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Objectives. Review emerging multidrug resistant gram negative organisms Describe their relevance to infection prevention and controlIdentify current challenges in infection prevention response. The Impact of Antimicrobial- Resistant Gram-Negative Infections . Resistance to antimicrobial agents is
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1. Pesky Gram Negatives: Just When You Thought It Couldn’t Get Worse Ruth Carrico PhD RN CIC
Assistant Professor
School of Public Health and Information Sciences
University of Louisville
ruth.carrico@louisville.edu
2. Objectives Review emerging multidrug resistant gram negative organisms
Describe their relevance to infection prevention and control
Identify current challenges in infection prevention response
3. The Impact of Antimicrobial-Resistant Gram-Negative Infections
Resistance to antimicrobial agents is increasing among many gram-negative pathogens
Infection with resistant pathogens is associated with negative health outcomes
Mortality/morbidity
Length of ICU and hospital stay
Healthcare costs
Few antibiotic choices remain
Highlights the need to optimize existing classes of antimicrobials through stewardship and infection prevention
4. Resistance Impact Over past decade, CDC has documented downward trend in infection rates in four major anatomic sites:
Bloodstream
Respiratory tract
Urinary tract
Wounds
At same time, infection rates due to resistant pathogens are increasing
5. Multi-Drug Resistant Gram Negative Rods (GNR): CDC Definition MDR: Resistant to =3 classes*
XDR: Susceptible to =2 agents
Pan resistance: Resistant to all available antimicrobials
Current MDRO gram negatives include E. coli, P. aeruginosa, K. pneumoniae, K. oxytoca, A. baumanii
* Classes: Beta-lactams, fluoroquinolones, aminoglycosides, carbapenems
6. Review of Selected Antimicrobials Beta-lactams
Penicillins and cephalosporins
Fluoroquinolones
Ciprofloxacin, Gemifloxacin, Levofloxacin, Moxifloxacin
Aminoglycosides
Amikacin, Gentamicin, Streptomycin, Tobramycin, Kanamycin, Neomycin
Carbapenems
Doripenem, Meropenem, Ertapenem, Imipenem
7. Emergence of MDR Organisms
8. Normal Antimicrobial function Enzyme from your own body activates the antibiotic (metabolizes it) and it becomes active or available for use. The active antibiotic is able to bind to the receptor (wherever it is--) and start to workEnzyme from your own body activates the antibiotic (metabolizes it) and it becomes active or available for use. The active antibiotic is able to bind to the receptor (wherever it is--) and start to work
9. Normal Antimicrobial Function When it works, all of the antibiotics are able to bind to their appropriate receptors and the result it cell death (lysis). Everything worked like it is supposed to. There are ample opportunities for the process to fail at specific steps in the process. When it works, all of the antibiotics are able to bind to their appropriate receptors and the result it cell death (lysis). Everything worked like it is supposed to. There are ample opportunities for the process to fail at specific steps in the process.
10. Inability to Get to the Targeted Site
11. Change in the Receptor Bacterial cell receptor changes so the antibiotic cannot attach and get into the cell. The target site changes shape. Square peg into round hole.Bacterial cell receptor changes so the antibiotic cannot attach and get into the cell. The target site changes shape. Square peg into round hole.
12. Inactivation by an Enzyme Enzyme made by bacterium changes the active antibiotic into a different inactive formEnzyme made by bacterium changes the active antibiotic into a different inactive form
13. Inactivation by an Enzyme Enzyme made by bacterium changes the active antibiotic into a different inactive formEnzyme made by bacterium changes the active antibiotic into a different inactive form
14. Gram-Negative Pathogens:the Reality Pathogens encountered in healthcare institutions in North America, Europe, and Asia are, for the most part, similar
Truly a worldwide problem
Risk factors universal:
Device use
Antimicrobial overprescribing
15. Antimicrobial Resistance in Gram-Negative Infections Resistance is a complex problem
Multiple/concurrent mechanisms
Expanding mechanisms
>500 discrete b-lactamases
Evolution of carbapenemases
Efflux pumps
Permeability changes
Selective antimicrobial pressure favors amplification of resistant bacteria
16. Extended Spectrum Beta-Lactamase (ESBL) Producers Enterobacterial resistance to 3rd generation cephalosporins caused by production of ESBL
Beta-lactamase enzymes destroy the beta-lactam ring so that the antibiotic cannot bind to the PBP and interfere with cell wall synthesis
Renders several classes of antimicrobials ineffective against the producing organism(s)
Leads to difficulty in treatment, use of broader spectrum agents, increases collateral damage
Carbapenems used for treatment
17. Enterobacteriaceae Citrobacter
Enterobacter
Escherichia coli
Klebsiella
Morganella morganii
Proteus Providencia
Salmonella
Serratia
Shigella
Yersenia
18. Why Don’t We Treat ESBLs Like Other MDROs? Colonized state less profound and problematic than gram positives (MRSA, VRE)- we think!
Less readily recognized in the laboratory setting
Our practice evidence is very thin
If isolation is not used, standard precautions and hand hygiene must be a main prevention activity
19. Extended Spectrum ?-lactamases (ESBLs) Risk Factors for Colonization/Infection* Hospitalization
Nursing home residency
Length of hospital/ICU stay
Severity of illness
Antibiotic exposure (esp. ceftazidime, aztreonam)
Invasive devices/instrumentation
20. Carbapenem Resistance Widespread use of carbapenems for suspected ESBL infection has contributed to resistance due to selection
Emergence of carbapenemase (a group of beta-lactamases) in enterobacteriaceae
Klebsiella pneumoniae carbapenemase (KPC)-producing organisms
Klebsiella spp.
Enterobacter spp.
E. coli
Serratia spp.
21. Klebsiella pneumoniae carbapenemase (KPC)-producing organisms Resistant to carbapenems: MICs >32 mg/L
Generally susceptible to tigecycline
Further studies are needed to ascertain risk factors (East coast)
Available data describe patients with infections caused by KPC-producing organisms as:
Receiving long courses of broad spectrum antibiotics
Prolonged ICU stays
22. Current Status of Antimicrobials No new classes 1968-2000
Since 2000, only 4 new classes approved by FDA
Linezolid
Streptogramins
Daptomycin
Tigecycline
Apart from Tigecycline, no new class of agents against Gram-negative organisms
23. Principles of Antimicrobial Use
24. Principles of Antimicrobial Use
25. Mechanisms of Action
27. Antimicrobial Therapy
28. Aminoglycosides
29. Transmission of Resistant Organisms Contact with healthcare worker
Lack of hand hygiene, inadequate patient care techniques, contaminated supplies/equipment
Failure to implement contact precautions (at all or early enough)
Inadequate environmental attention
Promoting of resistance through inappropriate antimicrobial therapy
Failure to identify prevention breaches and intervene
32. MDR Infection: General Principles
34. Strategies to Prevent Selection
36. Strategies to Prevent Selection
38. Elements of a Prevention Program
39. Competent Workforce Understands how transmission occurs
Able to apply this knowledge in preventing transmission
Recognizes who is involved in preventing transmission
Able to apply the knowledge regarding transmission prevention in all settings
Applies critical thinking skills to problem solve
Actively collaborates with others in working toward the goal of transmission prevention
40. Applying Competencies KPCs/ESBLs/C. difficile/MRSA
Role of microbes in disease
Transmission
Precautions
Occupational/Employee health-protecting patient
Occupational/Employee health-protecting HCW
Problem solving
Preparedness
41. The Healthcare Worker of Tomorrow
42. Shared Learning Website
www.infectionpreventiontools.com