Johns Hopkins Antibiotic (ABX) Guide

Staphylococcus aureus

MICROBIOLOGY

  • Gram-positive cocci, usually seen in clusters.
  • Easily grown on blood agar or other conventional media.
    • Coagulase positive and thermonuclease positive.
  • Antimicrobial resistance: rare isolates remain penicillin susceptible. In many areas, MRSA > MSSA.

CLINICAL[Top]

  • Carried in anterior nares by 20-30% of population.
    • Higher carriage rates seen in diabetics, injection drug users (IDU), HIV or dialysis pts.
    • Carriers have > risk of subsequent infection.
  • Risk factors: skin disease, venous catheters, other foreign bodies (e.g., prosthetic joints, pacemakers), IDU, hemodialysis, recent surgical procedure.
  • Methicillin resistance increasing. MRSA traditionally associated w/ healthcare system interaction; CA-MRSA has emerged as significant pathogen, especially in children, prisoners, IDUs (although rates also increased in adults with no clear risk factors).
    • CA-MRSA mostly causes skin/soft tissue infections; these are relatively benign with good response to I&D ± antibiotics, although recurrent disease can occur. Rarely, serious disease with pyomyositis or necrotizing fasciitis may occur.
    • CA-MRSA also a cause of necrotizing pneumonia. Consider diagnosis in a severe pneumonia with evidence of cavitation/necrosis, particularly after influenza-like illness.
  • Dx: positive cx from sterile site (blood, joint, CSF), abscess or wound.
    • Positive cx from nares = colonization, not infection.
  • Staphylococcal toxic shock syndrome (see separate module) caused by TSST-1 or other enterotoxin producing strains. Constellation of fever, low BP, red rash & multiorgan failure. Risks: tampon use, nasal packing, surgical wounds.
  • Diarrhea: ingestion of preformed Staphylococcal enterotoxin causes acute, self-limited gastroenteritis. Incubation 2-6h.
  • Severe MRSA infections with vancomycin MIC 1.5-2.0 not responding to therapy, consider alternative agent (e.g., daptomycin). Several studies have worse clinical outcomes with vancomycin in these settings.

SITES OF INFECTION[Top]

  • Bloodstream: primary risk is presence of intravascular catheter, which should be removed.
  • Skin/soft tissues:folliculitis, cellulitis, furuncle, carbuncle, abscess, impetigo (may occur in combination with Streptococcus pyogenes). Breast:mastitis.
  • Abscesses: spleen, kidney, epidural space; visceral or deep abscesses occur almost always due to hematogenous seeding from bacteremia.
  • Cardiac: endocarditis, occurs in 6-25% of S. aureus bacteremia; afflicts both native and prosthetic valves.
  • Bone: osteomyelitis (S. aureus leading cause, most common is vertebral osteomyelitis secondary to bacteremia/discitis).
  • Prosthetic devices: e.g., pacemaker leads and pocket, prosthetic joints.
  • Lung: nosocomial pneumonia or following influenza. Septic pulmonary emboli: associated with right-sided endocarditis.
  • Mucosal surfaces: related to release of TSST-1 and subsequent toxic shock syndrome.
  • GI: toxin-associated gastroenteritis.
  • CNS: post-operative meningitis, meningitis or cerebritis associated with bacteremia/endocarditis

TREATMENT[Top]

Pneumonia

  • Consider MRSA pneumonia in any patient with severe CAP (e.g., ICU admission, necrotizing/cavitary disease, empyema) pending sputum or blood culture results.
  • Treatment: use susceptibilities to guide final choice.
    • Vancomycin 15mg/kg IV q12h
    • Linezolid 600mg IV/PO q12h
    • Clindamycin 600mg IV/PO q8h
  • Daptomycin cannot be used for pulmonary infections because it is inactivated by pulmonary surfactant.
  • Drain or proceed with thoracic surgical consultation for empyema.
  • Duration of therapy: 7-21d course, depending on severity; many cases of ventilator associated pneumonia can be treated for 8d; necrotizing pneumonia usually requires longer courses 14d; bacteremic pneumonia requires at least 14d.

Bone/joint infections

  • Osteomyelitis (OM)
    • MRI with gadolinium often best study to employ to diagnose infection and its extent.
    • Drainage and debridement of devitalized bone should be done if possible.
    • No clear data to suggest preference regarding parenteral or oral route of antibiotic.
    • Treatment:
    • MSSA: select from bacteremia choices above.
    • MRSA:
    • Some add rifampin to any of the above dosing as 600mg once daily or 300-450mg PO twice daily. If patient bacteremic, only add rifampin after bacteremia clear to avoid emergence of resistance.
    • Duration: unclear best course, many choose 6-8 wks. Some treat for additional 4-12 wks especially if OM of longstanding nature or if complete debridement not achieved. ESR/CRP may be used to follow response.
  • Septic arthritis
    • Always drain or debride joint. Repeat as needed. No clear preference for closed or open drainage.
    • Treatment: select from MSSA or MRSA choices as above.
  • Prosthetic joint infection: see module for additional details.
    • Early (< 2 mos post-op) or acute hematogenous infection w/ stable joint < 3wks symptoms:
      • Debride/washout joint and retain.
      • Select abx from OM choices above + rifampin 600mg or 300-450mg PO twice daily x 2 weeks. Follow by TMP/SMX, fluoroquinolone, tetracycline or clindamycin + rifampin x 3-6 months.
    • Late (> 2 mos post-op): or if unstable, later-onset infection or > 3wks symptoms--remove hardware and administer abx as above.

CNS

  • Meningitis
    • MRSA:
      • Preferred: vancomycin 15-20 mg/kg IV 12h (consider loading dose; guidelines recommend 25-30 mg/kg, although we favor 20-25 mg/kg, particularly in patients with any baseline renal dysfunction). Strive for trough level ~20 µg/mL.
      • Alternatives:
      • Some add rifampin 600mg PO/IV q24 or 300-450mg IV/PO q12h.
      • Refractory infection: consider intrathecal vancomycin, 5-20mg daily.
    • Duration: 14d.
    • CNS shunt infection: remove device. Replace only when CSF cultures repeatedly sterile.
  • Brain abscess, subdural empyema, epidural abscess
    • Consult neurosurgery urgently for drainage.
    • MSSA or MRSA: choices as above.
    • Duration: 4-6 wks.

Toxic Shock Syndrome

  • See Staphylococcal TSS module for details.
  • Remove focus of staphylococcal colonization or infection.
  • Stabilize blood pressure w/ aggressive hydration +/- pressors.
  • MSSA: oxacillin or nafcillin 2g IV q4h PLUS clindamycin 600mg IV q8h.
  • MRSA: vancomycin 15-20 mg/kg IV q12h PLUS clindamycin 600mg IV q8h (if susceptible) or linezolid 600 mg IV/PO q12h.
  • Consider intravenous immunoglobulin infusions.

FOLLOW UP[Top]

  • For patients with bacteremia or endocarditis, follow up blood cultures should be obtained to document clearance of bacteremia while on therapy.
  • Endocarditis treatment failure or persistent bacteremia: typically occurs on vancomycin therapy. Select an alternative antibiotic regimen as for bacteremia; ID and cardiac surgery consults recommended.
    • Always search for focus of infection or removal of any devices.
    • Salvage regimens not well studied, but options include both changing therapy and using combination therapy. Use susceptibilities to guide.
  • For patients with serious S. aureus infections treated with vancomycin, trough levels should be 15-20 mcg/ml (20 mcg/ml for CNS infection and severe pneumonia).

OTHER INFORMATION[Top]

  • Mortality associated with S. aureus bacteremia is 20-40%.
  • S. aureus bacteremia is associated with heart valve involvement in 25% when studied with transesophageal echo (TEE). Clinicians must rule out endocarditis before treating S. aureus bacteremia with short (i.e. 2 week) course antibiotics.
  • All patients with S. aureus bacteremia should undergo at least a good quality transthoracic echo (TTE). TEE is preferred for patients with prosthetic valves or with inadequate TTE.
  • Be alert for the development of metastatic abscess formation w/ any S. aureus bacteremia. S. aureus in urine cx should alert to the possibility of associated bacteremia.
  • Patients with MRSA colonization or infection should be placed on contact precautions.

Basis for recommendation[Top]

  • Liu C et al: Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 52:285, 2011 Feb. 1  [PMID:21217178]

    Comment: Guidelines looking at the MRSA compendium of diseases with recommendations that also include vancomycin dosing recommendations.
    Rating: Basis for recommendation

  • Rybak MJ et al: Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis 49:325, 2009 Aug. 1  [PMID:19569969]

    Comment: New guidelines for vancomycin dosing and monitoring.
    Rating: Basis for recommendation

  • Baddour LM et al: Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 111:e394, 2005 June 14  [PMID:15956145]

    Comment: Guidelines for the management of infective endocarditis
    Rating: Basis for recommendation

  • Stevens DL et al: Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 41:1373, 2005 Nov. 15  [PMID:16231249]

    Comment: Latest set of guidelines from the Infectious Diseases Society of American, incorporating recommendations for CA-MRSA.
    Rating: Basis for recommendation

References[Top]

  1. Dhand A et al: Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis 53:158, 2011 July 15  [PMID:21690622]

    Comment: Authors able to clear persistent bacteremia in 7 pts with combination of daptomycin and oxacillin or nafcillin (2g IV q4h) in seven patients. Mechanism not entirely clear but may be due to enhanced membrane binding of daptomycin in the presence of the beta-lactam.

  2. Thwaites GE et al: Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis 11:208, 2011   [PMID:21371655]

    Comment: Important to note that only 16 studies with < 1500 patients in RCTs form basis for guidance in this difficult infection. Authors rightly point out that much guideline recommendations are based on observational or limited case studies. Key questions that remain to be answered in their opinion include: 1) How should SAB be defined?, 2) Is identification and removal of infection focus important? 3) Should all SAB pts have echocardiography? 4) Are glycopeptides equivalent to beta-lactams? 5) Are cephalosporins equivalent to penicillins?, 6) Is teicoplanin as effective as vancomycin? 7) What is the optimum duration of treatment for SAB? 8) Is oral therapy the equivalent to parenteral? 9) Is combination therapy better than monotherapy? 10) what is the role of linezolid, daptomycin and newer antimicrobials?
    Rating: Important

  3. Simor AE: Staphylococcal decolonisation: an effective strategy for prevention of infection? Lancet Infect Dis 11:952, 2011   [PMID:22115070]

    Comment: Best data regarding decolonization efficacy exists in pre-surgical patients and those on dialysis. Efficacy for decreasing CA-MRSA recurrent infections doesn’t yet exist in robust fashion.
    Rating: Important

  4. Figueroa DA et al: Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis 49:177, 2009 July 15  [PMID:19500039]

    Comment: Single center study evaluating the safety of higher doses of daptomycin.
    Rating: Important

  5. Cosgrove SE et al: Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis 48:713, 2009 March 15  [PMID:19207079]

    Comment: Evidence for nephrotoxicity associated with short course synergy dose gentamicin in the treatment of S. aureus bacteremia and endocarditis.

  6. Fowler VG et al: Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 355:653, 2006 Aug. 17  [PMID:16914701]

    Comment: Recent publication demonstrating that daptomycin is not inferior to standard therapy in the treatment of S. aureus bacteremia and right-sided endocarditis.
    Rating: Important

  7. Cosgrove SE, Carroll KC, Perl TM: Staphylococcus aureus with reduced susceptibility to vancomycin. Clin Infect Dis 39:539, 2004 Aug. 15  [PMID:15356818]

    Comment: Review of the epidemiology, diagnosis, and management of patients with S. aureus with reduced susceptibility to vancomycin.
    Rating: Important

  8. Naimi TS et al: Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 290:2976, 2003 Dec. 10  [PMID:14665659]

    Comment: A study that elucidates the clinical and microbiologic differences between healthcare-associated MRSA and community-associated MRSA.
    Rating: Important

  9. von Eiff C et al: Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med 344:11, 2001 Jan. 4  [PMID:11136954]

    Comment: A German study indicating that S. aureus bacteremia appears to frequently be caused by strains of S. aureus colonizing the patient's own nasal mucosa. An accompanying editorial emphasizes the importance of attempting to eradicate this colonization in order to control nosocomial infections, but highlights the failure of most currently used agents to achieve this goal (N Engl J Med 2001; 344: 55-57)

  10. Fowler VG et al: Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol 30:1072, 1997   [PMID:9316542]

    Comment: A study demonstrating the presence of endocarditis in 25% of patients with S. aureus bacteremia when evaluated with TEE.
    Rating: Important

  11. Heldman AW et al: Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med 101:68, 1996   [PMID:8686718]

    Comment: A study comparing standard therapy for right-sided endocarditis to oral ciprofloxacin and rifampin for 4 weeks that demonstrates the efficacy of the oral regimen.

  12. DiNubile MJ: Short-course antibiotic therapy for right-sided endocarditis caused by Staphylococcus aureus in injection drug users. Ann Intern Med 121:873, 1994 Dec. 1  [PMID:7978701]

    Comment: A review of the option of shorter course antibiotic therapy for right-sided heart infections in injection drug users.

  13. Markowitz N, Quinn EL, Saravolatz LD: Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med 117:390, 1992 Sep. 1  [PMID:1503330]

    Comment: A study of 101 injection drug users with S. aureus infection of whom 65% were bacteremic. The success rate for therapy of MRSA infections was equivalent for the TMP-SMX and vancomycin groups, although vancomycin was marginally more successful as a therapy in the non-MRSA group. The authors thus suggests that TMP-SMX may be a viable alternative to vancomycin for MRSA infection in this group of patients.
    Rating: Important

  14. Tranter HS: Foodborne staphylococcal illness. Lancet 336:1044, 1990 Oct. 27  [PMID:1977028]

    Comment: A review of GI tract infections caused by ingestion of certain toxin-producing strains of S. aureus.

  15. Lee BK, Crossley K, Gerding DN: The association between Staphylococcus aureus bacteremia and bacteriuria. Am J Med 65:303, 1978   [PMID:686015]

    Comment: The classic paper describing the presence of S. aureus bacteriuria in 27% of patients with S. aureus bacteremia in the absence of obvious renal infection.

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