Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review with a focus on Mediterranean countries

Abstract

Quinolones are a family of synthetic broad-spectrum antimicrobial drugs. These molecules have been widely prescribed to treat various infectious diseases and have been classified into several generations based on their spectrum of activity. Quinolones inhibit bacterial DNA synthesis by interfering with the action of DNA gyrase and topoisomerase IV. Mutations in the genes encoding these targets are the most common mechanisms of high-level fluoroquinolone resistance. Moreover, three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998 and include Qnr proteins, the aminoglycoside acetyltransferase AAC(6')-Ib-cr, and plasmid-mediated efflux pumps QepA and OqxAB. Plasmids with these mechanisms often encode additional antimicrobial resistance (extended spectrum beta-lactamases [ESBLs] and plasmidic AmpC [pAmpC] ß-lactamases) and can transfer multidrug resistance. The PMQR determinants are disseminated in Mediterranean countries with prevalence relatively high depending on the sources and the regions, highlighting the necessity of long-term surveillance for the future monitoring of trends in the occurrence of PMQR genes.

Plasmid‐mediated quinolone resistance in human non‐typhoidal Salmonella infections: An emerging public health problem in the United States

“…Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) have greater potency, broader spectra of activity, improved pharmacokinetics and a lower frequency of resistance development (Hooper & Jacoby, 2015). Fluoroquinolones have been widely used to treat various infections (Yanat, Rodríguez-Martínez, & Touati, 2017), including invasive non-typhoidal Salmonella infections, which can be life-threatening (Crump, Barrett, Nelson, & Angulo, 2003). They have also been used in animals to prevent, control and treat infections (Food and Drug Administration (n.d.); Yanat et al, 2017).…”

“…Fluoroquinolones have been widely used to treat various infections (Yanat, Rodríguez-Martínez, & Touati, 2017), including invasive non-typhoidal Salmonella infections, which can be life-threatening (Crump, Barrett, Nelson, & Angulo, 2003). They have also been used in animals to prevent, control and treat infections (Food and Drug Administration (n.d.); Yanat et al, 2017). Since quinolones were introduced into human and veterinary medicine, resistance to them has emerged and increased (Van, Nguyen, Smooker, & Coloe, 2012;Yanat et al, 2017).…”

“…They have also been used in animals to prevent, control and treat infections (Food and Drug Administration (n.d.); Yanat et al, 2017). Since quinolones were introduced into human and veterinary medicine, resistance to them has emerged and increased (Van, Nguyen, Smooker, & Coloe, 2012;Yanat et al, 2017).…”

“…Fluoroquinolones target two essential bacterial enzymes, DNA gyrase and topoisomerase IV. In Enterobacteriaceae including Salmonella, quinolone resistance typically develops from the accumulation of chromosomal mutations in the quinolone resistance-determining region (QRDR) of target enzyme genes, primarily gyrA and parC (Cavaco & Aarestrup, 2009;Yanat et al, 2017); one mutation generally mediates resistance to nalidixic acid and decreases susceptibility to fluoroquinolones, while additional mutations lead to full fluoroquinolone resistance (Aarestrup, Wiuff, Mølbak, & Threlfall, 2003). Since the late 1990s, three types of plasmid-mediated quinolone resistance (PMQR) mechanisms have been identified: qnr genes, which protect target enzymes; aac(6′)-Ib-cr gene, which mediates acetylation of certain quinolones; and oqxAB and qepA genes, which produce mobile efflux pumps (Jacoby, Strahilevitz, & Hooper, 2014).…”

“…PMQR genes are particularly frequent among Enterobacteriaceae with decreased susceptibility to fluoroquinolones combined with nalidixic acid susceptibility (Rodríguez-Martínez et al, 2016); consequently, this phenotype is a clue to the presence of PMQR (Hooper & Jacoby, 2015). During the last decade, PMQR has been increasingly reported in Enterobacteriaceae worldwide (Yanat et al, 2017).…”