Infectious Disease in Illinois

Methicillin-Resistant Staphylococcus aureus in Illinois:
Guidelines for the Primary Care Provider

Introduction

This document is intended to provide interim clinical guidance for management of Staphylococcus aureus skin and soft tissue infections (SSTI) in outpatients in Illinois, in the setting of increasing levels of community-associated methicillin resistant S. aureus (CA-MRSA).

Background

Methicillin-resistant S. aureus (MRSA) are resistant to currently available ß-lactam antibiotics, including penicillinase-resistant penicillins (methicillin, oxacillin, nafcillin, dicloxacillin), penicillins combined with a ß-lactamase inhibitor (e.g. amoxicillin-clavulanate), cephalosporins (e.g. cefazolin, cephalexin), and carbapenems (imipenem, meropenem, ertapenem). Prior to the mid-1990s, MRSA infections were uncommon in patients without prior contact with the health care system, history of injection drug use, or recent receipt of antimicrobial therapy. However, recent reports suggest that the frequency of MRSA infections is increasing in Illinois and nationally among healthy patients without the traditional risk factors for MRSA infections. Current evidence suggests that these CA-MRSA strains are genetically distinct from those identified from patients with health care-associated MRSA, have different antibiotic susceptibility patterns, and may cause a different spectrum of illness (including SSTIs of varying severity). CA-MRSA, like other S. aureus strains, may cause serious invasive infections including osteomyelitis, serious respiratory disease including necrotizing pneumonia, secondary pneumonia associated with influenza, septic phlebitis, as well as Waterhouse Friderichsen and toxic shock syndrome.

Clinical approach to potential S. aureus skin and soft tissue infections (SSTI)

  • Incision and drainage (I & D) must be emphasized as a primary treatment of fluctuant abscesses and should be performed whenever possible. For mild uncomplicated abscesses [those with no or minimal (e.g. < 2-5 cm) cellulitis], in immuncompetent patients without diabetes mellitus, I & D without the use of antimicrobials can be a reasonable treatment option. Adjunctive antimicrobial therapy may be useful in decreasing spread by sterilizing ongoing wound drainage, if present. Antimicrobial therapy alone (either topical or oral) without I & D is not recommended for treatment of fluctuant abscesses.

  • While CA-MRSA should now always be considered as a potential pathogen in all cases of SSTI, clinicians should maintain an especially high index of suspicion in high risk patients, e.g. in crowded living conditions (especially homeless shelters, military barracks, and other institutional settings), recent incarceration, injection drug use, participation in contact sports, and those who have failed treatment for SSTI with a ß-lactam antibiotic (e.g. dicloxicillin or cephalexin). CA-MRSA also has been described in newborn infants, in association with any situation where there is increased close contact (e.g. sexual activity), and in contacts of high-risk patients.

  • For outpatients with potential MRSA infections, it is important to obtain specimens for culture and susceptibility testing before initiating antibiotic treatment. If I & D is not possible, other options include culture of spontaneously draining wounds and/or biopsy and culture of the advancing edge of cellulitis. Culture of the superficial surface of open wounds is not recommended because it may yield skin-colonizing bacteria and not the true pathogen. If smaller satellite lesions are present, these may be opened and cultured.

Clinicians should determine if household or other close contacts of the patient have SSTI or other infections compatible with MRSA, and facilitate their evaluation and treatment, if indicated.

Empiric oral antimicrobial therapy for suspected MRSA infections (see also Table 1)

  • There are no randomized clinical trials regarding the most effective treatment for CA-MRSA. Therefore, these recommendations are based on expert judgment, experience gained from the use of non-beta lactam antimicrobials for treatment of S. aureus infections in patients with penicillin allergies, and recent published experience with treatment of CA-MRSA.

  • In many patients with mild infections, I & D of abscesses without antimicrobial therapy is an appropriate and sufficient treatment option.

  • Antimicrobial therapy should be reserved for infections that cannot be managed with I & D alone, and for patients who are systemically ill or have more serious infections. In addition, antimicrobial therapy should be considered for patients with immunosuppression or underlying diseases, such as diabetes mellitus, and for young children, especially those younger than a year of age.

  • Oral antimicrobial therapy is not recommended for critically ill patients.

  • All patients should be monitored for response to therapy. Instruct outpatients to return if they develop signs or symptoms of systemic illness, have worsening local symptoms, or if no improvement is seen in 48-72 hours.

  • Antibiotic regimens should be modified based on results of culture and susceptibility testing of isolates from affected skin and soft tissue or wound drainage.

  • MRSA is resistant to all penicillins (including nafcillin and dicloxacillin), beta-lactamase inhibitor combinations (including Augmentin), and all cephalosporins.

All laboratories should routinely evaluate S. aureus isolates that initially test as resistant to erythromycin and susceptible to clindamycin for inducible clindamycin resistance using the “D-zone test.” When inducible clindamycin resistance is present, the isolate is presumed to be resistant, and use of an alternative agent should be considered.1

NOTE: Group A streptococci (GAS) are another common cause of SSTI, particularly cellulitis and impetigo. If Group A streptococcal infection is suspected, therapy should include an agent active against this organism [ß-lactam (penicillins or cephalosporins), macrolide (erythromycin, clarithromycin, azithromycin) or clindamycin]. Tetracyclines and trimethoprim-sulfamethoxazole (TMP-SMX), although active against many CA-MRSA isolates, are not recommended treatments for suspected GAS infections based on resistance (tetracyclines), and lack of supporting data (TMP-SMX). Clindamycin is usually effective against both GAS and most strains of CA-MRSA.


  1. The clinical relevance of inducible clindamycin resistance is not fully understood; clindamycin has been successfully used for treatment of some patients with MRSA and a positive “D-zone test.”

Reporting, infection control and patient education

Clusters of MRSA in community settings (two or more laboratory confirmed cases occurring in a two week period with a suspected epidemiologic link) should be reported to the local health department.

Patients with S. aureus infections (including MRSA), their family members and close contacts should be counseled about measures to prevent spread of infection. Information about S. aureus and MRSA, including infection control messages for patients, is available at http://www.idph.state.il.us/public/hb/hbmrsa.htm.

CA-MRSA can be easily transmitted in the health care setting, either by transfer from patient to patient by health care workers’ hands that are contaminated from patient contact, or by contact with contaminated items. In addition to standard precautions, contact precautions should be used in hospitals for all patients with MRSA infections, and in all healthcare settings for patients with uncontained wound drainage.

Additional information on infection control in health care settings can be accessed at http://www.cdc.gov/ncidod/dhqp/gl_isolation.html.

Additional information about CA-MRSA for clinicians and patients can be accessed at: http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.

Acknowledgements

Thank you to the following individuals for their contributions to this document:

1.

Robert Daum, M.D.

University of Chicago Children’s Hospital

2.

Arthur Frank, M.D.

University of Illinois Hospital

3.

Susan Gerber, M.D.

Chicago Department of Public Health

4.

Janet Jokela, M.D.

University of Illinois College of Medicine, Urbana

5.

Nancy Khadori, M.D.

Memorial Medical Center, Springfield

6.

Gary Noskin, M.D.

Northwestern Memorial Hospital

7.

Tina Tan, M.D.

Children’s Memorial Hospital

8.

Richard (Tom) Thomson, Ph.D.

Evanston Northwestern Healthcare

9.

Stephen Weber, M.D.

University of Chicago Hospitals

10.

Robert A. Weinstein, M.D.

Stroger Hospital of Cook County, Rush University Medical Center

Important Note: This document is provided as an information resource for physicians and other health care professionals to assist in the appropriate management of patients with CA-MRSA. Recommendations for care and treatment change rapidly, and opinion can be controversial; therefore, physicians and other health care providers are encouraged to consult with other sources, especially manufacturers’ package inserts, to confirm information provided in this document. The individual physician or other health care professional should use his/her best medical judgment in determining appropriate patient care or treatment. IDPH and the authors make no warranty as to the reliability, accuracy, timeliness, usefulness, or completeness of the information provided. Determination of appropriate treatment is the responsibility of the treating health care provider.

Comments and corrections may be addressed to Craig S. Conover, M.D. (craig.conover@illinois.gov, fax 312-814-4844).

Table 1. Interim Guidelines for Empiric Oral Antimicrobial Treatment of Outpatients with Suspected MRSA Skin and Soft Tissue Infections (SSTI)

Many lesions do not require antibiotic therapy; I & D alone is sufficient. When empiric therapy is needed based on clinical assessment, the following antibiotics may be used while awaiting susceptibility results. The duration of therapy for most SSTI is usually seven to 10 days, but may vary depending on severity of infection and clinical response. NOTE: Before prescribing antimicrobial therapy, clinicians should consult complete drug prescribing information in the manufacturer’s package insert or the Physicians’ Desk Reference.

Interim Guidelines for Empiric Oral Antimicrobial Treatment of Outpatients with Suspected MRSA Skin and Soft Tissue Infections (SSTI)

Antimicrobial

Adult Dose2**

Pediatric Dose2**

Trimethoprim-sulfamethoxazole (TMP/SMX) DS

1-2 double strength tablets q 8-12 hours3

Base dose on TMP: 8-12 mg TMP (& 40-60 mg SMX) per kg/day in 2 doses; not to exceed adult dose

Minocycline or Doxycycline

100 mg PO q 12 hours4

Not recommended for children younger than 9 years of age. For children 9 years or older: 4 mg/kg/day in 2 divided doses, not to exceed 200 mg/day.

Clindamycin1

300-450 mg PO q 8-12 hours

10-30 mg/kg/day in 3-4 divided doses; not to exceed adult dose


Linezolid

Outpatient use of linezolid in SSTI. Linezolid has great potential for inappropriate use, inducing antimicrobial resistance, and toxicity. It is not recommended for empiric treatment or routine use because of these concerns as well as the high cost of this medication. It is strongly recommended that linezolid only be considered after consultation with an infectious disease specialist.

  1. If considering clindamycin, isolates resistant to erythromycin and susceptible to clindamycin should be evaluated for inducible clindamycin resistance using the “D- zone test.”
  2. Before treating, clinicians should consult complete prescribing information in the manufacturer’s package insert or the Physicians’ Desk Reference.
  3. Each DS tablet contains 160 mg TMP/ 800 mg SMX.
  4. Not recommended for pregnant women

NOTE: Outpatient use of quinolones or macrolides. Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin) and macrolides (e.g., erythromycin, clarithromycin, azithromycin) are NOT recommended for treatment of MRSA because of ready development of resistance. If fluoroquinolones are being considered, consult with an infectious disease specialist before use.


April 2008





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