Parenteral antimicrobial regimens for definitive treatment of bacteremia and other invasive methicillin-resistant* Staphylococcus aureus infections in children older than 28 days when antimicrobial susceptibilities are known^[1-5]

Parenteral antimicrobial regimens for definitive treatment of bacteremia and other invasive methicillin-resistant* Staphylococcus aureus infections in children older than 28 days when antimicrobial susceptibilities are known^[1-5]

Clinical scenario	Antimicrobial regimens
Clinical scenario	Our preferred regimen(s)	Alternate regimen(s)
Health care-associated MRSA infection	Vancomycin 15 mg/kg IV every 6 hours (maximum daily dose 4 g/day)*^¶	Consultation with an expert in infectious diseases is recommended. The preferred regimen varies with clinical features, including the site of infection and the antibiotic susceptibilities of the isolate^Δ. Possibilities include (only if isolate is susceptible): Linezolid^◊ <12 years: 30 mg/kg per day IV in 3 doses ≥12 years: 600 mg twice per day IV Daptomycin^◊^§ 1 through 6 years: 12 mg/kg per day IV once daily 7 through 11 years: 9 mg/kg per day IV once daily 12 through 17 years: 7 mg/kg per day IV once daily Ceftaroline^◊ 15 mg/kg IV every 8 hours (maximum dose 600 mg) TMP-SMX 8 to 12 mg/kg: TMP 40 to 60 mg/kg, SMX per day in 4 doses
Community-associated MRSA infection
Sepsis Endocarditis CNS infection Endovascular infection Infection complicated by venous thrombosis	Vancomycin 15 mg/kg IV every 6 hours (maximum daily dose 4 g/day)*^¶	Consultation with an expert in infectious diseases is recommended. Alternate agents include ceftaroline^◊, daptomycin^◊^§, or linezolid^◊^¥.
Pneumonia-complicating influenza^‡	Vancomycin 15 mg/kg IV every 6 hours (maximum daily dose 4 g/day)^¶ plus* a second anti-MRSA agent (eg, clindamycin, ceftaroline^◊, linezolid^◊)^‡ plus anti-influenza therapy	Ceftaroline^◊ 15 mg/kg IV every 8 hours (maximum dose 600 mg) plus anti-influenza therapy
Pneumonia without concomitant influenza	Clindamycin 40 mg/kg per day IV divided in 3 or 4 doses (maximum daily dose 2.7 g) (only if the isolate is susceptible)	One of the following: Vancomycin 15 mg/kg IV every 6 to 8 hours (maximum daily dose 4 g/day)* Linezolid^◊ (for infections caused by clindamycin-resistant isolates in children who cannot tolerate vancomycin or who have renal dysfunction) <12 years: 30 mg/kg per day IV in 3 doses ≥12 years: 600 mg twice per day IV Ceftaroline^◊ 15 mg/kg IV every 8 hours (maximum dose 600 mg)
Septic arthritis Osteomyelitis	Clindamycin 40 mg/kg per day IV divided in 3 or 4 doses (maximum daily dose 2.7 g) (only if the isolate is susceptible and blood culture is negative)	One of the following: Vancomycin 15 mg/kg IV every 6 to 8 hours (maximum daily dose 4 g/day)* Linezolid^◊ <12 years: 30 mg/kg per day IV in 3 doses ≥12 years: 600 mg twice per day IV Daptomycin^◊^§ 1 through 6 years: 12 mg/kg per day IV once daily 7 through 11 years: 9 mg/kg per day IV once daily 12 through 17 years: 7 mg/kg per day IV once daily Ceftaroline^◊ 15 mg/kg IV every 8 hours (maximum dose 600 mg)

This table is meant to be used in conjunction with UpToDate content on S. aureus infections in children. Methicillin resistance is defined by oxacillin minimum inhibitory concentration (MIC) ≥4 mcg/mL. Refer to UpToDate content for additional information about choice of antimicrobial therapy. Consultation with an expert in infectious diseases may be warranted for guidance regarding choice and duration of antimicrobial therapy.

MRSA: methicillin-resistant S. aureus; IV: intravenously; TMP-SMX: trimethoprim sulfamethoxazole; CNS: central nervous system; AUC: area under the curve.

* Alternative dosing is suggested for clinicians/institutions who follow AUC-guided therapeutic monitoring for vancomycin for serious MRSA infections as suggested by consensus guidelines^[6]; this strategy requires input from a clinical pharmacist, who will provide recommendations for initial dosing. Refer to UpToDate content on invasive staphylococcal infections in children for details of trough-guided and AUC-guided vancomycin dosing.

¶ For prosthetic valve endocarditis, we add gentamicin 1 mg/kg three times per day IV and rifampin 10 mg/kg orally or IV twice per day (maximum daily dose 600 mg) for the first two weeks of treatment. For other device-related infections (eg, spinal instrumentation, pacemaker, cochlear implant, baclofen pump, prosthetic joint), we add rifampin orally or 10 mg/kg IV twice per day (maximum daily dose 600 mg) for up to two months if rifampin is tolerated and the device remains in place.

Δ Alternatives to vancomycin for CNS infections include linezolid^◊, daptomycin^◊, or TMP-SMX.^[1] Daptomycin should not be used for children with concomitant pneumonia.

◊ Experience with these agents in children is limited. Consultation with an expert in infectious diseases may be warranted.

§ Daptomycin should not be used in children with concomitant pulmonary involvement. Daptomycin is active in vitro against multidrug-resistant gram-positive organisms, including S. aureus, but is not well studied in children. It is approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections in patients ≥1 year of age, the treatment of S. aureus bacteremia in children 1 through 17 years of age, and the treatment of S. aureus bacteremia (including right-sided endocarditis) in patients ≥18 years of age. Dosing for other indications is not well established.

¥ Cases of apparent failures of linezolid to treat or prevent endocarditis in patients with intravascular MRSA infection have been described. Refer to UpToDate content on treatment of invasive S. aureus infections in children for details.

‡ For pneumonia complicating influenza, addition of a second anti-MRSA agent (eg, clindamycin, ceftaroline, linezolid) within the first 24 hours of admission may be associated with decreased mortality. Refer to UpToDate content on treatment of invasive S. aureus infections in children for details.

References:

Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis 2017.
American Academy of Pediatrics. Staphylococcus aureus. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32^nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.678.
American Academy of Pediatrics. Tables of antibacterial drug dosages. In: Red Book: 2021 Report of the Committee on Infectious Diseases, 32^nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.876.
Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18.
Cubicin (daptomycin for injection). United States Prescribing Information. Revised September, 2017. US Food and Drug Administration. Available online: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (Accessed on August 1, 2018).
Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2020; 77:835.

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Parenteral antimicrobial regimens for definitive treatment of bacteremia and other invasive methicillin-resistant* Staphylococcus aureus infections in children older than 28 days when antimicrobial susceptibilities are known[1-5]

Parenteral antimicrobial regimens for definitive treatment of bacteremia and other invasive methicillin-resistant* Staphylococcus aureus infections in children older than 28 days when antimicrobial susceptibilities are known^[1-5]