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  • Nutman, AmirTel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. (author)

Colistin plus meropenem for carbapenem-resistant Gram-negative infections : in vitro synergism is not associated with better clinical outcomes

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • Elsevier BV,2020
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-420891
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-420891URI
  • https://doi.org/10.1016/j.cmi.2020.03.035DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • ObjectivesIn vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem.MethodsThis was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin–meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin–meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure.ResultsThe sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31–1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22–2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26–1.04) or 14-day mortality (aOR1.09, 95% CI 0.60–1.96).DiscussionIn vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

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  • Lellouche, JonathanTel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel. (author)
  • Temkin, ElizabethTel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel. (author)
  • Daikos, GeorgeLaikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece. (author)
  • Skiada, AnnaLaikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece. (author)
  • Durante-Mangoni, EmanueleUniv Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy. (author)
  • Dishon-Benattar, YaelRambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.;Univ Haifa, Cheryl Spencer Inst Nursing Res, Haifa, Israel. (author)
  • Bitterman, RoniRambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel. (author)
  • Yahav, DafnaTel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Rabin Med Ctr, Infect Dis Unit, Petah Tiqwa, Israel. (author)
  • Daitch, VeredTel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Rabin Med Ctr, Infect Dis Unit, Petah Tiqwa, Israel. (author)
  • Bernardo, MarianoUniv Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy. (author)
  • Iossa, DomenicoUniv Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy. (author)
  • Zusman, OrenBeilinson Med Ctr, Dept Med E, Rabin Med Ctr, Peta Tikva, Israel. (author)
  • Friberg, LenaUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)lenasimo (author)
  • Mouton, Johan W.Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands. (author)
  • Theuretzbacher, UrsulaCtr Antiinfect Agents, Vienna, Austria. (author)
  • Leibovici, LeonardTel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Dept Med E, Rabin Med Ctr, Peta Tikva, Israel. (author)
  • Paul, MicalRambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.;Techion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel. (author)
  • Carmeli, YehudaTel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. (author)
  • Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel. (creator_code:org_t)

Related titles

  • In:Clinical Microbiology and Infection: Elsevier BV26:9, s. 1185-11911198-743X1469-0691

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