In vitro effectiveness of ceftazidime-avibactam in combination with aztreonam on carbapenemase-producing Enterobacterales

Romina, Papa-Ezdra; Lucía, Araújo; Leticia, Caiata; Federica, Ferreira; Pablo, Ávila; Verónica, Seija; Antonio, Galiana; Inés, Bado; Rafael, Vignoli

doi:10.1016/j.jgar.2023.08.010

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…We can assume that this result could be related to the level of bla VIM-1 gene expression. As ceftazidime/avibactam is not effective against metallo-carbapenemases, many authors have suggested an addition of aztreonam to ceftazidime/avibactam to increase the efficacy of the combination [49,57].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antimicrobial Activity of Five Newly Approved Antibiotics against Carbapenemase-Producing Enterobacteria—A Pilot Study in Bulgaria

Markovska,

Stankova,

Stoeva

et al. 2024

Antibiotics

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To solve the problem with pan-drug resistant and extensively drug-resistant Gram-negative microbes, newly approved drugs such as ceftazidime/avibactam, cefiderocol, plazomicin, meropenem/vaborbactam, and eravacycline have been introduced in practice. The aim of the present study was to collect carbapenemase-producing clinical Enterobacterales isolates, to characterize their carbapenemase genes and clonal relatedness, and to detect their susceptibility to commonly used antimicrobials and the above-mentioned newly approved antibiotics. Sixty-four carbapenemase producers were collected in a period of one year from four Bulgarian hospitals, mainly including Klebsiella pneumoniae (89% of the isolates) and also single Proteus mirabilis, Providencia stuartii and Citrobacter freundii isolates. The main genotype was blaNDM-1 (in 61%), followed by blaKPC-2 (23%), blaVIM-1 (7.8%) and blaOXA-48 (7.8%). Many isolates showed the presence of ESBL (blaCTX-M-15/-3 in 76.6%) and AmpC (blaCMY-4 in 37.5% or blaCMY-99 in 7.8% of isolates). The most common MLST type was K. pneumoniae ST11 (57.8%), followed by ST340 (12.5%), ST258 (6.3%) and ST101 (6.3%). The isolates were highly resistant to standard-group antibiotics, except they were susceptible to tigecycline (83.1%), colistin (79.7%), fosfomycin (32.8%), and aminoglycosides (20.3–35.9%). Among the newly approved compounds, plazomicin (90.6%) and eravacycline (76.3%) showed the best activity. Susceptibility to ceftazidime/avibactam and meropenem/vaborbactam was 34.4% and 27.6%, respectively. For cefiderocol, a large discrepancy was observed between the percentages of susceptible isolates according to EUCAST susceptibility breakpoints (37.5%) and those of CLSI (71.8%), detected by the disk diffusion method. This study is the first report to show patterns of susceptibility to five newly approved antibiotics among molecularly characterized isolates in Bulgaria. The data may contribute to both the improvement of treatment of individual patients and the choice of infection control strategy and antibiotic policy.

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Section: Discussionmentioning

confidence: 99%

In Vitro Antimicrobial Activity of Five Newly Approved Antibiotics against Carbapenemase-Producing Enterobacteria—A Pilot Study in Bulgaria

Markovska,

Stankova,

Stoeva

et al. 2024

Antibiotics

View full text Add to dashboard Cite

show abstract

“…In theory, the combination of CZA + AZT is a rational choice for strains producing multiple carbapenemases, due to the proven efficacy of the combination against MBL producers and the known efficacy of CZA against OXA enzymes. Romina et al have demonstrated the synergistic effect of CZA + AZT in carbapenemase-producing isolates, including those with a double production of KPC plus NDM [ 98 ], and Jayol et al have demonstrated the efficacy of this combination against strains that co-produce NDM and OXA enzymes [ 99 ]. Additionally, it has been demonstrated that both CZA + AZT and MEV + AZT combinations can be used for the treatment of double carbapenemase producers, with MEV + AZT possibly being more effective [ 100 ].…”

Section: Antibiotic Synergy and Treatment Of Carbapenem-resistant Ent...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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Ceftazidime-avibactam combination therapy versus monotherapy for treating carbapenem-resistant gram-negative infection: a systemic review and meta-analysis

Hsu,

Chuang,

Tsai

et al. 2024

Infection

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In vitro effectiveness of ceftazidime-avibactam in combination with aztreonam on carbapenemase-producing Enterobacterales

Cited by 5 publications

References 18 publications

In Vitro Antimicrobial Activity of Five Newly Approved Antibiotics against Carbapenemase-Producing Enterobacteria—A Pilot Study in Bulgaria

In Vitro Antimicrobial Activity of Five Newly Approved Antibiotics against Carbapenemase-Producing Enterobacteria—A Pilot Study in Bulgaria

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

Ceftazidime-avibactam combination therapy versus monotherapy for treating carbapenem-resistant gram-negative infection: a systemic review and meta-analysis

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