Emergence of Multidrug-resistant (MDR) Gram-negative bacteria (GNB) in South Africa
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA488070 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR8268420_1.fastq.gz | Fastqsanger.gz | |||
| SRR8268420_2.fastq.gz | Fastqsanger.gz | |||
| SRR8268430_1.fastq.gz | Fastqsanger.gz | |||
| SRR8268430_2.fastq.gz | Fastqsanger.gz |
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Project description:Background:A multitude of definitions determining multidrug resistance (MDR) of Gram-negative organisms exist worldwide. The definitions differ depending on their purpose and on the issueing country or organization. The MDR definitions of the European Centre for Disease Prevention and Control (ECDC) were primarily chosen to harmonize epidemiological surveillance. The German Commission of Hospital Hygiene and Infection Prevention (KRINKO) issued a national guideline which is mainly used to guide infection prevention and control (IPC) measures. The Swiss University Hospital Zurich (UHZ) - in absentia of national guidelines - developed its own definition for IPC purposes. In this study we aimed to determine the effects of different definitions of multidrug-resistance on rates of Gram-negative multidrug-resistant organisms (GN-MDRO). Methods:MDR definitions of the ECDC, the German KRINKO and the Swiss University Hospital Zurich were applied on a dataset comprising isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Pseudomonas aeruginosa, and Acinetobacter baumannii complex. Rates of GN-MDRO were compared and the percentage of patients with a GN-MDRO was calculated. Results:In total 11'407 isolates from a 35?month period were included. For Enterobacterales and P. aeruginosa, highest MDR-rates resulted from applying the 'ECDC-MDR' definition. 'ECDC-MDR' rates were up to four times higher compared to 'KRINKO-3/4MRGN' rates, and up to six times higher compared to UHZ rates. Lowest rates were observed when applying the 'KRINKO-4MRGN' definitions. Comparing the 'KRINKO-3/4MRGN' with the UHZ definitions did not show uniform trends, but yielded higher rates for E. coli and lower rates for P. aeruginosa. On the patient level, the percentages of GN-MDRO carriers were 2.1, 5.5, 6.6, and 18.2% when applying the 'KRINKO-4MRGN', 'UHZ-MDR', 'KRINKO-3/4MRGN', and the 'ECDC-MDR' definition, respectively. Conclusions:Different MDR-definitions lead to considerable variation in rates of GN-MDRO. Differences arise from the number of antibiotic categories required to be resistant, the categories and drugs considered relevant, and the antibiotic panel tested. MDR definitions should be chosen carefully depending on their purpose and local resistance rates, as definitions guiding isolation precautions have direct effects on costs and patient care.
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Project description:There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
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