Empirical treatment of lower urinary tract infections in the face of spreading multidrug resistance: in vitro study on the effectiveness of nitroxoline.

The spread of antimicrobial resistance challenges the empirical treatment of urinary tract infections (UTIs). Among others, nitrofurantoin is recommended for first-line treatment, but acceptance among clinicians is limited due to chronic nitrofurantoin-induced lung toxicity and insufficient coverage of Enterobacteriaceae other than Escherichia coli. Nitroxoline appears to be an alternative to nitrofurantoin owing to its favourable safety profile, however data on its current in vitro susceptibility are sparse. In this study, susceptibility to nitroxoline was tested against 3012 urinary clinical isolates (including multidrug-resistant bacteria and Candida spp.) by disk diffusion test and/or broth microdilution. At least 91% of all Gram-negatives (n = 2000), Gram-positives (n = 403) and yeasts (n = 132) had inhibition zone diameters for nitroxoline ≥18 mm. Except for Pseudomonas aeruginosa, nitroxoline MIC90 values were ≤16 mg/L and were 2- to >16-fold lower compared with nitrofurantoin. In extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), MIC90 values of nitroxoline were two-fold higher compared with non-ESBL-producing enterobacteria and methicillin-susceptible S. aureus (MSSA). The in vitro efficacies of nitroxoline and nitrofurantoin against ATCC strains of E. coli, Enterococcus faecalis and Proteus mirabilis were compared by time-kill curves in Mueller-Hinton broth and artificial urine. Nitroxoline was non-inferior against E. coli, P. mirabilis and E. faecalis in artificial urine. In conclusion, nitroxoline showed a broad antimicrobial spectrum, with inhibition zone diameters and MICs of nitroxoline well below the EUCAST breakpoint for E. coli for most organisms, and thus may also be a target for therapy of uncomplicated UTIs.

The urinary antibiotic 5-nitro-8-hydroxyquinoline (Nitroxoline) reduces the formation and induces the dispersal of Pseudomonas aeruginosa biofilms by chelation of iron and zinc.

Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations in Pseudomonas aeruginosa, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity.

Pathogenesis of toxic thyroid adenomas and nodules: relevance of activating mutations in the TSH-receptor and Gs-alpha gene, the possible role of iodine deficiency and secondary and TSH-independent molecular mechanisms.

In iodine deficiency areas, activating mutations in the TSH receptor and Gs-alpha gene are found in the majority of toxic thyroid adenomas and in some toxic goiter nodules. Since TSH receptor and Gs-alpha gene mutations are very rare in areas with high iodine supply, iodine deficiency has been suspected to favor the occurrence of these mutations by yet unknown pathways. However, TSH receptor and Gs-alpha gene mutations alone are not sufficient to cause toxic adenomas and nodules. There is compelling evidence that other secondary and cAMP-independent mechanisms, including enhanced expression of various growth factors, their corresponding receptors and of signaling proteins, may affect the mutated cell and thus promote cell proliferation and in turn generation of the tumor.