Ceftaroline is a novel, broad-spectrum, advanced-generation cephalosporin whose action is mediated by binding to penicillin-binding proteins in bacteria, consistent with other beta-lactam antibiotics. Ceftaroline is distinct in that it has antimicrobial activity against multidrug-resistant Staphylococcus aureus (including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus [VISA], heteroresistant VISA, and vancomycin-resistant S. aureus), Streptococcus pneumonia (including drug-resistant strains), and respiratory gram-negative pathogens such as Moraxella catarrhalis and Haemophilus influenzae (including beta-lactamase-positive strains). Development of resistance to ceftaroline occurs rarely in gram-positive bacteria and at a similar rate to that of other oxyimino-cephalosporins in gram-negative bacteria. The inactive prodrug, ceftaroline fosamil, is administered by intravenous infusion and rapidly undergoes biotransformation to ceftaroline. Ceftaroline then follows a two-compartment pharmacokinetic model and is eliminated primarily by renal excretion, with a half-life of approximately 3 hours. Similar to other cephalosporins, time above the minimum inhibitory concentration is the pharmacodynamic parameter that best predicts efficacy for ceftaroline. Ceftaroline 600 mg intravenously every 12 hours has been shown to have similar efficacy to vancomycin plus aztreonam for the treatment of complicated skin and skin structure infections and to ceftriaxone for the treatment of community-acquired bacterial pneumonia in phase III clinical trials. Ceftaroline displayed a safety profile similar to that of other cephalosporins in clinical trials. Dosage adjustment is required for moderate renal impairment and for patients receiving hemodialysis. Ceftaroline breakpoints have been proposed but not confirmed. Ceftaroline is a renally excreted broad-spectrum cephalosporin that is clinically effective for the treatment of complicated skin and skin structure infections and community-acquired bacterial pneumonia, and it has distinctive activity against some difficult-to-treat multidrug-resistant gram-positive organisms.
"drug, FR-264205 2 in phase I, and TD-1792 3 in phase II clinical trials (Fig. 1) are three examples of new derivatives of cephalosporin class (Steed and Rybak, 2010; Newman and Cragg, 2009). 1,2,3-Triazole ring is an attractive group in peptidomimetic synthesis and drug discovery. "
[Show abstract][Hide abstract] ABSTRACT: New derivatives of 1,2,3-triazolyl 7-carboxamidodesacetoxy cephalosporanic acid were synthesized using alkyne-azide 1,3-dipolar cycloaddition. The synthesized compounds were evaluated for their antibacterial activity against a collection of Gram-positive and Gram-negative bacteria and also in synergy with cefixime and cephalexin. Some compounds inhibited vancomycin-resistant strain of Enterococcus faecium (MIC = 8 µg/mL) and in the synergy experiments compounds 13a, 13f, and 13g decreased the level of MIC against an ESBL strain of Klebsiella pneumonia. A comparative molecular field analysis has been carried out, and the effect of substituents on the antibacterial activities of the synthesized compounds was explained.
Medicinal Chemistry Research 10/2014; 23(10). DOI:10.1007/s00044-014-1014-0 · 1.40 Impact Factor
"isolates with elevated vancomycin MICs (≥1.5 g/mL) or strains that harbour the hVISA phenotype, the treatment of choice remains unclear. Ceftaroline, the active agent of the prodrug ceftaroline fosamil, is an extended-spectrum cephalosporin with activity against MRSA . Use of ceftaroline in MRSAB and endocarditis with low vancomycin MICs has been described . "
[Show abstract][Hide abstract] ABSTRACT: Elevated minimum inhibitory concentrations (MICs) of vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) and the emergence of heteroresistant S. aureus strains have led to increased use of anti-MRSA antibiotics other than vancomycin. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA, but there are limited clinical data on its use for MRSA bacteraemia (MRSAB) and against strains exhibiting high vancomycin MICs (2–4 μg/mL). This multicentre, retrospective, case–control study compared the microbiological and clinical effectiveness of ceftaroline used after vancomycin failure with that of vancomycin-treated controls for the treatment of MRSA with vancomycin MICs ≥ 2 μg/mL. In total, 32 patients were matched 1:1 with respect to vancomycin MIC, age and origin of bacteraemia. In the ceftaroline group, patients received prior MRSA therapy for a median of 5 days [interquartile range (IQR), 3–15.8 days] prior to switching to ceftaroline. Median time to eradication of MRSA was significantly less after treatment with ceftaroline compared with vancomycin [4 days (IQR, 3–7.5 days) vs. 8 days (IQR, 5.8–19.5 days); P = 0.02]. Both clinical success at the end of treatment and recurrence of MRSA at Day 7 were trending towards being inferior in the vancomycin group, although the results did not attain statistical significance [81% vs. 44% (P = 0.06) and 6% vs. 38% (P = 0.08), respectively]. Ceftaroline added at the point of vancomycin failure resolves MRSAB more rapidly and with a higher rate of clinical success, therefore ceftaroline should be considered as an alternative for these difficult-to-treat infections.
International Journal of Antimicrobial Agents 09/2014; 44(6). DOI:10.1016/j.ijantimicag.2014.07.024 · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: MEDICATION SAFETY Overlooked Renal Dosage Adjustments A retrospective analysis of 647 patients at hospital discharge com-pared required renal dosage adjust-ments to dosage actually prescribed. This study was conducted at VieCuri Medical Centre in Venlo, Netherlands. Patient demographics and renal function data were col-lected, and dosage adjustment needs were assessed via the pharmacy-supported discharge counseling ser-vice. The incidence of inappropriate dosing based on renal function was measured at hospital discharge. Thirty-seven percent of patients evaluated during the study period (237/647) had a creatinine clear-ance less than 51 mL/min/1.73 m 2 ; dosage adjustment was warranted in 23.9% (411/1,718) of prescrip-tions. When dosage adjustment should have been performed, more than 40% of prescriptions (169/411; 41.1%) were inappropri-ate for renal function (9.8% of pre-scriptions overall; 169/1,718). Fur-thermore, 60.4% (102/169) of inappropriate prescriptions pos-sessed the potential for moderate or severe clinical consequences, as evaluated by a panel of two clinical pharmacologists and one nephrolo-gist. Study authors also noted a lack of standardized dosing guidelines for agents requiring renal dosage adjustment. The authors also sug-gested that augmenting medication systems by adding dynamic renal dosing alerts would improve moni-toring. Summary: A comparison of suggested renal dosing and actual dosing at hospital discharge revealed that appropriate prescribing may be overlooked. van Dijk EA, Drabbe NRG, Kruijtbosch M, De Smet PAGM. Drug dosage adjust-ments according to renal function at hos-pital discharge. Ann Pharmacother. 2006;40:1254-1260.
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