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1.
Konstantinos Z. Vardakas Georgios L. Voulgaris George Samonis Matthew E. Falagas 《International journal of antimicrobial agents》2018,51(1):1-9
Background
Inhaled colistin is becoming increasingly popular against respiratory tract infections caused by multidrug resistant (MDR) Gram-negative bacteria because it may overcome the problems associated with intravenous (IV) administration.Objective
To investigate the effectiveness and safety of inhaled colistin as monotherapy (without concomitant IV administration of colistin) in the treatment of respiratory tract infections caused by MDR or colistin–only susceptible Gram–negative bacteria.Methods
PubMed and Scopus databases were searched. A systematic review and meta-analysis were conducted.Results
Twelve studies (373 patients receiving inhaled colistin for respiratory tract infection) were included. Ten studies evaluated patients with pneumonia (including 8 studies with ventilator-associated pneumonia) and 2 studies evaluated patients with ventilator-associated tracheobronchitis. Patients with infections due to MDR Acinetobacter baumannii and Pseudomonas aeruginosa were mainly studied. Daily dose of inhaled colistin and treatment duration varied in the individual studies. The pooled all-cause mortality was 33.8% (95% CI 24.6% – 43.6%), clinical success was 70.4% (58.5% – 81.1%) and eradication of Gram-negative bacteria was shown in 71.3% (57.6% – 83.2%) of cases.Conclusions
Inhaled colistin monotherapy may deserve further consideration as a mode for colistin administration for the treatment of respiratory tract infections caused by MDR A. baumannii and P. aeruginosa. 相似文献2.
Michael A. Pfaller Robert K. Flamm Mariana Castanheira Helio S. Sader Rodrigo E. Mendes 《International journal of antimicrobial agents》2018,51(4):608-611
Background
Osteomyelitis is a difficult-to-treat infection that regularly involves prolonged use of systemic antibiotics. Dalbavancin has demonstrated activity against Gram-positive isolates, and has been considered as a candidate for the treatment of osteomyelitis in adults and children. This study evaluated the activity of dalbavancin against pathogens isolated from bone and joint infections (BJI).Methods
Eight hundred and one Staphylococcus aureus, 160 coagulase-negative staphylococci (CoNS), 164 β-haemolytic streptococci (BHS), 82 Enterococcus faecalis and 45 viridans group streptococci (VGS) causing BJI were collected consecutively (2011–2016) and tested for susceptibility by broth microdilution methods.Results
S. aureus (64.0%) was the most common pathogen associated with BJI, followed by BHS (13.1%) and CoNS (12.8%). All S. aureus (33.3% meticillin-resistant) isolates were susceptible to dalbavancin, linezolid and vancomycin, while daptomycin and clindamycin showed susceptibility rates of 99.5% and 89.0%, respectively. The minimum inhibitory concentration (MIC) results for dalbavancin were at least eight-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS (63.1% meticillin-resistant), followed by daptomycin, linezolid and vancomycin. All E. faecalis isolates were inhibited by dalbavancin at ≤0.25?mg/L (US Food and Drug Administration susceptibility breakpoint), except for three vancomycin-resistant isolates. High susceptibility rates for ampicillin (98.8%), daptomycin (100.0%), linezolid (100.0%) and vancomycin (95.1%) were obtained against E. faecalis. Dalbavancin was very active against BHS (MIC90 ≤0.03?µg/mL), and was the most active agent against VGS (highest MIC ≤0.06?mg/L). Ceftriaxone, daptomycin and vancomycin were also active (93.3–100.0% susceptible) against VGS, whereas clindamycin (84.4% susceptible) had marginal activity.Conclusion
Dalbavancin appears to be a viable candidate for treating BJI/osteomyelitis caused by Gram-positive cocci. 相似文献3.
Alejandro Pérez-Pitarch Rafael Ferriols-Lisart Gerardo Aguilar Carlos Ezquer-Garín F. Javier Belda Beatriz Guglieri-López 《International journal of antimicrobial agents》2018,51(1):115-121
Introduction
The study objective was to evaluate the efficacy of different dosages of caspofungin in the treatment of invasive candidiasis and aspergillosis, in relation to the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment, using modelling and Monte Carlo simulations in critically ill adult patients on continuous haemodiafiltration.Methods
Critically ill adult patients on continuous venovenous haemodiafiltration treated with caspofungin were analysed. A population PK model was developed. Four caspofungin dosing regimens were simulated: the licensed regimen, 70 mg/day, 100 mg/day or 200 mg/day. A PK/PD target was defined as the ratio between the area under the caspofungin concentration-time curve over 24 hours and the minimal inhibitory concentration (AUC/MIC) for candidiasis or the minimal effective concentrations (AUC/MEC) for Aspergillus spp. Target attainment based on preclinical target for Candida and Aspergillus was assessed for different MIC or MEC, respectively.Results
Concentration-time data were described by a two-compartment model. Body–weight and protein concentration were the only covariates identified by the model. Goodness-of-fit plots and bootstrap analysis proved the model had a satisfactory performance. As expected, a higher maintenance dose resulted in a higher exposure. Target attainment was >90% for candidiasis (MIC≤0.06 mg/L) and aspergillosis (MEC≤0.5 mg/L), irrespective of the dosing regimen, but not for C. parapsilosis. Standard regimen was insufficient to reach the target for C. albicans and C. parapsilosis with MIC≥0.1 mg/L.Conclusion
The licensed regimen of caspofungin is insufficient to achieve the PK/PD targets in critically ill patients on haemodiafiltration. The determination of MICs will enable dose scheme selection. 相似文献4.
Konstantinos Z. Vardakas Andreas D. Mavroudis Maria Georgiou Matthew E. Falagas 《International journal of antimicrobial agents》2018,51(4):535-547
Background
To evaluate whether intravenous colistin in combination with other antibiotics (IVCC) is associated with lower mortality compared with intravenous colistin monotherapy (IVCM), and to identify factors influencing study outcomes.Methods
PubMed and Scopus were searched up to November 2016. Studies were included if they evaluated adult patients with multi-drug-resistant (MDR) or extensively-drug-resistant Gram-negative infections, and reported comparative mortality data (adjusted and unadjusted) for patients receiving IVCC vs. IVCM. Random effects meta-analyses were performed.Findings
Thirty-two studies (29 observational, three randomized) were included. The overall quality of data was low to very low, and studies were characterized by the lack of adjusted data. The majority of studies were not designed to evaluate the outcome of the meta-analysis, and focused mainly on infections due to Acinetobacter baumannii and Klebsiella pneumoniae. Colistin was administered at variable doses, with or without a loading dose, and in combination with several antibiotics. Overall, IVCC was not associated with lower mortality than IVCM [32 studies, 2328 patients, risk ratio (RR) 0.91, 95% confidence interval (CI) 0.81–1.02, I2 8%]. A significant difference was observed in favour of IVCC when high-dose (>6 million international units) colistin was used (RR 0.80, 95% CI 0.69–0.93), in studies conducted in Asia (RR 0.82, 95% CI 0.71–0.95), in patients with bacteraemia (RR 0.75, 95% CI 0.57–0.98) and in patients with acinetobacter infections (RR 0.88, 95% CI 0.78–1.00).Interpretation
Overall, low-quality data suggest that IVCC did not lower mortality in patients with MDR Gram-negative infections. However, there is some evidence for a benefit observed with high intravenous doses of colistin. 相似文献5.
Barbara A. Santevecchi Tiffeny T. Smith Shawn H. MacVane 《International journal of antimicrobial agents》2018,51(4):629-635
Background
Ceftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited.Methods
A retrospective case series was performed to evaluate patients treated with ceftazidime/avibactam for infections caused by organisms other than K. pneumoniae at our institution over a 1-year period. Patients aged at least 18 years who received at least one dose of ceftazidime/avibactam were eligible for inclusion. Clinical and microbiological data were collected, and investigators assessed adverse effects, microbiological cure, clinical success, and 30-day in-hospital mortality following completion of ceftazidime/avibactam therapy.Results
Ten patients were included. The most common index infection was pneumonia (n?=?6/13, 46%) and the most frequently isolated organism was Pseudomonas aeruginosa (n?=?8/21, 38%). Fifty percent of patients received ceftazidime/avibactam as monotherapy. Microbiological cure was achieved in 67% (n?=?6/9) of patients and 70% (n?=?7/10) of patients met criteria for clinical success. The 30-day in-hospital mortality rate was 30%. No patients experienced adverse events because of ceftazidime/avibactam therapy.Conclusions
For infections caused by antibiotic-resistant Gram-negative organisms other than K. pneumoniae, clinical and microbiological success rates for patients treated with ceftazidime/avibactam were similar to those that have been reported for K. pneumoniae. Ceftazidime/avibactam appears to be a promising treatment option for infections caused by a variety of resistant Gram-negative organisms when limited alternatives exist. 相似文献6.
Michele Bartoletti Sara Tedeschi Renato Pascale Luigi Raumer Alberto Enrico Maraolo Giulia Palmiero Fabio Tumietto Francesco Cristini Simone Ambretti Maddalena Giannella Russell Edward Lewis Pierluigi Viale 《International journal of antimicrobial agents》2018,51(3):516-521
Objectives
We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra–abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.Methods
We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves.Results
We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002–0.72, P?=?0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68–2.78, P?=?0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03–0.71, P?=?0.02), but not CRE (HR 1.12, 95% CI 0.45–2.83, P?=?0.80). All-cause 30-day mortality was similar in the two groups (P?=?0.46).Conclusion
TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation. 相似文献7.
Marjan Wouthuyzen-Bakker Eduard Tornero Laura Morata Prashant V. Nannan Panday Paul C. Jutte Guillem Bori Greetje A. Kampinga Alex Soriano 《International journal of antimicrobial agents》2018,51(1):38-42
Objectives
The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin–susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin.Methods
Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005–2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up.Results
Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C–reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P?=?0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P?=?0.36), treatment was successful in 89% vs. 87.5%, respectively (P?=?0.89). None of the failures in the moxifloxacin group were due to rifampin– or moxifloxacin–resistant S. aureus strains.Conclusion
Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA. 相似文献8.
Eyal Kleinhendler Matan J. Cohen Allon E. Moses Ora Paltiel Jacob Strahilevitz Amos Cahan 《International journal of antimicrobial agents》2018,51(1):71-76
Background
There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols.Methods
Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given.Results
In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38?°C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P?=?0.13 and 76%, P?=?0.002, respectively) and imipenem (93%, P?=?0.004 and 92%, P?=?0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days.Conclusion
Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients. 相似文献9.
Takeshi Ide Yoshio Takesue Kazuro Ikawa Norifumi Morikawa Takashi Ueda Yoshiko Takahashi Kazuhiko Nakajima Kenta Takeda Shinichi Nishi 《International journal of antimicrobial agents》2018,51(5):745-751
Purpose
The purpose of this study was to identify the optimum dosing regimen of linezolid in sepsis patients with and without renal dysfunction and sepsis patients on low-dose continuous renal replacement therapy (CRRT) using a pharmacokinetics/pharmacokinetics (PK/PD) approach.Methods
Sepsis patients with and without renal dysfunction (creatinine clearance?<?50?mL/min), and sepsis patients on low-dose CRRT (dose: 800?mL/h) were studied. The PK data were modeled using a two-compartment model, and then used for simulation. The target PK/PD was the 24-h area under the concentration-time curve to minimum inhibitory concentration ratio of?≥?80. Dosing regimens were evaluated using cumulative fraction of response (CFR) and safety probability (trough level?<?7?µg/mL) by Monte Carlo simulation.Results
Twenty-seven patients, including 8 patients with preserved renal function, 9 patients with renal dysfunction, and 10 patients on CRRT, were studied. The proposed regimen to attain CFR?≥?90% was 800?mg every 12?h (safety probability 82.4%) for patients with preserved renal function. By contrast, the target CFR was attained with a decreased regimen in patients with renal dysfunction and those on CRRT [600?mg every 24h (safety probability 68.6%) and 800?mg every 24h (42.1%)].Conclusions
We identified different dosage strategies to achieve target linezolid concentrations according to renal function and use of CRRT in sepsis patients. Because of unassured safety probability in patients without preserved renal function, dosing regimens should be adjusted based on the therapeutic drug monitoring. 相似文献10.
11.
Justin Tenney Nicholas Hudson Hazar Alnifaidy Justin Ting Cheung Li Kathy Harriet Fung 《Saudi Pharmaceutical Journal》2018,26(5):678-684
Background
This is the first review to analyze literature identifying risk factors for a multidrug-resistant urinary tract infection (MDR UTI). Risk factors for other infections involving multidrug-resistant organisms have been evaluated in other reviews, but they do not assess urinary tract infections. The purpose of this study is to collect currently published data to determine the most commonly and consistently identified risk factors for UTIs.Material and methods
For this study, 3 independent researchers searched PubMed, Embase, and Cochrane database from 1966 to February 2016 for articles identifying risk factors for MDR UTI.Results
A total of 25 studies including 31,284 patients with positive cultures provide evidence for 12 possible risk factors for MDR UTI . The most commonly identified risk factor was previous antibiotic usage as evidenced in 16 of the 20 studies that evaluated this possible risk factor. The time range utilized to define previous antibiotic usage ranged from 2?days to 365?days. Other risk factors with the strongest supporting data were urinary catheterization, previous hospitalization, and nursing home residence.Conclusion
We identified 12 different possible risk factors for a MDR UTI, however several risk factors have minimal or conflicting evidence. The definitions of the risk factors varied widely among the studies, and should be standardized for future studies. 相似文献12.
Maddalena Giannella Enrico Maria Trecarichi Daniele Roberto Giacobbe Francesco Giuseppe De Rosa Matteo Bassetti Alessandro Bartoloni Michele Bartoletti Angela Raffaella Losito Valerio del Bono Silvia Corcione Sara Tedeschi Francesca Raffaelli Carolina Saffioti Teresa Spanu Gian Maria Rossolini Anna Marchese Simone Ambretti Roberto Cauda Mario Tumbarello 《International journal of antimicrobial agents》2018,51(2):244-248
Objectives
To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).Methods
Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.Results
595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16?mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20–1.43, P?<0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19–4.50, P?<0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02–2.24, P?=?0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25–0.78, P?=?0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47–1.00, P?=?0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43–0.95, P?=?0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16?mg/L.Conclusions
In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance. 相似文献13.
Eric Wenzler Kristen L. Bunnell Larry H. Danziger 《International journal of antimicrobial agents》2018,51(5):700-706
Background
There is a need to identify practice patterns of polymyxin use, quantify gaps in knowledge, and recognize areas of persistent confusion.Methods
A structured electronic survey was distributed to physicians, pharmacists and microbiologists. Demographic information was obtained, along with data regarding availability, stewardship principles, therapeutic usage, dosing, microbiological testing, and knowledge, attitudes and beliefs regarding the polymyxins.Results
In total, there were 420 respondents with a median of 8 (interquartile range 4–15) years of experience in infectious diseases (52.5%) and critical care (35%). Of the respondents who reported that only one polymyxin was available for use, 17.1% used polymyxin B. Over half (52.5%) of the respondents utilized a loading dose very often/always, and 66.8% dosed both polymyxins in milligrams, with the most common doses of colistin and polymyxin B being 2.5?mg/kg twice daily (60.3%) and 1.5?mg/kg twice daily (65%), respectively, for patients with normal renal function. Polymyxins were most often used for respiratory infections (63%) in combination with a carbapenem (63.6%). Approximately 85% of respondents reported their knowledge level to be fair, good or very good, although 34.9% answered two of the three knowledge questions incorrectly. More than 70% of respondents agreed that confusion exists in all surveyed areas of polymyxin use. Almost all respondents (91.2%) agreed that a polymyxin guideline would be a helpful resource.Conclusions
This survey revealed objective and subjective variability in the use and perception of the polymyxins, and identified several areas in which they were being used contrary to the available evidence. The information provided herein lays the framework to harmonize clinical practice, guide future research and shape consensus guidelines. 相似文献14.
Rajendar K. Mittapalli Patrick Marroum Yihong Qiu Kathleen Apfelbaum Hao Xiong 《Pharmaceutical research》2017,34(7):1527-1533
Purpose
To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations.Methods
Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability.Results
With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (Ae0–24h) and maximum urinary excretion rate (Rmax) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%.Conclusions
A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.15.
An-Kuo Chou Chong-Chi Chiu Yu-Wen Chen Jhi-Joung Wang Ching-Hsia Hung 《Pharmacological reports : PR》2018,70(6):1180-1184
Background
Pramoxine has been shown to produce spinal anesthesia, while cutaneous analgesia (peripheral) of pramoxine is not established. The experimental goal was to examine cutaneous antinociception produced by a local anesthetic (LA) pramoxine and compare this result with that of another well-known LA lidocaine.Methods
Cutaneous antinociception was evaluated by blockade of pinprick- induced cutaneous trunci muscle reflex (CTMR) on the skin of rat's back. After the dose–related curves were constructed, the quality and duration of drug's (lidocaine and pramoxine) cutaneous antinociception were compared.Results
We showed that pramoxine, as well as lidocaine produced skin antinociception in a dose–related fashion. The relative potency (ED50 [50% effective dose] basis) was lidocaine (5.44 [4.67–6.35] μmol) greater than pramoxine (42.1 [38.8–45.7] μmol) (p < 0.01). On the basis of equianalgesic doses (ED75, ED50, and ED25), pramoxine caused equivalent duration of cutaneous antinociception to lidocaine.Conclusions
These preclinical data indicated that pramoxine elicits skin antinociception dose-relatedly. Pramoxine exhibits a potency less than that of lidocaine while they have a comparable duration of skin antinociceptive action. 相似文献16.
Balkhi Balkhi Mabrouk Al-Rasheedi Abuabker Ibrahim Elbur Ahmad Alghamadi 《Saudi Pharmaceutical Journal》2018,26(1):145-149
Background
High satisfaction with, and adherence to, warfarin therapy are linked to better international normalized ratio (INR) control and good therapeutic outcomes.Objective
This study was conducted to identify the association between satisfaction with, and adherence to, warfarin therapy and the control of the INR within the target therapeutic range.Methods
A cross-sectional study was conducted from June 1 to August 31, 2016, at the Anticoagulation Clinic in the Cardiology Center at King Fahad Hospital, Qassim, Saudi Arabia. All adult patients included in the study were 18-years-old or older and were on warfarin therapy for 6?months or more. The data were collected through face-to-face interviews using a structured questionnaire.Results
A total of 298 patients were included. Of them, 194 patients (65.1%) were males and 152 (51.0%) were classified as satisfied with their warfarin therapy. Secondary educational level and above (P?=?.001) and being non-Saudi (P?=?.026) were identified as determinants of a high level of satisfaction. Ninety-five (31.8%) participants were classified as adherent to the therapy, and satisfaction with treatment was the only predictor of adherence (P?=?.009). One hundred thirty-six patients (45.6%) achieved their target INR range. Satisfaction (P?=?.038) and adherence (P?=?.023) were significantly associated with better INR control.Conclusion
Substantial efforts are needed to improve patient satisfaction and adherence to treatment through different strategies in order to achieve the target therapeutic goal for warfarin treatment. 相似文献17.
Mansour Alsharidah Metab. Algeffari Abdel-Moneim Hafez Abdel-Moneim Mohamed Faisal Lutfi Haila Alshelowi 《Saudi Pharmaceutical Journal》2018,26(1):1-6
Background
Type 2 diabetes is a chronic condition that requires pharmacotherapy interventions. Metformin and gliclazide are widely used drugs in monotherapy. However, their complementary action made utilization of the combination of these drugs an appealing approach.Aims
The study compared major therapeutic potentials of combined metformin/gliclazide treatment over metformin monotherapy based on the following parameters: oxidative stress, lipid profile, and hepatorenal functions.Subjects and methods
This is a comparative study was conducted from March 2015 to March 2016. The study screened 80 type 2 diabetic patients, of which 40 patients underwent combined metformin?+?gliclazide therapy (500?mg BD?+?80?mg OD, respectively). The other 40 were matched for age and duration of diabetes mellitus with the previous group and received metformin monotherapy (500?mg BD). The levels of fasting blood glucose (FBG), total glycated hemoglobin (HbA1c), lipid peroxidation, total antioxidant capacity, serum creatinine, aspartate and alanine transaminases, total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were measured according to the standard methods.Results
Oxidative stress, lipid profile, and hepatorenal functions were comparable in patients of both groups. However, patients on metformin treatment showed significantly lower levels of FBG [7.61 (6.70–8.89) mmol/L vs. 9.00 (7.30–10.68) mmol/L; P?=?.022] and HBA1c [7.00 (6.40–7.65)% vs. 8.20 (7.20–9.75)%; P?<?.001] compared to those on combined therapy.Conclusion
Oxidative stress, lipids profile, and hepatorenal functions were not different in patients who were on combined metformin/gliclazide therapy and compared to those metformin alone. In contrast, glycemic control was poor in the diabetic patients undergoing combined therapy. 相似文献18.
Therese Ericsson Markus Fridén Carina Kärrman-Mårdh Ian Dainty Ken Grime 《Pharmaceutical research》2017,34(12):2557-2567
Purpose
A scientifically robust prediction of human dose is important in determining whether to progress a candidate drug into clinical development. A particular challenge for inhaled medicines is that unbound drug concentrations at the pharmacological target site cannot be easily measured or predicted. In the absence of such data, alternative empirical methods can be useful. This work is a post hoc analysis based on preclinical in vivo pharmacokinetic/pharmacodynamic (PK/PD) data with the aim to evaluate such approaches and provide guidance on clinically effective dose prediction for inhaled medicines.Methods
Five empirically based methodologies were applied on a diverse set of marketed inhaled therapeutics (inhaled corticosteroids and bronchodilators). The approaches include scaling of dose based on body weight or body surface area and variants of PK/PD approaches aiming to predict the therapeutic dose based on having efficacious concentrations of drug in the lung over the dosing interval.Results
The most robust predictions of dose were made by body weight adjustment (90% within 3-fold) and by a specific PK/PD approach aiming for an average predicted 75% effect level during the dosing interval (80% within 3-fold). Scaling of dose based on body surface area consistently under predicted the therapeutic dose.Conclusions
Preclinical in vivo data and empirical scaling to man can be used as a baseline method for clinical dose predictions of inhaled medicines. The development of more sophisticated translational models utilizing free drug concentration and target engagement data is a desirable build.19.
Haibo Qu Marius C. Costache Saadet Inan Alan Cowan David Devore Paul Ducheyne 《Pharmaceutical research》2016,33(3):729-738
Purpose
Polymer-xerogel composite materials have been introduced to better optimize local anesthetics release kinetics for the pain management. In a previous study, it was shown that by adjusting various compositional and nano-structural properties of both inorganic xerogels and polymers, zero-order release kinetics over 7 days can be achieved in vitro. In this study, in vitro release properties are confirmed in vivo using a model that tests for actual functionality of the released local anesthetics.Methods
Composite materials made with tyrosine-polyethylene glycol(PEG)-derived poly(ether carbonate) copolymers and silica-based sol–gel (xerogel) were synthesized. The in vivo release from the composite controlled release materials was demonstrated by local anesthetics delivery in a rat incisional pain model.Results
The tactile allodynia resulting from incision was significantly attenuated in rats receiving drug-containing composites compared with the control and sham groups for the duration during which natural healing had not yet taken place. The concentration of drug (bupivacaine) in blood is dose dependent and maintained stable up to 120 h post-surgery, the longest time point measured.Conclusions
These in vivo studies show that polymer-xerogel composite materials with controlled release properties represent a promising class of controlled release materials for pain management.20.
Juanita A. Draime Douglas C. Anderson Timothy S. Anderson 《Journal of the American Pharmacists Association》2018,58(3):275-280