Oral Antibiotic Options for Methicillin-resistant Staphylococcus aureus (MRSA)

Oral Antibiotic Options for Methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Oral Treatment of Skin and Soft Tissue Infections (SSTI)

Patients with mild infection (localized involvement with no systemic symptoms) due to known or suspected MRSA may be treated with oral antibiotic therapy (kindly refer table below). 

Oral antibiotic agents of choice include trimethoprim-sulfamethoxazole (TMP-SMX), tetracyclines (such as doxycycline or minocycline), or clindamycin. In general, the choice between agents is guided by individual clinical circumstances including local antibiotic resistance patterns, allergy history, and concomitant medications.

The efficacy of clindamycin and TMP-SMX for treatment of uncomplicated skin infection is comparable; in two randomized trials including patients with uncomplicated skin infections, cure rates for clindamycin and TMP-SMX were between 78 and 83 percent. Use of the tetracyclines is supported by susceptibility testing and observational and retrospective reports; their efficacy for treatment of skin and soft tissue infections due to MRSA has not been rigorously evaluated or compared in clinical trials.

In the setting of empiric antibiotic therapy, the efficacy of the above agents against the potential pathogen group A Streptococcus(GAS) should be considered. Clindamycin and TMP-SMX are active against GAS; doxycycline has uncertain activity

Alternative oral agents include oxazolidinones (linezolid and tedizolid), the fluoroquinolone delafloxacin, and the tetracycline omadacycline; use of these drugs is limited by cost, clinical experience, and adverse drug effects. They should be reserved for patients who do not respond to or cannot tolerate other agents.

Fluoroquinolones (apart from delafloxacin) should NOT be used for treatment of skin and soft tissue infections due to MRSA; resistance may develop during therapy.

Oral Treatment (in Adult)	Adult Dose (Normal Renal Function)
Clindamycin	450 mg orally 3 times daily
Doxycycline	100 mg orally twice daily
Linezolid	600 mg orally twice daily
Trimethoprim-sulfamethoxazole (co-trimoxazole)*	1 or 2 DS tablets twice daily
* DS: double strength (ie, 160 mg trimethoprim with 800 mg sulfamethoxazole per tablet).

MRSA Skin and Soft Tissue Infections  -  Chahine & Sucher (PSAP 2015)

TOPICAL Option	Dosing Regimen (Adults)	Dosing Regimen (Children)	Adverse Effects	Significant Drug Interactions
Mupirocin (ointment, cream)	Skin infections for adults and children ≥ 2 months: Apply to affected area twice daily for 5 days MRSA decolonization for adults and children ≥ 12 years: Apply to anterior nares twice daily for 5 days		Hypersensitivity reactions, skin irritation, pruritus, burning	-
SYSTEMIC Option	Dosing Regimen (Adults)	Dosing Regimen (Children)	Adverse Effects	Significant Drug Interactions
Clindamycin	300–450 mg PO four times daily Adults: 600 mg IV three times daily	20–40 mg/kg/day IV/PO divided into 3 doses	Clostridium difficile infection, gastrointestinal upset	-
Doxycyline	Adults and children > 45 kg: 100 mg PO twice daily	Children ≥ 8 years and ≤ 45 kg: 2 mg/kg PO twice daily	Gastrointestinal upset, photosensitivity, permanent tooth discoloration in children < 8 years, not recommended for pregnant women and children < 8 years	Oral cations
Linezolid	Adults and children ≥ 12 years: 600 mg IV/PO twice daily	Children < 12 years: 10 mg/ kg/day IV/PO twice daily	Myelosuppression, neuropathy, serotonin syndrome	Serotonergic agents
Trimethoprim/ Sulfamethoxazole (Bactrim)	Adults: 1 to 2 DS tablet(s) PO twice daily	8–12 mg/kg/day of trimethoprim divided into 4 doses IV or 2 doses PO	Hypersensitivity reactions, nausea, vomiting, myelosuppression, hyperkalemia, hepatotoxicity, not recommended for women in the third trimester of pregnancy	Warfarin, renin-angiotensin aldosterone system inhibitors
Vancomycin (INTRAVENOUS)	30 mg/kg/day divided into 2 doses	40 mg/kg/day divided into 4 doses	Infusion reactions, red man syndrome, nephrotoxicity	Nephrotoxic agents

MRSA Infections (Other Sites)  -  IDSA 2011

Manifestation	Treatment	Adult Dose	Paediatric Dose	Strength of Recommen-dation	Comment
Purulent cellulitis (defined as cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess)	Clindamycin	300–450 mg PO TID	10–13 mg/kg/dose PO every 6–8 h, not to exceed 40 mg/kg/day	AII	Clostridium difficile–associated disease may occur more frequently, compared with other oral agents.
	TMP-SMX (Bactrim)	1–2 DS tab PO BID	Trimethoprim 4–6 mg/kg/dose, PO BID	AII	TMP-SMX is pregnancy category C/D and not recommended for women in the third trimester of pregnancy and for children <2 months of age.
	Doxycycline	100 mg PO BID	<45kg: 2 mg/kg/dose PO BID . 45kg: adult dose	All	Tetracyclines are not recommended for children under 8 years of age and are pregnancy category D.
	Linezolid	600 mg PO BID	10 mg/kg/dose PO TID, not to exceed 600 mg/dose	All	More expensive compared with other alternatives
Nonpurulent cellulitis (defined as cellulitis with no purulent drainage or exudate and no associated abscess)	Clindamycin	As above
	Linezolid	As above
Complicated SSTI	Linezolid	600 mg PO/IV BID	10 mg/kg/dose PO/IV TID not to exceed 600 mg/dose	AI/AII	For children >12 years of age, 600 mg PO/IV BID. Pregnancy category C
	Clindamycin	600 mg PO/IV TID	10–13 mg/kg/dose PO/IV every 6–8 h, not to exceed 40 mg/kg/day	AIII/AII	Pregnancy category B
Pneumonia	Linezolid	600 mg PO/IV BID	10 mg/kg/dose PO/IV TID not to exceed 600 mg/dose	AII	For children >12 years of age, 600 mg PO/IV BID. Pregnancy category C
	Clindamycin	600 mg PO/IV TID	10–13 mg/kg/dose PO/IV every 6–8 h, not to exceed 40 mg/kg/day	BIII/AII	Pregnancy category B
Osteomyelitis / Septic arthritis	Linezolid	600 mg PO/IV BID	10 mg/kg/dose PO/IV TID not to exceed 600 mg/dose	BII/CIII
	Clindamycin	600 mg PO/IV TID	10–13 mg/kg/dose PO/IV every 6–8 h, not to exceed 40 mg/kg/day	BIII/AII
	TMP-SMX and rifampin	3.5–4.0 mg/kg/dose PO/IV every 8–12 h & 600 mg PO QD	No Data (ND)	BII/ND

Alternative dosing for osteomyelitis (from Medscape 2018):

Preferred:
Vancomycin (INTRAVENOUS)	15 mg/kg IV q12hr if MIC
Linezolid	600 mg IV/PO q12hr
Alternative based on results of sensitivity testing and intolerance of vancomycin:
Trimethoprim-sulfamethoxazole PLUS Rifampin	4 mg/kg IV q12hr (dose based on trimethoprim component) 600 mg PO q24hr or 300-450 mg PO q12hr
Oral therapy based on results of sensitivity testing:
Doxycycline	100 mg PO q12hr
Clindamycin	450 mg PO q6hr or 600 mg PO q8hr
Trimethoprim-sulfamethoxazole	2 DS tablets PO q8-12hr
Levofloxacin PLUS Rifampin	500-750 mg PO daily 600-900 mg PO qd (only if the isolate is sensitive to both antibiotics)

Definitive Prosthetic Joint Infection Treatment       [National Antibiotic Guideline 2019]

Initial treatment: *Vancomycin 15-20 mg/kg (actual body weight) IV q8-12h; NOT to exceed 2 gm/dose PLUS Rifampicin 300-450 mg PO q12h

·   Duration: 2-6 weeks (according to treatment strategy) ·   Followed by an oral combination therapy according to susceptibility. ·   Rifampicin should be included if implant is in situ

References:

1.       UptoDate: Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections

2.       UptoDate: Oral antimicrobial therapy for treatment of skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus (MRSA) in adults (table)

3.       Skin and Soft Tissue Infections - Chahine & Sucher (PSAP 2015). Available from: https://www.accp.com/docs/bookstore/psap/2015B1.SampleChapter.pdf

4.       Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America.

5.       Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children, 2011.

6.       Medscape: Osteomyelitis Organism-Specific Therapy, 2018. Available from: https://emedicine.medscape.com/article/2018345-overview

7.       National Antibiotic Guideline (Malaysia) 2019

All information accessed on 24.02.2020