Copyright ©The Author(s) 2019.
World J Clin Infect Dis. May 21, 2019; 9(1): 1-10
Published online May 21, 2019. doi: 10.5495/wjcid.v9.i1.1
Table 1 Methicillin-resistant S. aureus treatment recommendations[6]
InfectionsAntibiotic Treatment
Skin and soft tissue infections (SSTIs)
Uncomplicated SSTIsClindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), a tetracycline (doxycycline or minocycline) (A-II), linezolid
Complicated SSTIsIV 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 SSTIsNasal decolonization - mupirocin twice daily +/- topical body decolonization - skin antiseptic solution (e.g. chlorhexidine) or dilute bleach baths.
Bacteraemia and infective endocarditis
Native valve endocarditisVancomycin; Daptomycin (6 mg/kg/dose IV once daily)
Prosthetic valve endocarditisVancomycin + Rifampin (300 mg PO/IV every 8 hour) followed by Gentamicin (1 mg/kg/dose IV every 8 hour)
Community acquired, or healthcare associatedIV 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 arthritisVancomycin; 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 SinusIV Vancomycin +/- Rifampin; OR; Linezolid 600 mg PO/IV twice daily or TMP-SMX 5 mg/kg/dose IV every 8-12 hour
Table 2 Limitations of current anti-methicillin resistant S. aureus treatments
VancomycinHigher 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
Red man syndrome
TeicoplaninTherapeutic drug monitoring may be necessary
Need to generate evidence on pharmacokinetics and clinical pharmacodynamics
DaptomycinResistance development
Possible cross-resistance in hVISA
Inactivation by alveolar surfactant
LinezolidSerious adverse drug reactions e.g., thrombocytopenia, optic neuropathy, peripheral neuropathy, lactic acidosis, monoamine oxidase inhibition
MIC creep
Limited efficacy in bacteraemia or endocarditis
TMP/SMXHigh degree of resistance
Limited efficacy in bacteraemia
Thymidine salvage in presence of pus
ClindamycinHigh rates of inducible and constitutive resistance
Risk of Clostridium difficile infection
TetracyclinesLimited utility in severe invasive infections
TigecyclineLow 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/ DalfopristinLimiting side effects like infusion-site inflammation, pain, and oedema, thrombophlebitis, arthralgia, myalgia, nausea, diarrhoea, vomiting, and rash
Drug interactions with CYP3A4 inhibitors
CeftarolineRisk of agranulocytosis
TelavancinRisk of nephrotoxicity
Oritavancin and DalbavancinLong 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