DELAFLOXACIN, A NOVEL FLUOROQUINOLONE ANTIBIOTIC WITH ACTIVITY AGAINST HOSPITAL-, COMMUNITY- AND LIVESTOCK- ASSOCIATED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

Editor,

Delafloxacin is a new fluoroquinolone antibiotic, approved for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by both Gram-positive and Gram-negative organisms.¹ It recently received its regulatory licence from the European Medicines Agency in December 2019 (https://www.ema.europa.eu/en/medicines/human/ EPAR/quofenix). For a seminal review on this background to this antibiotic, please see the recent seminal review by Mogle and colleagues.¹

As with any newly introduced antibiotic, it is important to evaluate a new antibiotic in the context of the local epidemiology and resistance rates, to aid physicians in the positioning of such a new antibiotic. To date, there have been no reports on the activity of delafloxacin against methicillin­sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, within the Northern Ireland context, hence we wished to examine the in vitro susceptibility of MSSA and MRSA isolates to this new antibiotic.

Staphylococcus aureus (n=23) isolates [15 MSSA & 8 MRSA] were employed in this study, as detailed in Table 1. Isolates were obtained from the MicroARK Microbiology Culture Repository housed within the Northern Ireland Public Health Laboratory, Belfast City Hospital. Isolates within each category were selected at random for employment in this study. No other criteria were used in the selection of these organisms. Prior to use, all isolates were passaged twice by subculturing on Columbia Blood agar (Oxoid CM0031, Oxoid Ltd., Basingstoke, UK), supplemented with 5% (v/v) defibrinated horse blood for 24h at 37^oC, under aerobic conditions. In vitro susceptibilities were examined on all 23 isolates, by employing Etest^® gradient for delafloxacin (range:0.002-32 mg/L), as per manufacturer's instructions (Biomerieux Ltd., France) and in accordance with EUCAST methodology² and interpretive criteria.³ Susceptibility of isolates to delafloxacin, as determined by the Minimum Inhibitory Concentration (MIC) value (mg/L), are quoted in Table 1.

Table 1.

In vitro susceptibility of NI methicillin-sensitive and resistant Staphylococcus aureus to delofloxacin

Organism (Source)	Number of isolates		Minimum Inhibitory
	Concentration (MIC) [mg/L]	Mean	Range
Staphylococcus aureus (methicillin-sensitive; MSSA) Sputum isolates from adult patients with cystic fibrosis (CF)	8	0.043	<0.002-0.19
Staphylococcus aureus (methicillin-resistant: MRSA) Hospital-associated (from blood culture)	6	0.147	<0.002 - 0.25
Hospital-associated (zoonotic; canine)	1	0.19	0.19
Community-associated MRSA [CA-MRSA ST35, 5134, 5090, 4526, 4266 & 4388]	6	0.0233	<0.002 - 0.125
Livestock-associated MRSA LA-MRSA (porcine source) CC398 & CC30	2	0.05	0.006 - 0.094

Given the current EUCAST breakpoint for S. aureus sensitivity (S) < 0.25 mg/L, none of the isolates tested were considered resistant to delafloxacin. Presently, there are no published reports of fluoroquinolone susceptibility to S. aureus solely in Northern Ireland, however when combined with data from England, the latest published ciprofloxacin resistance rates for 2018 in MSSA and MRSA bacteramia were 5% and 62%, respectively.⁴

Delafloxacin is the latest addition to the fluoroquinolones in the antibiotic armamentarium. Early indications show that it may have a good in vitro susceptibility profile against S. aureus. In a study involving ABSSSIs in 1,042 patients from which 685 S. aureus isolates were recovered, delafloxacin MIC₉₀ values against levofloxacin-non-susceptible S. aureus, MRSA and MSSA isolates were all 0.25 pg/ml and where S. aureus was eradicated/presumed eradicated in 98.4% (245/249) of delafloxacin-treated patients. These Phase 3 clinical trial data suggest that delafloxacin could be a good option for the treatment of infections caused by S. aureus isolates causing ABSSSIs, including MRSA isolates, where high rates of ciprofloxacin and levofloxacin non­susceptibility are observed.⁵

Physicians who think that the use of a fluoroquinolone may have a potential role in treating S. aureus infection in their patient should discuss options with their local microbiologist.

DECLARATION OF INTERESTS

The authors do not have any interests to declare. Delafloxacin E-test strips were kindly offered to hospitals throughout Europe (www.ihma.com) and were supplied gratis by Menarini Pharmaceuticals, Italy. Neither IHMA, nor Menarini Pharmaceuticals nor their agents were involved in study conceptualization, experimental design, experimental execution, data analyses, report writing nor had any role in the editorial process, funding or any other aspect of the study or writing.