SESSION TITLE: Miscellaneous Cases II
SESSION TYPE: Affiliate Case Report Slide
PRESENTED ON: Monday, October 27, 2014 at 03:15 PM - 04:15 PM
INTRODUCTION: Infection of the respiratory tract with Burkholderia cenocepacia (Bc) is associated with accelerated decline in lung function and increased mortality in cystic fibrosis (CF) patients.1Bc often possesses innate resistance to multiple antimicrobial classes, making eradication uncommon in established infection. We report the first use of clinafloxacin in the treatment of a CF patient with advanced Bc infection.
CASE PRESENTATION: A 30 year old male with CF (genotype F508del/3199del6), chronically infected with Bc and mucoid Pseudomonas aeruginosa (Pa), was admitted for pulmonary exacerbation. He carried a history of significant allergies to multiple antimicrobial classes including beta lactams, macrolides, and aminoglycosides. He had received multiple courses of standard IV antibiotics after desensitization over ten years (12 hospitalizations over the prior 3 years). He was maintained on chronic minocycline. During hospitalizations over the prior 12 months, the patient was treated with amikacin, cefepime, chloramphenicol and ciprofloxacin which failed to achieve clinical improvement, and FEV1 dropped from 75% predicted to 37% predicted. After obtaining institutional review board approval, an investigational, fourth generation fluoroquinolone, clinafloxacin, was administered intravenously under close monitoring, first at a dose of 200 mg Q12 hours for 14 days and then 400 mg Q12 hours for 8 days. There was no evidence of significant QTc prolongation, phototoxicity, symptomatic hypoglycemia, liver or renal toxicity over the duration of therapy. The patient reported subjective improvement and there was stabilization of pulmonary function and radiographic findings.
DISCUSSION: Clinafloxacin demonstrates superior in vitro activity against Pa and Bc when compared to other fluoroquinolones. This may be due to clinafloxacin being a poor substrate for multi-drug efflux systems in bacteria.2 Early clinical trials with this agent reported isolated cases of serious phototoxicity and hypoglycemia which hampered commercial development for use in humans.2 We did not observe such toxicity in our closely monitored patient.
CONCLUSIONS: Clinafloxacin may be a potential treatment option for patients with refractory Bc infection. Further clinical studies would be needed to confirm this.
Reference #1: Jones AM etal. Burkholderia cenocepacia and Burkholderia multivorans: influence on survival in cystic fibrosis. Thorax. 2004;59(11):948-51.
Reference #2: Zhanel GG etal. The new fluoroquinolones: A critical review. Can J Infect Dis. 1999;10(3):207-38
DISCLOSURE: The following authors have nothing to disclose: Akshu Balwan, Jonathan Zuckerman
Discussion about drug not approved for used in human subjects "Clinafloxacin" though prior human trials have been conducted.