War Wound Treatment Complications Due to Transfer of an IncN Plasmid Harboring bla _OXA-181 from Morganella morganii to CTX-M-27-Producing Sequence Type 131 Escherichia coli

Abstract

A 22-year-old male developed a recurrent sacral abscess associated with embedded shrapnel following a blast injury. Cultures grew extended-spectrum ␤-lactamase (ESBL)-producing, carbapenem-susceptible Escherichia coli. Ertapenem was administered, but the infection recurred after each course of antibiotics. Initial surgical interventions were unsuccessful, and subsequent cultures yielded E. coli and Morganella morganii, both nonsusceptible to carbapenems. The isolates were Carba NP test negative, gave ambiguous results with the modified Hodge test, and amplified the bla OXA48 -like gene by real-time PCR. All E. coli isolates were sequence type 131 (ST131), carried nine resistance genes (including bla CTX-M-27 ) on an IncF plasmid, and were identical by genome sequencing, except for 150 kb of plasmid DNA in carbapenem-nonsusceptible isolates only. Sixty kilobases of this was shared by M. morganii and represented an IncN plasmid harboring bla OXA-181 . In M. morganii, the gene was flanked by IS3000 and ISKpn19, but in all but one of the E. coli isolates containing bla OXA-181 , a second copy of ISKpn19 had inserted adjacent to IS3000. To the best of our knowledge, this is the first report of bla OXA-181 in the virulent ST131 clonal group and carried by the promiscuous IncN family of plasmids. The tendency of M. morganii to have high MICs of imipenem, a bla OXA-181 substrate profile that includes penicillins but not extended-spectrum cephalosporins, and weak carbapenemase activity almost resulted in the presence of bla OXA-181 being overlooked. We highlight the importance of surveillance for carbapenem resistance in all species, even those with intrinsic resistances, and the value of advanced molecular techniques in detecting subtle genetic changes. Blast injuries account for the overwhelming majority of combat injuries sustained by coalition forces in Iraq and Afghanistan (1). A specific type, dismounted complex blast injury (DCBI), has become significantly more prevalent and can cause extensive damage to the perineum/pelvic areas (2). Contamination of these wounds with environmental debris and contents from the gastrointestinal tract can impair wound healing and serve as sources of infection (2, 3). When these fragments lie close to vital organs or systems, it is often preferable to leave them in place rather than risk surgery (4). Although specific guidelines for infection prevention and prophylactic antibiotics exist for DCBI (2, 5), the increasing incidence of antibiotic-resistant strains has resulted in an ever dwindling arsenal of effective drugs (6).Escherichia coli is a leading cause of extraintestinal surgical site infections (7,8). In particular, strains belonging to E. coli sequence type 131 (ST131) (serotype O25:H4) appear to be more virulent, have disseminated worldwide (9, 10), and have a propensity to harbor multiple antibiotic resistance genes (11). A recent study from the United States showed that 67 to 69% of all extendedspectrum ␤-lactamase (ESBL)-producing E. coli strains tested belonged to this...

GlobalEscherichia coliSequence Type 131 Clade withblaCTX-M-27Gene

“…We selected all of the CTX-M-27 producers, 1 CTX-M-14 producer per country, and 2 CTX-M-15 producers. We also sought public databases for ST131 H 30 and included sequence data for 8 isolates from countries other than Japan: CTX-M-27 producers (3 raw reads, 2 draft genomes); CTX-M-14 producer (1 raw read); and CTX-M-15–producing C2/ H 30Rx (2 complete genomes) (Table; Technical Appendix Table 1) ( 5 , 9 , 16 – 18 ). …”

Screening and Characterization of Multidrug-Resistant Gram-Negative Bacteria from a Remote African Area, São Tomé and Príncipe

“…The PCR scheme was complemented with primers specific for the IncX3-type plasmid backbones (IncX3 Fw, 5=-GAG GCT TAT CGT GAA GAC AG-3=; IncX3 Rv, 5=-GAA CGA CTT TGT CAA ACT CC-3=) (13), as well as primers specific for IncX4 plasmids (39). The genetic environment of bla OXA-181 was investigated by PCR mapping with primers for insertion sequences ISKpn19 and IS3000, taking in account that those mobile elements have been previously identified in the close vicinity of the bla OXA-181 gene (7,40).…”

Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis

“…Although K. pneumoniae is most commonly found in soil and water, it frequently causes infections in immunocompromised individuals and has been connected to outbreaks of nosocomial infections (Podschun & Ullmann, 1998;Paczosa & Mecsas, 2016;Navon-Venezia et al, 2017). OXA-163 and OXA-181 have also been identified in other human pathogens such as Escherichia coli (McGann et al, 2015;Stoesser et al, 2016), and OXA-181 has been identified in Pseudomonas aeruginosa strains (Meunier et al, 2016). OXA-181 is reported to originate from a Shewanella xiamenensis chromosomal -lactamase and OXA-163 also appears to originate from Shewanella.…”