Treatments and limitations for methicillin-resistant Staphylococcus aureus: A review of current literature

Table 1 Methicillin-resistant S. aureus treatment recommendations[6]

Infections		Antibiotic Treatment
Skin and soft tissue infections (SSTIs)
Uncomplicated SSTIs	Clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), a tetracycline (doxycycline or minocycline) (A-II), linezolid
Complicated SSTIs	IV Vancomycin, Linezolid (oral or IV 600 mg twice daily), Daptomycin (4 mg/kg/dose IV once daily), Telavancin (10 mg/kg/dose IV once daily), Clindamycin (600 mg IV or PO 3 times a day)
Recurrent SSTIs	Nasal decolonization - mupirocin twice daily +/- topical body decolonization - skin antiseptic solution (e.g. chlorhexidine) or dilute bleach baths.
Bacteraemia and infective endocarditis
Native valve endocarditis	Vancomycin; Daptomycin (6 mg/kg/dose IV once daily)
Prosthetic valve endocarditis	Vancomycin + Rifampin (300 mg PO/IV every 8 hour) followed by Gentamicin (1 mg/kg/dose IV every 8 hour)
Pneumonia
Community acquired, or healthcare associated	IV vancomycin or linezolid (600 mg PO/IV twice daily) or clindamycin (600 mg PO/IV 3 times daily)
Bone and joint infections
Osteomyelitis or Septic arthritis	Vancomycin; Daptomycin (6 mg/kg/dose IV once daily); TMP-SMX [4 mg/kg/dose (TMP component) twice daily] + Rifampin (600 mg once daily)
Device-related osteo-articular infections (early onset < 2 mo - prosthetic joint infections)	Vancomycin or Daptomycin (6 mg/kg/dose IV once daily) + Rifampin (600 mg once daily) followed by; Rifampin + fluoroquinolone / TMP- SMX / tetracycline / clindamycin
Device-related osteo-articular infections (early onset < 2 mo - spinal implant infections)	Initial parenteral therapy + Rifampin followed by prolonged oral therapy
CNS infections
Meningitis, Brain abscess, subdural empyema, spinal epidural abscess, Septic Thrombosis of Cavernous or Dural Venous Sinus	IV Vancomycin +/- Rifampin; OR; Linezolid 600 mg PO/IV twice daily or TMP-SMX 5 mg/kg/dose IV every 8-12 hour

SSTIs: Skin and soft tissue infections; TMP-SMX: Trimethoprim-sulfamethoxazole; PO: Per oral; IV: Intravenous; CNS: Central nervous system.

Table 2 Limitations of current anti-methicillin resistant S. aureus treatments

Treatment	Limitations
Vancomycin	Higher MBC: MIC ratio
	Polymorphisms or changes in gene function (e.g. agr pathway)
	MIC creep
	Development of hetero-resistance (hVISA)
	Variable tissue penetration
	AUC: MIC ratio
	Nephrotoxicity
	Red man syndrome
Teicoplanin	Therapeutic drug monitoring may be necessary
	Need to generate evidence on pharmacokinetics and clinical pharmacodynamics
Daptomycin	Resistance development
	Possible cross-resistance in hVISA
	Inactivation by alveolar surfactant
Linezolid	Serious adverse drug reactions e.g., thrombocytopenia, optic neuropathy, peripheral neuropathy, lactic acidosis, monoamine oxidase inhibition
	MIC creep
	Limited efficacy in bacteraemia or endocarditis
TMP/SMX	High degree of resistance
	Limited efficacy in bacteraemia
	Thymidine salvage in presence of pus
Clindamycin	High rates of inducible and constitutive resistance
	Risk of Clostridium difficile infection
Tetracyclines	Limited utility in severe invasive infections
Tigecycline	Low serum levels with limited efficacy in bacteraemia
	Poor tissue penetration and AUC: MIC ratio
	Black box warning from the USFDA for all-cause mortality, Mortality Imbalance and Lower Cure Rates in VAP and pancreatitis
Quinupristin/ Dalfopristin	Limiting side effects like infusion-site inflammation, pain, and oedema, thrombophlebitis, arthralgia, myalgia, nausea, diarrhoea, vomiting, and rash
	Drug interactions with CYP3A4 inhibitors
Ceftaroline	Risk of agranulocytosis
Telavancin	Risk of nephrotoxicity
Oritavancin and Dalbavancin	Long half-life - delayed hypersensitivity if occurs may persist for weeks
	Clinical failure may get unnoticed if there is lack of daily follow-up evaluations
	Effectiveness in bacteraemia, pneumonia, bone and joint infections, and prosthetic infections has not been established
	Higher occurrence of osteomyelitis reported in clinical studies with oritavancin

AUC: Area under the curve; MBC: Minimum bactericidal concentration; MIC: Minimum inhibitory concentration; TMP/SMX: Trimethoprim-Sulfamethoxazole; USFDA: United States Food and Drugs Administration; VAP: Ventilator associated pneumonia.