The Efficacy and Safety of Eravacycline in the Treatment of Complicated Intra-Abdominal Infections: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

This study aims to assess the clinical efficacy and safety of eravacycline for treating complicated intra-abdominal infection (cIAI) in adult patients. The PubMed, Web of Science, EBSCO, Cochrane databases, Ovid Medline, Embase, and ClinicalTrials.gov were searched up to May 2019. Only randomized controlled trials (RCTs) that evaluated eravacycline and other comparators for the treatment of cIAI were included. The primary outcome was the clinical cure rate at the test-of-cure visit based on modified intent-to-treat population, microbiological intent-to-treat population, clinically evaluable population, and microbiological evaluable population, and the secondary outcomes were clinical failure rate and the risk of adverse event. Three RCTs were included. Overall, eravacycline had a clinical cure rate (88.7%, 559/630) at test-of-cure in modified intent-to-treat population similar to comparators (90.1%, 492/546) in the treatment of cIAIs (risk ratio (RR), 0.99; 95% confidence interval (CI), 0.95–1.03; I2 = 0%, Figure 3). In the microbiological intent-to-treat, clinically evaluable, and microbiological evaluable populations, no difference was found between eravacycline and comparators in terms of clinical cure rate at test-of-cure (microbiological intent-to-treat population, RR, 0.99; 95% CI, 0.95–1.04; I2 = 0%, clinically evaluable population, RR, 1.00; 95% CI, 0.97–1.03; I2 = 0%, microbiological evaluable population, RR, 0.98; 95% CI, 0.95–1.02; I2 = 0%). In addition, eravacycline had clinical failure rate similar to comparators at test-of-cure in modified intent-to-treat population (RR, 1.01; 95% CI, 0.61–0.69; I2 = 0%), microbiological intent-to-treat population (RR, 1.34; 95% CI, 0.77–2.31; I2 = 16%), clinically evaluable population (RR, 1.03; 95% CI, 0.61–1.76; I2 = 0%), and microbiological evaluable population (RR, 1.32; 95% CI, 0.75–2.32; I2 = 10%). Although eravacycline was associated with higher risk of treatment-emergent adverse event than comparators (RR, 1.34; 95% CI, 1.13–1.58; I2 = 0%), no significant differences were found between eravacycline and comparators for the risk of serious adverse event (RR, 1.04; 95% CI, 0.65–1.65; I2 = 0%), discontinuation of study drug because of adverse event (RR, 0.68; 95% CI, 0.23–1.99; I2 = 13%), and all-cause mortality (RR, 1.09; 95% CI, 0.41–2.9; I2 = 28%). In conclusion, the clinical efficacy of eravacycline is as high as that of the comparator drugs in the treatment of cIAIs and this antibiotic is as well tolerated as the comparators.

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Ceftaroline Efficacy and Safety in Treatment of Complicated Skin and Soft Tissue Infection: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

Journal of Clinical Medicine ◽

10.3390/jcm8060776 ◽

2019 ◽

Vol 8 (6) ◽

pp. 776 ◽

Cited By ~ 4

Author(s):

Shao-Huan Lan ◽

Shen-Peng Chang ◽

Chih-Cheng Lai ◽

Li-Chin Lu ◽

Chien-Ming Chao

Keyword(s):

Randomized Controlled Trials ◽

Clinical Cure ◽

Clinical Cure Rate ◽

Meta Analysis ◽

Adult Patients ◽

Controlled Trials ◽

Efficacy And Safety ◽

Cure Rate ◽

Randomized Controlled ◽

Complicated Skin

This study aims to assess the clinical efficacy and safety of ceftaroline for the treatment of complicated skin and skin structure infections (cSSSIs) in adult patients through meta-analysis. PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched up to April 2019. Only randomized controlled trials (RCTs) that evaluated ceftaroline and other comparators for treating cSSSIs in adult patients were included. The primary outcome was the clinical cure rate, whereas the secondary outcomes were clinical failure rate, microbiological eradication rate, relapse rate, and risk of an adverse event (AE). Five RCTs were included. Overall, ceftaroline had a clinical cure rate similar to comparators in the treatment of cSSSIs in the modified intent-to-treat population (risk ratio (RR), 1.00; 95% confidence interval (CI), 0.97–1.04; I2 = 0%) and in the clinically evaluable population (RR, 1.00; 95% CI, 0.97–1.03; I2 = 0%). In addition, no significant difference was observed between ceftaroline and comparators for the treatment of infection with Staphylococcus aureus (RR, 1.01; 95% CI, 0.98–1.05; I2 = 0%), methicillin-resistant S. aureus (RR, 0.99; 95% CI, 0.94–1.05; I2 = 0%), methicillin-susceptible S. aureus (RR, 1.01; 95% CI, 0.96–1.06; I2 = 26%), Streptococcus spp. (RR, 1.07; 95% CI, 0.92–1.24; I2 = 73%), and Gram-negative bacteria (RR, 0.94; 95% CI, 0.83–1.08; I2 = 0%). Furthermore, ceftaroline had a similar rate of microbiological eradication (92.2% vs. 92.6%, RR, 1.00; 95% CI, 0.97–1.03; I2 = 9%) and relapse (6.9% vs. 9.1%, RR, 0.48; 95% CI, 0.14–1.74; I2 = 0%) as comparators. Finally, the risks of treatment-emergent AEs (RR, 0.96; 95% CI, 0.88–1.05; I2 = 0%), serious AEs (RR, 1.03; 95% CI, 0.63–1.68; I2 = 0%), and discontinuation of study drug due to an AE (RR, 0.86; 95% CI, 0.50–1.49; I2 = 34%) did not differ significantly between ceftaroline and comparators. In conclusion, the clinical efficacy of ceftaroline is as high as that of comparators in the treatment of cSSSIs in adult patients, and this antibiotic is well tolerated like the comparators.

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Efficacy and Safety of Ceftaroline for the Treatment of Community-Acquired Pneumonia: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

Journal of Clinical Medicine ◽

10.3390/jcm8060824 ◽

2019 ◽

Vol 8 (6) ◽

pp. 824 ◽

Cited By ~ 8

Author(s):

Shao-Huan Lan ◽

Shen-Peng Chang ◽

Chih-Cheng Lai ◽

Li-Chin Lu ◽

Chien-Ming Chao

Keyword(s):

Randomized Controlled Trials ◽

Clinical Cure ◽

Clinical Cure Rate ◽

Meta Analysis ◽

Community Acquired Pneumonia ◽

Controlled Trials ◽

Efficacy And Safety ◽

Cure Rate ◽

Mitt Population ◽

Randomized Controlled

This study aimed to compare the clinical efficacy and safety of ceftaroline with those of ceftriaxone for treating community-acquired pneumonia (CAP). The PubMed, Cochrane Library, Embase, and clinicalTrials.gov databases were searched until April 2019. This meta-analysis only included randomized controlled trials (RCTs) that evaluated ceftaroline and ceftriaxone for the treatment of CAP. The primary outcome was the clinical cure rate, and the secondary outcome was the risk of adverse events (AEs). Five RCTs were included. Overall, at the test of cure (TOC), the clinical cure rate of ceftaroline was superior to the rates of ceftriaxone for the treatment of CAP (modified intent-to-treat population (MITT) population, odds ratio (OR) 1.61, 95% confidence interval (CI) 1.31–1.99, I2 = 0%; clinically evaluable (CE) population, OR 1.38, 95% CI 1.07–1.78, I2 = 14%). Similarly, the clinical cure rate of ceftaroline was superior to that of ceftriaxone at the end of therapy (EOT) (MITT population, OR 1.57, 95% CI 1.16–2.11, I2 = 0%; CE population, OR 1.64, 95% CI 1.15–2.33, I2 = 0%). For adult patients, the clinical cure rate of ceftaroline remained superior to that of ceftriaxone at TOC (MITT population, OR 1.66, 95% CI 1.34–2.06, I2 = 0%; CE population, OR 1.39, 95% CI 1.08–1.80, I2 = 30%) and at EOT (MITT population, OR 1.64, 95% CI 1.20–2.24, I2 = 0%; CE population, OR 1.65, 95% CI 1.15–2.36, I2 = 0%). Ceftaroline and ceftriaxone did not differ significantly in the risk of serious AEs, treatment-emergent AEs, and discontinuation of the study drug owing to an AE. In conclusion, the clinical efficacy of ceftaroline is similar to that of ceftriaxone for the treatment of CAP. Furthermore, this antibiotic is as tolerable as ceftriaxone.

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Cethromycin versus Clarithromycin for Community-Acquired Pneumonia: Comparative Efficacy and Safety Outcomes from Two Double-Blinded, Randomized, Parallel-Group, Multicenter, Multinational Noninferiority Studies

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05596-11 ◽

2012 ◽

Vol 56 (4) ◽

pp. 2037-2047 ◽

Cited By ~ 16

Author(s):

Marci L. English ◽

Christine E. Fredericks ◽

Nancy A. Milanesio ◽

Nestor Rohowsky ◽

Ze-Qi Xu ◽

...

Keyword(s):

Clinical Cure ◽

Clinical Cure Rate ◽

The United States ◽

Community Acquired Pneumonia ◽

Phase Iii ◽

Efficacy And Safety ◽

Cure Rate ◽

Content Type ◽

Dosing Regimens ◽

Double Blinded

ABSTRACTCommunity-acquired pneumonia (CAP) continues to be a major health challenge in the United States and globally. Factors such as overprescribing of antibiotics and noncompliance with dosing regimens have added to the growing antibacterial resistance problem. In addition, several agents available for the treatment of CAP have been associated with serious side effects. Cethromycin is a new ketolide antibiotic that may provide prescribing physicians with an additional agent to supplement a continually limited armamentarium. Two global phase III noninferiority studies (CL05-001 and CL06-001) to evaluate cethromycin safety and efficacy were designed and conducted in patients with mild to moderate CAP. Study CL05-001 demonstrated an 83.1% clinical cure rate in the cethromycin group compared with 81.1% in the clarithromycin group (95% confidence interval [CI], −4.8%, +8.9%) in the intent to treat (ITT) population and a 94.0% cethromycin clinical cure rate compared with a 93.8% clarithromycin cure rate (95% CI, −4.5%, +5.1%) in the per protocol clinical (PPc) population. Study CL06-001 achieved an 82.9% cethromycin clinical cure rate in the ITT population compared with an 88.5% clarithromycin cure rate (95% CI, −11.9%, +0.6%), whereas the clinical cure rate in the PPc population was 91.5% in cethromycin group compared with 95.9% in clarithromycin group (95% CI, −9.1%, +0.3%). Both studies met the primary endpoints for clinical cure rate based on predefined, sliding-scale noninferiority design. Therefore, in comparison with clarithromycin, these two noninferiority studies demonstrated the efficacy and safety of cethromycin, with encouraging findings of efficacy in subjects withStreptococcus pneumoniaebacteremia. No clinically significant adverse events were observed during the studies. Cethromycin may be a potential oral therapy for the outpatient treatment of CAP.

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Comparing Several Treatments with Antibiotics for CommunityAcquired Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Iranian Journal of Public Health ◽

10.18502/ijph.v50i6.6410 ◽

2021 ◽

Author(s):

Fusheng Bai ◽

Xinming Li

Keyword(s):

Randomized Controlled Trials ◽

Subgroup Analysis ◽

Clinical Cure ◽

Clinical Cure Rate ◽

Meta Analysis ◽

Controlled Trials ◽

Clinical Effects ◽

Cure Rate ◽

Ceftaroline Fosamil ◽

Randomized Controlled

Background: We aimed to review relevant randomized controlled trials to assess the relative clinical effects of antibiotic treatment of patients with community-acquired pneumonia (CAP). Methods: In this meta-analysis, we identified relevant studies from PubMed, Cochrane, and Embase using appropriate keywords. Key pertinent sources in the literature were also reviewed and all articles published through Oct 2019 were considered for inclusion. For each study, we assessed the risk ratios (RRs) or mean difference combined with the 95% confidence interval (CI) to assess and synthesize outcomes. Results: Overall, 36 studies were consistent with the meta-analysis, involving 17,076 patients. There was no significant difference in the mortality after subgroup analysis: individualized treatment vs. standard treatment; β-lactams plus macrolides vs. β-lactam and/or fluoroquinolone; ceftaroline fosamil vs. ceftriaxone; combination therapy vs. monotherapy or high-dose vs. low-dose. The drug-related adverse event incidence was significantly higher in the ceftriaxone group than in the other drug groups (P<0.05) and also higher in the tigecyline group than in the levofloxacin group (P<0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the test-of-cure (TOC) visit in the clinically evaluable population, modified intent-to-treat efficacy (MITTE) population, microbiologically evaluable (ME) population and the microbiological MITTE (mMITTE) population (all P<0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the TOC visit in the mMITTE population of Gram positiveStreptococcus pneumoniae (P<0.05) and multidrug-resistant S. pneumoniae (P<0.05). Conclusion: There was a limited number of included studies in the subgroup analysis, but it will still be necessary to conduct more high-quality randomized controlled trials to confirm the clinical efficacy of different antibiotics used to treat CAP.

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Efficacy and safety of linezolid versus teicoplanin for the treatment of MRSA infections: a meta-analysis

The Journal of Infection in Developing Countries ◽

10.3855/jidc.9447 ◽

2018 ◽

Vol 11 (12) ◽

pp. 926-934

Author(s):

Hao Chen ◽

Lan Li ◽

Maomao Wu ◽

Shuangli Xu ◽

Mingli Wang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Clinical Cure ◽

Eradication Rate ◽

Clinical Cure Rate ◽

Methicillin Resistant Staphylococcus Aureus ◽

Meta Analysis ◽

Efficacy And Safety ◽

Cure Rate ◽

Dosage Regimens ◽

Serious Infections

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of serious infections. Linezolid and teicoplanin are widely used in the treatment of infections caused by MRSA. However, the efficacy and safety of linezolid compared with teicoplanin remains controversial. The purpose of this study was to systematically review the efficacy and safety of linezolid versus teicoplanin for the treatment of MRSA infections. Methodology: A meta-analysis was performed on the published studies. Pooled relative risk (RR) and 95% confidence interval (95% CI) were calculated to determine whether there were significant differences between the linezolid group and the teicoplanin group on the efficacy and safety. Results: Seventeen studies were included, involving 2,040 patients. The results showed that linezolid was associated with better clinical cure rate (RR = 1.14, 95% CI = 1.08-1.21, p < 0.00001) and microbiological eradication rate (RR = 1.28, 95% CI = 1.18-1.39, p < 0.00001) compared with teicoplanin. There were no statistically significant differences between the two groups in the treatment of MRSA infections regarding the adverse events (RR = 1.15, 95% CI = 0.97-1.35, p = 0.10) and the mortality (RR = 0.85, 95% CI = 0.61-1.18, p = 0.33). Conclusions: The results suggest that linezolid may be a better choice for the treatment of patients with MRSA infections. However, our recommendation is that the decision about treating MRSA infections with linezolid or with teicoplanin should depend on local availability, patient population, dosage regimens, costs and safety, rather than presumed differences in efficacy.

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Efficacy of Azithromycin 1% and 1.5% ophthalmic solutions compared to tobramycin 0.3% eye drops: A systematic review and meta-analysis

10.21203/rs.2.22169/v1 ◽

2020 ◽

Author(s):

Birhanu Motbaynor ◽

Teshager Worku Kassie

Keyword(s):

Systematic Review ◽

Short Duration ◽

Clinical Cure ◽

Clinical Cure Rate ◽

Meta Analysis ◽

Eye Diseases ◽

Eye Drops ◽

Cure Rate ◽

Randomized Controlled ◽

Ophthalmic Solutions

Abstract Background: Azithromycin 1% and 1.5% ophthalmic preparations are used widely in clinical practice for the treatment of signs and symptoms of eye diseases. Despite individual studies, there have been no summarized evidence about the efficacy of azithromycin over tobramycin eye drops. Therefore, the aim of this study was to abridge this gap by rendering conclusive evidence by comparing the efficacy of azithromycin 1% and 1.5% over tobramycin 0.3% ophthalmic solutions for the treatment of eye diseases in short duration in terms of bacterial resolution, cure rate and resolving clinical sign and symptoms of eye diseases. Methods: Systematic searches were performed in both electronic (Medline (Ovid), EMBASE (Ovid), Emcare (Ovid), CINAHL (EBSCOhost), Scopus, PubMed, ProQuest, Web of Science and Cochrane Central Register of Controlled Trials) and other sources (Worldcat, Mednar, Google and Google scholar). Multicenter randomized controlled trial studies conducted in the English language were identified and screened. Joanna Briggs Institute quality assessment checklist for randomized controlled trials was used to critically appraise the methodological quality of studies. Analysis of individual studies was conducted using the OpenMeta-analyst and Review manager Version 5.3 software. The study was reported, according to the PRISMA reporting checklist. Results: Eleven studies were included in the systematic review and meta-analysis. In clinical cure rate, Azithromycin 1% and 1.5% eye drops were more effective than tobramycin 0.3% eye drops in short duration dosing (≤ 5 days) with a twice-a-day regimen (RR=1.138; 95% CI:1.008, 1.284) whereas on increased duration (>5days) azithromycin is almost similarly as effective as tobramycin with (RR=1.007; 95% CI: 0.964, 1.052). There was no significant difference in efficacy of bacterial resolution of azithromycin (1%, 1.5%) eye drops compared to tobramycin (0.3%) eye drops (RR=0.992; 95% CI: 0.967, 1.0183). Conclusion: Azithromycin 1% and 1.5% eye drops are more effective in clinical cure rate than tobramycin 0.3% eye drops for short duration treatment. So that it is recommended to use azithromycin instead of tobramycin eye drops to get good result in short duration dosage. Systematic Review Registration ID : CRD42019139911, registered on October 16,2019; https://www.crd.york.ac.uk/PROSPERO/#recordDetails Keywords: Azithromycin, Tobramycin, Efficacy, Eye drops, Eye diseases

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Berberine for diarrhea in children and adults: a systematic review and meta-analysis

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284820961299 ◽

2020 ◽

Vol 13 ◽

pp. 175628482096129

Author(s):

Mingkun Yu ◽

Xuejing Jin ◽

Changhao Liang ◽

Fanlong Bu ◽

Deng Pan ◽

...

Keyword(s):

Systematic Review ◽

Randomized Controlled Trials ◽

Clinical Cure ◽

Clinical Cure Rate ◽

Controlled Trials ◽

Cure Rate ◽

Control Groups ◽

Quality Of Evidence ◽

Randomized Controlled

Background: Diarrhea is a ubiquitous digestive system disease, leading to loss of fluid and electrolytes, and may be life-threatening, especially in children and adults who are immunosuppressed or malnourished. Berberine has a broad-spectrum antibiotic activity and is very widely used to treat diarrhea in China. No systematic review has been carried out to evaluate the evidence presented in clinical trials. The aim of this study was to assess the effectiveness and safety of berberine in diarrhea treatment among children and adults. Methods: Seven databases and two clinical trial registries were searched on 1 September 2019. Randomized controlled trials were included, where participants were diagnosed (first diagnosed) as having diarrhea according to clear diagnostic criteria. Berberine alone or in combination with Western medication as intervention were included. Subgroup analyses were conducted based on children or adults, acute or persistent diarrhea, infectious or noninfectious and treatment courses. Primary outcomes were clinical cure rate and duration of diarrhea. The GRADE tool was used to assess the quality of evidence. Results: A total of 38 randomized controlled trials were included involving 3948 participants (including 27 trials on 2702 children) were included. Compared with antibiotics, berberine plus antibiotics showed better results in both adults and in children in general, especially when given for 7 days or 3 days in acute infectious diarrhea of children. Compared with the control groups, using berberine alone or in combination with montmorillonite, probiotics, and vitamin B increased the clinical cure rate of diarrhea. The use of berberine alone or berberine combined with montmorillonite reduced the duration of hospitalization. Using berberine had significantly better laboratory indicators (isoenzyme, inflammatory factors, myocardial enzyme, and fecal trait) and fewer systemic symptoms than the no berberine groups. Overall, 22 of 27 trials on children used berberine as an enema. No deaths and serious adverse events were reported. The quality of evidence of included trials was moderate to low or very low. The impact of different dosages, frequencies and treatment durations on the outcomes was not evaluated due to insufficient number of trials. Conclusion: This review demonstrated that berberine was generally effective in improving clinical cure rates and shortening the duration of diarrhea compared with control groups. No severe adverse event was reported. However, there is still a lack of high-quality evidence for evaluating the efficacy and safety of berberine. Trial registration: PROSPERO CRD42020151001 (available from http://www.crd.york.ac.uk/PROSPERO/ ).

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Evaluation Outcomes Associated with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j33s4b ◽

2016 ◽

Vol 19 (2) ◽

pp. 274 ◽

Cited By ~ 3

Author(s):

Hui Yang ◽

Xiangli Cui ◽

Zhuo Ma ◽

Lihong Liu

Keyword(s):

Systematic Review ◽

Continuous Infusion ◽

Clinical Cure ◽

Observational Studies ◽

Clinical Cure Rate ◽

Meta Analysis ◽

Intermittent Infusion ◽

Cure Rate ◽

Randomized Controlled ◽

Dosing Strategies

A better dosing strategy can improve clinical outcomes for patients. We systematically reviewed the literatures to determine whether any clinical benefits exist for piperacillin/tazobactam by extended or continuous infusion. Methods - A search of PubMed, Web of Science, ProQuest, ScienceDirect, Cochrane, Embase and related ICAAC and ACCP conferences were conducted up to September 5, 2015. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently evaluated the methodology and extracted data from primary studies. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated. Results - Three randomized controlled trials and twelve observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significant cost effectiveness (OR -0.89.02, CI (-114.69,-63.35), P<0.00001). No statistical difference was observed for clinical cure rate (OR 1.64, 95% CI (0.88, 3.30), P=0.12) between the two dosing regimens. The sensitivity analysis showed the results were stable. Conclusions - Our systematic review and meta-analysis found that the outcomes associated with alternative dosing strategies of piperacillin/tazobactam have changed compared with conclusions before for several literatures with large samples published. Further data on the outcomes should be generated for a better understanding of the extended or continuous infusion strategy. On the whole, our meta-analysis suggested that the extended or continuous infusion should be recommended for clinical use only considering its economic advantage, but there was no significantly higher clinical cure rate and lower mortality rate compared with the conventional intermittent infusion. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Pegloticase in combination with methotrexate in patients with uncontrolled gout: A multicenter, open-label study (MIRROR)

The Journal of Rheumatology ◽

10.3899/jrheum.200460 ◽

2020 ◽

pp. jrheum.200460 ◽

Cited By ~ 1

Author(s):

John K. Botson ◽

John R.P. Tesser ◽

Ralph Bennett ◽

Howard M. Kenney ◽

Paul M. Peloso ◽

...

Keyword(s):

Controlled Trial ◽

Randomized Study ◽

Primary Study ◽

Efficacy And Safety ◽

Open Label ◽

Safety Study ◽

Open Label Study ◽

Randomized Controlled ◽

Intent To Treat ◽

Treat Population

Objective To examine the efficacy and safety of pegloticase in combination with methotrexate in patients with uncontrolled gout in an exploratory, open-label clinical trial (NCT03635957) prior to a randomized, controlled trial. Methods A multicenter, open-label, efficacy and safety study of pegloticase with methotrexate cotreatment was conducted in patients with uncontrolled gout. Patients were administered oral methotrexate (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase treatment. The primary study outcome was the proportion of responders, defined as sUA <6 mg/dL for ≥80% of the time during month 6 (weeks 20, 22, and 24). All analyses were performed on a modified intent-to-treat population, defined as patients who received ≥1 pegloticase infusion. Results Seventeen patients were screened and 14 patients (all men, average age: 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL and 12 of the 14 patients had visible tophi. At the 6 month timepoint, 11/14 (78.6%, 95%CI 49.2-95.3%) met the responder definition, with 3 patients discontinuing after meeting protocol-defined treatment discontinuation rules (pre-infusion sUA values greater than 6 mg/dL at 2 consecutive scheduled visits). All patients tolerated methotrexate. No new safety concerns were identified. Conclusion In this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with methotrexate and pegloticase when compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of methotrexate or placebo with pegloticase to validate these open label findings.

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1692. Retrospective Review on the Safety and Efficacy of Nitrofurantoin for the Treatment of Cystitis in the Veteran Population With or Without Renal Insufficiency

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1870 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S829-S830

Author(s):

Elwyn W Welch ◽

Shaila Sheth ◽

Chester Ashong ◽

Caroline Pham

Keyword(s):

Renal Function ◽

Renal Dysfunction ◽

Clinical Cure ◽

Clinical Cure Rate ◽

Retrospective Chart Review ◽

Outpatient Setting ◽

Secondary Outcome ◽

Cure Rate ◽

Acute Cystitis ◽

Significant Difference

Abstract Background Nitrofurantoin has been used to treat cystitis in women; however, data supporting its use in men is lacking. In addition, recent retrospective studies have challenged the manufacturer’s recommendation to avoid nitrofurantoin with creatinine clearances (CrCl) less than 60 mL/min. The purpose of this study is to compare the efficacy and safety of nitrofurantoin for the treatment of acute cystitis in male and female veterans with variable degrees of renal dysfunction. Methods A retrospective chart review was conducted in adult patients who received nitrofurantoin for acute cystitis in the outpatient setting between May 1, 2018 and May 1, 2019. The primary outcomes were rates of clinical cure as compared between males and females, and across various renal function groups (CrCl greater than 60 mL/min, 30 to 60 mL/min, and less than 30 mL/min) following treatment with nitrofurantoin. The secondary outcome was adverse event rates. Results A total of 446 patients were included with 278 females and 168 males. Overall clinical cure rate was 86.5% (n=386). Clinical cure rate did not vary between genders (p=0.0851) or CrCl ranges (p=1.0) as shown in the tables. Benign prostatic hyperplasia (BPH) was associated with decreased odds of clinical cure (OR 0.50 [95% CI 0.26-0.97], p=0.0404) in addition to cirrhosis (OR 0.22 [95% CI 0.06-0.91], p=0.0357). Adverse events occurred in 2% of patients and did not vary based on gender or renal function. RATES OF CLINICAL CURE Conclusion There was no statistically significant difference in clinical cure with nitrofurantoin between genders and various renal impairments. However, history of BPH and cirrhosis were associated with decreased efficacy. Subgroup analysis also revealed lower efficacy in males with CrCl greater than 60 mL/min versus females with similar renal function. This study adds to the growing body of literature suggesting that renal dysfunction with CrCl of 30 to 60 mL/min may not carry the risk of treatment failure and adverse effects previously associated with nitrofurantoin, but large randomized trials are needed to confirm these results. Disclosures All Authors: No reported disclosures

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