Multidrug-resistant &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime&amp;ndash;avibactam

Atkin, Stan; Abid, Shadaan; Foster, Michael; Bose, Moumita; Keller, Ashley; Hollaway, Rita; Sader, Hélio S.; Greenberg, David E.; Finklea, James D.; Castanheira, Mariana; Jain, Raksha

doi:10.2147/idr.s173804

Cited by 26 publications

(13 citation statements)

References 39 publications

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“…It was observed that almost all strains carried the ampC gene (97.9%), related to cephalosporins resistance. This alarming incidence of ampC (or its overexpression) in clinical isolates of P. aeruginosa was also reported by other authors [45,46]. Studies have shown that the rates of molecular detection of ampC has varied among clinical isolates of P. aeruginosa.…”

Section: Discussionsupporting

confidence: 75%

Molecular Detection of Drug-Resistance Genes of blaOXA-23-blaOXA-51 and mcr-1 in Clinical Isolates of Pseudomonas aeruginosa

Nitz¹,

Melo²,

Silva

et al. 2021

Microorganisms

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Pseudomonas aeruginosa has caused high rates of mortality due to the appearance of strains with multidrug resistance (MDR) profiles. This study aimed to characterize the molecular profile of virulence and resistance genes in 99 isolates of P. aeruginosa recovered from different clinical specimens. The isolates were identified by the automated method Vitek2, and the antibiotic susceptibility profile was determined using different classes of antimicrobials. The genomic DNA was extracted and amplified by multiplex polymerase chain reaction (mPCR) to detect different virulence and antimicrobial resistance genes. Molecular typing was performed using the enterobacterial repetitive intergenic consensus (ERIC-PCR) technique to determine the clonal relationship among P. aeruginosa isolates. The drug susceptibility profiles of P. aeruginosa for all strains showed high levels of drug resistance, particularly, 27 (27.3%) isolates that exhibited extensively drug-resistant (XDR) profiles, and the other isolates showed MDR profiles. We detected the polymyxin E (mcr-1) gene in one strain that showed resistance against colistin. The genes that confer resistance to oxacillin (blaOXA-23 and blaOXA-51) were present in three isolates. One of these isolates carried both genes. As far as we know from the literature, this is the first report of the presence of blaOXA-23 and blaOXA-51 genes in P. aeruginosa.

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Section: Discussionsupporting

confidence: 75%

Molecular Detection of Drug-Resistance Genes of blaOXA-23-blaOXA-51 and mcr-1 in Clinical Isolates of Pseudomonas aeruginosa

Nitz¹,

Melo²,

Silva

et al. 2021

Microorganisms

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“…An additional use could be the treatment of lung infections caused by P. aeruginosa in patients with cystic fibrosis, for which fluoroquinolones are the only available oral antibiotics. 76,77 Since >65% P. aeruginosa isolates express the AmpC β-lactamase, 78 it is possible that our prodrug approach could be used treat the infection without the associated damage to the microbiota.…”

Section: Discussionmentioning

confidence: 99%

Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug

Evans

Krishna

et al. 2019

J. Med. Chem.

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Expression of β-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to β-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a β-lactamase-cleavable motif. The prodrug is only bactericidal after activation by β-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E. coli isolates expressing diverse β-lactamases; bactericidal activity was not observed in strains without β-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target β-lactamase-producing bacteria using our prodrug approach, without adversely affecting bacteria that do not produce β-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.

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“…It was reported that C/T had higher in vitro efficacy against bloodstream and urinary tract infections than other beta-lactam antibiotics and carbapenems [14,[28][29][30][31][32][33] . In vitro susceptibility to CZA in lower respiratory tract infections caused by resistant P. aeruginosa was also reported to be high [34] .…”

Section: 1%mentioning

confidence: 99%

Investigation of Ceftalozan / tazobactam and Ceftazidim / avibaktam invitro activity against Karbapenemaz producing Pseudomonas aeruginosa strains

Aydemir¹,

Terzi²,

Köroğlu³

et al. 2019

mjima

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The emergence of multidrug-resistant (MDR) and extensively drug-resistant strains of Pseudomonas aeruginosa in recent years has become a major issue due to treatment difficulties as well as high morbidity and mortality rates. Treatment options for infections caused by these microorganisms are very limited. Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are recently developed cephalosporin/betalactamase inhibitor combinations for the treatment of infections caused by MDR P. aeruginosa strains. The aim of this study was to investigate the in vitro efficacy of C/T and CZA against MDR P. aeruginosa strains and to compare the in vitro efficacy of these two drugs. Materials and Methods: Thirty-two MDR P. aeruginosa isolates were included in the study. Identification and antimicrobial susceptibilities of the strains were performed using a VITEK 2® automated system. The efficacy of CZA and C/T was determined by the gradient strip test (Liofilchem MIC strip test, Italy). Modified carbapenemase inactivation method was used to detect carbapenemase production in all strains. Results: Rates of antibiotic resistance in the isolates were 78% for amikacin, 96.8% for levofloxacin, 90.6% for ciprofloxacin, 71.8% for gentamicin, and 78% for netilmicin. Ceftazidime/avibactam resistance was detected in 7 (21.8%) of the isolates and C/T resistance in 10 (31.2%). All strains with resistance to CZA also had resistance to C/T. Three strains were resistant to C/T but susceptible to CZA. Carbapenemase production was positive in all strains. Conclusion: The results of this study indicate that CZA and C/T may be an alternative treatment for some of the carbapenem-resistant P. aeruginosa infections. Further in vitro and in vivo studies are needed to evaluate the effectiveness of these new treatment options against the increasing threat of MDR P. aeruginosa.

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Multidrug-resistant <em>Pseudomonas aeruginosa</em> from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime–avibactam

Cited by 26 publications

References 39 publications

Molecular Detection of Drug-Resistance Genes of blaOXA-23-blaOXA-51 and mcr-1 in Clinical Isolates of Pseudomonas aeruginosa

Molecular Detection of Drug-Resistance Genes of blaOXA-23-blaOXA-51 and mcr-1 in Clinical Isolates of Pseudomonas aeruginosa

Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug

Investigation of Ceftalozan / tazobactam and Ceftazidim / avibaktam invitro activity against Karbapenemaz producing Pseudomonas aeruginosa strains

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