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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

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

epidemiology prevention of acinetobacter infections
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
acinetobacter
Acinetobacter
  • Akinetos, Greek adjective, unable to move
  • Bakterion, Greek noun, rod
  • Nonmotile rod

Brisou and Prévot, 1954

microbiology
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.

microbiology5
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
major infections due to acinetobacter
Major infections due to Acinetobacter
  • Ventilator-associated pneumonia
  • Urinary tract
  • Bloodstream infection infection
  • Secondary meningitis
  • Skin/wound infections
  • Endocarditis
  • CAPD-associated peritonitis
  • Ventriculitis
acinetobacter ventilator associated pneumonia
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
acinetobacter bloodstream infection
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
nosocomial bloodstream infections
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

scope acinetobacter nosocomial bsi
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

time to nosocomial bsi
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

source of a baumanii nosocomial bloodstream infection
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.

inflammatory response to a baumanii nosocomial bloodstream infection
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.

independent predictors of a baumanii nosocomial bloodstream infection
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.

acinetobacter meningitis
Acinetobacter Meningitis
  • Most cases are hospital-acquired
  • Often associated with neurosurgical procedures
  • Risk factors:
    • Ventriculostomy
    • Heavy use of antibiotics in the neurosurgical ICU
impact of acinetobacter infection in the icu historical cohort study
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.

impact of acinetobacter bloodstream infection in the icu
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.

impact of a baumanii ventilator associated pneumonia in the icu
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.

acinetobacter outbreaks
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

acinetobacter outbreaks 1977 2000
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

acinetobacter outbreaks 1977 200023
Acinetobacter outbreaks 1977-2000

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

acinetobacter outbreaks 1977 200024
Acinetobacter outbreaks 1977-2000

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

acinetobacter outbreaks 1977 200025
Acinetobacter outbreaks 1977-2000

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

acinetobacter outbreaks 1977 200026
Acinetobacter outbreaks 1977-2000

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

environmental contamination with acinetobacter
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
factors promoting transmission of of acinetobacter in the icu
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
acinetobacter transmission in the hospital setting
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.

evidence for airborne transmission of acinetobacter
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.

acinetobacter spp skin colonization
Acinetobacter spp Skin Colonization

Seifert H et al. J Clin Microbiol 1997;35:2819-2825.

A. baumanii isolated from 2 patients & 1 control only

acinetobacter transmission in the hospital setting colonization of healthcare workers
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.

hand contamination in hcws
Hand Contamination in HCWs

% of HCWs (n=328) with hand contamination

Bauer TM et al. J Hosp Infect 1990;15:301-309.

acinetobacter susceptibility us 2002 2003
Acinetobacter Susceptibility, US, 2002-2003

% susceptible

Increasing rate of antibiotic resistance

TSN Database. http://www.geis.ha.osd.mil/GEIS/SurveillanceActivities/AntimicrobialResistance/AcinetobacterGraphs.htm

antibiotic resistance community vs hospital acquisition
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.

polymyxin antibiotics
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
polymyxin antibiotics40
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
polymyxin antibiotics41
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

polymyxin antibiotics42
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.
polymyxin antibiotics43
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

polymyxin antibiotics44
Polymyxin antibiotics
  • Development of Resistance
    • Resistanceto colistin occurs through mutationor adaptation mechanisms
    • Almost complete cross-resistanceexists between colistin andpolymyxin B
polymyxin antibiotics45
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
polymyxin antibiotics46
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
polymyxin antibiotics47
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
preventing acinetobacter transmission in the icu general measures
Preventing Acinetobacter Transmission in the ICUGeneral Measures
  • Hand hygiene
    • Use of alcohol-based hand sanitizers
  • Contact precautions
    • Gowns/gloves
    • Dedicate non-critical devices to patient room
  • Environmental decontamination
  • Prudent use of antibiotics
  • Avoidance of transfer of patients to Burn Unit from other ICUs
preventing acinetobacter transmission in the icu outbreak interventions
Preventing Acinetobacter Transmission in the ICUOutbreak Interventions
  • Hand cultures
  • Surveillance cultures
  • Environmental cultures following terminal disinfection to document cleaning efficacy
  • Cohorting
  • Ask laboratory to save all isolates for molecular typing
  • Healthcare worker education
  • If transmission continues despite above interventions, closure of unit to new admissions
efficacy of handwashing agents against acinetobacter
Efficacy of Handwashing Agents against Acinetobacter
  • Experimental study to access removal of A. baumanii from the hands of volunteers
    • Fingertips inoculated with with either 103 CFU (light contamination) or 106 CFU (heavy contamination)

Cardoso CL et al. Am J Infect Control 1999;27:327-331.

in vitro activity of alcohol hand rubs
In Vitro Activity of Alcohol Hand Rubs
  • Each agent diluted 1/10 & tested against a strain of A. baumanii resistant to 3rd generation cephalosporins

Rochon-Edouard S et al. Am J Infect Control 2004;32:200-204.

chlorhexidine resistance in acinetobacter
Chlorhexidine Resistance in Acinetobacter
  • Biocide resistance in gram-negative organisms is mainly intrinsic & chromosomal (plasmid mediated in gram-positive organism)
  • 10 strains of A. baumanii tested for chlorhexidine susceptibility
    • Median MIC 32 mg/L
    • Median MBC 32 mg/mL
    • Chlorhexidine resistance increased with increased antibiotic resistance

Kõljalg S et al. J Hosp Infect 2002;51:106-113.

summary
Summary
  • Although commonly found on the skin of healthy humans, Acinetobacter plays the role of an opportunistic pathogen in the critically ill patient
  • High level of antibiotic resistance makes it well suited as a pathogen in areas with high use of antibiotics (e.g., ICU setting)
  • Control requires good hand hygiene, barrier precautions & environmental decontamination
    • Alcohol-based products containing chlorhexidine should be considered the hand hygiene agents of choice