Evaluation Of Acinetobacter Infection, Eastern States Presentation

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Presentation of original reseach completed during PGY1 residency at VCU Health System

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  • Talk about genus and species, acinetobacter calcoaceticus and baumannii
  • β -lactamase & ESBL production β -lactams, cephalosporins, carbapenems Alteration in porin structure carbapenems Overexpression of efflux pumps β -lactams, quinolones, tetracyclines, chloramphenicol, tigecycline, aminoglycosides, trimethoprim
  • Rationale: Infections with Acinetobacter have become problematic at MCVH MDR Acinetobacter infections have resulted in: Prolonged exposure to ineffective antibiotics Increased length of treatment and hospital stay Increased occurrence of adverse reactions, including renal failure
  • Antimicrobial Drug Therapy: Antimicrobial Therapy Drug Dose Duration Dosage formulation Alteration due to C&S results Monotherapy vs. Combination Therapy Presence of Adverse Effects SCr ( ≥2x baseline) and/or BUN ( ≥2x baseline) within 1 week of initiation of therapy
  • Evaluation Of Acinetobacter Infection, Eastern States Presentation

    1. 1. Evaluation of Acinetobacter Infection Sarah Nelson, Pharm.D. Pharmacy Practice Resident
    2. 2. Acinetobacter <ul><li>Non-fermenting, non-motile, aerobic gram negative coccobacilli </li></ul><ul><li>Isolated from soil, water, animals, and humans </li></ul><ul><li>Colonizes on inanimate objects with high stability </li></ul><ul><ul><ul><li>Ventilators, mattresses, pillows, bed rails, urine collection jugs, IV equipment, nebulizers, etc. </li></ul></ul></ul>Giamarellou, H. et al. Acinetobacter baumannii: a universal threat to public health? International Journal of Antimicrobial Agents.2008;32:106-119
    3. 3. Clinical Manifestations <ul><li>Pulmonary </li></ul><ul><li>Bacteremia </li></ul><ul><li>Skin & skin structure infections </li></ul><ul><li>Urinary tract infections </li></ul><ul><li>Post surgical meningitis </li></ul>Giamarellou, H. et al. Acinetobacter baumannii: a universal threat to public health? International Journal of Antimicrobial Agents.2008;32:106-119
    4. 4. Mechanisms of Resistance Munoz-Price, L. et al. Acinetobacter Infection. N Engl J Med. 2008;358(12):1271-81
    5. 5. Current Treatment Options <ul><ul><li>Sulbactam based β -lactams </li></ul></ul><ul><ul><li>Carbapenems </li></ul></ul><ul><ul><li>Tigecycline </li></ul></ul><ul><ul><li>Colistin </li></ul></ul>
    6. 6. Background <ul><li>29 critically ill patients with pneumonia or bacteremia causes by MDR Acinetobacter baumanii </li></ul><ul><ul><li>Treatment: IV Colistin (2 million IU three times daily) PLUS IV rifampicin (10mg/kg every 12 hours) </li></ul></ul><ul><ul><li>Mean duration of treatment: 17.6 days (+/- 10.4) </li></ul></ul><ul><ul><li>Clinical & microbiological response: 76% (22 pts) </li></ul></ul><ul><ul><li>Infection-related mortality: 21% (6 pts) </li></ul></ul><ul><ul><li>Nephrotoxicity: 10% (3 pts) </li></ul></ul>Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections. J Antimicrob Chemother. 2008;61(2):417-420
    7. 7. Background Kwon, KT et al. Impact of imipenem resistance on mortality in patients with Acinetobacter bacteremia. J antimicrob Chemother . 2007;59:525-530 <ul><li>Higher 30 day mortality with: </li></ul><ul><ul><li>MDR strain of Acinetobacter caused infection (57.5% vs. 27.5%) </li></ul></ul><ul><ul><li>Inappropriate empiric treatment was utilized (60% vs. 20%) </li></ul></ul>
    8. 8. Objectives <ul><li>Characterize the extent of Acinetobacter infection at VCUHS </li></ul><ul><li>Identify common treatment regimens currently utilized at VCUHS </li></ul><ul><li>Delineate adverse effects associated with the most utilized treatment regimens </li></ul><ul><li>Provide education regarding selection of treatment regimen if deemed necessary </li></ul>
    9. 9. Methods <ul><li>Retrospective </li></ul><ul><ul><li>July 1, 2007- July 31, 2008 </li></ul></ul><ul><li>Quality Improvement Project </li></ul><ul><li>IRB Approval, expedited </li></ul>
    10. 10. Patients <ul><li>Inclusion Criteria </li></ul><ul><ul><li>Adults ( ≥18 years of age) </li></ul></ul><ul><ul><li>≥ 1 positive culture of Acinetobacter calcoaceticus-baumannii complex </li></ul></ul><ul><ul><li>Received antimicrobial treatment for ≥ 2 days </li></ul></ul><ul><li>Exculsion Criteria </li></ul><ul><ul><li>Infection with other species of Acinetobacter </li></ul></ul><ul><ul><ul><li>A. lwoffii </li></ul></ul></ul><ul><ul><ul><li>Undifferentiated specimens </li></ul></ul></ul>
    11. 11. Data Collection <ul><li>Demographics </li></ul><ul><li>Specimen information </li></ul><ul><ul><ul><li>Source, sensitivities </li></ul></ul></ul><ul><li>Antimicrobial Therapy </li></ul><ul><ul><ul><li>Empiric & final drug therapy </li></ul></ul></ul><ul><li>Adverse Reactions </li></ul><ul><ul><ul><li>Serum Creatinine & BUN </li></ul></ul></ul>
    12. 12. Data Collection <ul><li>Efficacy Outcomes </li></ul><ul><ul><li>Favorable vs. unfavorable response </li></ul></ul><ul><ul><ul><li>Favorable: </li></ul></ul></ul><ul><ul><ul><ul><li>Signs & symptoms resolved within 48 hours of end of therapy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Negative repeat culture </li></ul></ul></ul></ul><ul><ul><ul><li>Unfavorable: </li></ul></ul></ul><ul><ul><ul><ul><li>Signs & symptoms persisted >48 hours after therapy ended </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Required additional antibiotic therapy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Positive repeat culture </li></ul></ul></ul></ul>
    13. 13. Statistical Analyses <ul><li>Descriptive statistics were used to describe variables </li></ul><ul><li>Chi-squared test was used to identify significant outcomes </li></ul><ul><li>Logistic regression was used to determine independent risk factors for favorable outcomes </li></ul>
    14. 14. Study Subjects <ul><li>207 patients with ≥ 1 positive culture for Acinetobacter calcoaceticus-baumannii complex </li></ul><ul><ul><li>83 patients excluded </li></ul></ul><ul><ul><ul><li>Other species </li></ul></ul></ul><ul><ul><ul><li><18 years old </li></ul></ul></ul><ul><ul><ul><li>Outpatients </li></ul></ul></ul><ul><ul><ul><li>23 hour observation </li></ul></ul></ul><ul><ul><li>12 charts not available </li></ul></ul><ul><li>112 patients included in study </li></ul>
    15. 15. Demographics 22 (20%) >1 source of Acinetobacter 2.6 2.5 2.5 Days to positive culture 32 27.5 28.5 LOS (days) 57.1 51.4 52.6 Age (years) 20 (59%) 38 (50%) 59 (53%) Male Unfavorable Outcome (n= 34) Favorable Outcome (n=76) Overall (n=112)
    16. 16. Source of Infection
    17. 17. Locality of Infection
    18. 18. Rates of Resistance 0% --- Colistin 31% --- Tigecycline 70% 48% Piperacillin/Tazobactam 64% 50% TMP/SMX 56% 31% Imipenem 68% 58% Gentamicin 76% 65% Ciprofloxacin 74% 60% Cefepime 72% --- Amikacin Study Group 2007 Antibiogram Antimicrobial
    19. 19. Empiric Therapy <ul><li>Appropriate empiric therapy is associated with a favorable outcome (p<0.0001) </li></ul><ul><li>29 patients (26%) were treated with appropriate empiric therapy </li></ul><ul><ul><li>28 (97%) had a favorable outcome </li></ul></ul><ul><li>Inappropriate empiric therapy accounts for 33 of the 34 unfavorable outcomes (97%) </li></ul><ul><li>17% of patients were not started on empiric antimicrobial therapy </li></ul>
    20. 20. Tailored Antimicrobial Therapy <ul><li>Appropriate tailored therapy is associated with a favorable outcome (p<0.0001) </li></ul><ul><li>79 (72%) patients were treated with appropriate antimicrobial therapy </li></ul><ul><ul><li>65 (82%) patients had a favorable outcome </li></ul></ul><ul><li>Average duration of tailored antimicrobial therapy was 12.4 days </li></ul><ul><li>Most common final antimicrobial therapy included imipenem (18), colistin (17), tigecycline (12), & piperacillin/tazobactam (10) </li></ul><ul><ul><li>14 patients were treated with combination therapy </li></ul></ul>
    21. 21. Colistin <ul><li>17 patients were treated with colistin </li></ul><ul><ul><li>Never used as empiric therapy </li></ul></ul><ul><ul><li>Used as monotherapy in 9 (53%) patients </li></ul></ul><ul><ul><li>Most commonly used with tigecycline for combination therapy </li></ul></ul><ul><li>Intravenous route most common; inhalation also utilized for respiratory infections </li></ul><ul><li>3 (18%) patients experienced an increase in serum creatinine & 4 (25%) patients experienced an increase in BUN </li></ul>
    22. 22. Limitations <ul><li>Retrospective analysis </li></ul><ul><ul><li>Documentation of assessment and plan </li></ul></ul><ul><li>Evaluation of only Acinetobacter calcoaceticus-baumannii complex </li></ul><ul><li>Withdrawl of care promoted an unfavorable endpoint </li></ul>
    23. 23. Conclusion <ul><li>Selection of correct empiric antimicrobial therapy is necessary for a favorable outcome </li></ul><ul><li>No independent risk factors exist that demonstrate a favorable outcome </li></ul><ul><li>Nosocomial strains of Acinetobacter calcoaceticus-baumannii complex exhibit increased resistance to common antimicrobials </li></ul><ul><li>Colistin is an effective and safe antimicrobial with 100% susceptibility to the MDR Acinetobacter baumanii-calcoaceticus complex </li></ul>

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