Transcript Antibiotic Resistant Pathogens in the Health Care Setting Focus On Infection Control

Antibiotic Resistant Pathogens in
the Health Care Setting
Focus On Infection
Control
VA APIC Conference 2005
Gonzalo Bearman MD, MPH
Assistant Professor of Medicine, Epidemiology and
Community Health
Associate Hospital Epidemiologist
Virginia Commonwealth University
Outline
• Nosocomial Infections
– Background, Epidemiology
– Changing Paradigm
• Important Nosocomial Pathogens
– MRSA
– CA MRSA
– VRE
– MDR- GNRs
– ESBL producing organisms
– C.difficile
• Importance of hand hygiene in decreasing cross transmission
– Alcohol based hand sanitizers
• Isolation Categories
– Contact Isolation
– Gowns and gloves
• Compliance with IC guideline
– The importance of process measure feedback
Nosocomial Infections
• 5-10% of patients admitted to acute care
hospitals acquire infections
– 2 million patients/year
– ¼ of nosocomial infections occur in ICUs
– 90,000 deaths/year
– Attributable annual cost: $4.5 – $5.7 billion
• Cost is largely borne by the healthcare facility not
3rd party payors
Weinstein RA. Emerg Infect Dis 1998;4:416-420.
Jarvis WR. Emerg Infect Dis 2001;7:170-173.
Major Sites of Nosocomial
Infections
•
•
•
•
Urinary tract infection
Surgical site infection
Bloodstream infection
Pneumonia (ventilator-associated)
Nosocomial Infections
• 70% are due to antibiotic-resistant
organisms
• Invasive devices are more important
than underlying diseases in determining
susceptibility to nosocomial infection
Burke JP. New Engl J Med 2003;348:651-656.
Safdar N et al. Current Infect Dis Reports 2001;3:487-495.
Nosocomial Infections in the US
1975
1995
Number of admissions (millions)
37.7
35.9
Number of patient days (millions)
299.0
190.0
Average length of stay (days)
7.9
5.3
Number of nosocomial infections
(millions)
2.1
1.9
Incidence of nosocomial infections
(per 1,000 patient-days)
7.2
9.8
Burke JP. New Engl J Med 2003;348:651-656.
Attributable Costs of Nosocomial
Infections
Cost per Infection
Wound infections
$3,000 - $27,000
Sternal wound infection
$20,000 - $80,000
Catheter-associated BSI
$5,000 - $34,000
Pneumonia
Urinary tract infection
$10,000 - $29,000
$700
Nettleman M. In: Wenzel RP, ed. Prevention and Control of Nosocomial Infections,
4th ed. 2003:36.
Shifting Vantage Points on
Nosocomial Infections
Many infections are
inevitable, although
some can be
prevented
Each infection is
potentially
preventable unless
proven otherwise
Gerberding JL. Ann Intern Med 2002;137:665-670.
Antibiotic Resistant Pathogens in
the Hospital Setting
NNIS Summary 2004
Fig 1. Selected antimicrobial-resistant pathogens associated with nosocomial infections in ICU patients, comparison of
resistance rates from January through December 2003 with 1998 through 2002, NNIS System. CNS, Coagulasenegative staphylococci; 3rd Ceph, resistance to 3rd generation cephalosporins (either ceftriaxone, cefotaxime, or
ceftazidime); Quinolone, resistance to either ciprofoxacin or ofloxacin. Percent (%) increase in resistance rate of
current year (January-December 2003) compared with mean rate of resistance over previous 5 years (1998-2002):
[(2003 rate – previous 5-year mean rate)/previous 5-year mean rate] × 100.
American Journal of Infection Control Volume 32, Issue 8 , December 2004, Pages 470-485
MRSA (Methicillin Resistant S.aureus)
•Appeared in 1980s
•50-70% of hospital S.aureus isolates are MRSA
•Carrier state (colonization)- asymptomatic
•Reduce transmission by detecting and treating all infected
and colonized patients
•Drug of choice is vancomycin
•Patients with MRSA infection/colonization are placed on
contact isolation
•Recent reports of a vancomycin resistant strains of
S.aureus
•Certain to be an increasingly difficult management
problem
Methicillin-resistant–Staphylococcus aureus
Hospitalizations, United States
• National Hospital Discharge Survey used to calculate the
number of US hospital discharges listing S. aureus–specific
diagnoses
• From 1999 to 2000:
– 125,969 hospitalizations with a diagnosis of MRSA infection
occurred annually
•
•
•
•
31,440 for septicemia (BSI)
29,823 for pneumonia
64,706 for other infections
3.95 per 1,000 hospital discharges
• National burden of serious MRSA disease is substantial
Kuehnert MJ, Hill HA, Kupronis BA, Tokars JI, Solomon SL, Jernigan DB. Methicillin-resistant–Staphylococcus
aureus Hospitalizations, United States. Emerg Infect Dis [serial on the Internet]. 2005 Jun. Available from
http://www.cdc.gov/ncidod/EID/vol11no06/04-0831.htm
Community Acquired MRSA
Comment
Epidemiology
CA-MRSA infections were first recognized in the 1980s
Persons with CA-MRSA infections are typically younger
and healthier than persons with healthcare-associated
MRSA.
CA-MRSA bacteria are usually susceptible to more
types of antibiotics than are healthcare-associated
strains of MRSA
• Typically susceptible to Bactrim, Clindamycin, Doxycycline
Clinical
Presentation
Most infections caused by Staphylococcus aureus are
skin and soft tissue infections such as abscesses or
cellulitis
Necrotizing pneumonia
VRE (vancomycin resistant enterococci)
• Enterococcus faecalis and E. faecium
•E. faecium is the most frequently isolated species of
VRE in hospitals and typically produces high
vancomycin (>128 µg/ml) and teicoplanin (>16 µg/ml)
minimum inhibitory concentrations (MICs)
• Normal inhabitants of bowel
• Can cause UTI, BSI, VAP and wound infections in
critically ill patients
•Cross infection via contaminated equipment documented
•Thermometers
MRSA and VRE
• Prevention of MRSA/VRE infections is based upon standard
infection control precautions including:
• Hand Washing
• Wash hands immediately after gloves are removed, between
patient contacts and between tasks and procedures.
• Gloving – contact isolation
• Wear gloves when touching blood, body fluids and
contaminated items
• Remove gloves between patient contacts and wash hands
immediately.
• Gowning –contact isolation
• Wear a gown during procedures that are likely to generate
splashes or droplets of blood and body fluids.
• Dedicated Patient Care Equipment
• Appropriate cleaning, disinfection and sterilization of patient
care equipment are important in limiting the transmission of
organisms.
MDR Gram Negative Rods
• MDR gram negative rods are defined as
isolates that are susceptible to no more
than one class of antimicrobial agents
(excluding colistin).
• Increasingly problematic
– Acinetobacter baumanii
– Stenotrophomonas maltophilia
– Pseudomonas aeruginosa
Application of control measures for
infections caused by multi-resistant
gram-negative bacteria in intensive
care unit patients
Prospective study of ICU patients in the Hospital Sao
Paulo, between March-June 1997 and March-June
1998.
Surveyed nosocomial infections with multi-resistant
microorganisms:
•A.baumannii and P.aeruginosa: resistant to :
aminoglycosides, quinolones, third-generation
cephalosporins, and carbapenems.
Mem. Inst. Oswaldo Cruz vol.99 no.3 Rio de Janeiro May 2004
Application of control measures for
infections caused by multi-resistant
gram-negative bacteria in intensive
care unit patients
Promotion of hand hygiene (PVP-I or chlorexidine) before and after contact
with the patient
Application of contact isolation measures
Daily surface cleaning and disinfection with alcohol at 70%
Separation of articles and equipment for exclusive use of the patient
Study showed significant increase in percentage of multi-resistant
pathogens in second period vs first period
UTI with multi-resistant increased from 22.7% to 30%, pneumonia 8.3%
to 33.3% , and in BSI from 4.7% to 60%
Infections with MDR GNR are difficult to manage and will likely require
more than just stringent IC practice
Mem. Inst. Oswaldo Cruz vol.99 no.3 Rio de Janeiro May 2004
Relatively Poor Outcome after
Treatment of Clostridium difficile Colitis
with Metronidazole
Prospective, observational study of 207 patients who
were treated with metronidazole for C. difficile colitis
•103 patients (50%) were cured by the initial course of
therapy and had no recurrence of disease.
•22% continued to have symptoms of colitis for 10
days despite treatment
• 28% responded initially but had a recurrence within
the ensuing 90 days.
•The mortality rate higher among patients who did not
respond fully to an initial course of therapy, compared
with those who did (33% vs. 21%; P < .05)
Clinical Infectious Diseases
2005;40:1586-1590
Increasing Risk of Relapse after Treatment of
Clostridium difficile Colitis in Quebec, Canada
Kaplan-Meier plots of
the 60-day probabilities
of recurrence among
patients with Clostridium
difficile associated
diarrhea treated with
only metronidazole,
comparing 1991-2002 to
2003-2004 (top).
Treatment with only
vancomycin during 1991
2002 to 2003-2004
(bottom)
Clinical Infectious Diseases
2005;40:1591-1597
Clostridium difficile
• Because of the increasingly poor response to therapy,
additional approaches to prevention and/or treatment
of C. difficile colitis are in order
• Newer therapies
– nitazoxanide or tinidazole
– probiotics, such as Saccharomyces boulardii and
Lactobacillus species
• Stringent application of infection control measures
– Contact isolation
– Meticulous hand hygiene
– Thorough terminal disinfection of patient rooms
• (sporicidal agent)
The ABC’s of ESBL for
Infection Control Nurses:
-Extended-Spectrum Beta-Lactamases-
Epidemiology
• Today, 30 – 50% of E. coli are resistant
to ampicillin and amoxicillin due to a
beta-lactamase
• ESBLs have been reported for E.coli,
Klebsiella, Enterobacter,
Proteus,Pseudomonas, Salmonella, Serratia
Beta-Lactamases: What are they ?
• Enzymes produced by certain bacteria
that provide resistance to certain
antibiotics
• Produced by both gram positive and
gram negative bacteria
• Found on both chromosomes and
plasmids
Beta-lactamases
• Are primary mode of resistance to betalactam antibiotics
• Produced by some gram positive
bacteria and virtually all gram negative
bacteria
ESBL?
• Resistance that is produced through the
actions of beta-lactamases.
• Extended spectrum cephalosporins, such as
the third generation cephalosporins, were
originally thought to be resistant to hydrolysis
by beta-lactamases!
• Not so!
– mid 1980's it became evident that a new type of
beta-lactamase was being produced by Klebsiella
& E coli that could hydrolyze the extended
spectrum cephalosporins.
– These are collectively termed the
• 'extended spectrum beta-lactamases' (ESBL's)
Mechanism of Action
• Hydrolysis of beta-lactam ring of basic
penicillin structure
• Hydrolysis = adding a molecule of H2O to C-N
bond with enzyme action
– This opens up the ring, thus making the drug
ineffective!
Plasmids
Bacterial
Conjugation
• Rings of extrachromosomal DNA
• Can be transferred between different
species of bacteria conjugation
• Carry resistance genes
• Most common and effective mechanism
of spreading resistance from bacteria to
bacteria
Beta-lactam Antibiotic Examples
• Penicillins:
– Penicillin, amoxicillin, ampicillin
• Cephalosporins:
– Ancef, Rocephin, Keflex, Cefotan
• Carbapenems:
– Imipenem, meropenem
Beta-lactamase inhibitor
•
•
•
•
Clavulanic acid + amoxicillin = Augmentin
Clav. Acid + ticarcillin = Timentin
Sulbactam + ampicillin = Unasyn
Tazobactam + piperacillin = Zosyn
Good News: Beta-lactamase inhibitors inhibit the beta
lactamase thereby not allowing the molecule to hydrolyze
the antibiotic. Most ESBLS remain susceptible to Betalactamase inhibitors
Bad News: some ESBL producing bacteria produce large
amounts of beta-lactamase thereby overwhelming the betalactamase inhibitors
The story is more complicated….
• Multiple antimicrobial resistance is often a
characteristic of ESBL producing gramnegative bacteria.
•
•
•
•
Ceftazidime
Cefotaxime
Ceftriaxone
Aztreonam
• Genes encoding for ESBLs are frequently
located on plasmids that also carry resistance
genes for:
•
•
•
•
•
Aminoglycosides
Tetracycline
TMP-SULFA
Chloramphenicol
Fluoroquinolones
NCCLS ESBL Screening
• For isolates:
– K.pneumoniae, E.coli and K.oxytoca :
– 1st step- screen using:
• Ceftazidime, ceftriaxone, cefotaxime, cefpodoxime, or
aztreaonam
– 2nd Step: If MIC> 2 mcg/ml then:
• Ceftazidime and cefotaxime alone and in combination with
clavulanate
• Positive test: greater than a three-fold reduction in MIC for
combination versus single agent
– ESBL status of organism is now highly likely
Take home message:
ESBLs are harbingers of
multidrug resistance
What are the clinical implications?
• Can result in treatment failure
– Morbidity and mortality
• Several outbreaks have occurred
• If an ESBL is detected, all penicillins,
cephalosporins, and aztreonam should be
reported as “resistant”, regardless of in vitro
susceptibility test results
Management of ESBL infections
• Pharmacotherapy:
– Treatment of choice for serious infections
• Carbapenems
– Stable in the presence of most beta-lactamases
– Examples
» Imipenem
» Meropenem
• Restrict the use of 3rd generation
cephalosporins.
Infection Control?
As infection control nurses your job is to ensure
that adequate precautions are taken to
minimize the risk of cross transmission!
– Contact precautions
• Cohort patients during outbreaks
– Promote meticulous hand hygiene practices
– Reminders to HCW staff about Patient ESBL
status
• Electronic flagging of medical record
• Placing stickers on charts
– When are contact precautions discontinued?
• No specific guidelines:
– Resolution of infectious process
Nosocomial Drug Resistant
Pathogens:
• Nosocomial pathogens of continued or
increasing concern
– MRSA
– CA-MRSA
– VRE
– C.difficile
– MDR GNR
– ESBL producing organisms
30%-40% of all Nosocomial
Infections are Attributed to
Cross Transmission
The inanimate environment is a
reservoir of pathogens
X represents a positive Enterococcus
culture
The pathogens are ubiquitous
~ Contaminated surfaces increase cross-transmission ~
Abstract: The Risk of Hand and Glove Contamination after Contact with
a VRE (+) Patient Environment. Hayden M, ICAAC, 2001, Chicago, IL.
The inanimate environment is a
reservoir of pathogens
Recovery of MRSA, VRE, C.diff CNS and GNR
Devine et al. Journal of Hospital Infection. 2001;43;72-75
Lemmen et al Journal of Hospital Infection. 2004; 56:191-197
Trick et al. Arch Phy Med Rehabil Vol 83, July 2002
Walther et al. Biol Review, 2004:849-869
The inanimate environment is a
reservoir of pathogens
Recovery of MRSA, VRE, CNS. C.diff and GNR
Devine et al. Journal of Hospital Infection. 2001;43;72-75
Lemmen et al Journal of Hospital Infection. 2004; 56:191-197
Trick et al. Arch Phy Med Rehabil Vol 83, July 2002
Walther et al. Biol Review, 2004:849-869
The inanimate environment is a
reservoir of pathogens
Recovery of MRSA, VRE, CNS. C.diff and GNR
Devine et al. Journal of Hospital Infection. 2001;43;72-75
Lemmen et al Journal of Hospital Infection. 2004; 56:191-197
Trick et al. Arch Phy Med Rehabil Vol 83, July 2002
Walther et al. Biol Review, 2004:849-869
Transfer of VRE via HCW Hands
16 transfers (10.6%) occurred in 151
opportunities.
•13 transfers occurred in rooms of
unconscious patients who were unable to
spontaneously touch their immediate
environment
Duckro et al. Archive of Int Med. Vol.165,2005
Alcohol Based Hand Sanitizers
• CDC/SHEA hand antiseptic agents of
choice
– Recommended by CDC based on strong
experimental,clinical, epidemiologic and
microbiologic data
– Antimicrobial superiority
• Greater microbicidal effect
• Prolonged residual effect
– Ease of use and application
Alcohol based hand hygiene
Easy to use
Quick
solutions
Very effective antisepsis due to bactericidal properties of alcohol
Impact of alcohol based hand
sanitizers at VCU: can this
improve hand hygiene?
Study Algorithm
Incremental Increase in Alcohol
Dispensers
Hand Hygiene
Educational
Program
Implemented
Direct Observation of Hand Hygiene
Arch Intern Med. 2000;160:1017-1021.
Results
Hand hygiene practice can be improved with education
and greater accessibility of alcohol hand sanitizers
•Improvement in Hand Hygiene Compliance
Arch Intern Med. 2000;160:1017-1021.
Hand Hygiene
• Single most important method to limit cross
transmission of nosocomial pathogens
• Multiple opportunities exist for HCW hand
contamination
– Direct patient care
– Inanimate environment
• Alcohol based hand sanitizers are ubiquitous
– USE THEM BEFORE AND AFTER PATIENT
CARE ACTIVITIES
Types of Isolation Precautions
Transmission-based Precautions
-for patients with documented or suspected infections
-3 Types:
airborne, droplet and contact
Standard Precautions
-Apply to all Patients
--Replace Universal Precautions
Contact
Precautions
for drug
resistant
pathogens.
Gowns and gloves
must be worn upon
entry into the
patient’s room
Contact Precautions
•
•
•
•
•
•
MRSA
CA-MRSA
VRE
MDR GNR
ESBL producing organisms
C.difficile
Gown and Glove use for
Infection Control
Glove Use for Infection Control
Variable
Rationale
Comment
Gloves
Prevent exposure to
bloodborne
pathogens
Even with proper glove
use, hands may
become contaminated
during the removal of
Prevent contamination the glove or with
micro-tears that allow
of hands with drug
for microorganism
resistant pathogens
transmission
during patient care
activities
Glove use should not be
used as a substitute for
hand hygiene
Gown Use for Infection Control
Variable
Rationale
Comment
Several studies have
documented
colonization of
healthcare worker
apparel and
instruments during
patient care activities
without the use of
gowns
The use of gloves and
gowns is the
convention for limiting
the cross
transmission of
nosocomial
pathogens, however,
the incremental
benefit of gown use,
in endemic settings,
may be minimal
Gowns
What about the role of Universal
Gloving For All Patient Care?
Feedback of infection control
process measures
Quality Improvement Initiative to Improve
Compliance with Infection Control Practice
Measurement and
feedback of
infection control
process measures
in the intensive
care unit: impact on
compliance
Mezgebe Berhe MD1, Mike Edmond MD, MHA, MPH1,2,
Gonzalo Bearman MD, MPH1,2
Divisions of Infectious Diseases1 and Quality Health
Care2
Department of Internal Medicine
Virginia Commonwealth University School of Medicine
Richmond, VA, USA
Measurement and feedback of infection control process
measures in the intensive care unit: impact on
compliance.
-
• To measure selected infection control
process measures
• To feedback the results of process indicator
measurement to ICU leadership
• To assess the impact of feedback on
compliance with infection control process
measures
Mezgebe Berhe MD1, Mike Edmond MD, MHA, MPH1,2, Gonzalo Bearman MD, MPH1,2
Measurement and feedback of infection control
process measures in the intensive care unit:
Impact on compliance
• Selected Infection Control Process Measures:
– Hand Hygiene
– Femoral Catheter use as proportion of CVC days
– Proportion of Head of bed (HOB) elevations in medical
(MRICU) and Surgical (STICU) Intensive Care Units
• All Data Collected by ICPs
– Baseline data- April-June 2004
– Follow up- 3rd, 4th quarters of 2004, 1st quarter 2005
– Baseline and follow up data presented to ICU nurses
and Physician staff
Mezgebe Berhe MD1, Mike Edmond MD, MHA, MPH1,2, Gonzalo Bearman MD, MPH1,2
Measurement and feedback of infection
control process measures in the intensive
care unit: impact on compliance
MRICU
STICU
Process
Measure
Baseline
Q2-2004
Q3
(2004)
Q4
(2004)
Q1
(2005)
P
value*
Baseline
Q2-2004
HH %
Opp
14/44
(32%)
31/91
(37%)
33/91
(36%)
50/108
(46%)
0.101
19/38
(50%)
HOB %
Opp
28/51
(55%)
320/333
(96%)
450/454
(99%)
551/556
(99%)
<0.001
Fem.
CVC
% of
Days
195/1093
(18%)
130/769
(16%)
80/879
(9.1%)
51/951
(5.4%)
<0.001
Q3
(2004
Q4
(2004)
Q1
(2005)
P
value*
42/80
(53%)
40/80
(50%)
49/100
(49%)
0.916
20/43
(47%)
229/307
(75%)
389/488
(79%)
275/361
(76%)
<0.001
93/1109
(8.4%)
49/970
(5.1%)
14/1077
(1.3%)
26/920
(2.8%)
0.01
Mezgebe Berhe MD1, Mike Edmond MD, MHA, MPH1,2, Gonzalo Bearman MD, MPH1,2
Head of Bed Elevation in VCU Medical ICU:
Effect of Feedback
% Compliance with HOB elevation
Pneumonia cases/1,000 ventilator-days
100
90
80
70
60
50
40
30
20
8
10
0
1
7
6
5
4
3
2
0
Q1-04
Baseline;
no feedback
Q2-04
Q3-04
Q4-04
Q1-05
Performance feedback quarterly
Q2-05
Pneumonia cases/1,000 ventilator-days
HOB compliance
Measurement and feedback of infection control process
measures in the intensive care unit: impact on compliance
• Feedback of process measures:
• lowered the use of femoral catheters
• Improved the proportion of elevated HOBs in both
ICUs
• There was no significant improvement in hand
hygiene.
• System level changes such as catheter
placement and HOB elevation appears to be
impacted by feedback whereas individual level
practices such as hand hygiene were not affected
Mezgebe Berhe MD1, Mike Edmond MD, MHA, MPH1,2, Gonzalo Bearman MD, MPH1,2
Conclusion
• Antimicrobial resistant pathogens are
becoming increasingly problematic in acute
care settings
– MRSA,VRE, CA-MRSA, MDR GNRs, C.difficile
and ESBL producing GNR
• Paradigm Shift in Nosocomial Infections
– Each infection is potentially preventable unless
proven otherwise
• Healthcare facilities must have up to date IC programs
and strive for maximum compliance with IC guidelines
Conclusion
• IC measures to limit cross transmission of
drug resistant pathogens
– Hand Hygiene
• Alcohol based hand sanitizers
– Contact Precautions
• Gown
• Gloves
– Surveillance and feedback of IC process
measures to maximize adherence to guidelines