Persistent Bacteremia fromPseudomonas aeruginosawithIn VitroResistance to the Novel Antibiotics Ceftolozane-Tazobactam and Ceftazidime-Avibactam

Abstract

Ceftazidime-avibactam and ceftolozane-tazobactam are new antimicrobials with activity against multidrug-resistant Pseudomonas aeruginosa. We present the first case of persistent P. aeruginosa bacteremia with in vitro resistance to these novel antimicrobials. A 68-year-old man with newly diagnosed follicular lymphoma was admitted to the medical intensive care unit for sepsis and right lower extremity cellulitis. The patient was placed empirically on vancomycin and piperacillin-tazobactam. Blood cultures from Day 1 of hospitalization grew P. aeruginosa susceptible to piperacillin-tazobactam and cefepime identified using VITEK 2 (Biomerieux, Lenexa, KS). Repeat blood cultures from Day 5 grew P. aeruginosa resistant to all cephalosporins, as well as to meropenem by Day 10. Susceptibility testing performed by measuring minimum inhibitory concentration by E-test (Biomerieux, Lenexa, KS) revealed that blood cultures from Day 10 were resistant to ceftazidime-avibactam and ceftolozane-tazobactam. The Verigene Blood Culture-Gram-Negative (BC-GN) microarray-based assay (Nanosphere, Inc., Northbrook, IL) was used to investigate underlying resistance mechanism in the P. aeruginosa isolate but CTX-M, KPC, NDM, VIM, IMP, and OXA gene were not detected. This case report highlights the well-documented phenomenon of antimicrobial resistance development in P. aeruginosa even during the course of appropriate antibiotic therapy. In the era of increasing multidrug-resistant organisms, routine susceptibility testing of P. aeruginosa to ceftazidime-avibactam and ceftolozane-tazobactam is warranted. Emerging resistance mechanisms to these novel antibiotics need to be further investigated.

Multicenter Evaluation of the Etest Gradient Diffusion Method for Ceftolozane-Tazobactam Susceptibility Testing of Enterobacteriaceae and Pseudomonas aeruginosa

“…Despite these limitations, in most clinical laboratory settings, C/T susceptibility testing options like gradient diffusion that are more accessible than BMD are critically needed because approximately 10% of infections for which C/T therapy is indicated are caused by a C/T-resistant organism and therefore susceptibility testing is needed to optimize therapy and antimicrobial stewardship (6, 7, 9-17, 24, 26, 27). Indeed, C/T resistance and treatment failures have already been described and appear to be acquired/mediated via a variety of mechanisms, emphasizing the need for widely accessible phenotypic C/T susceptibility testing (8,11,24,(28)(29)(30).…”

Where Did They Come from—Multi-Drug Resistant Pathogenic Escherichia coli in a Cemetery Environment?

“…However, the coupling of Ceftolozane with Tazobactam (a β-lactamase inhibitor) has facilitated the treatment of many infections, including those caused by ESBL-producing bacteria [ 50 ]. Despite the enhanced potency of this drug combination, the resistance of some clinical isolates, including E. coli , has been reported [ 51 , 52 ]. In our study, we observed that a surprisingly high percentage (52%) of our isolates were resistant to the drug formulation.…”

Prevalence of tet(X4) in Escherichia coli From Duck Farms in Southeast China

“…Carbapenems, colistin, and tigecycline are considered as the last-resort antibiotics against severe human infections caused by multidrug-resistant (MDR) bacteria. However, the discovery of a series of carbapenems resistance genes, such as bla OXA , bla NDM , bla VIM , and bla KPC , as well as the mobile colistin resistance mcr gene, has compromised the effectiveness of carbapenems and colistin in clinics ( Gangcuangco et al, 2016 ; Lunha et al, 2016 ; Wang et al, 2017 ; Gaibani et al, 2020 ). Under such circumstances, tigecycline was considered as the last chance for treatment of extensively drug-resistant pathogens.…”