Document

Report
MRSA: Medication Regimens for
Community and Hospital Acquired
-Gita Wasan Patel PharmD, Clinical Coordinator, Medical Center of Plano
-Joel McKinsey, MD, Infectious Disease Specialist, Co-director of Hospital
Epidemiology, Research Medical Center, Kansas City
-Tamara Fohr, PharmD, Clinical Coordinator, Denton Regional Medical Center
February 2007
Goals
• Provide information on peri-operative eradication of
MRSA
• Provide information on decolonization of MRSA
• Provide clinicians with knowledge about the etiology and
treatment of community and
healthcare-acquired MRSA
• Discuss the pharmacist’s role in making recommendations
to physicians for safe and appropriate treatment of the
disease.
Objectives
• Upon completion and mentored practice, the clinician
should be able to:
– Discuss the definition and diagnosis of the different
types of MRSA
– Understand the established guidelines for treatment
– Understand surgical prophylactic issues and therapy
– Understand decolonization recommendations
– Make appropriate recommendations to physicians
regarding ordered medication
– Appropriately document interventions and the results
Perioperative Eradication of MRSA Carriage
Perioperative Eradication of MRSA
Carriage
• Due to prevalence in community, some surgeons culturing
pt nares prior to procedure and if positive for MRSA, order
mupirocin nasally and/or on wound post surgery (esp.
orthopedics and CABG’s)
• Some inconsistent data regarding preventing SSIs in
orthopedic surgeries. Since mupirocin is inexpensive and
resistance rates are low (approx 5%), still a good option
• Data does suggest that nasal mupirocin can prevent
sternal wound infections after CABGs
CID 2002; 35: 353-358
Journal of Hospital Infection 2003; 54:196-201
Ann Thorac Surg 2001; 71: 1572-1579
Perioperative Eradication of MRSA
Carriage
Cardiac Surgery: Open Heart Procedures including,
– Coronary Artery Bypass
– Valve Replacements
Orthopedics: Open procedures of the Hip, Knee, and
spine including:
–
–
–
–
–
–
–
–
Total hip and knee
Revision total hip and knee
Partial total hip and knee
Unicompartmental knee
Endo/ Unipolar hip and bipolar hip
Lumbar spine with and without implants
Cervical spine with and without implants
Thoracic spine with and without implants
Perioperative Eradication of MRSA
Carriage
• Surgical Scrub (CHG 2-4%) night before and morning of
surgery with instruction/informational handout
• Mupirocin nasal ointment applied pre-op and post-op
twice daily for 5 days total
• Vancomycin 15 mg/kg IV pre-op (120 minutes prior) and
additional dose may be required if therapeutic level (5-10
mcg/ml trough) cannot be maintained for 24 hours postprocedure
– Renal dosing considerations
• Contact Precautions
Perioperative Eradication of MRSA
Carriage
• Mupirocin Nasal Ointment is not recommended for
patients who are not known to be colonized with MRSA
– May increase risk of subsequent MRSA colonization
• Vancomycin is currently not recommended for patients
who are not known to be colonized with MRSA
Antimicrobial Agents and Chemotherapy 2004; 49(4):1465
Clinical Infectious Diseases 2004; 38:1706
MRSA Decolonization
• Completely inappropriate if patient has active infection
• Unsuccessful if pt has open or draining sites or if
indwelling lines or tubes needed for ongoing care
• No consensus regarding use/effectiveness
• Not routinely recommended
• May be prudent to consider if:
– Patient has recurring infections (admissions with MRSA) despite
treatment
– Ongoing MRSA transmission in a well-defined cohort with ongoing
contact
Infection 2006; 34: 117
MRSA Infection Versus Colonization
• Clinicians must be able to differentiate between
colonization and active infection to provide appropriate
therapy.
• Colonization cultures are obtained from nasal swabs
versus active infections that are usually in the blood,
tissue, etc.
• The number of colonies isolated also indicate a true
infection versus colonization
• Clinical picture of patient is imperative to the diagnosis of
an active infection.
Hospital Acquired MRSA
Hospital-Acquired MRSA
• Initially reported in the 1970’s
• Infections seen all over the body: respiratory,
bloodstream, skin, bone, etc., typically bacteremia
with no infection focus
• Resistant to non-Beta-Lactam antibiotics
• Usually non-virulent and slowly progressing
• Typically diagnosed in an inpatient setting
• Typical patient is elderly, debilitated and/or critically
or chronically ill
• Community spread is limited
• PVL (Panton-Valentine leukocidin) gene absent
Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases. Philadelphia: Elsevier,
2005:2328-2333.
HA-MRSA Therapy Options
Vancomycin
• Glycopeptide
• Dose 15 mg/kg - adjust frequency for renal function
• Target trough of 15-20 mcg/ml for pneumonia or bone
infections
• Side Effects: “Red Man Syndrome”, nephrotoxicity,
ototoxicity
• 10-14 day length of therapy unless endocarditis or
osteomyelitis (6 weeks)
• Bacteriostatic agent
Mayo Clin Proc 199; 74:928-935
Lexi-Comp
Amin A, Batts D. Community Acquired and Healthcare Associated MRSA. Medscape 2006
Linezolid (Zyvox)
• Oxazolidinone
• Dose 600mg IV or orally q12h with no renal or
hepatic adjustment
• Penetrates lung tissue better than vancomycin
• Side effects: thrombocytopenia (higher incidence
seen in patients with end-stage renal disease),
myelosuppression
• Should not give to patients on SSRIs (multiple reports
of serotonin syndrome)
• Bacteriostatic against enterococci and staphylococci
• Bactericidal against a majority of streptococci
CID 2006; 42:66-72
Lexi-Comp
Amin A, Batts D. Community Acquired and Healthcare Associated MRSA. Medscape 2006
Daptomycin (Cubicin)
• Lipopeptide
• Dose:
– 4 mg/kg for skin/skin structure infections
– 6 mg/kg for bacteremia or endocarditis; renal
adjustment needed if CrCl <30 ml/min
• Side Effects: anemia, myopathies
• Monitor CPK levels
• Does not penetrate the lungs and is inactivated by
pulmonary surfactants - cannot be used to treat
pneumonia
• Bactericidal
Lexi-Comp
Tigecycline (Tygacil)
• Glycylcycline
• Dose: 100mg IV X1 then 50mg q12h;
– no renal adjustment needed, but does need to be
adjusted for severe hepatic impairment
• Side Effects: nausea/vomiting, diarrhea; similar side
effects of the tetracyclines
• Not a good choice for monotherapy in patients with
intestinal perforation
• Also has broad-spectrum gram-negative activity, but
does not cover Pseudomonas
• Bacteriostatic
CID 2005; 41: S303-314
Therapy Issues Regarding
HA-MRSA Pneumonia
• Much concern regarding the penetration of
Vancomycin into the lung tissue
• New IDSA/ATS Guidelines recommend a target
trough of 15-20 mcg/ml
• Meta-analysis showed that linezolid may be more
efficacious than vancomycin when treating HA-MRSA
pneumonia
• Head-to-head trial currently enrolling patients
• Definitive clinical data not yet available
Chest 2003; 124: 1789-1797
Am J Respir Crit Care Med 2005; 171: 388-416
Therapy Issues Regarding
HA-MRSA Pneumonia
• 2 recent articles have examined the pharmacokinetic
parameters of vancomycin and MRSA pneumonia
• Jeffries et al. showed that greater vancomycin
concentrations did not correlate with improved
hospital outcome
• Hidayat et al. showed that 54% of their MRSA had a
high vancomycin MIC (>2 mcg/ml) and that these
patients had higher infection-related mortality despite
achieving high vancomycin trough levels (>15
mcg/ml)
Chest 2006; 130: 947-955
Arch Intern Med 2006; 166: 2138-2144
Vancomycin for Surgical
Prophylaxis
• No concensus among ID physicians or regulatory bodies
• Look to your antibiogram to provide direction
– If there is a large percentage of MRSA (>50%) in CABG or joint
replacement patients, there may be a need in these specific
populations
– No definitive clinical data available that would warrant the use of
pre-operative vancomycin on all CABG or joint replacement
patients
• Overuse of vancomycin in penicillin-allergic patients
– Watch for routine use of vancomycin without investigation of a
stated penicillin “allergy”. In many cases, there was no significant
reaction or the patient has a history of taking cephalosporins,
therefore cross resistance is not a problem
Vancomycin Resistance
• 3 cases of VRSA have been reported in the U.S.
• Attributed to plasmid-based vanA genes of E. faecalis
origin
• Vancomycin MICs > 32 mcg/ml
• Can emerge in the absence of prior vancomycin
treatment
• Remain susceptible to older agents and newer
compounds
• Linezolid-resistant S. aureus has also been reported
CID 2006; 42: S25-34
IV Medication Combination Effects
Vancomycin
Vancomy
Aminogly
Quinolones
B-lactam
Linezolid
Quin/Dal
Dapto
S
I
I
A
A if MLSb
I
I
S
I
I
DI
I
A
A
N
N
S&A
S
N
N
Aminogly
S
Quinolones
I
I
B-lactam
I
S
I
Linezolid
A
I
A
N
Quin/Dal
A if MLSb
I
A
S&A
N
I
DI
N
S
N
Daptomycin
N
N
A = Antagonism, DI = drug interactions, I = indifferent, N = no data, S = synergy,
MLSb=macrolide, lincosamide resistant MRSA
New drugs……
Dalbavancin
• Lipoglycopeptide related to teicoplanin
• Covers VISA, VRSA, and linezolid-resistant S. aureus
• Dosing: 1000mg IV x 1 dose
– then 500mg IV x 1 dose 7 days later
• Studied in skin/skin structure and catheter-related
bloodstream infections
• Side Effects: nausea, diarrhea, constipation, oral
candidiasis
• Not yet FDA approved
• Also on the horizon: Telavancin and Ortivancin
Pharmacotherapy 2006; 26(7): 908-918
Community Acquired MRSA
Community-Acquired MRSA
• Initially reported in the 1990’s
• Infections usually seen in skin and soft tissue, bone and
joint, and pneumonia
• Predilection for skin; cellulitis, abscesses; often mistaken
for spider bites (note: abscesses must be drained in order
for therapy to be effective)
• Non-Beta-Lactam antibiotics usually work
• Very virulent, especially due to toxins
Ann Pharmacother 2006; 40: 1125-1133
CA-MRSA (‘cont)
• Typically diagnosed initially in outpatient setting
• Patients can be young, healthy people; common in
athletes
• CA-MRSA has different genotype than HA-MRSA
• Contains SCCmec IV and the PVL virulence factor
Ann Pharmacother 2006; 40: 1125-1133
Therapy for CA-MRSA
• Expert consensus recommendations not available
• Double antibiotic coverage should be considered
due to resistance issues:
–
–
–
–
–
–
Doxycycline/Minocycline: bacteriostatic, minimal data
TMP/SMX: dose at 10-15mg/kg… seeing resistance issues
Clindamycin: Inducible resistance may be a problem
Levofloxacin (750mg)
Vancomycin
Linezolid and Daptomycin
Note: Rifampin an be added to any of the above - never use
alone as resistance will develop
Ann Pharmacother 2006; 40: 1125-1133
Dosing for CA-MRSA (Adults)
• TMP-SMX: 1-2 DS (double strength) tabs orally q8-12h
– typically dosed 2 twice daily; if pt can’t tolerate, give 1 QID
– take with FULL glass of water.
•
•
•
•
Doxycycline or Minocycline: 100mg orally BID
Clindamycin: 300-450mg orally QID
Levofloxacin: 750mg orally daily x 5 days
Rifampin (in combination with other agents): 300mg orally
BID for 5 days
2006 Georgia Guideline ; GUARD Coalition, June 2006
CA-MRSA in Children
• Clindamycin and TMP-SMX are reasonable empiric
choices for mild to moderate CA-MRSA
• Vancomycin should be given with or without rifampin
and/or gentamicin for severe infections
• Linezolid should be reserved for VRE, VISA or VRSA
Pharmacotherapy 2006; 26 (12):1758-1770
Dosing for CA-MRSA (Children)
• TMP/SMX (Base dose on TMP): 8-12mg TMP per
kg/day in 2 doses
• Clindamycin: 10-20 mg/kg per day in 3-4 doses
• Rifampin (in combination with other agents): 10-12
mg/kg per day in 2 doses
• Do not exceed adult doses
• Doxycycline or Minocycline not recommended in
children.
• Tetracycline can be used in children greater than 8
years old
2006 Georgia Guidelines; GUARD Coalition June 2006
Inducible Clindamycin Resistance
• If a sensitivity report shows a CA-MRSA is erythromycin
resistant and clindamycin sensitive, clindamycin might not
work
• 20-26% of CA-MRSA has inducible clindamycin
resistance
• Local susceptibility patterns should be taken into account
when making treatment decisions
Inducible Clindamycin Resistance
• Macrolides can induce Clindamycin resistance
• D-test can be done to confirm and visualize resistance
• Place an erythromycin and clindamycin disk on an agar
plate
• If exposure to erythromycin triggers inducible clindamycin
resistance, the normally circular zone of inhibition around
the clindamycin disk will appear flattened, creating a “D”
shape
Inducible Clindamycin Resistance
Antimicrob Agents Chemother 2005; 49(3): 1222-1224
Antimicrobial Susceptibilities:
CA- and HA-MRSA
JAMA 2003, 290: 2976-2984
Estimated Susceptibility
CA-MRSA
•
•
•
•
•
100% to linezolid, vancomycin, and daptomycin
95-100% to TMP-SMX, doxycycline, minocylcine
91-99% to rifampin
80-95% to clindamycin
64-79% to levofloxacin (750mg) and moxifloxacin (do not
use Cipro)
NEJM 2006; 355: 666-674
Therapy Considerations
• Resistance will continue to grow
– Use your hospital’s antibiogram to direct therapy
– Make sure dose is adequate to achieve penetration
– Reserve the newer agents for pts unable to tolerate/unresponsive
to traditional choices
• Direct comparative trials between new and old drugs are
lacking
• Oral options are more limited than IV
– If pt unable to afford oral Zyvox, consider Pfizer’s RSVP program
(1-888-327-7787)
MRSA ABX Acq. Cost Comparison
Drug
Dose
Freq/Day
$0.25
1
3
$0.75
10 days
$0.25
2
2
$0.50
10 days
$0.61
300
4
$2.44
10 days
4mg/KG
1
$0.00
7-14 days
$0.37
100
2
$0.74
10 days
Levaquin 750mg IV
$17.21
750
1
$17.21
5 days
Levaquin 750mg PO
$15.14
750
1
$15.14
5 days
Minocin 100mg PO
$0.42
100
2
$0.84
10 days
Minocin 50mg PO
$0.21
50
4
$0.84
10 days
Mupirocin 0.9gm PKT***
$0.47
1
2
$0.94
5 days
Rifampin 300mg PO
$1.03
300
2
$2.06
5 days
Rifampin 600mg IV
$76.38
300
2
$152.76
5 days
Synercid 500mg IV
$110.13
7.5mg/KG
2
$0.00
Min 7 days
$41.07
50
2
$82.14
5-14 days
Vancomycin 1GM ADV
$6.33
wt/renal based
$0.00
10-14 days
Vancomycin 1GM FRZ
$7.35
wt/renal based
$0.00
10-14 days
Vancomycin 1GM IV
$5.85
wt/renal based
$0.00
10-14 days
Vancomycin 500mg IV
$2.92
wt/renal based
$0.00
10-14 days
Vancomycin 500mg IV ADV
$3.19
wt/renal based
$0.00
10-14 days
Zyvox 600mg IV
$70.47
600
2
$140.94
10-14 days
Zyvox 600mg PO
$55.00
600
2
$110.00
10-14 days
Bactrim DS PO
alternative regimen
Cleocin 300mg PO
Cubicin 500mg IV
Doxycycline 100mg PO
Tygacil 50mg IV
Acq Cost
$156.70
Cost/Day**
Duration
Short Case Studies
Case Study #1
A 24 year old woman presented in the ER with a large
abscess that she thought was caused by a spider bite.
She has an elevated temperature and white blood cell
count and has been admitted to the facility. The
attending physician ordered Levaquin and Rifampin.
The dose seems appropriate, but she is not getting
better.
What is the next step to best treat this patient?
Case Study #2
A surgeon has a patient with MRSA he wants to put on
Zyvox as she has previously failed treatment with
Vancomycin. The physician would like to discharge
patient on oral therapy. The patient has a history of
thrombocytopenia invoking concern of medication side
effects.
How should this patient be monitored?
Case Study #3
A 66 year old nursing home patient was brought to the ER in
an unresponsive state with vomit on his gown. He has
dark urine and decreased urinary output. He has
diabetes, HTN, chronic renal disease, COPD and
dyslipidemia. His history is significant for bypass
surgery, stents, hip fracture and back surgery. He is
admitted to the ICU and placed on a ventilator. The ID
physician consultant placed him on Zosyn and
Vancomycin. Today a sputum culture came back
positive for MRSA.
The attending physician asks you for a decolonization
protocol for MRSA. What is your response?
If the intervention is not documented…
Document your interventions!
– If the intervention is not documented, it did not happen
– Receive credit for your efforts
– If the patient is readmitted, the information is necessary
for optimal care
– Physician trending is a useful P&T tool for identifying
credentialing issues
– Successful interventions are a corporate goal for
improving patient safety, reducing LOS, and controlling
supply costs

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