In Vitro Activity of Ceftolozane/Tazobactam vs Nonfermenting, Gram-Negative Cystic Fibrosis Isolates

Achromobacter is a genus of non-fermenting Gram negative bacteria under order Burkholderiales. Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g. most cephalosporins, aztreonam and aminoglycosides), and are increasingly acquiring resistance to carbapenems. Carbapenem resistance is mainly caused by multidrug efflux pumps and metallo-β-lactamases, which are not expected to be overcome by new β-lactamase inhibitors. Among the other new antibiotics, cefiderocol and eravacycline were used as salvage therapy for a limited number of patients with Achromobacter infections. In this article, we aim to give an overview of the antimicrobial resistance in Achromobacter species, highlighting the possible place of new antibiotics in their treatment.

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“…(89). Ceftolozane-tazobactam does not have any activity against Achromobacter species, as demonstrated in vitro (87,(90)(91)(92).…”

Section: New Therapeutic Options Against Achromobacter Infections Cefiderocolmentioning

confidence: 90%

Achromobacter Infections and Treatment Options

Isler

Kidd

Stewart

et al. 2020

Antimicrob Agents Chemother

113

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“…although the majority of the isolates included in this study were susceptible to meropenem (76.6%) (21). (22,25).…”

Section: Susceptibility To Ceftazidime/avibactam and Ceftolozane/tazomentioning

confidence: 81%

Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients

Zamudio

Hijazi

Joshi

et al. 2019

International Journal of Antimicrobial Agents

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Pseudomonas aeruginosa is one of the most important pathogens in cystic fibrosis. In this study we analysed the genetic basis and phylogenetic profile of resistance to ceftazidime/avibactam and ceftolozane/tazobactam as well as carbapenems in cystic fibrosis P. aeruginosa isolates. We conducted whole genome sequence analysis of a collection of isolates resistant to piperacillin/tazobactam from seven hospitals in Scotland since the introduction of these two cephalosporin/β-lactamase inhibitor combinations. Ceftazidime resistance was primarily related to AmpC induction, as tested by cloxacillin inhibition assays, while amino acid variations in AmpC were associated with high-level ceftazidime resistance not reversed by cloxacillin. Only isolates resistant to both ceftazidime/avibactam and ceftolozane/tazobactam carried AmpD mutations, likely resulting in ampC overexpression. All isolates resistant to ceftazidime/avibactam and/or ceftolozane/tazobactam were resistant to carbapenems and showed inactivating mutations in the chromosomal oprD gene. None of the isolates bore class A, B, D plasmid-encoded carbapenemases. Critically, we show that mutational resistance emerged in phylogenetically distant lineages suggesting that the mutations occur independently without conferring a selective advantage to any phylogenetic lineage. Our findings confirm the strong contribution of mutation-driven evolution to the population structure of P. aeruginosa. 1590 1664 88 5 256 256 12 8 A31V (n); V239 A(d); G242 R(d); G248 S(n) >3 2 2 Q402f s(d) A205 V(d), G300 A(n),

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“…Microbiological efficacy of ceftolozanetazobactam against P. aeruginosa isolates from CF patients was demonstrated in various studies listed in Table 1. [10][11][12][13][14] Ceftolozanetazobactam was reported to be well-tolerated in CF patients (Table 1).…”

Section: Ceftolozane-tazobactammentioning

confidence: 99%

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins latest update

Epps

Zobell

2021

Pediatric Pulmonology

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To the Editor, We are writing this letter to provide an update of published information on ceftolozane-tazobactam, and ceftazidime-avibactam in cystic fibrosis (CF) to the State of the Art article "Optimization of Anti-pseudomonal Antibiotics for CF Pulmonary Exacerbations: II. Cephalosporins and Penicillins" by Zobell and colleagues. 1 This published information on ceftolozane-tazobactam and ceftazidime-avibactam were not available when the original State of the Art article was published. We would like to update the article with this information. Cephalosporins have a wide range of antimicrobial activity. However, only four of them have activity against Pseudomonas aeruginosa. 1,2 These are ceftolozane, ceftazidime, cefepime, and cefiderocol. 1-3 No information exists for cefiderocol in CF, and no new information exists for cefepime in CF so refer to the previous published article by Zobell and collegues. 1 Ceftolozane is available in combination with the beta-lactamase inhibitor, tazobactam. 2 Ceftazidime is available in combination with the beta-lactamase inhibitor, avibactam. 4 Both antibiotics share pharmacodynamic properties and side-effect profiles similar to other cephalosporins as mentioned in the previous article by Zobell et al. 1,2,4 2 | PHARMACOKINETICS/ PHARMACODYNAMICS 2.1 | Ceftolozane-tazobactam Stokem et al. 5 described the pharmacokinetic-pharmacodynamic (PK/PD) of ceftolozane-tazobactam 3 g given intravenously (IV) every 12 h (2 g ceftolozane/1 g tazobactam) in a 35-year-old female CF patient with renal insufficiency and multidrug-resistant pseudomonas. PK/PD parameters are listed in Table 1. 5 Davis et al. 6 obtained serum concentrations in a 30-year-old female CF patient with an estimated glomerular filtration of 215 ml/min at the time of serum sampling. The patient received a ceftolozane-tazobactam 3 g (2 g ceftolozane/1 g tazobactam) loading dose followed by 6 g (4 g ceftolozane/2 g tazobactam) continuous infusion over 24 h. Serum concentrations and PK/PD parameters are listed in Table 1. 6Romano et al. 7 described how patient-specific PK were used in a 63-year-old female CF patient with stage III chronic kidney disease.Ceftolozane-tazobactam 3 g was given IV every 8 h over 60 min

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In Vitro Activity of Ceftolozane/Tazobactam vs Nonfermenting, Gram-Negative Cystic Fibrosis Isolates

Cited by 20 publications

References 20 publications

Achromobacter Infections and Treatment Options

Achromobacter Infections and Treatment Options

Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins latest update

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