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1.
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2.
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3.
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4.
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5.
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6.
J. Nicholas O&#x;Donnell Nathaniel J. Rhodes Cristina M. Miglis Lejla Catovic Jiajun Liu Cameron Cluff Gwendolyn Pais Sean Avedissian Medha D. Joshi Brooke Griffin Walter Prozialeck Anil Gulati Thomas P. Lodise Marc H. Scheetz 《International journal of antimicrobial agents》2018,51(2):239-243
Background
Although the exposure-dependent efficacy thresholds of vancomycin have been probed, less is known about acute kidney injury (AKI) thresholds for this drug. Sensitive urinary biomarkers, such as kidney injury molecule 1 (KIM-1), have shown high sensitivity and specificity for vancomycin-associated AKI. The aims of the study were to determine if there were dose–response curves with urinary KIM-1, and to evaluate the impact of therapy duration and sex on observed relationships.Methods
A systematic review was conducted via PubMed/MEDLINE. Data were compiled from preclinical studies that reported individual subject data for urinary KIM-1 concentrations, vancomycin dose (mg/kg), duration of treatment, and sex. Sigmoidal Hill-type models were fit to the individual dose-response data.Results
A total of 15 studies were identified, 6 of which reported vancomycin dose and KIM-1 data. Of these, three included individual animal-level data suitable for analysis. For all pooled rats, increasing total daily vancomycin doses displayed a dose-response curve with urinary KIM-1 concentrations (50% maximal toxic response=130.4?mg/kg/day). Dose-response curves were shifted left for females vs. males (P?=?0.05) and for long (i.e. ≥7 days) vs. short (i.e. <4 days) duration of vancomycin therapy (P=0.02).Conclusions
The collective findings demonstrate a clear dose–response relationship between vancomycin dose and AKI. As these analyses focused exclusively on dose-response relationships, additional preclinical data are needed to more clearly define vancomycin exposures that predict the onset of AKI. 相似文献7.
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8.
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9.
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10.
Fatema Suliman Alatawi Uzma A. Faridi Mohsen Suliaman Alatawi 《Saudi Pharmaceutical Journal》2018,26(8):1208-1213
Background
In diabetes mellitus, uncontrolled hyperglycemia has been reported to induce oxidative stress, which may lead to health complications. Vitamin D, however, acts as a non-enzymatic antioxidant to protect cells against oxidative stress and damage.Objective
To investigate the antioxidative effect of vitamin D combined with calcium in streptozotocin (STZ)-induced diabetic rats.Methods
Rats were divided into four groups (ten rats in each group). The first group (control) received a normal diet and water. The second group, including STZ-induced diabetic rats (diabetic controls), received a normal diet and water. The third group, also including STZ-induced diabetic rats, received vitamin D (2000?IU/day) with calcium (500?mg/kg/day) orally for 28 consecutive days. The fourth group consisted of STZ-induced diabetic rats that received insulin treatment for 28 consecutive days. Activities of superoxide dismutase (SOD), glutathione peroxidase (GPO) and catalase were measured in the liver tissues. The level of malonaldehyde (MDA) was measured in the plasma.Results
Diabetic rats showed a significant decrease in the activities of SOD, GPO and catalase compared to normal rats. Oral administration of vitamin D with calcium to diabetic rats caused a significant increase in the activities of SOD, GPO and catalase compared with the untreated group. Furthermore, the plasma level of MDA was significantly elevated in diabetic rats compared to normal rats. Diabetic rats treated with vitamin D and calcium had a significantly reduced level of MDA, suggesting that vitamin D with calcium played a vital role in the protection of tissues from damage by free radicals.Conclusion
Oral supplementation with vitamin D and calcium may be a useful treatment for diabetic patients to reduce/prevent the pathological complications of diabetes. 相似文献11.
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12.
13.
Joana Sousa Gilberto Alves Ana Fortuna Amílcar Falcão 《Pharmaceutical research》2017,34(11):2260-2269
Purpose
To evaluate the potential of levofloxacin intranasal administration as a promising alternative approach to treat local infections such as chronic rhinosinusitis, by delivering drug concentrations directly to the site of infection.Methods
Drug concentrations were measured in plasma, olfactory bulb and nasal mucosa of anterior (ANM) and posterior regions after intranasal (0.24 mg/kg) and intravenous (10 mg/kg) administration to rats, and pharmacokinetic parameters were compared between routes. For intranasal administration a thermoreversible in-situ gel was used.Results
Plasma and olfactory bulb exposure to levofloxacin was minimal following intranasal dose, preventing systemic and central nervous system adverse effects. Levofloxacin concentration-time profile in ANM revealed higher concentrations during the first 60 min of the study following intranasal administration than the corresponding ones obtained after intravenous administration. A rapid and continuous decay of levofloxacin concentration in this nasal region was observed after intranasal delivery, resulting in much lower values at the last sampling time-points.Conclusion
The higher dose-normalized concentrations and pharmacokinetic exposure parameters of levofloxacin in ANM after intranasal administration, demonstrates that intranasal delivery of the formulated gel is, by itself, advantageous for delivering levofloxacin to biophase and thus an attractive approach in management of chronic rhinosinusitis.14.
Blisse Vakkalagadda Charles Frost Wonkyung Byon Rebecca A. Boyd Jessie Wang Donglu Zhang Zhigang Yu Clapton Dias Andrew Shenker Frank LaCreta 《Am J Cardiovasc Drugs》2016,16(2):119-127
Objective
Apixaban is a substrate of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein. The effects of rifampin, a strong inducer of CYP3A4 and P-glycoprotein, on the pharmacokinetics of oral and intravenous apixaban were evaluated in an open-label, randomized, sequential crossover study.Methods
Twenty healthy participants received single doses of apixaban 5 mg intravenously on day 1 and 10 mg orally on day 3, followed by rifampin 600 mg once daily on days 5–15. Finally, participants received single doses of apixaban 5 mg intravenously and 10 mg orally separately on days 12 and 14 in one of two randomized sequences.Results
Apixaban, given intravenously and orally, was safe and well tolerated when administered in the presence and absence of rifampin. Apixaban absolute oral bioavailability was 49 % when administered alone and 39 % following induction by rifampin. Rifampin reduced apixaban area under the plasma concentration–time curve from time zero to infinity (AUC∞) by 39 % after intravenous administration and by 54 % after oral administration. Rifampin induction increased mean clearance by 1.6-fold for intravenous apixaban and mean apparent clearance by 2.1-fold for oral apixaban, indicating rifampin affected both pre-systemic and systemic apixaban elimination pathways.Conclusion
Co-administration of apixaban with rifampin reduced apixaban exposure via both decreased bioavailability and increased systemic clearance.15.
Balakeshwa Ramaiah Sree Harsha Nagaraja Usha Ganganahalli Kapanigowda Prakash Rao Boggarapu 《Journal of pharmaceutical innovation》2016,11(4):289-299
Purpose
High dosage and repeated ingestion of antibiotics in the treatment of pneumonia lead to inappropriate disposition of the drug and thus increase undesirable effects. Hence, this study was intended to achieve high levofloxacin concentration in lungs by targeted levofloxacin gelatin microspheres (LGMs).Methods
The optimized LGM prepared by emulsion method was characterized for particle size, drug encapsulation efficiency, in vitro study, X-ray diffraction (XRD), and stability studies. The in vivo lung targeting efficiency parameters such as intake rate (r e), targeting efficacy (t e), overall drug targeting efficacy (T e), percentage of drug distributed to lungs (j), and ratio of peak concentration (C e) were investigated.Results
The mean particle size ranged from 6.28 to 19.72 μm, which can get deposited in lungs by mechanical entrapment. The curve fitting analysis showed significance for Koresmeyer–Peppas model (R-square?=?0.9959). The levofloxacin area under the curve (AUC; 899.62 μg h mL?1) and r e (5.74) for lung were higher and statistically significant in LGM group. Compared with spleen and liver, the t e in mice lung increased by a factor of 33.45 and ～12.74, respectively. The targeting ratio of LGM increased by a factor of 26.22 (compared to spleen) and ～10.58 (compared to liver). Subsequently by a factor of 4.63, C e in lung was higher in LGM-treated mice. An overall 87.14 % of the drug was distributed to lungs when administrated as LGM formulation. The histopathology confirmed tissue tolerability.Conclusions
The gelatin microsphere allows for surface modification, and mechanically entrapped in endothelial capillary of the lung further increases affinity leading to higher levofloxacin concentration in lungs, which helps in optimizing the therapeutic efficacy in the treatment of pneumonia.16.
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17.
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18.
Iman A. Basheti Nathir M. Obeidat Helen K. Reddel 《Saudi Pharmaceutical Journal》2018,26(8):1127-1136
Objectives
To investigate the effect of inhaler technique education delivered by a clinical pharmacist to patients hospitalised for asthma, on inhaler technique scores and asthma control at three months post-discharge.Methods
This pre-post interventional study in Jordan enrolled patients who had been admitted for asthma and were using controller medication by Accuhaler [Diskus] (ACC), Turbuhaler (TH) or Pressurized metered dose inhalers (pMDI). Inhaler technique was assessed using published checklists (score 0–9). Asthma symptom control was assessed by Asthma Control Test (ACT, range 5–25). Patients were assessed on admission (baseline), pre-discharge, and 3?months later. All patients received a ‘Show-and-Tell’ inhaler technique counseling service prior to discharge.Results
Baseline data were available for 140 patients, 71% females, mean age 52.7 (SD 16.64) years, mean ACT score 10.0 (SD 4.8). Mean inhaler score was 7.5 (SD 1.52) with no significant difference between the inhaler groups (p?=?0.174). After pre-discharge training, all patients had correct technique (score 9/9). After 3?months, mean inhaler scores were significantly higher than at baseline (8.14 (SD 0.87, p?<?0.001), with mean change significantly higher for TH 1.21 (SD 2.25) and ACC 0.85 (SD 0.97) than pMDI (0.16; SD 0.72), p?=?0.001. Symptom control improved significantly for all patients, with a mean increase in ACT score of 7.54 (SD 8.18), with no significant difference between the inhaler device groups (p?=?0.326).Conclusions
Patients hospitalized for asthma achieved correct inhaler technique after training by a pharmacist, and maintained better technique at 3?months than on admission. Significant improvements in ACT scores were documented for all inhaler groups. 相似文献19.
Abdullah T. Khoja Mohammad H. Aljawadi Sulaiman A. Al-Shammari Ashry G. Mohamed Hamad A. Al-Manaa Laura Morlock Saifuddin Ahmed Tawfik A.M. Khoja 《Saudi Pharmaceutical Journal》2018,26(2):292-300
Objectives
To Describe the Saudi older adult (SOA) characteristics and Introduce the Saudi National Survey for Elderly Health (SNSEH).Methods
The SNSEH, a population-based nationally-representative survey, was used. Subjects were included in 2006–2007, using random-cluster sampling utilizing probability proportional to size approach, and followed-up to determine their vital status until June 2015. In the analyses, survey weights were incorporated. Parametric, non-parametric and logistic regression were used. Cox-proportional hazard regression was used to determine gender effects on mortality.Results
We included 2,946 SOA. The mean age was 70.1(SD?=?0.3). Around, 70% were illiterate. Almost 50% had monthly income of 2500 (2007-Saudi-Riyals). The most reported diseases were hypertension, diabetes and joints pain. The most reported medications were over the counter, antidiabetics and antihypertensive. The nine-years age-adjusted death hazard was 42% higher in SOA males.Conclusion
This is an introductory paper for a series of papers that describe SOA health. These efforts will help in guiding the development of a national healthcare model for SOA, evidence-based health policies and public intervention programs that address SOA health-related issues. 相似文献20.
Yoshiki Seto Gen Suzuki Sharon Shui Yee Leung Hak-Kim Chan Satomi Onoue 《Pharmaceutical research》2016,33(6):1447-1455