Multiresistant Escherichia coli has been disseminated worldwide, and it is one of the major causative agents of nosocomial infections. E. coli has a remarkable and complex genomic plasticity for taking up and accumulating genetic elements; thus, multiresistant high-risk clones can evolve. In this review, we summarise all available data about internationally disseminated extraintestinal pathogenic high-risk E. coli clones based on whole-genome sequence (WGS) data and confirmed outbreaks. Based on genetic markers, E. coli is clustered into eight phylogenetic groups. Nowadays, the E. coli ST131 clone from phylogenetic group B2 is the predominant high-risk clone worldwide. Currently, strains of the C1-M27 subclade within clade C of ST131 are circulating and becoming prominent in Canada, China, Germany, Hungary and Japan. The C1-M27 subclade is characterised by bla_CTX-M-27. Recently, the ST1193 clone has been reported as an emerging high-risk clone from phylogenetic group B2. ST38 clone carrying bla_OXA-244 (a bla_OXA-48-like carbapenemase gene) caused several outbreaks in Germany and Switzerland. Further high-risk international E. coli clones include ST10, ST69, ST73, ST405, ST410, ST457. High-risk E. coli strains are present in different niches, in the human intestinal tract and in animals, and persist in environment. These strains can be transmitted easily within the community as well as in hospital settings. WGS analysis is a useful tool for tracking the dissemination of resistance determinants, the emergence of high-risk mulitresistant E. coli clones and to analyse changes in the E. coli population on a genomic level.

Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future.

Pseudomonas aeruginosa (P. aeruginosa) possesses a plethora of virulence determinants, including the production of biofilm, pigments, exotoxins, proteases, flagella, and secretion systems. The aim of our present study was to establish the relationship between biofilm-forming capacity, the expression of some important virulence factors, and the multidrug-resistant (MDR) phenotype in P. aeruginosa. A total of three hundred and two (n = 302) isolates were included in this study. Antimicrobial susceptibility testing and phenotypic detection of resistance determinants were carried out; based on these results, isolates were grouped into distinct resistotypes and multiple antibiotic resistance (MAR) indices were calculated. The capacity of isolates to produce biofilm was assessed using a crystal violet microtiter-plate based method. Motility (swimming, swarming, and twitching) and pigment-production (pyoverdine and pyocyanin) were also measured. Pearson correlation coefficients (r) were calculated to determine for antimicrobial resistance, biofilm-formation, and expression of other virulence factors. Resistance rates were the highest for ceftazidime (56.95%; n = 172), levofloxacin (54.97%; n = 166), and ciprofloxacin (54.64%; n = 159), while lowest for colistin (1.66%; n = 5); 44.04% (n = 133) of isolates were classified as MDR. 19.87% (n = 60), 20.86% (n = 63) and 59.27% (n = 179) were classified as weak, moderate, and strong biofilm producers, respectively. With the exception of pyocyanin production (0.371 ± 0.193 vs. non-MDR: 0.319 ± 0.191; p = 0.018), MDR and non-MDR isolates did not show significant differences in expression of virulence factors. Additionally, no relevant correlations were seen between the rate of biofilm formation, pigment production, or motility. Data on interplay between the presence and mechanisms of drug resistance with those of biofilm formation and virulence is crucial to address chronic bacterial infections and to provide strategies for their management.

Pseudomonas aeruginosa high-risk clones are disseminated worldwide and they are common causative agents of hospital-acquired infections. In this review, we will summarize available data of high-risk P. aeruginosa clones from confirmed outbreaks and based on whole-genome sequence data. Common feature of high-risk clones is the production of beta-lactamases and among metallo-beta-lactamases NDM, VIM and IMP types are widely disseminated in different sequence types (STs), by contrast FIM type has been reported in ST235 in Italy, whereas GIM type in ST111 in Germany. In the case of ST277, it is most frequently detected in Brazil and it carries a resistome linked to bla_SPM. Colistin resistance develops among P. aeruginosa clones in a lesser extent compared to other resistance mechanisms, as ST235 strains remain mainly susceptible to colistin however, some reports described mcr positive P. aeurigonsa ST235. Transferable quinolone resistance determinants are detected in P. aeruginosa high-risk clones and aac(6′)-Ib-cr variant is the most frequently reported as this determinant is incorporated in integrons. Additionally, qnrVC1 was recently detected in ST773 in Hungary and in ST175 in Spain. Continuous monitoring and surveillance programs are mandatory to track high-risk clones and to analyze emergence of novel clones as well as novel resistance determinants.

Novel antimicrobial agents, approved for clinical use in past years, represent potential treatment options for various infections. In this review, we summarize the most important medical and microbiological features of three recently approved fluoroquinolones, namely delafloxacin, finafloxacin, and zabofloxacin. Delafloxacin possesses an anionic chemical structure, and represents broad-spectrum activity, as it targets both bacterial DNA gyrase and topoisomerase IV enzymes of gram-positive and gram-negative bacteria with equal affinity. Its molecular surface is larger than that of other fluoroquinolones, and it has enhanced antibacterial efficacy in acidic environments. Delafloxacin has been approved to treat acute bacterial skin and skin-structure infections, as well as community-acquired bacterial pneumonia. Finafloxacin has a zwitterionic chemical structure, and targets both DNA gyrase and topoisomerase IV enzymes. This enables a broad antibacterial spectrum; however, finafloxacin has so far only been approved in ear-drops to treat bacterial otitis externa. Zabofloxacin is also a broad-spectrum fluoroquinolone agent, and was first approved in South Korea to treat acute bacterial exacerbation of chronic obstructive pulmonary disease. The introduction of these novel fluoroquinolones into daily practice extends the possible indications of antibiotics into different bacterial infections, and provides treatment options in difficult-to-treat infections. However, some reports of delafloxacin resistance have already appeared, thus underlining the importance of the prudent use of antibiotics.

A multidrug-resistant Pseudomonas aeruginosa PS1 isolated from urine clinical sample was investigated in this study. The strain exhibited resistance to piperacillin/tazobactam, ciprofloxacin, imipenem, ceftazidime but it was susceptible to colistin. Analysis of whole-genome sequencing data by ResFinder detected various resistance determinants including qnrVC1 and bla NDM-1. The multiresistant P. aeruginosa isolate belonged to ST773 high-risk clone. The qnrVC1 and bla NDM-1 determinants were incorporated into different integrons. Expression of bla NDM-1 was fourfold and qnrVC1 was twofold increased, compared to that of rpsL housekeeping gene. Mutations in gyrA Thr83Leu and parC Ser87Leu were detected and additionally qnrVC1 expression indicates protective effect of QnrVC1 pentapeptid protein on gyrase and topoisomerase. High-risk P. aeruginosa clones integrate various carbapenemase and other resistance determinants into their genomes that facilitates further dissemination of multiresistance among clinical isolates. We report bla NDM-1 and qnrVC1 genes in P. aeruginosa ST773 international high-risk clone.