Ceftaroline Fosamil Synthesis Essay

Objective: To summarize published data regarding the use of ceftaroline as salvage monotherapy for persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Data Sources: PubMed (January 1980-June 2016) was searched using combinations of the search terms methicillin-resistant Staphylococcus aureus, MRSA, bacteremia, ceftaroline, refractory, and persistent. Supplemental references were generated through review of identified literature citations. Study Selection and Data Extraction: Available English-language, full-text articles pertaining to the use of ceftaroline for persistent MRSA bacteremia (MRSAB) were included. Data Synthesis: The PubMed search yielded 23 articles for evaluation. There are no randomized controlled trials to date—only case series and reports. Four retrospective case series detailing the use of ceftaroline as monotherapy for persistent MRSAB were included. Most patients received at least 4 days of an appropriate anti-MRSA antimicrobial prior to ceftaroline and were able to clear bacteremia within 3 days. The most common rationales for ceftaroline use were progression of disease or nonresponse to current therapy. Higher off-label dosing of ceftaroline is often utilized to achieve optimal pharmacokinetic/pharmacodynamic parameters. Adverse events are not well described due to lack of follow-up; however, neutropenia has been associated with prolonged use. Conclusions: Treatment options for persistent MRSAB remain few and far between. Ceftaroline is an effective agent for the salvage treatment of MRSAB. Off-label doses up to 600 mg every 8 hours are often used to achieve optimal pharmacokinetic/pharmacodynamic parameters. Because of lack of follow-up in these reports, the incidence of adverse effects of prolonged use of ceftaroline is not well defined.

Indication

Ceftaroline fosamil is indicated for the treatment of patients with the following infections caused by susceptible isolates of the designated microorganisms.

Structured Indications
Pharmacodynamics

The time that unbound plasma concentration of ceftaroline exceeds the minimum inhibitory concentration (MIC) of the infecting organism has been shown to best correlate with efficacy in a neutropenic murine thigh infection model with S. aureus and S. pneumoniae.

No significant effect on QTc (corrected QT interval) interval was detected at peak plasma concentration or at any other time.

Mechanism of action

Ceftaroline fosamil is an antibacterial drug.

Absorption
Not Available
Volume of distribution

Median 20.3 L (18.3-21.6 L).

Protein binding

approximately 20%.

Metabolism

Ceftaroline fosamil is converted into bioactive ceftaroline in plasma by a phosphatase enzyme. Hydrolysis of the beta-lactam ring of ceftaroline occurs to form the microbiologically inactive, open-ring metabolite ceftaroline M-1.

Route of elimination

primarily eliminated by the kidneys (6% in feces within 48 hours).

Half life

1.60 hours (600 mg dose).

Clearance
Not Available
Toxicity

LD50/LC50: Draize test, rabbit, eye: 100 mg/24H Moderate; Oral, mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50 = 980 mg/kg.

Affected organisms
  • Gram-negative Bacteria
  • Gram-positive Bacteria
  • Streptococcus pneumoniae
  • Staphylococcus aureus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

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