scholarly journals 1232. Efficacy and Safety of Intravenous Sulopenem Followed by Oral Sulopenem etzadroxil/Probenecid Versus Intravenous Ertapenem Followed by Oral Ciprofloxacin or Amoxicillin-clavulanate in the Treatment of Complicated Urinary Tract Infections (cUTI): Results from the SURE-2 Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S636-S636
Author(s):  
Michael W Dunne ◽  
Steven I Aronin

Abstract Background Sulopenem is a broad-spectrum IV and oral penem antibiotic being developed for the treatment of infections caused by multidrug-resistant bacteria to allow for earlier discharge of hospitalized patients. Methods 1,395 hospitalized adults with pyuria, bacteriuria, and clinical signs and symptoms of cUTI were randomized to sulopenem IV once daily for 5 days followed by a bilayer tablet of sulopenem-etzadroxil and probenecid bid or ertapenem IV once daily for 5 days followed by either oral ciprofloxacin or amoxicillin-clavulanate bid, depending on susceptibility of the baseline uropathogen. The primary endpoint was overall (clinical and microbiologic) response at Day 21 [Test of Cure (TOC)] in the micro-MITT population. Results The sulopenem and ertapenem treatment arms were well-balanced at baseline. The difference in overall response was driven by a difference in asymptomatic bacteriuria occurring between the end of treatment (EOT) and TOC in the subgroup of patients with a ciprofloxacin susceptible uropathogen at baseline who received ertapenem IV followed by oral ciprofloxacin. No difference in overall response was identified at EOT [86.7% vs 88.9%, sulopenem and ertapenem, respectively; difference, 95% CI: -2.2% (-6.5, 2.2)]. 19% of patients remained on ertapenem IV as the baseline pathogen was both resistant to quinolones and ESBL positive; overall response for patients with these resistant pathogens on IV sulopenem who stepped down to oral sulopenem was higher [64/80 vs 55/84 on sulopenem IV/oral and ertapenem IV, respectively; difference, 95% CI: 14.5% (0.8, 27.8)]. Treatment emergent adverse events (all, 14.8% vs 16.1%; related, 6.0% vs 9.2%) and serious adverse events (2.0% vs 0.9%) were similar for patients on sulopenem and ertapenem, respectively. Overall Response at Test of Cure, micro-MITT Population Conclusion Sulopenem followed by oral sulopenem-etzadroxil probenecid was not non-inferior to ertapenem followed by oral step-down therapy for the treatment of cUTI driven by a lower rate of asymptomatic bacteriuria in patients receiving oral ciprofloxacin. Sulopenem, both IV and oral, was well-tolerated; its oral formulation allowed patients with baseline pathogens resistant to both quinolones and β-lactams an opportunity to successfully step down from IV therapy. Disclosures Michael W. Dunne, MD, Iterum Therapeutics (Employee, Shareholder) Steven I. Aronin, MD, Iterum Therapeutics (Employee, Shareholder)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S844-S844
Author(s):  
Michael W Dunne ◽  
Anita F Das ◽  
Michael Zelasky ◽  
Karthik Akinapelli ◽  
Helen Boucher ◽  
...  

Abstract Background Sulopenem is a broad-spectrum IV and oral penem antibiotic being developed for the treatment of infections caused by multidrug-resistant bacteria. Overall and Clinical Success in Patients with an Uncomplicated UTI at Test of Cure (TOC) and End of Treatment (EOT) Methods 1,671 adult women with pyuria, bacteriuria, and signs and symptoms of uUTI were randomized to sulopenem etzadroxil/probenecid bid for 5 days or ciprofloxacin bid for 3 days. Two independent primary analyses, each with a separate alpha assigned, were incorporated into the design of the study with the primary endpoint being overall success (combined clinical and microbiologic success) at the Test of Cure (TOC) visit. In the micro-MITTR population (patients with baseline pathogen resistant to ciprofloxacin), sulopenem was compared for superiority over ciprofloxacin; in the micro-MITTS population (patients with baseline pathogen susceptible to ciprofloxacin), the two agents were compared for non-inferiority. Using a pre-specified hierarchical testing procedure (Westfall 2001), the primary efficacy endpoint was then to be further tested if either superiority or non-inferiority was declared in the MITTR or MITTS populations, respectively. Results In the micro-MITTR population, sulopenem demonstrated superiority to ciprofloxacin (p < 0.001). In the micro-MITTS population, sulopenem was not non-inferior to ciprofloxacin for the primary endpoint, driven primarily by the higher rate of asymptomatic bacteriuria post treatment in patients on sulopenem. In the combined analysis of all randomized patients with an organism identified at baseline (MITTR+MITTS), sulopenem was non-inferior to ciprofloxacin. Treatment emergent adverse events occurred more frequently in sulopenem patients (all, 24.8% vs 13.9%; related, 17.0% vs 6.2%), accounted for by a higher incidence of self-limited diarrhea (12.4% vs 2.5%). Serious adverse events were similar on each regimen. Conclusion Sulopenem was superior to ciprofloxacin for the treatment of adult women with uUTI due to quinolone non-susceptible pathogens. Sulopenem was not non-inferior in the treatment of quinolone susceptible pathogens, driven by a lower rate of asymptomatic bacteriuria in patients receiving ciprofloxacin, but was non-inferior in the combined population of patients. Disclosures Michael W. Dunne, MD, Iterum Therapeutics (Employee, Shareholder) Anita F. Das, PhD, Iterum Therapeutics (Consultant) Michael Zelasky, BS, Iterum Therapeutics (Employee) Karthik Akinapelli, BS, Iterum Therapeutics (Employee) Steven I. Aronin, MD, Iterum Therapeutics (Employee)


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S233-S233
Author(s):  
Leslie Stach ◽  
Regina Orbach ◽  
Kanokporn Mongkolrattanothai

Abstract Background There has been an increase in antimicrobial resistance among GN pathogens, not only in adults, but also pediatrics. UTIs are common in pediatrics; however, reports of pediatric UTI with ESBL producing GN are limited. Methods All urine cultures positive for ESBL producing GN from 5/1/18 to December 31/18 were retrospectively reviewed. Proven infection (PI) defined as ≥50,000 colony-forming units (CFU)/mL of bacteria plus pyuria or positive leukocyte esterase for catheterized or clean catch specimens. Relapsed infection defined as same pathogen cultured within 30 days of infection. Abnormal urinary tract systems or functions (AUTS) include neurogenic bladder, structural anomalies, or intermittent catheterization. Results A total of 107 urine cultures for ESBL producing GN, from 85 patients, were included. Majority of specimens [78/107 (73%)] were obtained from the ED or outpatient clinics. 43% of specimens were from patients with AUTS. E. coli was the majority (95%) of ESBL isolates. 57% of ESBL producing GNs were susceptible to amoxicillin/clavulanate (AC) or trimethoprim/sulfamethoxazole (TMP/SMX). 88% were nitrofurantoin susceptible. Only 1 isolate was meropenem resistant. Antibiotics (ABX) were prescribed for UTI in 67/107 episodes. However, only 52 episodes were PI. Of these, 38 were empirically treated with oral ABX and 29 with intravenous ABX. The most commonly prescribed empiric ABX was oral cephalexin (25/67, 37%.) Ineffective empiric ABX for UTI was very common, 83% (43/52). Of these, 5/43 never received effective therapy and none had relapse. Most common duration of ABX was 10 days (range 5–17 days.) 43% (23/52) of PI were treated with oral AC or TMP/SMX. 15% (8/52) of PI were treated with nitrofurantoin. 12% of PI were treated with a once-daily aminoglycoside. Only 6% of PI were treated with a carbapenem. Conclusion Many ESBL UTI isolates remain susceptible to oral ABX. Although small numbers, patients treated with ineffective ABX did not return with relapsed infection. Non-carbapenem ABX are a reasonable option to minimize selective pressure or unnecessary use. Empiric narrow-spectrum antibiotic therapy may still be appropriate. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S212-S212
Author(s):  
Yuko Matsunaga ◽  
Mari Ariyasu ◽  
Miki Takemura ◽  
Yoshinori Yamano ◽  
Kiichiro Toyoizumi ◽  
...  

Abstract Background The efficacy and safety of cefiderocol (CFDC), a novel siderophore cephalosporin, for the treatment of serious infections due to carbapenem-resistant (CR) Gram-negative pathogens was assessed in the CREDIBLE-CR study. The current analysis evaluated clinical and microbiological outcomes by baseline CR pathogen. Methods An open-label, prospective, randomised 2:1, Phase 3 study (CREDIBLE-CR; NCT02714595) was conducted in adult patients with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, bloodstream infections or sepsis, and complicated urinary tract infections caused by CR Gram-negative pathogens. Patients received either intravenous (IV) CFDC 2g, q8h, 3-h infusion, or IV best available therapy (BAT: up to 3 drugs in combination), for 7–14 days (extendable to 21 days). Clinical and microbiological outcomes were assessed in the CR microbiological intent-to-treat (CR-MITT) population by CR pathogen, baseline MIC and by mechanism of carbapenem resistance at test of cure (TOC). Only summary statistics were collected. Results In the CR-MITT population (CFDC N=80; BAT N=38), Acinetobacter baumannii (46.3% and 44.7%), Klebsiella pneumoniae (33.8% and 31.5%), and Pseudomonas aeruginosa (15% and 26%) were the most frequent pathogens in CFDC and BAT arms, respectively. For all CR pathogens, clinical cure rates were achieved in 52.5% in the CFDC arm and 50.0% in the BAT arm at TOC; rates were similar between treatment arms by baseline CR pathogen (Table 1). Numerically higher clinical cure and microbiological outcomes were observed with CFDC for Enterobacterales (Table 1), especially against NDM-producing bacteria or those with porin-channel mutations (Table 1). CFDC MIC values ranged between ≤0.03 and 4 μg/mL, except for one pathogen (Table 2). Microbiological outcomes for CR A. baumannii, CR K. pneumoniae, and CR P. aeruginosa at TOC by baseline MICs of ≤4 μg/mL ranged between 0–40%, 0–100%, and 0–100%, respectively; at MIC ≤4 μg/mL, clinical and microbiological outcomes were equal (Table 2). Conclusion CFDC, via a novel mechanism of entry and its stability against β-lactamases, was effective against serious infections caused by CR pathogens with various resistance mechanisms or baseline MIC values. Disclosures Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee)


2019 ◽  
Vol 7 ◽  
pp. 232470961983233 ◽  
Author(s):  
Deeti J. Pithadia ◽  
Erena N. Weathers ◽  
Rhonda E. Colombo ◽  
Stephanie L. Baer

Soft tissue infections occur in over 30% of patients with chemotherapy-induced neutropenia. Gram-positive bacterial infections predominate early in neutropenia, and likelihood of infection by resistant bacteria and fungi increases with prolonged neutropenia. Prior infections and exposures influence the risk of rare pathogens. A 55-year-old woman with chemotherapy-induced neutropenia was scratched on her forearm by a dog. She cleaned the wound with isopropanol and was treated empirically with amoxicillin-clavulanate. Over the next 4 days, she developed fever along with erythema, edema, and mild tenderness of the forearm without purulence or crepitus. She was hospitalized and received empiric treatment with intravenous vancomycin, piperacillin-tazobactam, tobramycin, and voriconazole. Despite therapy, her fevers persisted and the cellulitis progressed for over a week. After 10 days of hospitalization, her neutrophil count began to recover and a bulla developed at the wound site. Culture of the bullous fluid grew Serratia marcescens, and antibiotics were switched to cefepime based on susceptibility. She defervesced and showed substantial improvement of cellulitis within 48 hours and was discharged on oral ciprofloxacin. Serratia marcescens skin infections are rare, and this may be the first report of Serratia cellulitis associated with trauma from dog contact. This case highlights the need to consider unusual pathogens based on exposure history and immune status and to obtain cultures from fluid collections or tissue in cases of treatment-resistant soft tissue infections.


Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 523
Author(s):  
Răzvan-Cosmin Petca ◽  
Silvius Negoiță ◽  
Cristian Mareș ◽  
Aida Petca ◽  
Răzvan-Ionuț Popescu ◽  
...  

Urinary tract infections (UTIs) are a leading cause of morbidity for both males and females. The overconsumption of antibiotics in general medicine, veterinary, or agriculture has led to a spike in drug-resistant microorganisms; obtaining standardized results is imposed by standard definitions for various categories of drug-resistant bacteria—such as multiple-drug resistant (MDR), extensive drug-resistant (XDR), and pan drug-resistant (PDR). This retrospective study conducted in three university teaching hospitals in Romania has analyzed urine probes from 15,231 patients, of which 698 (4.58%) presented multidrug-resistant strains. Escherichia coli was the leading uropathogen 283 (40.54%), presenting the highest resistance to quinolones (R = 72.08%) and penicillin (R = 66.78%) with the most important patterns of resistance for penicillin, sulfonamides, and quinolones (12.01%) and aminoglycosides, aztreonam, cephalosporins, and quinolones (9,89%). Klebsiella spp. followed—260 (37.24%) with the highest resistance to amoxicillin-clavulanate (R = 94.61%) and cephalosporins (R = 94.23%); the leading patterns were observed for aminoglycosides, aminopenicillins + β-lactams inhibitor, sulfonamides, and cephalosporins (12.69%) and aminoglycosides, aztreonam, cephalosporins, quinolones (9.23%). The insufficient research of MDR strains on the Romanian population is promoting these findings as an important tool for any clinician treating MDR-UTIs.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S157-S158
Author(s):  
Logan White ◽  
Andrea Dooley-Wood ◽  
Hien Nguyen ◽  
Aiman Bandali

Abstract Background In the acute care setting, urinary tract infections (UTIs) may be over diagnosed in up to 40% of cases. In most scenarios, asymptomatic bacteriuria (ASB) is not an indication for antibiotic therapy; inappropriate therapy is associated with a higher incidence of antibiotic-resistant bacteria and adverse drug reactions. Limiting inappropriate collection of urine cultures may decrease unnecessary treatment of ASB. The objective of this study is to assess the impact of a urine culture best practice advisory (BPA) on collection of unnecessary urine cultures. Methods This retrospective, observational, single-center study included adult inpatients with an order for urinalysis/urine culture. Those who were pregnant, had a concomitant infection other than UTI and/or were taking antimicrobials for a non-UTI indication, and were undergoing urological procedures were excluded. Duplicate urine culture collections and/or admissions were excluded. Incorporation of a BPA into computerized provider order entry, allowing providers to assess need and document indication for urine culture collection, was implemented on July 2019. The following clinical outcomes were assessed: number of unnecessary urine cultures collected, number of antibiotic treatments, and antibiotic-associated adverse reactions. Results Two hundred met criteria for inclusion; 96 in the pre-BPA group (Aug – Oct 2018) and 104 in the post-BPA group (Aug – Oct 2019). Seventy-four (37%) were male and the mean age was 64 and 70 years (p=0.249), respectively. The Charlson Comorbidity Index (CCI) was similar between groups (4 vs. 5, p=0.162) and majority were admitted to a general medical ward (94.5%). Seventy patients (72.9%) in the pre-BPA group and 47 (51.6%) in the post-BPA group had inappropriately ordered urinalysis/urine cultures (OR 0.40; 95% CI 0.22-0.73; p=0.003). Of these patients, 15 (21.4%) and 9 (19.1%) from the pre- and post-BPA groups, respectively, were treated (p=0.077). Among those treated, only two adverse drug reactions were reported. Conclusion Implementation of a BPA significantly reduced the number of inappropriate urinalysis/urine culture orders. There was a trend towards decreased antibiotic use for ASB. Future studies are warranted to assess sustainability of these results. Disclosures All Authors: No reported disclosures


2003 ◽  
Vol 47 (9) ◽  
pp. 2770-2774 ◽  
Author(s):  
Dan C. Henry ◽  
Ernie Riffer ◽  
William N. Sokol ◽  
Naumann I. Chaudry ◽  
Robert N. Swanson

ABSTRACT A randomized, double-blind, multicenter study of adults with acute bacterial sinusitis (ABS) compared the efficacy and safety of two azithromycin (AZM) regimens, 500 mg/day once daily for 3 days (AZM-3) or 6 days (AZM-6) to the efficacy and safety of an amoxicillin-clavulanate (AMC) regimen of 500-125 mg three times daily for 10 days. A total of 936 subjects with clinically and radiologically documented ABS were treated (AZM-3, 312; AZM-6, 311; AMC, 313). Clinical success rates were equivalent among per-protocol subjects at the end of therapy (AZM-3, 88.8%; AZM-6, 89.3%; AMC, 84.9%) and at the end of the study (AZM-3, 71.7%; AZM-6, 73.4%; AMC, 71.3%). Subjects treated with AMC reported a higher incidence of treatment-related adverse events (AE) (51.1%) than AZM-3 (31.1%, P < 0.001) or AZM-6 (37.6%, P < 0.001). More AMC subjects discontinued the study (n = 28) than AZM-3 (n = 7) and AZM-6 (n = 11) subjects. Diarrhea was the most frequent treatment-related AE. AZM-3 and AZM-6 were each equivalent in efficacy and better tolerated than AMC for ABS.


1998 ◽  
Vol 42 (12) ◽  
pp. 3193-3199 ◽  
Author(s):  
Valerie Berry ◽  
Christine E. Thorburn ◽  
Sarah J. Knott ◽  
Gary Woodnutt

ABSTRACT Comparative antibacterial efficacies of erythromycin, clarithromycin, and azithromycin were examined againstStreptococcus pneumoniae and Haemophilus influenzae, with amoxicillin-clavulanate used as the active control. In vitro, the macrolides at twice their MICs and at concentrations achieved in humans were bacteriostatic or reduced the numbers of viable S. pneumoniae slowly, whereas amoxicillin-clavulanate showed a rapid antibacterial effect. AgainstH. influenzae, erythromycin, clarithromycin, and clarithromycin plus 14-hydroxy clarithromycin at twice their MICs produced a slow reduction in bacterial numbers, whereas azithromycin was bactericidal. Azithromycin at the concentrations achieved in the serum of humans was bacteriostatic, whereas erythromycin and clarithromycin were ineffective. In experimental respiratory tract infections in rats, clarithromycin (equivalent to 250 mg twice daily [b.i.d.]) and amoxicillin-clavulanate (equivalent to 500 plus 125 mg b.i.d., respectively) were highly effective against S. pneumoniae, but azithromycin (equivalent to 500 and 250 mg once daily) was significantly less effective (P < 0.01). Against H. influenzae, clarithromycin treatment (equivalent to 250 or 500 mg b.i.d.) was similar to no treatment and was significantly less effective than amoxicillin-clavulanate treatment (P < 0.01). Azithromycin demonstrated significant in vivo activity (P < 0.05) but was significantly less effective than amoxicillin-clavulanate (P < 0.05). Overall, amoxicillin-clavulanate was effective in vitro and in vivo. Clarithromycin and erythromycin were ineffective in vitro and in vivo against H. influenzae, and azithromycin (at concentrations achieved in humans) showed unreliable activity against both pathogens. These results may have clinical implications for the utility of macrolides in the empiric therapy of respiratory tract infections.


Author(s):  
I.N. Zaharova ◽  
◽  
E.B. Mumladze ◽  
E.B. Machneva ◽  
A.N. Kasyanova ◽  
...  

2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X696833 ◽  
Author(s):  
Leah Ffion Jones ◽  
Emily Cooper ◽  
Cliodna McNulty

BackgroundEscherichia coli bacteraemia rates are rising with highest rates in older adults. Mandatory surveillance identifies previous Urinary Tract Infections (UTI) and catheterisation as risk factors.AimTo help control bacteraemias in older frail patients by developing a patient leaflet around the prevention and self-care of UTIs informed by the Theoretical Domains Framework.MethodFocus groups or interviews were held with care home staff, residents and relatives, GP staff and an out of hours service, public panels and stakeholders. Questions explored diagnosis, management, prevention of UTIs and antibiotic use in older adults. The leaflet was modified iteratively. Discussions were transcribed and analysed using Nvivo.ResultsCarers of older adults reported their important role in identifying when older adults might have a UTI, as they usually flag symptoms to nurses or primary care providers. Information on UTIs needs to be presented so residents can follow; larger text and coloured sections were suggested. Carers were optimistic that the leaflet could impact on the way UTIs are managed. Older adults and relatives liked that it provided new information to them. Staff welcomed that diagnostic guidance for UTIs was being developed in parallel; promoting consistent messages. Participants welcomed and helped to word sections on describing asymptomatic bacteriuria simply, preventing UTIs, causes of confusion and when to contact a doctor or nurseConclusionA final UTI leaflet for older adults has been developed informed by the TDF. See the TARGET website www.RCGP.org.uk/targetantibiotics/


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