Dissemination of a clone carrying a fosA3-harbouring plasmid mediates high fosfomycin resistance rate of KPC-producing Klebsiella pneumoniae in China

Fosfomycin

“…Thus, MIC 50 and MIC 90 values were one dilution lower for ESBL-producing than for CR/KPC-producing K. pneumoniae strains (75,88,93). The presence of rmtB genes was also associated with higher MIC values in KPC-producing strains (95).…”

“…Table 2 shows the susceptibility of contemporary bacteria to fosfomycin from the larger studies published from 2010 onwards (36,56,57,61,. Regarding Gram-positive bacteria, contemporary studies showed that fosfomycin is active against the majority of S. aureus strains (Ͼ90%), including MRSA, as well as coagulase-negative staphylococci (CoNS) (36,56,61,72,75,82,83,87,88,90). However, one study reported that only 33.2% of MRSA strains were susceptible to fosfomycin (90).…”

“…New subtypes, with similar structure, of the gene have been described (fosA2, fosA3, fosA4, and fosA5) (108)(109)(110). Cooccurrence in plasmids with bla CTX-M , bla NDM , bla KPC , bla OXA , bla CMY , bla AmpC , bla TEM , bla SHV , bla SFO-1 , gyrA, parC, parE, sul1, sul2, strA, strB, aac(6=)-Ib, aadA5, aphA6, tetA(A), mphA, floR, dfrA7, rmtB, and merA genes has been reported, conferring resistance to ␤-lactams, quinolones, aminoglycosides, macrolides, sulfonamides, and tetracyclines (75,80,(111)(112)(113)(114). The genes conferring resistance to fosfomycin could be transferred together with genes conferring resistance to other antibiotics in either the same or a conjugate plasmid (114).…”

Fosfomycin: Mechanism and Resistance

“…The reports on plasmid-borne fosfomycin resistance forewarn of increased levels of resistance, likely through spread of problematic clones in which resistance to fosfomycin is linked to resistance to other drugs, especially b-lactams. The Chinese report of FosA3 and KPC-2 on a single plasmid and its likely clonal spread (Jiang et al 2015) are very worrying. Whereas drugs to treat the growing threat of MDR bacteria are sorely needed, and fosfomycin has some attractive properties that could favor its use for treatment of certain life-threatening infections, to retain its productive use as a single-dose oral therapy for cystitis, stewardship and monitoring the spread of plasmid-borne resistance will be needed.…”

“…Of these, 80% carried the fosA3 gene; the fosA3 gene of 42% of those isolates was transferable, presumably via a conjugative plasmid. With growing interest in the possible use of fosfomycin to combat resistant Gram-negative infections, a study was done to ascertain the prevalence of fosfomycin resistance in 278 K. pneumoniae isolates carrying the K. pneumoniae carbapenemase (KPC) and in 80 extended-spectrum b-lactams (ESBLs) (non-KPC) K. pneumoniae from 12 hospitals in China (Jiang et al 2015). Fosfomycin resistance was 60.8% in KPC producers, compared to 12.5% among ESBL producers.…”