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Acinetobacter Infections in a Hospital Setting

Acinetobacter Infections in a Hospital Setting. University Medical Center-Medical Grand Rounds Las Vegas, Nevada February 17, 2006. Gonzalo Bearman MD, MPH Assistant Professor of Medicine, Epidemiology and Community Health Associate Hospital Epidemiologist Virginia Commonwealth University.

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Acinetobacter Infections in a Hospital Setting

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  1. Acinetobacter Infections in a Hospital Setting University Medical Center-Medical Grand Rounds Las Vegas, Nevada February 17, 2006 Gonzalo Bearman MD, MPHAssistant Professor of Medicine, Epidemiology and Community HealthAssociate Hospital EpidemiologistVirginia Commonwealth University

  2. Epidemiology & Prevention of Acinetobacter Infections • Microbiology • Infections: • Scope of the problem • Impact • Outbreaks • Reservoirs of Acinetobacter in the hospital • Colonization • HCWs, patients, environment • Cross transmission • Treatment of Acinetobacter infections • Limiting cross transmission of Acinetobacter • Infection control • Summary

  3. Acinetobacter • Akinetos, Greek adjective, unable to move • Bakterion, Greek noun, rod • Nonmotile rod Brisou and Prévot, 1954

  4. 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.

  5. 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. baumanii • Highly antibiotic resistant • Numerous mechanisms of resistance to β-lactams described in A. baumanii • 15 aminoglycoside-modifying enzymes described • Quinolone resistance due to mutations in DNA gyrase

  6. Hospital acquired Acinetobacter infections

  7. Major infections due to Acinetobacter • Ventilator-associated pneumonia • Urinary tract • Bloodstream infection infection • Secondary meningitis • Skin/wound infections • Endocarditis • CAPD-associated peritonitis • Ventriculitis

  8. Acinetobacter Ventilator-Associated Pneumonia • Acinetobacter accounts for 5-25% of all cases of VAP • Risk factors: • Advanced age • Chronic lung disease • Immunosuppression • Surgery • Use of antimicrobial agents • Invasive devices • Prolonged ICU stay

  9. 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

  10. Nosocomial Bloodstream Infections 49 US centers 1995-2002 N= 24,179 Wisplinghoff H, Edmond MB et al. Clin Infect Dis. 2004 Aug 1;39(3):309-17

  11. SCOPEAcinetobacter Nosocomial BSI • Incidence = 0.6/10,000 admissions • Accounts for 1.3% of all nosocomial BSI • Accounts for 1.6% of all nosocomial BSI in the ICU setting • Crude mortality: • Overall 34% • ICU 43% Despite the low incidence, the mortality is high Wisplinghoff H, Edmond MB et al. Clin Infect Dis. 2004 Aug 1;39(3):309-17

  12. Time to Nosocomial BSI Acinetobacter BSI tends to be a late onset, hospital acquired phenomenon Wisplinghoff H, Edmond MB et al. Clin Infect Dis. 2004 Aug 1;39(3):309-17

  13. Source of A. baumanii Nosocomial Bloodstream Infection Abdominal infection 19% The respiratory tract is an important reservoir for Acinetobacter bloodstream infections Central venous line 8% Respiratory tract 71% N=37 Garcia-Garmendia J-L et al. Clin Infect Dis 2001;33:939-946.

  14. Inflammatory Response to A. baumanii Nosocomial Bloodstream Infection Severe sepsis 21% Septic shock 24% Sepsis 55% N=42 Garcia-Garmendia J-L et al. Clin Infect Dis 2001;33:939-946.

  15. Independent Predictors of A. baumanii Nosocomial Bloodstream Infection No. of invasive procedure-days/number of days in ICU prior to BSI Garcia-Garmendia J-L et al. Clin Infect Dis 2001;33:939-946.

  16. Acinetobacter Meningitis • Most cases are hospital-acquired • Often associated with neurosurgical procedures • Risk factors: • Ventriculostomy • Heavy use of antibiotics in the neurosurgical ICU

  17. Impact of Acinetobacter Infection in the ICU

  18. Impact of Acinetobacter Infection in the ICU: historical cohort study 48 patients with Acinetobacter infection matched 1:1 to patients without infection Controls were matched to cases on: age (+6yrs), APACHE II (+ 4 points), admission date, principal diagnosis at ICU admission, LOS at least as long as case until isolation of AB, requirement for mechanical ventilation Garcia-Garmendia JL et al. Crit Care Med 1999;27:1794-1799.

  19. Impact of Acinetobacter Bloodstream Infection in the ICU • Historical cohort study of 45 patients with Acinetobacter bloodstream infection matched 1:2 to patients without infection • Controls were matched to cases on: APACHE II (+ 2 points), principal diagnosis at ICU admission, LOS at least as long as case until bacteremia Blot S. Intensive Care Med 2003;29:471-475.

  20. Impact of A. baumanii Ventilator-Associated Pneumonia in the ICU Historical cohort study of 60 patients with A. baumanii VAP matched 1:1 to patients without A. baumanii infection Controls were matched to cases on: age, APACHE II score, admission date, principal diagnosis, LOS at least as long as case until onset of pneumonia, chronic health status Garnacho J et al. Crit Care Med 2003;10:2478-2482.

  21. Acinetobacter outbreaks 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

  22. Acinetobacter outbreaks 1977-2000 Extensive Literature review and summary of 51 Acinetobacter outbreaks Villegas M, Hartstein A. Infect Control Hosp Epidemiol. 2003;24:284-295

  23. Acinetobacter outbreaks 1977-2000 Villegas M, Hartstein A. Infect Control Hosp Epidemiol. 2003;24:284-295

  24. Acinetobacter outbreaks 1977-2000 Villegas M, Hartstein A. Infect Control Hosp Epidemiol. 2003;24:284-295

  25. Acinetobacter outbreaks 1977-2000 Villegas M, Hartstein A. Infect Control Hosp Epidemiol. 2003;24:284-295

  26. Acinetobacter outbreaks 1977-2000 Villegas M, Hartstein A. Infect Control Hosp Epidemiol. 2003;24:284-295

  27. Reservoirs of Acinetobacter:Where do these organisms reside?

  28. Bed rails Bedside tables Ventilators Infusion pumps Mattresses Pillows Air humidifers Patient monitors X-ray view boxes Curtain rails Curtains Equipment carts Sinks Ventilator circuits Floor mops Environmental Contamination with Acinetobacter

  29. Factors Promoting Transmission of 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

  30. 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 Simor AE et al. Infect Control Hosp Epidemiol 2002;23:261-267.

  31. Evidence for Airborne Transmission of Acinetobacter • Sedimentation plates placed in 7 patients’ rooms with respiratory infection or colonization % of plates growing Acinetobacter Brooks SE et al. Infect Control Hosp Epidemiol 2000;21:304.

  32. Acinetobacter spp Skin Colonization Seifert H et al. J Clin Microbiol 1997;35:2819-2825. A. baumanii isolated from 2 patients & 1 control only

  33. Acinetobacter Transmission in the Hospital SettingColonization of Healthcare Workers • Outbreak of multidrug resistant A. baumanii 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) Wagenvoort JHT et al. Eur J Clin Microbiol Infect Dis 2002;21:326-327.

  34. Hand Contamination in HCWs % of HCWs (n=328) with hand contamination Bauer TM et al. J Hosp Infect 1990;15:301-309.

  35. Opportunities for cross transmission are multiple

  36. Treatment of Acinetobacter infections

  37. Acinetobacter Susceptibility, US, 2002-2003 % susceptible Increasing rate of antibiotic resistance TSN Database. http://www.geis.ha.osd.mil/GEIS/SurveillanceActivities/AntimicrobialResistance/AcinetobacterGraphs.htm

  38. Antibiotic ResistanceCommunity vs. Hospital Acquisition • Comparison of A. baumanii isolates obtained from the hands of homemakers to isolates obtained from 2 US hospitals • 23/222 (10.4%) homemakers had A.baumanii isolated from hands *3rd gen. cephalosporins + carbapenem + aminoglycoside Zeana C. Infect Control Hosp Epidemiol 2003;24:275-279.

  39. Polymyxin antibiotics • A group of polypeptide antibioticsthat consists of 5chemically different compounds (polymyxinsA E). • Only polymyxinB and polymyxin E(colistin) have been usedin clinically. • Intravenous colistin should beconsidered for the treatmentof infections caused bygram-negative bacteria resistant toother available antimicrobial agents,confirmed by appropriate invitro susceptibility testing

  40. Polymyxin antibiotics: • History • Used extensivelyworldwide in topical oticand ophthalmic solutions fordecades • Intravenous Colistin wasinitially used inJapan and in Europeduring the 1950s, andin the United Statesin the form ofcolistimethate sodium in 1959 • The intravenousformulations of colistin andpolymyxin B were graduallyabandoned in most partsof the world inthe early 1980s becauseof the reported highincidence of nephrotoxicity • Colistin was mainlyrestricted during the past2 decades for thetreatment of lung infectionsdue to multidrug-resistant (MDR),gram-negative bacteria in patientswith cystic fibrosis

  41. Polymyxin antibiotics colistin sulfate: oral, used for bowel decontamination colistimethatesodium: (also called colistinmethanesulfate, pentasodium colistimethanesulfate, andcolistin sulfonyl methate)- Intravenous formulation Clinical Infectious Diseases 2005;40:1333-1341

  42. Polymyxin antibiotics • Mechanism of action: • Target: • Bacterial cellmembrane • Colistin binding with thebacterial membrane occurs throughelectrostatic interactions between thecationic polypeptide (colistin) andanionic lipopolysaccharide (LPS) moleculesin the outer membraneof the gram-negative bacteria • leads to a derangement ofthe cell membrane • The resultof this isan increase in thepermeability of the cellenvelope, leakage of cellcontents, and, subsequently, celldeath.

  43. Polymyxin antibiotics Sectionsof a Pseudomonas aeruginosa strainshowing the alterations inthe cell following theadministration of polymyxin B(25 g/mL for 30min) and colistin methanesulfate(250 g/mL for 30min). A: untreatedcell; B: cell treatedwith polymyxin C:cell treated with colistinmethanesulfate; D: cell treatedwith polymyxin B at highermagnification.= 0.1 m Clinical Infectious Diseases 2005;40:1333-1341

  44. Polymyxin antibiotics • Development of Resistance • Resistanceto colistin occurs through mutationor adaptation mechanisms • Almost complete cross-resistanceexists between colistin andpolymyxin B

  45. Polymyxin antibiotics • Important pharmacokinetic parameters • Colistinsulfate and colistimethate sodiumare not absorbed bythe gastrointestinal tract withoral administration • Primary routeof excretion is throughglomerular filtration • Experimental studieshave shown that colistinis tightly bound tomembrane lipids of tissues,including liver, lung, kidney,brain, heart, and muscles • Concentration of colistinin the CSF is 25% of the serumconcentration

  46. Polymyxin antibiotics • Spectrum of activity • Mostgram-negative aerobic bacilli: • Acinetobacter species, P. aeruginosa, Klebsiella species,Enterobacter species, Escherichia coli, Salmonella species,Shigella species, Citrobacter species,Yersinia pseudotuberculosis, Morganella morganii, and Haemophilus influenzae • No activity against: • Pseudomonas mallei, Burkholderia cepacia, Proteus species,Providencia species, Serratia species,Edwardsiella species, and Brucella

  47. Polymyxin antibiotics • Susceptibility testing: • Disk diffusion- Colistin • Disk diffusion method thatuses a 10-ug colistinsulfate disk • Isolatesis susceptible ifthe zone of inhibitionis >11 mm • Dilution method- colistimethate sodium • TheMIC break pointfor susceptibility is <4 mg/L • If the MIC is >8 mg/L, the isolateshould be considered resistant

  48. Polymyxin antibiotics

  49. Polymixin adverse effects

  50. Polymixin adverse effects

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