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• W2084571297 abstract "We agree with the Comment by Michael Head and colleagues that more investment is urgently needed in pneumonia and pneumococcal research.1Head MG Fitchett JR Newell M-L et al.Investment in pneumonia and pneumococcal research.Lancet Infect Dis. 2014; 14: 1037-1038Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar However, the authors are incorrect in stating that investment has been lacking for the development of antibiotics to treat pneumonia. Ceftaroline, an injectable antibiotic, was approved as a treatment for pneumococcal pneumonia in 2011. Cempra has invested more than US$200 million in the development of solithromycin, a fourth-generation macrolide and the first fluoroketolide, for the treatment of pneumococcal pneumonia. Solithromycin, which has potent activity against pneumococci, is being developed as oral capsules, as an intravenous formulation, and also as a paediatric suspension that will provide flexibile dosing for all age groups. In the phase 3 trial for the oral treatment of PORT Class II-IV community acquired bacterial pneumonia (NCT01756339) solithromycin was shown to have similar activity to moxifloxacin. In a phase 2 clinical trial in moderate to moderately severe community-acquired bacterial pneumonia solithromycin used as a monotherapy had similar activity, but showed better safety than levofloxacin.2Oldach D Clark K Schranz J Das A et al.Randomized, double-blind, multicenter, phase 2 study comparing the efficacy and safety of oral solithromycin (CEM-101) to those of oral levofloxacin in the treatment of patients with community-acquired bacterial pneumonia.Antimicrob Agts Chemother. 2013; 57: 2526-2534Crossref PubMed Scopus (68) Google Scholar A second international phase 3 trial with intravenous to oral therapy is open for enrolment (NCT01968733). So far, solithromycin has been active against all pneumococci tested, which have been collected from various regions of the world. The molecule is unique because it interacts with three regions on the bacterial ribosomes by contrast with the one-site interaction by the old macrolides, making it more complex for bacteria to acquire resistance. Additionally, unlike the old macrolides which are bacteriostatic, solithromycin can be bactericidal through synthesis of mistranslated peptides.3Gupta P Kannan K Mankin AS et al.Regulation of gene expression by macrolide-induced ribosomal frameshifting.Mol Cell. 2013; 52: 629-642Summary Full Text Full Text PDF PubMed Scopus (44) Google Scholar An important factor to note is the poor investment in primary care antibiotics over the past few decades. Unlike ceftaroline, solithromycin is being developed for use in both hospital and primary care settings. In a longitudinal analysis of the proportion of patients who did not respond to antibiotic treatment in primary care from 1991 to 2012, Currie and colleagues4Currie CJ Berni E Jenkins-Jones S et al.Antibiotic treatment failure in four common infections in UK primary care 1991–2012: longitudinal analysis.BMJ. 2014; 349: g5493Crossref PubMed Scopus (82) Google Scholar reported that of 3 148 947 lower respiratory tract infections, 16·9% were not cured by primary antibiotic monotherapy. The failure rate was the highest in lower respiratory tract infections among the four types of infections studied: skin and skin structure infections, acute otitis media, upper respiratory tract infections, and lower respiratory tract infections. Failure to respond to primary antibiotic therapy leads to hospital admission, progression to severe infections during the initial failure, and a risk of secondary hospital-acquired infection.5Reynolds CA Finkelstein JA Ray GT et al.Attributable healthcare utilization and cost of pneumonia due to drug-resistant Streptococcus pneumoniae: a cost analysis.Antimicrob Resist Infect Control. 2014; 3: 16Crossref PubMed Scopus (24) Google Scholar The risk of Clostridium difficile colitis increases with the use of broad-spectrum cephalosporins and fluoroquinolones. Therefore, not only is there a need for pneumococcal pneumonia treatment, but also an increasing need to successfully treat pneumonia with a first-line primary care antibiotic and to avoid hospital admission. I am the President and CEO of Cempra, which is developing solithromycin to treat pneumonia. Investment in pneumonia and pneumococcal researchThe worldwide burden of pneumonia is high—the disease caused 1·2 million deaths in 2010, mostly in children younger than 2 years.1 In the same year, at least 76·7 million disability-adjusted life-years (DALYs) were attributed to pneumonia and pneumococcal disease,2 although DALYs are inevitably increased in diseases that mostly affect young children. Infections of the lower respiratory tract (many of which are probably pneumonia-related) were the single largest cause of worldwide DALYs in children younger than 1 year. Full-Text PDF Challenges in mapping research investments for treatments against pneumoniaWe thank Prabhavathi Fernandes for her interest in our work on pneumonia-related research investments1 and welcome her response.2 It is encouraging to see the investments of Cempra and the progress made in developing treatments for pneumococcal pneumonia, alongside the success of pneumococcal vaccination programmes.3 Full-Text PDF" @default.
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• W2084571297 title "Investment in antibiotics against pneumonia" @default.
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• W2084571297 doi "https://doi.org/10.1016/s1473-3099(15)70057-5" @default.
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