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

  • 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 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.
    • Probably not a frequent cause of cellulitis in the absence of purulence (abscess) or wound [1].
  • 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

  • Bloodstream: primary risk is presence of intravascular catheter, which should be removed.
    • May occur without apparent focus or entry site.
    • Evaluate if without focus for endocarditis (TTE/TEE), mycotic aneurysms or vertebral infection (discitis, osteomyelitis, epidural abscess)
  • 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

Bacteremia

  • Perform detailed history and physical to detect source and if metastatic spread has occurred. Infectious diseases consultation recommended in most cases.
    • Remove foci of infection whenever possible; remove implicated venous catheter if present.
    • May occur without apparent focus or entry site.
    • Evaluate if without focus for endocarditis (TTE/TEE), mycotic aneurysms or vertebral infection (discitis, osteomyelitis, epidural abscess).
    • Rule out endocarditis with echocardiography (TEE preferred).
  • Treatment:
    • MSSA: superiority of β-lactams make clear favorite over using vancomycin.
      • Preferred: oxacillin or nafcillin 2g IV q4h.
      • Alternative for non-life threatening PCN allergy: cefazolin 2g IV q8h. Cefazolin can be given to hemodialysis patients: 2 gm after dialysis if next dialysis in 2 days and 3 gm after dialysis if next dialysis in 3 days.
      • Consider oxacillin/nafcillin desensitization for life-threatening Type 1 PCN allergy (hives/anaphylaxis).
    • MRSA or life-threatening PCN allergy:
      • Preferred: vancomycin 15-20mg/kg q 12h. Consider loading dose for severe infections: guidelines recommend 25-30 mg/kg, although at Johns Hopkins, favor 20-25 mg/kg, particularly in patients with any baseline renal dysfunction.
      • Alternatives: for severe allergy or treatment failure, consider infectious diseases consultation. Little robust data to guide choices. Unclear if monotherapy or combination therapy needed for salvage therapy.
        • Daptomycin 6mg/kg IV daily (FDA approved for S. aureus bacteremia and right-sided endocarditis, preferred in most instances); some experts recommend higher doses 8-10 mg/kg daily for severe infections.
        • Linezolid 600mg IV/PO q12h (not FDA approved for S. aureus bacteremia)
        • Quinupristin/dalfopristin 7.5mg/kg IV q12h. (not FDA approved for S. aureus bacteremia
        • TMP/SMX 5 mg/kg IV q8-12h (not FDA approved for S. aureus bacteremia).
        • Ceftaroline 600mg IV q12h (not FDA approved for S. aureus bacteremia).
        • Telavancin 10mg/kg IV once daily (not FDA approved for S. aureus bacteremia).
  • Duration of therapy:
    • Bacteremia: 28d is the standard course of therapy
      • Short course therapy, 14d only if following criteria met:
        • Endocarditis is ruled out by transesophageal echocardiography
        • No implanted prostheses (e.g., prosthetic valves, cardiac devices, or arthroplasties)
        • Blood cultures drawn 2-4 days after the initial cultures were negative, the patient defervesces within 72 hours of appropriate therapy
        • No evidence of metastatic infection
    • Endocarditis or epidural abscess: 42d minimum.

Endocarditis, native valve

  • Perform detailed history and physical to detect source and metastatic spread.
  • Diagnostic and therapeutic considerations:
    • Remove or drain foci of infection whenever possible.
    • Obtain brain & CNS vessel imaging if neurologic symptoms or persistent headache present.
    • Consult cardiac surgery if patient has persistently positive blood cultures, evidence of heart failure or ongoing embolic disease.
      • Evaluation especially recommended if vegetation > 10mm, new heart block, persistent fevers.
    • Obtain MRI w/ contrasts spine imaging if back pain present to assess for discitis, verterbral osteomyelitis or epidural abscess.
    • Echocardiography recommended, TEE favored over TTE.
  • Treatment:
    • MSSA, native valve, left-sided:
      • Preferred: oxacillin or nafcillin 2g IV q4h for 4-6 weeks with optional addition of gentamicin 1 mg/kg IV q8h for 1st 3-5 days.
      • Alternative for non-life threatening PCN allergy: cefazolin 2g IV q8h with optional addition of gentamicin 1 mg/kg IV q8h for 1st 3-5 days. Use of synergistic gentamicin does not decrease mortality and is associated with nephrotoxicity--avoid in patients with baseline decreased CrCl, diabetes, advanced age.
      • Many clinicians no longer employ gentamicin.
    • MSSA, native valve, right-sided involvement ONLY: pt w/o AIDS, vascular prosthesis or embolic dz other than septic pulmonary emboli.
      • Preferred: oxacillin or nafcillin 2g IV q4h ± gentamicin 1 mg/kg IV q8h for 14d.
        • Use of synergistic gentamicin does not decrease mortality and is associated with nephrotoxicity--avoid in patients with baseline decreased CrCl, diabetes, advanced age.
        • IDSA MRSA endocarditis recommendations no longer favor gentamicin for native valve infection.
    • Alternate oral regimen: only for IDU, TV MSSA endocarditis.
      • Ciprofloxacin 750 mg PO twice daily PLUS rifampin 300 mg PO twice daily for 28 days, if isolate proven susceptible to both agents.
    • Alternate, if life-threatening penicillin allergy:
      • Desensitize to oxacillin/nafcillin (preferred).
      • Vancomycin 15-20 mg/kg IV q12h (consider loading dose; guidelines recommend 25-30 mg/kg, although at Johns Hopkins favor 20-25 mg/kg, particularly in patients with any baseline renal dysfunction).
    • MRSA, native valve, right or left sided involvement:
      • Preferred: vancomycin 15-20 mg/kg IV q12h for 4-6 wks.
      • Alternative: daptomycin 6 mg/kg IV daily for 4-6 weeks; some experts recommend higher doses 8-12 mg/kg daily.

Endocarditis, prosthetic valve

  • TEE recommended for all cases to evaluate for significant perivalvular abscess, leak or if other valves involved.
  • Early evaluation for potential valve replacement suggested.
  • See diagnostic and therapeutic considerations listed above.
  • MSSA, prosthetic valve:
    • Oxacillin or nafcillin 2g IV q4h for 6 weeks PLUS gentamicin 1 mg/kg IV q8h for 1st 2 weeks PLUS rifampin 300 mg PO q8h for 6 weeks after blood cultures have cleared; confirm susceptibility to all agents.
  • MRSA, prosthetic valve:
    • Vancomycin 15-20 mg/kg IV q12h for 6 weeks (consider loading dose of 25-30 mg/kg) PLUS gentamicin 1 mg/kg IV q8h for 1st 2 weeks PLUS rifampin 300 mg PO q8h for 6 weeks after blood cultures have cleared; confirm susceptibility to all agents.

Soft tissue infections

  • Surgical drainage for any collection. For cutaneous abscess, I & D may be sufficient.
  • For non-purulent cellulitis, this usually is due to β-hemolytic streptococci rather than CA-MRSA.
  • Antibiotics indicated for severe/rapidly progressive infections, signs and symptoms of systemic illness, diabetes or other significant immunosuppression, advanced age, location of abscess in an area where complete drainage is difficult, lack of response to initial I&D (also assess for need for additional I&D), extensive abscess-associated cellulitis.
  • If antibiotics employed, obtaining cultures recommended to help guide therapy.
  • Treatment:
    • Parenteral: IV antibiotics generally not needed unless severe infection, concomitant bacteremia or systemic toxicity.
      • If using parenteral abx,choices the same as listed above for bacteremia, exceptions:
        • Vancomycin 1g q12h IV (if routine infections), 15mg/kg IV q12h (severe infections)
        • Daptomycin dose is 4mg/kg IV daily
    • Oral regimens:
    • Duration of therapy: depends on extent of disease, usual range 5-10 days.
  • Recurrent soft tissue infections: education regarding hand hygiene and personal hygiene (e.g., regular bathing, no sharing of personal items, clean personal sporting equipment, avoid shaving).
    • Clean high touch areas in contact with bare skin (e.g., counters, sinks, door knobs, tubs, toilet seats, etc) with commercial cleaners
    • Indications for decolonization include recurrent infection despite optimal hygeine or household transmission. Evaluate contacts for evidence of S. aureus infection. Routine screening cultures of nares not recommended.
    • Consider decolonization for recurrent soft tissue infections: potential approaches include (both index patient ± contacts/household)
      • Mupirocin 2% ointment to nares twice daily for 5-10 days. Some repeat for a period of months, e.g, first five days of each month.
      • Mupirocin 2% as above + chlorhexidine (Hibiclens) washes daily for 5-14d or dilute bleach bath (1 tsp/gallon, ¼ cup per 13 gallons) twice weekly x ~3 months.
      • Oral antibiotics not usually recommended. Some use if above measures fail. Typically choose one drug from oral MRSA regimen above plus rifampin (e.g., doxycycline 100mg twice daily + rifampin 600mg daily x 7-10d).
  • Some clinicians add rifampin to oral agents for MRSA for patients with recurrent soft tissue infections; rifampin should NEVER be used as monotherapy; efficacy of this strategy is unproven and rifampin is associated with significant drug interactions so we do not recommend it in most cases.

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 help guide final choice. Linezolid may have better PK/PD data in lung compared to vancomycin; recent study shows better initial clinical success than vancomycin, but similar 60d mortality [2].
  • Daptomycin cannot be used for pulmonary infections because it is inactivated by 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, at least 14d.

Bone/joint infections

  • Osteomyelitis (OM)
    • MRI with gadolinium often best study to employ to diagnose infection in verterbral bones or feet.
    • 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:
    • 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 closed drainage as needed.
      • No clear preference for closed or open drainage.
      • Consult orthopedics for 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.

Selected Drug Comments

Drug

Recommendation

Amoxicillin/clavulanate

Good activity against MSSA and other Gram + organisms (not MRSA). Useful for skin and skin structure infections when some Gram (-) and anaerobic coverage is also desirable (bite, mixed abscess). Not recommended for S. aureus bacteremia or endocarditis.

Ampicillin/sulbactam

Good activity against MSSA and other Gram + organisms (not MRSA). Useful for skin and skin structure infections when some Gram (-) and anaerobic coverage is also desirable (bite, mixed abscess). Not recommended for S. aureus bacteremia or endocarditis.

Cefazolin

First generation cephalosporin antibiotic with excellent general Gram + activity except for enterococci and MRSA. A practical alternative for S. aureus endocarditis or bacteremia therapy when CNS involvement is not suspected (only 1-4% penetration into CSF)

Clindamycin

A good choice for skin and skin structure infections due to S. aureus, particularly CA-MRSA. CA-MRSA susceptibilities to clindamycin vary by geographic location. Erythromycin resistance predicts inducible clindamycin resistance in many isolates; thus, the microbiology lab should perform a D-test to assess for clindamycin susceptibility. Excellent oral absorption, although GI intolerance (including C. difficile) is more likely with higher doses. Not recommended for S. aureus bacteremia or endocarditis.

Minocycline

A good choice for skin and skin structure infections due to S. aureus, particularly CA-MRSA; poor anti-streptococcal activity. Has the best in vitro Gram + activity of the tetracyclines. Side effects include photosensitivity, reversible vestibular dysfunction, and blue skin discoloration. Often used for long-term suppressive therapy in orthopedic infections, sometimes in combination with rifampin. Not recommended for S. aureus bacteremia or endocarditis.

Nafcillin

Well-established agent for serious systemic S. aureus infections (not MRSA). No dose adjustment for renal failure. Main toxicity is neutropenia. Agent is administered intravenously q4h or by pump for home therapy.

Oxacillin

Well-established agent for serious systemic S. aureus infections (not MRSA). No dose adjustment for renal failure. Main toxicity is elevation of hepatic enzymes. Agent is administered intravenously q4h or by pump for home therapy.

Piperacillin/tazobactam

Good activity against MSSA and other Gram + organisms (not MRSA) as well as most Gram (-) organisms. Useful for broad spectrum empiric therapy when MSSA, streptococcus, enterococcus, Gram (-), and anaerobic coverage is desirable. Not recommended for S. aureus bacteremia or endocarditis.

Quinupristin/dalfopristin

Combination streptogramin antibiotic active against MRSA and Vancomycin resistant Enterococcus faecium. E. faecalis is intrinsically resistant. Not FDA approved for S. aureus bacteremia. Must be given IV via a central line because of phlebitis risk. Other side effects are severe arthralgia and myalgia. Has a variety of drug-drug interactions mediated via the cytochrome P450 system. No dose adjustment is required for renal or hepatic insufficiency.

Rifampin

Excellent bactericidal agent against S. aureus but SHOULD NEVER BE USED AS MONOTHERAPY because of rapid development of resistance. Can be used in combination with fluoroquinolones, TMP/SMX, clindamycin, or minocycline after a course of appropriate IV therapy for complicated bone and joint infections requiring long-term therapy/suppression. Also used as part of combination therapy for PVE. No robust studies have proven beneficial role independently, and some have suggested use equates with poorer outcomes.

Trimethoprim/sulfamethoxazole

A good choice for skin and skin structure infections due to S. aureus, particularly CA-MRSA; poor anti-streptococcal activity . Use compared to vancomycin has been studied in a cohort of injection drug users with MSSA and MRSA infections with good clinical results, particularly with MRSA. Not recommended for S. aureus bacteremia or endocarditis except in salvage situations in conjunction with infectious diseases consultation.

Vancomycin

  • Active against MRSA and MSSA (but less effective so if MSSA, prefer beta-lactam therapy for serious infections).
    • Clinical failure rate is higher for staphylococcal endocarditis treated with vancomycin than with alternate beta-lactam agents. Use is thus reserved for MRSA or for patients with documented severe beta-lactam allergy.
  • Must be given IV (no oral absorption).
  • When using this agent it is prudent to follow serum trough levels (aiming for a trough of 15-20 mcg/ml for serious infections). No single dose should exceed 2g. Loading dose should be considered in patients who are critically ill.
  • Trough concentrations are most accurate method to guide dosing; obtain after steady state likely following 4th or 5th dose. For routine SSTI infections, 1g q12h dosing should be adequate.

Linezolid

  • An oxazolidinone antibiotic available both orally and intravenously with activity against both MSSA and MRSA as well as VRE. No dose alteration required in renal or hepatic insufficiency.
  • Not FDA approved for S. aureus bacteremia.
  • Side effects include thrombocytopenia, anemia, neutropenia as well as optic neuritis and irreversible peripheral neuropathy. Side effects are more common in patients receiving the drug for > 3 weeks.
  • Because it is a monoamine oxidase inhibitor (MAO-I), it should not be used with MAO-Is and should be used with caution with serotonergic drugs (SSRIs) given case reports of serotonin syndrome. Patient on both drugs should be monitored for mental status changes, myoclonus, diaphoresis and other symptoms of serotonin syndrome.

Daptomycin

  • A lipopeptide antibiotic FDA approved for MSSA and MRSA bacteremia and right-sided endocarditis and complicated skin and skin structure infections due to MSSA, MRSA, GAS, and VSE.
  • It is inactivated by pulmonary surfactant and cannot be used for pneumonia.
  • Dose is 6 mg/kg/day when used for S. aureus bacteremia or endocarditis and 4 mg/kg/day when used for skin infections. Some experts recommend higher doses (8-12 mg/kg daily) for MRSA bacteremia and endocarditis. Dose reduction required for CrCl < 30mL/min (same doses but administered every other day).
  • Main side effect is myopathy; CK must be checked at least weekly.
  • Cases of emergence of resistance during therapy have been reported, particularly in patients without source control who have received prior vancomycin; monitor for recurrent positive blood cultures during therapy.

Doxycycline

A good choice for skin and skin structure infections due to S. aureus, particularly CA-MRSA but has poor anti-streptococcal activity. Side effects include photosensitivity (patients should be warned to avoid the sun). Often used for long-term suppressive therapy in orthopedic infections, sometimes in combination with rifampin . Not recommended for S. aureus bacteremia or endocarditis.

Tigecycline

FDA approved for skin and soft tissue infections. Low serum levels make this a drug not typically employed for bacteremia. FDA warning issued based on review of clinical trials warned of increased mortality with its use.

Telavancin

  • Lipoglycopeptide that was initially FDA approved for SSTI on the basis of non-inferiority studies compared to vancomycin. Unclear if lower MRSA MIC of telavancin compared to vancomycin has clinical significance.
  • May cause red man syndrome and should not be used in pregnancy.
  • May be slightly more nephrotoxic than vancomycin.
  • After an absence, drug is now again available in US.
  • In 2013 FDA approved drug to be used for HAP but only when other alternatives are not suitable, i.e., not a first line agent. Concern with the drug is that studies have suggested a substantially higher rate of mortality in patients with diabetes or renal failure compared to those treated with vancomycin.

Ceftaroline

New generation cephalosporin with MRSA activity as well as Gram negative spectrum similar to ceftriaxone. FDA approved for CAP and SSTIs, but some clinicians using off label with success in the treatment of difficult MRSA infections including persistent bacteremia (typically dosed 600mg IV q 8 +/- another agent [e.g., TMP/SMX] in salvage situations).

FOLLOW UP

  • 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.
  • 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

  • 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

  1. 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  [PMID:15956145]

    Comment: Guidelines for the management of infective endocarditis

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

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

  3. 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  [PMID:21217178]

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

  4. 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  [PMID:19569969]

    Comment: New guidelines for vancomycin dosing and monitoring.

References

  1. Pallin DJ et al: Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis 56:1754, 2013  [PMID:23457080]

    Comment: Interestingly this trial did not suggest that adding an agent with activity against CA-MRSA (TMP/SMX) did not substantially improve outcomes [82% cephalexin alone, 85% combination]. This suggests that MRSA is not a common driver of cellulitis in the absence of purulence.

  2. Wunderink RG et al: Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 54:621, 2012  [PMID:22247123]

    Comment: Fairly large trial in a difficult to study condition. RCT examined linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) x 7-14d. Enrolled pts numbered 1184, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). Howvever, all-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). This study suggests that the PK/PD elements favoring linezolid may in fact have clinical efficacy favorable over vancomycin but the larger 60d picture is not telling. For the very ill with potential for added complications such as renal failure, linezolid may be the better option.

  3. 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  [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.

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

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

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

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

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

  7. 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.

  8. 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

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

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

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

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

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

  12. Fowler VG et al: Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 355:653, 2006  [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

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

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

  14. 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

  15. 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  [PMID:19500039]

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

  16. 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.

  17. 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

  18. Vos FJ et al: Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia. Medicine (Baltimore) 91:86, 2012  [PMID:22391470]

    Comment: Study of 115 patients with staph or strep bacteremia using FDG-PET/CT technology looking for metastatic infections found foci in 84 of 115 (73%) patients: endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. Signs or symptoms directing a diagnostic work-up were only present in 41%, suggesting that additional studies may be helpful even in absence of specific findings: for example in this study PET was the first to detect problems in 30%.

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