What antibiotics are effective against Staphylococcus (Staph) infections?

Antibiotics Effective Against Staphylococcus Infections

For methicillin-susceptible Staphylococcus aureus (MSSA), penicillinase-resistant penicillins (flucloxacillin, dicloxacillin, oxacillin) are the antibiotics of choice, while for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin or daptomycin should be used as first-line therapy. 1, 2

Methicillin-Susceptible Staphylococcus aureus (MSSA)

First-Line Agents

• Penicillinase-resistant penicillins are superior to all other options for serious MSSA infections, including flucloxacillin 12 g/day IV in 4-6 divided doses, dicloxacillin 250 mg every 6 hours for severe infections, or oxacillin 12 g/day IV in 4-6 divided doses. 3, 4, 5
• Beta-lactams demonstrate lower recurrence rates than vancomycin for MSSA and should always be preferred over vancomycin when susceptibility is confirmed. 1
• First-generation cephalosporins (cefazolin 6 g/day IV in 3 doses, cephalexin) are effective alternatives for MSSA, particularly in patients with non-anaphylactic penicillin allergies. 3, 5

Alternative Agents for Penicillin Allergy

• Clindamycin can be used when susceptibility is documented and clindamycin resistance is <10%. 2, 5
• Vancomycin 30-60 mg/kg/day IV should be reserved for patients with true anaphylactic penicillin reactions (urticaria, angioedema, bronchospasm, anaphylaxis). 3
• Cephalosporins are contraindicated in patients with immediate-type penicillin hypersensitivity reactions. 5

Methicillin-Resistant Staphylococcus aureus (MRSA)

Empirical Therapy (Pending Culture Results)

• Vancomycin 15-20 mg/kg IV every 8-12 hours or daptomycin 6 mg/kg IV once daily should be initiated as empirical therapy for suspected MRSA, with both agents providing equivalent coverage. 1
• A loading dose of 25-30 mg/kg vancomycin should be administered in seriously ill patients to rapidly achieve therapeutic levels. 3
• Empirical therapy should include a lipo/glycopeptide in high-risk patients with previous hospitalizations, previous antibiotics, or prior MRSA colonization. 3

Targeted Therapy for Confirmed MRSA

Parenteral Options

• Vancomycin with target trough levels of 15-20 mcg/mL remains the standard for serious MRSA infections, including bacteremia and endocarditis. 3, 1, 6
• Daptomycin 6 mg/kg IV once daily is equally effective as vancomycin for MRSA bacteremia and right-sided endocarditis, with some experts recommending 8-10 mg/kg for complicated cases or when vancomycin MIC >1 mg/L. 1, 6, 7
• Teicoplanin 6-12 mg/kg IV every 12 hours for three doses, then daily is an alternative glycopeptide with better tissue penetration than vancomycin. 3, 6
• Linezolid 600 mg IV/PO twice daily can be considered for MRSA skin and soft tissue infections and is probably the drug of choice for complicated MRSA SSTIs. 3, 7

Oral Options for Outpatient MRSA

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160-320/800-1600 mg PO every 12 hours is effective for outpatient purulent skin and soft tissue infections. 3, 2
• Doxycycline 100 mg PO every 12 hours or minocycline 200 mg loading dose, then 100 mg PO every 12 hours are alternatives for non-multiresistant MRSA. 3, 2
• Clindamycin is the antibiotic of choice for less serious non-multiresistant MRSA infections such as skin and soft tissue infections when susceptibility is confirmed. 5
• Linezolid 600 mg PO twice daily can be used for oral step-down therapy after initial IV treatment. 3

Biofilm-Associated Staphylococcal Infections (Implant-Related)

Combination Therapy Requirements

• Rifampicin is the agent of choice for treating biofilm in staphylococcal implant-related infections but must never be used as monotherapy due to rapid resistance development within 48-72 hours. 3, 6
• Rifampicin should only be initiated after thorough debridement to diminish bacterial load and when wounds are dry to avoid superinfection with resistant organisms. 3
• The first choice for oral combination therapy is rifampicin plus a fluoroquinolone (ciprofloxacin or levofloxacin), though fluoroquinolone monotherapy is not recommended due to rapid resistance emergence. 3
• Alternative rifampicin combinations include cotrimoxazole, minocycline, or fusidic acid, though these have been less intensively studied. 3

Duration for Implant-Related Infections

• 12 weeks total treatment duration is recommended with implant retention. 3
• 6 weeks of treatment is sufficient after implant removal. 3
• IV therapy should be limited to 1-2 weeks until the patient is clinically stable and culture results are known, then transition to oral therapy. 3

Treatment Duration by Infection Type

Bacteremia

• Uncomplicated bacteremia requires at least 14 days of treatment to prevent relapse, defined as negative follow-up blood cultures, defervescence within 72 hours, no endocarditis, no implanted prostheses, and no metastatic sites. 1
• Complicated bacteremia should be treated for 4-6 weeks if any criterion for uncomplicated bacteremia is not met. 3, 1

Endocarditis

• Native valve endocarditis requires 4-6 weeks of vancomycin or daptomycin. 3
• Prosthetic valve endocarditis requires ≥6 weeks of vancomycin plus rifampicin 900-1200 mg daily in 2-3 divided doses, with rifampicin started 3-5 days after vancomycin. 3

Skin and Soft Tissue Infections

• Outpatient SSTI: 5-10 days of oral antibiotics after incision and drainage. 3
• Inpatient complicated SSTI: 7-14 days of IV antibiotics. 3

Osteomyelitis and Bone/Joint Infections

• At least 14 days for acute staphylococcal infections, with therapy continued for at least 48 hours after the patient becomes afebrile and asymptomatic. 4
• Endocarditis and osteomyelitis may require longer-term therapy of 4-6 weeks or more. 4

Critical Management Principles

Source Control

• Remove all infected intravascular catheters and implanted devices immediately, as failure to do so is a major cause of treatment failure. 2
• Drain abscesses and perform surgical debridement of infected tissue, which remains mandatory regardless of antibiotic choice. 6

Monitoring

• Obtain blood cultures before initiating antibiotics to guide definitive therapy based on susceptibility results. 2
• Follow-up blood cultures should be obtained 2-4 days after initial positive cultures to document clearance. 1
• Monitor vancomycin trough levels closely, targeting 15-20 mcg/mL, and check renal function every 2-3 days during vancomycin therapy. 6
• Perform transthoracic echocardiography on all patients with S. aureus bacteremia, with transesophageal echocardiography preferred for persistent bacteremia or metastatic infection. 1

Critical Pitfalls to Avoid

• Never add gentamicin or aminoglycosides to vancomycin for uncomplicated bacteremia or simple skin infections, as this increases nephrotoxicity without improving outcomes. 3, 2, 6
• Never use rifampicin as monotherapy or add it to vancomycin for simple skin and soft tissue infections or uncomplicated bacteremia due to rapid resistance development. 2, 6
• Never use fluoroquinolone monotherapy against staphylococci due to rapid resistance emergence and high treatment failure rates. 3
• Do not use oral penicillinase-resistant penicillins as initial therapy in serious, life-threatening infections; parenteral agents should be used first. 4