

HOSPITAL ACQUIRED ACINETOBACTER

INFECTIONS

ENVIRONMENTAL FACTORS

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

Factors Promoting Transmission of Acinetobacter

in the ICU• Frequent contamination of the hands of healthcare

workers• Long survival time on inanimate surfaces• Extensive environmental contamination• Airborne transmission via aerosol production• High antibiotic & disinfectant resistance• High proportion of colonized patients

Clinical Manifestations

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

Ventilator-Associated Pneumonia

• A. baumannii a/w 41.8% of all pneumonias acquired in ICU (K Prashanth et al. JIPMER 2005)

• Risk factors: – Advanced age– Chronic lung disease– Immunosuppression– Surgery– Excessive use of antimicrobial agents– Invasive devices– Prolonged ICU stay

Bloodstream Infections

Predisposing factors:– Malignancy– Trauma– Burns– Surgical wound infections– Neonates

• Low birth weight• Need for mechanical ventilation• Presence of neonatal convulsions

Source of A. baumanii Nosocomial Bloodstream Infection

Respiratory tract71%

Abdominal infection 19%

Central venous line 8%

The respiratory tract is an important reservoir for Acinetobacter BSI

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

Acinetobacter Meningitis

• Most cases are hospital-acquired• Associated with neurosurgical procedures• Risk factors:

– Ventriculostomy– Heavy use of antibiotics in neurosurgical ICU

Acinetobacter UTI• Pre-disposing factors

– Elderly debilitated patients– Patients confined to ICUs– Patients with permanent indwelling catheters

Community acquired Acinetobacter infection

• Mostly common in tropical and subtropical countries

• Pneumonia > bacteremia (Falagas et al.2007)

• Risk factors– COPD– Renal disease– Diabetes mellitus– Smoking & alcohol abuse

• MDR strains uncommon

LAB DIAGNOSIS

Specimens

• Sputum• ET Aspirate• BAL• Pleural fluid• Urine • CSF• Blood• Pus• Peritoneal fluid• Wound swabs

Growth characteristics

Blood agar : 0.5 - 2 mm in diameter, translucent to opaque, convex, smooth surface and entire margins

MacConkey agar : non lactose fermenting colonies

MICROSCOPY

Gram’s Stain – gram negative coccobacillus

Biochemical reactions

• Acid production without gas with glucose (oxidatively by members of A.calcoaceticus – baumannii complex)

• Non fermentative• Oxidase -ve• Nitrate -ve• Catalase +ve• Citrate +ve• Urease -ve• Gelatin hydrolysis -ve• Growth at 37oC,41oC and 44oC• Assimilation test for 14 different carbon sources

PREVENTION

Preventing Acinetobacter Transmission in the ICU

General measures• Hand hygiene

– Use of alcohol-based hand sanitizers• Contact precautions

– Gowns/gloves– Disinfect machines and other materials in use by the

patient regularly• Environmental decontamination• Prudent use of antibiotics• Avoidance of transfer of patients to Burn Unit

from other ICUs

Efficacy of Hand washing Agents against Acinetobacter

Experimental study to access removal of A. baumanii from the hands of volunteers

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

Agent

Removal Rate

Light contamination Heavy contamination

Plain 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.

TREATMENTA. baumannii is one of the “Red Alert”

pathogens

Empirical Therapy

 Carbapenems

(imipenem or meropenem)

or    

β-Lactam/ β-lactamase inhibitor

Acinetobacter infection

(piperacillin–tazobactam)

plus    

Antipseudomonal Fluoroquinolones   

(ciprofloxacin or levofloxacin)

or    

Aminoglycoside

(amikacin, gentamicin, or tobramycin)

(2005 , American Thoracic Society )

Treatment

Novel combinations showing enhanced activity

1. Colistin + Imipenem

2. Colistin + Rifampin

3. Colistin + Rifampin + Imipenem

4. Rifampin + Azithromycin

5. Sulbactam + Rifampin + Azithromycin/Quinolones

 

TIGECYCLINE

• 9-t-butylglycylamido semi-synthetic derivative of Minocycline

• Inhibits 30S ribosomal subunit • Evades determinants of tetracycline resistance

i.e. tet (A) to tet (E) and tet (K) efflux pumps and tet (M) and tet (O) determinants that provide ribosomal protection

• Not recommended A. baumannii bacteremia• Gets concentrated in tissues, clinical efficacy

under evaluation for tissue based infections• Most common side effect - Nausea

DRUG RESISTANCE

Some definitions

• MDR: “Multi-drug resistant strains” are resistant to at least 2 classes of the following 5 drug classes:1. Antipseudomonal cephalosporins2. Antipseudomonal carbapenems3. β-lactam+ β- lactamase inhibitor4. Fluoroquinolones5. Aminoglycosides

• XDR: “Extensively drug resistant strains” are resistant to all standard antimicrobial agents tested except colistin

• PDR: “Pan-drug resistant strains” are resistant to all

commercially available antimicrobial drugs, including colistin

( Clin Microbiol Rev, July 2008.p538-582 )

( ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 2009, p. 1295–1296 )