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Johnson-Louis KLT, Nguyen ML, K Zvonar R. A Comparison of Vancomycin Area Under the Curve and Trough Concentration in Specific Populations. J Pharm Pract 2025; 38:305-313. [PMID: 39348402 DOI: 10.1177/08971900241287274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Abstract
Background: Vancomycin is an antibiotic known to cause nephrotoxicity, particularly when a vancomycin trough of 15 to 20 mg/L, a surrogate for an area under the curve (AUC) of at least 400 mgh/L, is targeted. Although monitoring vancomycin AUC is more resource intensive, it may especially benefit populations expected to be at higher risk of nephrotoxicity. Objective: To describe the proportion of discordance between vancomycin AUC and trough concentration in targeted high-risk populations. Methods: A prospective observational review was conducted on adults receiving intravenous vancomycin for more than 48 hours from May 9 to June 3, 2022. Patients included were elderly, obese, had renal dysfunction, and/or received 4 grams or more of vancomycin daily with a pending vancomycin trough concentration. A peak concentration was ordered by a project team member to calculate AUC to assess discordance. Results: A total of 47 patients were included with 87 vancomycin minimum concentration (Cmin)/AUC pairs analyzed. Discordance was observed in 52.9% of Cmin/AUC pairs in the entire cohort. The majority (79%) of the 43 Cmin levels <15 mg/L had an associated AUC >400 mgh/L and 57% of 21 Cmin levels within the 15 to 20 mg/L range had an AUC >600 mgh/L. Conclusion: A high degree of discordance between vancomycin Cmin and AUC was present in patients considered to be at high risk of nephrotoxicity. Monitoring vancomycin AUC in these patients may reduce the risk of nephrotoxicity.
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Affiliation(s)
| | - My-Linh Nguyen
- Pharmacy Department, The Ottawa Hospital, Ottawa ON, Canada
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Tan L, Chao A, Liang H, Liu Q, Han M, Guan Y. Vancomycin individual dosing regimens via Bayesian simulation: a 5-year retrospective study on preterm and term neonates. Per Med 2025:1-9. [PMID: 40304294 DOI: 10.1080/17410541.2025.2499442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 04/25/2025] [Indexed: 05/02/2025]
Abstract
AIM Vancomycin dosing in neonates is challenging due to developmental pharmacokinetic variability. The study was to characterize vancomycin pharmacokinetics in a large cohort of preterm and term neonates and develop individualized dosing regimens. MATERIALS & METHODS A 5-year retrospective study of a cohort of 255 neonates was included. RESULTS An allometric one-compartment model with first-order elimination best described the vancomycin concentrations. The population pharmacokinetic estimates (between subject variability) of clearance (CL) and volume of distribution (V) were 2.58 L·h-1·70 kg-1 (9.00 %) and 52.09 L·70 kg-1 (29.00%), respectively. CL and V were significantly influenced by body weight and postmenstrual age. Vancomycin CL reached 50% of adult values at 43.6 weeks PMA (a sigmoid Emax model). Renal maturation, estimated by creatinine production rate, was a significant covariate. Bayesian-guided individualized dosage regimens were developed and evaluated. CONCLUSIONS Vancomycin overdosage should be avoided in very young premature babies (PMA = 25 weeks). Optimization of efficacy while minimizing toxicity of vancomycin in preterm and term neonates is needed, especially guided by personalized body weight, postmenstrual age, and renal function.
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Affiliation(s)
- Lu Tan
- Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
| | - Ailing Chao
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Heng Liang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Qian Liu
- Department of Pharmacy, The Second Affiliated Hospital of Guizhou Medical University, Kaili, Guizhou, China
| | - Minzhen Han
- Department of Pharmacy, The Second Affiliated Hospital of Guizhou Medical University, Kaili, Guizhou, China
| | - Yanping Guan
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China
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3
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Okuwaki T, Kobayashi M, Kikuchi R, Tomoda Y, Ogawa M, Kasugai K, Seto Y, Tomizawa A, Otori K. Vancomycin-associated acute kidney injury in underweight patients: a propensity score matching analysis. Int Urol Nephrol 2025; 57:1329-1336. [PMID: 39652231 DOI: 10.1007/s11255-024-04306-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 11/22/2024] [Indexed: 03/14/2025]
Abstract
PURPOSE To investigate the effect of being underweight on the incidence of vancomycin-associated acute kidney injury (AKI) using propensity score matching analysis. METHODS This study is a retrospective analysis of patients who received vancomycin and had their serum concentration measured at Kitasato University Hospital between January 1, 2016 and December 31, 2020. Patients were divided into underweight and non-underweight groups based on body mass index (BMI), and propensity score matching analysis was used to evaluate whether underweight affected the incidence of acute kidney injury. RESULTS 480 patients met the selection criteria, and 111 patients from each group (BMI < 18.5 and BMI ≥ 18.5) were successfully matched using propensity score matching. After matching, there were no differences in non-physical characteristics between the two groups. The incidence of AKI was 23.4% (26 of 111) in the BMI < 18.5 group and 37.8% (42 of 111) in the BMI ≥ 18.5 group, with the BMI < 18.5 group having a significantly lower incidence. The odds ratio was 0.503 [95% CI 0.281-0.900]. CONCLUSION This study showed that underweight patients (BMI < 18.5) had a significantly lower incidence of vancomycin-associated AKI compared to those with BMI ≥ 18.5. As there have been no previous reports on the association between underweight and vancomycin-associated AKI, this study provides novel insights.
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Affiliation(s)
- Tatsuya Okuwaki
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
| | - Masahiro Kobayashi
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan.
| | - Rino Kikuchi
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Yoshinori Tomoda
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Moeka Ogawa
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Kumi Kasugai
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Yoshinori Seto
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
| | - Atsushi Tomizawa
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- Department of Patient Safety, Kitasato University Hospital, Sagamihara, Japan
| | - Katsuya Otori
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- School of Pharmacy, Kitasato University, Tokyo, Japan
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Guidry CM, Siegrist EA, Neely SB, Springer L, White BP. Rates of Acute Kidney Injury Utilizing Area Under the Concentration-Time Curve Versus Trough-Based Vancomycin Dosing Strategies in Patients With Obesity. Open Forum Infect Dis 2025; 12:ofaf205. [PMID: 40242067 PMCID: PMC12002009 DOI: 10.1093/ofid/ofaf205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 04/01/2025] [Indexed: 04/18/2025] Open
Abstract
Background Vancomycin is commonly utilized for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Dosing recommendations for vancomycin have shifted in recent years to favor area under the concentration-time curve (AUC) instead of trough-based dosing strategies to decrease vancomycin exposure and rates of acute kidney injury (AKI). However, little data exist on the safety and efficacy of AUC-based dosing in patients with obesity. Methods This was a single-center retrospective cohort study conducted between 1 January 2014 and 31 December 2022. Adult patients aged ≥18 years were included if they were obese and received vancomycin for treatment of a severe MRSA infection for at least 72 hours. The primary outcome was incidence of AKI based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results After initial screening, 398 patients were included, with 230 in the trough group and 168 in the AUC group. Rates of AKI were lower in the AUC group compared to the trough group (11.3% vs 25.2%, P < .001). After adjusting for potential confounders, logistic regression maintained a reduction in AKI with AUC-based dosing for cumulative doses less than the median of 10 250 mg (odds ratio, 0.47 [95% confidence interval, .25-.88]) but not for doses above. Rates of initial target attainment were also higher with AUC-based dosing (50.0% vs 23.9%, P < .001). Conclusions Patients with obesity receiving vancomycin for treatment of severe MRSA infections experienced lower rates of AKI when utilizing an AUC- versus trough-based dosing strategy.
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Affiliation(s)
- Corey M Guidry
- Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma, USA
| | | | - Stephen B Neely
- Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma, USA
| | - Lyndee Springer
- Department of Pharmacy, United States Public Health Service Lawton Indian Hospital, Lawton, Oklahoma, USA
| | - Bryan P White
- Department of Pharmacy, OU Health, Oklahoma City, Oklahoma, USA
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Yahia R, Hassan GG, Abo-Youssef AM, Mahmoud HM. Piribedil and thymol mitigate vancomycin-evoked nephrotoxicity in rats through modulation of Keap-1/Nrf2/HO-1 and NF-κB/Bax/caspase 3 signalings. Drug Chem Toxicol 2025:1-16. [PMID: 40143539 DOI: 10.1080/01480545.2025.2481857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 02/18/2025] [Accepted: 03/15/2025] [Indexed: 03/28/2025]
Abstract
Nephrotoxicity is a sign in which endogenous or exogenous toxicants have damaged the kidney-specific detoxification and excretion processes. Vancomycin (VAN) exposure mostly causes kidney damage and a loss of body homeostasis regulation. This study aimed to investigate the protective effects of piribedil and thymol and its basic mechanisms against nephrotoxicity caused by VAN. Randomly, the animals were categorized into six groups (n = 8). For 7 d, Group I only received vehicles, Group II received piribedil (5 mg/kg/once daily, i.p.), Group III received thymol (25 mg/kg/once daily, i.p), Group IV was administered a single daily dose of VAN (200 mg/kg, i.p.), VAN+ piribedil was administered to Group V, and VAN + thymol was administered to Group VI. The findings showed that piribedil or thymol improved renal function parameters by an increase in serum albumin level in parallel to a decrease in serum creatinine and blood urea nitrogen (BUN) levels in addition to decreased levels of KIM-1 and serum cystatin C. Furthermore, enhanced oxidative stress biomarkers as GSH, myeloperoxidase (MPO), and malondialdehyde (MDA) as well as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), indicators of inflammatory mediators, were markedly reduced compared to VAN group. Moreover, piribedil or thymol markedly improved the histopathological aberrations provoked by VAN, increased the Nrf-2 and HO-1 renal protein expressions and reduced VAN-induced elevation of Keap-1 protein expression. In addition, NF-kB, Bax, and caspase 3 expression levels were considerably declined after piribedil or thymol co-treatment. These findings revealed that co-administration of piribedil or thymol with VAN may be a sensible therapeutic approach for reducing renal intoxication caused by VAN.
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Affiliation(s)
- Rania Yahia
- Department of Pharmacology, Egyptian Drug Authority, Cairo, Egypt
| | - Gehad Gamal Hassan
- Central Administration of Pharmaceutical Products, Egyptian Drug Authority, Cairo, Egypt
| | - Amira M Abo-Youssef
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Heba M Mahmoud
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
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Matsuki Y, Kozima Y, Yanagi M, Sako KI, Watanabe T, Yasuno N, Watanabe S. Vancomycin dosing design method considering risk factors for nephrotoxicity. J Pharm Health Care Sci 2025; 11:14. [PMID: 39985007 PMCID: PMC11846157 DOI: 10.1186/s40780-025-00416-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 01/31/2025] [Indexed: 02/23/2025] Open
Abstract
BACKGROUND Vancomycin (VCM) induces nephrotoxicity in a dose-dependent manner, and patients with risk factors for nephrotoxicity have been reported to develop nephrotoxicity even within the effective concentration range. In the present study, we investigated measures to set an appropriate AUCss for each case by assessing the risk of developing nephrotoxicity using logistic regression curves, separating patients into a High-risk group with risk factors associated with nephrotoxicity when VCM is used and a Low-risk group without risk factors. METHODS A multivariate logistic regression analysis was used to identify risk factors for nephrotoxicity. The AUCss threshold was selected by a CART analysis and ROC curves, and a logistic regression analysis was used to examine the relationship between AUCss and the probability of developing nephrotoxicity. RESULTS AND DISCUSSION The incidence of nephrotoxicity was 31.7% (33/104) in the High-risk group and 13.0% (14/108) in the Low-risk group, and was significantly higher in the former (p = 0.001). The AUCss threshold was set at 575 mg·h/L for the High-risk group and 650 mg·h/L for the Low-risk group. The probability of developing nephrotoxicity in the High-risk group (104 patients) was high: AUCss 400 mg·h/L (16.8%), 500 mg·h/L (23.3%), and 575 mg·h/L (29.3%). The target concentration range was newly set at 400 ≤ AUCss < 500, suggesting that the target AUCss needs to be considered for each patient based on the balance between therapeutic efficacy and the prevention of adverse effects. The probability of developing nephrotoxicity in the Low-risk group (108 patients) was AUCss 500 mg·h/L (4.7%), 575 mg·h/L (8.4%), and 650 mg·h/L (14.6%). Since the Low-risk group has a high safety profile, the target concentration range was newly set at 400 ≤ AUCss < 650, suggesting the safe administration of the drug up to AUCss 650 mg·h/L while aiming for AUCss 600 mg·h/L from the initial dose design. CONCLUSION In the present study, the risk of nephrotoxicity for each AUCss was quantitatively analyzed using logistic regression curves for the High- and Low-risk groups. This allowed for the proposal of strategic individual target concentrations based on the balance between risk and benefit.
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Affiliation(s)
- Yoshihiko Matsuki
- Center for Promotion of Pharmaceutical Education & Research, Teiyo University, Tokyo, Japan.
- Department of Pharmacy, Kashiwa Kousei General Hospital, Ageo Medical Group, Ageo, Japan.
| | - Yutaro Kozima
- Department of Pharmacy, Kashiwa Kousei General Hospital, Ageo Medical Group, Ageo, Japan
| | - Megumi Yanagi
- Department of Pharmacy, Kashiwa Kousei General Hospital, Ageo Medical Group, Ageo, Japan
| | - Ken-Ichi Sako
- Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan
| | - Tamaki Watanabe
- Laboratory of Hospital Pharmacy, Teikyo University, Tokyo, Japan
- Department of Pharmacy, Teikyo University Hospital, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Nobuhiro Yasuno
- Laboratory of Hospital Pharmacy, Teikyo University, Tokyo, Japan
- Department of Pharmacy, Teikyo University Hospital, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Shigekazu Watanabe
- Center for Promotion of Pharmaceutical Education & Research, Teiyo University, Tokyo, Japan
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Epperson AB, Awad ME, Gorman M, Loker K, Alfonso NA, Stoneback JW. Clinical practice guidelines for antimicrobial-loaded cements and beads in orthopedic trauma and arthroplasty. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY & TRAUMATOLOGY : ORTHOPEDIE TRAUMATOLOGIE 2024; 35:25. [PMID: 39585403 DOI: 10.1007/s00590-024-04132-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 10/26/2024] [Indexed: 11/26/2024]
Abstract
PURPOSE Implants in orthopedic trauma and arthroplasty surgery establish a milieu conducive to biofilm formation. Antimicrobial-loaded cements (ABCs) and beads have become popular in treating acute and chronic orthopedic surgery-related infections. The growing incidence of antimicrobial resistance has necessitated the exploration of alternative antibiotic medications. This review aims to demonstrate meaningful clinical decision-making guidance for orthopedic surgeons in approaching the management of these complex infections. METHODS This study protocol was conducted following the PRISMA checklist and guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. PubMed, Ovid MEDLINE, Web of Science, and other databases were queried using applicable search terms. Relevant dosing, efficacy, and elution profiles were reviewed and compiled from 74 articles published between 1976 and 2019. First-line and targeted therapies were identified against rare and resistant bacteria. Drug therapies not recommended due to excessive cytotoxicity or poor delivery kinetics were also elucidated. RESULTS This compilation describes thirty-two antibiotics and three antifungals that have successfully managed orthopedic surgery-related infections, including infections with numerous recalcitrant and multidrug-resistant species. Optimized ratios of carrier to antimicrobial are provided for each delivery method. The elution and efficacy profiles of the various antibiotics are described when available. DISCUSSION/CONCLUSION These recommendations offer the most up-to-date and comprehensive practice guidelines for using antimicrobials in cements and beads for treating orthopedic hardware-related infections. With the ever-evolving propensity of bacteria to develop antibiotic resistance, these recommendations are dynamic. Collaboration with medicine, infectious disease, and/or pharmacology teams is recommended to create institutional protocols for antibiotic-eluting implants and close comanagement to ensure efficacy and patient safety.
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Affiliation(s)
- Aaron B Epperson
- Department of Orthopedics, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, Mail Stop B202, Aurora, CO, 80045, USA.
| | - Mohamed E Awad
- Department of Orthopedics, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, Mail Stop B202, Aurora, CO, 80045, USA
| | - Melissa Gorman
- Department of Orthopedics, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, Mail Stop B202, Aurora, CO, 80045, USA
| | - Kristin Loker
- Department of Orthopedics, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, Mail Stop B202, Aurora, CO, 80045, USA
| | - Nicholas A Alfonso
- Department of Orthopedics, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, Mail Stop B202, Aurora, CO, 80045, USA
| | - Jason W Stoneback
- Department of Orthopedics, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, Mail Stop B202, Aurora, CO, 80045, USA
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Chander S, Kumari R, Wang HY, Mohammed YN, Parkash O, Lohana S, Sorath F, Lohana AC, Sadarat F, Shiwlani S. Effect of low vs. high vancomycin trough level on the clinical outcomes of adult patients with sepsis or gram-positive bacterial infections: a systematic review and meta-analysis. BMC Infect Dis 2024; 24:1114. [PMID: 39375599 PMCID: PMC11457423 DOI: 10.1186/s12879-024-09927-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 09/13/2024] [Indexed: 10/09/2024] Open
Abstract
BACKGROUND & OBJECTIVE The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15-20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. METHOD A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. RESULTS Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41-2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23-0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73-3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31-1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73-1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62-0.90), p = 0.002]. CONCLUSION Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections.
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Affiliation(s)
- Subhash Chander
- Department of Medicine, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
- Mount Sinai Beth Israel Hospital, 281 1st Ave, New York, NY, 10003, USA.
| | - Roopa Kumari
- Department of Pathology, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | - Hong Yu Wang
- Department of Medicine, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | | | - Om Parkash
- Department of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Sindhu Lohana
- Department of Medicine, AGA khan University Hospital, Karachi, Pakistan
| | - Fnu Sorath
- Department of Medicine, Dow University Health Sciences, Karachi, Pakistan
| | - Abhi Chand Lohana
- Department of Medicine, Western Michigan University, Kalamazoo, WV, USA
| | - Fnu Sadarat
- Department of Medicine, University at Buffalo, Buffalo, NY, USA
| | - Sheena Shiwlani
- Department of Medicine, Icahn School of Medicine, Mount Sinai, New York, NY, USA
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Mu W, Xu B, Wang F, Maimaitiaimaier Y, Zou C, Cao L. Low incidence of acute kidney injury with combined intravenous and topical antibiotic infusions in periprosthetic joint infection after total knee arthroplasty. Bone Joint Res 2024; 13:525-534. [PMID: 39348916 PMCID: PMC11442033 DOI: 10.1302/2046-3758.1310.bjr-2024-0114.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/02/2024] Open
Abstract
Aims This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. Methods We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development. Results AKI was identified in 9.26% (15/162) of the cohort, predominantly presenting as stage 1 AKI, which was transient in nature and resolved prior to discharge. The analysis highlighted moderate anaemia and lower baseline serum creatinine levels as significant predictors for the development of AKI. Notably, the study found no instances of severe complications such as wound dehiscence, skin erosion, or the need for haemodialysis following treatment. Conclusion The findings suggest that the combined use of IV and topical antibiotic therapy in the management of PJIs post-TKA is associated with a low incidence of primarily transient stage 1 AKI. This indicates a potentially favourable renal safety profile, advocating for further research to confirm these outcomes and potentially influence treatment protocols in PJI management.
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Affiliation(s)
- Wenbo Mu
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Boyong Xu
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Fei Wang
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | | | - Chen Zou
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Li Cao
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- Key Laboratory of High Incidence Disease Research in Xingjiang (Xinjiang Medical University), Ministry of Education, Urumqi, China
- Xinjiang Clinical Research Center for Orthopedics, Urumqi, China
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10
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Hughes MSA, Lee T, Faldasz JD, Hughes JH. Impacts of age and BMI on vancomycin model choice in a Bayesian software: Lessons from a very large multi-site retrospective study. Pharmacotherapy 2024; 44:794-802. [PMID: 39382218 DOI: 10.1002/phar.4613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 08/23/2024] [Accepted: 08/28/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND Model-informed precision dosing (MIPD) optimizes drug doses based on pharmacokinetic (PK) model predictions, necessitating careful selection of models tailored to patient characteristics. This study evaluates the predictive performance of various vancomycin PK models across diverse age and BMI categories, drawing insights from a large multi-site database. METHODS Adults receiving vancomycin intravenous therapy at United States health systems between January 1, 2022, and December 31, 2023, were included. Patient demographics, vancomycin administration records, and therapeutic drug monitoring levels (TDMs) were collected from the InsightRX database. Age and body mass index (BMI)-based subgroups were formed to assess model performance, with predictions made iteratively. The optimal model for each age-BMI subgroup was chosen based on predefined criteria: models were filtered for mean percentage error (MPE) ≤ 20% and normalized root mean squared error (RMSE) < 8 mg/L, and then the most accurate among them was selected. RESULTS A total of 384,876 treatment courses across 155 US health systems were analyzed, contributing 841,604 TDMs. Eleven models were compared, showing varying accuracy across age-BMI categories (41%-73%), with higher accuracy observed once TDMs were available for Bayesian estimates of individual PK parameters. Models performed more poorly in younger adults compared to older adults, and the optimal model differed depending on age-BMI categories and prediction methods. Notably, in the a priori period, the Colin model performed best in adults aged 18-64 years across most BMI categories; the Goti/Tong model performed best in the older, non-obese adults; and the Hughes model performed best in many of the obese categories. CONCLUSION Our study identifies specific vancomycin PK models that demonstrate superior predictions across age-BMI categories in MIPD applications. Our findings underscore the importance of tailored model selection for vancomycin management, especially highlighting the need for improved models in younger adult patients. Further research into the clinical implications of model performance is warranted to enhance patient care outcomes.
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Payne W, Thompson S, Burton BN. Comparing Two Vancomycin Loading Dose Regimens in Patients With Obesity: A Single-Center Prospective Clinical Trial. Cureus 2024; 16:e70849. [PMID: 39493211 PMCID: PMC11531792 DOI: 10.7759/cureus.70849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/04/2024] [Indexed: 11/05/2024] Open
Abstract
BACKGROUND Obesity can significantly influence the pharmacokinetics of several medications, including vancomycin. Consequently, specialized dosing strategies may be required to ensure efficacy and safety in patients with obesity (PwO) requiring treatment with vancomycin. This single-center, prospective study evaluated two vancomycin loading dose regimens in PwO, comparing serum vancomycin concentrations, adverse events, and the impact on renal function. METHODS Adult patients weighing over 100 kg were randomized into two study groups. A 20 mg/kg loading dose of vancomycin was administered to both groups, with one group restricted to a maximum dose of 2000 mg (n=33) and the other group receiving up to 4000 mg (n=34). RESULTS Patients receiving the 4000 mg maximal dose achieved significantly higher median vancomycin concentrations at the initial trough (9.1 mg/L vs. 11.3 mg/L, p=0.0497), mean concentrations at the 7.5-hour interval trough (14.4 mg/L vs. 17.1 mg/L, p=0.0151), and mean concentrations at the post-load peak (23.9 mg/L vs. 30.9 mg/L, p=0.0023), without a corresponding increase in adverse renal outcomes, hospital length of stay, or mortality as compared with the 2000 mg maximum dose group. CONCLUSIONS The study's findings demonstrate that higher vancomycin doses in PwO are safely tolerated and do not result in short-term adverse effects on renal function. This study helps us better understand vancomycin pharmacotherapy in PwO, supporting the need for further research to refine dosing guidelines for these patients.
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Affiliation(s)
- William Payne
- Emergency Medicine, Charleston Area Medical Center, Charleston, USA
| | | | - Brian N Burton
- Research, Charleston Area Medical Center, Charleston, USA
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12
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Bao P, Sun Y, Qiu P, Li X. Development and validation of a nomogram to predict the risk of vancomycin-related acute kidney injury in critical care patients. Front Pharmacol 2024; 15:1389140. [PMID: 39263571 PMCID: PMC11387168 DOI: 10.3389/fphar.2024.1389140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 08/14/2024] [Indexed: 09/13/2024] Open
Abstract
Background Vancomycin-associated acute kidney injury (AKI) leads to underestimated morbidity in the intensive care unit (ICU). It is significantly important to predict its occurrence in advance. However, risk factors and nomograms to predict this AKI are limited. Methods This was a retrospective analysis of two databases. A total of 1,959 patients diagnosed with AKI and treated with vancomycin were enrolled from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. According to the 7:3 ratio, the training set (n = 1,372) and the internal validation set (n = 587) were randomly allocated. The external validation set included 211 patients from the eICU Collaborative Research Database (eICU). Next, to screen potential variables, the least absolute shrinkage and selection operator (LASSO) regression was utilized. Subsequently, the nomogram was developed by the variables of the selected results in the multivariable logistic regression. Finally, discrimination, calibration, and clinical utility were evaluated to validate the nomogram. Results The constructed nomogram showed fine discrimination in the training set (area under the receiver operator characteristic curve [AUC] = 0.791; 95% confidence interval [CI]: 0.758-0.823), internal validation set (AUC = 0.793; 95% CI: 0.742-0.844), and external validation set (AUC = 0.755; 95% CI: 0.663-0.847). Moreover, it also well demonstrated calibration and clinical utility. The significant improvement (P < 0.001) in net reclassification improvement (NRI) and integrated differentiation improvement (IDI) confirmed that the predictive model outperformed others. Conclusion This established nomogram indicated promising performance in determining individual AKI risk of vancomycin-treated critical care patients, which will be beneficial in making clinical decisions.
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Affiliation(s)
- Peng Bao
- Fuwai Central China Cardiovascular Hospital, Zhengzhou University, Zhengzhou, China
| | - Yuzhen Sun
- Fuwai Central China Cardiovascular Hospital, Zhengzhou University, Zhengzhou, China
| | - Peng Qiu
- Department of Rehabilitation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China
| | - Xiaohui Li
- Fuwai Central China Cardiovascular Hospital, Zhengzhou University, Zhengzhou, China
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El-Shoura EAM, Sharkawi SMZ, Abdelzaher LA, Abdel-Wahab BA, Ahmed YH, Abdel-Sattar AR. Reno-protective effect of fenofibrate and febuxostat against vancomycin-induced acute renal injury in rats: Targeting PPARγ/NF-κB/COX-II and AMPK/Nrf2/HO-1 signaling pathways. Immunopharmacol Immunotoxicol 2024; 46:509-520. [PMID: 38918173 DOI: 10.1080/08923973.2024.2373216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 06/22/2024] [Indexed: 06/27/2024]
Abstract
BACKGROUND Vancomycin (VCM) is used clinically to treat serious infections caused by multi-resistant Gram-positive bacteria, although its use is severely constrained by nephrotoxicity. This study investigated the possible nephroprotective effect of febuxostat (FX) and/or fenofibrate (FENO) and their possible underlying mechanisms against VCM-induced nephrotoxicity in a rat model. METHODS Male Wistar rats were randomly allocated into five groups; Control, VCM, FX, FENO, and combination groups. Nephrotoxicity was evaluated histopathologically and biochemically. The oxidative stress biomarkers (SOD, MDA, GSH, total nitrite, GPx, MPO), the apoptotic marker, renal Bcl-2 associated X protein (Bax), and inflammatory and kidney injury markers (IL-1β, IL-6, TNF-α, Nrf2, OH-1, kappa-light-chain-enhancer of activated B cells (NF-κB), NADPH oxidase, Kim-1, COX-II, NGAL, Cys-C were also evaluated. RESULTS VCM resulted in significant elevation in markers of kidney damage, oxidative stress, apoptosis, and inflammatory markers. Co-administration of VCM with either/or FX and FENO significantly mitigated nephrotoxicity and associated oxidative stress, inflammatory and apoptotic markers. In comparison to either treatment alone, a more notable improvement was observed with the FX and FENO combination regimen. CONCLUSION Our findings show that FX, FENO, and their combination regimen have a nephroprotective impact on VCM-induced kidney injury by suppressing oxidative stress, apoptosis, and the inflammatory response. Renal recovery from VCM-induced injury was accomplished by activation of Nrf2/HO-1 signaling and inhibition of NF-κB expression. This study highlights the importance of FX and FENO as effective therapies for reducing nephrotoxicity in VCM-treated patients.
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Affiliation(s)
- Ehab A M El-Shoura
- Department of Clinical Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
- Department of Pharmacy Practice, Faculty of Pharmacy, Horus University in Egypt, New Damietta, Egypt
| | - Souty M Z Sharkawi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Lobna A Abdelzaher
- Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Basel A Abdel-Wahab
- Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia
| | - Yasmine H Ahmed
- Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
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14
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Song X, Zeng M, Yang T, Han M, Yan S. Individualized, dynamic, and full-course vancomycin dosing prediction: a study on the customized dose model. Front Pharmacol 2024; 15:1414347. [PMID: 39021838 PMCID: PMC11252542 DOI: 10.3389/fphar.2024.1414347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 06/06/2024] [Indexed: 07/20/2024] Open
Abstract
Purpose The single-point trough-based therapeutic drug monitoring (TDM) and Bayesian forecasting approaches are still limited in individualized and dynamic vancomycin delivery. Until recently, there has not yet been enough focus on the direct integration of pharmacokinetic/pharmacodynamic (PK/PD) and TDM to construct a customized dose model (CDM) for vancomycin to achieve individualized, dynamic, and full-course dose prediction from empirical to follow-up treatment. This study sought to establish CDM for vancomycin, test its performance and superiority in clinical efficacy prediction, formulate a CDM-driven full-course dosage prediction strategy to overcome the above challenge, and predict the empirical vancomycin dosages for six Staphylococci populations and four strains in patients with various creatinine clearance rates (CLcr). Methods The PK/PD and concentration models derived from our earlier research were used to establish CDM. The receiver operating characteristic (ROC) curve, with the area under ROC curve (AUCR) as the primary endpoint, for 21 retrospective cases was applied to test the performance and superiority of CDM in clinical efficacy prediction by comparison to the current frequently-used dose model (FDM). A model with an AUCR of at least 0.8 was considered acceptable. Based on the availability of TDM, the strategy of CDM-driven individualized, dynamic, and full-course dose prediction for vancomycin therapy was formulated. Based on the CDM, Monte Carlo simulation was used to predict the empirical vancomycin dosages for the target populations and bacteria. Results Four CDMs and the strategy of CDM-driven individualized, dynamic, and full-course dose prediction for vancomycin therapy from empirical to follow-up treatment were constructed. Compared with FDM, CDM showed a greater AUCR value (0.807 vs. 0.688) in clinical efficacy prediction. The empirical vancomycin dosages for six Staphylococci populations and four strains in patients with various CLcr were predicted. Conclusion CDM is a competitive individualized dose model. It compensates for the drawbacks of the existing TDM technology and Bayesian forecasting and offers a straightforward and useful supplemental approach for individualized and dynamic vancomycin delivery. Through mathematical modeling of the vancomycin dosage, this study achieved the goal of predicting doses individually, dynamically, and throughout, thus promoting "mathematical knowledge transfer and application" and also providing reference for quantitative and personalized research on similar drugs.
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Affiliation(s)
- Xiangqing Song
- Department of Pharmacy, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Meizi Zeng
- Department of Pharmacy, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Tao Yang
- Department of Pharmacy, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Mi Han
- Department of Pharmacy, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Shipeng Yan
- Office of Cancer Prevention Research, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
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15
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Aldardeer NF, Alshreef MM, Alharbi EA, Aljabri AK, Aljawadi MH, Almangour TA, Alobaili S, Alarifi MI, Alomari A, Alhammad AM. Early Versus Late Antipseudomonal β-Lactam Antibiotic Dose Adjustment in Critically Ill Sepsis Patients With Acute Kidney Injury: A Prospective Observational Cohort Study. Open Forum Infect Dis 2024; 11:ofae059. [PMID: 38434610 PMCID: PMC10906704 DOI: 10.1093/ofid/ofae059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 01/25/2024] [Indexed: 03/05/2024] Open
Abstract
Background Acute kidney injury (AKI) is a common complication of sepsis, contributing to an increased mortality rate. However, some studies have demonstrated that renal function improves in sepsis patients with AKI within 48 hours, raising questions about the necessity for early antibiotic adjustment. This study evaluates the association between the timing of antipseudomonal β-lactam dose adjustment and the outcomes of critically ill sepsis patients with AKI. Methods A prospective, multicenter observational study of critically ill patients aged ≥18 years admitted to the intensive care unit with sepsis and AKI and started on antipseudomonal β-lactam therapy. After the initial dose, eligible patients were grouped as early β-lactam antibiotic (E-BLA) or late β-lactam antibiotic (L-BLA) dose adjustments based on the administration of subsequent renally adjusted doses within 24 hours and after 24 hours of sepsis recognition, respectively. The main outcome of interest was in-hospital mortality. Results Among 1185 patients screened, 224 (mean age, 62.7 ± 16.8 years; 62% were male) met inclusion criteria. Eighty-four and 140 patients were included in the E-BLA and L-BLA groups, respectively. Approximately half of the cohort presented with AKI stage II, and piperacillin-tazobactam was prescribed as initial empirical therapy in more than 50% of the cohort. In the multivariable Cox proportional hazards model, L-BLA was associated with a significant reduction in in-hospital mortality compared to E-BLA (hazard ratio, 0.588 [95% confidence interval, .355-.974]). Conclusions In sepsis patients with AKI, L-BLA was associated with in-hospital mortality benefits.
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Affiliation(s)
- Namareq F Aldardeer
- Department of Pharmacy Services, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Maram M Alshreef
- Department of Pharmacy Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Emad A Alharbi
- Department of Pharmacy Services, King Fahad Hospital, Madinah, Saudi Arabia
| | - Ahmad K Aljabri
- Department of Pharmacy Services, King Fahad Hospital, Madinah, Saudi Arabia
| | - Mohammad H Aljawadi
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Thamer A Almangour
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Saad Alobaili
- Department of Medicine, Nephrology Unit, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed I Alarifi
- Department of Critical Care Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Awad Alomari
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Abdullah M Alhammad
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
- Corporate Department of Pharmacy Services, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
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Pais GM, Marianski S, Valdez K, Melicor RP, Liu J, Rohani R, Chang J, Tong SYC, Davis JS, Scheetz MH. Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model. Br J Pharmacol 2024; 181:670-680. [PMID: 37696768 PMCID: PMC10872794 DOI: 10.1111/bph.16234] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 08/11/2023] [Accepted: 08/28/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND AND PURPOSE Vancomycin is one of the most common clinical antibiotics, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin-induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem-cilastatin on kidney injury when combined with vancomycin in our translational rat model. EXPERIMENTAL APPROACH Male Sprague-Dawley rats received allometrically scaled (1) vancomycin, (2) flucloxacillin, (3) vancomycin + flucloxacillin, (4) vancomycin + imipenem-cilastatin or (5) saline for 4 days. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule-1 (KIM-1), clusterin and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored. KEY RESULTS Urinary output increased every study day for vancomycin + flucloxacillin, but after the first dose only in the vancomycin group. In the vancomycin + flucloxacillin group, urinary KIM-1 increased on all days compared with vancomycin. In the vancomycin + imipenem-cilastatin group, urinary KIM-1 was decreased on Days 1 and 2 compared with vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin + flucloxacillin compared with vancomycin and vancomycin + imipenem-cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM-1. CONCLUSIONS AND IMPLICATIONS Vancomycin + flucloxacillin caused more kidney injury compared with vancomycin alone and vancomycin + imipenem-cilastatin in a translational rat model. The combination of vancomycin + imipenem-cilastatin was nephroprotective.
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Affiliation(s)
- Gwendolyn M. Pais
- Midwestern University- Downers Grove Campus, Department of Pharmacy Practice, Downers Grove, IL, USA
- Midwestern University- Downers Grove Campus, Pharmacometrics Center of Excellence, Downers Grove, IL, USA
| | - Sylwia Marianski
- Midwestern University- Downers Grove Campus, Department of Pharmacy Practice, Downers Grove, IL, USA
| | - Kimberly Valdez
- Midwestern University- Downers Grove Campus, Department of Pharmacy Practice, Downers Grove, IL, USA
| | - Renz Paulo Melicor
- Midwestern University- Downers Grove Campus, Department of Pharmacy Practice, Downers Grove, IL, USA
| | - Jiajun Liu
- Present affiliation: Division of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, United States Food and Drug Administration, Silver Spring, MD, USA; work was carried out while employed at Midwestern University College of Pharmacy, Downers Grove, IL, USA
| | - Roxane Rohani
- Midwestern University- Downers Grove Campus, Department of Pharmacy Practice, Downers Grove, IL, USA
- Midwestern University- Downers Grove Campus, Pharmacometrics Center of Excellence, Downers Grove, IL, USA
- Present affiliation: Discipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
| | - Jack Chang
- Midwestern University- Downers Grove Campus, Department of Pharmacy Practice, Downers Grove, IL, USA
- Midwestern University- Downers Grove Campus, Pharmacometrics Center of Excellence, Downers Grove, IL, USA
- Northwestern Memorial Hospital, Department of Pharmacy, Chicago, IL, USA
| | - Steven Y. C. Tong
- Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
| | - Joshua S Davis
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
| | - Marc H. Scheetz
- Midwestern University- Downers Grove Campus, Department of Pharmacy Practice, Downers Grove, IL, USA
- Midwestern University- Downers Grove Campus, Pharmacometrics Center of Excellence, Downers Grove, IL, USA
- Northwestern Memorial Hospital, Department of Pharmacy, Chicago, IL, USA
- Midwestern University- Downers Grove Campus, Department of Pharmacology, Downers Grove, IL, USA
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Tyler Pitcock C, Schadler A, Burgess DS, Burgess DR, Cotner SE, Van Hoose J, Gregory ER, Wallace KL. Association of vancomycin-induced acute kidney injury with trough versus AUC monitoring in patients receiving extended durations of therapy. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2023; 3:e225. [PMID: 38156206 PMCID: PMC10753493 DOI: 10.1017/ash.2023.490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/14/2023] [Accepted: 10/16/2023] [Indexed: 12/30/2023]
Abstract
Objective Vancomycin therapy is associated with an increased risk of acute kidney injury (AKI). Previous studies suggest that area under the curve (AUC) monitoring reduces the risk of AKI, but literature is lacking to support this in patients receiving longer durations of vancomycin therapy. Design Retrospective cohort study. Method Patients ≥18 years old, admitted between August 2015 and July 2017 or October 2017 and September 2019, and received at least 14 days of intravenous (IV) vancomycin therapy were included in the study. Our primary outcome was the incidence of AKI between trough monitoring and AUC monitoring groups using Kidney Disease Improving Global Outcomes criteria. Secondary outcomes included inpatient mortality, median inpatient length of stay, and median intensive care unit length of stay. Results Overall, 582 patients were included in the study, with 318 patients included in the trough monitoring group and 264 included in the AUC monitoring group. The median duration of vancomycin therapy was 23 days (interquartile range, 16-39). Patients within the trough monitoring group had a higher incidence of AKI compared to the AUC monitoring group (45.6% vs 28.4%, p < 0.001). Furthermore, logistic regression analysis showed that AUC monitoring was associated with a 54% lower incidence of AKI (OR 0.46, 95% CI [0.31-0.69]). All-cause inpatient mortality was numerically higher in the trough monitoring group (12.9% vs 8.3%, p = 0.078). Conclusions In patients who received at least 14 days of IV vancomycin therapy, AUC monitoring was associated with a lower incidence of AKI.
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Affiliation(s)
- C. Tyler Pitcock
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA
| | - Aric Schadler
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA
- Department of Pediatrics, Kentucky Children’s Hospital, Lexington, KY, USA
| | - David S. Burgess
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA
| | - Donna R. Burgess
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA
| | - Sarah E. Cotner
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA
| | - Jeremy Van Hoose
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA
| | - Eric R. Gregory
- Department of Pharmacy Services, The University of Kansas Health System, Kansas City, KS, USA
| | - Katie L. Wallace
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA
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Wuerger A, Bowden J, Mitchell A, Marler J. The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity. Hosp Pharm 2023; 58:605-613. [PMID: 38560542 PMCID: PMC10977066 DOI: 10.1177/00185787231172388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Background: Increasing evidence suggests that administration of combination vancomycin and piperacillin-tazobactam (VPT) increases the incidence of acute kidney injury (AKI) beyond that of vancomycin alone. But these investigations have not evaluated AKI risk specifically in an increasingly prevalent obese population in whom VPT pharmacokinetics are altered. Objective: To evaluate AKI risk with VPT administration to patients with obesity. Methods: We conducted a multicenter retrospective study of obese patients admitted to 2 separate academic teaching hospitals from January 2010 to December 2021, who received VPT, or vancomycin plus either cefepime, meropenem, or ceftazidime. The primary outcome evaluated AKI when patients were treated with or without VPT. Results: A total of 227 patients were evaluated (114 in VPT, vs 113 in control group). Overall, body mass index (35.6 kg/m2 ± 4.8vs 36.1 kg/m2 ± 5.2; P = .44) was similar between the VPT and control groups respectively. Total vancomycin dose on day 1 of antibiotic therapy (3,432 mg ± 935 vs 2,732 mg ± 912; P < .01) and nephrotoxin administration (75.4% vs 62.8%; P = .04) were higher in the VPT group. Incidence of AKI was higher in the VPT group (37.7%vs 14.2%; P = .01) and on regression analysis VPT was predictive of developing AKI (OR = 3.9; 95% CI = 2.0-7.7; P < .01). Conclusion and Relevance: In this retrospective study, the incidence of AKI was increased in obese patients receiving therapy with VPT. Vancomycin combination therapy with ceftazidime, cefepime, and meropenem appeared to be safe and was associated with less nephrotoxicity. Cautious use of VPT and further investigation with larger studies are warranted in this area.
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Affiliation(s)
| | - Jarred Bowden
- Veterans Affairs Hospital, Memphis, TN, USA
- University of Tennessee Health Sciences Center (UTHSC), Memphis, TN, USA
| | | | - Jacob Marler
- Veterans Affairs Hospital, Memphis, TN, USA
- University of Tennessee Health Sciences Center (UTHSC), Memphis, TN, USA
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Yue Y, Chen K, Sun C, Ahmed S, Ojha SC. Antimicrobial peptidase lysostaphin at subinhibitory concentrations modulates staphylococcal adherence, biofilm formation, and toxin production. BMC Microbiol 2023; 23:311. [PMID: 37884887 PMCID: PMC10601153 DOI: 10.1186/s12866-023-03052-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 10/09/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND The ability of antimicrobial agents to affect microbial adherence to eukaryotic cell surfaces is a promising antivirulence strategy for combating the global threat of antimicrobial resistance. Inadequate use of antimicrobials has led to widespread instances of suboptimal antibiotic concentrations around infection sites. Therefore, we aimed to examine the varying effect of an antimicrobial peptidase lysostaphin (APLss) on staphylococcal adherence to host cells, biofilm biomass formation, and toxin production as a probable method for mitigating staphylococcal virulence. RESULTS Initially, soluble expression in E. coli and subsequent purification by immobilized-Ni2+ affinity chromatography (IMAC) enabled us to successfully produce a large quantity of highly pure ~ 28-kDa His-tagged mature APLss. The purified protein exhibited potent inhibitory effects against both methicillin-sensitive and methicillin-resistant staphylococcal strains, with minimal inhibitory concentrations (MICs) ranging from 1 to 2 µg/mL, and ultrastructural analysis revealed that APLss-induced concentration-specific changes in the morphological architecture of staphylococcal surface membranes. Furthermore, spectrophotometric and fluorescence microscopy revealed that incubating staphylococcal strains with sub-MIC and MIC of APLss significantly inhibited staphylococcal adherence to human vaginal epithelial cells and biofilm biomass formation. Ultimately, transcriptional investigations revealed that APLss inhibited the expression of agrA (quorum sensing effector) and other virulence genes related to toxin synthesis. CONCLUSIONS Overall, APLss dose-dependently inhibited adhesion to host cell surfaces and staphylococcal-associated virulence factors, warranting further investigation as a potential anti-staphylococcal agent with an antiadhesive mechanism of action using in vivo models of staphylococcal toxic shock syndrome.
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Affiliation(s)
- Yuan Yue
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Shaanxi Normal University, Xi'an, China
| | - Ke Chen
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
- Southwest Medical University, Jiangyang District, Luzhou, 646000, Sichuan, China
| | - Changfeng Sun
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
- Southwest Medical University, Jiangyang District, Luzhou, 646000, Sichuan, China
| | - Sarfraz Ahmed
- Wellman Centre for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston MA 02114, USA
| | - Suvash Chandra Ojha
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Southwest Medical University, Jiangyang District, Luzhou, 646000, Sichuan, China.
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20
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Gorham J, Taccone FS, Hites M. Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Obese Patients. Antibiotics (Basel) 2023; 12:1099. [PMID: 37508195 PMCID: PMC10376599 DOI: 10.3390/antibiotics12071099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/14/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023] Open
Abstract
Obesity is a significant global public health concern that is associated with an elevated risk of comorbidities as well as severe postoperative and nosocomial infections. The treatment of infections in critically ill obese patients can be challenging because obesity affects the pharmacokinetics and pharmacodynamics of antibiotics, leading to an increased risk of antibiotic therapy failure and toxicity due to inappropriate dosages. Precision dosing of antibiotics using therapeutic drug monitoring may help to improve the management of this patient population. This narrative review outlines the pharmacokinetic and pharmacodynamic changes that result from obesity and provides a comprehensive critical review of the current available data on dosage adjustment of antibiotics in critically ill obese patients.
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Affiliation(s)
- Julie Gorham
- Department of Intensive Care, Hôpital Universitaire de Bruxelles (H.U.B), 1070 Brussels, Belgium
| | - Fabio S Taccone
- Department of Intensive Care, Hôpital Universitaire de Bruxelles (H.U.B), 1070 Brussels, Belgium
| | - Maya Hites
- Clinic of Infectious Diseases, Hôpital Universitaire de Bruxelles (H.U.B), 1070 Brussels, Belgium
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21
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Sherwin CM, Tran NK, Sullivan K, Wead S, Birnbaum AK, Avachat C, Healy DP, Kagan RJ. Exploring the Past to Inform the Future to Optimize the Pharmacokinetics of Vancomycin in Children With Severe Burn Injuries. J Burn Care Res 2023; 44:353-362. [PMID: 36194537 DOI: 10.1093/jbcr/irac147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Indexed: 11/12/2022]
Abstract
Sepsis remains one of the leading causes of death among pediatric patients with burn injuries. Despite limited vancomycin pharmacokinetic (PK) information within this population, it is widely used to treat severe burn injuries. Those with severe burns are at risk of nephrotoxicity, with an incidence of acute kidney injury (AKI) over 50%. Delivering an effective vancomycin dose and avoiding unnecessary toxicity is essential for improved patient outcomes. This was a retrospective analysis of 115 children aged 0.2 months to 18 years with severe burns, >10% total body surface area. Vancomycin was given via intravenous infusion; blood samples were drawn between 6- and 12-hour postinfusion. A population pharmacokinetic model was developed using nonlinear mixed-effect modeling (Monolix, version 2016R1). A one-compartment model described a steady-state volume of distribution (V), dependent on weight. Vancomycin clearance (CL) was influenced by age and estimated creatinine clearance (CrCL). The study population's (median age = 4 years, median weight = 20 kg, median total body surface area (%TBSA) = 40%) median V and CL were calculated to be 1.25 L/kg (95% CI, 1.04-1.46) and 0.15 L/h/kg (95% CI, 0.126-0.165), respectively. The PK model was explicitly developed to characterize the impact of physiological changes in children under 18 years of age and the percentage of the burn surface area using limited data. The analysis determined that weight, age, and estimated CrCL were important covariates in predicting vancomycin PK with high variability in CL and V.
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Affiliation(s)
- Catherine M Sherwin
- Dept of Pediatrics, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.,Dayton Children's Hospital, Dayton, OhH, USA.,James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA.,Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
| | - Nam K Tran
- Department of Pathology and Laboratory Medicine, University of California, School of Medicine, Davis, CA, USA
| | - Kevin Sullivan
- University of Tennessee Medical Center and College of Pharmacy, Knoxville, TN, USA
| | | | - Angela K Birnbaum
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
| | - Charul Avachat
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
| | - Daniel P Healy
- James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA
| | - Richard J Kagan
- The Shriners Hospitals for Children®, Dayton (Cincinnati), OH, USA.,Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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22
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Huang J, Chan JD, Nguyen T, Jain R, Escobar ZK. Doing More With Less: Pragmatic Implementation of Vancomycin Area-Under-the-Curve (AUC) Monitoring. J Pharm Pract 2023; 36:10-14. [PMID: 34159816 DOI: 10.1177/08971900211027271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Universal area-under-the-curve (AUC) guided vancomycin therapeutic drug monitoring (TDM) is resource-intensive, cost-prohibitive, and presents a paradigm shift that leaves institutions with the quandary of defining the preferred and most practical method for TDM. We report a step-by-step quality improvement process using 4 plan-do-study-act (PDSA) cycles to provide a framework for development of a hybrid model of trough and AUC-based vancomycin monitoring. We found trough-based monitoring a pragmatic strategy as a first-tier approach when anticipated use is short-term. AUC-guided monitoring was most impactful and cost-effective when reserved for patients with high-risk for nephrotoxicity. We encourage others to consider quality improvement tools to locally adopt AUC-based monitoring.
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Affiliation(s)
- Joanne Huang
- Department of Pharmacy Services, 2348Massachusetts General Hospital, Boston, MA, USA
| | - Jeannie D Chan
- Department of Pharmacy Services, UW Medicine, 21618Harborview Medical Center, Seattle, WA, USA.,21616University of Washington School of Pharmacy, Seattle, WA, USA
| | - Thu Nguyen
- Department of Pharmacy Services, 21616UW Medicine, Valley Medical Center, Renton, WA, USA
| | - Rupali Jain
- 21616University of Washington School of Pharmacy, Seattle, WA, USA.,Department of Pharmacy Services, UW Medicine, University of Washington Medical Center, Seattle, WA, USA
| | - Zahra Kassamali Escobar
- 21616University of Washington School of Pharmacy, Seattle, WA, USA.,Department of Pharmacy Services, 21616UW Medicine, Valley Medical Center, Renton, WA, USA
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23
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Tarabichi S, Goh GS, Zanna L, Qadiri QS, Baker CM, Gehrke T, Citak M, Parvizi J. Time to Positivity of Cultures Obtained for Periprosthetic Joint Infection. J Bone Joint Surg Am 2023; 105:107-112. [PMID: 36574630 DOI: 10.2106/jbjs.22.00766] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Despite its well-established limitations, culture remains the gold standard for microbial identification in periprosthetic joint infection (PJI). However, there are no benchmarks for the time to positivity (TTP) on culture for specific microorganisms. This study aimed to determine the TTP for pathogens commonly encountered in PJI. METHODS This retrospective, multicenter study reviewed prospectively maintained institutional PJI databases to identify patients who underwent hip or knee revision arthroplasty from 2017 to 2021 at 2 tertiary centers in the United States and Germany. Only patients who met the 2018 International Consensus Meeting (ICM) criteria for PJI and had a positive intraoperative culture were included. TTP on culture media was recorded for each sample taken intraoperatively. The median TTP was compared among different microbial species and different specimen types. Data are presented either as the mean and the standard deviation or as the median and the interquartile range (IQR). RESULTS A total of 536 ICM-positive patients with positive cultures were included. The mean number of positive cultures per patient was 3.9 ± 2.6. The median TTP, in days, for all positive cultures was 3.3 (IQR, 1.9 to 5.4). Overall, gram-negative organisms (TTP, 1.99 [1.1 to 4.1]; n = 225) grew significantly faster on culture compared with gram-positive organisms (TTP, 3.33 [1.9 to 5.8]; n = 1,774). Methicillin-resistant Staphylococcus aureus (TTP, 1.42 [1.0 to 2.8]; n = 85) had the fastest TTP, followed by gram-negative rods (TTP, 1.92 [1.0 to 3.9]; n = 163), methicillin-sensitive Staphylococcus aureus (TTP, 1.95 [1.1 to 3.3] n = 393), Streptococcus species (TTP, 2.92 [1.2 to 4.3]; n = 230), Staphylococcus epidermidis (TTP, 4.20 [2.4 to 5.5]; n = 555), Candida species (TTP, 5.30 [3.1 to 10]; n = 63), and Cutibacterium acnes (TTP, 6.97 [5.9 to 8.2]; n = 197). When evaluating the median TTP according to specimen type, synovial fluid (TTP, 1.97 [1.1 to 3.1]; n = 112) exhibited the shortest TTP, followed by soft tissue (TTP, 3.17 [1.4 to 5.3]; n = 1,199) and bone (TTP, 4.16 [2.3 to 5.9]; n = 782). CONCLUSIONS To our knowledge, this is the first study to examine the TTP of common microorganisms that are known to cause PJI. Increased awareness of these data may help to guide the selection of appropriate antimicrobial therapy and to predict treatment outcomes in the future. Nonetheless, additional studies with larger cohorts are needed to validate these benchmarks. LEVEL OF EVIDENCE Diagnostic Level IV . See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Saad Tarabichi
- Rothman Orthopaedic Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Graham S Goh
- Rothman Orthopaedic Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Luigi Zanna
- Traumatology and General Orthopedics Department, Careggi University Hospital, Florence, Italy.,Department of Orthopaedic Surgery, Helios ENDO-Klinik Hamburg, Hamburg, Germany
| | - Qudratullah S Qadiri
- Rothman Orthopaedic Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Colin M Baker
- Rothman Orthopaedic Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Thorsten Gehrke
- Department of Orthopaedic Surgery, Helios ENDO-Klinik Hamburg, Hamburg, Germany
| | - Mustafa Citak
- Department of Orthopaedic Surgery, Helios ENDO-Klinik Hamburg, Hamburg, Germany
| | - Javad Parvizi
- Rothman Orthopaedic Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
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24
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Chavva H, Meka Y, Long TE. Antimicrobial pharmacodynamics of vancomycin and disulfiram (Antabuse®) in Staphylococcus aureus. Front Microbiol 2023; 13:1092257. [PMID: 36687633 PMCID: PMC9854118 DOI: 10.3389/fmicb.2022.1092257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023] Open
Abstract
Introduction Intravenous vancomycin (VAN) is the primary treatment for systemic infections due to methicillin-resistant Staphylococcus aureus (MRSA). Pharmacokinetic/pharmacodynamic target (PK/PD) indices for VAN therapies are more difficult to achieve for MRSA isolates with a minimum inhibitory concentration (MIC) greater than 1 µg mL-1. This research investigated the in vitro antimicrobial PD interaction of disulfiram (DSF) with VAN as a potential adjuvant therapy for infections due to these bacteria. Methods The antimicrobial interaction was assessed by differential analysis using checkerboard titration testing, time-kill studies, flow cytometry, and the post-antibiotic effect (PAE) experiment. Ten MRSA strains with MICs ranging from 1 to >256 µg mL-1 for VAN were evaluated. A comprehensive PD assessment of the VAN/DSF interaction was performed using the VAN-intermediate (VISA) strain Mu50 (MIC 8 µg mL-1). Results The addition of DSF lowered the MIC and minimum bactericidal concentration (MBC) of VAN in either a synergistic or additive manner for the MRSA panel. Optimal bactericidal effects and suppression of VISA Mu50 growth were observed with a 4/8 µg mL-1 combination of VAN/DSF, but not the individual drugs. Flow cytometry further confirmed the enhanced killing action on a cellular level; however, the addition of DSF had an overall antagonistic effect on the PAEs for VAN. Discussion This research established that DSF exhibits additive to synergistic killing action with VAN for MRSA. Conversely, antagonism was observed on the PAE of VAN with DSF addition for the Mu50 strain. Flow cytometry further confirmed the enhanced bactericidal effect on a cellular level while revealing that DSF may counteract the muropeptide fortification mechanism against VAN in VISA.
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Affiliation(s)
- Hasitha Chavva
- Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, United States
| | - Yogesh Meka
- Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, United States
| | - Timothy E. Long
- Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, United States,Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United States,*Correspondence: Timothy E. Long,
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25
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Altowayan WM, Mobark MA, ALharbi A, Alduhami AA, Rabbani SI. The influence of vancomycin on renal functions, the predictors and associated factors for nephrotoxicity. PLoS One 2023; 18:e0284223. [PMID: 37068067 PMCID: PMC10109467 DOI: 10.1371/journal.pone.0284223] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Accepted: 03/27/2023] [Indexed: 04/18/2023] Open
Abstract
BACKGROUND Vancomycin has been widely used in the last six decades to treat methicillin-resistant S. aureus (MRSA) and other resistant gram-positive infections. The risk of vancomycin toxicity increases with the utilization of higher doses while treating the resistant form of bacterial infections. Nephrotoxicity is one of the major complications reported to be a hinderance in the prognosis of vancomycin therapy. OBJECTIVES This hospital-based study aimed to highlight the influence of vancomycin on renal function with special emphasis on identifying the predictors and augmenting factors for nephrotoxicity. METHODOLOGY A cross-sectional, unicentric, hospital-based study was conducted at King Fahad Specialist Hospital (KFSH) in Qassim region in Saudi Arabia (KSA). It included 319 hospitalized patients who received vancomycin at intermittent doses (15 to 30 mg/kg IV per day) based on the diseased state. Data regarding vancomycin dose, frequency, duration and data of renal function tests and type of admission were analysed to evaluate their influence on the renal function using parameters such as blood urea, serum creatinine levels and creatinine clearance. One-way ANOVA and Spearman correlation test were used in the analysis of data. RESULTS Both male and female patients treated with vancomycin had significantly (p<0.05) elevated blood urea and serum creatinine levels compared to baseline levels while creatinine clearance was non-significantly varied. Increasing age, increasing body weight, higher vancomycin dose and trough levels, increased vancomycin frequency and duration, critically ill patients and site of infection were factors associated with significant (p<0.05) increases in blood urea and serum creatinine levels with reduction in creatinine clearance. CONCLUSION Data suggested that vancomycin treatment reduced the renal function in patients and indicated its association with several predictors and confounding factors. The findings of the study might assist in identifying the patients under risk from the vancomycin-induced nephrotoxicity and in designing the preventive strategies to reduce such complications.
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Affiliation(s)
- Waleed M Altowayan
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia
| | - Mugahid A Mobark
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia
- Department of Pathology, Faculty of Medicine, University of Kordofan, El-Obeid, Sudan
| | - Abdulmajed ALharbi
- Clinical Pharmacy, King Fahad Specialist Hospital, Buraydah, Qassim, Saudi Arabia
| | - Abdullah Ali Alduhami
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia
| | - Syed Imam Rabbani
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia
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26
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Chinzowu T, Chyou T, Nishtala PS. Antibacterial-associated acute kidney injury among older adults: A post-marketing surveillance study using the FDA adverse events reporting system. Pharmacoepidemiol Drug Saf 2022; 31:1190-1198. [PMID: 35670078 PMCID: PMC9795977 DOI: 10.1002/pds.5486] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 05/18/2022] [Accepted: 06/05/2022] [Indexed: 12/30/2022]
Abstract
PURPOSE Antibacterials induce a differential risk of acute kidney injury (AKI) in older adults. This study investigated the reporting risk of AKI associated with antibacterials using the individual case safety reports (ICSRs) submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS A case/non-case method was used to assess AKI risk associated with antibacterials between 1 January 2000 and 30 September 2021. Cases were ICSRs for antibacterials with AKI as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'Renal and urinary disorders' disorders. The analyses were completed on a de-duplicated data set containing only the recent version of the ICSR. Signals were defined by a lower 95% confidence interval (CI) of reporting odds ratio (ROR) ≥ 2, proportional reporting ratio (PRR) ≥ 2, information component (IC) > 0, Empirical Bayes Geometric Mean (EBGM) > 1 and reports ≥4. Sensitivity analyses were conducted a priori to assess the robustness of signals. RESULTS A total of 3 680 621 reports on ADEs were retrieved from FAERS over the study period, of which 92 194 were antibacterial reports. Gentamicin, sulfamethoxazole, trimethoprim and vancomycin consistently gave strong signals of disproportionality on all four disproportionality measures and across the different sensitivity analyses: gentamicin (ROR = 2.95[2.51-3.46]), sulfamethoxazole (ROR = 2.97[2.68-3.29]), trimethoprim (ROR = 2.81[2.29-3.46]) and vancomycin (ROR = 3.35[3.08-3.64]). CONCLUSION Signals for gentamicin, sulfamethoxazole, trimethoprim and vancomycin were confirmed by using antibacterials as a comparator, adjusting for drug-related competition bias and event-related competition bias.
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Affiliation(s)
| | - Te‐Yuan Chyou
- Department of BiochemistryUniversity of OtagoDunedinNew Zealand
| | - Prasad S. Nishtala
- Department of Pharmacy & PharmacologyUniversity of BathBath,Centre for Therapeutic InnovationUniversity of BathBathUK
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27
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Mullaney SR. Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: CON. KIDNEY360 2022; 3:1488-1490. [PMID: 36245666 PMCID: PMC9528368 DOI: 10.34067/kid.0007932021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 01/24/2022] [Indexed: 11/27/2022]
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28
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Perazella MA. Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: COMMENTARY. KIDNEY360 2022; 3:1491-1493. [PMID: 36250736 PMCID: PMC9528384 DOI: 10.34067/kid.0008112021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 12/22/2021] [Indexed: 11/27/2022]
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29
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Song X, Han M. Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode. Front Cell Infect Microbiol 2022; 12:874401. [PMID: 35873144 PMCID: PMC9300975 DOI: 10.3389/fcimb.2022.874401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 05/20/2022] [Indexed: 11/13/2022] Open
Abstract
ObjectiveThe study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) vs. intermittent infusion (II) vs. continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.MethodsWith PK/PD modeling and Monte Carlo simulations, the PK/PD exposure of 15 OTSI, 13 II, and 6 CI regimens for vancomycin, at 1, 2, 3, 4, 5, and 6 g daily dose, was evaluated. Using the Monte Carlo simulations, the vancomycin population PK parameters derived from critical patients, the PD parameter for MRSA isolates [i.e., minimum inhibitory concentration (MIC)], and the dosing parameters of these regimens were integrated into a robust mdel of vancomycin PK/PD index, defined as a ratio of the daily area under the curve (AUC0–24) to MIC (i.e., AUC0–24/MIC), to estimate the probability of target attainment (PTA) of these regimens against MRSA isolates with an MIC of 0.5, 1, 2, 4, and 8 mg/L in patients with varying renal function. The PTA at an AUC0–24/MIC ratio of >400, 400–600, and >600 was estimated. A regimen with a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, which is supposed to maximize both efficacy and safety, was considered optimal.ResultsAt the same daily dose, almost only the OTSI regimens showed a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, and this profile seems evident especially in patients with creatinine clearance (CLcr) of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L. However, for patients with CLcr of <60 ml/min and for isolates with an MIC of ≥4 mg/L, the II regimens often displayed a higher or even ≥90% PTA at an AUC0–24/MIC ratio of >400 and of >600. The CI regimens frequently afforded a reduced PTA at an AUC0–24/MIC ratio of >400 and of >600, regardless of CLcr and MIC.ConclusionsThe data indicated that the OTSI regimens allowed preferred PK/PD exposure in terms of both efficacy and safety, and thus should be focused more on, especially in patients with CLcr of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L.
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30
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La YJ, Kim HR, Oh DH, Ahn JY, Kim YC. Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections. Yonsei Med J 2022; 63:611-618. [PMID: 35748072 PMCID: PMC9226830 DOI: 10.3349/ymj.2022.63.7.611] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 04/05/2022] [Accepted: 04/20/2022] [Indexed: 11/27/2022] Open
Abstract
PURPOSE This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI). MATERIALS AND METHODS We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis. RESULTS A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71-6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis. CONCLUSION Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.
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Affiliation(s)
- Yeon Ju La
- Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea
| | - Hye Rim Kim
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Hyun Oh
- Department of Internal Medicine, Seoul Medical Center, Seoul, Korea
| | - Jin Young Ahn
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
| | - Yong Chan Kim
- Department of Internal Medicine, Division of Infectious Disease, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea.
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31
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Xu KY, Li D, Hu ZJ, Zhao CC, Bai J, Du WL. Vancomycin dosing in an obese patient with acute renal failure: A case report and review of literature. World J Clin Cases 2022; 10:6218-6226. [PMID: 35949852 PMCID: PMC9254177 DOI: 10.12998/wjcc.v10.i18.6218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/19/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vancomycin is the most commonly used drug for methicillin-resistant Staphylococcus aureus. The empirical clinical doses of vancomycin based on non-obese patients may not be optimal for obese ones.
CASE SUMMARY This study reports a case of vancomycin dosing adjustment in an obese patient (body mass index 78.4 kg/m2) with necrotizing fasciitis of the scrotum and left lower extremity accompanied with acute renal failure. Dosing adjustment was performed based on literature review and factors that influence pharmacokinetic parameters are analyzed. The results of the blood drug concentration monitoring confirmed the successful application of our dosing adjustment strategy in this obese patient. Total body weight is an important consideration for vancomycin administration in obese patients, which affects the volume of distribution and clearance of vancomycin. The alterations of pharmacokinetic parameters dictate that vancomycin should be dose-adjusted when applied to obese patients. At the same time, the pathophysiological status of patients, such as renal function, which also affects the dose adjustment of the patient, should be considered.
CONCLUSION Monitoring vancomycin blood levels in obese patients is critical to help adjust the dosing regimen to ensure that vancomycin concentrations are within the effective therapeutic range and to reduce the incidence of renal injury.
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Affiliation(s)
- Kun-Yan Xu
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Dan Li
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Zhen-Jie Hu
- Department of Intensive Care Unit, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Cong-Cong Zhao
- Department of Intensive Care Unit, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Jing Bai
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Wen-Li Du
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
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Coye TL, Foote C, Stasko P, Demarco B, Farley E, Kalia H. Predictive Value of MRSA Nares Colonization in Diabetic Foot Infections: A Systematic Review and Bivariate Random Effects Meta-Analysis. J Foot Ankle Surg 2022; 62:576-582. [PMID: 36922315 DOI: 10.1053/j.jfas.2022.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/06/2022] [Accepted: 06/10/2022] [Indexed: 03/18/2023]
Abstract
The primary objective of this study was to assess the negative predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs in MRSA diabetic foot infections. MEDLINE and Cochrane Library were searched from inception to May 1, 2020. The following search string was used: (methicillin-resistant S. aureus OR MRSA) AND (nasal OR nares) AND (diabetic OR foot OR diabetic foot infections). All studies that contained data comparing MRSA nasal swab positivity to wound cultures from diabetic foot infections and met the inclusion criteria were included. Among the 86 relevant studies, 6 studies with 8706 diabetic patients were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline extension for Diagnostic Test Accuracy reviews was followed. The primary meta-analysis outcomes were the negative and positive predictive values of MRSA nasal swabs for MRSA diabetic foot infections. The pooled specificity and pooled sensitivity were determined by generating hierarchical summary receiver characteristic operating curves. In the bivariate meta-analysis, involving the 6 studies, pooled sensitivity and specificity was 41.7% (95% confidence interval = 32.9, 51) and 94.1% (95% confidence interval = 89.5, 96.8), respectively. In low-moderate MRSA prevalence levels (<15%), negative predictive value of MRSA nasal swab was >90% and positive predictive value was <55%. This meta-analysis suggests that in patients with diabetic foot infections, the nasal swab MRSA screen has a poor positive predictive value but an excellent negative predictive value in regions of low to moderate prevalence of MRSA diabetic foot infections.
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Affiliation(s)
- Tyler L Coye
- Resident (PGY-3), Division of Podiatric Medicine and Surgery, Department of Orthopedics, Rochester General Hospital, Rochester, NY.
| | - Courtney Foote
- Resident (PGY-3), Division of Podiatric Medicine and Surgery, Department of Orthopedics, Rochester General Hospital, Rochester, NY
| | - Paul Stasko
- Physician, Division of Podiatric Medicine and Surgery, Department of Orthopedics, Rochester General Hospital, Rochester, NY
| | - Bethany Demarco
- Resident (PGY-2), Division of Podiatric Medicine and Surgery, Department of Orthopedics, Rochester General Hospital, Rochester, NY
| | - Eileen Farley
- Resident (PGY-2), Division of Podiatric Medicine and Surgery, Department of Orthopedics, Rochester General Hospital, Rochester, NY
| | - Hemant Kalia
- Department of Physical Medicine & Rehabilitation, Rochester Regional Health System, Rochester, NY
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Song X, Wu Y. Predicted Vancomycin Dosage Requirement in Patients With Hematological Malignancies and Dosage Dynamic Adjustment. Front Pharmacol 2022; 13:890748. [PMID: 35734407 PMCID: PMC9207402 DOI: 10.3389/fphar.2022.890748] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 04/27/2022] [Indexed: 11/28/2022] Open
Abstract
Purpose: The purpose of this study was 1) to predict the requisite vancomycin daily dose (Dvan) used in the target patients suffering from both bacterial infection and hematological malignancies and 2) to construct a vancomycin-dose-graphical tool to assist clinicians to develop vancomycin dosing regimens and further 3) to establish a programming process for vancomycin dynamic dosage adjustment to help clinicians to adjust vancomycin dosing regimens according to physiological and pathogenic factors of the target patients. Methods: The Dvan model associated with microbial susceptibility, vancomycin pharmacokinetics, and dosing parameters was established, and the Dvan was estimated based on the established Dvan model and using Monte Carlo simulations. Dvan achieving 90% of probability of target attainment (PTA) for bacterial isolate or cumulative fractions of response (CFR) for the bacterial population at a ratio of daily area under the curve (AUC24) to the minimum inhibitory concentration (MIC) [i.e., AUC24/MIC] of 400–600 was considered sufficient to treat infection occurring in the target patients. On the basis of the predicted Dvan, the physiological states of patients, and the pathogenic variables of infection, a vancomycin-dose-graphical tool for the target patients and a programming process for vancomycin dynamic dosage adjustment were constructed. Results: This study predicted the requisite Dvan used in patients suffering from both bacterial infection and hematological malignancies and constructed a vancomycin-dose-graphical tool for the target patients, at different physiological states and pathogenic variables, to formulate vancomycin dosing regimens. Also, this study established and expounded the formulation process of vancomycin dosage dynamic adjustment according to fluctuant renal function of the target patients. Conclusion: With the tools, the required Dvan or vancomycin dosing regimens for the target patients, at different physiological states and pathogenic variables, can be readily known, whether or not vancomycin dynamic dosage adjustment is required.
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Wei J, Tong K, Wang H, Wen Y, Chen L. Intra-articular versus systemic vancomycin for the treatment of periprosthetic joint infection after debridement and spacer implantation in a rat model. Bone Joint Res 2022; 11:371-385. [PMID: 35708551 PMCID: PMC9233408 DOI: 10.1302/2046-3758.116.bjr-2021-0319.r3] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Aims Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model. Methods Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation. Results Rats receiving intra-articular vancomycin showed the best outcomes among the four treatment groups, with negative bacterial cultures, increased weight gain, increased capacity for weightbearing activities, increased residual bone volume preservation, and reduced inflammatory reactions in the joint tissues, indicating MRSA eradication in the knee. The vancomycin-spacer and/or systemic vancomycin failed to eliminate the MRSA infections following a two-week antibiotic course. Serum vancomycin levels did not reach nephrotoxic levels in any group. Mild renal histopathological changes, without changes in serum creatinine levels, were observed in the intraperitoneal vancomycin group compared with the intra-articular vancomycin group, but no changes in hepatic structure or serum alanine aminotransferase or aspartate aminotransferase levels were observed. No local complications were observed, such as sinus tract or non-healing surgical incisions. Conclusion Intra-articular vancomycin injection was effective and safe for PJI control following debridement and spacer implantation in a rat model during two-stage revision arthroplasties, with better outcomes than systemic vancomycin administration. Cite this article: Bone Joint Res 2022;11(6):371–385.
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Affiliation(s)
- Jian Wei
- Department of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.,Joint Disease Research Center of Wuhan University, Wuhan, China
| | - Kai Tong
- Department of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.,Joint Disease Research Center of Wuhan University, Wuhan, China
| | - Hui Wang
- Department of Pharmacology, Department of Basic Medicine, Wuhan University, Wuhan, China
| | - Yinxian Wen
- Department of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.,Joint Disease Research Center of Wuhan University, Wuhan, China
| | - Liaobin Chen
- Department of Joint Surgery and Sports Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.,Joint Disease Research Center of Wuhan University, Wuhan, China
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Chuphan C, Sukarnjanaset W, Puthanakit T, Wattanavijitkul T. Population Pharmacokinetics and Pharmacodynamics of Vancomycin in Pediatric Patients With Various Degrees of Renal Function. J Pediatr Pharmacol Ther 2022; 27:419-427. [DOI: 10.5863/1551-6776-27.5.419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/18/2021] [Indexed: 11/11/2022]
Abstract
OBJECTIVE
Although vancomycin dosage recommendations in the pediatric setting for methicillin-resistant Staphylococcus aureus (MRSA) infection indicate that ≥60 mg/kg/day is correlated to a desired area under the vancomycin concentration time curve from 0 to 24 hours to minimum inhibitory concentration ratio (AUC0–24 hr/MIC) ≥400, for some patients this dosage is inadequate or relates to toxicity. This study purposed to explore vancomycin dosing for pediatrics with various degrees of renal function.
METHODS
Routine monitoring data were retrospectively collected from patients, aged 1 month to 18 years. Population pharmacokinetic analysis was performed by using non-linear mixed-effect model with NONMEM software, and Monte Carlo simulation was conducted by using Crystal Ball software.
RESULTS
Two hundred twelve patients with 348 vancomycin serum concentrations were included. Median age was 3.5 years (IQR, 0.9–10.9), median weight was 14.0 kg (IQR, 7.2–30.4), with baseline estimated glomerular filtration rate (eGFR) ranging from 15.5 to 359.3 mL/min/1.73 m2. A 1-compartment model with first-order elimination sufficiently described vancomycin PK. The dosing targeting AUC0–24hr/MIC ≥400 and AUC0–24hr <800 mg•h/L for pediatric patients with eGFRs of 15 to 29, 30 to 59, 60 to 89, 90 to 129, and 130 to 160 mL/min/1.73 m2 was 12.5, 25, 40, 60, and 70 mg/kg/day, respectively. All vancomycin dosing obtained >85% of the cumulative fraction of response across the MIC distribution of MRSA.
CONCLUSIONS
Vancomycin dosing of 12.5, 25, 40, 60, and 70 mg/kg/day is suggested for pediatric patients with eGFRs of 15 to 29, 30 to 59, 60 to 89, 90 to 129, and 130 to 160 mL/min/1.73 m2, respectively.
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Affiliation(s)
- Chanika Chuphan
- Department of Pharmacy Practice (CC, TW), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | | | - Thanyawee Puthanakit
- Department of Pediatrics (TP), Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thitima Wattanavijitkul
- Department of Pharmacy Practice (CC, TW), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
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Abstract
Vancomycin usage is often unavoidable in pregnant patients; however, literature suggests vancomycin can cross the placental barrier and reach the fetus. Understanding the mass transit of vancomycin to the fetus is important in pregnancy. We aimed to (i) identify a relevant population pharmacokinetic (PK) model for vancomycin in pregnancy and (ii) estimate PK parameters and describe the mass transit of vancomycin from mother to pup kidneys. Pregnant Sprague-Dawley rats (i.e., trimester 1 and trimester 3) received 250 mg/kg vancomycin once daily for three days through intravenous injection via an internal jugular vein catheter. Vancomycin concentrations in maternal plasma and pup kidneys were quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple compartment models were fitted and assessed using a nonparametric approach with Pmetrics. A total of 10 vancomycin-treated rats and 48 pups contributed PK data. A 3-compartment model adjusted for trimester fit the data well (maternal plasma Bayesian, observed versus predicted R2 = 0.978; pup kidney Bayesian, observed versus predicted R2 = 0.999). The mean rate constant for vancomycin mass transit to the pup kidney was 0.72 h-1 for trimester 1 dams and 0.75 h-1 for trimester 3 dams. Median vancomycin concentrations in pup kidneys from trimester 3 were significantly higher than those in trimester 1 (8.62 versus 0.36 μg/mL, P < 0.001). Vancomycin transited to the fetus from the mother and was; kidney accumulation differed by trimester. This model may be useful for a translational understanding of vancomycin distribution in pregnancy to ensure efficacious and safe doses to both mother and fetus.
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Li L, Zhang L, Li S, Xu F, Li L, Li S, Lyu J, Yin H. Effect of First Trough Vancomycin Concentration on the Occurrence of AKI in Critically Ill Patients: A Retrospective Study of the MIMIC-IV Database. Front Med (Lausanne) 2022; 9:879861. [PMID: 35492325 PMCID: PMC9049893 DOI: 10.3389/fmed.2022.879861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 03/21/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Vancomycin can effectively inhibit Gram-positive cocci and is widely used in critically ill patients. This study utilized a large public database to explore the effect of patients' first vancomycin trough concentration (FVTC) on the occurrence of acute kidney injury (AKI) and mortality after receiving vancomycin treatment in intensive care unit (ICU). METHODS Critically ill patients who used vancomycin in the Medical Information Mart for Intensive Care (MIMIC) IV have been retrospectively studied. The outcomes included the occurrence of AKI during the use of vancomycin or within 72 h of withdrawal, ICU mortality and hospital mortality. Restricted cubic splines (RCS) were used to analyze the linear relationship between FVTC and the outcomes. Multivariate logistic/Cox regression analysis was used to analyze the association between patient's FVTC and the occurrence of AKI, ICU mortality, and in-hospital mortality. RESULTS The study ultimately included 3,917 patients from the MIMIC-IV database who had been treated with vancomycin for more than 48 h. First of all, the RCS proved the linear relationship between FVTC and the outcomes. After controlling for all covariates as confounders in logistic/Cox regression, FVTC was a risk factor with the occurrence of AKI (OR: 1.02; 95% CI: 1.01-1.04), ICU mortality (HR: 1.02; 95% CI: 1.01-1.03), and in-hospital mortality (HR: 1.02; 95% CI: 1.01-1.03). Moreover, patients were divided into four groups in the light of the FVTC value: group1 ≤ 10 mg/L, 10 20 mg/L. Categorical variables indicated that group 3 and group 4 had a significant relationship on the occurrence of AKI [group 3: (OR: 1.36; 95% CI: 1.02-1.81); group 4: (OR: 1.76; 95% CI: 1.32-2.35)] and ICU mortality [group 3: (HR: 1.47; 95% CI: 1.03-2.09); group 4: (HR: 1.87; 95% CI: 1.33-2.62)], compared to group 1, while group 4 had a significant effect on in-hospital mortality (HR: 1.48; 95% CI: 1.15-1.91). CONCLUSIONS FVTC is associated with the occurrence of AKI and increased ICU and in-hospital mortality in critically ill patients. Therefore, in clinical practice, patients in intensive care settings receiving vancomycin should be closely monitored for FVTC to prevent drug-related nephrotoxicity and reduce patient mortality.
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Affiliation(s)
- Longzhu Li
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Luming Zhang
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Shaojin Li
- Department of Orthopaedics, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Fengshuo Xu
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Li Li
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Shuna Li
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jun Lyu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, China
| | - Haiyan Yin
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, China
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Bian X, Qu X, Zhang J, Nang SC, Bergen PJ, Tony Zhou Q, Chan HK, Feng M, Li J. Pharmacokinetics and pharmacodynamics of peptide antibiotics. Adv Drug Deliv Rev 2022; 183:114171. [PMID: 35189264 PMCID: PMC10019944 DOI: 10.1016/j.addr.2022.114171] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 01/23/2022] [Accepted: 02/16/2022] [Indexed: 01/05/2023]
Abstract
Antimicrobial resistance is a major global health challenge. As few new efficacious antibiotics will become available in the near future, peptide antibiotics continue to be major therapeutic options for treating infections caused by multidrug-resistant pathogens. Rational use of antibiotics requires optimisation of the pharmacokinetics and pharmacodynamics for the treatment of different types of infections. Toxicodynamics must also be considered to improve the safety of antibiotic use and, where appropriate, to guide therapeutic drug monitoring. This review focuses on the pharmacokinetics/pharmacodynamics/toxicodynamics of peptide antibiotics against multidrug-resistant Gram-negative and Gram-positive pathogens. Optimising antibiotic exposure at the infection site is essential for improving their efficacy and minimising emergence of resistance.
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Affiliation(s)
- Xingchen Bian
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; School of Pharmacy, Fudan University, Shanghai, China
| | - Xingyi Qu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; School of Pharmacy, Fudan University, Shanghai, China; Phase I Unit, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Jing Zhang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; Phase I Unit, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Sue C Nang
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia
| | - Phillip J Bergen
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia
| | - Qi Tony Zhou
- Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, USA
| | - Hak-Kim Chan
- Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Meiqing Feng
- School of Pharmacy, Fudan University, Shanghai, China
| | - Jian Li
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia.
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Olney KB, Wallace KL, Mynatt RP, Burgess DS, Grieves K, Willett A, Mani J, Flannery AH. Comparison of Bayesian-derived and first-order analytic equations for calculation of vancomycin area under the curve. Pharmacotherapy 2022; 42:284-291. [PMID: 35134264 PMCID: PMC9750735 DOI: 10.1002/phar.2670] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/10/2021] [Accepted: 12/10/2021] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Consensus guidelines recommend targeting a vancomycin area under the curve to minimum inhibitory concentration (AUC24 :MIC) ratio of 400-600 to improve therapeutic success and reduce nephrotoxicity. Although guidelines specify either Bayesian software or first-order equations may be used to estimate AUC24 , there are currently no large studies directly comparing these methods. OBJECTIVE To compare calculated vancomycin AUC24 using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations. METHODS This was a single-center, retrospective cohort study of 978 adult hospitalized patients receiving intravenous vancomycin between 2017 and 2019. Patients were included if they received at least 72 h of vancomycin and had two-serum drug concentrations obtained. AUC24 was calculated using first-order analytic (linear), Bayesian two-concentration, and Bayesian one-concentration methods for each patient. The InsightRx™ software platform was used to calculate Bayesian AUC24 . Pearson's correlation and clinical agreement (based on AUC24 classified as subtherapeutic, therapeutic, or supratherapeutic) were used to assess agreement between methods. Bland-Altman plots were used to assess mean difference (MD) and 95% limits of agreement (LOA). RESULTS Excellent agreement was observed between linear and Bayesian two-concentration methods (r = 0.963, clinical agreement = 87.4%) and Bayesian two-concentration and one-concentration methods (r = 0.931, clinical agreement = 88.5%); however, a degree of variability was noted with 95% LOA -99 to 76 (MD = -11.5 mg*h/L) and -92 to 113 (MD = -10.4 mg*h/L), for the respective comparisons. The agreement between linear and Bayesian one-concentration approaches was less than prior comparisons (r = 0.823, clinical agreement = 76.8%) and demonstrated the greatest amount of variability with 95% LOA -197 to 153 (MD = -21.9 mg*h/L). CONCLUSIONS Linear and Bayesian two-concentration methods demonstrated high-level agreement with acceptable variability and may be considered comparable to estimate vancomycin AUC24 . As linear and Bayesian one-concentration methods demonstrated significant variability and suboptimal agreement, concerns exist surrounding the interchangeability of these methods in clinical practice, particularly at higher extremes of AUC24 .
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Affiliation(s)
- Katie B. Olney
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky,Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
| | - Katie L. Wallace
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky,Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
| | - Ryan P. Mynatt
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky
| | - David S. Burgess
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
| | - Kaitlyn Grieves
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
| | - Austin Willett
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
| | - Johann Mani
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
| | - Alexander H. Flannery
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky,Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY
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40
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The association of high Vancomycin trough concentration with acute kidney injury during combination therapy of Piperacillin/Tazobactam and Vancomycin. Pract Lab Med 2022; 29:e00266. [PMID: 35111893 PMCID: PMC8789664 DOI: 10.1016/j.plabm.2022.e00266] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/05/2021] [Accepted: 01/14/2022] [Indexed: 11/24/2022] Open
Abstract
Background Co-administration of Piperacillin/Tazobactam (PIPC/TAZ) and Vancomycin (VCM) as an antibiotic therapy for severe infectious diseases increases the risk of nephrotoxicity. We retrospectively investigated the utility of monitoring VCM trough concentration in early stage of developing acute kidney injury (AKI) on this combination therapy. Methods We enrolled all infectious disease patients who were managed with concurrent PIPC/TAZ and VCM. The record of dosage and the administration interval of each antibiotic and its clinical parameters, as well as the VCM trough concentrations, blood culture for bacteria, and serum creatinine values, were collected. VCM trough concentration was measured during the initial 48–72 h of VCM administration. Nephrotoxicity was evaluated as the degree of AKI. Results A total of 47 patients fulfilling the criteria were registered, and AKI developed in 10 patients. There was no statistical difference between the AKI and non-AKI groups with regard to age, height, weight, basal creatinine level, body surface area, body mass index, PIPC/TAZ dose, VCM dose, gender, artificial management, and death within around 30 days. The VCM trough level was increased significantly in the AKI group (mean [standard deviation {SD}]: 25.9 [7.8] μg/mL) compared to that in the non-AKI group (mean [SD]: 15.7 [6.9] μg/mL) (p = 0.003). During the clinical course, renal function returned to normal levels in three out of four AKI stage 2 patients, whereas only partial recovery was achieved in all AKI stage 3 patients. Conclusions A high VCM trough concentration may have an influence on the occurrence of AKI during combination therapy of PIPC/TAZ and VCM. Careful monitoring of VCM trough concentration will be required to prevent AKI progression.
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Matsuzaki T, Kato Y, Mizoguchi H, Yamada K. A machine learning model that emulates experts’ decision making in vancomycin initial dose planning. J Pharmacol Sci 2022; 148:358-363. [DOI: 10.1016/j.jphs.2022.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 01/26/2022] [Accepted: 02/14/2022] [Indexed: 10/19/2022] Open
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Kim Y, Kim S, Park J, Lee H. Clinical Response and Hospital Costs of Therapeutic Drug Monitoring for Vancomycin in Elderly Patients. J Pers Med 2022; 12:jpm12020163. [PMID: 35207653 PMCID: PMC8875716 DOI: 10.3390/jpm12020163] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/01/2022] [Accepted: 01/03/2022] [Indexed: 12/04/2022] Open
Abstract
Cost-effectiveness analysis has been widely used to assess and compare the costs and benefits of a clinical service. The cost-effectiveness of vancomycin therapeutic drug monitoring (TDM) has not been studied in the elderly, who are susceptible to vancomycin-induced adverse effects. This study was performed to evaluate if vancomycin TDM is cost-effective in elderly patients in the Republic of Korea. Using the electronic medical records at a tertiary university hospital, we performed a retrospective observational study to evaluate the cost-effectiveness of vancomycin TDM in 850 elderly patients who underwent vancomycin TDM with an appropriate, recommended dosing regimen and 1094 elderly patients who did not. Cost-effectiveness variables such as clinical outcomes and medical expenses were evaluated using univariate and multivariate analyses. The TDM group spent significantly less than the non-TDM group per patient for total medical expenses (by USD 841.40) and medication expenses (by USD 16.70). However, no significant difference was noted between the TDM and non-TDM groups in clinical outcomes such as microbiological cure, prevention of nephrotoxicity, or reduced mortality, irrespective of admission to the intensive care unit. Vancomycin TDM in elderly patients was associated with economic benefits, but not with better clinical outcomes.
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Affiliation(s)
- Yun Kim
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea; (Y.K.); (J.P.)
- Hanyang Medicine-Engineering-Bio Collaborative & Comprehensive Center for Drug Development (MEBC), Hanyang University, Seoul 04763, Korea
| | - Soohyun Kim
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea;
- Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03087, Korea
| | - Jinsook Park
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea; (Y.K.); (J.P.)
| | - Howard Lee
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea; (Y.K.); (J.P.)
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea;
- Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03087, Korea
- Advanced Institute of Convergence Technology, Suwon-si 16229, Korea
- Correspondence: ; Tel.: +82-2-3668-7602
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Stokes MB, Stevens JS. Vancomycin-Associated Cast Nephropathy: Reality or Fantasy? KIDNEY360 2021; 3:372-375. [PMID: 35373135 PMCID: PMC8967645 DOI: 10.34067/kid.0007282021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 11/30/2021] [Indexed: 01/10/2023]
Affiliation(s)
- Michael B. Stokes
- Department of Pathology, College of Physicians and Surgeons, New York, New York
| | - Jacob S. Stevens
- Department of Medicine, College of Physicians and Surgeons, New York, New York
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Naidu ECS, Olojede SO, Lawal SK, Peter AI, Akang EA, Azu OO. Effects of vancomycin linoleic acid nanoparticles on male reproductive indices of Sprague-Dawley rats. ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY 2021; 49:587-595. [PMID: 34425727 DOI: 10.1080/21691401.2021.1968883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 08/09/2021] [Indexed: 10/20/2022]
Abstract
The management of bacterial infections, especially trains of methicillin-resistant Staphylococcus aureus observe in health care settings, has markedly improved with the introduction of established drugs but using newer nano-based formulations. This study investigates the effects of vancomycin-linoleic acid nanoparticles on testicular tissue in an experimental animal model. Twenty-five adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit were assigned to five groups namely E - solid lipid nanoparticles; F - vancomycin solid lipid nanoparticle; G - linoleic acid nanoparticle; H - vancomycin linoleic acid; and A - control. Perturbations in seminal fluid parameters showed a reduced sperm count in groups F & G which was statistically significant (p < .05) but motility and morphology were not significant when compared to controls (A). Reduced testosterone levels were found in groups E, F and H but were not statistically significant (p > .05). There was also increased luteinizing hormone (LH) and decreased in follicular stimulating hormone (FSH) levels was statistically significant (p < .05). Hypoplasia, tubular atrophy and shrinkage were observed in histologic sections of the treated groups with basement membrane thickening. Vancomycin solid lipid nanoparticle and its constituents SLN and LA disrupted testicular morphometry and the hormonal milieu sufficient to potentially induce altered reproductive function.
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Affiliation(s)
- Edwin Coleridge Stephen Naidu
- Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa
| | - Samuel Oluwaseun Olojede
- Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa
| | - Sodiq Kolawole Lawal
- Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa
| | - Aniekan Imo Peter
- Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa
| | - Edidiong Anamso Akang
- Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa
| | - Onyemaechi Okpara Azu
- Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa
- Department of Anatomy, School of Medicine, University of Namibia, Windhoek, Namibia
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Krueger KM, LaCloche L, Buros Stein A, Kates R, Murray M, Angarone MP. Risk Factors Associated With Nephrotoxicity During Outpatient Intravenous Vancomycin Administration. J Pharm Technol 2021; 38:10-17. [DOI: 10.1177/87551225211054378] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background: Many studies have described an association between intravenous vancomycin and nephrotoxicity; however, the majority have evaluated incidence and risk factors among hospitalized patients. Outpatient administration of intravenous antibiotics is a growing practice and presents its own set of unique challenges. Objective: The aim of this study was to identify risk factors for vancomycin-associated nephrotoxicity in the outpatient setting. Methods: A case-control study of patients who received intravenous vancomycin through an Outpatient Parenteral Antimicrobial Therapy (OPAT) program was conducted. Patients were identified who developed an acute kidney injury (AKI) during treatment. The primary outcome was the incidence of AKI during treatment. Results: A total of 37 out of 130 patients (28.5%) met the criteria for AKI. AKI was more likely to occur in patients with a longer duration of therapy, higher maximum trough concentration, co-administration of a fluoroquinolone or metronidazole, and those who received another potentially nephrotoxic medication. Co-administration of a fluoroquinolone (OR = 5.96, P = 0.009, [CI: 1.59, 24.38]), any nephrotoxic medication (OR = 11.17, P < 0.001, [CI 3.14, 51.23]), and a higher maximum vancomycin trough (OR = 1.29, P < 0.001, [CI 1.17, 1.44]) were all indicative of a higher odds of an AKI. Conclusion: In this cohort, vancomycin-associated nephrotoxicity was common during outpatient intravenous antibiotic therapy. Co-administration of a fluoroquinolone, any nephrotoxic medication, and a higher maximum vancomycin trough were associated with AKI development. Further study is needed to determine how this impacts long-term clinical outcomes and what measures can be taken to reduce nephrotoxicity risk.
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Affiliation(s)
- Karen M. Krueger
- Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Lisa LaCloche
- Infectious Diseases Center, Northwestern Memorial Hospital, Chicago, IL, USA
| | - Amy Buros Stein
- Office of Research and Sponsored Programs, Midwestern University College of Pharmacy, Glendale, AZ, USA
| | - Ryan Kates
- Northwestern Medicine Specialty Pharmacy, Chicago, IL, USA
| | - Milena Murray
- Department of Pharmacy Practice, Midwestern University College of Pharmacy, Downers Grove, IL, USA
- Northwestern Memorial Hospital, Chicago, IL, USA
| | - Michael P. Angarone
- Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Vancomycin-induced nephrotoxicity in non-intensive care unit pediatric patients. Sci Rep 2021; 11:20681. [PMID: 34667202 PMCID: PMC8526611 DOI: 10.1038/s41598-021-00214-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 10/07/2021] [Indexed: 12/30/2022] Open
Abstract
Previous data suggested several risk factors for vancomycin-induced nephrotoxicity (VIN), including higher daily dose, long-term use, underlying renal disease, intensive care unit (ICU) admission, and concomitant use of nephrotoxic medications. We conducted this study to investigate the prevalence and risk factors of VIN and to estimate the cut-off serum trough level for predicting acute kidney injury (AKI) in non-ICU pediatric patients. This was a retrospective, observational, single-center study at Samsung Medical Center tertiary hospital, located in Seoul, South Korea. We reviewed the medical records of non-ICU pediatric patients, under 19 years of age with no evidence of previous renal insufficiency, who received vancomycin for more than 48 h between January 2009 and December 2018. The clinical characteristics were compared between patients with AKI and those without to identify the risk factors associated with VIN, and the cut-off value of serum trough level to predict the occurrence of VIN was calculated by the Youden's index. Among 476 cases, 22 patients (4.62%) developed AKI. The Youden's index indicated that a maximum serum trough level of vancomycin above 24.35 μg/mL predicted VIN. In multivariate analysis, longer hospital stay, concomitant use of piperacillin-tazobactam and serum trough level of vancomycin above 24.35 μg/mL were associated independently with VIN. Our findings suggest that concomitant use of nephrotoxic medication and higher serum trough level of vancomycin might be associated with the risk of VIN. This study suggests that measuring serum trough level of vancomycin can help clinicians prevent VIN in pediatric patients.
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Acute kidney injury associated with area under the curve versus trough monitoring of vancomycin in obese patients. Antimicrob Agents Chemother 2021; 66:e0088621. [PMID: 34633843 DOI: 10.1128/aac.00886-21] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-hour area under the concentration-time curve (AUC24) monitoring, but its safety is unknown in obese populations. Patients ≥18 years, with Body Mass Indices (BMI) ≥30 kg/m2, admitted between August 2015-July 2017 or October 2017-September 2019, who received vancomycin for ≥72 hours and had level(s) drawn within 96 hours of initiation were included. The primary outcome was incidence of AKI. Secondary outcomes included inpatient mortality rate, median inpatient length of stay, median vancomycin trough concentration, and median vancomycin AUC24. AKI was identified using the highest serum creatinine value compared to the value immediately prior to vancomycin initiation based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Overall, 1024 patients met inclusion criteria, with 142 out of 626 patients in the trough group and 65 out of 398 patients in the AUC24 group meeting criteria for AKI (22.7% vs. 16.3%, p=0.008). Logistic regression of the data to account for confounding factors maintained significance for the reduction in incidence of AKI with AUC24 monitoring compared to trough monitoring (p=0.010). Monitoring of vancomycin with AUC24 was associated with a decreased risk of AKI when compared with trough monitoring in obese patients.
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Garreau R, Falquet B, Mioux L, Bourguignon L, Ferry T, Tod M, Wallet F, Friggeri A, Richard JC, Goutelle S. Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient. Antibiotics (Basel) 2021; 10:1228. [PMID: 34680809 PMCID: PMC8532763 DOI: 10.3390/antibiotics10101228] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/30/2021] [Accepted: 09/30/2021] [Indexed: 11/22/2022] Open
Abstract
Background: Vancomycin is widely used for empirical antimicrobial therapy in critically ill patients with sepsis. Continuous infusion (CI) may provide more stable exposure than intermittent infusion, but optimal dosing remains challenging. The aims of this study were to perform population pharmacokinetic (PK) analysis of vancomycin administered by CI in intensive care unit (ICU) patients to identify optimal dosages. Methods: Patients who received vancomycin by CI with at least one measured concentration in our center over 16 months were included, including those under continuous renal replacement therapy (CRRT). Population PK was conducted and external validation of the final model was performed in a dataset from another center. Simulations were conducted with the final model to identify the optimal loading and maintenance doses for various stages of estimated creatinine clearance (CRCL) and in patients on CRRT. Target exposure was defined as daily AUC of 400-600 mg·h/L on the second day of therapy (AUC24-48 h). Results: A two-compartment model best described the data. Central volume of distribution was allometrically scaled to ideal body weight (IBW), whereas vancomycin clearance was influenced by CRRT and CRCL. Simulations performed with the final model suggested a loading dose of 27.5 mg/kg of IBW. The maintenance dose ranged from 17.5 to 30 mg/kg of IBW, depending on renal function. Overall, simulation showed that 55.8% (95% CI; 47-64%) of patients would achieve the target AUC with suggested dosages. Discussion: A PK model has been validated for vancomycin administered by CI in ICU patients, including patients under CRRT. Our model-informed precision dosing approach may help for early optimization of vancomycin exposure in such patients.
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Affiliation(s)
- Romain Garreau
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, France
- Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, UMR CNRS 5558, 69100 Villeurbanne, France
| | - Benoît Falquet
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, France
| | - Lisa Mioux
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, France
| | - Laurent Bourguignon
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, France
- Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, UMR CNRS 5558, 69100 Villeurbanne, France
- Facultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, France
| | - Tristan Ferry
- Facultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, France
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, 69004 Lyon, France
| | - Michel Tod
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, France
- Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, UMR CNRS 5558, 69100 Villeurbanne, France
- Facultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, France
| | - Florent Wallet
- Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Critical Care, 69495 Pierre-Bénite, France
| | - Arnaud Friggeri
- Facultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, France
- Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Critical Care, 69495 Pierre-Bénite, France
- Centre International de Recherche en Infectiologie (CIRI) Inserm, Public Health, Epidemiology and Evolutionary Ecology of Infectious Diseases (PHE3ID), U1111, UCBL Lyon 1, CNRS, UMR5308, ENS de Lyon, 69364 Lyon, France
| | - Jean-Christophe Richard
- Facultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, France
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Service de Médecine Intensive-Réanimation, 69004 Lyon, France
| | - Sylvain Goutelle
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, France
- Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, UMR CNRS 5558, 69100 Villeurbanne, France
- Facultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, France
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He J, Xu W, Zheng X, Zhao B, Ni T, Yu P, Deng S, Pan X, Chen E, Mao E, Bian X. Vitamin C reduces vancomycin-related nephrotoxicity through the inhibition of oxidative stress, apoptosis, and inflammation in mice. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1319. [PMID: 34532456 PMCID: PMC8422136 DOI: 10.21037/atm-21-3294] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/09/2021] [Indexed: 11/22/2022]
Abstract
Background Vancomycin (VCM) is an antibiotic widely used to treat a range of serious bacterial infections; however, it is associated with nephrotoxicity. Vitamin C (VC) is a classical antioxidant that can alleviate various organ injuries and inflammatory responses by reducing inflammation and oxidative stress. This study aimed to examine the effect of VC on VCM-related nephrotoxicity in mice. Methods Mice were randomized into four groups: control, VCM (400 mg/kg/day), VCM (400 mg/kg/day) + VC (200 mg/kg/day), and VC (200 mg/kg/day) groups. Both VCM and VC were administered via intraperitoneal injection for 7 d, after which kidney and blood samples were collected and evaluated. Creatinine (Cr), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and nuclear factor-κB (NF-κB) were measured. Results In the VCM group, kidney index, renal injury score, cell apoptosis, serum Cr and BUN, and kidney Cr, BUN, MDA, IL-1β, IL-6, TNF-α, and NF-κB were higher compared to the control group (all P<0.05), while body weight and kidney SOD activity were lower (both P<0.05). By contrast, no differences were observed between the control and VC groups (VC and VCM + VC groups) for all these indicators. Conclusions The antioxidant VC reduces VCM-related renal injury by reducing oxidative stress, cell apoptosis, and inflammation.
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Affiliation(s)
- Juan He
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenyun Xu
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoxiao Zheng
- Department of Pharmacy, Xuzhou First People's Hospital, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, China
| | - Bing Zhao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tongtian Ni
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ping Yu
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Siyu Deng
- Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoxia Pan
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Erzhen Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Enqiang Mao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaolan Bian
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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A Monocentric Retrospective Study of AUC/MIC Ratio of Vancomycin Associated with Clinical Outcomes and Nephrotoxicity in Patients with Enterococcal Infections. Pharmaceutics 2021; 13:pharmaceutics13091378. [PMID: 34575453 PMCID: PMC8464995 DOI: 10.3390/pharmaceutics13091378] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/28/2021] [Accepted: 08/30/2021] [Indexed: 12/30/2022] Open
Abstract
Vancomycin is an antibiotic commonly used for the treatment of enterococcal infections. However, there is no clear correlation regarding of vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) ratio and clinical outcomes for the treatment of enterococcal infections. The aims of this study were to evaluate the relationship of vancomycin AUC/MIC ratio in patients with clinical outcomes and nephrotoxicity for patients with documented enterococcal infections. A Bayesian technique was used to calculate the average vancomycin AUC0–24. The MIC was determined using the VITEK 2 automated microbiology system, and the average AUC0–24/MIC value was calculated for the first 72 h of therapy. All medical records of patients prescribed vancomycin with therapeutic drug monitoring were collected during January 2010–October 2020 at Chiang Mai University Hospital (CMUH). A retrospective single-center cohort of 312 participants were met the inclusion criteria. The results of this study showed that, a vancomycin AUC/MIC of ≥400 mg·h/L was associated with significant differences in clinical response compared to a vancomycin AUC/MIC of <400 mg·h/L (aHR: 0.50, 95% CI: 0.26–0.97; p = 0.042). Likewise, a vancomycin AUC/MIC of ≥400 mg·h/L was associated with significant differences in the microbiological response (aHR: 0.37, 95% CI: 0.14–0.94; p = 0.036), compared to a vancomycin AUC/MIC of <400 mg·h/L. However, nephrotoxicity in patients with a vancomycin AUC/MIC of ≥400 mg·h/L was higher than those with a vancomycin AUC/MIC of <400 mg·h/L (aHR: 3.96, 95% CI: 1.09–14.47; p = 0.037). Declining renal function may be a result of high vancomycin concentrations. In addition, declining renal function (e.g., failure to resolve the focus of infection, co-administration of other antibiotics) might result in higher AUC/MIC. We found a target vancomycin AUC/MIC of ≥400 mg·h/L and this AUC/MIC target value could be optimal for the use for monitoring treatment of enterococcal infections. Thus, vancomycin dosage must be adjusted to achieve the AUC/MIC target and closely monitored for renal function. These findings are not transferable to critically ill patients.
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