Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries

Munita, José M.

doi:10.3389/fmicb.2022.1035609

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…The overexpression or mutation of this enzyme, both of which would increase the rate of ceftolozane hydrolysis, results in resistance amongst P. aeruginosa isolates [ 65 ]. In addition, mutated Ambler C class β-lactamases and the inactivation of AmpC-negative regulators have also been implicated [ 66 ]. Moreover, C/T can be ineffective against isolates that produce carbapenemases or ESBLs that are not inhibited by tazobactam [ 67 ].…”

Section: The New β-Lactam and β-Lactamase Inhibitor Combinations: Ind...mentioning

confidence: 99%

Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa

Ferous,

Anastassopoulou,

Pitiriga

et al. 2024

Antibiotics

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Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations—namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and ceftolozane/tazobactam—have been approved for infections attributed to carbapenem-resistant Enterobacterales species and Pseudomonas aeruginosa. Nevertheless, although these antimicrobials are increasingly being used in place of other drugs such as polymyxins, their optimal clinical use is still challenging. Furthermore, there is evidence that resistance to these agents might be increasing, so urgent measures should be taken to ensure their continued effectiveness. Therefore, clinical laboratories play an important role in the judicious use of these new antimicrobial combinations by detecting and characterizing carbapenem resistance, resolving the presence and type of carbapenemase production, and accurately determining the minimum inhibitor concentrations (MICs) for BL/BLIs. These three targets must be met to ensure optimal BL/BLIs use and prevent unnecessary exposure that could lead to the development of resistance. At the same time, laboratories must ensure that results are interpreted in a timely manner to avoid delays in appropriate treatment that might be detrimental to patient safety. Thus, we herein present an overview of the indications and current applications of the new antimicrobial combinations and explore the diagnostic limitations regarding both carbapenem resistance detection and the interpretation of MIC results. Moreover, we suggest the use of alternative narrower-spectrum antibiotics based on susceptibility testing and present data regarding the effect of synergies between BL/BLIs and other antimicrobials. Finally, in order to address the absence of a standardized approach to using the novel BL/BLIs, we propose a diagnostic and therapeutic algorithm, which can be modified based on local epidemiological criteria. This framework could also be expanded to incorporate other new antimicrobials, such as cefiderocol, or currently unavailable BL/BLIs such as aztreonam/avibactam and cefepime/taniborbactam.

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Section: The New β-Lactam and β-Lactamase Inhibitor Combinations: Ind...mentioning

confidence: 99%

Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa

Ferous,

Anastassopoulou,

Pitiriga

et al. 2024

Antibiotics

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“…Tazobactam, which also blocks the hydrolysis of ceftolozane, inhibits the majority of class A b- lactamases and some AmpC cephalosporinases (plasmid-mediated class C b-lactamases). The drugs ceftolozane/tazobactam and C/A have been authorized in South Africa (SA) since 2022 (Mojica et al, 2022;Perovic et al, 2023). C/T is licensed to treat complex intra-abdominal infections (cIAI), nosocomial pneumonia, and pyelonephritis in adults.…”

Section: Ceftolozane-tazobactammentioning

confidence: 99%

A review of the mechanisms that confer antibiotic resistance in pathotypes of E. coli

Nasrollahian,

Graham,

Halaji

2024

Front. Cell. Infect. Microbiol.

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The dissemination of antibiotic resistance in Escherichia coli poses a significant threat to public health worldwide. This review provides a comprehensive update on the diverse mechanisms employed by E. coli in developing resistance to antibiotics. We primarily focus on pathotypes of E. coli (e.g., uropathogenic E. coli) and investigate the genetic determinants and molecular pathways that confer resistance, shedding light on both well-characterized and recently discovered mechanisms. The most prevalent mechanism continues to be the acquisition of resistance genes through horizontal gene transfer, facilitated by mobile genetic elements such as plasmids and transposons. We discuss the role of extended-spectrum β-lactamases (ESBLs) and carbapenemases in conferring resistance to β-lactam antibiotics, which remain vital in clinical practice. The review covers the key resistant mechanisms, including: 1) Efflux pumps and porin mutations that mediate resistance to a broad spectrum of antibiotics, including fluoroquinolones and aminoglycosides; 2) adaptive strategies employed by E. coli, including biofilm formation, persister cell formation, and the activation of stress response systems, to withstand antibiotic pressure; and 3) the role of regulatory systems in coordinating resistance mechanisms, providing insights into potential targets for therapeutic interventions. Understanding the intricate network of antibiotic resistance mechanisms in E. coli is crucial for the development of effective strategies to combat this growing public health crisis. By clarifying these mechanisms, we aim to pave the way for the design of innovative therapeutic approaches and the implementation of prudent antibiotic stewardship practices to preserve the efficacy of current antibiotics and ensure a sustainable future for healthcare.

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Activity of ceftolozane/tazobactam and imipenem/relebactam against Gram-negative clinical isolates collected in Mexico—SMART 2017–2021

Karlowsky,

Lob,

Siddiqui

et al. 2024

JAC-Antimicrobial Resistance

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Objectives To investigate the activities of ceftolozane/tazobactam and imipenem/relebactam against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from hospitalized patients in Mexico in 2017–2021. Methods MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 breakpoints. β-Lactamase genes were identified in ceftolozane/tazobactam-, imipenem/relebactam-, and/or imipenem-non-susceptible isolates. Results Ceftolozane/tazobactam and imipenem/relebactam inhibited 89% and 99% of E. coli isolates (n = 2337), and 87% and 94% of K. pneumoniae isolates (n = 1127). Sixty-four percent of E. coli and 47% of K. pneumoniae had an ESBL non-carbapenem-resistant Enterobacterales (ESBL non-CRE) phenotype. Eighty-six percent and 91% of ESBL non-CRE E. coli and K. pneumoniae were ceftolozane/tazobactam susceptible, and 99.9% and 99.8% were imipenem/relebactam susceptible. Ceftolozane/tazobactam was the most active agent studied against P. aeruginosa (n = 1068; 83% susceptible), 9–28 percentage points higher than carbapenems and comparator β-lactams excluding imipenem/relebactam (78% susceptible). Ceftolozane/tazobactam remained active against 35%–58%, and imipenem/relebactam against 32%–42%, of P. aeruginosa in meropenem-, piperacillin/tazobactam-, and cefepime-non-susceptible subsets. The majority of isolates of ceftolozane/tazobactam-non-susceptible E. coli carried an ESBL, whereas among ceftolozane/tazobactam-non-susceptible K. pneumoniae and P. aeruginosa, the majority carried carbapenemases. The most prevalent carbapenemase observed among E. coli (estimated at 0.7% of all isolates), K. pneumoniae (4.8%) and P. aeruginosa (10.0%) was an MBL. Almost all imipenem/relebactam-non-susceptible E. coli and K. pneumoniae carried MBL or OXA-48-like carbapenemases, whereas among imipenem/relebactam-non-susceptible P. aeruginosa, 56% carried MBL or GES carbapenemases. Conclusions Ceftolozane/tazobactam and imipenem/relebactam may provide treatment options for patients infected with β-lactam-non-susceptible Gram-negative bacilli, excluding isolates carrying an MBL- or OXA-48-like carbapenemase.

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Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries

Cited by 5 publications

References 39 publications

Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa

Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa

A review of the mechanisms that confer antibiotic resistance in pathotypes of E. coli

Activity of ceftolozane/tazobactam and imipenem/relebactam against Gram-negative clinical isolates collected in Mexico—SMART 2017–2021

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