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

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

Nutman, Amir (författare): Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.

Lellouche, Jonathan (författare): Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.

Temkin, Elizabeth (författare): Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.

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Daikos, George (författare): Laikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece.

Skiada, Anna (författare): Laikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece.

Durante-Mangoni, Emanuele (författare): Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy.

Dishon-Benattar, Yael (författare): Rambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.;Univ Haifa, Cheryl Spencer Inst Nursing Res, Haifa, Israel.

Bitterman, Roni (författare): Rambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.

Yahav, Dafna (författare): Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Rabin Med Ctr, Infect Dis Unit, Petah Tiqwa, Israel.

Daitch, Vered (författare): Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Rabin Med Ctr, Infect Dis Unit, Petah Tiqwa, Israel.

Bernardo, Mariano (författare): Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy.

Iossa, Domenico (författare): Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy.

Zusman, Oren (författare): Beilinson Med Ctr, Dept Med E, Rabin Med Ctr, Peta Tikva, Israel.

Friberg, Lena (författare): Uppsala universitet,Institutionen för farmaceutisk biovetenskap

Mouton, Johan W. (författare): Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands.

Theuretzbacher, Ursula (författare): Ctr Antiinfect Agents, Vienna, Austria.

Leibovici, Leonard (författare): Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Dept Med E, Rabin Med Ctr, Peta Tikva, Israel.

Paul, Mical (författare): Rambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.;Techion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.

Carmeli, Yehuda (författare): Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.

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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)

Elsevier BV, 2020
2020
Engelska.
Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 26:9, s. 1185-1191

Relaterad länk:: http://www.clinicalm...; visa fler...; https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

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

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