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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 -
SAGE Open Medical Case Reports 2024This case report highlights a severe eczematous rash manifesting broadly across the scalp, face, and neck of a 54-year-old female following a resolved herpes zoster...
This case report highlights a severe eczematous rash manifesting broadly across the scalp, face, and neck of a 54-year-old female following a resolved herpes zoster infection. Notably, such cutaneous reactions post-varicella zoster virus infection, which may present weeks to years after the acute phase, have been documented but remain poorly understood in their pathogenesis. This patient exhibited a blistering rash diagnosed as shingles with overlying cellulitis, initially treated with valacyclovir and cefalexin. Upon returning with a diffuse rash post-treatment, further examination and tests led to a differential diagnosis that most closely aligned with eczema exacerbation with superimposed bacterial infection, confirmed by the presence of methicillin-resistant . Treatment encompassed intravenous vancomycin, ciprofloxacin eye drops, topical hydrocortisone, betamethasone lotion, and gabapentin, leading to substantial improvement. This case underscores the complexity of diagnosing and managing cutaneous reactions post-varicella zoster virus infection and suggests a multimodal treatment approach may yield favorable outcomes.
PubMed: 38835426
DOI: 10.1177/2050313X241259273 -
MBio Jun 2024Bacterial communities are highly complex, with interaction networks dictating ecosystem function. Bacterial interactions are constrained by the spatial organization of...
UNLABELLED
Bacterial communities are highly complex, with interaction networks dictating ecosystem function. Bacterial interactions are constrained by the spatial organization of these microbial communities, yet studying the spatial organization of microbial communities at the single-cell level has been technically challenging. Here, we use the recently developed high-phylogenetic-resolution microbiota mapping by fluorescence hybridization technology to image the gut microbiota at the species and single-cell level. We simultaneously image 63 different bacterial species to spatially characterize the perturbation and recovery of the gut microbiota to ampicillin and vancomycin in the cecum and distal colon of mice. To decipher the biology in this complex imaging data, we developed an analytical framework to characterize the spatial changes of the gut microbiota to a perturbation. The three-tiered analytical approach includes image-level diversity, pairwise colocalization analysis, and hypothesis-driven neighborhood analysis. Through this workflow, we identify biogeographic and antibiotic-based differences in the spatial organization of the gut microbiota. We demonstrate that the cecal microbiota has increased micrometer-scale diversity than the colon at baseline and recovers better from perturbation. Also, we identify potential foundation and keystone species that have high baseline neighborhood richness and that are associated with recovery from antibiotics. Through this workflow, we add a spatial layer to the characterization of bacterial communities and progress toward a better understanding of bacterial interactions leading to improved microbiome modulation strategies.
IMPORTANCE
Antibiotics have broad off-target effects on the gut microbiome. When the microbial community is unable to recover from antibiotics, it can lead to increased susceptibility to gastrointestinal infections and increased risk of immunological and metabolic diseases. In this study, we work to better understand how the gut microbiota recovers from antibiotics by employing a recent technology to image the entire bacterial community at once. Through this approach, we characterize the spatial changes in the gut microbiota after treatment with model antibiotics in both the cecum and colon of mice. We find antibiotic- and biogeographic-dependent spatial changes between bacterial species and that many of these spatial colocalizations do not recover to baseline levels even 35 days after antibiotic administration.
PubMed: 38832780
DOI: 10.1128/mbio.00707-24