Pharmacotherapy最新文献

{"title":"Evolving resistance landscape in gram-negative pathogens: An update on β-lactam and β-lactam-inhibitor treatment combinations for carbapenem-resistant organisms.","authors":"Christina Koenig, Joseph L Kuti","doi":"10.1002/phar.2950","DOIUrl":"10.1002/phar.2950","url":null,"abstract":"<p><p>Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β-lactamase inhibitors (BLIs) with activity against extended-spectrum β-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-β-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β-lactamases including MBL and OXA-enzymes.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"658-674"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on the clinical applications of SGLTis: Insight to benefits beyond hypoglycemic and cardiorenal protection.","authors":"Shibing Tao, Shanlan Guo, Nanwei Tong","doi":"10.1002/phar.2952","DOIUrl":"10.1002/phar.2952","url":null,"abstract":"<p><p>Sodium glucose cotransporter inhibitor (SGLTi) drugs have been widely used in clinical practice. In addition to their benefits in hyperglycemia, heart failure (HF), and kidney disease, their effects on obesity, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly named nonalcoholic fatty liver disease [NAFLD]), polycystic ovarian syndrome (PCOS), abnormal lipid metabolism, hyperuricemia, obstructive sleep apnea syndrome (OSAS), anemia, and syndrome of inappropriate antidiuresis (SIAD, formerly named syndrome of inappropriate antidiuretic hormone [SIADH]) have been explored. In this review, we searched the data of clinical randomized controlled trials (RCTs) and meta-analyses of SGLTis in patients with diabetes from the PubMed library between January 1, 2020, and February 1, 2024. According to our review, certain SGLTis exhibit relatively superior clinical safety and effectiveness for treating the abovementioned diseases. Proper utilization of SGLTis in these patients can provide additional medication options for patients with different disease scenarios. However, studies of SGLTis in these diseases are relatively rare, with shortcomings such as small sample sizes and short intervention periods. Therefore, further large-scale, long-term, well-designed studies are needed to clarify the findings.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"642-657"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fixed dose daptomycin: An opportunity for pharmacokinetic/pharmacodynamic optimization in Staphylococcus aureus infections.","authors":"Katie B Olney, Manjunath P Pai, Jenni K Thomas, Donna R Burgess, William J Olney, Rebecca A Bruning, Kamron A Griffith, Danielle V Casaus, Elizabeth Crance, James Z Porterfield, David S Burgess","doi":"10.1002/phar.4602","DOIUrl":"10.1002/phar.4602","url":null,"abstract":"<p><strong>Background: </strong>Daptomycin is a high-use intravenous antimicrobial agent affording the convenience of once-daily dosing. Prior studies suggest an opportunity to use a more operationally convenient fixed rather than weight-based dosing but this approach has not been studied prospectively.</p><p><strong>Methods: </strong>This study quantified the probability of toxicity and efficacy end points by prospectively testing a fixed dose regimen of daptomycin (750 mg) in obese and non-obese adults. At least, three daptomycin concentrations were measured at steady-state for each patient. A population pharmacokinetic model was constructed to evaluate concentration-time profiles and investigate covariates of daptomycin clearance. Simulations were performed to evaluate the probability of achieving efficacy (24-h area under the curve (AUC_0-24) ≥ 666 mg∙h/L) and toxicity (minimum concentration (C _min) ≥24.3 mg/L) targets for fixed (500-1000 mg) and weight-based (6-12 mg/kg) daptomycin doses.</p><p><strong>Results: </strong>Thirty-one patients (16 females, 15 males) with median (interquartile range (IQR)) age of 50 (30, 62) years and weight of 74 (54, 156) kg were included in the final analysis. Fixed dose daptomycin (750 mg) resulted in similar exposure across weights with a median (IQR) AUC_0-24 of 819 (499, 1501) mg∙h/L and 749 (606, 1265) mg∙h/L in patients weighing ≤74 kg and >74 kg, respectively. Overall, male sex and increased kidney function necessitate higher fixed and weight-based doses to achieve efficacy. Creatine phosphokinase elevation was observed in two patients (6.5%) and predicted to be lower with fixed versus weight-based regimens.</p><p><strong>Conclusions: </strong>Fixed daptomycin dosing adjusted for sex and kidney function is expected to improve the efficacy-to-toxicity ratio, transitions of care, and costs compared to weight-based doses. However, no empiric dosing approach is predicted to achieve ≥90% efficacy while minimizing the risk of toxicity, so therapeutic drug monitoring should be considered on a patient-specific basis.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"615-622"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amoxicillin and penicillin G dosing in pediatric community-acquired pneumococcal pneumonia in the era of conjugate pneumococcal vaccines.","authors":"Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le","doi":"10.1002/phar.2756","DOIUrl":"10.1002/phar.2756","url":null,"abstract":"<p><strong>Background: </strong>Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.</p><p><strong>Methods: </strong>Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%-50% of the dosing interval.</p><p><strong>Results: </strong>In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard-dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high-dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%-50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens.</p><p><strong>Conclusion: </strong>Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"606-614"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute kidney injury with intravenous colistin sulfate compared with polymyxin B in critically ill patients: A real-world, retrospective cohort study.","authors":"Qin-Jie Yang, Bi-Xiao Xiang, Mong-Hsiu Song, Chien-Yi Yang, Jun-Hao Liang, Yue-Liang Xie, Xiao-Cong Zuo","doi":"10.1002/phar.4601","DOIUrl":"10.1002/phar.4601","url":null,"abstract":"<p><strong>Background: </strong>Polymyxins have re-emerged as a last-resort therapeutic option for infections caused by carbapenem-resistant gram-negative bacteria. Nephrotoxicity induced by polymyxins is a significant limitation of its use in the clinic. Polymyxin B and colistin sulfate are two widely used active formulations of polymyxins. However, there is a lack of studies conducting a comparative assessment of nephrotoxicity between the two formulations. This study aimed to compare the nephrotoxicity of polymyxin B and colistin sulfate in critically ill patients.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study among critically ill patients who received intravenous polymyxin B or colistin sulfate for over 48 h from January 2017 to January 2024. The primary outcome was the incidence of acute kidney injury (AKI) associated with polymyxins, and the secondary outcome was 30-day all-cause mortality. Additionally, the risk factors of polymyxins-induced AKI and 30-day all-cause mortality were identified by Cox proportional hazard regression analysis.</p><p><strong>Results: </strong>A total of 473 patients were included in this study. The overall incidence of AKI was significantly higher in patients who received polymyxin B compared to those who received colistin sulfate in the unmatched cohort (20.8% vs. 9.0%, p = 0.002) and in the propensity score matching cohort (21.1% vs. 7.0%, p = 0.004), respectively. However, there was no significant difference in 30-day all-cause mortality between the two groups. Polymyxin type, septic shock, and concomitant use of vasopressors were identified as independent risk factors for polymyxin-induced AKI.</p><p><strong>Conclusions: </strong>The prevalence of AKI was higher among patients who received polymyxin B compared to those treated with colistin sulfate. However, there was no significant difference in 30-day all-cause mortality between the two groups. Further prospective, multicenter studies with larger sample sizes are needed to validate these findings.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"631-641"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactated Ringer's versus normal saline in the management of acute diabetic ketoacidosis (RINSE-DKA).","authors":"Auriene Jamison, Adham Mohamed, Courtney Chedester, Kyle Klindworth, Majdi Hamarshi, Erik Sembroski","doi":"10.1002/phar.4600","DOIUrl":"10.1002/phar.4600","url":null,"abstract":"<p><strong>Introduction: </strong>A mainstay in the acute management of diabetic ketoacidosis (DKA) is fluid resuscitation. Normal saline is recommended by the American Diabetes Association; however, it has been associated with hyperchloremic metabolic acidosis and acute kidney injury. Limited literature is available to determine the most appropriate crystalloid fluid to treat patients with DKA.</p><p><strong>Objective: </strong>The purpose of this study was to compare lactated Ringer's (LR) to normal saline (NS) in the acute management of DKA.</p><p><strong>Methods: </strong>This was a retrospective, multicenter single health system cohort study. The primary outcome was to evaluate the time to high anion gap metabolic acidosis (HAGMA) resolution using LR compared to NS. Secondary outcomes included the incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy. Other secondary outcomes included insulin infusion duration and hospital and intensive care unit length of stay. The Cox proportional hazards model was used for the primary outcome.</p><p><strong>Results: </strong>A total of 771 patient encounters were included. Lactated Ringer's was associated with faster time to HAGMA resolution compared to NS (adjusted hazard ratio 1.325; 95% confidence interval 1.121-1.566; p < 0.001). No difference was found in complications such as incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy between the LR and NS groups. Additionally, there was no difference in insulin infusion duration and hospital or intensive care unit length of stay.</p><p><strong>Conclusion: </strong>Treatment with LR as the primary crystalloid for acute DKA management was associated with faster HAGMA resolution compared with NS. Similar incidence in complications and length of stay was observed between the two groups. The findings of this study add to the accumulating literature suggesting that balanced crystalloids may offer an advantage over NS for the treatment of patients with DKA.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"623-630"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet glycoprotein IIb/IIIa antagonists in ischemic stroke patients without endovascular therapy: A meta-analysis.","authors":"Dongjun Xu, Cheng Yang, Wei Cao, Xinyu Zhang, Shucong Yang, Xuning Shen, Jun Xu, Huijie Yu","doi":"10.1002/phar.2949","DOIUrl":"10.1002/phar.2949","url":null,"abstract":"<p><p>Platelet glycoprotein (GP) IIb/IIIa antagonists have been employed in selective patients after endovascular therapy (EVT) for acute ischemic stroke (AIS), yet application in patients without EVT is debated. This meta-analysis of randomized controlled studies on AIS patients without EVT assessed the effectiveness and safety of platelet GP IIb/IIIa antagonists compared with traditional antiplatelet or thrombolysis therapy. Articles were retrieved from databases, including PubMed, Web of Science, EMBASE, and Cochrane. The risk of bias and certainty level of evidence were assessed. Fifteen studies were included. GP IIb/IIIa antagonists increased the proportion of patients with modified Rankin Scale (mRS) 0-1 (odd ratio [OR] 1.37, 95% confidence interval [CI] 1.04-1.81, p = 0.03), mRS 0-2 (OR 1.27, 95% CI 1.12-1.46, p = 0.0004), and Barthel Index (BI) 95-100 (OR 1.25, p = 0.005); decreased the proportion of stroke progression within 5 days (OR 0.66, p = 0.006); and lowered the mean mRS score at 90 days (mean difference [MD] -0.43, p = 0.002) and the National Institute of Health stroke scale score at 7 days (MD -1.64, p < 0.00001) compared with conventional treatment. Proportions of stroke recurrence within 90 days (OR 1.20, p = 0.60), any intracranial hemorrhage (aICH) (OR 1.20, p = 0.12), symptomatic intracranial hemorrhage (sICH) (OR 0.91, p = 0.88), and death (OR 0.87, p = 0.25) had no statistical difference between both groups. This meta-analysis finds that compared with traditional antiplatelet or thrombolysis therapy, GP IIb/IIIa antagonists administered within 24-96 h of ischemic stroke onset significantly improve functional prognosis of patients with AIS not receiving EVT, as indicated by mRS and BI at 90 days, and do not increase the incidence of aICH, sICH, and death.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"675-691"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of proton pump inhibitors versus histamine-2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers.","authors":"Hua-Ping Fan, Yu Zhou, Mei-Li Chen, Kun-Hua Qiu, Xue Feng, Chao Zhou, Min-Li Zhu, Rong-Zhong Huang, Tian-Yang Hu","doi":"10.1002/phar.2947","DOIUrl":"10.1002/phar.2947","url":null,"abstract":"<p><strong>Background: </strong>To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers.</p><p><strong>Methods: </strong>Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size.</p><p><strong>Results: </strong>4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012).</p><p><strong>Conclusions: </strong>Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"539-548"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists: An executive summary.","authors":"Elizabeth M Sherman, Allison L Agwu, Juan Ambrosioni, Georg M N Behrens, Carolyn Chu, Lauren F Collins, Humberto R Jimenez, David E Koren, Leslie McGorman, Nancy N Nguyen, Melanie R Nicol, Neha Sheth Pandit, Natacha Pierre, Kimberly K Scarsi, Gary F Spinner, Alice Tseng, Jeremy D Young, Melissa E Badowski","doi":"10.1002/phar.2921","DOIUrl":"10.1002/phar.2921","url":null,"abstract":"<p><p>Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment - cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs in routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements of safe and optimal use of LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are identified and discussed.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"44 7","pages":"488-493"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study.","authors":"Flory T Muanda, Matthew A Weir, Fatemeh Ahmadi, Eric McArthur, Jessica M Sontrop, Sheikh S Abdullah, Brad L Urquhart, Hasti Sadeghi, Richard B Kim, Amit X Garg","doi":"10.1002/phar.2948","DOIUrl":"10.1002/phar.2948","url":null,"abstract":"<p><strong>Importance: </strong>Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity.</p><p><strong>Objective: </strong>To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin.</p><p><strong>Design, settings, and participants: </strong>Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688).</p><p><strong>Exposure: </strong>Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin.</p><p><strong>Main outcome and measure: </strong>The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD.</p><p><strong>Results: </strong>A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]).</p><p><strong>Conclusion and relevance: </strong>In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"558-569"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}