Treatment of methicillin-resistant Staphylococcus aureus infections: Importance of high vancomycin minumum inhibitory concentrations

Table 1 Staphylococcus aureus glycopeptide minimum inhibitory concentration cut-off values (μg/mL) as defined by Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing (determined by broth microdilution)

Antibiotic	CLSI (2011)			EUCAST (2011)
	S	VISA	R	S	R
Vancomycin	≤ 2	4-8	≥ 16	≤ 2	> 2
Teicoplanin	≤ 8	-	≥ 32	≤ 2	> 2

CLSI: Clinical and Laboratory Standards Institute; EUCAST: European Committee on Antimicrobial Susceptibility Testing; S: Sensitive; VISA: Vancomycin-intermediate Staphylococcus aureus; R: Resistant.

Table 2 Treatment recommendations in Staphylococcus aureus with reduced vancomycin susceptibility infections¹

General recommendations
Removal of indwelling hardware (prosthetic devices, surgical material, intravascular catheter, etc.)
Surgical debridement of infected wounds and abscess drainage Follow specific guidelines and local protocols, based on infection site, for treatment duration decisions
Antibiotic treatment considerations
Vancomycin	If used aim: AUC0-24/MIC ≥ 400 or trough blood concentrations of 15-20 mg/L Careful monitoring of renal function is imperative
Daptomycin	Bactericidal. Good results with VISA and VRSA endovascular infections Consider administration of higher doses (i.e., 10 mg/kg per day) in severe infections and if vancomycin MIC > 2 μg/mL (including VISA)2 Consider synergic combinations (i.e., cloxacillin, aminoglycosides, betalactans, fosfomycin) in infections involving high inoculum (as in IE) and prosthetic devises It is inhibited by pulmonary surfactant, therefore should be avoided in SA respiratory or lung infections Monitor CK and liver function
Linezolid	Bacteriostatic Protein synthesis inhibitor. Inhibits bacterial toxin synthesis High tissue bioavailability Good results in SSTI and pneumonia (including VAP) Oral formulation with similar bioavailability Myelotoxicity: Monitor CBC Severe interactions with SSRIs and MAOIs, must not be given simultaneously
Tigecycline	Low plasma concentrations. Bacteriostatic. Avoid monotherapy

¹Treatment recomendations for SA with reduced vancomycin susceptibility usually take methicillin resistance for granted. If the strain were methicillin sensitive, the latter would be the treatment of choice;

²In VISA and SA with MIC > 2 μg/mL, worse results with lower daptomycin doses have been observed, probably related to cell wall thickness changes in these strains. AUC: Area under the curve; MIC: Minimum inhibitory concentration; VISA: Vancomycin-intermediate Staphylococcus aureus; VRSA: Vancomycin-resistant Staphylococcus aureus; IE: Infective endocarditis; SA: Staphylococcus aureus; CK: Creatinine kinase; SSTI: Skin and soft tissue infections; VAP: Ventilator associated pneumonia; CBC: Complete blood count; SSRI: Selective serotonine reuptake inhibitor; MAOI: Monoamine oxidase inhibitor.

Table 3 Infection control recommendations for patients colonized or infected by drug-resistant Staphylococcus aureus (vancomycin-intermediate Staphylococcus aureus, vancomycin-resistant Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus, Centers for Disease Control and Prevention recommendations¹）

Spread prevention

Isolate patient in a private room

Facilitate gowns and gloves to enter the room

Facilitate mask protection

If risk of aerosol spread consider mask use

Practice hand hygiene with an antibacterial agent (preferably chlorhexidine-based soaps or solutions)

Avoid sharing equipment among patients

Continue isolation until results of tests of nares and infected sites are negative 3 times over 3 wk (including hospital readmission)

Minimize number of staff caring for patient

Educate staff about appropriate precautions and assess compliance

Infection control in nosocomial spread and evaluation

Perform baseline and weekly cultures of hands and nares of healthcare workers in charge of index patient

Consider baseline and weekly cultures for other healthcare workers and persons with extensive contact

Decolonize index patient and healthcare workers with topical mupirocine

Consider avoiding direct patient-contact of colonized healthcare workers until negative culture

¹Centers for Disease Control and Prevention Healthcare-associated Infections recommendations and guidelines (http://www.cdc.gov/HAI/prevent/prevent_pubs.html).