Table 3.

Potential Antimicrobial Agents for the Management of AHO

Antimicrobial	Bacteriostatic/Bactericidal	Antimicrobial Spectra*	Adverse Effects	Other Considerations
Antistaphylococcal penicillins	Bactericidal	MSSA, Group A Streptococcus	Potential for drug induced neutropenia, nephritis. Oxacillin associated with hepatotoxicity. Phlebitis and/or local discomfort may develop with IV infusion, particularly with nafcillin.	One of the agents of choice for MSSA. Limited activity against K. kingae. Liquid formulations of oral flucloxacillin and dicloxacillin have poor palatability.
First-generation cephalosporins	Bactericidal	MSSA, Group A Streptococcus, K. kingae	Potential for drug induced neutropenia, nephritis.	Poor CNS penetration. Some concern exists for inactivation of these drugs in the presence of large inoculum of S. aureus (i.e., cefazolin inoculum effect), although data are limited
Vancomycin	Bactericidal	MRSA, MSSA, Group A Streptococcus, Group B Streptococcus	Potential for drug induced neutropenia, thrombocytopenia. Infusion reactions (“Red Man Syndrome”). Nephrotoxicity associated with vancomycin is well described.	Optimal monitoring parameters not established in children. Close monitoring of renal function recommended. Intravenous only administration.
Clindamycin	Bacteriostatic	Clindamycin-susceptible MRSA and MSSA, Group A Streptococcus. Some K. kingae strains are susceptible.	Gastrointestinal distress, diarrhea are common. Potential for transaminitis.	May be administered intravenously but has high oral bioavailability. Local rates of clindamycin-resistance among S. aureus should be considered prior to empiric use. Poor CNS penetration. Not recommended if endovascular disease present. Many liquid formulations have poor palatability.
Linezolid	Bacteriostatic	S. aureus, Group A Streptococcus, Pneumococcus	Potential for drug induced neutropenia, thrombocytopenia. Prolonged use has been associated with optic neuritis and peripheral neuropathy. Tyramine containing foods should be avoided.	May be administered intravenously but has high oral bioavailability. Close monitoring for adverse events, particularly myelosuppression, is advised. Cost of this agent may be prohibitive
Daptomycin	Bactericidal	S. aureus, Group A Streptococcus, Pneumococcus	Potential for transaminitis. Rhabdomyolysis is a reported but rare adverse event	In animal models, inactivated by pulmonary surfactant. Good CNS penetration. Intravenous only administration. Limited data in the setting of pediatric AHO.
Trimethoprim-Sulfamethoxazole	Bactericidal	S. aureus, K. kingae, some gram-negative enterics	Drug induced cytopenias, nephritis, rash. May rarely be associated with erythema multiforme/Stevens Johnson	Excellent in vitro activity against S. aureus in most studies. Data are limited in the setting of invasive S. aureus infection particularly AHO.
Tetracyclines	Bacteriostatic	S. aureus	Potential for transaminitis. Patients may become very photosensitive and should be advised to wear sun screen while outdoors. Dental staining in young children with prolonged use (relative contraindication in those < 8 years)	Excellent in vitro activity against S. aureus in most studies. Data are limited in setting of invasive S. aureus infection, particularly AHO.
Penicillins, Aminopenicillins	Bactericidal	Group A Streptococcus, Group B Streptococcus penicillin-susceptible pneumococci, β-lactamase negative H. influenza	Rash. Drug-induced cytopenias with prolonged use. Nephritis
Third Generation Cephalosporins	Bactericidal	Group A Streptococcus, K. kingae, pneumococci, H. influenzae, many gram-negative enterics (including Salmonella)	Diarrhea. Rash. Drug induced cytopenias, transaminitis, nephritis are possible with prolonged use.	Generally well tolerated class of drugs with agents that can be administered either intravenously or orally. Ceftriaxone with in vitro activity against MSSA, however clinical data in children with invasive MSSA are limited.

Notes: *The description of antimicrobial spectra is not intended to be comprehensive, but to briefly describe a few relevant AHO pathogens included within the antimicrobial spectra of the agent of interest.