MRSA: Medication Regimens for Community and Hospital Acquired

1
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
2
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 pharmacists role in making
  recommendations to physicians for safe and
  appropriate treatment of the disease.

3
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

4
Perioperative Eradication of MRSA Carriage
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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
  CABGs)
• 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 54196-201
• Ann Thorac Surg 2001 71 1572-1579

6
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

7
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 post-procedure
• Renal dosing considerations
• Contact Precautions

8
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
381706
9
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

10
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.

11
Hospital Acquired MRSA
12
Hospital-Acquired MRSA

• Initially reported in the 1970s
• 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, 20052328-2333.

13
HA-MRSA Therapy Options
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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 74928-935
• Lexi-Comp

15
Amin A, Batts D. Community Acquired and
Healthcare Associated MRSA. Medscape 2006
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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 4266-72
• Lexi-Comp

17
Amin A, Batts D. Community Acquired and
Healthcare Associated MRSA. Medscape 2006
18
Daptomycin (Cubicin)

• Lipopeptide
• Dose
• 4 mg/kg for skin/skin structure infections
• 6 mg/kg for bacteremia or endocarditis renal
  adjustment needed if CrCl lt30 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

19
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

20
Therapy Issues RegardingHA-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

21
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 (gt2 mcg/ml) and that these
  patients had higher infection-related mortality
  despite achieving high vancomycin trough levels
  (gt15 mcg/ml)
• Chest 2006 130 947-955
• Arch Intern Med 2006 166 2138-2144

22
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 (gt50) 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

23
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 gt 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

24
IV Medication Combination Effects
A Antagonism, DI drug interactions, I
indifferent, N no data, S synergy,
MLSbmacrolide, lincosamide resistant MRSA
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New drugs
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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

27
Community Acquired MRSA
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Community-Acquired MRSA

• Initially reported in the 1990s
• 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

29
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

30
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

31
Dosing for CA-MRSA (Adults)

• TMP-SMX 1-2 DS (double strength) tabs orally
  q8-12h
• typically dosed 2 twice daily if pt cant
  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

32
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

33
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

34
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

35
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

36
Inducible Clindamycin Resistance
Antimicrob Agents Chemother 2005 49(3) 1222-1224
37
Antimicrobial Susceptibilities CA- and HA-MRSA
JAMA 2003, 290 2976-2984
38
Estimated SusceptibilityCA-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

39
Therapy Considerations

• Resistance will continue to grow
• Use your hospitals 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
  Pfizers RSVP program (1-888-327-7787)

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MRSA ABX Acq. Cost Comparison
41
Short Case Studies
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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?

43
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?

44
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?

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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 PT tool for
  identifying credentialing issues
• Successful interventions are a corporate goal for
  improving patient safety, reducing LOS, and
  controlling supply costs