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.

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 blaSPM. 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.

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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 blaCTX-M-27. Recently, the ST1193 clone has been reported as an emerging high-risk clone from phylogenetic group B2. ST38 clone carrying blaOXA-244 (a blaOXA-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.

Plasmid-mediated quinolone resistance (PMQR) determinants including, qnrA, qnrB, qnrC, qnrD, qnrS, aac(6')-Ib-cr, oqxAB, and qepA, were investigated in 214 Enterobacteriaceae strains from urine clinical samples. Antimicrobial susceptibility testing for ciprofloxacin, ceftriaxone, and imipenem was performed by broth microdilution method. All strains were screened for PMQR genes by PCR. Virulence determinants, namely afa, pap, pil, sfa/foc, and kpsMT of eight Escherichia coli strains proven positive for at least one qnr gene, were investigated by PCR. All of the eight investigated strains carried the pil gene, showing that P fimbria is a common virulence determinant among qnr positive E. coli. Out of 214 tested strains, 38 yielded any PMQR determinant, altogether 45 genes were detected namely, 6 qnrA, 1 qnrB, 2 qnrD and 8 qnrS, 9 aac(6')-Ib-cr, and 19 oqxAB; however, neither qepA nor qnrC were detected. Notably, 18 Klebsiella spp., harbored oqxAB, nine E. coli were positive for qnrS and two Morganella morganii yielded qnrD resistance determinant. In this study, we demonstrated 17.7% prevalence of PMQR-positive Enterobacteriaceae and first reported qnrD-resistance determinant in Hungary. Altogether, 25 PMQR-positive strains were susceptible or low-level resistant to ciprofloxacin with minimum inhibitory concentration (MIC) between 0.06 and 1 mg/L, suggesting that prevalence of PMQR determinants is underestimated and screening among clinical isolates exhibiting reduced susceptibility is necessary. Fluoroquinolone resistance breakpoints of Enterobacteriaceae were revised in 2017 by European Committee of Antimicrobial Susceptibility Testing indicating ciprofloxacin susceptibility only until 0.25 mg/L MIC value.