Delafloxacin a promising treatment option for atypical pneumonia in adults

Delafloxacin monotherapy is effective for treating community-acquired pneumonia caused by atypical pathogens and may be considered a useful addition to the treatment toolbox, according to data from the phase III study DEFINE-CABP.

The novel fluoroquinolone antibiotic possesses Gram-positive, Gram-negative, and atypical activity including that against fluoroquinolone nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA) isolates, according to researchers. “[It] offers flexibility of intravenous and oral treatment with no QT restrictions or phototoxicity, as well as no major drug-drug interactions.” [Antimicrob Agents Chemother 2017;61:e00772-17; Open Forum Infect Dis 2018;5:ofy220; https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208610s000,208611s000lbl.pdf]

DEFINE-CABP has shown the noninferiority of delafloxacin 300 mg twice daily to moxifloxacin 400 mg once daily in terms of the primary endpoint of early clinical response (88.9 percent vs 89.0 percent) in adults with community-acquired bacterial pneumonia (CABP). The current analysis was conducted to provide data regarding atypical pathogens. [Open Forum Infect Dis 2020;7:ofz514]

In the microbiological intent-to-treat (MITT) population of 520 patients, 156 (30 percent) had at least one atypical bacterial pathogen identified at baseline with the use of multiple diagnostic methods (respiratory or blood culture, PCR, serology, and urinary antigen). Of these, 68 patients had monomicrobial atypical infection and 12 had polymicrobial all-atypical infections. [Int J Infect Dis 2020;doi:10.1016/j.ijid.2020.06.018]

Among those with polymicrobial infections, Streptococcus pneumoniae was the most commonly isolated co-infecting organism while Chlamydia pneumoniae was the most frequently occurring co-infecting atypical organism.

When comparing diagnostic yields, serology gave the highest number of diagnoses for Mycoplasma pneumoniae and Legionella pneumophila. Delafloxacin and moxifloxacin demonstrated similar in-vitro activity against M. pneumoniae, while the former had greater activity against L. pneumophila. Two macrolide-resistant M. pneumoniae isolates were recovered, and none that was resistant to fluoroquinolone.

Rates of microbiological success (documented or presumed eradication) at test-of-cure did not significantly differ between the two treatment groups. There was no evidence of a correlation between minimum inhibitory concentration (MIC) and outcome, and favourable outcomes were observed across all delafloxacin baseline MICs.

In conclusion, delafloxacin may be used in the treatment of CABP in adults, "where broad-spectrum coverage including atypical activity is desirable,” the researchers said.

“Since delafloxacin is a broad-spectrum antibiotic, it also has in vitro and clinical activity against the frequently occurring co-infecting Gram-positive and Gram-negative bacterial pathogens including S. pneumoniae, H. influenzae, H. parainfluenzae, Enterobacteriaceae (K. pneumoniae and E. coli), S. aureus, and P. aeruginosa. Coverage for Gram-positive, Gram-negative, and atypical pathogens may be an important consideration for treatment of patients, especially those with comorbidities,” they added. [https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208610s000,208611s000lbl.pdf]