Global antibiotic resistance: of contagion, confounders, and the COM-B model.

Comment - No abstract available

Carbapenem resistance determinants acquired through novel chromosomal integrations in extensively drug-resistant pseudomonas aeruginosa

Two novel blaDIM-1- or blaIMP-1-containing genomic islands (GIs) were discovered by whole-genome sequence analyses in four extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates from inpatients at a tertiary hospital in Ghana. The strains were of sequence type 234 (ST234) and formed a phylogenetic clade together with ST111, which is recognized as a global high-risk clone. Their carbapenem resistance was encoded by two Tn402-type integrons, In1592 (blaDIM-1) and In1595 (blaIMP-1), both carrying complete tni mobilization modules. In1595 was bound by conserved 25-bp inverted repeats (IRs) flanked by 5-bp direct repeats (DRs) associated with target site duplication. The integrons were embedded in two GIs that contained cognate integrases and were distinguished by a lower GC content than the chromosomal average. PAGI-97A (52.659 bp; In1592), which encoded a P4-type site-specific integrase of the tyrosine recombinase family in its 3′ border, was integrated into tRNA-Pro(ggg) and bracketed by a 49-bp perfect DR created by 3′-end target duplication. GIs with the same structural features, but diverse genetic content, were identified in 41/226 completed P. aeruginosa genomes. PAGI-97B (22,636 bp; In1595), which encoded an XerC/D superfamily integrase in its 5′ border, was inserted into the small RNA (sRNA) PrrF1/PrrF2 locus. Specific insertions into this highly conserved locus involved in iron-dependent regulation, all leaving PrrF1 intact, were identified in an additional six phylogenetically unrelated P. aeruginosa genomes. Our molecular analyses unveiled a hospital-associated clonal dissemination of carbapenem-resistant ST234 P. aeruginosa in which the XDR phenotype resulted from novel insertions of two GIs into specific chromosomal sites

Antibiotic resistance trends of ESKAPE pathogens in Kwazulu-Natal, South Africa: A five-year retrospective analysis.

BACKGROUND: To combat antimicrobial resistance, the World Health Organization developed a global priority pathogen list of antibiotic-resistant bacteria for prioritisation of research and development of new, effective antibiotics. OBJECTIVE: This study describes a five-year resistance trend analysis of the ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp., from Kwazulu-Natal, South Africa. METHODS: This retrospective study used National Health Laboratory Services data on 64 502 ESKAPE organisms isolated between 2011 and 2015. Susceptibility trends were ascertained from minimum inhibitory concentrations and interpreted using Clinical and Laboratory Standards Institute guidelines. RESULTS: S. aureus was most frequently isolated (n = 24, 495, 38%), followed by K. pneumoniae (n = 14, 282, 22%). Decreasing rates of methicillin-resistant S. aureus (28% to 18%, p 70%). CONCLUSION: This study describes the magnitude of antimicrobial resistance in KwaZulu-Natal and provides a South African perspective on antimicrobial resistance in the global priority pathogen list, signalling the need for initiation or enhancement of antimicrobial stewardship and infection control measures locally

Diversity and proliferation of metallo-β-lactamases : a clarion call for clinically effective metallo-β-lactamase inhibitors

The worldwide proliferation of life-threatening metallo-β-lactamase (MBLs)-producing Gram-negative bacteria is a serious concern to public health. MBLs are compromising the therapeutic efficacies of β-lactams, particularly carbapenems, which are last-resort antibiotics indicated for various multidrug-resistant bacterial infections. Inhibiting enzymes mediating antibiotic resistance in bacteria is one of the major promising means in overcoming bacterial resistance. Compounds having potential MBLs-inhibitory activity have been reported, but none are currently under clinical trials. The need for developing safe and efficient MBL inhibitors (MBLIs) is obvious, particularly with the continuous spread of MBLs worldwide. In this review, the emergence and escalation of MBLs in Gram-negative bacteria are dicussed. The relationship between different class B β-lactamases identified up to 2017 are represented by a phylogenetic tree and summarized. On the other hand, approved and/or clinical-phase serine β-lactamase inhibitors are recapitulated to reflect the successful advances made in developing class A β-lactamase inhibitors. Reported MBLIs, their inhibitory properties and purported mode of inhibition are herein delineated. Insights into MBLs' structural variations and the challenges involved in developing potent MBLIs are also elucidated and discussed. Currently, natural products and MBL-resistant β-lactam analogues are the most promising agents that can become clinically efficient MBLIs. A deeper comprehension of the mechanism of action and activity spectrum of the various MBLs and their inhibitors will serve as a bedrock for further investigations that can result in clinically useful MBLIs to curb this global menace.http://aem.asm.org2019-03-01hj2018Medical Microbiolog

Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A position paper

Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of health care facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country\u27s Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in health care settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies, and health care professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR

Genomic analysis of two drug-resistant clinical Morganella morganii strains isolated from UTI patients in Pretoria, South Africa

Morganella morganii is an opportunistic bacterial pathogen of the Enterobacteriaceae family that is occasionally isolated from clinical (animal and human) specimens with varying resistance profiles. Detailed genomic analyses of drug‐resistant M. morganii strains are relatively limited, particularly in Africa, which is also due to their relatively low isolation rates from clinical settings. Here we report on two multidrug‐resistant clinical M. morganii isolates from urine specimens of two hospitalized patients in South Africa who presented with urinary tract infections in 2013. The isolates, M006 and E042, were only susceptible to carbapenems, amikacin and tigecycline. One strain, M006, had a novel class 1 integron, ln1484, associated with aadA7, sul1and gcuD gene cassettes and a Col3M plasmid replicase gene. The ln1484 intI1:aadA7:sul1 genes were bracketed by a TnAs3 composite transposon while a tet(B) gene was found on an IS4 family transposon. The rare blaDHA‐4 and blaDHA‐1 AmpC β‐lactamase genes were identified on the isolates’ chromosome. The isolates were phylogenetically distant and closely related to other international strains, suggesting that they were not obtained from a single epidemiological source. Further molecular surveillance is necessary to establish the prevalence of these MDR strains in the tertiary hospital. Moreover antibiotic stewardship and antibiotic sensitivity testing of all clinical isolates should be undertaken after empirical treatment to inform tailored therapy as well as reduce escalation of resistance and associated morbidities and mortalities.Supplementary Data S1. Metadata of isolates included in phylogenomic analysis.The National Health Laboratory Services (Grant No.: 94445), the University of Pretoria (Grant No.: A0702) and the South African Medical Research Council.https://onlinelibrary.wiley.com/journal/1472765x2021-01-01hj2020Medical Microbiolog

Іконографічні розвідки родинних портретів Рєпніних з Яготина (На матеріалах колекції Національного музею історії України)

Статтю присвячено дослідженню родинних портретів князів Рєпніних з яготинського маєтку в Національному музеї історії України. Портрети становлять важливе іконографічне джерело XVII – XX ст. в системі історичних дисциплін.The article is dedicated to research family portraits of the Repnin а princes from Jаgotinscka palace in The National museum of history of Ukraine. The portraits become are important iconography source XVII–XX cent. in the system historical branches of science

Molecular Epidemiological Characterisation of ESBL- and Plasmid-Mediated AmpC-Producing Escherichia coli and Klebsiella pneumoniae at Kamuzu Central Hospital, Lilongwe, Malawi

The global rise in infections caused by multidrug resistant (MDR) Enterobacterales poses a public health problem. We have performed a molecular epidemiological characterisation of representative plasmid-mediated AmpC (pAmpC) and ESBL-positive clinical isolates of Escherichia coli (n = 38) and Klebsiella pneumoniae (n = 17) from a tertiary hospital in Malawi collected in 2017. BlaCTX-M-15 was the most prevalent ESBL-determinant in E. coli (n = 30/38) and K. pneumoniae (n = 17/17), whereas blaCMY-2 was detected in nearly all AmpC-phenotype E. coli (n = 15/17). Whole genome sequencing revealed dominant globally disseminated E. coli sequence types (STs); ST410 (n = 16), ST131 (n = 7), and ST617 (n = 6). The ST distribution in K. pneumoniae was more diverse but included ST101 (n = 2), ST14 (n = 2), and ST340 (n = 2), all considered high-risk MDR clones. The isolates expressed an MDR profile, including resistance against commonly used antibiotics, such as fluoroquinolones, aminoglycosides, and/or trimethoprim-sulfamethoxazole, and harboured corresponding resistance determinants. Clonal analyses of the major STs of E. coli revealed closely related genetic clusters within ST410, ST131, and ST617 supporting within-hospital transmission between patients and/or via a common reservoir. The overall findings add to the limited knowledge on the molecular epidemiology of MDR E. coli and K. pneumoniae in Malawi and may help health policy makers to identify areas to target when addressing this major threat of antibiotic resistance