Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial
The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. To determine whether fosfomycin is noninferior to ceftriaxone or...
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| Veröffentlicht in: | JAMA network open 2022-01, Vol.5 (1), p.e2137277-e2137277 |
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| creator | Sojo-Dorado, Jesús López-Hernández, Inmaculada Rosso-Fernandez, Clara Morales, Isabel M Palacios-Baena, Zaira R Hernández-Torres, Alicia Merino de Lucas, Esperanza Escolà-Vergé, Laura Bereciartua, Elena García-Vázquez, Elisa Pintado, Vicente Boix-Palop, Lucía Natera-Kindelán, Clara Sorlí, Luisa Borrell, Nuria Giner-Oncina, Livia Amador-Prous, Concha Shaw, Evelyn Jover-Saenz, Alfredo Molina, Jose Martínez-Alvarez, Rosa M Dueñas, Carlos J Calvo-Montes, Jorge Silva, Jose T Cárdenes, Miguel A Lecuona, María Pomar, Virginia Valiente de Santis, Lucía Yagüe-Guirao, Genoveva Lobo-Acosta, María Angeles Merino-Bohórquez, Vicente Pascual, Alvaro Rodríguez-Baño, Jesús |
| description | The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option.
To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.
This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.
Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.
The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.
Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01).
This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an incr |
| doi_str_mv | 10.1001/jamanetworkopen.2021.37277 |
| format | Article |
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To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.
This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.
Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.
The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.
Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01).
This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections.
ClinicalTrials.gov Identifier: NCT02142751.</description><identifier>ISSN: 2574-3805</identifier><identifier>EISSN: 2574-3805</identifier><identifier>DOI: 10.1001/jamanetworkopen.2021.37277</identifier><identifier>PMID: 35024838</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Aged ; Aged, 80 and over ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; Bacteremia - drug therapy ; Bacteremia - microbiology ; Clinical trials ; Drug resistance ; Drug Resistance, Multiple, Bacterial ; E coli ; Escherichia coli ; Escherichia coli Infections - drug therapy ; Escherichia coli Infections - microbiology ; Female ; Fosfomycin - therapeutic use ; Humans ; Infectious Diseases ; Male ; Middle Aged ; Multidrug resistant organisms ; Online Only ; Original Investigation ; Spain ; Urinary tract diseases ; Urinary tract infections ; Urogenital system</subject><ispartof>JAMA network open, 2022-01, Vol.5 (1), p.e2137277-e2137277</ispartof><rights>2022. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright 2022 Sojo-Dorado J et al. .</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a364t-c0a5b94767c1c08bb2bb8e4d224c5df51d6cfead28c3300633330626e43a7ca43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,861,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35024838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sojo-Dorado, Jesús</creatorcontrib><creatorcontrib>López-Hernández, Inmaculada</creatorcontrib><creatorcontrib>Rosso-Fernandez, Clara</creatorcontrib><creatorcontrib>Morales, Isabel M</creatorcontrib><creatorcontrib>Palacios-Baena, Zaira R</creatorcontrib><creatorcontrib>Hernández-Torres, Alicia</creatorcontrib><creatorcontrib>Merino de Lucas, Esperanza</creatorcontrib><creatorcontrib>Escolà-Vergé, Laura</creatorcontrib><creatorcontrib>Bereciartua, Elena</creatorcontrib><creatorcontrib>García-Vázquez, Elisa</creatorcontrib><creatorcontrib>Pintado, Vicente</creatorcontrib><creatorcontrib>Boix-Palop, Lucía</creatorcontrib><creatorcontrib>Natera-Kindelán, Clara</creatorcontrib><creatorcontrib>Sorlí, Luisa</creatorcontrib><creatorcontrib>Borrell, Nuria</creatorcontrib><creatorcontrib>Giner-Oncina, Livia</creatorcontrib><creatorcontrib>Amador-Prous, Concha</creatorcontrib><creatorcontrib>Shaw, Evelyn</creatorcontrib><creatorcontrib>Jover-Saenz, Alfredo</creatorcontrib><creatorcontrib>Molina, Jose</creatorcontrib><creatorcontrib>Martínez-Alvarez, Rosa M</creatorcontrib><creatorcontrib>Dueñas, Carlos J</creatorcontrib><creatorcontrib>Calvo-Montes, Jorge</creatorcontrib><creatorcontrib>Silva, Jose T</creatorcontrib><creatorcontrib>Cárdenes, Miguel A</creatorcontrib><creatorcontrib>Lecuona, María</creatorcontrib><creatorcontrib>Pomar, Virginia</creatorcontrib><creatorcontrib>Valiente de Santis, Lucía</creatorcontrib><creatorcontrib>Yagüe-Guirao, Genoveva</creatorcontrib><creatorcontrib>Lobo-Acosta, María Angeles</creatorcontrib><creatorcontrib>Merino-Bohórquez, Vicente</creatorcontrib><creatorcontrib>Pascual, Alvaro</creatorcontrib><creatorcontrib>Rodríguez-Baño, Jesús</creatorcontrib><creatorcontrib>REIPI-GEIRAS-FOREST group</creatorcontrib><title>Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial</title><title>JAMA network open</title><addtitle>JAMA Netw Open</addtitle><description>The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option.
To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.
This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.
Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.
The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.
Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01).
This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections.
ClinicalTrials.gov Identifier: NCT02142751.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Bacteremia - drug therapy</subject><subject>Bacteremia - microbiology</subject><subject>Clinical trials</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple, Bacterial</subject><subject>E coli</subject><subject>Escherichia coli</subject><subject>Escherichia coli Infections - drug therapy</subject><subject>Escherichia coli Infections - microbiology</subject><subject>Female</subject><subject>Fosfomycin - therapeutic use</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multidrug resistant organisms</subject><subject>Online Only</subject><subject>Original Investigation</subject><subject>Spain</subject><subject>Urinary tract diseases</subject><subject>Urinary tract 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Luisa</creatorcontrib><creatorcontrib>Borrell, Nuria</creatorcontrib><creatorcontrib>Giner-Oncina, Livia</creatorcontrib><creatorcontrib>Amador-Prous, Concha</creatorcontrib><creatorcontrib>Shaw, Evelyn</creatorcontrib><creatorcontrib>Jover-Saenz, Alfredo</creatorcontrib><creatorcontrib>Molina, Jose</creatorcontrib><creatorcontrib>Martínez-Alvarez, Rosa M</creatorcontrib><creatorcontrib>Dueñas, Carlos J</creatorcontrib><creatorcontrib>Calvo-Montes, Jorge</creatorcontrib><creatorcontrib>Silva, Jose T</creatorcontrib><creatorcontrib>Cárdenes, Miguel A</creatorcontrib><creatorcontrib>Lecuona, María</creatorcontrib><creatorcontrib>Pomar, Virginia</creatorcontrib><creatorcontrib>Valiente de Santis, Lucía</creatorcontrib><creatorcontrib>Yagüe-Guirao, Genoveva</creatorcontrib><creatorcontrib>Lobo-Acosta, María Angeles</creatorcontrib><creatorcontrib>Merino-Bohórquez, Vicente</creatorcontrib><creatorcontrib>Pascual, Alvaro</creatorcontrib><creatorcontrib>Rodríguez-Baño, 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Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JAMA network open</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sojo-Dorado, Jesús</au><au>López-Hernández, Inmaculada</au><au>Rosso-Fernandez, Clara</au><au>Morales, Isabel M</au><au>Palacios-Baena, Zaira R</au><au>Hernández-Torres, Alicia</au><au>Merino de Lucas, Esperanza</au><au>Escolà-Vergé, Laura</au><au>Bereciartua, Elena</au><au>García-Vázquez, Elisa</au><au>Pintado, Vicente</au><au>Boix-Palop, Lucía</au><au>Natera-Kindelán, Clara</au><au>Sorlí, Luisa</au><au>Borrell, Nuria</au><au>Giner-Oncina, Livia</au><au>Amador-Prous, Concha</au><au>Shaw, Evelyn</au><au>Jover-Saenz, Alfredo</au><au>Molina, Jose</au><au>Martínez-Alvarez, Rosa M</au><au>Dueñas, Carlos J</au><au>Calvo-Montes, Jorge</au><au>Silva, Jose T</au><au>Cárdenes, Miguel A</au><au>Lecuona, María</au><au>Pomar, Virginia</au><au>Valiente de Santis, Lucía</au><au>Yagüe-Guirao, Genoveva</au><au>Lobo-Acosta, María Angeles</au><au>Merino-Bohórquez, Vicente</au><au>Pascual, Alvaro</au><au>Rodríguez-Baño, Jesús</au><aucorp>REIPI-GEIRAS-FOREST group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial</atitle><jtitle>JAMA network open</jtitle><addtitle>JAMA Netw Open</addtitle><date>2022-01-04</date><risdate>2022</risdate><volume>5</volume><issue>1</issue><spage>e2137277</spage><epage>e2137277</epage><pages>e2137277-e2137277</pages><issn>2574-3805</issn><eissn>2574-3805</eissn><abstract>The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option.
To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.
This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.
Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.
The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.
Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01).
This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections.
ClinicalTrials.gov Identifier: NCT02142751.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>35024838</pmid><doi>10.1001/jamanetworkopen.2021.37277</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2574-3805 |
| ispartof | JAMA network open, 2022-01, Vol.5 (1), p.e2137277-e2137277 |
| issn | 2574-3805 2574-3805 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8759008 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Aged Aged, 80 and over Anti-Bacterial Agents - therapeutic use Antibiotics Bacteremia - drug therapy Bacteremia - microbiology Clinical trials Drug resistance Drug Resistance, Multiple, Bacterial E coli Escherichia coli Escherichia coli Infections - drug therapy Escherichia coli Infections - microbiology Female Fosfomycin - therapeutic use Humans Infectious Diseases Male Middle Aged Multidrug resistant organisms Online Only Original Investigation Spain Urinary tract diseases Urinary tract infections Urogenital system |
| title | Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T11%3A47%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effectiveness%20of%20Fosfomycin%20for%20the%20Treatment%20of%20Multidrug-Resistant%20Escherichia%20coli%20Bacteremic%20Urinary%20Tract%20Infections:%20A%20Randomized%20Clinical%20Trial&rft.jtitle=JAMA%20network%20open&rft.au=Sojo-Dorado,%20Jes%C3%BAs&rft.aucorp=REIPI-GEIRAS-FOREST%20group&rft.date=2022-01-04&rft.volume=5&rft.issue=1&rft.spage=e2137277&rft.epage=e2137277&rft.pages=e2137277-e2137277&rft.issn=2574-3805&rft.eissn=2574-3805&rft_id=info:doi/10.1001/jamanetworkopen.2021.37277&rft_dat=%3Cproquest_pubme%3E2667743404%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2667743404&rft_id=info:pmid/35024838&rfr_iscdi=true |