Suggested approach to the choice of empiric parenteral therapy for the treatment of suspected Staphylococcus aureus bacteremia and other invasive infections in infants and children older than 28 days^[1-4]

Suggested approach to the choice of empiric parenteral therapy for the treatment of suspected Staphylococcus aureus bacteremia and other invasive infections in infants and children older than 28 days^[1-4]

Clinical scenario	Antimicrobial regimens
Clinical scenario	Our preferred regimen	Alternate regimen(s)
Life-threatening infection suspected to be caused by S. aureus (health care- or community-associated)
Health care-associated or community-associated: Sepsis CNS infection Endocarditis Endovascular infection Infection complicated by venous thrombosis	Vancomycin 15 mg/kg IV every 6 hours (maximum daily dose 4 g/day), plus* Nafcillin or oxacillin 37.5 to 50 mg/kg IV every 6 hours (maximum daily dose 12 g/day)	One of the following: Ceftaroline^Δ 15 mg/kg IV every 8 hours (maximum dose 600 mg) Linezolid^Δ <12 years: 30 mg/kg per day IV in 3 doses ≥12 years: 600 mg twice per day IV Daptomycin^Δ^◊ (for patients without pneumonia) 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
Suspected health care-associated or community MRSA pneumonia complicating influenza^¶	Vancomycin, plus A second anti-MRSA agent (eg, clindamycin, ceftaroline^Δ, linezolid^Δ), plus Either nafcillin or oxacillin, plus Anti-influenza therapy	One of the following: Ceftaroline^Δ 15 mg/kg IV every 8 hours (maximum dose 600 mg) Linezolid^Δ <12 years: 30 mg/kg per day IV in 3 doses ≥12 years: 600 mg twice per day IV Plus Anti-influenza therapy
Nonlife-threatening, nonendovascular infection (eg, pneumonia, septic arthritis, osteomyelitis) without signs of sepsis suspected to be caused by S. aureus
Health care-associated^§	Vancomycin 15 mg/kg IV every 6 to 8 hours (maximum daily dose 4 g/day)*	One of the following: Ceftaroline^Δ 15 mg/kg IV every 8 hours (maximum dose 600 mg) Linezolid^Δ <12 years: 30 mg/kg per day IV in 3 doses ≥12 years: 600 mg twice per day IV Daptomycin^Δ^◊ (for patients without pneumonia) 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
Community-associated >10% of S. aureus isolates are MRSA^¥ Prevalence of clindamycin resistance ≥15%^‡	Vancomycin 15 mg/kg IV every 6 to 8 hours (maximum daily dose 4 g/day)*	One of the following: Ceftaroline^Δ 15 mg/kg IV every 8 hours (maximum dose 600 mg) Linezolid^Δ <12 years: 30 mg/kg per day IV in 3 doses ≥12 years: 600 mg twice per day IV Daptomycin^Δ^◊ (for patients without pneumonia) 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
Community-associated >10% of S. aureus isolates are MRSA^¥ Prevalence of clindamycin resistance <15%^‡ Bacteremia unlikely	Clindamycin 40 mg/kg per day IV divided in 3 or 4 doses (maximum daily dose 2.7 g/day)	One of the following: Vancomycin 15 mg/kg IV every 6 to 8 hours (maximum daily dose 4 g/day)* Ceftaroline^Δ 15 mg/kg IV every 8 hours (maximum dose 600 mg) Daptomycin^Δ^◊ (for patients without pneumonia) 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
Community-associated ≤10% of S. aureus isolates are MRSA^¥	Nafcillin or oxacillin 150 to 200 mg/kg per day IV in 4 to 6 doses (maximum daily dose 12 g/day)	One of the following: Cefazolin 100 to 150 mg/kg per day IV in 3 doses Vancomycin 15 mg/kg IV every 6 to 8 hours (maximum daily dose 4 g/day)*

This table is meant to be used in conjunction with UpToDate content on S. aureus infections in children. In most cases, invasive S. aureus infection is suspected because there are clinical findings suggestive of a clinical syndrome or focal source that is associated with S. aureus infection (eg, osteomyelitis, septic arthritis, intravascular catheter). Less commonly, S. aureus is suspected because of underlying risk factors or Gram stain demonstrating gram-positive cocci in clusters. Additional antibiotics may be required for nonstaphylococcal pathogens until the pathogen is identified. Final therapy decisions are based on results of cultures and susceptibility testing. 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.

CNS: central nervous system; IV: intravenous; MRSA: methicillin-resistant S. aureus; 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^[5]; 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 suspected MRSA 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.

Δ 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.

§ Risk factors for health care-associated infection include personal history of or frequent contact with an individual with a history of hospitalization, surgery, dialysis, or residence in a long-term care facility within the previous year, frequent contact with the health care environment, presence of an invasive device (eg, intravascular catheter or tracheal tube), and history of MRSA infection or colonization.

¥ Information regarding local susceptibility patterns can be obtained from local public health officials or hospital laboratories. We provide coverage for MRSA when >10% of community isolates are MRSA; other experts may use a different threshold.

‡ Information regarding local susceptibility patterns can be obtained from local public health officials or hospital laboratories. The threshold prevalence of clindamycin-resistant MRSA for choosing vancomycin varies from center to center, usually ranging from 10 to 25%, in an effort to balance the benefit of definitive therapy for the patient with the risk of increasing vancomycin resistance in the community. Additional considerations in the decision to choose vancomycin include the prevalence of MRSA in the community, the severity of illness, and the turn-around time for susceptibilities.

References:

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: 2021-2024 Report of the Committee on Infectious Diseases, 32^nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, 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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Suggested approach to the choice of empiric parenteral therapy for the treatment of suspected Staphylococcus aureus bacteremia and other invasive infections in infants and children older than 28 days[1-4]

Suggested approach to the choice of empiric parenteral therapy for the treatment of suspected Staphylococcus aureus bacteremia and other invasive infections in infants and children older than 28 days^[1-4]