1. Acinetobacter infection : Epidemiology & clinical manifestations

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

3. 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

4. Acinetobacter Akinetos, Greek adjective, unable to move Bakterion, Greek noun, rod Non-motile rod

5. Scientific Classification Kingdom Bacteria Phylum Proteobacteria Class Gammaproteobacteria Order Pseudomonadales Family Moraxellaceae Genus Acinetobacter

6. 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

7. 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

8. 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

9. EPIDEMIOLOGY

10. 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

11. Hospital acquired Acinetobacter infection 82.9% Community acquired Acinetobacter infection 17.1% Col K K Lahiri et al.,AFMC, Pune 2004

12. 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

13. HOSPITAL ACQUIRED ACINETOBACTER INFECTIONS

14. ENVIRONMENTAL FACTORS

15. 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

16. 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

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

18. 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

19. Bloodstream Infections Predisposing factors: –Malignancy –Trauma –Burns –Surgical wound infections –Neonates Low birth weight Need for mechanical ventilation Presence of neonatal convulsions

20. Source of A. baumanii Nosocomial Bloodstream Infection Respiratory tract 71% 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

21. Acinetobacter Meningitis Most cases are hospital-acquired Associated with neurosurgical procedures Risk factors: –Ventriculostomy –Heavy use of antibiotics in neurosurgical ICU

22. Acinetobacter UTI Pre-disposing factors –Elderly debilitated patients –Patients confined to ICUs –Patients with permanent indwelling catheters

23. 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

24. LAB DIAGNOSIS

25. Specimens Sputum ET Aspirate BAL Pleural fluid Urine CSF Blood Pus Peritoneal fluid Wound swabs

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

27. MacConkey agar : non lactose fermenting colonies

28. MICROSCOPY

29. Gram’s Stain – gram negative coccobacillus

30. 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 37 o C,41 o C and 44 o C Assimilation test for 14 different carbon sources

31. PREVENTION

32. 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 patientregularly Environmental decontamination Prudent use of antibiotics Avoidance of transfer of patients to Burn Unit from other ICUs

33. Efficacy of Hand washing Agents against Acinetobacter Experimental study to access removal of A. baumanii from the hands of volunteers Fingertips inoculated with either 10 3 CFU (light contamination) or 10 6 CFU (heavy contamination) Agent Removal Rate Light contaminationHeavy 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.

34. TREATMENT A. baumannii is one of the “Red Alert” pathogens

35. 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

36. Novel combinations showing enhanced activity 1.Colistin + Imipenem 2.Colistin + Rifampin 3.Colistin + Rifampin + Imipenem 4.Rifampin + Azithromycin 5.Sulbactam + Rifampin + Azithromycin/Quinolones

37. 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

38. DRUG RESISTANCE

39. Some definitions MDR: “Multi-drug resistant strains” are resistant to at least 2 classes of the following 5 drug classes: 1. Antipseudomonal cephalosporins 2. Antipseudomonal carbapenems 3. β-lactam+ β- lactamase inhibitor 4. Fluoroquinolones 5. 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 )