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2.
Front Cell Infect Microbiol ; 14: 1323054, 2024.
Article En | MEDLINE | ID: mdl-38567022

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.


Coxiella burnetii , Endocarditis, Bacterial , Q Fever , Male , Humans , Adult , Q Fever/diagnosis , Q Fever/drug therapy , Vancomycin/therapeutic use , Doxycycline/therapeutic use , Hydroxychloroquine , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy
3.
Sr Care Pharm ; 39(5): 185-192, 2024 May 01.
Article En | MEDLINE | ID: mdl-38685618

Objective Infections from methicillin-resistant Staphylococcus aureus are increasingly treated in longterm care facilities, but long-term care pharmacies face high costs in the provision of sterile vancomycin for intravenous administration. This study compares pharmaceutical costs of outsourced, compounded, and room temperature premixed vancomycin formulations in a long-term care pharmacy. Design This retrospective observational study reviewed 124 orders of vancomycin. Means for total pharmacy preparation time, pharmacist labor time, and extrapolated time over complete course of treatment were compared for three vancomycin preparations: outsourced, compounded by pharmacy, and room temperature premixed vancomycin formulations. Cost calculations were generated using ingredient costs as reported by the pharmacy and median pharmacist labor costs as published from national sources. Results Mean total preparation times and pharmacist preparation times were shortest for premixed vancomycin. Over full courses of treatment, mean pharmacy preparation time for compounded was 5 hours 3 minutes (mean of 28 treatments) and 2 hours 8 minutes for premixed (mean of 54 treatments). Data on pharmacist time in outsourced orders were not available. Total pharmacy costs were $993.94 for compounded vancomycin, $2220.34 for outsourced, and $809.36 for room temperature premixed vancomycin. Conclusion There were reduced preparation times for room temperature premixed vancomycin compared with compounded and outsourced formulations for skilled nursing facilities. As multiple drug-resistant organism infections are increasingly treated in long-term care, finding cost-effective approaches to medication provision from pharmacies is critical.


Anti-Bacterial Agents , Vancomycin , Vancomycin/economics , Vancomycin/administration & dosage , Vancomycin/therapeutic use , Retrospective Studies , Humans , Anti-Bacterial Agents/economics , Anti-Bacterial Agents/administration & dosage , Drug Compounding/economics , Time Factors , Methicillin-Resistant Staphylococcus aureus/drug effects , Drug Costs , Long-Term Care/economics , Pharmacists/economics
4.
Antimicrob Agents Chemother ; 68(5): e0159123, 2024 May 02.
Article En | MEDLINE | ID: mdl-38578080

We recruited 48 neonates (50 vancomycin treatment episodes) in a prospective study to validate a model-informed precision dosing (MIPD) software. The initial vancomycin dose was based on a population pharmacokinetic model and adjusted every 36-48 h. Compared with a historical control group of 53 neonates (65 episodes), the achievement of a target trough concentration of 10-15 mg/L improved from 37% in the study to 62% in the MIPD group (P = 0.01), with no difference in side effects.


Anti-Bacterial Agents , Vancomycin , Vancomycin/pharmacokinetics , Vancomycin/administration & dosage , Vancomycin/therapeutic use , Humans , Infant, Newborn , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Male , Female , Software
5.
Antimicrob Agents Chemother ; 68(5): e0108523, 2024 May 02.
Article En | MEDLINE | ID: mdl-38606975

Piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 with VAN > 72 hours were included. Patients with AKI prior to or within 48 hours of VAN or baseline CrCl of ≤30 mL/min were excluded. Four cohorts were defined: FEP/MEM/Tr, FEP/MEM/AUC, TZP/Tr, and TZP/AUC. A Cox Proportional Hazard Model was used to model AKI as a function of the incidence rate of at-risk days, testing monitoring strategy as a treatment effect modification. Multivariable logistic regression was used to model MAKE-30. Overall incidence of AKI was 18.6%; FEP/MEM/Tr = 115 (14.6%), FEP/MEM/AUC = 52 (14.9%), TZP/Tr = 189 (26%), and TZP/AUC = 96 (17.1%) (P < 0.001). Both drug group [(TZP; P = 0.0085)] and monitoring strategy [(Tr; P = 0.0007)] were highly associated with the development of AKI; however, the effect was not modified with interaction term [(TZP*Tr); 0.085)]. The odds of developing MAKE-30 were not different between any group and FEP/MEM/AUC. The effect of VAN/TZP on the development of AKI was not modified by the VAN monitoring strategy (AUC vs trough). MAKE-30 outcomes were not different among the four cohorts.


Acute Kidney Injury , Anti-Bacterial Agents , Cefepime , Meropenem , Piperacillin, Tazobactam Drug Combination , Vancomycin , Humans , Vancomycin/adverse effects , Vancomycin/administration & dosage , Vancomycin/therapeutic use , Meropenem/administration & dosage , Meropenem/therapeutic use , Meropenem/adverse effects , Acute Kidney Injury/chemically induced , Cefepime/administration & dosage , Cefepime/therapeutic use , Cefepime/adverse effects , Piperacillin, Tazobactam Drug Combination/adverse effects , Piperacillin, Tazobactam Drug Combination/administration & dosage , Piperacillin, Tazobactam Drug Combination/therapeutic use , Male , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Female , Middle Aged , Aged , Area Under Curve , Drug Therapy, Combination , Retrospective Studies , Sepsis/drug therapy
6.
Prev Vet Med ; 226: 106170, 2024 May.
Article En | MEDLINE | ID: mdl-38493570

Antimicrobial resistance within Staphylococcus pseudintermedius poses a significant risk for the treatment of canine pyoderma and as a reservoir for resistance and potential zoonoses, but few studies examine long-term temporal trends of resistance. This study assesses the antimicrobial resistance prevalence and minimum inhibitory concentration (MIC) trends in S. pseudintermedius (n=1804) isolated from canine skin samples at the Cornell University Animal Health Diagnostic Center (AHDC) between 2007 and 2020. Not susceptible (NS) prevalence, Cochran-Armitage tests, logrank tests, MIC50 and MIC90 quantiles, and survival analysis models were used to evaluate resistance prevalence and temporal trends to 23 antimicrobials. We use splines as predictors in accelerated failure time (AFT) models to model non-linear temporal trends in MICs. Multidrug resistance was common among isolates (47%), and isolates had moderate to high NS prevalence to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, the macrolides/lincosamides, the tetracyclines, and trimethoprim-sulfamethoxazole. However, low levels of NS to amikacin, rifampin, and vancomycin were observed. Around one third of isolates (38%) were found to be methicillin resistant S. pseudintermedius (MRSP), and these isolates had a higher prevalence of NS to all tested antimicrobials than methicillin susceptible isolates. Amongst the MRSP isolates, one phenotypically vancomycin resistant isolate (MIC >16 µg/mL) was identified, but genomic sequence data was unavailable. AFT models showed increasing MICs across time to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, and the macrolides/lincosamides, and decreasing temporal resistance (decreasing MICs) to doxycycline was observed amongst isolates. Notably, ATF modeling showed changes in MIC distributions that were not identified using Cochran-Armitage tests on prevalence, MIC quantiles, and logrank tests. Increasing resistance amongst these S. pseudintermedius isolates highlights the need for rational, empirical prescribing practices and increased antimicrobial resistance (AMR) surveillance to maintain the efficacy of current therapeutic agents. AFT models with non-linear predictors may be a useful, breakpoint-independent, surveillance tool alongside other modeling methods and antibiograms.


Anti-Infective Agents , Dog Diseases , Staphylococcal Infections , Staphylococcus , Humans , Animals , Dogs , Vancomycin/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Chloramphenicol/therapeutic use , Lincosamides/therapeutic use , Fluoroquinolones , beta-Lactams/therapeutic use , Gentamicins/therapeutic use , Macrolides/therapeutic use , Microbial Sensitivity Tests/veterinary , Dog Diseases/epidemiology , Dog Diseases/drug therapy , Staphylococcal Infections/epidemiology , Staphylococcal Infections/veterinary , Staphylococcal Infections/drug therapy
7.
Clin Neurol Neurosurg ; 239: 108222, 2024 Apr.
Article En | MEDLINE | ID: mdl-38484602

OBJECTIVE: This study aimed to assess the effectiveness of Vancomycin Power (VP) and the occurrence of resistant organisms after four-year of routine VP use. METHODS: The study included 1063 patients who underwent posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) between January 2010 and February 2020. Intrawound VP was applied to all instrumented fusions starting in January 2016. The patients were divided into two groups: those who did not apply VP (non-VP) (n = 605) between 2010 and 2015, and those who did apply VP (VP) (n = 458) between 2016 and 2020. The baseline characteristics, clinical symptoms, infection rate, and causative organisms were compared between the two groups. RESULTS: The rate of PSI was not significantly different between the non-VP group (1.32 %, n = 8) and the VP group (1.09 %, n = 5). Although adjusted by diabetes mellitus, VP still did not show statistical significance (OR = 0.757 (0.245-2.345), p = 0.630). There were no critical complications that were supposed to relation with vancomycin powder. In the 13 cases of PSI, seven pathogens were isolated, with a gram-negative organism identified in the non-VP group. However, the type of organism was not significantly different between the two groups. CONCLUSIONS: The use of intrawound VP may not affect the PSI and occurrence of resistant organism and may not cause critical complications. Therefore, clinicians may decide whether to use VP for preventing PSI not worrying about its safety.


Spinal Fusion , Vancomycin , Humans , Vancomycin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Powders , Lumbar Vertebrae/surgery , Surgical Wound Infection/epidemiology , Spinal Fusion/adverse effects , Retrospective Studies
8.
Clin Lab ; 70(3)2024 Mar 01.
Article En | MEDLINE | ID: mdl-38469769

BACKGROUND: The goal was to report a rare case of lymphadenitis caused by Corynebacterium tuberculostearicum, and the laboratory's coping approach in the isolation and identification of this rare pathogen to improve the understanding of the disease. METHODS: Lymph node biopsy was performed in a patient with suspected tuberculous lymphadenitis, and the biopsy tissue was isolated and cultured. RESULTS: The culture was Gram positive Corynebacterium, which was identified as Corynebacterium tuberculostearicum by microbial mass spectrometry and 16S rRNA gene sequencing. Antimicrobial susceptibility test showed that the drug was sensitive to daptomycin, doxycycline, gentamicin, linezolid, vancomycin, and meropenem, but resistant to ciprofloxacin, clindamycin, erythromycin, rifampicin, compound sulfamethoxazole, ceftriaxone, and cefepime. CONCLUSIONS: This is a case of Corynebacterium tuberculostearicum infection. Case reports of Corynebacterium tuberculostearicum infection are relatively rare in China. Through case study, we can provide help for laboratory isolation, identification, clinical diagnosis, and treatment.


Corynebacterium Infections , Corynebacterium , Humans , RNA, Ribosomal, 16S/genetics , Corynebacterium/genetics , Corynebacterium Infections/diagnosis , Corynebacterium Infections/drug therapy , Corynebacterium Infections/microbiology , Vancomycin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests
9.
Sci Rep ; 14(1): 5947, 2024 03 11.
Article En | MEDLINE | ID: mdl-38467719

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.


Clostridium Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia , Adult , Humans , Vancomycin/therapeutic use , Metronidazole/therapeutic use , Retrospective Studies , Poland , Prospective Studies , Graft vs Host Disease/etiology , Leukemia/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Clostridium Infections/drug therapy , Clostridium Infections/etiology
10.
Int Immunopharmacol ; 131: 111898, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38513573

Vancomycin (VCM) is the first-line antibiotic for severe infections, but nephrotoxicity limits its use. Leonurine (Leo) has shown protective effects against kidney damage. However, the effect and mechanism of Leo on VCM nephrotoxicity remain unclear. In this study, mice and HK-2 cells exposed to VCM were treated with Leo. Biochemical and pathological analysis and fluorescence probe methods were performed to examine the role of Leo in VCM nephrotoxicity. Immunohistochemistry, q-PCR, western blot, FACS, and Autodock software were used to verify the mechanism. The present results indicate that Leo significantly alleviates VCM-induced renal injury, morphological damage, and oxidative stress. Increased intracellular and mitochondrial ROS in HK-2 cells and decreased mitochondrial numbers in mouse renal tubular epithelial cells were reversed in Leo-administrated groups. In addition, molecular docking analysis using Autodock software revealed that Leo binds to the PPARγ protein with high affinity. Mechanistic exploration indicated that Leo inhibited VCM nephrotoxicity via activating PPARγ and inhibiting the TLR4/NF-κB/TNF-α inflammation pathway. Taken together, our results indicate that the PPARγ inhibition and inflammation reactions were implicated in the VCM nephrotoxicity and provide a promising therapeutic strategy for renal injury.


Gallic Acid/analogs & derivatives , Renal Insufficiency , Vancomycin , Mice , Animals , Vancomycin/metabolism , Vancomycin/pharmacology , Vancomycin/therapeutic use , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , PPAR gamma/metabolism , Toll-Like Receptor 4/metabolism , Molecular Docking Simulation , Kidney/pathology , Renal Insufficiency/metabolism , Inflammation/drug therapy
11.
Aliment Pharmacol Ther ; 59(11): 1335-1349, 2024 Jun.
Article En | MEDLINE | ID: mdl-38534216

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies. AIM: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections. METHODS: A narrative review was performed to evaluate the current literature between 1986 and 2023. RESULTS: The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon. CONCLUSION: Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future.


Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Fecal Microbiota Transplantation , Humans , Clostridium Infections/epidemiology , Clostridium Infections/drug therapy , Clostridium Infections/therapy , Clostridium Infections/prevention & control , Anti-Bacterial Agents/therapeutic use , Cross Infection/epidemiology , Cross Infection/drug therapy , Cross Infection/prevention & control , Fidaxomicin/therapeutic use , Incidence , Vancomycin/therapeutic use
12.
Diagn Microbiol Infect Dis ; 109(1): 116205, 2024 May.
Article En | MEDLINE | ID: mdl-38422663

External ventricular drain-related cerebrospinal fluid infection represents a fearsome complication of neurosurgical interventions. Although vancomycin represents the standard of care for methicillin-resistant CoNS healthcare-associated ventriculitis, resistance phenomena have been described. We reported a case of a persistent external ventricular fluid drain infection after device removal by pandrug-resistant Staphylococcus epidermidis successfully treated with intravenous ceftaroline in combination with fosfomycin and vancomycin. No evidence regarding pandrug-resistant S. epidermidis therapy currently exists to our knowledge. In this case, the S. epidermidis phenotype emerged during the therapy course, possibly due to initial device retention, biofilm formation and the host immune impaired response. Despite being poorly studied in vivo, ceftaroline may be considered an option when other alternatives are unavailable, thanks to its described activity against CoNS in vitro. This case extends the experience with ceftaroline for central nervous system infections suggesting it could also be used in high antimicrobial resistance settings for immunocompromised people.


Fosfomycin , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Ceftaroline , Vancomycin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Staphylococcus epidermidis/genetics , Fosfomycin/therapeutic use , Cephalosporins/therapeutic use , Staphylococcal Infections/drug therapy , Drainage , Microbial Sensitivity Tests
13.
Res Social Adm Pharm ; 20(5): 498-505, 2024 May.
Article En | MEDLINE | ID: mdl-38365521

BACKGROUND: Optimising the management of vancomycin by achieving target therapeutic concentrations early during therapy has been associated with reduced mortality and morbidity. Despite the availability of guidelines and training, the management of vancomycin remains suboptimal. OBJECTIVES: The primary outcome was the development of interventions and associated implementation strategies to optimise the management of vancomycin therapy. This paper describes how co-design process was used to build a theory informed intervention package, which was implemented across a wide range of in-patient hospital settings in Queensland, Australia. METHODS: This multiple methods study was conducted in four phases: 1) a baseline audit to identify the nature of the problem and associated determinants informed by stakeholder interviews 2) mapping these findings to the Theoretical Domains Framework (TDF) to identify behavioural correlates and modifiers 3) prioritising the behavioural modifiers and associated implementation strategies to inform a protype of the intervention in a series of co-design sessions and 4) implementing and evaluating the intervention package. The study was conducted across the four teaching hospitals in a large Queensland Hospital and Health Service across multiple healthcare disciplines namely nurses, doctors, and pharmacists. This intervention package was subsequently implemented across Queensland Health with the support of the local champions under the guidance of the steering group. RESULTS: Clinicians identified that a multifaceted intervention package and training which can be tailored to the health-care professional disciplines, would be best suited to shift clinician behaviour to align with guidelines. The findings from the co-design process aligned with theory-informed intervention package. Each of the intervention strategies varied in their frequency and popularity of use. CONCLUSIONS: The use of theory-informed and participatory approach assisted with the intervention development process and aligned the intervention content with the priorities of stakeholders. The TDF provided a structured process for developing intervention content which is both acceptable and useful to stakeholders and may improve the management of vancomycin.


Health Personnel , Vancomycin , Humans , Vancomycin/therapeutic use , Health Personnel/education , Australia
14.
ACS Appl Bio Mater ; 7(3): 1888-1898, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38349328

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.


Exosomes , Garlic , Polyethylenes , Polypropylenes , Staphylococcal Infections , Mice , Animals , Vancomycin/pharmacology , Vancomycin/therapeutic use , Staphylococcus aureus , Hydrogen Peroxide/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/drug therapy , Bandages , Hydrogels/therapeutic use , Hydrogels/pharmacology
15.
Antimicrob Agents Chemother ; 68(3): e0157923, 2024 Mar 06.
Article En | MEDLINE | ID: mdl-38349160

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin-tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life (t1/2) on-SLED and off-SLED, and the fraction of removal by SLED (fD). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin-tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10-211). The t1/2 on-SLED was substantially lower than the off-SLED t1/2 for all antimicrobials, and the SLED fD varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.


Acute Kidney Injury , Daptomycin , Hybrid Renal Replacement Therapy , Adult , Humans , Male , Middle Aged , Aged , Female , Meropenem/therapeutic use , Vancomycin/therapeutic use , Cefepime/therapeutic use , Daptomycin/therapeutic use , Renal Dialysis , Anti-Bacterial Agents , Piperacillin, Tazobactam Drug Combination/therapeutic use , Critical Illness , Acute Kidney Injury/drug therapy , Retrospective Studies
16.
Antimicrob Agents Chemother ; 68(3): e0162123, 2024 Mar 06.
Article En | MEDLINE | ID: mdl-38364016

Antimicrobial resistance is emerging in clinical strains of Clostridioides difficile. Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent in vitro activity against wild-type, susceptible strains but its effect on C. difficile strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested. The primary objective of this study was to test the antibacterial properties of IBZ against multidrug-resistant C. difficile strains. The in vitro activity, bactericidal, and time-kill activity of IBZ versus comparators were evaluated against 100 clinical strains of which 59 had reduced susceptibility to other C. difficile antibiotics. Morphologic changes against a multidrug resistance strain were visualized by light and scanning electron microscopy. The overall IBZ MIC50/90 values (µg/mL) for evaluated C. difficile strains were 4/8, compared with 2/4 for VAN, 0.5/1 for FDX, and 0.25/4 for MTZ. IBZ MIC50/90 values did not differ based on non-susceptibility to antibiotic class or number of classes to which strains were non-susceptible. IBZ bactericidal activity was similar to the minimum inhibitory concentration (MIC) and maintained in wild-type and non-susceptible strains. Time-kill assays against two laboratory wild-type and two clinical non-susceptible strains demonstrated sustained IBZ activity despite reduced killing by comparator antibiotics for IBZ and VAN non-susceptible strains. Microscopy visualized increased cell lengthening and cellular damage in multidrug-resistant strains exposed to IBZ sub-MIC concentrations. This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile.


Anti-Infective Agents , Clostridioides difficile , Clostridium Infections , Purine Nucleosides , Humans , Clostridioides , Clostridium Infections/drug therapy , Clostridium Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Vancomycin/pharmacology , Vancomycin/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Fidaxomicin/pharmacology , Fidaxomicin/therapeutic use , Microbial Sensitivity Tests
17.
J Antimicrob Chemother ; 79(4): 891-896, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38412336

OBJECTIVES: This study aims to elucidate the genomic dynamics driving the emergence of antimicrobial resistance (AMR), with a specific focus on the interplay between AMR and antimicrobial usage. METHODS: We conducted a comprehensive analysis using a ST239 methicillin-resistant Staphylococcus aureus (MRSA) dataset over a continuous 12-year period from a single hospital. Genomic analyses were performed tracking the changes in MRSA populations, particularly the emergence of reduced vancomycin susceptibility, and assessing the impact of glycopeptide use on these emergence events. RESULTS: Our findings reveal a significant correlation between hospital glycopeptide usage and the selection of MRSA strains with reduced vancomycin susceptibility. Genomic analyses provided insights into the molecular mechanisms driving resistance emergence, including the slowing of the molecular clock rate in response to heightened antimicrobial consumption. CONCLUSIONS: In conclusion, this study the highlights the complex dynamics between AMR and antimicrobial use at the hospital level. The observed correlation between antimicrobial consumption and the development of less susceptible MRSA strains underscores the importance of antimicrobial stewardship programmes and the establishment of optimal consumption thresholds for mitigating AMR effectively.


Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Methicillin-Resistant Staphylococcus aureus/genetics , Vancomycin/pharmacology , Vancomycin/therapeutic use , Staphylococcal Infections/drug therapy , Glycopeptides , Microbial Sensitivity Tests
19.
Article En | MEDLINE | ID: mdl-38385716

INTRODUCTION: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success. METHODS: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure. RESULTS: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147). CONCLUSION: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure.


Arthritis, Infectious , Prosthesis-Related Infections , Humans , Anti-Bacterial Agents/therapeutic use , Vancomycin/therapeutic use , Prosthesis-Related Infections/drug therapy , Bone Cements/therapeutic use , Treatment Outcome , Arthritis, Infectious/chemically induced , Arthritis, Infectious/drug therapy
20.
Clin Nephrol ; 101(4): 164-170, 2024 Apr.
Article En | MEDLINE | ID: mdl-38329920

INTRODUCTION: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime. MATERIALS AND METHODS: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed. RESULTS: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression. CONCLUSION: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.


Diabetes Mellitus , Peritoneal Dialysis, Continuous Ambulatory , Peritoneal Dialysis , Peritonitis , Adult , Humans , Ceftazidime/therapeutic use , Cefazolin/therapeutic use , Vancomycin/therapeutic use , Levofloxacin/therapeutic use , Retrospective Studies , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Drug Therapy, Combination , Anti-Bacterial Agents/therapeutic use , Peritoneal Dialysis/adverse effects , Peritonitis/etiology , Peritonitis/microbiology
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