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Microb Drug Resist ; 27(9): 1167-1175, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1406451


Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Acinetobacter Infections/mortality , COVID-19/mortality , Drug Resistance, Multiple, Bacterial , Klebsiella Infections/mortality , Opportunistic Infections/mortality , Pneumonia/mortality , SARS-CoV-2/pathogenicity , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Acinetobacter Infections/virology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/growth & development , Acinetobacter baumannii/pathogenicity , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Aspirin/therapeutic use , COVID-19/drug therapy , COVID-19/microbiology , COVID-19/virology , Carbapenems/therapeutic use , Critical Illness , Female , Hospital Mortality , Humans , Intensive Care Units , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella Infections/virology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/pathogenicity , Length of Stay/statistics & numerical data , Male , Middle Aged , Opportunistic Infections/drug therapy , Opportunistic Infections/microbiology , Opportunistic Infections/virology , Piperacillin, Tazobactam Drug Combination/therapeutic use , Pneumonia/drug therapy , Pneumonia/microbiology , Pneumonia/virology , Retrospective Studies , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Steroids/therapeutic use , Survival Analysis , Treatment Outcome
Appl Biochem Biotechnol ; 194(2): 671-693, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1375835


The growth of respiratory diseases, as witnessed through the SARS and COVID-19 outbreaks, and antimicrobial-resistance together pose a serious threat to humanity. One reason for antimicrobial resistance is formation of bacterial biofilms. In this study the sulphated polysaccharides from green algae Chlamydomonas reinhardtii (Cr-SPs) is tested for its antibacterial and antibiofilm potential against Klebsiella pneumoniae and Serratia marcescens. Agar cup assay clearly indicated the antibacterial potential of Cr-SPs. Minimum inhibitory concentration (MIC50) of Cr-SPs against Klebsiella pneumoniae was found to be 850 µg/ml, and it is 800 µg/ml in Serratia marcescens. Time-kill and colony-forming ability assays suggest the concentration-dependent bactericidal potential of Cr-SPs. Cr-SPs showed 74-100% decrease in biofilm formation in a concentration-dependent manner by modifying the cell surface hydrophobic properties of these bacteria. Cr-SPs have also distorted preformed-biofilms by their ability to interact and destroy the extra polymeric substance and eDNA of the matured biofilm. Scanning electron microscopy analysis showed that Cr-SPs effectively altered the morphology of these bacterial cells and distorted the bacterial biofilms. Furthermore reduced protease, urease and prodigiosin pigment production suggest that Cr-SPs interferes the quorum sensing mechanism in these bacteria. The current study paves way towards developing Cr-SPs as a control strategy for treatment of respiratory tract infections.

Biofilms/drug effects , Polysaccharides/pharmacology , Quorum Sensing/drug effects , Respiratory Tract Infections/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , COVID-19/drug therapy , COVID-19/virology , Chlorophyta/chemistry , Humans , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/pathogenicity , Microbial Sensitivity Tests , Polysaccharides/chemistry , Respiratory Tract Infections/microbiology , SARS-CoV-2/drug effects , Serratia marcescens/growth & development , Serratia marcescens/pathogenicity
Genome Med ; 12(1): 113, 2020 12 09.
Article in English | MEDLINE | ID: covidwho-964565


BACKGROUND: Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany. METHODS: Here, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone. RESULTS: Phylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, which K. pneumoniae ST307 likely donated to other K. pneumoniae isolates of different STs and even other bacterial species (e.g., Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulent K. pneumoniae strain (hvKP1). CONCLUSIONS: The combination of extensive drug resistance and virulence, partly conferred through a "mosaic" plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.

Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Iron/metabolism , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Bacterial Proteins/genetics , Biofilms/growth & development , Disease Outbreaks , Genes, Bacterial/genetics , Germany/epidemiology , Humans , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/classification , Klebsiella pneumoniae/growth & development , Phylogeny , Plasmids , Polymorphism, Single Nucleotide , Virulence/drug effects , Virulence/genetics , Virulence Factors/genetics , Whole Genome Sequencing