Ceftazidime/Avibactam and Other Commonly Used Antibiotics Activity Against Enterobacterales and Pseudomonas aeruginosa Isolated in Poland in 2015–2019

Abstract

Purpose Infections caused by resistant Gram-negative bacteria are becoming increasingly common and now pose a serious public health threat worldwide, because they are difficult to treat due to few treatment options and they are associated with high morbidity and mortality. The combination of ceftazidime with the beta-lactamase inhibitor avibactam – seems to be the right choice in this situation. The aim of the study was to evaluate the activity of ceftazidime/avibactam and other commonly used antibiotics against Enterobacterales and Pseudomonas aeruginosa strains isolated within last years in Poland. Patients and Methods This study analyzed the antibiotic susceptibility of 1607 Enterobacterales isolates and 543 nonfermenting P. aeruginosa strains collected between 2015 and 2019 in 4 medical laboratories participating in the ATLAS (Antimicrobial Testing Leadership And Surveillance) program in Poland. Unduplicated clinically significant Enterobacterales and P. aeruginosa strains were collected from patients with respiratory, skin and musculoskeletal, genitourinary, abdominal, bloodstream or other infections (ear, eye). Results The ceftazidime/avibactam combination demonstrates the highest activity against Enterobacterales (98.9%), in both adults and children, including strains presenting MDR (multidrug-resistant) (97.5%) and ESBL (extended spectrum β-lactamase) (96.3%) phenotypes. The activity of ceftazidime/avibactam increased to 100% when only MBL (metallo-β-lactamase)-negative subset of Enterobacterales was considered. This combination also achieved the second highest activity result (89.3%) after colistin in P. aeruginosa , including isolates of MDR (65.9%) and carbapenem-resistant (CR) phenotypes (54.8%). When MBL-positive isolates were excluded, susceptibility rate of P. aeruginosa increased to 94.7%. It is worth to note that susceptibility of the examined P. aeruginosa strains to ceftazidime/avibactam was very high in children (93.3%), especially in a pediatric intensive care unit (94.2%). Conclusion Enterobacterales and P. aeruginosa included in this analysis presented high susceptibility rates to ceftazidime/avibactam. Ceftazidime/avibactam showed the highest activity against Enterobacterales strains among all antibiotics studied, both for the total population as well as for MDR phenotype and ESBL phenotype. Ceftazidime/avibactam also achieved the second highest activity result against P. aeruginosa strains (including MDR and CR phenotypes). These results are much higher when excluding MBL-positive isolates that exhibit intrinsic resistance to ceftazidime/avibactam.

Synergistic Effect of Ceftazidime-Avibactam with Aztreonam on Carbapenemase-Positive Klebsiella pneumoniae MBL+, NDM+

“…The average treatment time for patients in Group A was 6.5 days (4-9). There were much greater discrepancies in treatment time in Group B, where the average treatment time was 8.5 days (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). In this group, the shortest time was for patients who, despite the treatment administered, died during therapy.…”

“…The correlations noted are consistent with reports by authors from other centers that focused on the comparison of ceftazidime-avibactam treatment versus other alternative antibiotic combinations. [13][14][15] However, the authors of the studies emphasize that broader investigations and additional data on such treatment regimens are necessary. 8,[15][16][17] It should also be noted that a delay in the initiation of targeted treatment is associated with a statistically significant increase in mortality.…”

Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics

“…By definition, the MDR strains display acquired resistance to at least one agent in three antimicrobial categories, whereas the XDR strains show susceptibility to antibiotics in 2 or fewer categories and display resistance to at least one agent in the rest of available antibiotic categories [236,237]. Ceftazidime, (a third-generation broad-spectrum cephalosporin antibiotic [238]) is also used in combination with avibactam (a synthetic non-β-lactam, β-lactamase inhibitor which inactivates β-lactamase targets via covalent acylation [239]), and has shown to be highly effective against MDR and XDR P. aeruginosa strains (>90% effectiveness) [240,241]. However, P. aeruginosa strains resistant to ceftazidime/avibactam have been reported and are on the rise, adding to the challenges associated with P. aeruginosa therapeutics [242,243].…”