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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 -
Heliyon May 2024The challenges facing metallic implants for reconstructive surgery include the leaching of toxic metal ions, a mismatch in elastic modulus between the implant and the...
The challenges facing metallic implants for reconstructive surgery include the leaching of toxic metal ions, a mismatch in elastic modulus between the implant and the treated tissue, and the risk of infection. These problems can be addressed by passivating the metal surface with an organic substrate and incorporating antibiotic molecules. Nitinol (NiTi), a nickel-titanium alloy, is used in devices for biomedical applications due to its shape memory and superelasticity. However, unmodified NiTi carries a risk of localized nickel toxicity and inadequately supports angiogenesis or neuroregeneration due to limited cell adhesion, poor biomineralization, and little antibacterial activity. To address these challenges, NiTi nanoparticles were modified using self-assembled phosphonic acid monolayers and functionalized with the antibiotics ceftriaxone and vancomycin via the formation of an amide. Surface modifications were monitored to confirm that phosphonic acid modifications were present on NiTi nanoparticles and 100% of the samples formed ordered films. Modifications were stable for more than a year. Elemental composition showed the presence of nickel, titanium, and phosphorus (1.9% for each sample) after surface modifications. Dynamic light scattering analysis suggested some agglomeration in solution. However, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy confirmed a particle size distribution of <100 nm, the even distribution of nanoparticles on coverslips, and elemental composition before and after cell culture. B35 neuroblastoma cells exhibited no inhibition of survival and extended neurites of approximately 100 μm in total length when cultured on coverslips coated with only poly-l-lysine or with phosphonic acid-modified NiTi, indicating high biocompatibility. The ability to support neural cell growth and differentiation makes modified NiTi nanoparticles a promising coating for surfaces in metallic bone and nerve implants. NiTi nanoparticles functionalized with ceftriaxone inhibited and at doses of 375 and 750 μg whereas the growth of was inhibited by a dose of only 37.5 μg. NiTi-vancomycin was effective against at all doses even after mammalian cell culture. These are common bacteria associated with infected implants, further supporting the potential use of functionalized NiTi in coating reconstructive implants.
PubMed: 38831845
DOI: 10.1016/j.heliyon.2024.e31434 -
Journal of Medical Case Reports Jun 2024Although the correlation between liver toxicity and vancomycin is generally considered low, it has been observed that the use of vancomycin can lead to abnormal liver...
BACKGROUND
Although the correlation between liver toxicity and vancomycin is generally considered low, it has been observed that the use of vancomycin can lead to abnormal liver function indicators, such as elevated aspartate aminotransferase, alanine aminotransferase, alpha fetoprotein, and jaundice. To further understand the clinical features associated with vancomycin-induced liver toxicity and to provide clinical guidance, we conducted an analysis of the characteristics and clinical manifestations of vancomycin-induced liver injury.
METHODS
Patients with liver function injury who received vancomycin treatment at the Third Xiangya Hospital of Central South University and Hunan Maternal and Child Health Hospital between 2016 and 2021 were selected for retrospective analysis of their general characteristics, vancomycin course, dose, liver function index, severity of liver injury, and concomitant medications.
RESULTS
Of the 4562 patients who received vancomycin, 17 patients were finally included, with an incidence rate of 0.37%. Of these patients, 12 were male (70.6%) and 5 were female (29.4%), ranging in age from 17 to 84 years with a mean average age of 45.41 ± 20.405 years. All patients were evaluated using Naranjo's score, with score ≥ 3. The dosage, time, and plasma concentration of vancomycin were analyzed and it was found that nine patients (52.94%) had abnormal liver function when initially given a dose of 1 g every 12 hours. In total, 14 patients (82.35%) with liver injury were taking vancomycin in combination with two to four drugs, and severe liver injury occurred in patients taking vancomycin in combination with two drugs. The occurrence time of liver injury was 2-12 days after starting vancomycin, with a mean of 4.53 ± 2.401 days. Of these patients, 16 patients (94.1%) showed liver function abnormalities within 7 days of taking the drug, and 2 patients with grade 3-4 liver injury both showed liver function abnormalities within 3 days of taking the drug. Only 4 of the 17 patients (23.53%) had vancomycin blood concentrations within the normal range, and there was no correlation found between blood concentration and severity of liver injury. Analysis of the correlation between the severity of liver injury and vancomycin showed that none of the patients had allergies such as rash, two patients (11.76%) had jaundice, and fatigue occurred in five patients (29.41%). The remaining ten patients (58.82%) had no symptoms related to liver injury. All 17 patients had abnormal aspartate aminotransferase/alanine aminotransferase levels and 9 patients also had abnormal bilirubin levels. In 15 patients (88.24%), the severity of liver injury was grade 1, indicating mild liver injury, and no correlation was observed between the severity of liver injury and creatinine. Of the 17 patients, 1 patient received no intervention, 4 patients stopped taking vancomycin after developing liver injury, 1 patient reduced the dose, and 11 patients (64.7%) were treated with hepatic protectant.
CONCLUSION
Although the study concluded that the incidence of liver injury was not high, the liver toxicity of vancomycin should still be considered and liver function indicators should be monitored during the clinical use of vancomycin.
Topics: Humans; Vancomycin; Female; Chemical and Drug Induced Liver Injury; Male; Middle Aged; Adult; Retrospective Studies; Anti-Bacterial Agents; Adolescent; Aged; Young Adult; Aged, 80 and over; Liver Function Tests
PubMed: 38831463
DOI: 10.1186/s13256-024-04574-4 -
Environmental Health Insights 2024Nosocomial pathogens are known to exacerbate morbidity and mortality in contemporary critical healthcare. Hospital fomites, which include inanimate surfaces, have been... (Review)
Review
BACKGROUND
Nosocomial pathogens are known to exacerbate morbidity and mortality in contemporary critical healthcare. Hospital fomites, which include inanimate surfaces, have been identified as "breeding grounds" for pathogens that cause nosocomial infections. This systematic review aimed to deliver incisive insights on nosocomial pathogens in intensive care units (ICUs) and the role of fomites as potential reservoirs for their transmission.
METHOD
An extensive exploration of electronic databases, including PubMed and Scopus, from 1990 to 2023, was carried out between 25 and 29 May 2023, per standard PRISMA guidelines. Information were extracted from articles that reported on fomites in the ICU. Studies that did not quantitatively report the fomite contamination, and those that exclusively took samples from patients in the ICU were excluded from the analysis.
RESULTS
About 40% of the total samples collected on fomites from all the studies yielded microbial growth, with species of being the most predominant. Other prevalent microbes were , , , spp., sp., and sp. The neonatal intensive care unit (NICU) had the highest proportion of contaminated fomites. Among known fomites, the sphygmomanometer exhibited a 100% detection rate of nosocomial pathogens. This included , , coagulase-negative (CoNS), , and Multidrug-resistant (MDR) bacteria, such as methicillin-resistant (MRSA), vancomycin-resistant (VRE), extended-spectrum beta-lactamase (ESBL)-producing , and MDR were commonly isolated on fomites in the ICUs.
CONCLUSION
Many fomites that are readily used in patient care in the ICU harbour nosocomial pathogens. The most common fomite appeared to be mobile phones, sphygmomanometers, and stethoscopes, with being the most common contaminant. Consequently, the need for rigorous disinfection and sterilization protocols on fomites in the ICU cannot be overemphasized. Additionally, heightened awareness on the subject among health professionals is crucial to mitigating the risk and burden of nosocomial infections caused by drug-resistant bacteria.
PubMed: 38828046
DOI: 10.1177/11786302241243239