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Background and Objective Community-acquired bacterial pneumonia (CABP) affects millions of people each year in the USA. The majority of patients with CABP are treated in the community setting with empirical antimicrobial therapy. Delafloxacin is an anionic fluoroquinolone approved for the treatment of adult patients with CABP. This de novo analysis sought to estimate the budget impact of delafloxacin in the treatment of adult patients with CABP in the outpatient setting from the payer’s perspective. Methods A budget impact model (BIM) was developed from the perspective of a US third-party payer to estimate the cost of introducing delafloxacin for the outpatient treatment of CABP over a 1-year time horizon. Population, clinical, and cost inputs were based on the available literature, clinical trial data, and real-world evidence studies. Scenario analyses were conducted to evaluate the potential budget impact among COPD/asthma patients based on the findings from the phase III trial of delafloxacin for CABP, which indicated that patients with COPD or asthma may experience improved effectiveness with delafloxacin compared to moxifloxacin. Results In the base-case analysis, with a hypothetical plan of 1,000,000 members, the model estimated that adding delafloxacin to the formulary resulted in a total budget impact of $58,987. This increase was mainly attributed to treatment acquisition costs. In the scenario analysis that was restricted to COPD/asthma patients, adding delafloxacin to the formulary was estimated to result in a total budget impact of $5,042. Conclusion The results of the budget impact analyses provide conservative estimates of the impact of adding delafloxacin to outpatient formularies in substitution of moxifloxacin. Electronic supplementary material The online version of this article (10.1007/s40261-020-00938-y) contains supplementary material, which is available to authorized users.

The most common adverse effects of the fluoroquinolones involve the gastrointestinal tract, skin and CNS, and are mainly mild and reversible. Of the gastrointestinal events, nausea and vomiting are the most common. Mild hepatic reactions are a class effect, usually presenting as mild transaminase level increases without clinical symptoms. However, postmarketing surveillance has revealed significant hepatotoxicity with trovafloxacin. It is not currently known whether the severe reactions to trovafloxacin are specific to that agent or simply represent an extreme of an emerging class effect. The enormous worldwide usage of, and extensive published adverse effect data on the other fluoroquinolones and naphthyridones suggests the former. In perspective, rare but serious hepatotoxicity has been reported with other fluoroquinolones and the overall incidence of trovafloxacin hepatotoxicity is not dissimilar to that reported with flucloxacillin and amoxicillin-clavulanic acid. CNS reactions vary in severity and include dizziness, convulsions (notably with lomefloxacin) and psychoses. Fluoroquinolones differ in their pro-convulsive activity, relating to their differing potential as gamma-aminobutyric acid antagonists and binding to the N-methyl-D-aspartate receptor. The basis for the increased seizure potential following the coadministration of nonsteroidal anti-inflammatory drugs with certain fluoroquinolones is not fully understood. Fluoroquinolone phototoxicity, caused by the generation of toxic free oxygen species under exposure to UVA radiation, is significantly more common with 8-halogenated compounds. Certain patient groups, e.g. patients with cystic fibrosis, are predisposed to this adverse effect. Murine photocarcinogenicity has been demonstrated with lomefloxacin, but no such effects have been reported in humans. Prolongation of the QTc interval is also a class effect, although cardiac arrhythmias have only been linked with sparfloxacin. Among the newer fluoroquinolones, clinically significant cardiac events are rare or absent but possible interactions in patients receiving other drugs capable of causi ng QT prolongation should be anticipated. Tendinitis and rupture, usually of the Achilles tendon, are rare, class-effects of fluoroquinolones, most frequently reported with pefloxacin. Predisposing factors include aging, corticosteroid use, renal disease, haemodialysis and transplantation. Use of fluoroquinolones in paediatric patients remains contentious. However, accruing human data suggest that restrictions on paediatric use imposed because of fluoroquinolone-induced cartilage damage in juvenile animals, may soon be relaxed. Data from over 1700 children in the UK failed to disclose arthropathy and extensive paediatric use of norfloxacin in Japan and ciprofloxacin in developing countries has been free of articular effects.

New fluoroquinolones have been in clinical use for 10 years and have an excellent record of safety and tolerance. The main elements of their adverse reaction profile were predictable from human experience with precursor naphthyridines and quinolones, and from toxicological studies in animals. Thus gastrointestinal reactions (1 to 5%), skin disturbances (less than 2.5%) and central nervous system (CNS) effects (usually around 1 to 2%) were anticipated. Individual group members exhibit particular properties in relation to their chemical structures, for example the phototoxicity associated with 8-halogenation of the nucleus and found to be a particular problem with lomefloxacin and sparfloxacin. Other members, for example ofloxacin, are linked to a higher than usual incidence of CNS reactions and psychological disturbance. However, despite increasing usage, none of the present group have been implicated in joint damage in children, which had been a major concern following reports of this effect in juvenile animals in chronic toxicity studies. Furthermore, intravenous formulations appear to have no associated increase in toxicity. Crystalluria with associated renal damage, originally thought likely to limit intravenous dosage, has not proved to be a problem in humans. Clinically significant interactions may occur but, as with those involving various NSAIDs and potentially leading to convulsions, they have been defined and are thus avoidable. Postmarketing surveillance studies and prescription event monitoring have largely confirmed the limited adverse reaction profile defined during clinical trials. However, some unexpected reactions have appeared after launch, most notably the episodes of haemolysis, renal failure and hypoglycaemia which led to the withdrawal of temafloxacin. These effects have not been observed with other fluoroquinolones. However, severe tendinitis appears to be a group effect, albeit rare, and anaphylactoid reactions have been reported with several of the fluoroquinolone group, often in AIDS patients. The new fluoroquinolones are essentially a well tolerated group of antibacterials, the benefits of which clearly outweigh their disadvantages in a wide range of indications. Clinical efficacy has been a larger determinant of which members have succeeded in the marketplace than potential toxicity. However, the lesser potential for adverse effects of some of the class, e.g. norfloxacin, ofloxacin and ciprofloxacin, has undoubtedly led to their more widespread use. For others, e.g. enoxacin, limited clinical utility and a perception of increased toxicity have resulted in sidelining. There remains the potential for development of safer and yet more active fluoroquinolones via chemical manipulation both of the nucleus and the side chain substituents.

Sinusitis is an inflammatory condition often complicated by the development of secondary bacterial infection.[1] Frequently, acute sinusitis is a sequela of the common cold or viral upper respiratory tract infection. It is often preceded by rhinitis; hence the term rhinosinusitis.[2] The objectives of treating acute rhinosinusitis include eradication of the infection, decreased duration of illness and prevention of complications (e.g. chronic sinusitis). Effective therapy should restore sterility and normal mucociliary function to the sinus cavity. Appropriate antibiotic therapy should take into consideration not only the national increasing prevalence of β-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis, but also the penicillinand other drug-resistant pneumococci.[3-6] The primary objective of this multicentre, community-based, randomised, open-label, prospective clinical trial was to compare the efficacy and tolerability of ciprofloxacin and cefuroxime axetil for the treatment of acute rhinosinusitis.