Evidence based approach to the treatment of community-associated methicillin-resistant Staphylococcus aureus

Figures & data

Table 1 Risk factors for infection with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)^2,3,16,17

Children < 2 years old

Children attending daycare centers

Injection drug users

Military personnel

Inmates

Homeless persons

Those in crowded living conditions

Household contact with a person known to be colonized and/or infected with MRSA

Men who have sex with men

HIV-infected persons

Athletes of contact sports

Adults ≥ 65 years old

Poor personal hygiene

History of colonization or recent infection with CA-MRSA

Recent influenza-like illness or pneumonia

African Americans

Pacific Islanders

Native Americans

Table 2 In vitro activity of select antimicrobial agents against community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)

	CA-MRSA
Antimicrobial agent	No. of isolates	% susceptible	MIC50 (μg/mL)	MIC90 (μg/mL)	MIC range (μg/mL)	Reference
Clindamycin	152	100	≤0.25	≤0.25	≤0.25	Sader et al 2008^Citation76
	157	97	na	na	na	King et al 2006^Citation89
	127	96	na	na	na	Huang et al 2006^Citation88
	348	93	na	na	na	Naimi et al 2001^Citation90
	200	92	0.25	0.5	0.03 to >32	Tsuji et al 2007^Citation91
	23	91	na	0.13	0.06–64	Johnson et al 2006^Citation49
	1301	87	na	na	na	Fridkin et al 2005^Citation87
	191	80.6	na	na	na	Crum et al 2006^Citation86
	1989	34.2	>8	>8	≤0.06 to >8	Mendes et al 2008^Citation45
Daptomycin	23	100	na	0.25	0.12–0.25	Johnson et al 2006^Citation49
	60	100	0.25	0.25	0.12–0.5	Saravolatz et al 2007^Citation44
	152	100	0.25	0.5	0.25–1	Sader et al 2008^Citation76
	200	100	0.5	1	0.13–2	Tsuji et al 2007^Citation91
Erythromycin	318	64	na	na	na	Naimi et al 2001^Citation90
	185	20	na	na	na	Crum et al 2006^Citation86
	1236	18	na	na	na	Fridkin et al 2005^Citation87
	157	13	na	na	na	King et al 2006^Citation89
	127	7	na	na	na	Huang et al 2006^Citation88
	1989	5.7	>8	>8	≤0.06 to >8	Mendes et al 2008^Citation45
	200	4	>16	>16	0.13 to >16	Tsuji et al 2007^Citation91
	152	1.3	>8	>8	2 to >8	Sader et al 2008^Citation76
	23	0	na	64	2.0–64	Johnson et al 2006^Citation49
Fluoroquinolones
Ciprofloxacin	325	93	na	na	na	Naimi et al 2001^Citation90
	23	83	na	16	0.12–64	Johnson et al 2006^Citation49
	861	65	na	na	na	Fridkin et al 2005^Citation87
	127	53	na	na	na	Huang et al 2006^Citation88
	1989	15.1	>4	>4	≤0.03 to >4	Mendes et al 2008^Citation45
Levofloxacin	152	92.8	0.25	0.5	≤0.12 to >4	Sader et al 2008^Citation76
	157	90	na	na	na	King et al 2006^Citation89
	23	87	na	4	0.06–32	Johnson et al 2006^Citation49
	1989	15.5	>4	>4	0.06 to >4	Mendes et al 2008^Citation45
	200	12	>16	>16	0.125 to >16	Tsuji et al 2007^Citation91
Moxifloxacin	23	96	na	1	0.03–4	Johnson et al 2006^Citation49
Linezolid	23	100	na	2	2.0–2.0	Johnson et al 2006^Citation49
	200	100	2	4	0.24–4	Tsuji et al 2007^Citation91
	60	100	2	2	2	Saravolatz et al 2007^Citation44
	152	100	2	2	1–2.0	Sader et al 2008^Citation76
	1989	>99.9	2	2	≤0.06–16	Mendes et al 2008^Citation45
	25	96	na	na	na	Fridkin et al 2005^Citation87
Quinupristin–dalfopristin	60	100	0.25	0.5	0.25–1	Saravolatz et al 2007^Citation44
	1989	>99.9	0.5	1	≤0.25–2	Mendes et al 2008^Citation45
Rifampin	23	100	na	0.03	0.03–0.03	Johnson et al 2006^Citation49
	127	100	na	na	na	Huang et al 2006^Citation88
	157	99	na	na	na	King et al 2006^Citation89
	211	99	na	na	na	Naimi et al 2001^Citation90
	887	98	na	na	na	Fridkin et al 2005^Citation87
	1989	93.7	≤0.5	≤0.5	≤0.5–>2	Mendes et al 2008^Citation45
Tetracyclines
Doxycycline	200	86	0.5	8	0.06–>16	Tsuji et al 2007^Citation91
Minocycline	166	100	na	na	na	Crum et al 2006^Citation86
Tetracycline	249	95	na	na	na	Naimi et al 2001^Citation90
	152	94.7	≤0.5	≤0.5	≤0.5–>16	Sader et al 2008^Citation76
	23	91	na	0.5	0.13–32	Johnson et al 2006^Citation49
	1063	88	na	na	na	Fridkin et al 2005^Citation87
	127	80	na	na	na	Huang et al 2006^Citation88
	1989	9.1	≤2	4	≤2–>8	Mendes et al 2008^Citation45
Tigecycline	76	100	na	na	na	McAlesse et al 2005^Citation60
	1989	98.2–100	≤0.12	0.5	≤0.12–0.5	Mendes et al 2008^Citation45
Trimethoprim–sulfamethoxazole	23	100	na	0.06/1.19	0.03/0.59–0.5/9.5	Johnson et al 2006^Citation49
	152	100	≤0.25	≤0.25	≤0.25	Sader et al 2008^Citation76
	157	100	na	na	na	King et al 2006^Citation89
	127	100	na	na	na	Huang et al 2006^Citation88
	186	98.3	na	na	na	Crum et al 2006^Citation86
	60	98	0.06/1.19	0.5/9.5	0.03/32–0.59/608	Saravolatz et al 2007^Citation44
	342	97	na	na	na	Naimi et al 2001^Citation90
	1218	97	na	na	na	Fridkin et al 2005^Citation87
	200	92	0.25	1	0.03–>8	Tsuji et al 2007^Citation91
	1989	91.1	≤0.5	≤0.5	≤0.5–>2	Mendes et al 2008^Citation45
Vancomycin^a	23	100	na	0.5	0.25–0.5	Johnson et al 2006^Citation49
	1989	100	1	1	0.25–4	Mendes et al 2008^Citation45
	60	100	0.5	0.5	0.25–1	Saravolatz et al 2007^Citation44
	152	100	1	1	0.5–2	Sader et al 2008^Citation76
	157	100	na	na	na	King et al 2006^Citation89
	1345	100	na	na	na	Fridkin et al 2005^Citation87
	127	100	na	na	na	Huang et al 2006^Citation88
	343	100	na	na	na	Naimi et al 2001^Citation90
	200	100	2	2	0.5–2	Tsuji et al 2007^Citation91

a Not all vancomycin data are reflective of Clinical and Laboratory Standards Institute breakpoint changes made in 2006 specific to Staphylococcus aureus and may overestimate susceptibility.

Abbreviation: na, not available.

Table 3 Antimicrobials recommended for outpatient treatment of suspected methicillin-resistant (MRSA) skin and skin structure infections

Selection of empiric therapy should be guided by local susceptibility and modified based on results of culture and susceptibility testing. The duration of therapy for most SSSI is 7–10 days, but may vary depending upon the severity of infection and clinical response. Some infections may require a more prolonged treatment course.

Antimicrobial	Adult dose	Pediatric dose	Considerations
Clindamycin^1	300–450 mg PO QID	10–20 mg/kg PO per DAY divided into 3–4 doses per day; not to exceed adult dose.	See below^1
Doxycycline or minocycline^2	100 mg PO BID	Do not use in children < 8 years old. Age ≥ 8 years old: 4 mg/kg PO per DAY divided BID; not to exceed adult dose.	Chelated by divalent cations. Separate from iron, calcium, and multivitamins. May make skin more sensitive to sunlight, sunburn may result. Do not use if pregnant or breastfeeding.
Linezolid^3	600 mg PO BID	Age > 7 days–11 years old: 10 mg/kg PO per DOSE given every 8 hours; not to exceed 1200 mg daily. Age ≥ 12 years old: 600 mg PO BID.	Low-tyramine diet required. Avoid concominant MAO-I or SSRI agents due to potential for serotonin syndrome. Monitor CBC with prolonged courses (potential for leukopenia, thrombocytopenia). Monitor for peripheral neuropathy.
Rifampin^4	300 mg PO BID	15–20 mg/kg PO per DAY divided BID; not to exceed 600 mg daily.	NUMEROUS CYP450 drug–drug interactions. INR should be closely followed (for rapid decrease) in patients on warfarin. Causes bodily fluids (urine, sweat, etc.) to turn orange/red while on therapy.
Trimethoprim–sulfamethoxazole^2	1–2 DS tablets (160 mg TMP/800 mg SMX per tab) PO BID. May consider dose increase for morbidly obese patients (8–10 mg/kg TMP per DAY divided BID–TID, maximum dose 2 DS tablets TID).	Base dose on TMP. Age ≥ 2 months: 8–2 mg/kg TMP (40–60 mg/kg SMX) PO per DAY divided BID; not to exceed adult dose.	Dose adjustment required in renal dysfunction. Significant drug interaction with warfarin; INR should be closely followed for rapid increase. Avoid in patients with G6PD deficiency. May make skin more sensitive to sunlight, sunburn may result.

1 Clindamycin resistance is becoming increasingly prevalent. Pay close attention to the patient’s culture and sensitivity reports when considering Clindamycin use. Clindamycin should not be used if isolate is erythromycin resistant or if “inducible resistance” is present (D-test).

2 For cellulitis of unknown cause where Group A Streptococcus may be a concern, clindamycin in combination with doxycycline/minocycline provides additional coverage for both organisms. Adjunctive clindamycin therapy may also be useful in toxigenic Staphylococci/Streptococci infections.

3 Due to significant drug interactions and expense, infectious disease consultation is recommended when considering linezolid.

4 Rifampin must always be used in combination with another antibiotic.

Notes: Outpatient use of fluoroquinolones or macrolides is NOT RECOMMENDED for routine treatment of MRSA. Resistance to fluoroquinolones can develop rapidly on therapy, so these agents should not be routinely used even if the isolate is reported to be susceptible. Consider a consultation with an infectious disease physician before prescribing.

Abbreviations: SSSI, skin and skin structure infections; MAO-I, monoamine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitor; CBC, complete blood count; INR, international normalized ratio; G6PD, glucose-6-phosphate dehydrogenase.

Table 4 Parenteral agents for the treatment of severe community-associated methicillin-resistant Staphylococcus aureus infections^{34,43,48,57,85}

Drug	Drug class	Indication	Dose (Intravenous)	Considerations
Daptomycin	Lipoglycopeptide	cSSSI, bacteremia with right-sided infective endocarditis	4–6 mg/kg (actual body weight) every 24 hours	Dose adjust to every 48 hours if CrCl <30 mL/min. Monitor CPK.
Linezolid	Oxazolidinone	uSSSI, cSSSI, CAP including concurrent bacteremia, NP	600 mg every 12 hours	Low-tyramine diet required. Avoid concominant MAO-I or SSRI agents due to potential for serotonin syndrome. Monitor CBC with prolonged courses (potential for leukopenia, thrombocytopenia). Monitor for peripheral neuropathy.
Quinupristin–dalfopristin	Streptogramin	Bacteremia, cSSSI	7.5 mg/kg (actual body weight) every 8–12 hours	Monitor LFTs. Use often limited by high incidence of arthralgias and myalgias.
Tigecycline	Glycylcycline	cSSSI, cIAI	100 mg once, then 50 mg every 12 hours	Does not achive optimal concentrations in blood or urine as highly distributed to the tissues.
Vancomycin	Glycopeptide	Severe gram-positive infections	15 mg/kg every 12 hours	Dose adjust in renal dysfunction. Monitor levels and SCr.

Abbreviations: cSSSI, complicated skin and skin structure infections; uSSSI, uncomplicated skin and skin structure infections; CAP, community-acquired pneumonia; NP, nosocomial pneumonia; cIAI, complicated intra-abdominal infections; SCr, serum creatinine; LFTs, liver function tests; MAO-I, monoamine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitor; CBC, complete blood count; CrCl, creatinine clearance; CPK, creatine phosphokinase.

Table 5 Investigational agents with in vitro activity against methicillin-resistant Staphylococcus aureus

Drug	Route	Dose	Indication under evaluation	Phase
Carbapenem
Multiple in early development	na	na	na	pre-clinical
Cephalosporin
Ceftopbiprole	iv	500 mg every 12 hours	cSSSI	III
Ceftaroline	iv	500 mg every 12 hours	cSSSI	III
Dihydrofolate reductase inhibitor
Iclaprim	iv	0.8 mg/kg every 24 hours	cSSSI	III
	iv	na	HAP (VAP and HCAP)	II
	iv to enteral switch	na	cSSSI	II
Oxazolidinone
Multiple in early development	na	na	na	pre-clinical
Synthetic glycopeptide
Dalbavancin	iv	1000 mg on day 1, 500 mg on day 8	cSSSI	III
	iv	1000 mg on day 1, 500 mg on day 8	bloodstream	II
Ortivancin	iv	200 mg every 24 hours	cSSSI	III
Telavancin	iv	10 mg/kg every 24 hours	cSSSI	III

Abbreviations: iv, intravenous; cSSSI, complicated skin and skinstructure infections; HAP, hospital-acquired pneumonia; VAP, ventilator-acquired pneumonia; HCAP, healthcare-associated pneumonia; na, not applicable.

Figure 1 Outpatient management of suspected community-associated methicillin-resistant Staphylococcus aureus skin and skin structure infections. Adapted from Aurora Health Care MRSA Clinical Guidelines 2008. Kathryn Leonhardt, MD, MPH, Editor.

Abbreviations: I&D, incision and drainage; MRSA, methicillin-resistant S. aureus; CA-MRSA, community-associated MRSA.

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