scholarly journals A Monocentric Retrospective Study of AUC/MIC Ratio of Vancomycin Associated with Clinical Outcomes and Nephrotoxicity in Patients with Enterococcal Infections

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1378
Author(s):  
Wasan Katip ◽  
Peninnah Oberdorfer
Keyword(s):  
Renal Function ◽  
Clinical Outcomes ◽  
Area Under The Curve ◽  
University Hospital ◽  
Therapeutic Drug ◽  
Clear Correlation ◽  
Focus Of Infection ◽  
Relationship Of ◽  
Monitoring Treatment ◽  
Enterococcal Infections

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•·hr/L was associated with significant differences in clinical response compared to a vancomycin AUC/MIC of <400 mg•hr/L (aHR: 0.50, 95% CI: 0.26–0.97; p = 0.042). Likewise, a vancomycin AUC/MIC of ≥400 mg*hr/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•hr/L. However, nephrotoxicity in patients with a vancomycin AUC/MIC of ≥400 mg•hr/L was higher than those with a vancomycin AUC/MIC of <400 mg•hr/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•hr/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.

scholarly journals Relationship of Halitosis with Gastric Helicobacter Pylori Infection

2021 ◽  
Vol 15 (7) ◽  
pp. 2285-2288
Author(s):  
Rakhshinda Jabeen ◽  
Ajmaal Jami ◽  
Aiman Shahab ◽  
Armash Shahab
Keyword(s):  
Helicobacter Pylori ◽  
Epigastric Pain ◽  
Human Condition ◽  
Helicobacter Pylori Infection ◽  
University Hospital ◽  
Clear Correlation ◽  
P Value ◽  
Pathophysiological Mechanism ◽  
H Pylori ◽  
Relationship Of

Background: Halitosis is a common human condition; however, the pathophysiological mechanism of halitosis is still unclear. Halitosis is mostly attributed with oral pathological conditions, in addition, halitosis resulting from gastrointestinal disorders is not rare either. Halitosis is often reported with symptoms related to Helicobacter pylori infection, epigastric pain and gastroesophageal reflux disease. Objective: Halitosis can stem from a number of gastric conditions and one of the most common causes of halitosis include the presence of a gastric infection with Helicobacter pylori. This study was conducted to evaluate the incidence ofhalitosis in patients presenting with Helicobacter pylori infection and epigastric pain. Additionally, to review whether there is a correlation between H pylori infection and halitosis; moreover, to determine whether halitosis is a valid indication for H pylori infection. Methods and Materials: This case control, comparative study was done at Medicine department of Isra University hospital and Civil hospital, Karachi during the period of January 2019 to December 2019. Participants were enrolled only after taking verbal and signed consent. Prior permission from the hospital management was taken as well. Result: Halitosis and H pylori are statistically significant with p value of 0.026. There was a clear correlation between halitosis and H pylori infection, and it may be a common contributor to halitosis.

scholarly journals Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and Considerations for Use in the Treatment of Infections Due to KPC-Producing Klebsiella pneumoniae

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Piergiorgio Cojutti ◽  
Assunta Sartor ◽  
Elda Righi ◽  
Claudio Scarparo ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Renal Function ◽  
Klebsiella Pneumoniae ◽  
Monte Carlo Simulations ◽  
Continuous Infusion ◽  
Population Pharmacokinetics ◽  
University Hospital ◽  
Therapeutic Drug ◽  
High Dose ◽  
Content Type

ABSTRACT We assessed the population pharmacokinetics of high-dose continuous-infusion (HDCI) meropenem in a cohort of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) infections. Monte Carlo simulations were used to define the permissible HDCI meropenem regimens that could be safely considered for the treatment of KPC-Kp infections due to meropenem-resistant strains. Permissible doses were arbitrarily defined as those associated with a ≤10% to 15% likelihood of meropenem steady-state concentrations (C ss) of >100 mg/liter. Probabilities of target attainment (PTA) of four incremental pharmacodynamic determinants for meropenem efficacy (100% T>1×MIC, 100% T>2×MIC, 100% T>3×MIC, and 100% T>4×MIC, where “T>MIC” represents the time during which the plasma concentration of this time-dependent antibacterial agent is maintained above the MIC for the pathogen) in relation to different classes of renal function were calculated. The cumulative fractions of response (CFR) for the permissible HDCI meropenem regimens were calculated against the MIC distribution of the KPC-Kp clinical isolates that were collected routinely at our University Hospital between 2013 and 2016 (n = 169). Ninety-seven meropenem C ss were included in the analysis. The final model included creatinine clearance (CrCL) as a covariate and explained 94% of the population variability. Monte Carlo simulations based on licensed dosages of up to 6 g/day predicted an acceptable PTA (>80%) of 100% T>1×MIC against KPC-Kp with a meropenem MIC of ≤32 mg/liter in patients with a CrCL level of <130 ml/min. Dosages of 8 g/day were needed for achieving the same target in patients with CrCL at levels of 130 to 200 ml/min. In dealing with pathogens with a meropenem MIC of 64 mg/liter, HDCI regimens using meropenem at higher than licensed levels should be considered. In these cases, real-time therapeutic drug monitoring could be a useful adjunct for optimized care. The predicted CFR were >75% in all of the classes of renal function.

scholarly journals P428 Early and Late Fecal Calprotectin Remission - Analysis of a proactive Therapeutic Drug Monitoring Treatment Protocol

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S432-S432
Author(s):  
J Pedro ◽  
I Rodrigues ◽  
F Damião ◽  
S Fernandes ◽  
A R Gonçalves ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Outcomes ◽  
Drug Monitoring ◽  
Clinical Remission ◽  
Treatment Protocol ◽  
Surrogate Marker ◽  
Fecal Calprotectin ◽  
Therapeutic Drug ◽  
Monitoring Treatment

Abstract Background Fecal calprotectin (Fc) is an adequate surrogate marker for endoscopic activity in inflammatory bowel disease. The timing of Fc remission may have prognostic implications in patients under biologic therapy. Methods Using a prospectively maintained database we followed 135 patients under a proactive therapeutic drug monitoring (pTDM) protocol aiming at an Infliximab trough level (IFXTL) between 5-10 µg/mL with sequential measurements of Fc. We evaluated the rates of early (at week 14) and late (after week 14) Fc remission (&lt;250 µg/g) and associated clinical outcomes at 2-years of follow up. Results 77 patients (57.0%) reached early Fc remission and 30 patients (22.2%) reached late Fc remission. Patients with late Fc remission presented higher Fc at baseline (1708.5 μg/g [681-3483] vs 803 μg/g [339-1477], P=0.006) and lower IFXTL at week 14 (2.71 µg/mL [1.24-6.30] vs 6.59 µg/mL [3.41-10.63], P=0.001) than patients with early Fc remission. However, by the end of follow-up, IFXTL were similar in both groups: 7.94 µg/mL (4.79-11.25) vs 8.54 µg/mL (6.49-11.07), P=0.514. In patients without early Fc remission, week 14 IFXTL did not differ between those with and without late Fc remission (2.71 µg/mL [1.24-6.30] vs 3.47 µg/mL [0.945-6.94], P=0.957), but significantly increased in late responders by the end of follow-up: 8.54 µg/mL (6.49-11.07) vs 4.37 µg/mL (1.77-7.49), P=0.002. Patients with early and late Fc remission presented similar rates of clinical remission (88.3% vs 83.0%, P=0.493), steroid-free clinical remission (79.1% vs 92.9% P=0.239), lower rates of IFX discontinuation (14.3% vs 16.7%, P=0.756), hospitalization (11.7% vs 13.3%, P=0.815), and surgery (1.3% vs 3.3%, P=0.485). Conclusion The magnitude of Fc at baseline and IFXTL at week 14 significantly influence the timing of Fc remission. The use of PTDM results in similar pharmacokinetics and clinical outcomes in both groups.

Benefits and Limits of Antiretroviral Drug Monitoring in Routine Practice

2019 ◽  
Vol 17 (3) ◽  
pp. 190-197
Author(s):  
Thomas Maitre ◽  
Patrice Muret ◽  
Mathieu Blot ◽  
Anne Waldner ◽  
Michel Duong ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Antiretroviral Treatment ◽  
University Hospital ◽  
Therapeutic Drug ◽  
Routine Practice ◽  
Hiv Viral Load ◽  
Measured Concentration ◽  
The University

Background: HIV infection is a chronic disease for which therapeutic adherence and tolerance require particular attention. Objective: This study aimed to assess whether and when therapeutic drug monitoring (TDM) could be associated with a benefit in routine practice. Methods: All HIV-infected patients who underwent at least one TDM at the University Hospital of Dijon (France) between 1st January 2009 and 31st December 2012 were retrospectively included. Compliance with the recommendations, the results (antiretroviral concentrations), any subsequent therapeutic modifications, and the virological results at 4-8 months were analysed each time TDM was performed. TDM was defined as “practically relevant” when low or high antiretroviral concentrations led to a change in therapy. Results: Of the 571 patients who followed-up, 43.4% underwent TDM. TDM complying with recommendations (120 patients) was associated with a higher proportion of antiretroviral concentrations outside the therapeutic range (p=0.03). Antiretroviral treatment was modified after TDM in 22.6% of patients. Protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir were more significantly modified when the measured concentration was outside the therapeutic range (p=0.008, p=0.05 and p=0.02, respectively). Overall, 11.7% of TDM was considered “practically relevant”, though there was no significant correlation between subsequent changes in antiretroviral treatment and undetectable final HIV viral load. Conclusions: TDM may be a useful tool in the management of HIV infection in specific situations, but the overall benefit seems moderate in routine practice. TDM cannot be systematic and/or a decision tool per se, but should be included in a comprehensive approach in certain clinical situations.

scholarly journals Effect of Obesity on Clinical Failure of Patients Treated with Beta-Lactams

2021 ◽  
Author(s):  
Nathan A Pinner ◽  
Natalie G Tapley ◽  
Katie E Barber ◽  
Kayla R Stover ◽  
Jamie L Wagner
Keyword(s):  
Treatment Failure ◽  
Clinical Outcomes ◽  
Hospital Length Of Stay ◽  
Source Control ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Definitive Therapy ◽  
All Cause Mortality ◽  
The Impact

Abstract Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a beta-lactam (BL) have worse clinical outcomes compared to non-obese patients and to identify if therapeutic drug monitoring (TDM) may be beneficial. Methods This multi-center, retrospective cohort included hospitalized adults admitted from July 2015-July 2017 treated with a BL as definitive monotherapy against a Gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required &gt;1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): non-obese (BMI ≤29.9 kg/m 2) and obese (BMI ≥30.0 kg/m 2). The primary outcome was clinical treatment failure, and secondary were hospital length of stay (LOS), inpatient all-cause mortality, and 30-day all-cause readmission. Results There were 257 (43.6%) obese patients and 332 (56.4%) non-obese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by 3 rd generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) non-obese patients (p&lt;0.001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than non-obese patients (p=0.002), but no differences were found for all-cause mortality (p=0.117) or infection-related readmission (0=0.112). Conclusions Obese patients treated with BLs have higher rates of treatment failure and longer hospitalization periods than non-obese patients. Future studies are needed to assess the impact of TDM and specific dosing recommendations for targeted infection types.

scholarly journals Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19

2021 ◽  
Vol 14 ◽  
pp. 175628482110356
Author(s):  
Lina Zhang ◽  
Huanqin Han ◽  
Xuan Li ◽  
Caozhen Chen ◽  
Xiaobing Xie ◽  
...  
Keyword(s):  
Propensity Score ◽  
Hospital Stay ◽  
Clinical Outcomes ◽  
Clinical Improvement ◽  
Standard Care ◽  
Cox Model ◽  
Improvement Rate ◽  
Viral Shedding ◽  
Microbial Dysbiosis ◽  
Relationship Of

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p < 0.001], and hospital stay [−3 (−5 to −1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

scholarly journals Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure: Joint Analyses with Metabolite Data

2021 ◽  
Vol 14 (2) ◽  
pp. 162
Author(s):  
Félicien Le Louedec ◽  
Fanny Gallais ◽  
Fabienne Thomas ◽  
Mélanie White-Koning ◽  
Ben Allal ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Sampling Strategy ◽  
Predictive Performance ◽  
Pharmacokinetic Profile ◽  
Limited Sampling Strategy ◽  
Joint Analysis ◽  
Therapeutic Drug ◽  
Post Dose ◽  
Limited Sampling ◽  
Three Samples

Therapeutic drug monitoring of ibrutinib is based on the area under the curve of concentration vs. time (AUCIBRU) instead of trough concentration (Cmin,ss) because of a limited accumulation in plasma. Our objective was to identify a limited sampling strategy (LSS) to estimate AUCIBRU associated with Bayesian estimation. The actual AUCIBRU of 85 patients was determined by the Bayesian analysis of the full pharmacokinetic profile of ibrutinib concentrations (pre-dose T0 and 0.5, 1, 2, 4 and 6 h post-dose) and experimental AUCIBRU were derived considering combinations of one to four sampling times. The T0–1–2–4 design was the most accurate LSS (root-mean-square error RMSE = 11.0%), and three-point strategies removing the 1 h or 2 h points (RMSE = 22.7% and 14.5%, respectively) also showed good accuracy. The correlation between the actual AUCIBRU and Cmin,ss was poor (r2 = 0.25). The joint analysis of dihydrodiol-ibrutinib metabolite concentrations did not improve the predictive performance of AUCIBRU. These results were confirmed in a prospective validation cohort (n = 27 patients). At least three samples, within the pre-dose and 4 h post-dose period, are necessary to estimate ibrutinib exposure accurately.

Doing More With Less: Pragmatic Implementation of Vancomycin Area-Under-the-Curve (AUC) Monitoring

2021 ◽  
pp. 089719002110272
Author(s):  
Joanne Huang ◽  
Jeannie D. Chan ◽  
Thu Nguyen ◽  
Rupali Jain ◽  
Zahra Kassamali Escobar
Keyword(s):  
Quality Improvement ◽  
High Risk ◽  
Therapeutic Drug Monitoring ◽  
Paradigm Shift ◽  
Area Under The Curve ◽  
Cost Effective ◽  
Practical Method ◽  
Therapeutic Drug ◽  
Short Term ◽  
Quality Improvement Process

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.

scholarly journals Population Pharmacokinetics and Pharmacodynamics of Levofloxacin in Acutely Hospitalized Older Patients with Various Degrees of Renal Function

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Pier Giorgio Cojutti ◽  
Virginia Ramos-Martin ◽  
Isabella Schiavon ◽  
Paolo Rossi ◽  
Massimo Baraldo ◽  
...  
Keyword(s):  
Renal Function ◽  
Clinical Outcome ◽  
Creatinine Clearance ◽  
Population Pharmacokinetics ◽  
Older Patients ◽  
Classification And Regression Tree ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Content Type ◽  
Cart Analysis

ABSTRACT A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The aim was to assess the population pharmacokinetics (popPK) and pharmacodynamics of levofloxacin among older patients. PopPK and Monte Carlo simulation were performed to define the permissible doses in older patients according to various degrees of renal function. Classification and regression tree (CART) analysis was used to detect the cutoff 24-hour area under the concentration-time curve (AUC24)/MIC ratio that best correlated with the clinical outcome. The probability of target attainment (PTA) of this value was calculated against different pathogens. A total of 168 patients were included, and 330 trough and 239 peak concentrations were used for the popPK analysis. Creatinine clearance (CrCL) was the only covariate that improved the model fit (levofloxacin CL = 0.399 + 0.051 × CrCLCKD-EPI [creatinine clearance estimated by means of the chronic kidney disease epidemiology]). Drug doses ranged between 500 mg every 48 h and 500 mg every 12 h in relation to different renal functions. The identified cutoff AUC24/MIC ratio (≥95.7) was the only covariate that correlated with a favorable clinical outcome in multivariate regression analysis (odds ratio [OR], 20.85; 95% confidence interval [CI], 1.56 to 186.73). PTAs were optimal (>80%) against Escherichia coli and Haemophilus influenzae, borderline against Staphylococcus aureus, and suboptimal against Pseudomonas aeruginosa. The levofloxacin doses defined in our study may be effective for the treatment of infections due to bacterial pathogens, with an MIC of ≤0.5 mg/liter in older patients with various degrees of renal function, while minimizing the toxicity risk. Conversely, the addition of another active antimicrobial should be considered whenever treating infections caused by less susceptible pathogens.

Patient Satisfaction and Short-Term Outcome in Elective Cranial Neurosurgery

Neurosurgery ◽  
2015 ◽  
Vol 77 (5) ◽  
pp. 769-776 ◽  
Author(s):  
Elina Reponen ◽  
Hanna Tuominen ◽  
Juha Hernesniemi ◽  
Miikka Korja
Keyword(s):  
Patient Satisfaction ◽  
Quality Of Care ◽  
Health Status ◽  
Patient Experience ◽  
University Hospital ◽  
Term Outcome ◽  
Major Morbidity ◽  
Patient Reported ◽  
Relationship Of

Abstract BACKGROUND: Patient-reported experience is often used as a measure for quality of care, but no reports on patient satisfaction after cranial neurosurgery exist. OBJECTIVE: To study the association of overall patient satisfaction and surgical outcome and to evaluate the applicability of overall patient satisfaction as a proxy for quality of care in elective cranial neurosurgery. METHODS: We conducted an observational study on the relationship of overall patient satisfaction at 30 postoperative days with surgical and functional outcome (modified Rankin Scale [mRS] score) in a prospective, consecutive, and unselected cohort of 418 adult elective craniotomy patients enrolled between December 2011 and December 2012 at Helsinki University Hospital, Helsinki, Finland. RESULTS: Postoperative overall (subjective and objective) morbidity was present in 194 (46.4%) patients; yet almost 94% of all study patients reported high overall satisfaction. Low overall patient satisfaction at 30 days was not associated with postoperative major morbidity in elective cranial neurosurgery. Dependent functional status (mRS score ≥3) at 30 days, minor infections, poor postoperative subjective overall health status, and patient-reported severe symptoms (double vision, poor balance) may contribute to unsatisfactory patient experience. CONCLUSION: Overall patient satisfaction with elective cranial neurosurgery is high. Even 9 of 10 patients with postoperative major morbidity rated high overall patient satisfaction at 30 days. Overall patient satisfaction may merely reflect patient experience and subjective postoperative health status, and therefore it is a poor proxy for quality of care in elective cranial neurosurgery.

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