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The Journal of Infection Jun 2024
PubMed: 38848967
DOI: 10.1016/j.jinf.2024.106191 -
Euro Surveillance : Bulletin Europeen... Jun 2024BackgroundVancomycin-resistant enterococci (VRE) are increasing in Denmark and Europe. Linezolid and vancomycin-resistant enterococci (LVRE) are of concern, as treatment...
BackgroundVancomycin-resistant enterococci (VRE) are increasing in Denmark and Europe. Linezolid and vancomycin-resistant enterococci (LVRE) are of concern, as treatment options are limited. Vancomycin-variable enterococci (VVE) harbour the gene complex but are phenotypically vancomycin-susceptible.AimThe aim was to describe clonal shifts for VRE and VVE in Denmark between 2015 and 2022 and to investigate genotypic linezolid resistance among the VRE and VVE.MethodsFrom 2015 to 2022, 4,090 Danish clinical VRE and VVE isolates were whole genome sequenced. We extracted vancomycin resistance genes and sequence types (STs) from the sequencing data and performed core genome multilocus sequence typing (cgMLST) analysis for . All isolates were tested for the presence of mutations or genes encoding linezolid resistance.ResultsIn total 99% of the VRE and VVE isolates were From 2015 through 2019, 91.1% of the VRE and VVE were . During 2020, to the number of increased to 254 of 509 VRE and VVE isolates. Between 2015 and 2022, seven clusters dominated: ST80-CT14 , ST117-CT24 , ST203-CT859 ST1421-CT1134 (VVE cluster) ST80-CT1064 , ST117-CT36 and ST80-CT2406 We detected 35 linezolid vancomycin-resistant and eight linezolid-resistant VVEfm.ConclusionFrom 2015 to 2022, the numbers of VRE and VVE increased. The spread of the VVE cluster ST1421-CT1134 in Denmark is a concern, especially since VVE diagnostics are challenging. The finding of LVRE, although in small numbers, ia also a concern, as treatment options are limited.
Topics: Vancomycin-Resistant Enterococci; Enterococcus faecium; Humans; Denmark; Gram-Positive Bacterial Infections; Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Linezolid; Multilocus Sequence Typing; Microbial Sensitivity Tests; Vancomycin Resistance; Whole Genome Sequencing; Vancomycin; Genotype
PubMed: 38847117
DOI: 10.2807/1560-7917.ES.2024.29.23.2300633 -
Frontiers in Immunology 2024bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA...
INTRODUCTION
bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA bacteremia (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs. RB outcomes are poorly understood. Here, integrated transcriptomic, IL-10 cytokine levels, and genomic analyses sought to identify signatures differentiating PB vs. RB outcomes.
METHODS
Whole-blood transcriptomes of propensity-matched PB (n=28) versus RB (n=30) patients treated with vancomycin were compared in one independent training patient cohort. Gene expression (GE) modules were analyzed and prioritized relative to host IL-10 cytokine levels and DNA methyltransferase-3A () genotype.
RESULTS
Differential expression of T and B lymphocyte gene expression early in MRSA bacteremia discriminated RB from PB outcomes. Significant increases in effector T and B cell signaling pathways correlated with RB, lower IL-10 cytokine levels and heterozygous A/C genotype. Importantly, a second PB and RB patient cohort analyzed in a masked manner demonstrated high predictive accuracy of differential signatures.
DISCUSSION
Collectively, the present findings indicate that human PB involves dysregulated immunity characterized by impaired T and B cell responses associated with excessive IL-10 expression in context of the A/A genotype. These findings reveal distinct immunologic programs in PB vs. RB outcomes, enable future studies to define mechanisms by which host and/or pathogen drive differential signatures and may accelerate prediction of PB outcomes. Such prognostic assessment of host risk could significantly enhance early anti-infective interventions to avert PB and improve patient outcomes.
Topics: Humans; Bacteremia; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Male; Female; Middle Aged; Gene Expression Profiling; Transcriptome; Aged; Interleukin-10; DNA Methyltransferase 3A; Anti-Bacterial Agents; Adult
PubMed: 38846955
DOI: 10.3389/fimmu.2024.1373553 -
Medecine Tropicale Et Sante... Mar 2024To determine the etiology of cervico-vaginal infections by cytobacteriology and the efficacy of qPCR for the diagnosis of sensitive strains such as and
OBJECTIVE
To determine the etiology of cervico-vaginal infections by cytobacteriology and the efficacy of qPCR for the diagnosis of sensitive strains such as and
METHODOLOGY
This prospective cross-sectional study was performed between January and September 2021 in 346 women who were examined for cervico-vaginal infection at the Hôpital Principal de Dakar (HPD). Cytobacteriological (direct examination, agar culture) and molecular analyses were performed.
RESULTS
Vaginal flora imbalances predominated, with a rate of 72.3%. The proportion of type IV vaginal flora was 46.5%. Of the 199 germs isolated, (25.1%), (17.6%), (7.8%), (6.6%) and nonalbicans (5.5%) were the main pathogens responsible for cervico-vaginal infections in patients. Among women tested for mycoplasma, was identified in 43.3% of patients. Among those tested for the proportion of infected women was low (4%). The prevalence of was higher in pregnant women (38.3%) than in nonpregnant women (19.2%). strains showed high resistance to certain beta-lactam antibiotics (pristinamycin 100%, gentamycin 100%, ampicillin 92.5% and cefalotin 85.2%) and to a glycopeptide antibiotic (vancomycin 100%). The strain had good sensitivity to antibiotics except gentamycin (100%) and kanamycin (100%). The enterobacteria tested were all sensitive to phenicols, carbapenems, cephalosporins and aminoglycosides. However, showed high resistance to tetracycline. The different methods showed low prevalences of and so comparisons Test RapidChlamydia/qPCR for and culture/qPCR for N. were not possible. For on the other hand, qPCR was more advantageous than culture. The χ test showed a significant difference (Yates χ = 33.77 and p = 1) for the diagnosis of qPCR had a sensitivity of 40.7%, a specificity of 94%, and positive and negative predictive values of 36.7% and 94.9% respectively, as well as a kappa = 0.33.
CONCLUSION
The methods applied enabled us to identify the pathogens that cause cervicovaginal infections. The results suggest that qPCR may be an alternative, at least for the diagnosis of However, culture remains indispensable for studying antibiotic sensitivity. In order to improve patient care, molecular techniques need to be integrated into the HPD testing toolbox. To broaden the repertoire of pathogens to be diagnosed by qPCR, targeted comparison studies will be needed to increase the probability of encountering infected individuals.
Topics: Humans; Female; Senegal; Cross-Sectional Studies; Adult; Prospective Studies; Young Adult; Real-Time Polymerase Chain Reaction; Middle Aged; Adolescent; Vaginitis
PubMed: 38846122
DOI: 10.48327/mtsi.v4i1.2024.298 -
The Brazilian Journal of Infectious... 2024C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as...
Molecular epidemiology and antimicrobial resistance in Clostridioides difficile strains isolated from children and adolescents in a tertiary referral pediatric hospital in Fortaleza, Brazil.
BACKGROUND
C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon. Only two pediatric research groups reported the presence of C. difficile infection in Brazilian children, but no previous research has examined C. difficile infection among children in northeastern Brazil. This prospective cross-sectional study investigated the molecular epidemiology and antimicrobial resistance of C. difficile strains isolated from children and adolescents with diarrhea referred to a tertiary pediatric hospital in Brazil while exploring the associated risk factors.
RESULTS
Toxin positivity or C. difficile isolation was found in 30.4 % (17/56) samples. C. difficile was isolated from 35 % (6/17) samples. Four toxigenic strains were identified (tpi+, tcdA+, tcdB+, cdtB-, without tcdC deletions) belonging to PCR ribotypes and PFGE-pulsotypes: 046 (new pulsotype 1174), 106 (NAP11), 002 (new pulsotype 1274), 012 (new pulsotype NML-1235). Two of the six isolates belonging to ribotypes 143 and 133 were non-toxigenic. All toxigenic strains were sensitive to metronidazole and vancomycin. Regarding the clinical manifestation, diarrhea lasted an average of 11 days, ranging from 3 to 50 days and was often associated with mucus and/or blood. All six patients from whom the C. difficile was isolated had a chronic disease diagnosis, with these comorbidities as the main risk factors.
CONCLUSION
Our study enhances our understanding of the present epidemiological landscape of C. difficile-associated diarrhea (CDI) among children in northeastern Brazil, reveling a substantial CDI frequency of 30.4 %, with toxigenic strains detected in 76.4 % of cases, highlighting a higher prevalence compared to earlier Brazilian studies. In the globalized world, an understanding of disease-generating strains, the associated risk factors, clinical manifestation, and antimicrobial sensitivity has fundamental epidemiological importance and draws attention to preventive measures, allowing for more decisive action.
Topics: Humans; Clostridioides difficile; Child; Adolescent; Female; Male; Brazil; Cross-Sectional Studies; Prospective Studies; Tertiary Care Centers; Child, Preschool; Anti-Bacterial Agents; Clostridium Infections; Microbial Sensitivity Tests; Risk Factors; Infant; Hospitals, Pediatric; Molecular Epidemiology; Diarrhea; Ribotyping; Drug Resistance, Bacterial
PubMed: 38843868
DOI: 10.1016/j.bjid.2024.103767 -
International Journal of Medical... Jun 2024Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S....
Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S. aureus infections have become increasingly challenging. Vancomycin is considered to be one of the last-resort drugs for treating most methicillin-resistant S. aureus (MRSA), so it is of great significance to further reveal the mechanism of vancomycin resistance. VraFG is one of the few important ABC (ATP-binding cassette) transporters in S. aureus that can form TCS (two-component systems)/ABC transporter modules. ABC transporters can couple the energy released from ATP hydrolysis to translocate solutes across the cell membrane. In this study, we obtained a strain with decreased vancomycin susceptibility after serial passaging and selection. Subsequently, whole-genome sequencing was performed on this laboratory-derived strain MWA2 and a novel single point mutation was discovered in vraF gene, leading to decreased sensitivity to vancomycin and daptomycin. Furthermore, the mutation reduces autolysis of S. aureus and downregulates the expression of lytM, isaA, and atlA. Additionally, we observed that the mutant has a less net negative surface charge than wild-type strain. We also noted an increase in the expression of the dlt operon and mprF gene, which are associated with cell surface charge and serve to hinder the binding of cationic peptides by promoting electrostatic repulsion. Moreover, this mutation has been shown to enhance hemolytic activity, expand subcutaneous abscesses, reflecting an increased virulence. This study confirms the impact of a point mutation of VraF on S. aureus antibiotic resistance and virulence, contributing to a broader understanding of ABC transporter function and providing new targets for treating S. aureus infections.
Topics: Virulence; Staphylococcal Infections; Anti-Bacterial Agents; Vancomycin; Animals; ATP-Binding Cassette Transporters; Bacterial Proteins; Staphylococcus aureus; Microbial Sensitivity Tests; Vancomycin Resistance; Whole Genome Sequencing; Daptomycin; Mice; Autolysis; Humans; Point Mutation; Mutation; Female
PubMed: 38838390
DOI: 10.1016/j.ijmm.2024.151624 -
Journal of Ophthalmic Inflammation and... Jun 2024To report a case of endogenous endophthalmitis caused by the dematiaceous fungus Cladophialophora devriesii.
PURPOSE
To report a case of endogenous endophthalmitis caused by the dematiaceous fungus Cladophialophora devriesii.
METHODS
Observational case report and literature review.
CASE PRESENTATION
A 73-year-old female with a history of chronic obstructive pulmonary disease presented with a red and painful left eye. Examination revealed anterior segment inflammation and vitritis, indicative of endophthalmitis. She underwent core vitrectomy and intravitreal injection of vancomycin and amphotericin B. The vitreous sample showed inflammatory cells and fungal hyphae, and systemic amphotericin B and itraconazole were commenced for fungal endophthalmitis. Targeted amplification of the sample for bacterial DNA (V2-V3 region of 16 S rDNA) was negative, but fungal DNA targets (ITS1 and ITS2) were present, and their sequences were consistent with Cladophialophora devriesii. Phenotypic characterisation and sequencing of ITS1 and ITS2, carried out on cultured fungus from the sample, also revealed Cladophialophora devriesii. She received repeated intravitreal injections of voriconazole, and based on the antifungal susceptibility results, her systemic medication was changed to posaconazole. After 12 months, the eye showed no signs of inflammation, and posaconazole therapy was discontinued. After 3 months without antifungal medication, the inflammation recurred, and she was restarted on antifungal therapy for an additional 20 months. Another recurrence occurred 3 months after discontinuation of treatment, and a repeat vitreous sample confirmed the presence of Cladophialophora devriesii. She was started on isavuconazole, but developed seclusio pupillae and painful secondary glaucoma. Due to the duration and severity of the infection, the eye was enucleated. Histopathology revealed persistent fungal elements at the ciliary processes and the posterior lens surface.
CONCLUSIONS
This second reported case of endogenous endophthalmitis caused by Cladophialophora devriesii illustrates the role of vitreous sampling and molecular methods in diagnosis and treatment of fungal endophthalmitis. Despite early diagnosis and prolonged local and systemic antifungal therapy, it was not possible to achieve long-term control of the fungal infection.
PubMed: 38836962
DOI: 10.1186/s12348-024-00408-y -
JAC-antimicrobial Resistance Jun 2024A limited ability to eliminate drug-resistant strains of is a major contributor to the morbidity of TB. Complicating this problem, little is known about how drug...
BACKGROUND
A limited ability to eliminate drug-resistant strains of is a major contributor to the morbidity of TB. Complicating this problem, little is known about how drug resistance-conferring mutations alter the ability of to tolerate antibiotic killing. Here, we investigated if drug-resistant strains of have an altered ability to tolerate killing by cell wall-targeting inhibitors.
METHODS
Bacterial killing and MIC assays were used to test for antibiotic tolerance and synergy against a panel of drug-resistant strains.
RESULTS
Our results demonstrate that vancomycin and thioacetazone exhibit increased killing of diverse drug-resistant strains. Mutations in and increased vancomycin killing, which was consistent with vancomycin synergizing with thioacetazone and MmpL3-targeting inhibitors. In contrast, mutations in the operon conferred tolerance to vancomycin.
CONCLUSIONS
Overall, this work demonstrates how drug-resistant strains experience perturbations in cell-wall production that alters their tolerance to killing by cell wall-targeting inhibitors.
PubMed: 38836195
DOI: 10.1093/jacamr/dlae086 -
ACG Case Reports Journal Jun 2024Treating and coinfection presents a challenging clinical dilemma. Treating may increase the risk of , and antibiotics generally have been shown to increase the risk...
Treating and coinfection presents a challenging clinical dilemma. Treating may increase the risk of , and antibiotics generally have been shown to increase the risk of infection/recurrence. While it may be reasonable to delay treatment, this is especially challenging when there is an acute indication to treat such as peptic ulceration or bleeding. There are no guidelines on the management of and coinfection. We report a patient who had and recurrent coinfection and suggest a management algorithm based on literature review and our institutional experience. Our patient received quadruple therapy for along with vancomycin prophylaxis, taper, and a dose of bezlotoxumab and experienced good outcomes with resolution of his gastrointestinal bleeding and diarrhea.
PubMed: 38835648
DOI: 10.14309/crj.0000000000001369 -
Open Forum Infectious Diseases Jun 2024Non- non- (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients...
BACKGROUND
Non- non- (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described.
METHODS
We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood culture <14 days after clearance). Whole-genome sequencing was performed on all available NFF (n = 65).
RESULTS
Patients with hematological malignancies made up 56% of the cohort (77% had leukemia). The majority of solid malignancies (87%) were gastrointestinal in origin. The majority of infections (83%) originated from an intra-abdominal source. The most common NFF species were (50%) and (30%). Most (61%) patients received combination therapy. Bacteremia recurred in 4.3% of patients, there was a 30-day mortality of 23%, and 4.3% had microbiological failure. and isolates were genetically diverse with no spatiotemporal clustering to suggest a single strain. Frequencies of ampicillin resistance (4.3%) and daptomycin resistance (1.9%) were low. Patients with hematologic malignancy had infections with NFF enterococci that harbored more resistance genes than patients with solid malignancy ( = .005).
CONCLUSIONS
NFF bacteremia is caused by a heterogeneous population of isolates and is associated with significant mortality. Hematological malignancy is an important risk factor for infection with NFF resistant to multiple antibiotics.
PubMed: 38835498
DOI: 10.1093/ofid/ofae288