*4.2.4 Antidepressive drugs*

Regarding the antidepressive drugs, amitriptyline has reduced the inflammation in the lung of cystic fibrosis mice and prevented infection by *P. aeruginosa* [77]. At clinical stage, a phase II clinical trial evaluating the effect of amitriptyline on the

improvement of lung function in 18 patients with cystic fibrosis patients showed that amitriptyline improves the lung function by increasing the forced expiratory volume and weight of these patients [78, 79].

## *4.2.5 Other drugs*

Other drugs with different modes of action and clinical indications have been evaluated as antibacterial agents against *P. aeruginosa*. Metformin has been reported to inhibit QS, biofilm formation, and swimming and twitching motilities of PAO1 strain [21]. Calcitriol has enhanced the bactericidal activity against *P. aeruginosa*, modulating the activity of monocytes and macrophages to increase their bacterial killing [37]. Compared with *A. baumannii*, robenidine has been recently showed to present only synergy with polymyxin B nanpeptide against reference strains of *P. aeruginosa in vitro* [60]. Polymyxin B and colistin have been also combined with auronafin and simvastatin, respectively. Both drugs exhibited synergy with sub-inhibitory concentrations of polymyxin B and colistin against a collection of reference strains of *P. aeruginosa*, reducing the MIC of auronafin from >256 mg/L to 0.125–0.5 mg/L and the MIC of simvastatin from >256 mg/L to 16–32 mg/L [58, 59]. At clinical stage, a phase IV trial determining the role of atorvastatin, another statin, in patients with bronchiectasis and infection with *P. aeruginosa* showed that atorvastatin reduced systemic inflammation and improved quality of life of these patients [80, 81]. In addition, sodium nitrite, used for treatment of acute cyanide poisoning, has been shown in vitro to kill mucoid *P. aeruginosa* strains isolated from patients with cystic fibrosis, under anaerobic planktonic and biofilm conditions [82, 83]. Two early stage (I/II and II) clinical trials have been conducted to evaluate sodium nitrite as antimicrobial agent and as disrupter of biofilm formation in patients with cystic fibrosis by *P. aeruginosa* [84, 85]. The results from both studies have not yet published.
