Italian nationwide survey on Pseudomonas aeruginosa from invasive infections: activity of ceftolozane/tazobactam and comparators, and molecular epidemiology of carbapenemase producers

Giani, Tommaso; Arena, Fabio; Pollini, Simona; Pilato, Vincenzo Di; D’Andrea, Marco Maria; Angelis, Lucia Henrici De; Bassetti, Matteo; Rossolini, Gian María; Vismara, Chiara; Luzzaro, Francesco; Cavallo, Rossana; Dusi, Pier Andrea; Pagani, Elisabetta; Sarti, Mario; Farina, Claudio; Rigoli, Roberto; Scarparo, Claudio; Pecile, Patrizia; Cusi, Maria Grazia; Mencacci, Antonella; Manso, Esther; Spanu, Teresa; Labonia, Maria; Tassi, V; Amato, Gerardino; Stefani, Stefania; Giraldi, Cristina; Rassu, Mario

doi:10.1093/jac/dkx453

Cited by 77 publications

(45 citation statements)

References 45 publications

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“…All of the strains in our study were positive for carbapenemase production. Similar to results reported in the literature, we believe this may be responsible for the high C/T and CZA resistance rates in our study [21][22][23][24] . However, the inability to determine carbapenemase type or carbapenemase resistance genes was the major limitation of our study.…”

Section: Discussionsupporting

confidence: 92%

“…In another study, resistance to C/T in strains producing VIM-2 carbapenemase was found to be 55%, and this high resistance rate was attributed to the fact that the antibiotic does not inhibit Ambler class B carbapenemases [2] . Giani et al [21] detected carbapenemase production in 56.5% of C/T resistant P. aeruginosa strains, while 5.1% of all Pseudomonas strains produced carbapenemase. Among the carbapenemase-producing strains, the rate of bla VIM production was highest at 66.6%, followed by bla IMP at 25%.…”

Section: Discussionmentioning

confidence: 99%

“…They reported that while all VIM-and IMP-producing strains were resistant to C/T, strains with bla GES-5 were susceptible to C/T. They also determined that 9.1% of all isolates were resistant to C/T, but did not mention the proportion of carbapenemase-producing isolates that were C/T-resistant [21] . These studies demonstrate that identifying carbapenemase resistance genes is important for CZA and C/T susceptibility.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…P. aeruginosa izolatları için EUCAST ve CLSI kriterleri aynı olup, MİK değeri ≤4 mg/l olanlar duyarlı, >4 mg/l olanlar dirençlidir [16,17] . Seftolozan/ tazobactam'ın E. coli, K. pneumoniae ve P. aeruginosa izolatlarındaki etkinliğinin değerlendirildiği önde gelen in vitro çalışmalar Tablo 2'de sunulmuştur [5,[16][17][18][19][20][21] . Antibiyotik özellikle P. aeruginosa izolatlarına karşı yüksek aktivite göstermiş olup, %84,4-99 oranında etkili bulunmuştur.…”

Section: İn Vitro Etkinlikunclassified

A Novel β-lactam/β-lactamase inhibitor: Ceftolozane/tazobactam

Şerefhanoğlu¹

2019

mjima

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Seftolozan/tazobaktam yeni kuşak sefalosporin ve β-laktamaz inhibitörü kombinasyonu olan bir antibiyotiktir. On sekiz yaş ve üzerindeki erişkinlerde meydana gelen komplike üriner sistem enfeksiyonları ve metronidazol ile kombine edilerek komplike intraabdominal enfeksiyonların tedavisinde Amerikan Gıda ve İlaç Dairesi onayı almıştır. Başlıca etki spektrumu çoklu ilaç dirençli (ÇİD) Pseudomonas aeruginosa ve diğer aerobik Gram-olumsuz bakterilerdir (GNB). Başlıca karakteristik özellikleri: (1) P. aeruginosa'nın penisilin bağlayan proteinlerine yüksek afinitesi olması, (2) dış membran penetrasyonunun yüksek olması ve bu nedenle efluks pompası aktivitesinden daha az etkilenmesi, (3) AmpC β-laktamaz, primitif β-laktamazlar (TEM-1, TEM-2, SHV-1 ve OXA-1) ve genişlemiş spektrumlu β-laktamaz olumlu bakterilere etkili olmasıdır. Buna karşın, metallo-β-laktamaz ve Klebsiella pneumoniae karbapenemazları enzimleri üreten patojenlere etkisizdir. Seftolozan/tazobaktamın özellikle tedavi seçeneğinin kısıtlı olduğu ÇİD GNB'nin neden olduğu enfeksiyonların tedavisinde faydalı olacağı düşünülmektedir. Bu yazıda, henüz ülkemizde kullanıma girmemiş olan bu antibiyotiğin farmakokinetik özellikleri, antimikrobiyal spektrumu ve güncel çalışmalardaki verileri derlenmiştir. Anahtar Kelimeler: CRE, GSBL, hemodiyaliz, kronik böbrek yetmezliği, komplike intra-abdominal enfeksiyonlar Ceftolozane/tazobactam is a novel generation cephalosporin and β-lactamase inhibitor combination antibiotic. It was approved for the treatment of adults (18 years and older) with complicated intraabdominal infections used in combination with metronidazole and complicated urinary tract infections by the United States Food and Drug Administration. Its primary activity is against multidrug-resistant Pseudomonas aeruginosa and other aerobic Gram-negative bacteria. The main characteristic features of the antibiotic include: (1) a greater affinity for penicillin-binding proteins produced by P. aeruginosa; (2) better outer membrane permeability that displays resistance mechanisms against upregulation of efflux pumps, and (3) effectiveness against pathogens producing AmpC β-lactamases, primitive β-lactamases (TEM-1, TEM-2, SHV-1, and OXA-1), and extended spectrum β-lactamases. However, it is not effective against pathogens producing metallo-β-lactamases and Klebsiella pneumoniae carbapenemases. Ceftolozane/tazobactam is promising for difficult-to-treat infections caused by multidrug-resistant Gram-negative bacteria. Herein, the features of ceftolozane/tazobactam, including its pharmacokinetics, antimicrobial spectrum, and data from recent clinical studies are reviewed.

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“…For example, a large Italian multicenter study, conducted from September 2013 to November 2014, showed that TOL/TAZ was the most active antibiotic against PA [6]. The authors collected 935 PA strains (related to pneumonia or bloodstream infections), of which 37.2% expressed an MDR phenotype: overall, TOL/TAZ turned out to be activity against 90.9% of PA isolates, followed by amikacin (88.0% susceptibility) [6].…”

Section: Letter To the Editormentioning

confidence: 99%

Response to: ‘Letter to the Editor: “Management of multidrug-resistant Pseudomonas aeruginosa in the Intensive Care Unit: state of the art”’

Maraolo

Cascella

Corcione

et al. 2018

Expert Review of Anti-infective Therapy

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Italian nationwide survey on Pseudomonas aeruginosa from invasive infections: activity of ceftolozane/tazobactam and comparators, and molecular epidemiology of carbapenemase producers

Abstract: Ceftolozane/tazobactam exhibited potent in vitro activity against P. aeruginosa causing invasive infections in Italy. Carbapenemase production was the most common mechanism of resistance to ceftolozane/tazobactam.

Cited by 77 publications

References 45 publications

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

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

A Novel β-lactam/β-lactamase inhibitor: Ceftolozane/tazobactam

Response to: ‘Letter to the Editor: “Management of multidrug-resistant Pseudomonas aeruginosa in the Intensive Care Unit: state of the art”’

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