Meropenem vs standard of care for treatment of neonatal late onset sepsis

The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated anti...

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Veröffentlicht in:PloS one 2020-03, Vol.15 (3), p.e0229380
Hauptverfasser: Lutsar, Irja, Chazallon, Corine, Trafojer, Ursula, de Cabre, Vincent Meiffredy, Auriti, Cinzia, Bertaina, Chiara, Calo Carducci, Francesca Ippolita, Canpolat, Fuat Emre, Esposito, Susanna, Fournier, Isabelle, Hallik, Maarja, Heath, Paul T, Ilmoja, Mari-Liis, Iosifidis, Elias, Kuznetsova, Jelena, Meyer, Laurence, Metsvaht, Tuuli, Mitsiakos, George, Pana, Zoi Dorothea, Mosca, Fabio, Pugni, Lorenza, Roilides, Emmanuel, Rossi, Paolo, Sarafidis, Kosmas, Sanchez, Laura, Sharland, Michael, Usonis, Vytautas, Warris, Adilia, Aboulker, Jean-Pierre, Giaquinto, Carlo
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container_start_page e0229380
container_title PloS one
container_volume 15
creator Lutsar, Irja
Chazallon, Corine
Trafojer, Ursula
de Cabre, Vincent Meiffredy
Auriti, Cinzia
Bertaina, Chiara
Calo Carducci, Francesca Ippolita
Canpolat, Fuat Emre
Esposito, Susanna
Fournier, Isabelle
Hallik, Maarja
Heath, Paul T
Ilmoja, Mari-Liis
Iosifidis, Elias
Kuznetsova, Jelena
Meyer, Laurence
Metsvaht, Tuuli
Mitsiakos, George
Pana, Zoi Dorothea
Mosca, Fabio
Pugni, Lorenza
Roilides, Emmanuel
Rossi, Paolo
Sarafidis, Kosmas
Sanchez, Laura
Sharland, Michael
Usonis, Vytautas
Warris, Adilia
Aboulker, Jean-Pierre
Giaquinto, Carlo
description The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged 44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% o
doi_str_mv 10.1371/journal.pone.0229380
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However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged &lt;90 days with LOS. NeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of [less than or equal to]44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA &gt;44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0229380</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Aminoglycosides ; Ampicillin ; Analysis ; Bacteria ; Blood tests ; Care and treatment ; Clinical trials ; Infants ; Infection ; Menstruation ; Meropenem ; Microbial drug resistance ; Microorganisms ; Mortality ; Newborn infants ; Pathogenic microorganisms ; Penicillins ; Reason</subject><ispartof>PloS one, 2020-03, Vol.15 (3), p.e0229380</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,866,27931,27932</link.rule.ids></links><search><creatorcontrib>Lutsar, Irja</creatorcontrib><creatorcontrib>Chazallon, Corine</creatorcontrib><creatorcontrib>Trafojer, Ursula</creatorcontrib><creatorcontrib>de Cabre, Vincent Meiffredy</creatorcontrib><creatorcontrib>Auriti, Cinzia</creatorcontrib><creatorcontrib>Bertaina, Chiara</creatorcontrib><creatorcontrib>Calo Carducci, Francesca Ippolita</creatorcontrib><creatorcontrib>Canpolat, Fuat Emre</creatorcontrib><creatorcontrib>Esposito, Susanna</creatorcontrib><creatorcontrib>Fournier, Isabelle</creatorcontrib><creatorcontrib>Hallik, Maarja</creatorcontrib><creatorcontrib>Heath, Paul T</creatorcontrib><creatorcontrib>Ilmoja, Mari-Liis</creatorcontrib><creatorcontrib>Iosifidis, Elias</creatorcontrib><creatorcontrib>Kuznetsova, Jelena</creatorcontrib><creatorcontrib>Meyer, Laurence</creatorcontrib><creatorcontrib>Metsvaht, Tuuli</creatorcontrib><creatorcontrib>Mitsiakos, George</creatorcontrib><creatorcontrib>Pana, Zoi Dorothea</creatorcontrib><creatorcontrib>Mosca, Fabio</creatorcontrib><creatorcontrib>Pugni, Lorenza</creatorcontrib><creatorcontrib>Roilides, Emmanuel</creatorcontrib><creatorcontrib>Rossi, Paolo</creatorcontrib><creatorcontrib>Sarafidis, Kosmas</creatorcontrib><creatorcontrib>Sanchez, Laura</creatorcontrib><creatorcontrib>Sharland, Michael</creatorcontrib><creatorcontrib>Usonis, Vytautas</creatorcontrib><creatorcontrib>Warris, Adilia</creatorcontrib><creatorcontrib>Aboulker, Jean-Pierre</creatorcontrib><creatorcontrib>Giaquinto, Carlo</creatorcontrib><title>Meropenem vs standard of care for treatment of neonatal late onset sepsis</title><title>PloS one</title><description>The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged &lt;90 days with LOS. NeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of [less than or equal to]44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA &gt;44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating.</description><subject>Aminoglycosides</subject><subject>Ampicillin</subject><subject>Analysis</subject><subject>Bacteria</subject><subject>Blood tests</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Infants</subject><subject>Infection</subject><subject>Menstruation</subject><subject>Meropenem</subject><subject>Microbial drug resistance</subject><subject>Microorganisms</subject><subject>Mortality</subject><subject>Newborn infants</subject><subject>Pathogenic microorganisms</subject><subject>Penicillins</subject><subject>Reason</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kE9LAzEUxIMoWKvfwENOgoet2fzZJMdStC5UClq8ltfdt-2WNFk2qfjxrehhvQgD8xh-DLwh5DZnk1zo_GEfjr0HN-mCxwnj3ArDzsgot4JnBWfifHBfkqsY94wpYYpiRMoX7EOHHg_0I9KYwNfQ1zQ0tIIeaRN6mnqEdECfvlOPwUMCRx0kpMFHTDRiF9t4TS4acBFvfn1MVk-Pq9lztljOy9l0kW2ttdkGlNS10NzUvLIKCqM32qKWWoLZaCEbZYRUCjkwaRpWSY6AVlhjT8q1GJP7n9otOFy3vgo-4WfawjHGdfn2up4WecGVUacV_meX73_ZuwG7Q3BpF4M7pvb05BD8ApPubOo</recordid><startdate>20200304</startdate><enddate>20200304</enddate><creator>Lutsar, Irja</creator><creator>Chazallon, Corine</creator><creator>Trafojer, Ursula</creator><creator>de Cabre, Vincent Meiffredy</creator><creator>Auriti, Cinzia</creator><creator>Bertaina, Chiara</creator><creator>Calo Carducci, Francesca Ippolita</creator><creator>Canpolat, Fuat Emre</creator><creator>Esposito, Susanna</creator><creator>Fournier, Isabelle</creator><creator>Hallik, Maarja</creator><creator>Heath, Paul T</creator><creator>Ilmoja, Mari-Liis</creator><creator>Iosifidis, Elias</creator><creator>Kuznetsova, Jelena</creator><creator>Meyer, Laurence</creator><creator>Metsvaht, Tuuli</creator><creator>Mitsiakos, George</creator><creator>Pana, Zoi Dorothea</creator><creator>Mosca, Fabio</creator><creator>Pugni, Lorenza</creator><creator>Roilides, Emmanuel</creator><creator>Rossi, Paolo</creator><creator>Sarafidis, Kosmas</creator><creator>Sanchez, Laura</creator><creator>Sharland, Michael</creator><creator>Usonis, Vytautas</creator><creator>Warris, Adilia</creator><creator>Aboulker, Jean-Pierre</creator><creator>Giaquinto, Carlo</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20200304</creationdate><title>Meropenem vs standard of care for treatment of neonatal late onset sepsis</title><author>Lutsar, Irja ; Chazallon, Corine ; Trafojer, Ursula ; de Cabre, Vincent Meiffredy ; Auriti, Cinzia ; Bertaina, Chiara ; Calo Carducci, Francesca Ippolita ; Canpolat, Fuat Emre ; Esposito, Susanna ; Fournier, Isabelle ; Hallik, Maarja ; Heath, Paul T ; Ilmoja, Mari-Liis ; Iosifidis, Elias ; Kuznetsova, Jelena ; Meyer, Laurence ; Metsvaht, Tuuli ; Mitsiakos, George ; Pana, Zoi Dorothea ; Mosca, Fabio ; Pugni, Lorenza ; Roilides, Emmanuel ; Rossi, Paolo ; Sarafidis, Kosmas ; Sanchez, Laura ; Sharland, Michael ; Usonis, Vytautas ; Warris, Adilia ; Aboulker, Jean-Pierre ; Giaquinto, Carlo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g999-ba547d3728d2c95a687b79e7474a8b734f583455e2a048f0c42eae93989989173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aminoglycosides</topic><topic>Ampicillin</topic><topic>Analysis</topic><topic>Bacteria</topic><topic>Blood tests</topic><topic>Care and treatment</topic><topic>Clinical trials</topic><topic>Infants</topic><topic>Infection</topic><topic>Menstruation</topic><topic>Meropenem</topic><topic>Microbial drug resistance</topic><topic>Microorganisms</topic><topic>Mortality</topic><topic>Newborn infants</topic><topic>Pathogenic microorganisms</topic><topic>Penicillins</topic><topic>Reason</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lutsar, Irja</creatorcontrib><creatorcontrib>Chazallon, Corine</creatorcontrib><creatorcontrib>Trafojer, Ursula</creatorcontrib><creatorcontrib>de Cabre, Vincent Meiffredy</creatorcontrib><creatorcontrib>Auriti, Cinzia</creatorcontrib><creatorcontrib>Bertaina, Chiara</creatorcontrib><creatorcontrib>Calo Carducci, Francesca Ippolita</creatorcontrib><creatorcontrib>Canpolat, Fuat Emre</creatorcontrib><creatorcontrib>Esposito, Susanna</creatorcontrib><creatorcontrib>Fournier, Isabelle</creatorcontrib><creatorcontrib>Hallik, Maarja</creatorcontrib><creatorcontrib>Heath, Paul T</creatorcontrib><creatorcontrib>Ilmoja, Mari-Liis</creatorcontrib><creatorcontrib>Iosifidis, Elias</creatorcontrib><creatorcontrib>Kuznetsova, Jelena</creatorcontrib><creatorcontrib>Meyer, Laurence</creatorcontrib><creatorcontrib>Metsvaht, Tuuli</creatorcontrib><creatorcontrib>Mitsiakos, George</creatorcontrib><creatorcontrib>Pana, Zoi Dorothea</creatorcontrib><creatorcontrib>Mosca, Fabio</creatorcontrib><creatorcontrib>Pugni, Lorenza</creatorcontrib><creatorcontrib>Roilides, Emmanuel</creatorcontrib><creatorcontrib>Rossi, Paolo</creatorcontrib><creatorcontrib>Sarafidis, Kosmas</creatorcontrib><creatorcontrib>Sanchez, Laura</creatorcontrib><creatorcontrib>Sharland, Michael</creatorcontrib><creatorcontrib>Usonis, Vytautas</creatorcontrib><creatorcontrib>Warris, Adilia</creatorcontrib><creatorcontrib>Aboulker, Jean-Pierre</creatorcontrib><creatorcontrib>Giaquinto, Carlo</creatorcontrib><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lutsar, Irja</au><au>Chazallon, Corine</au><au>Trafojer, Ursula</au><au>de Cabre, Vincent Meiffredy</au><au>Auriti, Cinzia</au><au>Bertaina, Chiara</au><au>Calo Carducci, Francesca Ippolita</au><au>Canpolat, Fuat Emre</au><au>Esposito, Susanna</au><au>Fournier, Isabelle</au><au>Hallik, Maarja</au><au>Heath, Paul T</au><au>Ilmoja, Mari-Liis</au><au>Iosifidis, Elias</au><au>Kuznetsova, Jelena</au><au>Meyer, Laurence</au><au>Metsvaht, Tuuli</au><au>Mitsiakos, George</au><au>Pana, Zoi Dorothea</au><au>Mosca, Fabio</au><au>Pugni, Lorenza</au><au>Roilides, Emmanuel</au><au>Rossi, Paolo</au><au>Sarafidis, Kosmas</au><au>Sanchez, Laura</au><au>Sharland, Michael</au><au>Usonis, Vytautas</au><au>Warris, Adilia</au><au>Aboulker, Jean-Pierre</au><au>Giaquinto, Carlo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Meropenem vs standard of care for treatment of neonatal late onset sepsis</atitle><jtitle>PloS one</jtitle><date>2020-03-04</date><risdate>2020</risdate><volume>15</volume><issue>3</issue><spage>e0229380</spage><pages>e0229380-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged &lt;90 days with LOS. NeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of [less than or equal to]44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA &gt;44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0229380</doi><tpages>e0229380</tpages></addata></record>
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subjects Aminoglycosides
Ampicillin
Analysis
Bacteria
Blood tests
Care and treatment
Clinical trials
Infants
Infection
Menstruation
Meropenem
Microbial drug resistance
Microorganisms
Mortality
Newborn infants
Pathogenic microorganisms
Penicillins
Reason
title Meropenem vs standard of care for treatment of neonatal late onset sepsis
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