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1.
Sci Rep ; 12(1): 8763, 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1873545

ABSTRACT

Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1, genes associated with resistance to ß-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii.


Subject(s)
Acinetobacter baumannii , Albumins/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , Cephalosporins , Humans , Iron/pharmacology , Microbial Sensitivity Tests , Siderophores , beta-Lactamases/genetics
2.
J Med Microbiol ; 71(4)2022 Apr.
Article in English | MEDLINE | ID: covidwho-1788579

ABSTRACT

Introduction. Carbapenem-resistant Acinetobacter baumannii (CRAB) is the primary pathogen causing hospital-acquired infections. The spread of CRAB is mainly driven by the dissemination of resistant clones, and in Latin America, International Clones IC-1 (also known as clonal complex CC1), IC-4 (CC15) and IC-5 (CC79) are the most prevalent.Gap Statement. There are no documented outbreaks of CRAB International Clone 2 (IC-2) reported in Brazil.Aim. To describe a large outbreak of CRAB caused by the uncommon IC-2 in a Brazilian COVID-19 hospital.Methodology. From May 2020 to May 2021, 224 patients infected or colonized with CRAB were identified in a single hospital; 92 % of them were also infected with SARS-CoV-2. From these patients, 137 isolates were recovered and subjected to antimicrobial susceptibility testing, PCR analysis and molecular typing. Whole-genome sequencing and downstream analysis were carried out on a representative isolate (the first available isolate).Results. In 76 % of the patients, a single OXA-23-producing CRAB IC-2 was identified. All the isolates were susceptible to polymyxin B, but highly resistant (>95 %) to aminoglycosides, fluoroquinolones and beta-lactams. Genomic analysis revealed that the representative isolate also carried the 16S rRNA Methylase ArmA, which was detected for the first time in this species in Brazil.Conclusion. We report the rapid spread of an emerging CRAB clone responsible for causing a large outbreak in a hospital in Brazil, a country with predominance of other CRAB clones. Continuous and prospective surveillance is warranted to evaluate the impact of this clone in Brazilian hospital settings.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Acinetobacter Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Brazil/epidemiology , COVID-19/epidemiology , Clone Cells , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Pandemics , Prospective Studies , RNA, Ribosomal, 16S , SARS-CoV-2/genetics , beta-Lactamases/genetics
3.
J Antimicrob Chemother ; 77(3): 625-632, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1713678

ABSTRACT

OBJECTIVES: Tigecycline is a last-resort antibiotic used to treat lethal infections caused by carbapenem-resistant Enterobacterales; however, plasmid-borne tigecycline resistance tmexCD-toprJ gene clusters can confer tigecycline resistance. The aim of the study was to identify novel subtypes and the spread of tmexCD-toprJ. METHODS: Five non-duplicate isolates of different species, carrying tmexCD-toprJ gene clusters or novel subtypes, were isolated from patients across China between November 2018 and June 2019. WGS was performed using Illumina and Nanopore platforms. A phylogenetic tree was constructed using a dataset of 77 sequences carrying the tmexCD-toprJ gene clusters, 72 of which were downloaded from NCBI with a blastn identity cut-off of 95%. RESULTS: We detected six different transfer units and two novel subtypes (tmexC1D1.2-toprJ1 and tmexC2D2.2-toprJ2) of the tmexCD-toprJ gene clusters. Among the six transfer units, three were mediated by IS26, while the rest were presumably mediated by Tn5393, hypothetical integrases (xerD-hp clusters-umuC-integrases-tnfxB2-tmexC2D2-toprJ2-umuC) and hypothetical units (hp-hp-hp-tnfxB2-tmexC2D2.2-toprJ2-ΔTn5393-Tn6292). Moreover, two tmexCD-toprJ-like gene clusters co-located on the same plasmid with blaNDM in five isolates. Phylogenetic analysis revealed that tmexCD-toprJ gene clusters may have originated in Pseudomonas spp., being mainly distributed in Pseudomonas spp. and Klebsiella spp. (64/77). Most tmexCD-toprJ gene clusters in Enterobacterales were located on plasmids, indicating that the gene clusters have a high inter-species transfer risk after transfer to Enterobacterales. CONCLUSIONS: In summary, to the best of our knowledge, this is the first report of tmexCD-toprJ gene clusters being isolated from Enterobacter cloacae and Klebsiella oxytoca, revealing that these multiple transfer units should be further studied because of their clinical significance.


Subject(s)
Enterobacter cloacae , Klebsiella oxytoca , Carbapenems/pharmacology , Enterobacter cloacae/genetics , Humans , Klebsiella oxytoca/genetics , Microbial Sensitivity Tests , Multigene Family , Phylogeny , beta-Lactamases/genetics
4.
Eur J Clin Microbiol Infect Dis ; 41(4): 573-580, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1640882

ABSTRACT

PURPOSE: To evaluate the prevalence of multi-carbapenemase-producing Enterobacterales (EB) and the activity of cefiderocol (CFDC), meropenem-vaborbactam (MEV), ceftazidime-avibactam (CZA), and combinations of CZA plus aztreonam (ATM), MEV plus ATM and CFDC plus CZA against them. METHODS: A collection of carbapenemase-producing EB clinical isolates (n = 1242) was investigated by lateral flow immunoassay NG-Test CARBA-5 and molecular testing. Cefiderocol MICs were determined using broth microdilution SensititreTM panel. MICs of CZA and MEV were determined by the gradient diffusion method. Antimicrobial synergy testing was performed using gradient diffusion strip crossing. RESULTS: KPC were the most frequent carbapenemases (83.2%), followed by VIM (9.2 %), OXA-48-like (4.3 %) and NDM enzymes (4.1%). Multi-carbapenemase producers were found in 10 (0.8%) isolates. Three combinations of two different carbapenemases were observed: KPC+VIM (n = 4), NDM+OXA-48-like (n = 4), and VIM+OXA-48-like (n = 2). CFDC showed potent activity against eight out of ten dual-carbapenemases producers, while resistance or reduced susceptibility was shown towards CZA and MEV. CFDC in combination with CZA showed no synergistic effects and only two additive effects on seven (87.5%) of the CFDC-susceptible strains. Conversely, CZA plus ATM and MEV plus ATM combinations were synergistic against all ATM-resistant strains regardless of dual-carbapenemases phenotype. CONCLUSIONS: The occurrence of multi-carbapenemase producers is not uncommon in Northern Italy area. MEV in combination with ATM might be considered as a potential therapeutic option, alternative to CZA plus ATM. CFDC susceptibility testing and synergy evaluation of ATM-based combinations should be performed in the lab routine to evaluate the most in vitro active antimicrobial regimen.


Subject(s)
Aztreonam , COVID-19 , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds , Aztreonam/pharmacology , Bacterial Proteins/genetics , Boronic Acids , Ceftazidime/pharmacology , Cephalosporins , Drug Combinations , Humans , Meropenem/pharmacology , Microbial Sensitivity Tests , beta-Lactamases/genetics
5.
Microbiol Spectr ; 10(1): e0201521, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1622005

ABSTRACT

Emergency department areas were repurposed as intensive care units (ICUs) for patients with acute respiratory distress syndrome during the initial months of the coronavirus disease 2019 (COVID-19) pandemic. We describe an outbreak of New Delhi metallo-ß-lactamase 1 (NDM-1)-producing Escherichia coli infections in critically ill COVID-19 patients admitted to one of the repurposed units. Seven patients developed infections (6 ventilator-associated pneumonia [VAP] and 1 urinary tract infection [UTI]) due to carbapenem-resistant E. coli, and only two survived. Five of the affected patients and four additional patients had rectal carriage of carbapenem-resistant E. coli. The E. coli strain from the affected patients corresponded to a single sequence type. Rectal screening identified isolates of two other sequence types bearing blaNDM-1. Isolates of all three sequence types harbored an IncFII plasmid. The plasmid was confirmed to carry blaNDM-1 through conjugation. An outbreak of clonal NDM-1-producing E. coli isolates and subsequent dissemination of NDM-1 through mobile elements to other E. coli strains occurred after hospital conversion during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This emphasizes the need for infection control practices in surge scenarios. IMPORTANCE The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios.


Subject(s)
Cross Infection/microbiology , Escherichia coli Infections/microbiology , Escherichia coli/enzymology , Escherichia coli/isolation & purification , beta-Lactamases/metabolism , Adult , Aged , COVID-19/epidemiology , COVID-19/virology , Conjugation, Genetic , Cross Infection/epidemiology , Disease Outbreaks , Escherichia coli/classification , Escherichia coli/genetics , Escherichia coli Infections/epidemiology , Escherichia coli Infections/mortality , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Mexico/epidemiology , Middle Aged , Plasmids/genetics , SARS-CoV-2/physiology , Tertiary Care Centers/statistics & numerical data , beta-Lactamases/genetics
6.
Braz J Microbiol ; 53(1): 205-212, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1611548

ABSTRACT

The prevalence and risk factors for gut carriage of antimicrobial-resistant Escherichia coli among individuals living in the community in Rio de Janeiro, Brazil, are unknown. The aim of this study was to determine the prevalence of colonization with antimicrobial-resistant E. coli, including isolates producing ESBL and harboring plasmid-mediated quinolone resistant (PMQR) genes in this community. We performed a cross-sectional study and analyzed fecal specimens of individuals attending outpatient clinics in the city from January 2015 to July 2019. We investigated susceptibility to antimicrobial agents by disc diffusion tests and used PCR to determine ESBL types, PMQR, and the virulence genes that characterize an isolate as extraintestinal pathogenic E. coli (ExPEC). Among the 623 subjects, 212 (34%) carried an isolate resistant to at least one of the tested antimicrobial agents, with the highest frequencies of resistance to ampicillin (26%), trimethoprim-sulfamethoxazole (19%), cefazolin (14%), and ciprofloxacin (CIP, 9%). In addition, 13% (81) of subjects carried a multidrug-resistant-E. coli (MDR-E), including 47 (8% of all isolates) ESBL-producing E. coli (ESBL-E), mainly of CTX-M-8 (15, 32%) and CTX-M-15 (9, 20%) types. PMQR genes were present in 7% (42) of all isolates, including 60% (32) of the 53 resistant to CIP. Previous use of antimicrobial agents, particularly fluoroquinolones, was a risk factor for colonization with MDR-E (25%, 20/81 vs 13%, 70/542, p = 0.01), ESBL-E (28%, 13/47, vs 13%, 77/576, p = 0.01), and resistance to CIP (26%, 14/53, vs 12%, 70/570, p = 0.01). The most pathogenic phylogroups B2, C, and D were 37% of the MDR-E, 30% of the ESBL-E, 38% of the CIP-resistant, and 31% of PMQR gene carrying E. coli isolates. We show that carriage of MDR-E (mostly ESBL-E) reached high levels in the community in Rio de Janeiro, increased by the selection of antimicrobial agents. Much of the resistant E. coli isolates are potential pathogenic strains. The widespread use of antimicrobial agents during the COVID-19 pandemic in Brazil may have worsened this picture.


Subject(s)
COVID-19 , Escherichia coli Infections , Anti-Bacterial Agents/pharmacology , Brazil/epidemiology , Cross-Sectional Studies , Drug Resistance, Multiple, Bacterial , Escherichia coli , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Humans , Microbial Sensitivity Tests , Pandemics , SARS-CoV-2 , beta-Lactamases/genetics
7.
Eur J Clin Microbiol Infect Dis ; 41(3): 495-500, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1603573

ABSTRACT

The objective was to study ceftazidime-avibactam resistant and susceptible Klebsiella pneumoniae isolated from a patient admitted to the Policlinico Umberto I of Rome for SARS-CoV2. Data on the evolution of patient's conditions, antimicrobial therapies, and microbiological data were collected. Whole-genome sequencing performed by Illumina and Nanopore sequencing methods were used to type the strains. During the hospitalization, a SARS-CoV2-infected patient was colonized by a KPC-producing K. pneumoniae strain and empirically treated with ceftazidime-avibactam (CZA) when presenting spiking fever symptoms. Successively, ST2502 CZA-resistant strain producing the KPC-31 variant gave a pulmonary infection to the patient. The infection was treated with high doses of meropenem. The KPC-31-producing strain disappeared but the patient remained colonized by a KPC-3-producing K. pneumoniae strain. An interplay between highly conserved KPC-31- and KPC-3-producing ST2502 strains occurred in the SARS-CoV2 patient during the hospitalization, selected by CZA and carbapenem treatments, respectively.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Klebsiella Infections , Meropenem , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , COVID-19/complications , Ceftazidime/therapeutic use , Drug Combinations , Humans , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/genetics , Meropenem/therapeutic use , Microbial Sensitivity Tests , beta-Lactamases/genetics
8.
J Hosp Infect ; 120: 48-56, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1549920

ABSTRACT

BACKGROUND: An outbreak of VIM carbapenemase-expressing Enterobacter cloacae complex occurred between March and October 2020 in an intensive care unit (ICU) of a tertiary care and teaching hospital in France. At the same time, the hospital was facing the COVID-19 first wave. AIM: To describe the management of an outbreak caused by a VIM-producing Enterobacter cloacae complex strain during the COVID-19 pandemic in an ICU and to show the importance of an integrated approach. METHODS: A multi-focal investigation was conducted including descriptive and molecular epidemiology, environmental screening, and assessment of infection prevention and control measures. FINDINGS: A total of 14 cases were identified in this outbreak with a high attributable mortality rate (85.7%). The outbreak management was coordinated by a crisis cell, and involved the implementation of multi-disciplinary actions such as: enhanced hygiene measures, microbiological and molecular analysis of patients and environmental E. cloacae complex strains, and simulation-based teaching. All 23 E. cloacae complex strains isolated from patients and environment samples belonged to multi-locus sequence type ST78 and carried bla-VIM4 gene. Using Fourier transform infrared spectroscopy, all but two isolates were also found to belong to a single cluster. Although the source of this outbreak could not be pinpointed, the spread of the strain was controlled thanks to this multi-focal approach and multi-disciplinary implementation. CONCLUSION: This investigation highlighted the usefulness of Fourier transform infra-red spectroscopy in the rapid typing of outbreak strains as well as the importance of an integrated approach to successfully fight against multidrug-resistant micro-organism dissemination and healthcare-associated infections.


Subject(s)
COVID-19 , Cross Infection , Enterobacteriaceae Infections , Anti-Bacterial Agents , Bacterial Proteins , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Outbreaks , Enterobacter cloacae/genetics , Enterobacteriaceae Infections/epidemiology , Hospitals , Humans , Intensive Care Units , Microbial Sensitivity Tests , Pandemics , SARS-CoV-2 , beta-Lactamases/genetics
9.
Genome Med ; 13(1): 182, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1523323

ABSTRACT

BACKGROUND: Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. METHODS: CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. RESULTS: An 8-h CMg workflow was 92% sensitive (95% CI, 75-99%) and 82% specific (95% CI, 57-96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of ß-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. CONCLUSION: CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.


Subject(s)
COVID-19/pathology , Cross Infection/transmission , Metagenomics , Anti-Bacterial Agents/therapeutic use , COVID-19/virology , Coinfection/drug therapy , Coinfection/microbiology , Corynebacterium/genetics , Corynebacterium/isolation & purification , Cross Infection/microbiology , DNA, Bacterial/chemistry , DNA, Bacterial/metabolism , Drug Resistance, Multiple, Bacterial/genetics , Female , Humans , Intensive Care Units , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/isolation & purification , Male , Middle Aged , Polymorphism, Single Nucleotide , SARS-CoV-2/isolation & purification , Sequence Analysis, DNA , beta-Lactamases/genetics
10.
Microbiol Spectr ; 9(3): e0112221, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1511426

ABSTRACT

Whole-genome sequencing was used to characterize carbapenemase-producing Enterobacterales (CPE) strains recovered from rectal screening swab samples obtained from children at a tertiary-care pediatric hospital in Qatar during a 3-year period. A total of 72 CPE isolates recovered from 61 fecal carriers were characterized. Escherichia coli (47 isolates [65.3%]) and Klebsiella pneumoniae (22 isolates [30.6%]) were the most common species identified. High levels of genetic diversity were observed for both species. These 72 isolates produced 78 carbapenemases, characterized as either NDM-type (41 enzymes [52.6%]) or OXA-48-type (37 enzymes [47.4%]). NDM-5 (24 enzymes [30.8%]), NDM-1 (15 enzymes [19.2%]), and OXA-181 (15 enzymes [19.2%]) were the most common variants detected within each type. Twenty-three NDM producers exhibited difficult-to-treat resistance, compared with only 2 of the OXA-48 producers. Multiple comorbidities were identified in 88.5% of the patients, whereas recent travel history to countries in which CPE are endemic was documented for 57.4% of the patients. All 9 blaOXA-48-type-gene-containing E. coli sequence type 38 (ST38) strains were isolated from patients without international travel history. The mean quarterly incidence of fecal carriage decreased more than 6-fold after the implementation of coronavirus disease 2019 (COVID-19)-related international travel restrictions in Qatar in mid-March 2020. Our data suggest that NDM-type and OXA-48-type carbapenemases expressed by a large diversity of E. coli and K. pneumoniae genotypes are largely dominant in the pediatric population of Qatar. Although our data indicate successful local expansion of E. coli ST38 strains harboring blaOXA-244 genes, at least within health care settings, blaOXA-48-type and blaNDM-type genes appear to have been mainly introduced sporadically by asymptomatic carriers who visited or received health care in some nearby countries in which the genes are endemic. IMPORTANCE To the best of our knowledge, this is the first study addressing the molecular characteristics of CPE in a pediatric population in Qatar using whole-genome sequencing. Since several countries in the Arabian Peninsula share relatively similar demographic patterns and international links, it is plausible that the molecular characteristics of CPE in children, at least in the middle and eastern parts of the region, are similar to those observed in our study.


Subject(s)
Bacterial Proteins/chemistry , Enterobacteriaceae/enzymology , Feces/chemistry , beta-Lactamases/chemistry , Adolescent , Anti-Bacterial Agents , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , COVID-19 , Child , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Escherichia coli/enzymology , Escherichia coli/genetics , Genotype , Humans , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , Mutation , Qatar , Retrospective Studies , SARS-CoV-2 , Whole Genome Sequencing , beta-Lactamases/genetics , beta-Lactamases/isolation & purification
11.
J Antimicrob Chemother ; 76(10): 2538-2545, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1447597

ABSTRACT

OBJECTIVES: To assess the spread of New Delhi metallo-ß-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae ST147 organisms in Poland since an introduction from Tunisia in March 2015, including their phylogenetic position in the global population of the high-risk clone. METHODS: Out of 8925 unique NDM-positive K. pneumoniae isolates identified in Poland from April 2015 till December 2019, 126 isolates, including the Tunisian imports, were related by PFGE and blaNDM gene-carrying Tn125 transposon derivatives. Forty-seven representative isolates were sequenced by Illumina MiSeq. The phylogeny, resistome, virulome and plasmid replicons were analysed and compared with the international ST147 strains. Plasmids of six isolates were studied by the MinION sequencing. RESULTS: A high homogeneity of the 47 isolates was observed, with minor variations in their resistomes and plasmid replicon profiles. However, the detailed SNP comparison discerned a strict outbreak cluster of 40 isolates. All of the organisms were grouped within the ST147 phylogenetic international lineage, and four NDM-1 producers from Tunisia, Egypt and France were the closest relatives of the Polish isolates. Yersiniabactin genes (YbST280 type) were located within the ICEKpn12-like element in most of the outbreak isolates, characterized by O2v1 and KL64 antigen loci. The blaNDM-1 genes were located in double-replicon IncFIIK2+IncFIBK plasmids. CONCLUSIONS: The continuous spread of K. pneumoniae ST147 NDM-1 in Poland since 2015, largely in the Warsaw area, is demonstrated by this genomic analysis. The isolates showed a high degree of homogeneity, and close relatedness to organisms spreading in the Mediterranean region.


Subject(s)
Klebsiella Infections , Klebsiella pneumoniae , Anti-Bacterial Agents , Humans , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , Phylogeny , Plasmids/genetics , Poland/epidemiology , beta-Lactamases/genetics
12.
BMC Infect Dis ; 21(1): 927, 2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1403227

ABSTRACT

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is among the most concerning cause of healthcare-associated infections (HAI) due to its high level of antibiotic resistance and high mortality. In the era of the COVID-19 pandemic, the key priority of infection control committees is to contain the dissemination of antibiotic resistant Gram-negative bacteria. Here, we aimed to timely recognize the emergence of CRAB in COVID-19 cases admitted to the wards of a tertiary referral hospital and to identify the genetic relatedness of the isolates. METHODS: From 30 March to 30 May 2020, a total of 242 clinical samples from COVID-19 cases were screened for CRAB isolates using standard microbiologic and antibiotic susceptibility tests. The PCRs targeting oxa23, oxa24, oxa58, blaTEM and blaNDM-1 genes were performed. Two multiplex PCRs for identifying the global clones (GC) of A. baumannii were also performed. The sequence type of CRABs was determined using Institut Pasteur (IP) multilocus sequence typing (MLST) scheme. RESULTS: Eighteen CRAB isolates were recovered from COVID-19 patients with the mean age of 63.94 ± 13.8 years. All but 4 COVID-19 patients co-infected with CRAB were suffering from an underlying disease. Death was recorded as the outcome in ICUs for 9 (50%) COVID-19 patients co-infected with CRAB. The CRAB isolates belong to GC2 and ST2IP and carried the oxa23 carbapenem resistance gene. CONCLUSION: This study demonstrated the co-infection of CRAB isolates and SARS-CoV-2 in the patients admitted to different ICUs at a referral hospital in Tehran. The CRAB isolates were found to belong to ST2IP, share the oxa23 gene and to have caused several outbreaks in the wards admitting COVID-19 patients.


Subject(s)
Acinetobacter Infections , COVID-19 , Coinfection , Acinetobacter Infections/epidemiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Aged , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , COVID-19/epidemiology , COVID-19/microbiology , Carbapenems/pharmacology , Coinfection/epidemiology , Humans , Iran/epidemiology , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , Pandemics , Tertiary Care Centers , beta-Lactamases/genetics
13.
Diagn Microbiol Infect Dis ; 100(4): 115399, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1315428

ABSTRACT

Between November 2018 and October 2019, carbapenem-resistant Enterobacterales carrying New Delhi Metallo-ß-lactamase (NDM) caused one of the largest and persistent outbreaks occurred in Italy and intensified surveillance measures have been taken in all Italian hospitals. In this study we analyzed NDM-5- producing Escherichia coli identified in 2 hospitals of the Lazio region in Italy. Epidemiological and microbiological data demonstrated that in 2018-2019 the NDM-5-producing high-risk E. coli ST167 clone circulated in patients from both hospitals. In 2019, another NDM-5-producing E. coli clone, identified by MLST as ST617 was introduced in one of the 2 hospitals and caused an outbreak. This study describes an application of genomics as a useful method to discern endemic and outbreak clones when applied to strains of the same species (E. coli) with the same resistance determinant (NDM-5) and the relevance of screening patients admitted in critical units for carbapenemase producers to prevent outbreaks.


Subject(s)
Escherichia coli Infections/epidemiology , Escherichia coli/genetics , beta-Lactamases/genetics , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , DNA, Bacterial/genetics , Disease Outbreaks/prevention & control , Disease Outbreaks/statistics & numerical data , Drug Resistance, Multiple, Bacterial , Escherichia coli/drug effects , Escherichia coli/enzymology , Female , Genome, Bacterial , Hospitals/statistics & numerical data , Humans , Italy/epidemiology , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Whole Genome Sequencing , beta-Lactamases/biosynthesis
14.
Am J Infect Control ; 49(10): 1324-1326, 2021 10.
Article in English | MEDLINE | ID: covidwho-1309130

ABSTRACT

An outbreak of Klebsiella pneumoniae producing the carbapenemase NDM-1 occurred in our ICU during the last COVID-19 wave. Twelve patients were tested positive, seven remained asymptomatic whereas 5 developed an infection. Resistome and in silico multilocus sequence typing confirmed the clonal origin of the strains. The identification of a possible environmental reservoir suggested that difficulties in observing optimal bio-cleaning procedures due to workload and exhaustion contributed to the outbreak besides the inappropriate excessive glove use.


Subject(s)
COVID-19 , Klebsiella Infections , Anti-Bacterial Agents , Bacterial Proteins/genetics , Disease Outbreaks , Dreams , Humans , Intensive Care Units , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , Multilocus Sequence Typing , Pandemics , SARS-CoV-2 , beta-Lactamases/genetics
15.
Am J Infect Control ; 49(6): 792-799, 2021 06.
Article in English | MEDLINE | ID: covidwho-1269213

ABSTRACT

BACKGROUND: Antibiotic-resistant Acinetobacter species are a growing public health threat, yet are not nationally notifiable, and most states do not mandate reporting. Additionally, there are no standardized methods to detect Acinetobacter species colonization. METHODS: An outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) was identified at a Utah ventilator unit in a skilled nursing facility. An investigation was conducted to identify transmission modes in order to control spread of CRAB. Culture-based methods were used to identify patient colonization and environmental contamination in the facility. RESULTS: Of the 47 patients screened, OXA-23-producing CRAB were detected in 10 patients (21%), with 7 patients (15%) having been transferred from out-of-state facilities. Of patients who screened positive, 60% did not exhibit any signs or symptoms of active infection by chart review. A total of 38 environmental samples were collected and CRAB was recovered from 37% of those samples. Whole genome sequencing analyses of patient and environmental isolates suggested repeated CRAB introduction into the facility and highlighted the role of shared equipment in transmission. CONCLUSIONS: The investigation demonstrated this ventilated skilled nursing facility was an important reservoir for CRAB in the community and highlights the need for improved surveillance, strengthened infection control and inter-facility communication within and across states.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins , Carbapenems/pharmacology , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Outbreaks , Humans , Infection Control , Microbial Sensitivity Tests , Skilled Nursing Facilities , Utah/epidemiology , beta-Lactamases/genetics
16.
J Antimicrob Chemother ; 76(9): 2225-2229, 2021 08 12.
Article in English | MEDLINE | ID: covidwho-1263669

ABSTRACT

The COVID-19 pandemic has increased relationships and interactions between human and companion animals, supported by widespread social distancing and isolation measures. Additionally, the COVID-19 pandemic has led to an exponential growth in antibiotic and biocide use worldwide, possibly inducing further pressure, contributing to the selection of antibiotic-resistant bacteria, including WHO critical priority pathogens. While data from global surveillance studies reveal a linear trend of increasing carbapenem resistance among Gram-negative pathogens from companion animals, the acquisition of carbapenemase-producing Enterobacterales through direct contact with colonized hosts and contaminated veterinary hospital environments has been documented. This article highlights the rapid spread of WHO critical priority carbapenemase-producing pathogens in companion animals, which is a One Health challenge for a post-pandemic world.


Subject(s)
COVID-19 , One Health , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins , Humans , Pandemics , SARS-CoV-2 , beta-Lactamases/genetics
19.
J Antimicrob Chemother ; 76(2): 380-384, 2021 01 19.
Article in English | MEDLINE | ID: covidwho-929995

ABSTRACT

BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.


Subject(s)
COVID-19/microbiology , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Bacterial Proteins/genetics , COVID-19/complications , COVID-19/drug therapy , COVID-19/epidemiology , Carbapenem-Resistant Enterobacteriaceae/enzymology , Carbapenem-Resistant Enterobacteriaceae/genetics , Cohort Studies , Comorbidity , Enterobacteriaceae Infections/complications , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Female , Hospitals , Humans , Male , Middle Aged , Nanopore Sequencing , New York City/epidemiology , Phylogeny , Retrospective Studies , SARS-CoV-2 , beta-Lactamases/genetics
20.
J Mol Model ; 26(8): 200, 2020 Jul 07.
Article in English | MEDLINE | ID: covidwho-650087

ABSTRACT

Beta-lactamase (ampC) in general causes the onset of antibiotic resistance in pathogenic bacteria against the ß-lactam antibiotics. Morganella morganii which belongs to the Proteae tribe of the Enterobacteriaceae family is a Gram-negative bacillus. Gram-negative bacteria are the key problematic agents among the human population in overexpressing resistance against ß-lactam antibiotics. These ß-lactam antibiotics being experimentally well studied still lack the key information and mechanism for their resistance. The structural information of the ampC protein is unknown and poorly studied; hence, it is the need of the hour to find effective inhibitors against it. In our study, the prediction of the three-dimensional structure of ampC protein from Morganella morganii was performed using a comparative modelling approach. The predicted structure was energetically stabilized and functional conformations were mapped through 100-ns molecular dynamics simulation runs. Also, Ramachandran plot shows the model to be stereo-chemically stable with most residues found under core allowed regions. Drug screening with several experimentally tested inhibitors was then confirmed to check the activity against ampC protein using an AutoDock tool. The results suggested OncoglabrinolC molecule as the best inhibitor (out of 21 drug molecules) with a binding affinity of - 11.44 kcal/mol. Anti-bacterial/anti-parasitic inhibitors have not only been used against bacterial infections, but later reports have also shown them to work against deadly viruses such as SARS-CoV2. This key structural and inhibitory information is certain to help in the discovery of specific and potent substitute therapeutic drugs and the development of experimental procedures against human infection.


Subject(s)
Anti-Bacterial Agents/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , beta-Lactamase Inhibitors/chemistry , beta-Lactamases/chemistry , Anti-Bacterial Agents/pharmacology , Base Sequence , Binding Sites , Chemical Phenomena , Drug Discovery , Drug Evaluation, Preclinical , Humans , Ligands , Mutation , Protein Binding , Protein Conformation , beta-Lactamase Inhibitors/pharmacology , beta-Lactamases/genetics
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