Clinical review of delafloxacin: a novel anionic fluoroquinolone

Mogle, Bryan T.; Steele, Jeffrey; Thomas, Stephen J.; Bohan, KarenBeth H.; Kufel, Wesley D

doi:10.1093/jac/dkx543

Cited by 51 publications

(65 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Older FQs (e.g. ciprofloxacin, levofloxacin and moxifloxacin) are not commonly used for treating ABSSSIs caused by MRSA, primarily reflecting the requirement for additional antibacterials to cover skin infections caused by FQ-resistant organisms and also because of their safety profile, especially in patients with comorbidities and the elderly [3][4][5]10]. Delafloxacin treatment was associated with high rates of microbiological cure against MRSA isolates (± levofloxacin-resistant strains and those with mutations in the QRDR) in pivotal phase 3 trials (Sect.…”

Section: Place Of Delafloxacin In the Management Of Absssismentioning

confidence: 99%

“…Patients with polymicrobial infections may be at higher risk of inadequate treatment and require broad-spectrum antibacterials [3]. Fluoroquinolones (FQs), given their broad spectrum of activity against clinically relevant Gram-positive and Gram-negative bacteria and availability as intravenous and oral formulations (provides flexibility to transition from intravenous to oral therapy), are amongst the most commonly utilized classes of antibacterials for treating infectious diseases [4]. However, in recent years, the global emergence of methicillin-resistant S. aureus (MRSA) strains and other resistant pathogens, including FQ-resistant and multi-drug resistant (MDR) bacteria, has posed a major concern for contemporary healthcare systems [3].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections

Scott

2020

Drugs

View full text Add to dashboard Cite

The global spread of antibacterial-resistant strains, especially methicillin-resistant Staphylococcus aureus (MRSA) for acute bacterial skin and skin structure infections (ABSSSIs), has driven the need for novel antibacterials. Delafloxacin [Quofenix™ (EU); Baxdela ® (USA)], a new fluoroquinolone (FQ), has a unique chemical structure that enhances its antibacterial activity in acidic environments such as occurs in ABSSSIs (including S. aureus infections). Delafloxacin (intravenous and oral formulations) is approved in several countries for the treatment of adults with ABSSSIs (featured indication). In intent-to-treat analyses in pivotal phase 3 trials in adults with ABSSSIs, including those with comorbid disease, intravenous delafloxacin monotherapy (± oral switch after six doses) twice daily was noninferior to intravenous vancomycin + aztreonam for primary endpoints, as specified by the FDA (objective response rate at 48-78 h after initiation of therapy) and the EMA [investigator-assessed clinical cure rate at the follow-up visit at day 14 (± 1 day)]. Delafloxacin was generally well tolerated, with most treatment-related adverse events mild to moderate in severity and few patients discontinuing treatment because of these events. Relative to vancomycin + aztreonam (a non-FQ regimen), delafloxacin treatment was not associated with an increased risk of FQ-associated AEs of special interest. Given its unique chemical structure that confers novel properties relative to other FQ and its broad spectrum of activity against common clinically relevant Gram-positive pathogens, including against MRSA strains (± FQ-resistance mutations), and Gram-negative pathogens, intravenous delafloxacin (± oral switch) provides a novel emerging option for the treatment of adult patients with ABSSSIs.

show abstract

Section: Place Of Delafloxacin In the Management Of Absssismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections

Scott

2020

Drugs

View full text Add to dashboard Cite

show abstract

“…Delafloxacin, an anionic FQ, has a unique structure and possesses distinct chemical characteristics. Delafloxacin is an anionic FQ, which means that it has increased intracellular penetration in bacteria allowing for enhanced bactericidal activity in acidic conditions [1]. The increased potency in low pH is a special feature of delafloxacin as many infection sites such as the urinary tract, abscess fluid, decubitus ulcers, epithelial lining fluid, and phagolysosomes of infected cells have an acidic environment [100].…”

Section: Delafloxacinmentioning

confidence: 99%

“…Delafloxacin, a recently approved anionic FQ, has a unique structure and possesses distinct chemical characteristics. As an anionic FQ, delafloxacin has increased intracellular penetration in bacteria allowing for enhanced bactericidal activity in acidic conditions [1]. Delafloxacin is has broad spectrum of activity against Gram-positive pathogens, including Staphylococcus aureus, S. pneumonia, and most fluoroquinolone-resistant strains, except enterococci [2,3].…”

Section: Introductionmentioning

confidence: 99%

Community-Acquired Bacterial Pneumonia—Changing Epidemiology, Resistance Patterns, and Newer Antibiotics: Spotlight on Delafloxacin

et al. 2020

View full text Add to dashboard Cite

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality both in the USA and globally. As the burden of CAP continues to increase due to several factors, the advances in its diagnosis, prevention, and treatment have taken on even greater interest and importance. The majority of CAP patients are treated empirically, and selection of appropriate antibiotic treatment is increasingly difficult because the epidemiology of CAP is changing, in part due to antimicrobial resistance, and the causative CAP pathogens differ between countries and regions. There is also an increasing prevalence of chronic co-morbid diseases among CAP patients. Treatment of CAP has become challenging because of these factors along with the varying safety profiles and efficacy of well-established antibiotics, as well as limited new therapeutic options. Recently, however, new antibiotics have been approved, which will expand the treatment options for CAP, particularly in those patients with underlying complications. Recently approved delafloxacin, an anionic fluoroquinolone, has a unique structure and distinct chemical characteristics; it demonstrated non-inferiority to moxifloxacin in a phase III clinical trial, but was shown to be superior to moxifloxacin at early clinical response in CAP patients who also have chronic obstructive pulmonary disease (COPD) or asthma as a co-morbidity, and in CAP patients who may have severe illness. Delafloxacin could offer an additional therapy against resistant isolates and among these difficult-to-treat patients. This review summarizes the development, latest research, and safety profile of the new antibiotic delafloxacin, and its potential future role in the treatment of CAP.

show abstract

“…We have provided further evidence (albeit from post hoc analyses) suggesting that the hazard of failure or relapse (FoR) may be higher in the short regimen than in the long regimen. Further optimization of short DR-TB regimens to improve efficacy is urgently needed including dose optimization, the use of new drugs, and the use of alternative fluoroquinolones such as the novel delafloxacin [ 23 ] or gatifloxacin which, while unavailable now in many countries, has shown recent promise in MDR-TB observational cohorts [ 24 ]. These analyses highlight the importance of how loss to follow-up and other censoring are accounted for in analyses of clinical trial data.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the efficacy of the short regimen for rifampicin-resistant TB from the STREAM trial

Phillips

Deun²,

Ahmed

et al. 2020

BMC Med

View full text Add to dashboard Cite

Background The STREAM trial demonstrated that a 9–11-month “short” regimen had non-inferior efficacy and comparable safety to a 20+ month “long” regimen for the treatment of rifampicin-resistant tuberculosis. Imbalance in the components of the composite primary outcome merited further investigation. Methods Firstly, the STREAM primary outcomes were mapped to alternatives in current use, including WHO programmatic outcome definitions and other recently proposed modifications for programmatic or research purposes. Secondly, the outcomes were re-classified according to the likelihood that it was a Failure or Relapse (FoR) event on a 5-point Likert scale: Definite, Probable, Possible, Unlikely, and Highly Unlikely. Sensitivity analyses were employed to explore the impact of informative censoring. The protocol-defined modified intention-to-treat (MITT) analysis population was used for all analyses. Results Cure on the short regimen ranged from 75.1 to 84.2% across five alternative outcomes. However, between-regimens results did not exceed 1.3% in favor of the long regimen (95% CI upper bound 10.1%), similar to the primary efficacy results from the trial. Considering only Definite or Probable FoR events, there was weak evidence of a higher risk of FoR in the short regimen, HR 2.19 (95%CI 0.90, 5.35), p = 0.076; considering only Definite FoR events, the evidence was stronger, HR 3.53 (95%CI 1.05, 11.87), p = 0.030. Cumulative number of grade 3–4 AEs was the strongest predictor of censoring. Considering a larger effect of informative censoring attenuated treatment differences, although 95% CI were very wide. Conclusion Five alternative outcome definitions gave similar overall results. The risk of failure or relapse (FoR) may be higher in the short regimen than in the long regimen, highlighting the importance of how loss to follow-up and other censoring is accounted for in analyses. The outcome of time to FoR should be considered as a primary outcome for future drug-sensitive and drug-resistant TB treatment trials, provided sensitivity analyses exploring the impact of departures from independent censoring are also included.

show abstract

Clinical review of delafloxacin: a novel anionic fluoroquinolone

Cited by 51 publications

References 60 publications

Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections

Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections

Community-Acquired Bacterial Pneumonia—Changing Epidemiology, Resistance Patterns, and Newer Antibiotics: Spotlight on Delafloxacin

Investigation of the efficacy of the short regimen for rifampicin-resistant TB from the STREAM trial

Contact Info

Product

Resources

About