3-92.3c Europe No. isolates [Ref] 1092 [42] 331 [42] 460 [42]d 799 [40] 130 Selleck OSI 906 [40] 515 [40] 323 [42] MIC 50 0.25 1 ≤0.008 ≤0.008 0.12 ≤0.008 0.25 MIC 90 0.25 2 0.015 0.12 0.25 0.015 >32 % susceptibleb 100/100 88.8/88.8 100/100 100/99.9 100/99.2 100/97.7 63.5/63.5 South Africa and Asia-Pacific No. isolates [Ref] 413 [41] 211 [41] 113 [41]d 616 [41] 202 [41] 453 [41] 137 [41] MIC 50 0.25 1 ≤0.008 0.015 0.12 ≤0.008 >32 MIC 90 0.25 2 0.015 0.25 0.5 0.03 >32 % susceptibleb 100/100 80.6/80.6 100/100 99.8/95.9 99.5/87.6 100/93.4 32.1/32.1 GAS, S. pyogenes; GBS, S. agalactiae; H. flu, Haemophilus influenzae; MIC 50, minimum
inhibitory concentration that inhibits 50% of bacterial isolates; MIC 90, minimum inhibitory concentration that inhibits 90% of bacterial isolates; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible S. aureus; NS, not stated; PNEUM, Streptococcus pneumoniae; PRSP, penicillin-resistant S. pneumoniae aSurveillance period 2008–2010 bCLSI, Clinical Laboratory Standards Institute/EUCAST, European Committee on Antimicrobial Susceptibility Testing cCLSI only, range dependent on geographic region of the USA dβ-Hemolytic streptococci Dose and Administration Following administration,
Pexidartinib nmr the water-soluble prodrug, ceftaroline fosamil, is rapidly dephosphorylated to the active form in plasma [17]. For adults 18 years and older, the recommended dose is 600 mg administered intravenously (IV) over 1 h every 12 h. A treatment duration of 5–7 days GNE-0877 for CABP and 5–14 days for ABSSSI is currently recommended, guided by the severity of infection and clinical response [5]. As with other β-lactam antibiotics, time above the MIC is the pharmacodynamic (PD) index that correlates best with efficacy [5]. Pharmacokinetic (PK) data in healthy adults with normal renal function following multiple doses administered every 12 h over 14 days show that the elimination half-life is about 2.7 h, the maximum observed concentration (C max) is 21 μg/mL and the area under the concentration–time curve
is 56 μg h/mL, with no appreciable accumulation [5]. Ceftaroline is primarily renally excreted and dosage adjustment is recommended for patients with creatinine clearance (CRCL) ≤50 mL/min. For patients with moderate renal impairment (CRCL >30 to ≤50 mL/min), the dose should be adjusted to 400 mg IV every 12 h. For those with severe renal impairment (CRCL ≥15 to ≤30 mL/min), the dose should be adjusted to 300 mg IV every 12 h and for patients with end-stage renal disease, including those receiving hemodialysis, adjustment to 200 mg IV every 12 h after dialysis should be made [5]. Following a single IV radiolabeled dose, approximately 88% of LY2835219 chemical structure radioactivity was recovered in urine and 6% in feces within 48 h [5]. Of the radioactivity recovered in urine, 64% was excreted as ceftaroline and approximately 2% as the microbiologically inactive ceftaroline M-1 metabolite, suggesting complete transformation of the prodrug [5].
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