Antibiotic resistance has turned into a global public health issue. Enterococci are intrinsically resistant to many antimicrobials groups. These bacteria colonize dairy and meat products and ...integrate the autochthonous microbiota of mammal's gastrointestinal tract. Over the last decades, detection of
genotype in
from animals and from food of animal origin has been reported. Vancomycin-resistant
has become a prevalent nosocomial pathogen. Hospitalized patients are frequently treated with broad-spectrum antimicrobials and this leads to an increase in the presence of VanA or VanB vancomycin-resistant enterococci in patients' gastrointestinal tract and the risk of invasive infections. In humans,
is the main reservoir of VanA and VanB phenotypes. Acquisition of high-level aminoglycoside resistance is a significant therapeutic problem for patients with severe infections because it negates the synergistic effect between aminoglycosides and a cell-wall-active agent. The
gene is widely spread in
and has been detected in strains of human origin and in the food of animal origin. Enzyme AAC(6
)-Ie-APH(2
)-Ia confers resistance to available aminoglycosides, except to streptomycin. Due to the fast dissemination of this genetic determinant, the impact of its horizontal transferability among enterococcal species from different origin has been considered. The extensive use of antibiotics in food-producing animals contributes to an increase in drug-resistant animal bacteria that can be transmitted to humans. Innovation is needed for the development of new antibacterial drugs and for the design of combination therapies with conventional antibiotics. Nowadays, semi-purified bacteriocins and probiotics are becoming an attractive alternative to the antibiotic in animal production. Therefore, a better understanding of a complex and relevant issue for Public Health such as high-level vancomycin and gentamicin resistance in enterococci and their impact is needed. Hence, it is necessary to consider the spread of
and high-level gentamicin resistant
strains of different origin in the environment, and also highlight the potential horizontal transferability of these resistance determinants to other bacteria.
:Enterobacter cloacae complex (ECC) has lately awakened interest due to its increasing resistance to carbapenems codified by several genes all over the globe. Even though there are some sequence ...types (ST) which represent high-risk clones, there is substantial clonal diversity in the ECC. This work aimed to perform whole-genome sequencing (WGS), genomic analysis and phylogenetic studies of a KPC-producing multidrug-resistant (MDR) ECC isolate from Argentina.
: We analysed the genome of an MDR KPC-producing ECC strain isolated from a urine sample from a patient in a hospital in Argentina. The WGS was done by Illumina MiSeq-I. The genome was assembled with SPAdes 3.9.0, and annotated with PROKKA, RAST, and Blast. Plasmids were identified with PlasmidFinder. Antibiotic resistance genes were detected using RESfinder, CARD, and Blastn. STs were identified with pubMLST.
: The strain was identified as Enterobacter hormaechei which is an important emerging human pathogen. No ST could be assigned; 6 out of 7 alleles of multilocus sequence typing (MLST) were the same as for E. hormaechei ST66, which is a high-risk clone. We found multiple acquired antibiotic resistance genes including blaKPC-2 in an IncM1 plasmid, and a secretion system VI, which can favour the prevalence of ECC strains while competing with other bacteria.
: Due to its MLST profile being so close to E. hormaechei ST66, the acquisition of multiple resistance genes, and the presence of the secretion systems, the potential of this strain for becoming a new high-risk clone cannot be discarded.
Two metallo-β-lactamase-producing
Klebsiella pneumoniae
(HA30 and HA31) were isolated in a hospital in Argentina during 2018.
K. pneumoniae
HA30 was isolated from a rectal swab during the ...epidemiological surveillance for carbapenemase-producing strains, while
K. pneumoniae
HA31 was collected from the same patient 4 days after hospitalization. The aim of the present study was to identify the clonal relationships and resistome of these two NDM-producing
K. pneumoniae
strains isolated from a patient with a fatal outcome. Whole-genome sequencing (WGS) was performed using Illumina MiSeq-I, and subsequent analysis involved genome assembly, annotation, antibiotic resistance gene identification, multilocus sequence typing (MLST), and plasmid characterization using bioinformatics tools. Conjugation assays to
E. coli
J53 was conducted as previously described.
K. pneumoniae
HA30 exhibited extensively drug-resistant phenotype, while HA31 was multidrug-resistant as defined by Magiorakos et al., including both resistance to carbapenems, aminoglycosides and ciprofloxacin with
bla
NDM-5
,
bla
CTX-M-15
and
rmtB
genes found in both strains. MLST analysis showed that both strains belonged to ST11, differing by only 4 cgSNPs, indicating that
K. pneumoniae
HA30 and HA31 were the same strain. Conjugation assays revealed that
K. pneumoniae
HA31 strain possessed a transferable plasmid to
E. coli
J53. Bioinformatics studies identified that the same strain colonizing an inpatient during hospital admission subsequently caused the infection leading to a fatal outcome, being the first report of
bla
NDM-5
,
rmtB
and
bla
CTX-M-15
genes in a
K. pneumoniae
ST11 strain from Latin America. Our results also highlighted the importance of focusing on epidemiological surveillance programs.
•FilmArray Respiratory Panel was associated with fewer antimicrobial prescriptions.•The main impact was the reduction of macrolides and beta-lactams prescriptions.•Immunocompromised patients could be ...the most favored using rapid molecular testing.
This study aimed to assess the impact of the implementation of a rapid multiplex molecular FilmArray Respiratory Panel (FRP) on the medical management of immunocompromised patients from a community general hospital. We conducted a single-center, retrospective, and before–after study. Two periods were evaluated: before the implementation of the FRP (pre-FRP) from April 2017 to May 2018 and after the implementation of the FRP (post-FRP) from January to July 2019. The inclusion criteria were immunocompromised patients over 18 years of age with suspected acute respiratory illness tested by conventional diagnostic methods (pre-FRP) or the FilmArray™ Respiratory Panel v1.7 (post-FRP). A total of 142 patients were included, 64 patients in the pre-FRP and 78 patients in the post-FRP. The positive detection rate was significantly higher in the post-FRP (63% vs. 10%, p<0.01). There were more patients receiving antimicrobial treatment in the pre-FRP compared with the post-FRP period (94% vs. 68%, p<0.01). A decrease in beta-lactam (89% vs. 61%, p<0.01) and macrolide (44% vs. 13%, p<0.01) prescriptions were observed in the post-FRP. No differences were observed in oseltamivir use (22% vs. 13%, p=0.14), changes in antimicrobial treatment, hospital admission rate, days-reduction in droplet isolation precautions, hospital length of stay (LOS), admission to intensive care unit (ICU), LOS in ICU, treatment failure and 30-day mortality. The implementation of the FRP impacted patient care by improving diagnostic yield and optimizing antimicrobial treatment in immunocompromised adult patients.
El objetivo de este estudio fue evaluar el impacto de la implementación del panel respiratorio FilmArray® (FRP), un sistema automatizado de PCR multiplex, en el estándar de cuidado de pacientes adultos inmunocomprometidos en un hospital general. Es un estudio retrospectivo de un único centro con diseño antes/después. Los periodos evaluados fueron abril 2017-mayo 2018, previo a la implementación del FRP (pre-FRP), y enero 2019-julio 2019, luego de la implementación (post-FRP). Los criterios de inclusión fueron pacientes mayores de 18 años inmunocomprometidos con sospecha de infección respiratoria aguda a los que se les realizó, en pre-FRP, diagnóstico por métodos convencionales, y en post-FRP, el panel respiratorio FRP versión 1.7. Se incluyeron un total de 142 pacientes, 64 en pre-FRP y 78 en post-FRP. La tasa de positividad fue significativamente mayor en post-FRP frente a pre-FRP (63 vs. 10%, p<0,01). Hubo más pacientes con tratamiento antimicrobiano en pre-FRP que en post-FRP (94 vs. 68%, p<0,01). En pre-FRP hubo más pacientes tratados con betalactámicos (89 vs. 61%, p<0,01) y macrólidos (44 vs. 13%, p<0,01). No se observaron diferencias significativas en el uso de oseltamivir (22 vs. 13%, p=0,14), cambios en los tratamientos, número de hospitalizaciones, uso de aislamientos, duración de la estadía hospitalaria, ingreso a la unidad de cuidados intensivos, estadía en dicha unidad, falla de tratamiento y mortalidad a 30 días. El uso de FRP contribuyó a la atención del paciente mejorando el rendimiento diagnóstico y optimizando la terapia antimicrobiana en pacientes adultos inmunocomprometidos.
According to the World Health Organization, carbapenem-resistant
Enterobacteriaceae
(CRE) belong to the highest priority group for the development of new antibiotics. Argentina-WHONET data showed ...that Gram-negative resistance frequencies to imipenem have been increasing since 2010 mostly in two CRE bacteria:
Klebsiella pneumoniae
and
Enterobacter cloacae
Complex (ECC). This scenario is mirrored in our hospital. It is known that
K. pneumoniae
and the ECC coexist in the human body, but little is known about the outcome of these species producing KPC, and colonizing or infecting a patient. We aimed to contribute to the understanding of the rise of the ECC in Argentina, taking as a biological model both a patient colonized with two KPC-producing strains (one
Enterobacter hormaechei
and one
K. pneumoniae
) and
in vitro
competition assays with prevalent KPC-producing ECC (KPC-ECC) versus KPC-producing
K. pneumoniae
(KPC-Kp) high-risk clones from our institution. A KPC-producing
E. hormaechei
and later a KPC-Kp strain that colonized a patient shared an identical novel conjugative IncM1 plasmid harboring
bla
KPC-2
. In addition, a total of 19 KPC-ECC and 58 KPC-Kp strains isolated from nosocomial infections revealed that high-risk clones KPC-ECC ST66 and ST78 as well as KPC-Kp ST11 and ST258 were prevalent and selected for competition assays. The competition assays with KCP-ECC ST45, ST66, and ST78 versus KPC-Kp ST11, ST18, and ST258 strains analyzed here showed no statistically significant difference. These assays evidenced that high-risk clones of KPC-ECC and KPC-Kp can coexist in the same hospital environment including the same patient, which explains from an ecological point of view that both species can exchange and share plasmids. These findings offer hints to explain the worldwide rise of KPC-ECC strains based on the ability of some pandemic clones to compete and occupy a certain niche. Taken together, the presence of the same new plasmid and the fitness results that showed that both strains can coexist within the same patient suggest that horizontal genetic transfer of
bla
KPC-2
within the patient cannot be ruled out. These findings highlight the constant interaction that these two species can keep in the hospital environment, which, in turn, can be related to the spread of KPC.
The worldwide dissemination of carbapenemase-producing Escherichia coli lineages belonging to high-risk clones poses a challenging public health menace. The aim of this work was to investigate ...genomic features of a colonizing multidrug-resistant strain of Klebsiella pneumoniae carbapenemase (KPC)-producing E. coli from our institution.
Whole-genome sequencing was done by Illumina MiSeq-I, and de novo assembly was achieved using SPAdes. Resistome, mobilome, plasmids, virulome, and integrons were analysed using ResFinder, AMRFinder, ISFinder, PlasmidFinder, MOB-suite, VirulenceFinder, and IntegronFinder. Sequence types (STs) were identified with pubMLST and BIGSdb databases. Conjugation assays were also performed.
Escherichia coli HA25pEc was isolated from a rectal swab sample taken within the framework of the hospital epidemiological surveillance protocol for detection of carbapenemase-producing Enterobacterales. Escherichia coli HA25pEc corresponded to the first report of ST648 co-harbouring blaKPC-2 and blaCTX-M-15 in Latin America from a colonized patient. It had 19 antibiotic resistance genes (ARGs), including blaKPC-2, located on a Tn4401a isoform. Conjugation assays revealed that blaKPC-2 was not transferred by conjugation to E. coli J53 under our experimental conditions.
Escherichia coli ST648 has been detected previously in companion and farm animals as well as in hospital- and community-acquired infections worldwide. Although scarcely reported as KPC-producers, our finding in a culture surveillance with several acquired ARGs, including blaCTX-M-15, alerts the potential of this clone for worldwide unnoticed spreading of extreme drug resistance to β-lactams. These data reinforce the importance of carrying out molecular surveillance to identify reservoirs and warn about the dissemination of new international clones in carbapenemase-bearing patients.
The emergence of blaKPC-2 within nosocomial settings has become a major public health crisis worldwide. Our aim was to perform whole-genome sequencing (WGS) of three KPC-producing Gram-negative ...bacilli (KPC-GNB) strains isolated from a hospitalized patient to identify acquired antimicrobial resistance genes (ARGs).
WGS was performed using Illumina MiSeq-I, and de novo assembly was achieved using SPAdes. Bioinformatics analysis was done using Resfinder, AMRFinder, ISFinder, plasmidSPAdes, PlasmidFinder, MOB-suite, PLSDB database, and IntegronFinder. Conjugation assays were performed to assess the ability of blaKPC-2 to transfer via a plasmid-related mobilization mechanism.
High-risk clone KPC-producing Klebsiella pneumoniae sequence type (ST) 258 (HA3) was colonizing an inpatient who later was infected by KPC-producing Escherichia coli ST730 (HA4) and subsequently by KPC-producing K. pneumoniae ST11 (HA15) during hospitalization. Although belonging to different species, both strains causing infections harbored the same gene configuration for dissemination of blaKPC-2 in related IncM1 plasmids recently found in other KPC-GNB isolated from Hospital Alemán at Ciudad Autónoma de Buenos Aires. Conjugation assays revealed that only pDCVEA4-KPC from E. coli HA4 was successfully transferred with a conjugation frequency of 3.66 × 101.
Interchange of multidrug-resistant K. pneumoniae lineages ST258 replaced by ST11 in the framework of colonization and infection by KPC-GNB of an inpatient from our institution was found. In addition, the transfer of the gene configuration of blaKPC–2 between infecting strains may have occurred in the nosocomial environment, but we cannot rule out that the event took place in vivo, within the patient, during hospitalization.
Acute transverse myelitis in a traveler García Allende, Natalia; García Posada, Mara J; Radosta, Mariana F ...
Medicina (Buenos Aires),
2016, 20160101, Volume:
76, Issue:
4
Journal Article
Peer reviewed
Acute transverse myelitis is defined as an acquired neuroimmune disorder of the spinal cord, which occurs as a consequence of a primary event, or directly related to an autoimmune inflammatory ...disease, an infectious or post-infectious disease. Amongst infectious etiologies, Borrelia spp., a tick-bourne anthropozoonosis of the ixodidae family, prevails. Approximately 10 to 15% of patients with Lyme disease undergo neurologic manifestations, with an assorted and uncertain array of clinical syndromes. Transverse myelitis accounts for up to 5% of Lyme neuroborreliosis. We describe the case of a traveler from endemic zone for Lyme disease, with encephalomyelitis secondary to acute infection by Borrelia burgderfori, with complete resolution of symptoms after concluding adequate antibiotic treatment.
Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report ...the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety.
PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to <60 mL/min per 1·73 m2 and ≥60 mL/min per 1·73 m2) and urine protein excretion at screening (≤1·75 g/day and >1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein–creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850.
Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein–creatinine ratio was statistically significantly greater in the sparsentan group (–49·8%) than the irbesartan group (–15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51–0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups.
Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan.
Travere Therapeutics.
PDF
