Why are Acinetobacter and Pseudomonas so antibiotic resistant?. Robert A. Bonomo, MD Chief, Medical Service Director VISN 10 GRECC Louis Stokes Cleveland VAMC Vice Chairman, Department of Medicine University Hospitals Case Medical Center
Why are Acinetobacter and Pseudomonas so antibiotic resistant?
Robert A. Bonomo, MD
Chief, Medical Service
Director VISN 10 GRECC
Louis Stokes Cleveland VAMC
Vice Chairman, Department of Medicine
University Hospitals Case Medical Center
Professor, Case Western Reserve University School of Medicine
MDR and PDR Ab
Multi-Drug Resistant (MDR) A. baumanniiare among the most “problematic pathogens” encountered by clinicians
Acinetobacter has evolved many molecular strategies to escape ALL ANTIBIOTICS that resemble more the tactics of organized crime than traditional warfare
“The Resistance Island”
86 Kb, 88 orfs, 82 orfs from another source and 45 resistance genes
Fournier et al., PLoS Genet. 2006 Jan;2(1):e7. Epub 2006 Jan 13.
Poirel et al AAC 2010
The resistance challenge of the ages
Back to school: mechanism of action
Mechanisms of resistance
Do we have enough patients studied properly? Animal models may have (significant) limitations?
Colistin is King???
“Efficacy rate” of 57-76% in IV form; “microbiological eradication” of 67-90.9%Renal tox 0-37%
Nebulizedcolistin (CF studies + others) effective; FDA warning; impact of shift to more resistant strains ; use with IV!!
32+ cases “microbiological eradication” in the CNS with ITh/IVecolistin (safe e 1) (2.5 mg/kg, 10-20 mg ITh)
Colistin was independently associated with higher mortality vs. treatment with sulbactam in patients with A. b infections
Rapid resistance can emerge;
Cases of breakthrough bacteremia reported;
Adequacy of blood levels??
Major concerns…real ?
Pachon and Vila Curr Opin Investig Drugs. 2009 Feb;10(2):150-6.
Giamarellou & Poulakou, Drugs. 2009
Michalopoulos A, Falagas ME.
Expert Opin Pharmacother.
bacteremic patients treated with tige failed to clear their bacteremia 10-fold more commonly
than patients treated with comparator drugs
Gordon JAC 2009, Gardiner CID
Colistin and vanco??
The worst case scenario?
Extraordinary challenge against cunning pathogens
Basic understanding of molecular biology is needed (the complexities of resistance genes will only increase)
Research is needed in therapeutics and infection control
CALL TO ARMS: Coordinate scientific and clinical trials to answer these important questions