Background and Aim: The emergence of colistin-resistant strains is considered a great threat for patients with severe infections. Here, we investigate the prevalence and some possible mechanisms of colistin resistance among multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa). Methods: Antimicrobial susceptibility was performed using disc diffusion methods while colistin resistance was detected by agar dilution method. Possible mechanisms for colistin resistance were studied by detection of mcr-1 and mcr-2 genes by conventional PCR, detection of efflux mechanisms using Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP), studying outer membrane protein profile and Lipopolysaccharide (LPS) profile of resistant isolates. Results: It was found that MDR and XDR represented 96% and 87% of the isolated P. aeruginosa, respectively, and colistin resistance represented 21.3%. No isolates were positive for mcr-2 gene while 50% of colistin-resistant isolates were positive for mcr-1. Efflux mechanisms were detected in 3 isolates. Protein profile showed the presence of a band of 21.4 KDa in the resistant strains which may represent OprH while LPS profile showed differences among colistin-resistant mcr-1 negative strains, colistin-resistant mcr-1 positive strains and susceptible strains. Conclusion: The current study reports a high prevalence of colistin resistance and mcr-1 gene in P. aeruginosa strains isolated from Egypt that may result in untreatable infections. Our finding makes it urgent to avoid unnecessary clinical use of colistin.

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Bupropion efficacy in attenuation of morphine tolerance and dependence with its high safety and tolerability profile provide an alternative option to conventional agents e.g., ketamine and clonidine to modulate these phenomena.

Fluoxetine, a commonly prescribed antidepressant, use in nociceptive pain management represents one of the unsettled issues of fluoxetine therapeutics. By reviewing the literature about fluoxetine's possible roles in this setting, those could be solitary antinociceptive effect, enhancement of acute morphine analgesia, blocking morphine tolerance development, and blocking dependence development and associated abstinence syndrome. In this study, we examined those four alleged roles of fluoxetine. Moreover, as effective alleviation of morphine tolerance, dependence, and abstinence syndrome represents one of the most challenging medical needs, we biochemically analyzed fluoxetine effect on these phenomena. Fluoxetine (10 mg/kg, IP) was examined in hot plate test for assessment of possible analgesic activity and enhancement of morphine acute analgesia (1 and 5 mg/kg, SC). Repeated morphine (5 mg/kg, SC) administration for 9 days developed tolerance and dependence; fluoxetine was co-administered to evaluate its potential to modulate these processes. We also determined concomitant changes in neurotransmitters (glutamate and noradrenaline), inflammatory status, and prooxidant-antioxidant balance. Our results indicated that fluoxetine did not possess significant analgesia solely and did not enhance acute morphine analgesia. However, fluoxetine administration with morphine significantly attenuated tolerance and dependence development and abstinence syndrome with corresponding suppression of morphine-induced changes in neurotransmitters (glutamate and noradrenaline), inflammatory status, and prooxidant-antioxidant balance. These biochemical results may reflect both direct and indirect effects of fluoxetine. Our conclusion is that despite fluoxetine possesses low - if any - analgesic activity, it significantly adds to opioids not via enhancing analgesic activity but through modulation of tolerance and dependence development.

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