Pharmacokinetics and safety of recently approved drugs used to treat methicillin-resistantStaphylococcus aureusinfections in infants, children and adults

Abstract

Summary Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant cause of morbidity in hospitalized infants. Over the past 15 years, several drugs have been approved for the treatment of S. aureus infections in adults (linezolid, quinupristin/dalfopristin, daptomycin, telavancin, tigecycline, and ceftaroline). The use of there majority of these drugs has extended into the treatment of MRSA infections in infants, frequently with minimal safety or dosing information. Only linezolid is approved for use in infants, and pharmacokinetic data in infants are limited to linezolid and daptomycin. Pediatric trials are underway for ceftaroline, telavancin, and daptomycin; however, none of these studies includes infants. Here, we review current pharmacokinetic, safety, and efficacy data of these drugs with a specific focus in infants.

The global prevalence of Daptomycin, Tigecycline, Quinupristin/Dalfopristin, and Linezolid-resistant Staphylococcus aureus and coagulase–negative staphylococci strains: a systematic review and meta-analysis

“…Daptomycin can be one of the choices for treating staphylococci-induced infections if there is a strong possibility based on local microbiological data or recent treatment history of vancomycin in an infected patient with MIC of > 1 μg/mL. Q/D comprises quinupristin and dalfopristin in a 30:70 ratio, which prevents protein synthesis in bacteria [134]. Studies have shown that Q/D with 0.7% has the highest resistance rate amongst MRSA strains (Table 1).…”

Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections

“… 9 Daptomycin is renally excreted, and its systemic clearance in healthy adults is 0.011 L/kg/h. 10 Dosing must be adjusted for adult subjects who have impaired creatinine clearance. 11 , 12 In patients with chronic kidney disease stage 4 (creatinine clearance <30 mL/min) and in subjects undergoing hemodialysis or peritoneal dialysis, a dosage adjustment of daptomycin is recommended.…”

“… 87 Daptomycin’s role in pediatric Gram-positive infections has been evaluated in several studies, and a good safety profile has been observed. 9 , 10 , 86 – 89 The IDSA MRSA treatment guidelines recommend the use of daptomycin (6–10 mg/kg/day) for managing MRSA bacteremia, infective endocarditis, acute hematogenous osteomyelitis, and septic arthritis in pediatric patients. 16 …”

Linezolid-related adverse effects in clinical practice in children

“…1,2 It has an excellent activity against most methicillin-sensitive and methicillin-resistant Grampositive bacteria. 3 Linezolid was originally approved by Food and Drug Administration of United States for pediatric use in 2002, for treatment indicated infections, such as skin and skin structure infections, communityacquired and nosocomial pneumonia, and infections with vancomycinresistant Enterococcus faecium. 4 The advantages of linezolid compared to glycopeptide antibiotics include clinical and microbiological efficacy, excellent tissue penetration and lack of requirement for therapeutic drug monitoring.…”