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2.
Front Cell Infect Microbiol ; 14: 1323054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567022

RESUMO

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.


Assuntos
Coxiella burnetii , Endocardite Bacteriana , Febre Q , Masculino , Humanos , Adulto , Febre Q/diagnóstico , Febre Q/tratamento farmacológico , Vancomicina/uso terapêutico , Doxiciclina/uso terapêutico , Hidroxicloroquina , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico
3.
Sr Care Pharm ; 39(5): 185-192, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38685618

RESUMO

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.


Assuntos
Antibacterianos , Vancomicina , Vancomicina/economia , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Estudos Retrospectivos , Humanos , Antibacterianos/economia , Antibacterianos/administração & dosagem , Composição de Medicamentos/economia , Fatores de Tempo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Custos de Medicamentos , Assistência de Longa Duração/economia , Farmacêuticos/economia
4.
Antimicrob Agents Chemother ; 68(5): e0159123, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38578080

RESUMO

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.


Assuntos
Antibacterianos , Vancomicina , Vancomicina/farmacocinética , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Humanos , Recém-Nascido , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Estudos Prospectivos , Masculino , Feminino , Software
5.
Antimicrob Agents Chemother ; 68(5): e0108523, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38606975

RESUMO

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.


Assuntos
Injúria Renal Aguda , Antibacterianos , Cefepima , Meropeném , Combinação Piperacilina e Tazobactam , Vancomicina , Humanos , Vancomicina/efeitos adversos , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Meropeném/administração & dosagem , Meropeném/uso terapêutico , Meropeném/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Cefepima/administração & dosagem , Cefepima/uso terapêutico , Cefepima/efeitos adversos , Combinação Piperacilina e Tazobactam/efeitos adversos , Combinação Piperacilina e Tazobactam/administração & dosagem , Combinação Piperacilina e Tazobactam/uso terapêutico , Masculino , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Feminino , Pessoa de Meia-Idade , Idoso , Área Sob a Curva , Quimioterapia Combinada , Estudos Retrospectivos , Sepse/tratamento farmacológico
6.
Prev Vet Med ; 226: 106170, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493570

RESUMO

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.


Assuntos
Anti-Infecciosos , Doenças do Cão , Infecções Estafilocócicas , Staphylococcus , Humanos , Animais , Cães , Vancomicina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Cloranfenicol/uso terapêutico , Lincosamidas/uso terapêutico , Fluoroquinolonas , beta-Lactamas/uso terapêutico , Gentamicinas/uso terapêutico , Macrolídeos/uso terapêutico , Testes de Sensibilidade Microbiana/veterinária , Doenças do Cão/epidemiologia , Doenças do Cão/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/tratamento farmacológico
7.
Clin Neurol Neurosurg ; 239: 108222, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484602

RESUMO

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.


Assuntos
Fusão Vertebral , Vancomicina , Humanos , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Pós , Vértebras Lombares/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Fusão Vertebral/efeitos adversos , Estudos Retrospectivos
8.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469769

RESUMO

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.


Assuntos
Infecções por Corynebacterium , Corynebacterium , Humanos , RNA Ribossômico 16S/genética , Corynebacterium/genética , Infecções por Corynebacterium/diagnóstico , Infecções por Corynebacterium/tratamento farmacológico , Infecções por Corynebacterium/microbiologia , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
9.
Sci Rep ; 14(1): 5947, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467719

RESUMO

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.


Assuntos
Infecções por Clostridium , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Adulto , Humanos , Vancomicina/uso terapêutico , Metronidazol/uso terapêutico , Estudos Retrospectivos , Polônia , Estudos Prospectivos , Doença Enxerto-Hospedeiro/etiologia , Leucemia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/etiologia
10.
Int Immunopharmacol ; 131: 111898, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513573

RESUMO

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.


Assuntos
Ácido Gálico/análogos & derivados , Insuficiência Renal , Vancomicina , Camundongos , Animais , Vancomicina/metabolismo , Vancomicina/farmacologia , Vancomicina/uso terapêutico , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , PPAR gama/metabolismo , Receptor 4 Toll-Like/metabolismo , Simulação de Acoplamento Molecular , Rim/patologia , Insuficiência Renal/metabolismo , Inflamação/tratamento farmacológico
11.
Aliment Pharmacol Ther ; 59(11): 1335-1349, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38534216

RESUMO

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.


Assuntos
Antibacterianos , Clostridioides difficile , Infecções por Clostridium , Transplante de Microbiota Fecal , Humanos , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/terapia , Infecções por Clostridium/prevenção & controle , Antibacterianos/uso terapêutico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/prevenção & controle , Fidaxomicina/uso terapêutico , Incidência , Vancomicina/uso terapêutico
12.
Diagn Microbiol Infect Dis ; 109(1): 116205, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38422663

RESUMO

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.


Assuntos
Fosfomicina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Ceftarolina , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Staphylococcus epidermidis/genética , Fosfomicina/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Drenagem , Testes de Sensibilidade Microbiana
13.
Res Social Adm Pharm ; 20(5): 498-505, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38365521

RESUMO

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.


Assuntos
Pessoal de Saúde , Vancomicina , Humanos , Vancomicina/uso terapêutico , Pessoal de Saúde/educação , Austrália
14.
ACS Appl Bio Mater ; 7(3): 1888-1898, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38349328

RESUMO

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.


Assuntos
Exossomos , Alho , Polietilenos , Polipropilenos , Infecções Estafilocócicas , Camundongos , Animais , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Staphylococcus aureus , Peróxido de Hidrogênio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Bandagens , Hidrogéis/uso terapêutico , Hidrogéis/farmacologia
15.
Antimicrob Agents Chemother ; 68(3): e0157923, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38349160

RESUMO

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.


Assuntos
Injúria Renal Aguda , Daptomicina , Terapia de Substituição Renal Híbrida , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Meropeném/uso terapêutico , Vancomicina/uso terapêutico , Cefepima/uso terapêutico , Daptomicina/uso terapêutico , Diálise Renal , Antibacterianos , Combinação Piperacilina e Tazobactam/uso terapêutico , Estado Terminal , Injúria Renal Aguda/tratamento farmacológico , Estudos Retrospectivos
16.
Antimicrob Agents Chemother ; 68(3): e0162123, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38364016

RESUMO

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.


Assuntos
Anti-Infecciosos , Clostridioides difficile , Infecções por Clostridium , Nucleosídeos de Purina , Humanos , Clostridioides , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Fidaxomicina/farmacologia , Fidaxomicina/uso terapêutico , Testes de Sensibilidade Microbiana
17.
J Antimicrob Chemother ; 79(4): 891-896, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38412336

RESUMO

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.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Glicopeptídeos , Testes de Sensibilidade Microbiana
19.
Artigo em Inglês | MEDLINE | ID: mdl-38385716

RESUMO

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.


Assuntos
Artrite Infecciosa , Infecções Relacionadas à Prótese , Humanos , Antibacterianos/uso terapêutico , Vancomicina/uso terapêutico , Infecções Relacionadas à Prótese/tratamento farmacológico , Cimentos Ósseos/uso terapêutico , Resultado do Tratamento , Artrite Infecciosa/induzido quimicamente , Artrite Infecciosa/tratamento farmacológico
20.
Clin Nephrol ; 101(4): 164-170, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38329920

RESUMO

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.


Assuntos
Diabetes Mellitus , Diálise Peritoneal Ambulatorial Contínua , Diálise Peritoneal , Peritonite , Adulto , Humanos , Ceftazidima/uso terapêutico , Cefazolina/uso terapêutico , Vancomicina/uso terapêutico , Levofloxacino/uso terapêutico , Estudos Retrospectivos , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Diálise Peritoneal/efeitos adversos , Peritonite/etiologia , Peritonite/microbiologia
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