Ceftaroline fosamil for treatment of communityacquired pneumonia: findings from FOCUS 1 and 2 and potential role in therapy

Abstract

Cephalosporins have been widely used over the last few decades (often as first-line antibiotic therapy) for numerous infections, owing primarily to their broad spectrum of microbiologic activity and favorable safety profile. Current Infectious Diseases Society of America guidelines identify a third-generation cephalosporin in combination with a macrolide antibiotic as an option for treatment of hospitalized adult patients with community-acquired pneumonia (CAP) outside the intensive care unit setting. Although ceftriaxone is a frequently used agent for CAP, increasing incidence of multidrug-resistant Streptococcus pneumoniae and concerns regarding poor outcomes associated with ineffective therapy have prompted the search for a well-tolerated treatment alternative that is effective against bacteria that can cause CAP. Ceftaroline fosamil, the prodrug of ceftaroline, is a new extended-spectrum cephalosporin that exhibits time-dependant bactericidal activity against numerous Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. pneumoniae. Notable exceptions include Pseudomonas spp. and Gram-negative organisms that produce extended-spectrum β-lactamases or carbapenemases. Two large Phase III clinical trials (FOCUS 1 and 2) reported that ceftaroline fosamil was well tolerated, with a clinical cure rate of CAP that was noninferior to that with ceftriaxone in nonintensive care unit adult inpatients with moderately severe (Pneumonia Outcomes Research Team score of III or IV) community-acquired pneumonia.

Colonization, pathogenicity, host susceptibility, and therapeutics for Staphylococcus aureus: what is the clinical relevance?

“…First, ceftaroline also has activity against a narrow spectrum of gram-negative organisms; however, there is no intrinsic activity against Pseudomonas spp. , or other gram-negative pathogens that produce beta-lactamases, including AmpCs, extended-spectrum beta-lactamases and Klebsiella pneumoniae carbapenemases [141]. Second, there are some emerging data to suggest that ceftaroline might be more efficacious for invasive infections.…”

New antibiotics

“…Çok uluslu, çift kör, randomize faz 3 çalışması sonucuna göre (n=1240); toplumdan edinilmiş pnömoni nedeniyle hospitalize edilen hastalarda, klinik kür oranı seftriakson ile benzer bulunmuştur. Çok ilaca dirençli Staphylococcus aureus pnömonisi varlığında seftriakson %22.2 iken, seftarolin etkinliği %100 bulunmuştur (16,17) . lumdan edinilmiş pnömoni için 12 saatte bir 600 mg IV, 5-7 gün süre ile; komplike cilt enfeksiyonları için 12 saatte bir 600 mg IV, 5-14 gün süre ile kullanılma-sı önerilmektedir (16) .…”

“…Çok uluslu, çift kör, randomize faz 3 çalışması sonucuna göre (n=1240); toplumdan edinilmiş pnömoni nedeniyle hospitalize edilen hastalarda, klinik kür oranı seftriakson ile benzer bulunmuştur. Çok ilaca dirençli Staphylococcus aureus pnömonisi varlığında seftriakson %22.2 iken, seftarolin etkinliği %100 bulunmuştur (16,17) .…”

Current Status and Future Perspectives of Antibiotic Therapy for MRSA Infections

“…This has created a serious challenge for case management and infection control, particularly in limited resources settings. Therefore, there is an urgent need for novel effective antibiotics agents [7]. The primary strategies of pharmaceutical industries for developing new therapeutics is limited to pursue discovering new antibiotics or repurposing existing drugs, such as the groups of beta-lactams and aminoglycosides [8,9].…”