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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 -
BMC Infectious Diseases Sep 2023Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM).
Empirical cefepime+vancomycin versus ceftazidime+vancomycin versus meropenem+vancomycin in the treatment of healthcare-associated meningitis: results of the multicenter ephesus study.
BACKGROUND
Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM).
MATERIALS/METHODS
This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018.
RESULTS
Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3-5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34).
CONCLUSIONS
Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.
Topics: Humans; Vancomycin; Meropenem; Cefepime; Ceftazidime; Retrospective Studies; Anti-Bacterial Agents; Meningitis; Bacteria; Staphylococcus; Delivery of Health Care; Ampicillin
PubMed: 37770836
DOI: 10.1186/s12879-023-08596-z -
Pharmaceutics Aug 2023Drug incompatibility is defined as a physical-chemical reaction between two or more injectable drugs and that results mainly in precipitation or insolubility. Several...
BACKGROUND
Drug incompatibility is defined as a physical-chemical reaction between two or more injectable drugs and that results mainly in precipitation or insolubility. Several strategies for reducing incompatibilities have been implemented empirically in intensive care units. However, these strategies have never been compared directly (and particularly in terms of the particulate load and drug mass flow rate) under standardized conditions. The objective of the present in vitro study was to evaluate the impact of various strategies for preventing incompatibility between simultaneously infused vancomycin and piperacillin/tazobactam.
METHODS
An in-line filter, a dilute vancomycin solution (5 mg/mL), and an alternative saline administration line were evaluated separately. The infusion line outlet was connected to a dynamic particle counter. The antibiotic concentration was measured in an HPLC-UV assay.
RESULT
The use of an in-line filter and an alternative saline administration route did not significantly reduce the particulate load caused by vancomycin-piperacillin/tazobactam incompatibility. Dilution of the vancomycin solution was associated with a significantly lower particulate load and maintenance of the vancomycin mass flow rate.
DISCUSSION
It is important to systematically compare the efficacy of strategies for preventing drug incompatibility. The use of diluted vancomycin solution gave the best results in the case of vancomycin-piperacillin/tazobactam incompatibility.
PubMed: 37631283
DOI: 10.3390/pharmaceutics15082069 -
Bone Research Oct 2023Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and...
Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S. aureus infection with osseointegration in murine models of implant-associated osteomyelitis.
Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve "target-and-release" drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.
Topics: Mice; Animals; Vancomycin; Methicillin; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Methicillin Resistance; Staphylococcal Infections; Osseointegration; Disease Models, Animal; Osteomyelitis
PubMed: 37848449
DOI: 10.1038/s41413-023-00287-4 -
Clinical Microbiology and Infection :... Mar 2024Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined.
OBJECTIVES
We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe.
METHODS
A systematic review and meta-analysis.
DATA SOURCES
MEDLINE, Embase, and grey literature for the period January 1990 to May 2022.
STUDY ELIGIBILITY CRITERIA
Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries.
PARTICIPANTS
Paediatric and adult patients diagnosed with drug-resistant BSI.
INTERVENTIONS
Not applicable.
ASSESSMENT OF RISK OF BIAS
An adapted version of the Joanna-Briggs Institute assessment tool.
METHODS OF DATA SYNTHESIS
Random-effect models were used to pool pathogen-specific burden estimates.
RESULTS
We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively).
CONCLUSIONS
Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions.
Topics: Adult; Humans; Child; Methicillin-Resistant Staphylococcus aureus; Bacteremia; Escherichia coli; Vancomycin; Anti-Bacterial Agents; Europe; Sepsis; Cephalosporins; Drug Resistance, Bacterial
PubMed: 37802750
DOI: 10.1016/j.cmi.2023.09.001 -
Acta Biomaterialia Jul 2023Fracture-related infection (FRI) is a devastating complication in orthopedic surgery. A recent study showed that FRI causes more severe infection and further delays...
Hydrogel delivery of DNase I and liposomal vancomycin to eradicate fracture-related methicillin-resistant staphylococcus aureus infection and support osteoporotic fracture healing.
Fracture-related infection (FRI) is a devastating complication in orthopedic surgery. A recent study showed that FRI causes more severe infection and further delays healing in osteoporotic bone. Moreover, bacterial biofilm formed on implants cannot be eradicated by systemic antibiotics, warranting novel treatments. Here, we developed a DNase I and Vancomycin hydrogel delivery vehicle to eradicate Methicillin-resistant Staphylococcus aureus (MRSA) infection in vivo. Vancomycin was encapsulated in liposomes, and DNase I and Vancomycin/liposomal-Vancomycin was loaded on thermosensitive hydrogel. In vitro drug release test showed a burst release of DNase I (77.2%) within 72 h and sustained release of Vancomycin (82.6%) up to day 14. The in vivo efficacy was evaluated in a clinically relevant ovariectomy (OVX) induced osteoporotic metaphyseal fracture model with MRSA infection, and a total of 120 Sprague Dawley rats were used. In the OVX with infection group, biofilm development caused a drastic inflammatory response, trabecular bone destruction, and non-union. In the DNase I and Vancomycin co-delivery hydrogel group (OVX-Inf-DVG), bacteria on bone and implant were eradicated. X-ray and micro-CT showed preservation of trabecular bone and bone union. HE staining showed the absence of inflammatory necrosis, and fracture healing was restored. The local elevation of TNF-α and IL-6 and increased number of osteoclasts were prevented in the OVX-Inf-DVG group. Our findings suggest that dual release of DNase I and Vancomycin initially followed by Vancomycin only later up to 14 days effectively eliminates MRSA infection, prevents biofilm development and provides a sterile environment to promote fracture healing in osteoporotic bone with FRI. STATEMENT OF SIGNIFICANCE: The biofilm on implants are difficult to eradicate, causing recurrent infection and non-union in fracture-related infection (FRI). Here we developed a hydrogel therapy with high in vivo efficacy to eliminate MRSA biofilm infection in a clinically-relevant FRI model in osteoporotic bone. By loading DNase I and vancomycin/liposomal-vancomycin on thermosensitive poly-(DL-lactic acidco-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel, a dual release of DNase I and Vancomycin was achieved whilst preserving enzyme activity. In this model, the progressive development of infection caused a drastic inflammatory response, osteoclastogenesis, trabecular bone destruction, and non-union of fracture. These pathological changes were successfully prevented by the dual delivery of DNase I and vancomycin. Our findings provide a promising strategy for FRI in osteoporotic bone.
Topics: Rats; Animals; Female; Vancomycin; Methicillin-Resistant Staphylococcus aureus; Osteoporotic Fractures; Liposomes; Fracture Healing; Hydrogels; Rats, Sprague-Dawley; Anti-Bacterial Agents; Biocompatible Materials; Osteoporosis; Staphylococcal Infections
PubMed: 37019168
DOI: 10.1016/j.actbio.2023.03.044 -
Clinical and Experimental Allergy :... Jan 2024Vancomycin, a glycopeptide antibiotic used for Gram-positive bacterial infections, has been linked with drug reaction with eosinophilia and systemic symptoms (DRESS) in...
BACKGROUND
Vancomycin, a glycopeptide antibiotic used for Gram-positive bacterial infections, has been linked with drug reaction with eosinophilia and systemic symptoms (DRESS) in HLA-A*32:01-expressing individuals. This is associated with activation of T lymphocytes, for which glycolysis has been isolated as a fuel pathway following antigenic stimulation. However, the metabolic processes that underpin drug-reactive T-cell activation are currently undefined and may shed light on the energetic conditions needed for the elicitation of drug hypersensitivity or tolerogenic pathways. Here, we sought to characterise the immunological and metabolic pathways involved in drug-specific T-cell activation within the context of DRESS pathogenesis using vancomycin as model compound and drug-reactive T-cell clones (TCCs) generated from healthy donors and vancomycin-hypersensitive patients.
METHODS
CD4+ and CD8+ vancomycin-responsive TCCs were generated by serial dilution. The Seahorse XFe Analyzer was used to measure the extracellular acidification rate (ECAR) as an indicator of glycolytic function. Additionally, T-cell proliferation and cytokine release (IFN-γ) assay were utilised to correlate the bioenergetic characteristics of T-cell activation with in vitro assays.
RESULTS
Model T-cell stimulants induced non-specific T-cell activation, characterised by immediate augmentation of ECAR and rate of ATP production (JATPglyc). There was a dose-dependent and drug-specific glycolytic shift when vancomycin-reactive TCCs were exposed to the drug. Vancomycin-reactive TCCs did not exhibit T-cell cross-reactivity with structurally similar compounds within proliferative and cytokine readouts. However, cross-reactivity was observed when analysing energetic responses; TCCs with prior specificity for vancomycin were also found to exhibit glycolytic switching after exposure to teicoplanin. Glycolytic activation of TCC was HLA restricted, as exposure to HLA blockade attenuated the glycolytic induction.
CONCLUSION
These studies describe the glycolytic shift of CD4+ and CD8+ T cells following vancomycin exposure. Since similar glycolytic switching is observed with teicoplanin, which did not activate T cells, it is possible the master switch for T-cell activation is located upstream of metabolic signalling.
Topics: Humans; Vancomycin; Teicoplanin; CD8-Positive T-Lymphocytes; Lymphocyte Activation; Cytokines; Glycolysis
PubMed: 38177093
DOI: 10.1111/cea.14423 -
Cureus Apr 2024Vancomycin is a bactericidal antibiotic used for various infections but can cause hypersensitivity reactions, including vancomycin flushing syndrome (VFS) and...
Vancomycin is a bactericidal antibiotic used for various infections but can cause hypersensitivity reactions, including vancomycin flushing syndrome (VFS) and anaphylaxis. VFS, previously known as red man syndrome, is a pseudoallergic reaction characterized by flushing, erythema, and pruritus. We present a case of VFS in a female patient with recurrent Methicillin-resistant Staphylococcus aureus (MRSA) infections receiving vancomycin for back abscesses. Following the second dose, she developed a pruritic rash on her face, neck, and torso, which resolved with treatment. The differential diagnosis included hydromorphone allergy, ruled out due to previous tolerance. Anaphylaxis was unlikely due to the absence of respiratory distress, hypotension, or angioedema. Management involved discontinuing vancomycin, administering corticosteroids and antihistamines, and monitoring for anaphylaxis. The patient was transferred for surgical intervention and alternative antibiotic therapy. This case highlights the importance of recognizing and managing VFS, the significance of differential diagnoses, and the need for enhanced documentation and clinical support in managing vancomycin hypersensitivity reactions.
PubMed: 38765435
DOI: 10.7759/cureus.58487 -
Gut Microbes 2024Up to 40% of transplant recipients treated long-term with tacrolimus (TAC) develop post-transplant diabetes mellitus (PTDM). TAC is an important risk factor for PTDM,...
Up to 40% of transplant recipients treated long-term with tacrolimus (TAC) develop post-transplant diabetes mellitus (PTDM). TAC is an important risk factor for PTDM, but is also essential for immunosuppression after transplantation. Long-term TAC treatment alters the gut microbiome, but the mechanisms of TAC-induced gut microbiota in the pathogenesis of PTDM are poorly characterized. Here, we showed that vancomycin, an inhibitor of bacterial beta-glucuronidase (GUS), prevents TAC-induced glucose disorder and insulin resistance in mice. Metagenomics shows that GUS-producing bacteria are predominant and flourish in the TAC-induced hyperglycemia mouse model, with upregulation of intestinal GUS activity. Targeted metabolomics analysis revealed that in the presence of high GUS activity, the hydrolysis of bile acid (BAs)-glucuronic conjugates is increased and most BAs are overproduced in the serum and liver, which, in turn, activates the ileal farnesoid X receptor (FXR) and suppresses GLP-1 secretion by L-cells. The GUS inhibitor vancomycin significantly eliminated GUS-producing bacteria and inhibited bacterial GUS activity and BAs levels, thereby enhancing L-cell GLP-1 secretion and preventing hyperglycemia. Our results propose a novel clinical strategy for inhibiting the bacterial GUS enzyme to prevent hyperglycemia without requiring withdrawal of TAC treatment. This strategy exerted its effect through the ileal bile acid-FXR-GLP-1 pathway.
Topics: Mice; Animals; Tacrolimus; Vancomycin; Immunosuppressive Agents; Gastrointestinal Microbiome; Hyperglycemia; Diabetes Mellitus; Bacteria; Glucuronidase; Bile Acids and Salts; Glucagon-Like Peptide 1
PubMed: 38332701
DOI: 10.1080/19490976.2024.2310277 -
Cell Reports Sep 2023Outcomes of severe bacterial infections are determined by the interplay between host, pathogen, and treatments. While human genomics has provided insights into host...
Outcomes of severe bacterial infections are determined by the interplay between host, pathogen, and treatments. While human genomics has provided insights into host factors impacting Staphylococcus aureus infections, comparatively little is known about S. aureus genotypes and disease severity. Building on the hypothesis that bacterial pathoadaptation is a key outcome driver, we developed a genome-wide association study (GWAS) framework to identify adaptive mutations associated with treatment failure and mortality in S. aureus bacteremia (1,358 episodes). Our research highlights the potential of vancomycin-selected mutations and vancomycin minimum inhibitory concentration (MIC) as key explanatory variables to predict infection severity. The contribution of bacterial variation was much lower for clinical outcomes (heritability <5%); however, GWASs allowed us to identify additional, MIC-independent candidate pathogenesis loci. Using supervised machine learning, we were able to quantify the predictive potential of these adaptive signatures. Our statistical genomics framework provides a powerful means to capture adaptive mutations impacting severe bacterial infections.
Topics: Humans; Vancomycin; Staphylococcus aureus; Anti-Bacterial Agents; Genome-Wide Association Study; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Bacteremia; Microbial Sensitivity Tests; Treatment Outcome
PubMed: 37703880
DOI: 10.1016/j.celrep.2023.113069