scholarly journals 1043. Activity of Mecillinam Against Enterobacterales Isolates Collected From Patients With Urinary Tract Infections (UTIs) in the USA During 2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S611-S614
Author(s):  
Stephen Hawser ◽  
Ian Morrissey ◽  
Anne Santerre Henriksen
Keyword(s):  
Antimicrobial Agents ◽  
Hospital Setting ◽  
Clinical Development ◽  
Research Support ◽  
Extended Spectrum Beta Lactamase ◽  
Susceptibility Data ◽  
Frequent Use ◽  
Lactam Antibiotic ◽  
The Usa ◽  
Tract Infections

Abstract Background Mecillinam is a β-lactam antibiotic that exerts its antibacterial activity by binding to penicillin-binding protein 2. In the USA, intravenous (IV) mecillinam is in development for the treatment of complicated UTIs in the hospital setting and as step-down therapy transitioning from IV mecillinam to oral pivmecillinam so that patients can continue treatment at home. To support the clinical development of mecillinam in the USA for the treatment of both complicated and uncomplicated UTI, this observational study investigated the activity of mecillinam against Enterobacterales isolates from patients with UTI in the USA, collected during 2019. Methods This study evaluated the activity of mecillinam and other antimicrobial agents against 1075 selected Enterobacterales clinical isolates collected from patients with UTI in the USA during 2019. Antibiotic activity (minimum inhibitory concentration [MIC]) was determined by Clinical & Laboratory Standards Institute (CLSI) agar dilution methodology, and susceptibility was interpreted according to CLSI guidelines. Results Among the selected 1075 isolates, producers of extended-spectrum beta-lactamase (ESBL) represented 9.6% of Escherichia coli and 50% of Klebsiella pneumoniae. Ninety-five percent of the isolates tested were susceptible to mecillinam (Table 1). The MIC50 and MIC90 values for mecillinam were 0.25 and 2 µg/mL, respectively. Fosfomycin MIC50 and MIC90 were 1 and 32 µg/mL, respectively (97.6% of isolates were susceptible). Mecillinam showed the lowest MIC90 value of all single antibiotics tested. The highest MIC90 was 128 µg/mL for both nitrofurantoin and cefotaxime. The lowest percentage of resistance was obtained with fosfomycin (1.7%), followed by mecillinam (4%). Table 1: Summary MIC and susceptibility data for all isolates tested (n=1075) Conclusion Overall, mecillinam showed excellent activity and a comparable resistance profile to fosfomycin. Resistance rates to ceftazidime, cefotaxime, ciprofloxacin and trimethoprim/sulfamethoxazole of greater than 20% are concerning due to the frequent use of these antibiotics in clinical practice to treat UTIs. Taken together, these data demonstrate that mecillinam has promising activity, with low resistance observed in Enterobacterales species causing UTIs in the USA. Clinical development of mecillinam in the USA is ongoing. Disclosures Stephen Hawser, PhD, Utility Therapeutics (Grant/Research Support) Ian Morrissey, Utility Therapeutics (Grant/Research Support) Anne Santerre Henriksen, MS, Advanz (Consultant)Shionogi BV (Consultant)UTILITY Therapeutics (Consultant)

scholarly journals 1617. Mecillinam susceptibility against Enterobacterales isolated from urinary tract infections from US patients in 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S801-S802
Author(s):  
Stephen Hawser ◽  
Ian Morrissey ◽  
Cedric Charrier ◽  
Cyntia De Piano ◽  
Morton Alexander ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Clinical Development ◽  
Penicillin Binding Protein ◽  
Beta Lactams ◽  
Independent Contractor ◽  
Susceptibility Data ◽  
First Line Therapy ◽  
The Usa ◽  
Tract Infections

Abstract Background Mecillinam is a unique amidinopenicillin antibiotic, being the first and the only compound in its class. In contrast to other beta-lactams, it has a unique mechanism of action whereby it exerts its antibacterial activity through binding to penicillin binding protein 2. Pivmecillinam is the oral-prodrug of mecillinam and recommended as a first line therapy in the IDSA guidelines for uncomplicated urinary tract infections (uUTI), despite not yet being available in the USA. To support the clinical development of mecillinam and pivmecillinam in the USA for the treatment of both complicated UTI and uUTI this study investigated the activity of mecillinam against Enterobacterales isolates from the USA during 2018. Methods A total of 1,090 isolates from urinary tract infections from patients in the USA were tested. Activity of antibiotics was tested by CLSI methodology and susceptibility interpreted according to CLSI guidelines. Results Susceptibility and activity of each antibiotic are shown in the Table. Mecillinam MIC50 and MIC90 were 0.25 and 4 µg/mL, respectively and 94.5% of isolates were susceptible. Fosfomycin MIC50 and MIC90 were 2 and 32 µg/mL, respectively and 95.7% of isolates were susceptible. The other four comparator antibiotics showed MIC90 values >8 µg/mL and a 70.5 – 79.9% susceptible isolates. The highest MIC90 against all isolates combined was 64 µg/mL for nitrofurantoin and the highest percentage of resistance was obtained with trimethoprim-sulfamethoxazole with 29.5%. Resistance towards ceftriaxone and ciprofloxacin was 19.6% and 26.1%, respectively. Table Conclusion Overall, mecillinam showed the lowest MIC90 and a comparable susceptibility profile (94.5 % susceptible and 4.0 % resistant) to fosfomycin (i.e. 95.7% and 2.0% resistant) susceptible isolates). Resistance to ceftriaxone, ciprofloxacin and trimethoprim/sulfamethoxazole around or above 20% is concerning for their clinical usage to treat urinary tract infections. These encouraging susceptibility data warrant further studies to support the clinical development of mecillinam/pivmecillinam for the treatment of UTI in the USA. Disclosures Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Cedric Charrier, PhD, IHMA (Employee)Utility Therapeutics (Independent Contractor) Cyntia De Piano, PhD, IHMA (Employee)Utility Therapeutics (Independent Contractor) Morton Alexander, PhD, Utility Therapeutics (Employee, Shareholder) Anne Santerre Henriksen, MS, Maxel Consulting ApS (Employee)Utility Therapeutics (Independent Contractor)

scholarly journals Prevalence and Antibiotic Susceptibility Pattern of Extended Spectrum Beta Lactamases Producing Escherichia Coli Isolated from Outpatients with Urinary Tract Infections in Babol, Northern of Iran

2018 ◽  
Vol 31 (2) ◽  
pp. 61-64
Author(s):  
Mana Baziboroun ◽  
Masomeh Bayani ◽  
Zahra Poormontaseri ◽  
Mehran Shokri ◽  
Tahmineh Biazar
Keyword(s):  
Empirical Therapy ◽  
Urine Samples ◽  
Diffusion Method ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Susceptibility Data ◽  
Extended Spectrum ◽  
North Of Iran ◽  
Set Up ◽  
Tract Infections

AbstractReceived 08 November 2017 Accepted 15 February 2018 The incidence of community-acquired UTIs due to extended-spectrum beta-lactamase (ESBL) producing E. coli isolates, has increased worldwide and is considered a great problem in the treatment of infections. The aim of this study was to determine the prevalence of ESBL producing E. coli isolates in urine samples of outpatients in Babol, North of Iran. A total of 3 699 urine samples from outpatients referred to Yahyanejad Hospital, Babol, Iran, were collected during 15 months, from March 2016 to June 2017. The samples were processed for bacterial culture using conventional methods, while antimicrobial susceptibility testing for E. coli isolates was performed by the disc diffusion method. The prevalence of ESBL producing E. coli isolates were assessed by Double-Disc tests. Of 3699 tested sample, 201 samples showed the growth of pathogens and among them, 106 isolates (52/7%) were E. coli. The rate of ESBL producing E. coli isolates was 25/4%.The majority (81/5%) of the isolates were from females. High percent resistance was found against ceftazidime, cefotaxime, ceftriaxone, cefixime and ciprofloxacin, ranging from 61-100%, while the highest percent susceptibility was seen to meropenem, piperacillin- tazobactam (100%), followed by nitrofurantoin and amikacin (91%). The high prevalence of ESBL producing E. coli isolates from outpatients calls for the need to aware of this increasing resistance between uropathogens and update bacterial susceptibility data and to set up our empirical therapy accordingly.

An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Burcu Isler ◽  
Patrick Harris ◽  
Adam G Stewart ◽  
David L Paterson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Studies ◽  
Bacterial Infections ◽  
Animal Studies ◽  
Wide Spectrum ◽  
Clinical Development ◽  
Phase Iii ◽  
Lactam Antibiotic ◽  
Tract Infections

Abstract Cefepime, a wide-spectrum β-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with β-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.

Resistenze antibiotiche e nuove molecole: qual è lo scenario attuale?

2018 ◽  
Vol 85 (1_suppl) ◽  
pp. S5-S13 ◽  
Author(s):  
Andrea Novelli
Keyword(s):  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Public Health Problem ◽  
New Drugs ◽  
Beta Lactam ◽  
Important Public Health Problem ◽  
Extended Spectrum Beta Lactamase ◽  
First Choice ◽  
Tract Infections

Antibiotic resistance and new drugs in urologic setting: what we need to know? Urinary tract infections (UTIs) are among the most frequent infectious diseases, and represent an important public health problem with a substantial economic burden. In recent years the chemoresistance of the main uropathogens has significantly increased worldwide. Extended spectrum beta-lactamase (ESBL) production and multi-drug resistant (MDR) clones of Escherichia coli and Klebsiella pneumoniae are limiting available treatment options. Carbapenems and aminoglycosides are still effective in complicated UTI. New beta-lactam combinations such as ceftolozane-tazobactam and ceftazidime-avibactam may be highly useful in treating severe infections while contributing to the carbapenem sparing strategy. For uncomplicated UTI, within older antibiotics, fosfomycin trometamol may be considered a first-choice drug since it is still retaining a good activity against MDR uropathogens. On the other hand, there are extensive data showing that the administration of antimicrobials according to pharmacokinetic/pharmacodynamic (PK/PD) parameters improves the possibility of a positive clinical outcome, particularly in severely ill patients. Evidence is growing that when PK/PD parameters are used to target not only clinical cure. This article discusses the PK/PD characteristics of antimicrobial agents for the treatment of UTIs, and the pharmacological and therapeutic strategies for limiting or preventing bacterial resistance.

Is thyroid surgery performed too often in Germany?

2015 ◽  
Vol 54 (03) ◽  
pp. 101-105 ◽  
Author(s):  
F. A. Verburg
Keyword(s):  
Surgical Procedures ◽  
Thyroid Surgery ◽  
Needle Biopsy ◽  
Fine Needle Biopsy ◽  
Contributing Factors ◽  
Fine Needle ◽  
Diagnostic Measures ◽  
Frequent Use ◽  
Preoperative Diagnostic ◽  
The Usa

SummaryThyroid surgery is one of the more common surgical procedures in Germany. This is in contrast with the situation in some other countries, where this procedure is performed comparatively rarely. In this paper the number of thyroid surgeries in Germany is compared with other western countries (Netherlands, USA, England). In contrast to e. g. the USA and England the number of thyroid surgeries in Germany is declining, however with approximately 109/100 000/year in 2012 is still elevated (Netherlands: 16/100 000/year, USA: at least 42/100 000/year, England: at least 27/100 000/year).Possible contributing factors to this higher number of thyroid surgeries in Germany are explored. These factors include iodine deficiency, the frequent use of advanced diagnostics such as ultrasound, insufficient use of preoperative diagnostic measures such as fine needle biopsy and the practice of “defensive medicine”. How much each of these factors contributes is however unclear.

scholarly journals Patterns of infections and antimicrobial drugs’ prescribing among pregnant women in Saudi Arabia: a cross sectional study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mohamed A. Baraka ◽  
Lina Hussain AlLehaibi ◽  
Hind Nasser AlSuwaidan ◽  
Duaa Alsulaiman ◽  
Md. Ashraful Islam ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Pregnant Women ◽  
Antimicrobial Agents ◽  
Cross Sectional Study ◽  
Maternal Complications ◽  
Multicenter Studies ◽  
Antimicrobial Drugs ◽  
Cross Sectional ◽  
Categorization System ◽  
Tract Infections

Abstract Background Antimicrobial agents are among the most commonly prescribed drugs in pregnancy due to the increased susceptibility to infections during pregnancy. Antimicrobials can contribute to different maternal complications. Therefore, it is important to study their patterns in prescription and utilization. The data regarding this issue is scarce in Saudi Arabia. Therefore, the aim of this study is to generate data on the antimicrobial agents that are most commonly prescribed during pregnancy as well as their indications and safety. Methods This is a retrospective study focusing on pregnant women with a known antimicrobial use at Johns Hopkins Aramco Healthcare (JHAH). The sample included 344 pregnant women with a total of 688 antimicrobial agents prescribed. Data was collected on the proportion of pregnant women who received antimicrobial agents and on the drug safety during pregnancy using the risk categorization system of the U.S. Food and Drug Administration (FDA). Results The results showed that urinary tract infections (UTIs) were the most reported (59%) infectious diseases. Around 48% of pregnant women received antimicrobial medications at some point during pregnancy. The top two antimicrobial agents based on prescription frequency were B-lactams (44.6%) and azole anti-fungals (30%). The prescribed drugs in the study were found to be from classes B, C and D under the FDA risk classification system. Conclusion The study revealed a high proportion of antimicrobials prescribed during pregnancy that might pose risks to mothers and their fetuses. Future multicenter studies are warranted to evaluate the rational prescription of antimicrobial medications during pregnancy.

scholarly journals 1304. Characterization of Tebipenem Pivoxil Hydrobromide Pharmacokinetics-Pharmacodynamics (PK-PD) in a Neutropenic Murine Acute Pyelonephritis (AP) Model

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S666-S666
Author(s):  
Brian D VanScoy ◽  
Steven Fikes ◽  
Christopher M Rubino ◽  
Sujata M Bhavnani ◽  
Nicole S Cotroneo ◽  
...  
Keyword(s):  
Acute Pyelonephritis ◽  
Free Drug ◽  
Research Support ◽  
Model Free ◽  
Drug Concentrations ◽  
Drug Plasma ◽  
Dose Ranging ◽  
Tebipenem Pivoxil ◽  
Tract Infections ◽  
The Relationship

Abstract Background Tebipenem pivoxil hydrobromide (tebipenem HBr), an orally (PO) bioavailable prodrug of tebipenem, is a carbapenem with broad-spectrum activity against Gram-positive and -negative bacteria that is being developed for the treatment of patients with complicated urinary tract infections, including AP. Data from a one-compartment in vitro infection model demonstrated that the ratio of free-drug plasma area under the curve (AUC) to MIC with adjustment for dosing interval (τ) (AUC:MIC ratio•1/τ) was the PK-PD index most associated with tebipenem HBr efficacy [VanScoy BD et al., IDWeek 2019, Poster 1565]. Studies were undertaken to characterize the magnitude of tebipenem HBr free-drug plasma AUC:MIC ratio•1/τ associated with efficacy for Enterobacteriaceae using a neutropenic murine AP model. Methods A single dose pharmacokinetic study was completed in neutropenic mice infected via intra-renal injection with 104 CFU/kidney of Escherichia coli NCTC 13441. Following PO administration of 4 tebipenem HBr doses (1, 15, 45 and 100 mg/kg), plasma samples were collected at 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-treatment initiation and drug concentrations were determined using LC/MS/MS. Dose-ranging studies were completed using a panel of 7 Enterobacteriaceae isolates (tebipenem HBr MIC values of 0.015 to 0.5 mg/L). Mice were infected with 104 CFU/kidney via intra-renal injection. Two hours post-incubation, 8 total daily tebipenem HBr doses (0.3 to 135 mg/kg) were fractionated into regimens given every 8 hours. The relationship between change in log10 CFU/g from baseline at 24 hours and free-drug plasma AUC:MIC ratio•1/τ was fit using a Hill-type model. Free-drug plasma AUC:MIC ratio•1/τ values associated with net bacterial stasis and 1- and 2-log10 CFU/g reductions from baseline at 24 hours were determined. Results The relationship between change in log10 CFU/g from baseline at 24 hours and tebipenem HBr free-drug plasma AUC:MIC ratio•1/τ described the data well (r2 = 0.833). Free-drug plasma AUC:MIC ratio•1/τ values associated with net bacterial stasis and a 1-log10 CFU/g reduction from baseline were 26.2 and 54.1, respectively. A 2-log10 CFU/g reduction was not achieved. Relationship between change in log10 CFU/g from baseline at 24 hours and tebipenem HBr free-drug plasma AUC:MIC ratio•1/τ based on data for a panel of Enterobacteriaceae isolates evaluated in the dose-ranging studies conducted using a neutropenic murine acute pyelonephritis model Conclusion These data will be useful to support tebipenem HBr dose selection for clinical studies in patients with AP. Disclosures Brian D. VanScoy, B.S., Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Steven Fikes, BA, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Christopher M. Rubino, PharMD, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Sujata M. Bhavnani, PharMD, MS, FIDSA, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Nicole S. Cotroneo, BS, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, PhD, Spero Therapeutics (Employee, Shareholder) Thomas R. Parr, PhD, Spero Therapeutics (Employee, Shareholder) Paul G. Ambrose, PharMD, FIDSA, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support)

scholarly journals Phenotypic and Genotypic Properties of Fluoroquinolone-Resistant, qnr-Carrying Escherichia coli Isolated from the German Food Chain in 2017

2021 ◽  
Vol 9 (6) ◽  
pp. 1308
Author(s):  
Katharina Juraschek ◽  
Carlus Deneke ◽  
Silvia Schmoger ◽  
Mirjam Grobbel ◽  
Burkhard Malorny ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Point Mutations ◽  
Beta Lactamase ◽  
Resistance Development ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
German Food ◽  
Sequence Types ◽  
Ammonium Compounds ◽  
Additional Point

Fluoroquinolones are the highest priority, critically important antimicrobial agents. Resistance development can occur via different mechanisms, with plasmid-mediated quinolone resistance (PMQR) being prevalent in the livestock and food area. Especially, qnr genes, commonly located on mobile genetic elements, are major drivers for the spread of resistance determinants against fluoroquinolones. We investigated the prevalence and characteristics of qnr-positive Escherichia (E.) coli obtained from different monitoring programs in Germany in 2017. Furthermore, we aimed to evaluate commonalities of qnr-carrying plasmids in E. coli. We found qnr to be broadly spread over different livestock and food matrices, and to be present in various sequence types. The qnr-positive isolates were predominantly detected within selectively isolated ESBL (extended spectrum beta-lactamase)-producing E. coli, leading to a frequent association with other resistance genes, especially cephalosporin determinants. Furthermore, we found that qnr correlates with the presence of genes involved in resistance development against quaternary ammonium compounds (qac). The detection of additional point mutations in many isolates within the chromosomal QRDR region led to even higher MIC values against fluoroquinolones for the investigated E. coli. All of these attributes should be carefully taken into account in the risk assessment of qnr-carrying E. coli from livestock and food.

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