scholarly journals Vancomycin loading dose is associated with increased early clinical responses without attainment of initial target trough concentration at a steady state in patients with normal renal function

2019 ◽  
Author(s):  
Takashi Ueda ◽  
Yoshio Takesue ◽  
Kazuhiko Nakajima ◽  
Kaoru Ichiki ◽  
Kaori Ishikawa ◽  
...  
Keyword(s):  
Steady State ◽  
Clinical Response ◽  
Trough Concentration ◽  
Clinical Success ◽  
Quality Data ◽  
Loading Dose ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Significant Difference ◽  
Clinical Responses

Abstract Background Vancomycin therapeutic guidelines suggest a loading dose of 25–30 mg/kg for seriously ill patients. However, high-quality data to guide the use of loading dose are lacking. Evaluate whether a loading dose 1) achieves a target trough concentration (Cmin) at steady state and 2) improves early clinical responses. Methods Patients with an estimated glomerular filtration rate ≥90 mL/min/1.73 m2 were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48–72 h after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci, or Enterococcus faecium. Results There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 µg/mL and 10.2 µg/mL, P=0.538). Proportions of patients achieving 10–20 µg/mL and 15–20 µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, loading dose was associated with increased early clinical responses for all infections [adjusted odds ratio (OR): 4.829, 95% confidence interval (CI): 1.441–16.188] and MRSA infections (OR: 10.851, 95% CI: 1.701–69.233). Increased adverse events were not observed with the loading dose. Study limitations included no Cmin measurements within 24 hours, and the inclusion of less critically ill patients. Conclusions Although the loading dose did not achieve optimal Cmin at steady state, a higher early clinical response was obtained compared with traditional dosing.

scholarly journals Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days

2020 ◽  
Author(s):  
Takashi Ueda ◽  
Yoshio Takesue ◽  
Kazuhiko Nakajima ◽  
Kaoru Ichiki ◽  
Kaori Ishikawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Response ◽  
Clinical Efficacy ◽  
Trough Concentration ◽  
Treatment Efficacy ◽  
Odds Ratio ◽  
Efficacy And Safety ◽  
Conventional Regimen ◽  
Significant Difference ◽  
Clinical Responses

Abstract Background: A trough concentration (Cmin) ≥20 μg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However available data are limited because it is difficult to attain this target Cmin.Methods: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72–96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose.Results: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20–40 μg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥20 μg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25–12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥20 μg/mL.Conclusion: A target Cmin ≥20 μg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.

scholarly journals Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days

2020 ◽  
Author(s):  
Takashi Ueda ◽  
Yoshio Takesue ◽  
Kazuhiko Nakajima ◽  
Kaoru Ichiki ◽  
Kaori Ishikawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Response ◽  
Clinical Efficacy ◽  
Trough Concentration ◽  
Clinical Evidence ◽  
Efficacy And Safety ◽  
Target Concentration ◽  
Conventional Regimen ◽  
Significant Difference ◽  
Clinical Responses

Abstract Background: A trough concentration (Cmin) ≥20 μg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, sufficient clinical evidence to support the efficacy of this target Cmin has not been obtained. Even though the recommended high Cmin of teicoplanin was associated with better clinical outcome, reaching the target concentration is challenging.Methods: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72–96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose.Results: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20–40 μg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥20 μg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25–12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥20 μg/mL.Conclusion: A target Cmin ≥20 μg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.

Inadequacy of FDA Dosing Guidelines for Theophylline Use in Neonates

1986 ◽  
Vol 20 (6) ◽  
pp. 481-484 ◽  
Author(s):  
Jamie T. Gilman ◽  
Peter Gal
Keyword(s):  
Steady State ◽  
Serum Concentration ◽  
Oral Therapy ◽  
Loading Dose ◽  
Serum Concentrations ◽  
Steady State Concentration ◽  
Significant Difference ◽  
Postconceptional Age ◽  
State Concentration

The efficacy of the FDA guidelines for theophylline dosing in newborns was evaluated retrospectively in 224 patients who had clearance data available. Mean projected post loading dose serum concentration was 4.1 ± 1.0 mg/L in 160 patients. Mean projected steady-state concentration was 4.8 ± 1.6 mg/L in 189 patients receiving intravenous aminophylline and 4.2 ± 1.3 mg/L in 35 patients on oral therapy. Projected serum concentrations were subtherapeutic (<6.0 mg/L) in 181 of the 224 patients analyzed. There was a statistically significant difference in serum concentrations between asphyxiated and nonasphyxiated patients (p<0.001). There was no significant difference in mean projected serum concentrations between patients age 26–41 weeks (postconceptional age). This study suggests that the FDA dosing guidelines for theophylline in infants is inadequate and results in subtherapeutic (<6.0 mg/L) serum concentrations in the majority of newborns.

Efficacy and Safety of High Loading Dose of Colistin in Multidrug-Resistant Acinetobacter baumannii: A Prospective Cohort Study

2017 ◽  
Vol 34 (11-12) ◽  
pp. 996-1002 ◽  
Author(s):  
Wasan Katip ◽  
Methisa Meechoui ◽  
Phatchawan Thawornwittayakom ◽  
Dujrudee Chinwong ◽  
Peninnah Oberdorfer
Keyword(s):  
Cohort Study ◽  
Clinical Response ◽  
Prospective Cohort ◽  
Maintenance Dose ◽  
Dose Group ◽  
Multidrug Resistant ◽  
High Loading ◽  
Loading Dose ◽  
Efficacy And Safety ◽  
Significant Difference

Objectives: We aimed to assess the efficacy and safety of a high loading dose of colistin and no loading dose of colistin to treat multidrug-resistant (MDR) Acinetobacter baumannii infections. Methods: We conducted a prospective cohort study of patients with MDR A baumannii infections at a university-affiliated hospital from December 2014 to January 2016. In the high loading dose group, the patients received a high loading dose of 300 mg colistin base activity (CBA) followed by a maintenance dose of 150 mg CBA twice daily, and patients in the no loading dose group received only the maintenance dose. The primary outcome was clinical response. The secondary outcomes were 28-day mortality and microbiological response. Results: A total of 255 cases were identified. The high loading dose of colistin strategy provided no significant difference in good clinical response when compared to the no loading dose group (65.5% vs 70.4%; P = .442), without a significant difference in the development of renal dysfunction (52.3% vs 49.4%; P = .664). However, microbiological eradication was significantly higher among patients who received the high loading dose of colistin when compared to those who received the no loading dose (87.9% vs 70.4%; P = .0006). Conclusions: The high loading dose of colistin strategy was effective and safe for treating patients with MDR A baumannii.

Association of CYP2D6*10 (c. 100 C>T) Genotype with Z-END Concentration in Patients with Breast Cancer Receiving Tamoxifen Therapy in Indonesian Population

2019 ◽  
Vol 19 (8) ◽  
pp. 1198-1206 ◽  
Author(s):  
Yenny ◽  
Sonar S. Panigoro ◽  
Denni J. Purwanto ◽  
Adi Hidayat ◽  
Melva Louisa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Steady State ◽  
Ultra Performance Liquid Chromatography ◽  
Cross Sectional Study ◽  
Threshold Concentration ◽  
Breast Cancer Patients ◽  
Cross Sectional ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Liquid Chromatography Tandem Mass

Background: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Objective: The purpose of the study was to determine the association between CYP2D6*10 (c.100C>T) genotype and attainment of the plasma steady-state Z-END minimal threshold concentration (MTC) in Indonesian women with breast cancer. Methods: A cross-sectional study was performed in 125 ambulatory patients with breast cancer consuming TAM at 20 mg/day for at least 4 months. The frequency distribution of CYP2D6*10 (c.100C>T) genotypes (C/C: wild type; C/T: heterozygous mutant; T/T: homozygous mutant) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the results of which were subsequently confirmed by sequencing. The genotypes were categorized into plasma Z- END concentrations of <5.9 ng/mL and ≥5.9 ng/mL, which were measured using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results: Percentages of C/C, CT, and T/T genotypes were 22.4%, 29.6%, and 48.8%, respectively. Median (25-75%) Z-END concentrations in C/C, C/T, and T/T genotypes were 9.58 (0.7-6.0), 9.86 (0.7-26.6), and 3.76 (0.9-26.6) ng/mL, respectively. Statistical analysis showed a significant difference in median Z-END concentration between patients with T/T genotype and those with C/C or C/T genotypes (p<0.001). There was a significant association between CYP2D6*10 (c.100C>T) genotypes and attainment of plasma steady-state Z-END MTC (p<0.001). Conclusion: There was a significant association between CYP2D6*10 (c.100C>T) and attainment of plasma steady-state Z-END MTC in Indonesian breast cancer patients receiving TAM at a dose of 20 mg/day.

scholarly journals Efficacy of loading dose colistin versus carbapenems for treatment of extended spectrum beta lactamase producing Enterobacteriaceae

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wasan Katip ◽  
Jukapun Yoodee ◽  
Suriyon Uitrakul ◽  
Peninnah Oberdorfer
Keyword(s):  
Clinical Response ◽  
Clinical Information ◽  
Resistant Bacteria ◽  
Loading Dose ◽  
Extended Spectrum Beta Lactamase ◽  
Clinical Utilization ◽  
The Difference ◽  
Infection Types ◽  
Intra Abdominal Infection

AbstractColistin provides in vitro activity against numerous ESBL-producing and carbapenem-resistant bacteria. However, clinical information with respect to its utilization in infection caused by ESBL producers is limited. The aim of this study was a comparison of mortality rates of loading dose (LD) colistin and carbapenems as definitive therapies in a cohort of patients with infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae. A retrospective cohort study in 396 patients with ESBL-producing E.coli and K.pneumoniae infection at a university-affiliated hospital was conducted between 1 January 2005 and 30 June 2015 to compare outcomes of infected patients who received LD colistin (95 patients) with carbapenems (301 patients). The three primary outcomes were 30-day mortality, clinical response and microbiological response. The most common infection types were urinary tract infection (49.49%), followed by pneumonia (40.66%), bacteremia (13.64%), skin and soft tissue infections (4.80%) and intra-abdominal infection (3.03%). LD colistin group provided higher 30-day mortality when compared with carbapenems group (HR 7.97; 95% CI 3.68 to 17.25; P = 0.001). LD colistin was also independently associated with clinical failure (HR 4.30; 95% CI 1.93 to 9.57; P = 0.001) and bacteriological failure (HR 9.49; 95% CI 3.76 to 23.96; P = 0.001) when compared with those who received carbapenems. LD colistin treatment was associated with poorer outcomes, i.e. mortality rate, clinical response and microbiological response. Moreover, when adjusted confounding factors, LD colistin was still less effective than carbapenems. It should be noted that, however, the use of Vitek-2 to assess colistin susceptibility could provide inaccurate results. Also, the difference in baseline characteristics could still remain in retrospective study although compensation by hazard ratio adjustment was performed. Therefore, clinical utilization of LD colistin should be recommended as an alternative for treatment ESBL-producing Enterobacteriaceae only in the circumstances where carbapenems cannot be utilized, but this recommendation must be considered carefully.

scholarly journals Nasopharyngeal Carriage of Methicillin-Resistant Staphylococcus aureus (MRSA) among Sickle Cell Disease (SCD) Children in the Pneumococcal Conjugate Vaccine Era

2021 ◽  
Vol 13 (1) ◽  
pp. 191-204
Author(s):  
Nicholas T. K. D. Dayie ◽  
Deborah N. K. Sekoh ◽  
Fleischer C. N. Kotey ◽  
Beverly Egyir ◽  
Patience B. Tetteh-Quarcoo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Sickle Cell Disease ◽  
Conjugate Vaccine ◽  
Sickle Cell ◽  
Pneumococcal Conjugate Vaccine ◽  
Diffusion Method ◽  
Nasopharyngeal Carriage ◽  
Cell Disease ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant

The aim of this cross-sectional study was to investigate Staphylococcus aureus nasopharyngeal carriage epidemiology in relation to other nasopharyngeal bacterial colonizers among sickle cell disease (SCD) children about five years into pneumococcal conjugate vaccine 13 (PCV-13) introduction in Ghana. The study involved bacteriological culture of nasopharyngeal swabs obtained from 202 SCD children recruited from the Princess Marie Louise Children’s Hospital. S. aureus isolates were identified using standard methods and subjected to antimicrobial susceptibility testing using the Kirby-Bauer disc diffusion method. Cefoxitin-resistant S. aureus isolates were screened for carriage of the mecA, pvl, and tsst-1 genes using multiplex polymerase chain reaction. The carriage prevalence of S. aureus was 57.9% (n = 117), and that of methicillin-resistant S. aureus (MRSA) was 3.5% (n = 7). Carriage of the mecA, pvl, and tsst-1 genes were respectively demonstrated in 20.0% (n = 7), 85.7% (n = 30), and 11.4% (n = 4) of the cefoxitin-resistant S. aureus isolates. PCV-13 vaccination (OR = 0.356, p = 0.004) and colonization with coagulase-negative staphylococci (CoNS) (OR = 0.044, p < 0.0001) each protected against S. aureus carriage. However, none of these and other features of the participants emerged as a determinant of MRSA carriage. The following antimicrobial resistance rates were observed in MRSA compared to methicillin-sensitive S. aureus: clindamycin (28.6% vs. 4.3%), erythromycin (42.9% vs. 19.1%), tetracycline (100% vs. 42.6%), teicoplanin (14.3% vs. 2.6%), penicillin (100% vs. 99.1%), amoxiclav (28.6% vs. 3.5%), linezolid (14.3% vs. 0.0%), ciprofloxacin (42.9% vs. 13.9%), and gentamicin (42.9% vs. 13.0%). The proportion of S. aureus isolates that were multidrug resistant was 37.7% (n = 46). It is concluded that S. aureus was the predominant colonizer of the nasopharynx of the SCD children, warranting the continuous monitoring of this risk group for invasive S. aureus infections.

scholarly journals Short-Course Versus Long-Course Colistin for Treatment of Carbapenem-Resistant A.baumannii in Cancer Patient

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 484
Author(s):  
Wasan Katip ◽  
Suriyon Uitrakul ◽  
Peninnah Oberdorfer
Keyword(s):  
Clinical Response ◽  
Cancer Patients ◽  
Therapy Group ◽  
University Hospital ◽  
P Value ◽  
Chiang Mai ◽  
Carbapenem Resistant ◽  
Short Course ◽  
Significant Difference ◽  
Long Course

Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly reported nosocomial infections in cancer patients and could be fatal because of suboptimal immune defenses in these patients. We aimed to compare clinical response, microbiological response, nephrotoxicity, and 30-day mortality between cancer patients who received short (<14 days) and long (≥14 days) courses of colistin for treatment of CRAB infection. A retrospective cohort study was conducted in cancer patients with CRAB infection who received short or long courses of colistin between 2015 to 2017 at Chiang Mai University Hospital (CMUH). A total of 128 patients met the inclusion criteria. The results of this study show that patients who received long course of colistin therapy had a higher rate of clinical response; adjusted odds ratio (OR) was 3.16 times in patients receiving long-course colistin therapy (95%CI, 1.37–7.28; p value = 0.007). Microbiological response in patients with long course was 4.65 times (adjusted OR) higher than short course therapy (95%CI, 1.72–12.54; p value = 0.002). Moreover, there was no significant difference in nephrotoxicity (adjusted OR, 0.91, 95%CI, 0.39–2.11; p value = 0.826) between the two durations of therapy. Thirty-day mortality in the long-course therapy group was 0.11 times (adjusted OR) compared to the short-course therapy group (95%CI, 0.03–0.38; p value = 0.001). Propensity score analyses also demonstrated similar results. In conclusion, cancer patients who received a long course of colistin therapy presented greater clinical and microbiological responses and lower 30-day mortality but similar nephrotoxicity as compared with those who a received short course. Therefore, a long course of colistin therapy should be considered for management of CRAB infection in cancer patients.

scholarly journals Modeling and Optimizing the Multi-Objective Portfolio Optimization Problem with Trapezoidal Fuzzy Parameters

2021 ◽  
Vol 26 (2) ◽  
pp. 36
Author(s):  
Alejandro Estrada-Padilla ◽  
Daniela Lopez-Garcia ◽  
Claudia Gómez-Santillán ◽  
Héctor Joaquín Fraire-Huacuja ◽  
Laura Cruz-Reyes ◽  
...  
Keyword(s):  
Steady State ◽  
Portfolio Optimization ◽  
Optimization Problem ◽  
Solution Process ◽  
Density Estimator ◽  
Nsga Ii ◽  
Spatial Spread ◽  
Multi Objective ◽  
Significant Difference ◽  
Portfolio Optimization Problem

A common issue in the Multi-Objective Portfolio Optimization Problem (MOPOP) is the presence of uncertainty that affects individual decisions, e.g., variations on resources or benefits of projects. Fuzzy numbers are successful in dealing with imprecise numerical quantities, and they found numerous applications in optimization. However, so far, they have not been used to tackle uncertainty in MOPOP. Hence, this work proposes to tackle MOPOP’s uncertainty with a new optimization model based on fuzzy trapezoidal parameters. Additionally, it proposes three novel steady-state algorithms as the model’s solution process. One approach integrates the Fuzzy Adaptive Multi-objective Evolutionary (FAME) methodology; the other two apply the Non-Dominated Genetic Algorithm (NSGA-II) methodology. One steady-state algorithm uses the Spatial Spread Deviation as a density estimator to improve the Pareto fronts’ distribution. This research work’s final contribution is developing a new defuzzification mapping that allows measuring algorithms’ performance using widely known metrics. The results show a significant difference in performance favoring the proposed steady-state algorithm based on the FAME methodology.

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