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Colistin plus merop...
Colistin plus meropenem for carbapenem-resistant Gram-negative infections : in vitro synergism is not associated with better clinical outcomes
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- Nutman, Amir (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.
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- Lellouche, Jonathan (author)
- Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.
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- Temkin, Elizabeth (author)
- Tel Aviv Med Ctr & Sch Med, Natl Inst Infect Control & Antibiot Resistance, Tel Aviv, Israel.
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- Daikos, George (author)
- Laikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece.
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- Skiada, Anna (author)
- Laikon Gen Hosp, Dept Med 1, Athens, Greece.;Natl & Kapodistrian Univ Athens, Athens, Greece.
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- Durante-Mangoni, Emanuele (author)
- Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy.
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- Dishon-Benattar, Yael (author)
- Rambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.;Univ Haifa, Cheryl Spencer Inst Nursing Res, Haifa, Israel.
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- Bitterman, Roni (author)
- Rambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.
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- Yahav, Dafna (author)
- Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Rabin Med Ctr, Infect Dis Unit, Petah Tiqwa, Israel.
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- Daitch, Vered (author)
- Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Rabin Med Ctr, Infect Dis Unit, Petah Tiqwa, Israel.
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- Bernardo, Mariano (author)
- Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy.
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- Iossa, Domenico (author)
- Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy.;AORN Colli Monaldi Hosp, Naples, Italy.
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- Zusman, Oren (author)
- Beilinson Med Ctr, Dept Med E, Rabin Med Ctr, Peta Tikva, Israel.
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- Friberg, Lena (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Mouton, Johan W. (author)
- Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands.
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- Theuretzbacher, Ursula (author)
- Ctr Antiinfect Agents, Vienna, Austria.
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- Leibovici, Leonard (author)
- Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.;Beilinson Med Ctr, Dept Med E, Rabin Med Ctr, Peta Tikva, Israel.
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- Paul, Mical (author)
- Rambam Hlth Care Campus, Inst Infect Dis, Haifa, Israel.;Techion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.
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- Carmeli, Yehuda (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.
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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
- English.
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 26:9, s. 1185-1191
- Related links:
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http://www.clinicalm...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- Carbapenem resistance
- Checkerboard assay
- Colistin
- Combination treatment
- Gram-negative infections synergism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Nutman, Amir
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Lellouche, Jonat ...
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Temkin, Elizabet ...
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Daikos, George
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Skiada, Anna
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Durante-Mangoni, ...
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Dishon-Benattar, ...
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Bitterman, Roni
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Yahav, Dafna
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Daitch, Vered
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Bernardo, Marian ...
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Iossa, Domenico
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Zusman, Oren
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Friberg, Lena
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Mouton, Johan W.
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Theuretzbacher, ...
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Leibovici, Leona ...
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Paul, Mical
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Carmeli, Yehuda
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Clinical Microbi ...
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Uppsala University