scholarly journals Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
George G. Zhanel ◽  
Andrew J. Walkty ◽  
James A. Karlowsky
Keyword(s):  
Clinical Trials ◽  
Safety Profile ◽  
Cross Resistance ◽  
Adult Women ◽  
First Line ◽  
Favorable Safety Profile ◽  
E Coli ◽  
Acute Uncomplicated Cystitis ◽  
Uncomplicated Cystitis ◽  
Favorable Safety

Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates ofE. coliandEnterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared toβ-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR)E. coli. Resistance to fosfomycin inE. coliis rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin’s in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC.

1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses

2021 ◽  
pp. 106002802110313
Author(s):  
Diem-Phuong D. Dao ◽  
Vikram Nath Sahni ◽  
Dev Ram Sahni ◽  
Esther A. Balogh ◽  
Ayman Grada ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Safety Profile ◽  
Application Site ◽  
Phase 2 ◽  
Phase 3 ◽  
Local Skin ◽  
Actinic Keratoses ◽  
Favorable Safety Profile ◽  
Favorable Safety

Objective Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration. Data Sources The PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri. Data Extraction Phase 2 and phase 3 clinical trials were reviewed. Data Synthesis In phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile. Relevance to Patient Care and Clinical Practice Tirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias. Conclusion With a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.

scholarly journals Cefaclor as a first-line treatment for acute uncomplicated cystitis

2020 ◽  
Author(s):  
Dai Koguchi ◽  
Yasukiyo Murakami ◽  
Masaomi Ikeda ◽  
Masato Dobashi ◽  
Junichiro Ishii
Keyword(s):  
Treatment Failure ◽  
Success Rate ◽  
Clinical Efficacy ◽  
Wide Spectrum ◽  
White Blood Cells ◽  
Resistant Bacteria ◽  
First Line ◽  
E Coli ◽  
Acute Uncomplicated Cystitis ◽  
Uncomplicated Cystitis

Abstract Background: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC.Methods: We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy.Results: Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n=160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum β-lactamase (ESBL) (n=19; 8.1% and n=18; 7.7%). Overall success rate was 94.0% (n=219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P<0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n=24) or 93.3% (n=14). The rate in patients with resistance to both antibiotics was 60.0% (n=9), and the pathogens in the other 40.0% (n=6) of patients with treatment failure were E. coli-ESBL.Conclusion: Cefaclor showed an excellent efficacy in AUC patients, even in those with resistance to cefazolin or levofloxacin. Cefaclor has the potential to be the first-line and second-line therapies for patients with levofloxacin treatment failure.

scholarly journals 30 Lumateperone (ITI-007) for the Treatment of Schizophrenia: Overview of Placebo-Controlled Clinical Trials and an Open-label Safety Switching Study

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 190-191 ◽  
Author(s):  
Kimberly Vanover ◽  
Steven Glass ◽  
Susan Kozauer ◽  
Jelena Saillard ◽  
Juan Sanchez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Active Control ◽  
Primary Endpoint ◽  
Safety Profile ◽  
Standard Of Care ◽  
Controlled Clinical Trials ◽  
Open Label ◽  
Favorable Safety Profile ◽  
Favorable Safety ◽  
To Receive

AbstractBackgroundLumateperone is a first-in-class agent in development for schizophrenia that acts synergistically through serotonergic, dopaminergic and glutamatergic systems. Lumateperone is a potent 5-HT2A antagonist, a mesolimbic/mesocortical dopamine phosphoprotein modulator (DPPM) with pre-synaptic partial agonist and post-synaptic antagonist activity at D2, a glutamate GluN2B receptor phosphoprotein modulator with D1-dependent enhancement of both NMDA and AMPA currents via the mTOR protein pathway and an inhibitor of serotonin reuptake.MethodsLumateperone was evaluated in 3 controlled clinical trials to evaluate efficacy in patients with acute schizophrenia. The primary endpoint was change from baseline on the PANSS total score compared to placebo. In Study ‘005, 335 patients were randomized to receive ITI-007 60mg or 120mg , risperidone 4mg (active control) or placebo QAM for 4weeks. In Study ‘301, 450 patients were randomized to receive ITI-007 60mg or 40mg , or placebo QAM for 4weeks. In Study ‘302, 696 patients were randomized to receive ITI-007 60mg or 20mg , risperidone 4mg (active control) or placebo QAM for 6weeks. Also, an open-label safety switching study was conducted in which 302 patients with stable schizophrenia were switched from standard-of-care (SOC) antipsychotics and treated for 6weeks with lumateperone QPM and then switched back to SOC.ResultsIn Studies ‘005 and ‘301, lumateperone (60mg ITI-007) met the primary endpoint with statistically significant superior efficacy over placebo at Day 28. In Study ‘302, neither dose of lumateperone separated from placebo on the primary endpoint; a high placebo response was observed in this study. Across all 3 efficacy trials, lumateperone improved symptoms of schizophrenia with the same trajectory and same magnitude of improvement from baseline to endpoint on the PANSS total score.Lumateperone was well-tolerated with a favorable safety profile in all studies. In the two studies with risperidone included as an active control, lumateperone was statistically significantly better than risperidone on key safety and tolerability measures. In the open-label safety switching study statistically significant improvements from SOC were observed in body weight, cardiometabolic and endocrine parameters worsened again when switched back to SOC medication. In this study, symptoms of schizophrenia generally remained stable or improved. Greater improvements were observed in subgroups of patients with elevated symptomatology (comorbid symptoms of depression and those with prominent negative symptoms).DiscussionLumateperone represents a novel approach to the treatment of schizophrenia with a favorable safety profile in clinical trials. The lack of cardiometabolic and motor safety issues presents a safety profile differentiated from standard-of-care antipsychotic therapy.Funding Acknowledgements: Intra-Cellular Therapies, Inc.

scholarly journals Cefaclor as a first-line treatment for acute uncomplicated cystitis: a retrospective single-center study

2020 ◽  
Author(s):  
Dai Koguchi ◽  
Yasukiyo Murakami ◽  
Masaomi Ikeda ◽  
Masato Dobashi ◽  
Junichiro Ishii
Keyword(s):  
Treatment Failure ◽  
Success Rate ◽  
Clinical Efficacy ◽  
Wide Spectrum ◽  
White Blood Cells ◽  
Resistant Bacteria ◽  
First Line ◽  
E Coli ◽  
Acute Uncomplicated Cystitis ◽  
Uncomplicated Cystitis

Abstract Background: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. Methods : We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. Results : Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n=160; 68.6%), followed by Klebsiella species and E. coli -extended spectrum β-lactamase (ESBL) (n=19; 8.1% and n=18; 7.7%). Overall success rate was 94.0% (n=219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P<0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n=24) or 93.3% (n=14). The rate in patients with resistance to both antibiotics was 60.0% (n=9), and the pathogens in the other 40.0% (n=6) of patients with treatment failure were E. coli -ESBL. Conclusion : Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

scholarly journals Cefaclor as a first-line treatment for acute uncomplicated cystitis

2020 ◽  
Author(s):  
Dai Koguchi ◽  
Yasukiyo Murakami ◽  
Masaomi Ikeda ◽  
Masato Dobashi ◽  
Junichiro Ishii
Keyword(s):  
Treatment Failure ◽  
Success Rate ◽  
Clinical Efficacy ◽  
Wide Spectrum ◽  
White Blood Cells ◽  
Resistant Bacteria ◽  
First Line ◽  
E Coli ◽  
Acute Uncomplicated Cystitis ◽  
Uncomplicated Cystitis

Abstract Background: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. Methods : We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. Results : Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n=160; 68.6%), followed by Klebsiella species and E. coli -extended spectrum β-lactamase (ESBL) (n=19; 8.1% and n=18; 7.7%). Overall success rate was 94.0% (n=219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P<0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n=24) or 93.3% (n=14). The rate in patients with resistance to both antibiotics was 60.0% (n=9), and the pathogens in the other 40.0% (n=6) of patients with treatment failure were E. coli -ESBL. Conclusion : Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

scholarly journals The Management of Acute Uncomplicated Cystitis in Adult Women by Family Physicians in Canada

2008 ◽  
Vol 19 (4) ◽  
pp. 287-293 ◽  
Author(s):  
Warren J McIsaac ◽  
Preeti Prakash ◽  
Susan Ross
Keyword(s):  
Primary Care Physicians ◽  
Urine Culture ◽  
Family Physicians ◽  
Prescribing Patterns ◽  
Antibiotic Prescribing ◽  
Adult Women ◽  
First Line ◽  
Acute Cystitis ◽  
Acute Uncomplicated Cystitis ◽  
Uncomplicated Cystitis

INTRODUCTION: There are few Canadian studies that have assessed prescribing patterns and antibiotic preferences of physicians for acute uncomplicated cystitis. A cross-Canada study of adult women with symptoms of acute cystitis seen by primary care physicians was conducted to determine current management practices and first-line antibiotic choices.METHODS: A random sample of 2000 members of The College of Family Physicians of Canada were contacted in April 2002, and were asked to assess two women presenting with new urinary tract symptoms. Physicians completed a standardized checklist of symptoms and signs, indicated their diagnosis and antibiotics prescribed. A urine sample for culture was obtained.RESULTS: Of the 418 responding physicians, 246 (58.6%) completed the study and assessed 446 women between April 2002 and March 2003. Most women (412 of 420, for whom clinical information about antibiotic prescriptions was available) reported either frequency, urgency or painful urination. Physicians would have usually ordered a urine culture for 77.0% of the women (95% CI 72.7 to 80.8) and prescribed an antibiotic for 86.9% of the women (95% CI 83.3 to 90.0). The urine culture was negative for 32.8% of these prescriptions. The most commonly prescribed antibiotic was trimethoprim/sulfamethoxazole (40.8%; 95% CI 35.7 to 46.1), followed by fluoroquinolones (27.4%; 95% CI 22.9 to 32.3) and nitrofurantoin (26.6%; 95% CI 22.1 to 31.4).CONCLUSION: Empirical antibiotic prescribing is standard practice in the community, but is associated with high levels of unnecessary antibiotic use. While trimethoprim/sulfamethoxazole is the first-line empirical antibiotic choice, fluoroquinolone antibiotics have become the second most commonly prescribed empirical antibiotic for acute cystitis. The effect of current prescribing patterns on community levels of quinolone-resistantEscherichia colimay need to be monitored.

scholarly journals Preferential Use of Nitrofurantoin Over Fluoroquinolones for Acute Uncomplicated Cystitis and Outpatient Escherichia coli Resistance in an Integrated Healthcare System

2017 ◽  
Vol 38 (4) ◽  
pp. 461-468 ◽  
Author(s):  
Rebecca L. Pedela ◽  
Katherine C. Shihadeh ◽  
Bryan C. Knepper ◽  
Michelle K. Haas ◽  
William J. Burman ◽  
...  
Keyword(s):  
Healthcare System ◽  
First Line ◽  
Integrated Healthcare ◽  
Acute Cystitis ◽  
E Coli ◽  
First Line Therapy ◽  
System A ◽  
Line Therapy ◽  
Acute Uncomplicated Cystitis ◽  
Uncomplicated Cystitis

OBJECTIVESTo evaluate changes in outpatient fluoroquinolone (FQ) and nitrofurantoin (NFT) use and resistance among E. coli isolates after a change in institutional guidance to use NFT over FQs for acute uncomplicated cystitis.DESIGNRetrospective preintervention–postintervention study.SETTINGUrban, integrated healthcare system.PATIENTSAdult outpatients treated for acute cystitis.METHODSWe compared 2 time periods: January 2003–June 2007 when FQs were recommended as first-line therapy, and July 2007–December 2012, when NFT was recommended. The main outcomes were changes in FQ and NFT use and FQ- and NFT-resistant E. coli by time-series analysis.RESULTSOverall, 5,714 adults treated for acute cystitis and 11,367 outpatient E. coli isolates were included in the analysis. After the change in prescribing guidance, there was an immediate 26% (95% CI, 20%–32%) decrease in FQ use (P<.001), and a nonsignificant 6% (95% CI, −2% to 15%) increase in NFT use (P=.12); these changes were sustained over the postintervention period. Oral cephalosporin use also increased during the postintervention period. There was a significant decrease in FQ-resistant E. coli of −0.4% per quarter (95% CI, −0.6% to −0.1%; P=.004) between the pre- and postintervention periods; however, a change in the trend of NFT-resistant E. coli was not observed.CONCLUSIONSIn an integrated healthcare system, a change in institutional guidance for acute uncomplicated cystitis was associated with a reduction in FQ use, which may have contributed to a stabilization in FQ-resistant E. coli. Increased nitrofurantoin use was not associated with a change in NFT resistance.Infect Control Hosp Epidemiol 2017;38:461–468

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