Carbapenem-resistant and OXA-23-producing Acinetobacter baumannii isolates in the United Arab Emirates

ABSTRACTFive carbapenem-resistant Acinetobacter baumannii isolates, collected from the United Arab Emirates in 2006, were investigated to identify the mechanism(s) responsible for carbapenem resistance. Genotyping was performed by pulsed-field gel electrophoresis, and the location of the blaOXA-23 gene was determined by using the endonuclease I CeuI technique and mating-out assays. The four isolates in which the blaOXA-23 gene was located on the chromosome within a Tn2006 composite transposon were clonally related. The single nonclonally related isolate harboured the blaOXA-23 gene on a 70-kb transferable plasmid. This study provides the first description of the dissemination of carbapenem-resistant A. baumannii isolates carrying Tn2006 on their chromosome. It is also the first report of OXA-23-producing A. baumannii isolates in the Middle East

MCR: modern colistin resistance

Recently, plasmid-mediated and, therefore, transferable bacterial polymyxin resistance was discovered in strains from both humans and animals. Such a trait may widely spread geographically, while simultaneously crossing microbial species barriers. This may ultimately render the “last resort” polymyxin antibiotics therapeutically useless. Colistin is currently used to treat infections caused by Gram-negative carbapenemase producers and colistin resistance may lead to practical pan-antibiotic resistance. We here analyzed the medical and diagnostic consequences of (emerging) colistin resistance and propose pathways toward adequate diagnostics for timely detection of both asymptomatic carriage and infection. Culture-based testing using chromogenic and selective media for screening clinical (and veterinary) specimens may constitute key tools for that purpose. Relevant molecular tests are also discussed

Molecular characterization of multidrug-resistance in Gram-negative bacteria from the Peshawar teaching hospital, Pakistan

Extended-spectrum β-lactamases, carbapenemases, 16S rRNA methylases conferring pan-drug aminoglycoside resistance and colistin resistance were investigated among Gram-negative bacteria recovered from clinical samples (infections) from 200 individuals hospitalized at the Khyber Teaching Hospital of Peshawar, north Pakistan, from December 2017 to March 2018. Out of 65 isolates recovered, 19% were carbapenem resistant and 16% carried a bla NDM-1 gene, confirming the widespread distribution of NDM producers in this country. The association of the NDM carbapenem-resistance determinant, together with the extended-spectrum β-lactamase CTX-M-15 and 16S rRNA methylases, was frequent, explaining the multidrug-resistance pattern observed. All isolates remained susceptible to colistin

Dissemination of multiresistant Enterobacter cloacae isolates producing OXA-48 and CTX-M-15 in a Spanish hospital

Twenty-one multiresistant Enterobacter cloacae isolates producing OXA-48 (n = 10), CTX-M-15 (n = 7) or both (n = 4) β-lactamases were detected in a Spanish hospital during a 1-year period (June 2013 to June 2014). The isolates were also resistant to non-β-lactam antimicrobials, further complicating the therapeutic options. Genotyping of the isolates identified two major clones (ST74 and ST66) that caused prolonged outbreaks in different buildings of the hospital as well as some sporadic isolates (ST78, ST45 and ST295). Isolates belonging to clone 1 (n = 7) were carbapenem-resistant and carried the blaOXA-48 gene on a conjugative IncL/M plasmid of ca. 65 kb. Clone 2 isolates (n = 11) were resistant to cefepime and harboured the blaCTX-M-15 gene on an ca. 150-kb, non-conjugative plasmid of the IncF group, co-harbouring the qnrB and aac(6′)-Ib-cr genes encoding quinolone resistance. Four clone 2 isolates were also resistant to carbapenems owing to the co-production of OXA-48. Most of the isolates were recovered from critically ill patients and were admitted to intensive care units; a single patient was transferred from another Spanish hospital. Intrahospital and interhospital dissemination of multiresistant E. cloacae isolates is of major clinical concern as it could lead to endemic nosocomial situations

Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa.

We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12-0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-lactamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake, ampC gene overproduction, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription

Cross-reaction of naturally-produced β-lactamases from Citrobacter farmeri and Citrobacter amalonaticus with immunological detection of CTX-M enzymes.

The NG-Test CTX-M MULTI immunochromatographic assay has been developed to identify CTX-M-type β-lactamases in Enterobacterales, being the most widespread extended-spectrum β-lactamases. We showed here that the chromosomally-encoded ß-lactamases from Citrobacter farmeri and Citrobacter amalonaticus generated false-positive NG-Test CTX-M MULTI results, compromising the specificity of the test

Carbapenemase-producing organisms: a global scourge

The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid–based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control