Ceftolozane-tazobactam and ceftazidime-avibactam activity against β-lactam-resistant Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing Enterobacterales clinical isolates from U.S. medical centres

Hirsch, Elizabeth B.; Brigman, Hunter V; Zucchi, Paola C.; Chen, Alice; Anderson, Jadyn C; Eliopoulos, George M.; Cheung, Nicole; Gilbertsen, Adam; Hunter, Ryan C; Emery, Christopher L.; Bias, Tiffany

doi:10.1016/j.jgar.2020.04.017

Cited by 34 publications

(23 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CZA was demonstrated to be effective and have a better safety profile compared to the best available therapy (BAT) in OXA-48 infections; results were comparable to those observed in Enterobacterales infections due to KPC producers [ 27 ]. Hirsh and colleagues tried out CZA and ceftolozane/tazobactam against a collection of P. aeruginosa , obtaining outstanding results: both drugs were active in >80% of β-lactam resistant isolates (75% meropenem non-susceptible) and on 88% of DTR- Pa [ 28 ]. In an investigation in 360 P. aeruginosa strains, CZA was the most active compound against meropenem- and imipenem-resistant strains (92.6% and 93.8% susceptible, respectively) [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…CZA is the preferred choice and CFDC may represent a reasonable alternative [ 113 ]. Ceftolozane/tazobactam and CZA demonstrated optimal efficacy for DTR- Pa [ 28 ] and CFDC represents again another reasonable treatment option [ 113 ]. MBL-producing bacteria are an increasingly expanding threat, but treatment possibilities remain an unmet medical need.…”

Section: Algorithm Constructionmentioning

confidence: 99%

See 1 more Smart Citation

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

et al. 2021

View full text Add to dashboard Cite

The worldwide propagation of antimicrobial resistance represents one of the biggest threats to global health and development. Multi-drug-resistant organisms (MDROs), including carbapenem-resistant non-fermenting Gram-negatives and Enterobacterales, present a heterogeneous and mutating spread. Infections by MDRO are often associated with an unfavorable outcome, especially among critically ill populations. The polymyxins represented the backbone of antibiotic regimens for Gram-negative MDROs in recent decades, but their use presents multiple pitfalls. Luckily, new agents with potent activity against MDROs have become available in recent times and more are yet to come. Now, we have the duty to make the best use of these new therapeutic tools in order not to prematurely compromise their effectiveness and at the same time improve patients’ outcomes. We reviewed the current literature on ceftazidime/avibactam, meropenem/vaborbactam and cefiderocol, focusing on antimicrobial spectrum, on the prevalence and mechanisms of resistance development and on the main in vitro and clinical experiences available so far. Subsequently, we performed a step-by-step construction of a speculative algorithm for a reasoned prescription of these new antibiotics, contemplating both empirical and targeted use. Attention was specifically posed on patients with life-risk conditions and in settings with elevated prevalence of MDRO.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Algorithm Constructionmentioning

confidence: 99%

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although the frequency of CMY is lower than that of ESBL, it is clinically significant because when combined with the loss of porins (OmpC, OmpF), it can confer resistance to carbapenems, one of the last-line antibiotics for the treatment of infections [ 46 ]. On the other hand, CMY enzymes have relevance in resistance to recently introduced antimicrobials, for instance in a study carried out in centers in USA; two E. coli isolates were found, in which genes encoding the CTX-M-15 and CMY-2-like beta-lactamases coexisted; both isolates were resistant to ceftolozane-tazobactam with MIC 64 µg/mL and 128 µg/mL, respectively [ 47 ]. The existence of these two mechanisms of resistance in the same isolate can complicate the interpretation of the antibiogram and, consequently, the proper selection of antimicrobial treatment.…”

Section: Discussionmentioning

confidence: 99%

Detection of CMY-type beta-lactamases in Escherichia coli isolates from paediatric patients in a tertiary care hospital in Mexico

Mérida-Vieyra

Colsa-Ranero

Calderón-Castañeda

et al. 2020

Antimicrob Resist Infect Control

View full text Add to dashboard Cite

Background The aim of this study was to detect CMY-type beta-lactamases in E. coli isolates obtained from paediatric patients. Methods In total, 404 infection-causing E. coli isolates resistant to third and fourth generation cephalosporins (3GC, 4GC) were collected from paediatric patients over a 2 years period. The identification and susceptibility profiles were determined with an automated microbiology system. Typing of blaCMY and other beta-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaVIM, blaIMP, blaKPC, blaNDM, blaOXA and blaGES) was realized by PCR and sequencing. Phenotypic detection of AmpC-type enzymes was performed using boronic acid (20 mg/mL) and cloxacillin (20 mg/mL) as inhibitors, and the production of extended-spectrum beta-lactamases was determined with the double-disk diffusion test with cefotaxime (CTX) and ceftazidime (CAZ) discs alone and in combination with clavulanic acid. The CarbaNP test and modified carbapenem inhibition method (mCIM) were used for isolates with decreased susceptibility to carbapenems. The clonal origin of the isolates was established by pulsed-field gel electrophoresis (PFGE), phylotyping method and multilocus sequence typing. Results CMY-type beta-lactamases were detected in 18 isolates (4.5%). The allelic variants found were CMY-2 (n = 14) and CMY-42 (n = 4). Of the E. coli strains with CMY, the AmpC phenotypic production test was positive in 11 isolates with cloxacillin and in 15 with boronic acid. ESBL production was detected in 13 isolates. Coexistence with other beta-lactamases was observed such as CTX-M-15 ESBL and original spectrum beta-lactamases TEM-1 and TEM-190. In one isolate, the CarbaNP test was negative, the mCIM was positive, and OXA-48 carbapenemase was detected. Phylogroup A was the most frequent (n = 9) followed by B2, E and F (n = 2, respectively), and through PFGE, no clonal relationship was observed. Eleven different sequence types (ST) were found, with ST10 high-risk clone being the most frequent (n = 4). Seventy-two percent of the isolates were from health care-associated infections; the mortality rate was 11.1%. Conclusions This is the first report in Mexico of E. coli producing CMY isolated from paediatric patients, demonstrating a frequency of 4.5%. In addition, this is the first finding of E. coli ST10 with CMY-2 and OXA-48.

show abstract

“…About one-fourth of the isolates (n = 14) were classified as extensively drug resistant, and of these, 71.4% and 57.1% were susceptible to ceftazidimeavibactam and ceftolozane-tazobactam, respectively. 41 A retrospective observational study involving 20 US health systems (205 patients) concluded that ceftolozanetazobactam is an effective monotherapy for MDR P aeruginosa strains. Patients were required to have a MDR P aeruginosa isolate and to have received ceftolozane-tazobactam for at least 24 hours.…”

Section: Ceftolozane-tazobactammentioning

confidence: 99%

“…About one-fourth of the isolates (n = 14) were classified as extensively drug resistant, and of these, 71.4% and 57.1% were susceptible to ceftazidime-avibactam and ceftolozane-tazobactam, respectively. 41…”

Section: Newer Cephalosporin-bli Combinationsmentioning

confidence: 99%

A Critical Evaluation of Newer β-Lactam Antibiotics for Treatment of Pseudomonas aeruginosa Infections

Blomquist

Nix

2020

Ann Pharmacother

View full text Add to dashboard Cite

Objective: This article critically evaluates common Pseudomonas aeruginosa resistance mechanisms and the properties newer β-lactam antimicrobials possess to evade these mechanisms. Data Sources: An extensive PubMed, Google Scholar, and ClinicalTrials.gov search was conducted (January 1995 to July 2020) to identify relevant literature on epidemiology, resistance mechanisms, antipseudomonal agents, newer β-lactam agents, and clinical data available pertaining to P aeruginosa. Study Selection and Data Extraction: Relevant published articles and package inserts were reviewed for inclusion. Data Synthesis: Therapeutic options to treat P aeruginosa infections are limited because of its intrinsic and acquired resistance mechanisms. The goal was to identify advances with newer β-lactams and characterize improvements in therapeutic potential for P aeruginosa infections. Relevance to Patient Care and Clinical Practice: Multidrug-resistant (MDR) P aeruginosa isolates are increasingly encountered from a variety of infections. This review highlights potential activity gains of newer β-lactam antibacterial drugs and the current clinical data to support their use. Pharmacists will be asked to recommend or evaluate the use of these agents and need to be aware of information specific to P aeruginosa, which differs from experience derived from Enterobacterales infections. Conclusions: Newer agents, including ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and cefiderocol, are useful for the treatment of MDR P aeruginosa infections. These agents offer improved efficacy and less toxicity compared with aminoglycosides and polymyxins and can be used for pathogens that are resistant to first-line antipseudomonal β-lactams. Selection of one agent over another should consider availability, turnaround of susceptibility testing, and product cost. Efficacy data specific for pseudomonal infections are limited, and there are no direct comparisons between the newer agents.

show abstract

Ceftolozane-tazobactam and ceftazidime-avibactam activity against β-lactam-resistant Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing Enterobacterales clinical isolates from U.S. medical centres

Cited by 34 publications

References 19 publications

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

Detection of CMY-type beta-lactamases in Escherichia coli isolates from paediatric patients in a tertiary care hospital in Mexico

A Critical Evaluation of Newer β-Lactam Antibiotics for Treatment of Pseudomonas aeruginosa Infections

Contact Info

Product

Resources

About