Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics

Objectives: To support the clinical development of mecillinam and pivmecillinam in the United States for the treatment of complicated and uncomplicated urinary tract infections (UTIs), this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolate...

Full description

Saved in:
Bibliographic Details
Main Authors: Stephen Hawser, Ian Morrissey, Nimmi Kothari, Federica Monti, Anne Santerre Henriksen
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Journal of Global Antimicrobial Resistance
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213716524001656
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846113148125315072
author Stephen Hawser
Ian Morrissey
Nimmi Kothari
Federica Monti
Anne Santerre Henriksen
author_facet Stephen Hawser
Ian Morrissey
Nimmi Kothari
Federica Monti
Anne Santerre Henriksen
author_sort Stephen Hawser
collection DOAJ
description Objectives: To support the clinical development of mecillinam and pivmecillinam in the United States for the treatment of complicated and uncomplicated urinary tract infections (UTIs), this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolates from patients with UTIs in the United States during 2017 to 2020. Mecillinam is a first-in-class amidinopenicillin antibiotic, being the only β-lactam to exert its antibacterial activity through exclusive binding to penicillin-binding protein 2. Pivmecillinam is the oral prodrug of mecillinam and is recommended as a first-line therapy by the Infectious Disease Society of America guidelines for uncomplicated UTIs and is approved for the treatment of uncomplicated UTIs in Europe, Canada, and the United States. Methods: A total of 3303 isolates were collected and antimicrobial susceptibility determined according to Clinical Laboratory and Standards Institute (CLSI) guidelines. Results: Susceptibility was highest for fosfomycin (97.1% susceptible) and mecillinam (94.9% susceptible). Against extended-spectrum beta-lactamase (ESBL)-positive bacteria susceptibilities were highest for mecillinam (98.2% susceptible) and fosfomycin (97.3% susceptible) and against ESBL-positive K. pneumoniae only mecillinam and fosfomycin had > 80% susceptibility. Resistance to comparator antibiotics was highest for trimethoprim-sulfamethoxazole (27.1%), followed by ciprofloxacin (19.3%), ceftriaxone (19.2%), and nitrofurantoin (12.1%). Multi-drug-resistant isolates were most susceptible to mecillinam and fosfomycin. Conclusion: The data further support the clinical development and clinical utility of mecillinam. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
format Article
id doaj-art-6e9d55a0a13e443ea1cb7d6df3a0ff7e
institution Kabale University
issn 2213-7165
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series Journal of Global Antimicrobial Resistance
spelling doaj-art-6e9d55a0a13e443ea1cb7d6df3a0ff7e2024-12-22T05:28:00ZengElsevierJournal of Global Antimicrobial Resistance2213-71652024-12-0139137143Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibioticsStephen Hawser0Ian Morrissey1Nimmi Kothari2Federica Monti3Anne Santerre Henriksen4IHMA Europe Sàrl, Monthey/VS, Switzerland; Corresponding author. Mailing address: IHMA Europe Sàrl, Route de I'Ile-au-Bois 1A, 1870 Monthey, Switzerland.Antimicrobial Focus Ltd., Sawbridgeworth, Hertfordshire, UKIHMA Europe Sàrl, Monthey/VS, SwitzerlandIHMA Europe Sàrl, Monthey/VS, SwitzerlandMaxel Consulting ApS, Jyllinge, DenmarkObjectives: To support the clinical development of mecillinam and pivmecillinam in the United States for the treatment of complicated and uncomplicated urinary tract infections (UTIs), this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolates from patients with UTIs in the United States during 2017 to 2020. Mecillinam is a first-in-class amidinopenicillin antibiotic, being the only β-lactam to exert its antibacterial activity through exclusive binding to penicillin-binding protein 2. Pivmecillinam is the oral prodrug of mecillinam and is recommended as a first-line therapy by the Infectious Disease Society of America guidelines for uncomplicated UTIs and is approved for the treatment of uncomplicated UTIs in Europe, Canada, and the United States. Methods: A total of 3303 isolates were collected and antimicrobial susceptibility determined according to Clinical Laboratory and Standards Institute (CLSI) guidelines. Results: Susceptibility was highest for fosfomycin (97.1% susceptible) and mecillinam (94.9% susceptible). Against extended-spectrum beta-lactamase (ESBL)-positive bacteria susceptibilities were highest for mecillinam (98.2% susceptible) and fosfomycin (97.3% susceptible) and against ESBL-positive K. pneumoniae only mecillinam and fosfomycin had > 80% susceptibility. Resistance to comparator antibiotics was highest for trimethoprim-sulfamethoxazole (27.1%), followed by ciprofloxacin (19.3%), ceftriaxone (19.2%), and nitrofurantoin (12.1%). Multi-drug-resistant isolates were most susceptible to mecillinam and fosfomycin. Conclusion: The data further support the clinical development and clinical utility of mecillinam. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.http://www.sciencedirect.com/science/article/pii/S2213716524001656MethicillinEnterobacteralesEsblGram-negativeUnited StatesResistance
spellingShingle Stephen Hawser
Ian Morrissey
Nimmi Kothari
Federica Monti
Anne Santerre Henriksen
Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
Journal of Global Antimicrobial Resistance
Methicillin
Enterobacterales
Esbl
Gram-negative
United States
Resistance
title Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
title_full Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
title_fullStr Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
title_full_unstemmed Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
title_short Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
title_sort activity of mecillinam against usa urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics
topic Methicillin
Enterobacterales
Esbl
Gram-negative
United States
Resistance
url http://www.sciencedirect.com/science/article/pii/S2213716524001656
work_keys_str_mv AT stephenhawser activityofmecillinamagainstusaurinarytractclinicalisolatesfrom2017to2020includingisolatesresistanttocomparatorantibiotics
AT ianmorrissey activityofmecillinamagainstusaurinarytractclinicalisolatesfrom2017to2020includingisolatesresistanttocomparatorantibiotics
AT nimmikothari activityofmecillinamagainstusaurinarytractclinicalisolatesfrom2017to2020includingisolatesresistanttocomparatorantibiotics
AT federicamonti activityofmecillinamagainstusaurinarytractclinicalisolatesfrom2017to2020includingisolatesresistanttocomparatorantibiotics
AT annesanterrehenriksen activityofmecillinamagainstusaurinarytractclinicalisolatesfrom2017to2020includingisolatesresistanttocomparatorantibiotics