Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of.pdf
Acinetobacter infection : Epidemiology & clinical manifestations.
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Transcript of Acinetobacter infection : Epidemiology & clinical manifestations.
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Acinetobacter infection : Epidemiology & clinical
manifestations
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CONTENTS
• Historical aspects• Classification• Epidemiology• Risk factors and clinical manifestations• Laboratory diagnosis• Prevention• Treatment• Future therapeutic strategies
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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
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Acinetobacter
• Akinetos, Greek adjective, unable to move• Bakterion, Greek noun, rod• Non-motile rod
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Scientific ClassificationKingdom Bacteria
Phylum Proteobacteria
Class Gammaproteobacteria
Order Pseudomonadales
Family Moraxellaceae
Genus Acinetobacter
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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
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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
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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
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EPIDEMIOLOGY
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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
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Hospital acquired Acinetobacter infection
82.9%
Community acquired Acinetobacter infection
17.1%
Col K K Lahiri et al.,AFMC, Pune 2004
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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
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HOSPITAL ACQUIRED ACINETOBACTER
INFECTIONS
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ENVIRONMENTAL FACTORS
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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• 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
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Clinical Manifestations
• Ventilator-associated pneumonia • Urinary tract infections• Bloodstream infection• Secondary meningitis• Ventriculitis• Skin/wound infections• Endocarditis• CAPD-associated peritonitis• Cholangitis• Osteomyelitis
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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
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Bloodstream Infections
Predisposing factors:– Malignancy– Trauma– Burns– Surgical wound infections– Neonates
• Low birth weight• Need for mechanical ventilation• Presence of neonatal convulsions
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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
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Acinetobacter Meningitis
• Most cases are hospital-acquired• Associated with neurosurgical procedures• Risk factors:
– Ventriculostomy– Heavy use of antibiotics in neurosurgical ICU
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Acinetobacter UTI• Pre-disposing factors
– Elderly debilitated patients– Patients confined to ICUs– Patients with permanent indwelling catheters
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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
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LAB DIAGNOSIS
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Specimens
• Sputum• ET Aspirate• BAL• Pleural fluid• Urine • CSF• Blood• Pus• Peritoneal fluid• Wound swabs
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Growth characteristics
Blood agar : 0.5 - 2 mm in diameter, translucent to opaque, convex, smooth surface and entire margins
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MacConkey agar : non lactose fermenting colonies
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MICROSCOPY
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Gram’s Stain – gram negative coccobacillus
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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
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PREVENTION
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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
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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.
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TREATMENTA. baumannii is one of the “Red Alert”
pathogens
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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
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Novel combinations showing enhanced activity
1. Colistin + Imipenem
2. Colistin + Rifampin
3. Colistin + Rifampin + Imipenem
4. Rifampin + Azithromycin
5. Sulbactam + Rifampin + Azithromycin/Quinolones
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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
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DRUG RESISTANCE
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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 )