Test Of Cure Visit Research Articles

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients

Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

2513. CERTAIN-1 Subgroup Analysis: A Phase 3 Study of Cefepime-Taniborbactam Efficacy in the Treatment of Complicated Urinary Tract Infections (cUTI)

Abstract Background Cefepime-taniborbactam (FTB) is an investigational β-lactam/β-lactamase inhibitor combination that is active against carbapenem-resistant Enterobacterales and multidrug resistant Pseudomonas aeruginosa expressing serine and metallo-β-lactamases. CERTAIN-1 (Cefepime Rescue with Taniborbactam in cUTI) demonstrated that FTB was superior to meropenem (MEM) for the treatment of cUTI. Subgroup analyses were performed to determine the consistency of response, including for subgroups potentially more challenging to treat (e.g., bacteremia). Methods CERTAIN-1 was a randomized, double blind, double dummy, Phase 3 study comparing FTB to MEM in adults hospitalized with cUTI or Acute Pyelonephritis (AP). The primary endpoint was the composite (microbiologic and clinical) response at the test of cure (TOC) visit in the microITT population. A pre-specified test for superiority for the primary endpoint was performed following confirmation of non-inferiority. Patient demographic and baseline characteristics were analyzed for composite success. Treatment difference in success rate and corresponding 95% CI were calculated. Results 661 patients were randomized and 436 patients (66.0%) were included in the microITT population; 38.1% of patients were ≥ 65 years of age and 13.1% had baseline bacteremia. Composite success rates were 70.6% and 58.0% for FTB and MEM groups, respectively for the primary endpoint at the TOC visit and FTB was superior to MEM (treatment difference [FTB-MEM], 12.6%; 95% CI, 3.1 to 22.2; p=0.0088). Composite success rates were consistent with the primary analysis for subgroups, including BMI and renal impairment, in patients with potentially more serious infections (e.g., bacteremia, sepsis), and in at-risk patient subgroups (e.g., age ≥ 65, diabetes mellitus) (Table). No subgroup appears to have driven the overall result of superiority of FTB compared to MEM for the composite success rate. Conclusion FTB was superior to MEM for the primary endpoint at TOC and composite response rates were numerically higher in all subgroups, consistent with the primary efficacy response. Disclosures Mary Beth Dorr, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Merck and Co.: Shareholder|Pfizer: Shareholder|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder Leanne Gasink, MD, MSCE, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|CSL Behring: Advisor/Consultant|CSL Behring: Consulting fees|Everest Medicines: Grant/Research Support|Evopint Biosciences: Advisor/Consultant|Evopint Biosciences: Consulting fees|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|LBG Consulting, LLC: Principal|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Consulting fees|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Consulting fees|Vera Therapeutics: Advisor/Consultant|Vera Therapeutics: Consulting fees Tim Henkel, MD, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Employee, consulting fees, shareholder Greg Moeck, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder Hongzi Chen, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee|Venatorx Pharmaceuticals, Inc.: Stocks/Bonds Scott A. McConnell, PharmD, Venatorx: employee|Venatorx: Stocks/Bonds Paul McGovern, MD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Everest Medicines: Grant/Research Support|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Paratek Pharmaceuticals: Shareholder|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Employee, stock options and shareholder

(034) Secnidazole for Trichomoniasis: Results from a Clinical Trial with Women and a Systematic Literature Review for Men

Abstract Introduction Trichomoniasis is the most prevalent non-viral sexually transmitted infection (STI) in the world, affecting ~4.1% of women and ~1.3% of men aged 40–59 in the United States. Women with T. vaginalis are at 2- to 3-fold increased risk for acquiring human immunodeficiency virus (HIV). Trichomoniasis is also associated with vaginitis, pelvic inflammatory disease, post-hysterectomy cuff cellulitis and other STIs. In addition, it can cause infertility and increase a woman’s risk for adverse pregnancy outcomes including preterm birth, premature rupture of membranes, and delivery of low birthweight infants. In men, trichomoniasis is associated with non-gonococcal urethritis, although men are frequently asymptomatic and may seek treatment only after knowing that their female partners are infected. Current CDC treatment guidelines recommend concurrent treatment of both partners to prevent transmission and reinfection. Objectives To evaluate the efficacy and tolerability of secnidazole in women and men with trichomoniasis. Because logistical and statistical considerations precluded the inclusion of men in the clinical trial, we conducted a systematic literature search (19May2020) to identify other studies of secnidazole in male patients with trichomoniasis. Secnidazole is FDA-approved for the treatment of bacterial vaginosis in women. Methods In a randomized clinical trial (RCT), women with a diagnosis of trichomoniasis received a single, oral dose of secnidazole 2g or placebo at baseline (Visit 1). At Visit 2 (days 6–12), they were evaluated for test of cure (TOC) and switched to the opposite treatment. The primary endpoint was microbiological cure (ie, InPouch™ culture negative for T. vaginalis) at the TOC visit. Adverse events (AEs) were monitored. A trained research associate used ProQuest Dialog™ to search BIOSIS Previews, EMBASE, and MEDLINE using search terms related to secnidazole, clinical trials, men/males, and trichomoniasis. Results For the RCT, 147 women were enrolled; the modified intent-to-treat population included 131 randomized patients. Cure rates were 92.2% and 1.5% for secnidazole and placebo (P<0.001). The most commonly reported AEs were vulvovaginal candidiasis (2.7%) and nausea (2.7%). No serious AEs were reported. For the systematic review, 4 studies were identified, which included 211 men who received secnidazole for treatment of trichomoniasis. In one study that included only men (n=85), the cure rate 5 days after treatment was 100%. In the 3 studies that included men and women, cure rates were 92–97%. For studies reporting AEs, the most common were nausea (4–9%), and dyspepsia (0.5–1.1%). Pharmacokinetics data showed no clinically meaningful differences in secnidazole exposure (Cmax, AUC) between men and women; however, the mean (±SD) half-life (hours) was longer in men versus women (20.2 hours [±3.1] vs. 14.3 hours [±1.3]). Conclusions In a RCT of women with trichomoniasis, cure rates were significantly higher after single-dose secnidazole versus placebo, and tolerability profiles were comparable between treatment groups. In a systematic literature review of secnidazole for trichomoniasis in men, cure rates, tolerability, and pharmacokinetics data were comparable to those in women. Disclosure Yes - Lupin Pharmaceuticals, Inc. Industry initiated, executed and funded study – Yes.

Discordant Clinical and Microbiological Outcomes Are Associated With Late Clinical Relapse in Clinical Trials for Complicated Urinary Tract Infections.

Current US Food and Drug Administration guidance recommends that the primary endpoint for complicated urinary tract infection clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed point after therapy. Although some participants meet the criteria for clinical success, they do not meet the criteria for microbiological eradication and are classified as treatment failures. These discordant outcomes have raised questions about the utility of the microbiological endpoint. We analyzed participant data from 13 phase 3 clinical trials submitted to the US Food and Drug Administration (N = 4842). Outcomes were determined at the test of cure (TOC) visit, recommended to occur at least 5 days after therapy and at the late follow-up visit, recommended to occur 21 to 28 days after randomization. Clinical and microbiological success were defined as the resolution of complicated urinary tract infection symptoms present at study entry, with no new symptoms (clinical cure), and a reduction in density of the original pathogen to <103 CFU/mL on urine culture (microbiological eradication). Among included participants, 70.7% were concordant successes at the TOC visit, 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). Discordant participants were at an increased risk for clinical failure at the late follow-up visit, and the risk of late clinical failure increased with time. Discordant clinical and microbiological outcomes at the TOC visit were associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component of the endpoint.

2235. Discordance of Clinical and Microbiological Endpoints in Clinical Trials for Complicated Urinary Tract Infection (cUTI)

Abstract Background Complicated urinary tract infections (cUTI) are a clinical syndrome characterized by pyuria and a documented microbial pathogen on urine or blood culture, accompanied by local and systemic signs and symptoms, in the presence of urinary tract abnormalities or acute pyelonephritis. Current FDA guidance recommends that the primary endpoint for cUTI clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed time after therapy. In recent trials, it has been noted that while some patients have clinical resolution of symptoms, they are considered failures due to positive urine cultures. These discordant outcomes have raised questions about the utility of the microbiological endpoint. Methods We analyzed patient data from 13 phase 3 clinical trials submitted to the FDA. We focused on the microbiological modified intent-to-treat (m-MITT) population, including patients who have at least 1 bacterial pathogen known to cause cUTI and received at least one dose of study drug (N=4842). Outcomes were determined at the Test of Cure (TOC) visit 7-10 days after therapy, and the Late Follow Up (LFU) visit 3-4 weeks after therapy. Clinical and microbiological success were defined as the resolution of cUTI symptoms present at entry, with no new symptoms (clinical cure), and reduction of the pathogen at entry to ≤ 103 CFU/mL on urine culture (microbiological eradication). Results Among all included patients, 70.7% were overall successes at the TOC, exhibiting clinical and microbiological success. 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). In a multivariate logistic regression model, discordance was associated with obesity, lithiasis, use of analgesics, and receipt of carbapenem antibiotics. Discordant patients were at an increased risk for clinical failure at the LFU visit, and the risk of late clinical failure increased with longer time between the TOC and LFU visits. Conclusion Microbiological persistence at the TOC visit despite resolution of symptoms was associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component in the composite endpoint. Disclosures All Authors: No reported disclosures.

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

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 positive-Streptococcus 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.

A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia

Objectives To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). Patients and methods This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7–10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). Results A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. Conclusion Sitafloxacin 100 mg qd or 100 mg bid for 7–10 days is not inferior to moxifloxacin 400 mg qd for 7–10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

A randomized, active-controlled, multicentre clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated or complicated urinary tract infection

Purpose To evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated urinary tract infection (UTI) or complicated UTI. Methods In this randomized, active-controlled clinical trial, the patients with acute uncomplicated UTI were randomized to receive sitafloxacin 100-mg once-daily (qd) or levofloxacin 500-mg qd orally for 3–5 days. The patients with complicated UTI were randomized to receive sitafloxacin 100-mg twice daily or levofloxacin 500-mg qd orally for 10–14 days. The primary endpoint was the clinical efficacy at test-of-cure (TOC) visit. Results At TOC visit, the clinical cure rate was 89.2% (58/65) in sitafloxacin group and 97.1% (68/70) in levofloxacin group for the patients with acute uncomplicated UTI corresponding to the bacterial eradication rate of 97.1% (34/35) and 97.6% (41/42) (all p > .05), respectively. For the patients with complicated UTI, the clinical cure rate was 81.8% (27/33) in sitafloxacin group and 76.9% (20/26) in levofloxacin group corresponding to the bacterial eradication rate of 93.3% (14/15) and 63.6% (7/11) (all p > .05), respectively. Sitafloxacin and levofloxacin showed similar incidence of drug-related adverse events. Conclusions Oral sitafloxacin is as effective and safe as levofloxacin in treating acute uncomplicated and complicated UTI. KEY MESSAGE: Oral sitafloxacin showed similar clinical cure rate and bacterial eradication rate as levofloxacin for treatment of complicated and uncomplicated urinary tract infections (UTIs) in a randomized, active-controlled, multicentre clinical trial. Oral sitafloxacin is safe and well-tolerated in treating acute uncomplicated and complicated UTIs in Chinese adults. Sitafloxacin is a promising alternative treatment option for UTIs in adults.

Efficacy and Tolerability of Eravacycline in Bacteremic Patients with Complicated Intra-Abdominal Infection: A Pooled Analysis from the IGNITE1 and IGNITE4 Studies.

Background: Eravacycline is a novel, fully synthetic fluorocycline antibiotic that was evaluated for the treatment of complicated intra-abdominal infections (cIAI) in two phase 3 clinical trials. The objective of this analysis was to evaluate the clinical cure and microbiologic response at the test-of-cure (TOC) visit and the safety of eravacycline in patients with cIAI and baseline bacteremia who received eravacycline versus comparators. Patients and Methods: Pooled data of patients with bacteremia from the Investigating Gram-Negative Infections Treated with Eravacycline (IGNITE) 1 and IGNITE4 studies were analyzed. All patients were randomly assigned in a one-to-one ratio to receive eravacycline 1 mg/kg intravenously every 12 hours, ertapenem 1 g intravensouly every 24 hours (IGNITE1), or meropenem 1 g intravenously every eight hours (IGNITE4) for four to 14 days. Blood and intra-abdominal samples were collected from all patients at baseline. Clinical outcome and microbiologic eradiation at the TOC visit (28 days after randomization) and safety in the microbiologic-intent-to-treat population (micro-ITT) were assessed. Results: Of 415 patients treated with eravacycline and 431 treated with carbapenem comparators, concurrent bacteremia was identified in 32 (7.7%) and 31 (7.2%) patients, respectively. Demographic and baseline characteristics were similar among treatment groups. In the micro-ITT population, the pooled clinical response at the TOC visit for eravacycline was 28 of 32 (87.5%) and was 24 of 31 (77.0%) for comparators among the subgroup with baseline bacteremia (treatment difference 5.9; 95% confidence interval [CI], -6.5 to 17.4). At TOC, microbiologic eradication of pathogens isolated from blood specimens occurred for 34 of 35 (97.1%) pathogens with eravacycline and 35 of 36 (97.2%) pathogens with comparators. The incidence of adverse events was comparable between treated groups and similar to that observed in the non-bacteremic population. Conclusion: Eravacycline demonstrated a similar clinical outcome and microbiologic eradication rate as comparator carbapenems in patients with cIAI and associated secondary bacteremia. Future clinical trials of cIAI should report outcomes of this important clinical cohort (cIAI with concurrent bacteremia) given their high risk for adverse outcomes.

No Evidence for Ceftobiprole-Induced Immune Hemolytic Anemia in Three Phase 3 Clinical Trials.

PurposeDrug-induced immune hemolytic anemia (DIIHA) is a rare but serious adverse event associated with a number of drugs, including second- and third-generation cephalosporins. A positive direct antiglobulin test (DAT) is a reliable finding in DIIHA, but positive results without evidence of hemolysis can occur, particularly in hospitalized patients. There have been no reports of hemolytic anemia in four previous Phase 3 trials or from post-marketing surveillance of the advanced-generation, broad-spectrum cephalosporin, ceftobiprole. The aim of this analysis was to review the incidence of positive DAT results and any evidence of hemolytic anemia from three recent Phase 3 trials of ceftobiprole.Patients and MethodsPatients were enrolled in three Phase 3 randomized controlled trials: 94 pediatric patients with pneumonia received ceftobiprole in the BPR-PIP-002 trial; 335 adults with acute bacterial skin and skin structure infections received ceftobiprole in the TARGET trial; and 201 adults with Staphylococcus aureus bacteremia have been randomized 1:1 to ceftobiprole or daptomycin ± aztreonam in the ongoing ERADICATE trial. In all three trials, DAT results were obtained at baseline, and follow-up tests were performed either at the test of cure (TOC) visit (BPR-PIP-002), end-of-treatment (EOT) visit (TARGET), or both EOT and post-treatment Day 70 visits (ERADICATE).ResultsIn the BPR-PIP-002 trial, five patients (all ceftobiprole treated) had a documented negative DAT result at baseline followed by a positive result at the TOC visit. One patient in the ongoing, blinded ERADICATE trial had a positive DAT result at both baseline and EOT. Results from other laboratory investigations showed no evidence of hemolytic anemia in these patients. No positive DAT results were reported in the TARGET trial.ConclusionNo evidence of hemolytic anemia associated with ceftobiprole was observed in either adults or children across several indications in this analysis of three large Phase 3 trials.

2227. Outcomes in Patients with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane–Tazobactam (C/T) Treatment of Nosocomial Pneumonia (ASPECT-NP)

BackgroundASPECT-NP, a phase 3, randomized, double-blind study, evaluated C/T (at double the approved dose for other indications) vs. meropenem (MEM) in adults with ventilated nosocomial pneumonia. We compared safety and efficacy outcomes from this trial among patients with and without renal impairment (RI).MethodsPatients were stratified by age and diagnosis and were randomized 1:1 to intravenous (IV) C/T 3 g every 8 h or IV MEM 1 g every 8 h. Study drug was administered for 8–14 days; doses were adjusted for moderate and severe RI. Eligible patients were mechanically ventilated; those on renal replacement therapy or with creatinine clearance (CrCL) < 15 mL/minute were excluded. Key efficacy endpoints included clinical cure rates at the test of cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) populations and Day 28 all-cause mortality (ACM) in the ITT population. In this analysis, patients were stratified based on renal function for outcome comparisons: normal renal function (CrCL ≥ 80 mL/minute); mild RI (CrCL > 50 to < 80 mL/minute); moderate RI (CrCL ≥ 30 to ≤ 50 mL/minute); and severe RI (CrCL ≥ 15 to < 30 mL/minute).ResultsA total of 726 patients were enrolled (C/T, N = 362; MEM, N = 364). Clinical cure rates at the TOC visit (CE and ITT populations) were robust across CrCL subgroups in both treatment arms and were similar based on 95% confidence intervals for treatment differences that included 0 (table). Day 28 ACM rates for patients with moderate and severe RI were numerically higher than those with mild RI in the MEM treatment arm. Rates of treatment-emergent adverse events (TEAEs) were similar in both treatment arms and across CrCL subgroups, with rates generally increasing with increasing RI severity. Rates of treatment-related TEAEs were low across treatment arms and CrCL subgroups with no treatment-related deaths reported.ConclusionSimilar clinical cure and Day 28 ACM rates at the TOC visit were found across treatment groups for all CrCL subgroups, consistent with the overall primary and key secondary efficacy results for the ASPECT-NP study. Both drugs were well-tolerated. The results of this analysis indicate that the use of dose-adjusted C/T is appropriate in patients with nosocomial pneumonia and moderate or severe RI. Disclosures All authors: No reported disclosures.

704. Incidence and Patient Outcomes of S. aureus Isolates from Acute Bacterial Skin and Skin Structure Infections (ABSSSI) with High Iclaprim MIC values in Phase 3 REVIVE Trials

BackgroundThe incidence and outcomes of patients with S. aureus isolates with an iclaprim MIC >8 µg/mL, a concentration that is not systemically achievable, were determined among patients from two Phase 3 studies for the treatment of ABSSSI, REVIVE-1 and -2.MethodsREVIVE-1 and REVIVE-2 studies were 600-patient, double-blinded, randomized (1:1), active-controlled trials among patients with ABSSSI that compared the safety and efficacy of iclaprim 80 mg fixed dose with vancomycin 15 mg/kg (adjusted for renal function), both administered intravenously over 2 hours every 12 hours for 5–14 days. Patients had a bacterial skin infection suspected or confirmed to be due to a Gram-positive pathogen with a lesion size ≥75 cm2. An early clinical response (ECR) was defined as a ≥20% reduction in lesion size compared with baseline at the early time point (ETP) 48–72 hours after the start of administration of the study drug in the intent-to-treat (ITT) population. A clinical cure, defined as complete resolution of all signs and symptoms of ABSSSI was measured at the end of therapy (EOT) and test of cure (TOC) visit, 7–14 days after the last dose of study drug. At baseline, EOT and TOC visits, ABSSSIs were sampled for microbiological culture and broth microdilution susceptibility testing conducted in accordance with CLSI M7.ResultsThe incidence of culture confirmed S. aureus isolates among patients with ABSSSI with an iclaprim MIC >8 µg/mL was 2.0% (16/790). Six were MSSA and 10 were MRSA. The clinical outcomes of these infections included ECR of 63% (10/16), EOT response of 81.3% (13/16) and the TOC response of 75% (12/16). For microbiological outcomes of these infections, the end of therapy response was 92.9% (13/14) and the test of cure response was 92.3% (12/13). In comparison, there was less variation in vancomycin MICs among the S. aureus isolates. For patients who were randomized to vancomycin and had a pathogen identified from their ABSSSI, the pooled ECR was 82.6% (242 of 293) at a vancomycin MIC of 0.5–1 µg/mL and one isolate from a patient with ECR had a MIC of 2 µg/mL.ConclusionPatients receiving iclaprim had good clinical and microbiological responses against S. aureus isolates with an iclaprim MIC >8 µg/mL, which are uncommon (2.0%).Disclosures All authors: No reported disclosures.

1473. Structured Patient Interview in Complicated Urinary Tract Infections to Assess Clinical Outcomes vs. Investigator’s Evaluation in the APEKS-cUTI Study

BackgroundBased on the 2009 US FDA guidance, patient-reported outcome (PRO) measures are recommended in clinical study designs for certain indications to evaluate response to therapy from the patient’s perspective, and a PRO was recommended in the final complicated urinary tract infection (cUTI) guidance in 2014. Several PRO tools have been rigorously validated, but currently, no tool exists for evaluating cUTI. We included a “structured patient interview (SPI)“ while conducting a randomized, double-blind, study (NCT02321800) investigating cefiderocol (CFDC) vs. imipenem–cilastatin (IPM/CS) in cUTI patients to support the physician’s assessment of clinical response.MethodsPatients, who were fully alert and oriented, were interviewed at randomization, end of treatment, test of cure (TOC), and follow-up (FUP) by the same interviewer. The questionnaire identified the presence or absence of relevant symptoms pertinent to cUTI. Responses were graded as none, or if present, mild, moderate, or severe. Investigator assessment included objective measures of clinical outcome(s) and was performed independently from the patient-reported symptoms collected in the SPI. Changes in the patient’s responses were compared with the investigator’s assessment at randomization and at each study visit. A kappa correlation coefficient comparing the SPI and physician’s clinical assessment was calculated at each evaluation time point.ResultsBased on investigator assessment, 89.7% (226 out of 252 patients) in the CFDC arm and 87.4% (104 out of 119 patients) in the IPM/CS arm achieved clinical cure (adjusted treatment difference: 2.39%; 95% CI: –4.66; 9.44) at TOC. Based on the SPI responses, 89.7% (226 out of 252 patients) in the CFDC arm and 84.9% (101 out of 119 patients) in the IPM/CS arm achieved clinical cure (adjusted treatment difference: 4.96%; 95% CI: –2.48; 12.39) in favor of CFDC. The correlation between SPI evaluation and physician’s assessment of clinical outcomes was very high at TOC and FUP visits (Kappa coefficients: 0.820 and 0.766, respectively).ConclusionThe strong correlation between patients’ reported symptoms collected in the SPI and investigator assessment showed that SPI responses could be a useful alternative measure of clinical outcomes in cUTI studies.Disclosures All authors: No reported disclosures.

DIAGNOSIS AND OUTCOMES IN PATIENTS WITH ATYPICAL PATHOGENS IN A PHASE-3 COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA TRIAL COMPARING DELAFLOXACIN TO MOXIFLOXACIN

SESSION TITLE: Monday Electronic Posters 1 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: An etiological agent is often not identified at the time of diagnosis of community-acquired bacterial pneumonia (CABP) and as such, the Infectious Diseases Society of America/American Thoracic Society Guidelines recommend that empirical treatment cover atypical pathogens. Fluoroquinolones (FQ) have a spectrum of activity that covers gram-positive, gram-negative and atypical pathogens common in CABP. Delafloxacin (DLX) is a new FQ with activity against many Gram-positive FQ-resistant strains. A Phase 3 global, randomized, double-blind, active-controlled study was recently completed to evaluate IV-to-oral DLX compared with moxifloxacin (MOX) in the treatment of CABP. We report the clinical outcomes among patients with atypical pathogens. METHODS: CABP patients were randomized to receive 5-10 days of either DLX or MOX and could switch from IV to oral dosing after Day 3. Serologic diagnosis of Legionella pneumophila (Lp), Mycoplasma pneumoniae (Mp), and Chlamydophila pneumoniae (Cp) was made using paired acute and convalescent sera showing at least a 4-fold increase in titer. Additionally, Lp could be diagnosed by sputum culture or urinary antigen and Mp could be diagnosed by culture of oropharyngeal swabs. Susceptibility testing was performed on Lp and Mp isolates. Efficacy assessments were performed at 96 (±24) hours for Early Clinical Response (ECR) and at the Test of Cure (TOC) visit 5-10 days after the end of treatment. RESULTS: 859 patients were enrolled from sites in 18 countries, and a microbiological diagnosis (all pathogens) was established in 60.5% of patients. In the patients with baseline pathogens, Lp, Mp and Cp were detected in 11.9, 12.5 and 7.9% of these patients, respectively. Overall, 13.1% of microbial diagnoses were monomicrobial infections with atypical pathogens. DLX had potent activity against Mp and Lp. The DLX MIC90 was 0.5 μg/mL for Mp and the MICs ranged from 0.00025-0.001 μg/mL (n=4) for Lp. Overall DLX was non-inferior to MOX for the treatment of CABP in the primary outcome of ECR and by-pathogen success rates were high. In the evaluable population, ECR (DLX vs. MOX) was 93.1% vs. 87.5% for Lp, 85.7% vs. 96.7% for Mp, and 96.0% vs 87.5% for Cp. At the TOC visit, clinical success was 93.1% vs. 100% for Lp, 96.7% vs. 100% for Mp, and 100% vs 100% for Cp. CONCLUSIONS: Atypical pathogens were frequently identified in this Phase 3 study in CABP, including as monomicrobial infections. DLX, which is approved for treatment of acute bacterial skin and skin structure infections in the US, was confirmed as efficacious in monotherapy for CABP and provided comparable outcomes to MOX for the treatment of patients with atypical pathogens. CLINICAL IMPLICATIONS: DLX may be a useful treatment option for monotherapy in CABP on either an inpatient or outpatient basis when empirical coverage of atypical pathogens is desired. DISCLOSURES: Employee relationship with Melinta Please note: >$100000 Added 03/03/2019 by Sue Cammarata, source=Web Response, value=Salary Employee relationship with Melinta Therapeutics, Inc. Please note: >$100000 Added 03/04/2019 by Kara Keedy, source=Web Response, value=Salary Stock holder relationship with Melinta Therapeutics, Inc. Please note: $1001 - $5000 Added 03/12/2019 by Kara Keedy, source=Web Response, value=stock Employee relationship with Melinta Therapeutics Please note: >$100000 Added 03/12/2019 by Laura LAWRENCE, source=Web Response, value=Salary No relevant relationships by Yang Li, source=Web Response Employee $100000 Added 03/12/2019 by Sandra McCurdy, source=Web Response, value=Salary<br former employee relationship with Melinta Therapeutics Please note: >$100000 Added 03/12/2019 by Ashley Nenninger, source=Web Response, value=salary and stock Employee relationship with Melinta Therapeutics, Inc. Please note: >$100000 Added 03/12/2019 by Megan Quintas, source=Web Response, value=Salary Employee relationship with Melinta Therapeutics Inc Please note: >$100000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Salary Stock holder relationship with Melinta Therapeutics Inc Please note: $1-$1000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Consulting fee Removed 03/12/2019 by Amanda Sheets, source=Web Response Stock holder relationship with Melinta Therapeutics Inc Please note: $1001 - $5000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Stock

Comparative analysis of safety and efficacy of cefotaxime/sulbactam verses piperacillin/tazobactam combinations in the treatment of complicated urinary tract infections

Background: Complicated UTIs (cUTIs) are leading causes of the gram negative bacteraemia. The objective of this study was to compare efficacy and safety Cefotaxime/ Sulbactam (CTS) and Piperacillin/ Tazobactam (PT) combinations in complicated Urinary Tract Infections.Methods: Total 80 patients admitted in the hospital due to cUTI were enrolled. 31 patients were given CTS while 49 patients were given PT. Clinical symptoms were registered and scored as mild (1) moderate (2) or severe (3). The follow-up of were done daily till the patient is discharged. Thereafter, one follow up visit was done within 4 to 9 days of after discharge, termed as test of cure (TOC), and, one late follow up visit after 6 to 8 weeks was done, known as late follow up visit (LFU). Clinical assessments and microbiological analysis were done at the time of TOC and LFU.Results: At TOC visit, in CTS and PT groups, clinical scores were 1.25±3.47 and 0.86±2.35, respectively (p&lt;0.005). Rate of clinical improvement at TOC visit was 92.00% and 92.68% while microbiological clearance was 84.00% and 87.80% with CTS and PT groups respectively. At LFU visit, clinical scores CTS and PT in groups were 1.30±3.56 and 1.32±3.37, respectively, suggesting significant improvement from baseline (p&lt;0.005). Clinical cure rate at LFU visit was 88.00% and 87.80% while microbiological cure rate at LFU visit was 76.00% and 82.91% in CTS and PT groups respectively.Conclusions: Results suggest that both regimens have no significant difference for the treatment of cUTI. CTS and PT both are equally efficacious in treatment of cUTI.

Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli.

Cefiderocol is an injectable siderophore cephalosporin discovered and being developed by Shionogi & Co., Ltd., Japan. As with other β-lactam antibiotics, the principal antibacterial/bactericidal activity of cefiderocol occurs by inhibition of Gram-negative bacterial cell wall synthesis by binding to penicillin binding proteins; however, it is unique in that it enters the bacterial periplasmic space as a result of its siderophore-like property and has enhanced stability to β-lactamases. The chemical structure of cefiderocol is similar to both ceftazidime and cefepime, which are third- and fourth-generation cephalosporins, respectively, but with high stability to a variety of β-lactamases, including AmpC and extended-spectrum β-lactamases (ESBLs). Cefiderocol has a pyrrolidinium group in the side chain at position 3 like cefepime and acarboxypropanoxyimino group in the side chain at position 7 of the cephem nucleus like ceftazidime. The major difference in the chemical structures of cefiderocol, ceftazidime and cefepime is the presence of a catechol group on the side chain at position 3. Together with the high stability to β-lactamases, including ESBLs, AmpC and carbapenemases, the microbiological activity of cefiderocol against aerobic Gram-negative bacilli is equal to or superior to that of ceftazidime-avibactam and meropenem, and it is active against a variety of Ambler class A, B, C and D β-lactamases. Cefiderocol is also more potent than both ceftazidime-avibactam and meropenem versus Acinetobacter baumannii, including meropenem non-susceptible and multidrug-resistant (MDR) isolates. Cefiderocol's activity against meropenem-non-susceptible and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriales is comparable or superior to ceftazidime-avibactam. Cefiderocol is also more potent than both ceftazidime-avibactam and meropenem against all resistance phenotypes of Pseudomonas aeruginosa and against Stenotrophomonas maltophilia. The current dosing regimen being used in phase III studies is 2g administered intravenously every 8h (q8h) using a 3-h infusion. The pharmacokinetics of cefiderocol are best described by a three-compartment linear model. The mean plasma half-life (t½) was ~ 2.3h, protein binding is 58%, and total drug clearance ranged from 4.6-6.0 L/h for both single- and multi-dose infusions and was primarily renally excreted unchanged (61-71%). Cefiderocol is primarily renally excreted unchanged and clearance correlates with creatinine clearance. Dosage adjustment is thus required for both augmented renal clearance and in patients with moderate to severe renal impairment. In vitro and in vivo pharmacodynamic studies have reported that as with other cephalosporins the pharmacodynamic index that best predicts clinical outcome is the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (%fT > MIC). In vivo efficacy of cefiderocol has been studied in a variety of humanized drug exposure murine and rat models of infection utilizing a variety of MDR and extremely drug resistant strains. Cefiderocol has performed similarly to or has been superior to comparator agents, including ceftazidime and cefepime. A phase II prospective, multicenter, double-blind, randomized clinical trial assessed the safety and efficacy of cefiderocol 2000mg q8h versus imipenem/cilastatin 1000mg q8h, both administered intravenously for 7-14days over 1h, in the treatment of complicated urinary tract infection (cUTI, including pyelonephritis) or acute uncomplicated pyelonephritis in hospitalized adults. A total of 452 patients were initially enrolled in the study, with 303 in the cefiderocol arm and 149 in the imipenem/cilastatin arm. The primary outcome measure was a composite of clinical cure and microbiological eradication at the test-of-cure (TOC) visit, that is, 7days after the end of treatment in the microbiological intent-to-treat (MITT) population. Secondary outcome measures included microbiological response per pathogen and per patient at early assessment (EA), end of treatment (EOT), TOC, and follow-up (FUP); clinical response per pathogen and per patient at EA, EOT, TOC, and FUP; plasma, urine and concentrations of cefiderocol; and the number of participants with adverse events. The composite of clinical and microbiological response rates was 72.6% (183/252) for cefiderocol and 54.6% (65/119) for imipenem/cilastatin in the MITT population. Clinical response rates per patient at the TOC visit were 89.7% (226/252) for cefiderocol and 87.4% (104/119) for imipenem/cilastatin in the MITT population. Microbiological eradication rates were 73.0% (184/252) for cefiderocol and 56.3% (67/119) for imipenem/cilastatin in the MITT population. Additionally, two phase III clinical trials are currently being conducted by Shionogi & Co., Ltd., Japan. The two trials are evaluating the efficacy of cefiderocol in the treatment of serious infections in adult patients caused by carbapenem-resistant Gram-negative pathogens and evaluating the efficacy of cefiderocol in the treatment of adults with hospital-acquired bacterial pneumonia, ventilator-associated pneumonia or healthcare-associated pneumonia caused by Gram-negative pathogens. Cefiderocol appears to be well tolerated (minor reported adverse effects were gastrointestinal and phlebitis related), with a side effect profile that is comparable to other cephalosporin antimicrobials. Cefiderocol appears to be well positioned to help address the increasing number of infections caused by carbapenem-resistant and MDR Gram-negative bacilli, including ESBL- and carbapenemase-producing strains (including metallo-β-lactamase producers). A distinguishing feature of cefiderocol is its activity against resistant P. aeruginosa, A. baumannii, S. maltophilia and Burkholderia cepacia.

Cefoperazone + sulbactam versus cefotaxime + sulbactam combination therapy for the treatment of complicated urinary tract infections in hospitalized patients: Safety and efficacy analysis

Background: Complicated urinary tract infections (cUTIs) are one of the leading causes of the Gram-negative bacteremia which commonly seen in patients who have a functionally, metabolically, or anatomically abnormal urinary tract. In patients with cUTI, proper treatment can reduce the unnecessary rick and cost of disease progression. Aims and Objectives: The aim of the study was to compare efficacy and safety Cefoperazone + Sulbactam (CPS) versus Cefotaxime + Sulbactam (CTS) combinations in cUTI. Materials and Methods: At entry, a total of 74 patients admitted in the hospital due to cUTI were enrolled. Among 74 patients, 43 patients were given CPS while 31 patients were given CTS combinations. Five clinical symptoms (e.g., dysuria, frequency, suprapubic pain, back, and/or flank pain) were registered and scored as mild (1), moderate (2), or severe (3). The follow-up of the indoor patients was done daily until the patient is discharged. Thereafter, one follow-up visit was done within 4–9 days of after discharge, termed as a test of cure (TOC). Furthermore, one late follow-up visit (LFU) after 6–8 weeks was done, known as LFU. Clinical assessments and microbiological analysis were done at the time of TOC and LFU. The mean baseline clinical score for CPS and CTS was 10.28 ± 2.33 and 10.57 ± 2.02, respectively. Results: At TOC visit, in CPS and CTS groups, clinical scores were 1.36 ± 3.48 and 1.25 ± 3.47 in CPS and CTS, respectively, suggesting significant improvement from baseline (P < 0.005). Rate of clinical improvement at TOC visit was 87.50% and 92.00% while microbiological cure rate was 93.75% and 84.00% with CPS and CTS groups, respectively, while, at LFU visit, clinical scores in both groups were 1.65 ± 4.10 and 1.30 ± 3.56 suggesting significant improvement from baseline (P < 0.005). Clinical cure rate at LFU visit was 87.85% and 88.00% while microbiological cure rate at LFU visit was 77.00% and 76.00% with CPS and CTS groups, respectively. Conclusion: These results suggest that both regimens have no significant difference in the treatment of cUTI. The study concluded that both the combination, CTS and CTS are equally efficacious in the treatment of cUTI. The frequency and severity of drug-related adverse events were generally similar in both treatment groups.

1978. Efficacy of Eravacycline in Secondary Bacteremia: A Post Hoc Analysis of Two Phase 3 studies of Complicated Intra-Abdominal Infection

BackgroundEravacycline is a novel, fully synthetic fluorocycline antibiotic that was evaluated for the treatment of complicated intra-abdominal infections (cIAI) in two Phase 3 (IGNITE1 and IGNITE4) clinical trials. The objective of this analysis was to evaluate microbiological response at the test of cure (TOC) visit in patients with baseline bacteremia who received eravacycline vs. comparators (ertapenem and meropenem).MethodsPooled data from IGNITE1 and IGNITE4 studies were analyzed. All patients enrolled were randomized (1:1) to receive eravacycline (1 mg/kg IV q12h) or ertapenem 1 g IV q24h, (IGNITE1 study) or meropenem 1g IV q8h, (IGNITE4 study) for 4–14 days. Blood (aerobic and anaerobic bottles) and intra-abdominal samples were collected from all patients. Clinical outcome at the TOC visit (28 days after randomization) in the microbiological-intention to treat population (micro-ITT) was the primary efficacy endpoint.ResultsFour hundred fifteen patients were treated with eravacycline and 431 with comparators of which 39 (9.4%) and 40 (9.3%), respectively, had concurrent bacteremia. Demographic and baseline characteristics were similar among the groups. In the micro-ITT population, the pooled clinical response at the TOC visit for eravacycline vs. comparators was 88.7% and 89.3% (−0.7; 95% CI, −4.9, 3.6), respectively. The baseline pathogens associated with concurrent bacteremia and the microbiological eradication for selected pathogens are presented in Table 1.Table 1.Microbiological Eradication at the Test of Cure Visit by Baseline Pathogen from Blood SpecimenEravacycline, (N = 415), n (%)Comparatorsa, (N = 431), n (%)Gram-negative14/15 (93.3)14/15 (93.3) E. coli 5/6 (83.3)6/7 (85.7)Gram-positive15/15 (100)11/11 (100) Streptococcus spp.8/8 (100)4/4 (100) Enterococcus spp.2/2 (100)5/5 (100)Anaerobes9/9 (100)13/14 (92.9) Bacteroides spp.6/6 (100)8/8 (100) aMeropenem and ertapenem.ConclusionEravacycline demonstrated a similar microbiological eradication rate as comparator agents in patients with cIAI associated with secondary bacteremia.Disclosures K. Lawrence, Tetraphase Pharmaceuticals: Employee, Salary. M. Olesky, Tetraphase Pharmaceuticals: Employee and Shareholder, Salary. S. Izmailyan, Tetraphase Pharmaceuticals: Employee, Salary. L. Tsai, Tetraphase Pharmaceuticals: Employee and Shareholder, Salary.

1963. Combined Microbiological Response Rates From Two Phase 3 Trials Demonstrating the Activity of Eravacycline in the Treatment of Complicated Intra-abdominal Infections: A Pooled Analysis of IGNITE1 and IGNITE4

BackgroundIGNITE1 and IGNITE4 were randomized, double-blind, double-dummy, multicenter studies which demonstrated the efficacy and safety of eravacycline (ERV) compared with a carbapenem in subjects with complicated intra-abdominal infections (cIAIs). The primary objective of this analysis was to compare the microbiological response at the test-of-cure (TOC) visit for subjects in the two treatment groups.MethodsAppropriate aerobic and anaerobic specimens for culture at the time of the initial procedure were collected from the site of infection and directly inoculated into transport media. Blood and intra-abdominal specimens were cultured, and species identified according to local laboratory practice. Pure cultures of isolates were sent to a reference laboratory for susceptibility analysis to ERV and comparators. Favorable microbiological response rates at the TOC visit were determined for each baseline pathogen isolated from blood and/or intra- or extra-abdominal specimens in the micro-ITT population.ResultsFor subjects with infections caused by Enterobacteriaceae, the overall favorable microbiological response rates for ERV-treated subjects were 86.3% and 91.8% for IGNITE1 and IGNITE4, respectively. The favorable microbiological response rates among pooled ERV-treated subjects are shown in the Table.Baseline PathogenERV No./Total No. (%)Baseline PathogenERV No/Total No. (%) Enterobacteriaceae 277/314 (88.2) Streptococcus viridans group109/120 (90.8) E. coli 223/253 (88.1) E. faecalis 45/54 (83.3) E. cloacae 18/21 (85.7) E. faecium 39/45 (86.7) K. pneumoniae 38/39 (97.4) S. aureus 24/24 (100) A. baumannii 13/13 (100) B. fragilis 74/84 (88.1)ConclusionIn IGNITE1 and IGNITE4 studies, high favorable microbiological responses were observed for ERV. More than 88% of five Enterobacteriaceae spp. and B. fragilis, the most common bacteria associated with intraabdominal infections, were eradicated by ERV. Comparable eradication rates were observed following ertapenem and meropenem therapy, further establishing that ERV was at least as effective as carbapenem treatments. These data support in vitro observations that ERV has broad-spectrum activity against common isolates found in intra-abdominal infections.Disclosures J. Newman, Tetraphase Pharmaceuticals: Employee, Salary. S. Izmailyan, Tetraphase Pharmaceuticals: Employee, Salary. C. Fyfe, Tetraphase Pharmaceuticals: Employee, Salary. L. Tsai, Tetraphase Pharmaceuticals: Employee and Shareholder, Salary.

Frequency of Nucleic Acid Amplification Test Positivity Among Men Who Have Sex With Men Returning for a Test-of-Cure Visit 7 to 30 Days After Treatment of Laboratory-Confirmed Neisseria gonorrhoeae Infection at 2 Public Sexual Health Clinics, New York City, 2013 to 2016.

The Centers for Disease Control and Prevention 2015 Sexually Transmitted Disease Treatment Guidelines recommend that clinicians consider cephalosporin treatment failure in patients who deny interval sexual exposure and are nucleic acid amplification test (NAAT) positive for Neisseria gonorrhoeae (NG) at least 7 days after adequate treatment. We evaluate the real-world implications of the interval the Centers for Disease Control and Prevention recommends for a NAAT test-of-cure (TOC), by ascertaining the frequency of NG NAAT positivity at different anatomic sites among men who have sex with men (MSM) at TOC 7 to 30 days after treatment. We analyzed data from the medical records of MSM with laboratory-confirmed NG who were presumptively treated for NG during the period from June 2013 to April 2016 and returned for a TOC visit within 30 days. Data examined included symptoms, site of NG specimen collection, treatment regimen, follow-up testing, and intervening sexual activity. There were 1027 NG-positive specimens obtained from 763 MSM patients at 889 presumptive treatment visits. Of these, 44% (337/763) MSM returned for 1 or more TOC visits, and 413 specimens were collected a median of 10 days after presumptive treatment. Three percent (14/413) of specimens collected were NG NAAT positive at TOC a median of 13 days after treatment: 5% (12/256) of urethral specimens, 1% (1/147) of anorectal specimens (P = 0.037, urethral vs. anorectal), and 10% (1/10) of oropharyngeal specimens (P = 0.40, urethral vs. oropharyngeal). A small percent of patients were NG NAAT positive at TOC. Compared with anorectal specimens, urethral specimens were more frequently still positive at TOC. A large proportion of MSM will return for a TOC visit as part of standard clinical care.