Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates
Background Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update...
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| Veröffentlicht in: | Cochrane database of systematic reviews 2023-06, Vol.2023 (6), p.CD004205 |
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| description | Background
Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.
Objectives
To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference s.
Selection criteria
We included randomised controlled trials (RCTs) or quasi‐RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M‐enriched intravenous immunoglobulin (IgM‐enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM‐enriched IVIG with antibiotics.
Data collection and analysis
We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed‐effect model of meta‐analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD.
Main results
We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain.
Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all‐cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD −0.08, 95% CI −0.14 to −0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low‐certainty evidence) and may decrease length of hospital stay (LOS) (MD −7.74, 95% CI −11.72 to −3.76; 2 studies, 157 participants, low‐certainty evidenc |
| doi_str_mv | 10.1002/14651858.CD004205.pub4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10282162</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2827923399</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4264-7d26978e284be0c77088e0d1b1a6cd841114d247a21ba205091441aa5d4e68973</originalsourceid><addsrcrecordid>eNqFUctOwzAQtBCIlsIvVDlyabEdJ3ZOCMpTqkQPcLYcZ9MaJXGxU6B_j6M-VLhwsrUzO7O7g9CQ4DHBmF4RliZEJGI8ucOYUZyMl6ucHaF-B4w65Pjg30Nn3r9jHKcZ5aeoF_M4FpizPprNoGnttynXVWUaiErrotaBautQj2wZeVh64yPVFFED2tnWeNPMo4CCs9pWJhQi0wTQNqoFf45OSlV5uNi-A_T2cP86eRpNXx6fJzfTkWY0ZSNe0DTjAqhgOWDNORYCcEFyolJdCEYIYQVlXFGSq7AezghjRKmkYJCKjMcDdL3RDXvXUOgwkFOVXDpTK7eWVhn5G2nMQs7tpySYCkpSGhQutwrOfqzAt7I2XkNVqbDLystA4xmN4ywL1HRDDQfw3kG59yFYdnnIXR5yl0fnzkLj8HDKfdsugEC43RC-TAVrqa1euOD_j-4flx_mxpxF</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2827923399</pqid></control><display><type>article</type><title>Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><source>Cochrane Library</source><creator>Pammi, Mohan ; Pammi, Mohan ; Haque, Khalid N</creator><creatorcontrib>Pammi, Mohan ; Pammi, Mohan ; Haque, Khalid N</creatorcontrib><description>Background
Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.
Objectives
To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference s.
Selection criteria
We included randomised controlled trials (RCTs) or quasi‐RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M‐enriched intravenous immunoglobulin (IgM‐enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM‐enriched IVIG with antibiotics.
Data collection and analysis
We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed‐effect model of meta‐analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD.
Main results
We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain.
Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all‐cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD −0.08, 95% CI −0.14 to −0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low‐certainty evidence) and may decrease length of hospital stay (LOS) (MD −7.74, 95% CI −11.72 to −3.76; 2 studies, 157 participants, low‐certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low‐certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low‐certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low‐certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low‐certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low‐certainty evidence) in neonates with sepsis.
Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM‐enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low‐certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low‐certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported.
Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM‐enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low‐certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low‐certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported.
All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons.
Authors' conclusions
Low‐certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM‐enriched IVIG, or PTX with antibiotics compared to IgM‐enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well‐designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.</description><identifier>ISSN: 1465-1858</identifier><identifier>ISSN: 1469-493X</identifier><identifier>EISSN: 1465-1858</identifier><identifier>EISSN: 1469-493X</identifier><identifier>DOI: 10.1002/14651858.CD004205.pub4</identifier><identifier>PMID: 37338074</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Anti-Bacterial Agents ; Anti-Bacterial Agents - adverse effects ; Child health ; Enterocolitis, Necrotizing ; Enterocolitis, Necrotizing - drug therapy ; Gastrointestinal Tract Disorders ; Humans ; Immunoglobulin M ; Immunoglobulins, Intravenous ; Immunoglobulins, Intravenous - therapeutic use ; Infant, Newborn ; Infant, Premature ; Infections in newborns ; Infections in newborns: sepsis ; Infectious disease ; Lung Diseases ; Medicine General & Introductory Medical Sciences ; Necrotizing Enterocolitis ; Neonatal care ; Neonatal infections ; Neonatal infections: nosocomial sepsis ; Neonatal Sepsis ; Neonatal Sepsis - drug therapy ; Nosocomial sepsis ; Pentoxifylline ; Pentoxifylline - adverse effects ; Retinopathy of Prematurity ; Sepsis ; Sepsis - drug therapy</subject><ispartof>Cochrane database of systematic reviews, 2023-06, Vol.2023 (6), p.CD004205</ispartof><rights>Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4264-7d26978e284be0c77088e0d1b1a6cd841114d247a21ba205091441aa5d4e68973</citedby><cites>FETCH-LOGICAL-c4264-7d26978e284be0c77088e0d1b1a6cd841114d247a21ba205091441aa5d4e68973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37338074$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pammi, Mohan</creatorcontrib><creatorcontrib>Pammi, Mohan</creatorcontrib><creatorcontrib>Haque, Khalid N</creatorcontrib><title>Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates</title><title>Cochrane database of systematic reviews</title><addtitle>Cochrane Database Syst Rev</addtitle><description>Background
Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.
Objectives
To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference s.
Selection criteria
We included randomised controlled trials (RCTs) or quasi‐RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M‐enriched intravenous immunoglobulin (IgM‐enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM‐enriched IVIG with antibiotics.
Data collection and analysis
We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed‐effect model of meta‐analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD.
Main results
We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain.
Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all‐cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD −0.08, 95% CI −0.14 to −0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low‐certainty evidence) and may decrease length of hospital stay (LOS) (MD −7.74, 95% CI −11.72 to −3.76; 2 studies, 157 participants, low‐certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low‐certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low‐certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low‐certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low‐certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low‐certainty evidence) in neonates with sepsis.
Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM‐enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low‐certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low‐certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported.
Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM‐enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low‐certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low‐certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported.
All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons.
Authors' conclusions
Low‐certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM‐enriched IVIG, or PTX with antibiotics compared to IgM‐enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well‐designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.</description><subject>Anti-Bacterial Agents</subject><subject>Anti-Bacterial Agents - adverse effects</subject><subject>Child health</subject><subject>Enterocolitis, Necrotizing</subject><subject>Enterocolitis, Necrotizing - drug therapy</subject><subject>Gastrointestinal Tract Disorders</subject><subject>Humans</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulins, Intravenous</subject><subject>Immunoglobulins, Intravenous - therapeutic use</subject><subject>Infant, Newborn</subject><subject>Infant, Premature</subject><subject>Infections in newborns</subject><subject>Infections in newborns: sepsis</subject><subject>Infectious disease</subject><subject>Lung Diseases</subject><subject>Medicine General & Introductory Medical Sciences</subject><subject>Necrotizing Enterocolitis</subject><subject>Neonatal care</subject><subject>Neonatal infections</subject><subject>Neonatal infections: nosocomial sepsis</subject><subject>Neonatal Sepsis</subject><subject>Neonatal Sepsis - drug therapy</subject><subject>Nosocomial sepsis</subject><subject>Pentoxifylline</subject><subject>Pentoxifylline - adverse effects</subject><subject>Retinopathy of Prematurity</subject><subject>Sepsis</subject><subject>Sepsis - drug therapy</subject><issn>1465-1858</issn><issn>1469-493X</issn><issn>1465-1858</issn><issn>1469-493X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>RWY</sourceid><sourceid>EIF</sourceid><recordid>eNqFUctOwzAQtBCIlsIvVDlyabEdJ3ZOCMpTqkQPcLYcZ9MaJXGxU6B_j6M-VLhwsrUzO7O7g9CQ4DHBmF4RliZEJGI8ucOYUZyMl6ucHaF-B4w65Pjg30Nn3r9jHKcZ5aeoF_M4FpizPprNoGnttynXVWUaiErrotaBautQj2wZeVh64yPVFFED2tnWeNPMo4CCs9pWJhQi0wTQNqoFf45OSlV5uNi-A_T2cP86eRpNXx6fJzfTkWY0ZSNe0DTjAqhgOWDNORYCcEFyolJdCEYIYQVlXFGSq7AezghjRKmkYJCKjMcDdL3RDXvXUOgwkFOVXDpTK7eWVhn5G2nMQs7tpySYCkpSGhQutwrOfqzAt7I2XkNVqbDLystA4xmN4ywL1HRDDQfw3kG59yFYdnnIXR5yl0fnzkLj8HDKfdsugEC43RC-TAVrqa1euOD_j-4flx_mxpxF</recordid><startdate>20230620</startdate><enddate>20230620</enddate><creator>Pammi, Mohan</creator><creator>Pammi, Mohan</creator><creator>Haque, Khalid N</creator><general>John Wiley & Sons, Ltd</general><scope>7PX</scope><scope>RWY</scope><scope>ZYTZH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230620</creationdate><title>Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates</title><author>Pammi, Mohan ; Pammi, Mohan ; Haque, Khalid N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4264-7d26978e284be0c77088e0d1b1a6cd841114d247a21ba205091441aa5d4e68973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Anti-Bacterial Agents</topic><topic>Anti-Bacterial Agents - adverse effects</topic><topic>Child health</topic><topic>Enterocolitis, Necrotizing</topic><topic>Enterocolitis, Necrotizing - drug therapy</topic><topic>Gastrointestinal Tract Disorders</topic><topic>Humans</topic><topic>Immunoglobulin M</topic><topic>Immunoglobulins, Intravenous</topic><topic>Immunoglobulins, Intravenous - therapeutic use</topic><topic>Infant, Newborn</topic><topic>Infant, Premature</topic><topic>Infections in newborns</topic><topic>Infections in newborns: sepsis</topic><topic>Infectious disease</topic><topic>Lung Diseases</topic><topic>Medicine General & Introductory Medical Sciences</topic><topic>Necrotizing Enterocolitis</topic><topic>Neonatal care</topic><topic>Neonatal infections</topic><topic>Neonatal infections: nosocomial sepsis</topic><topic>Neonatal Sepsis</topic><topic>Neonatal Sepsis - drug therapy</topic><topic>Nosocomial sepsis</topic><topic>Pentoxifylline</topic><topic>Pentoxifylline - adverse effects</topic><topic>Retinopathy of Prematurity</topic><topic>Sepsis</topic><topic>Sepsis - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pammi, Mohan</creatorcontrib><creatorcontrib>Pammi, Mohan</creatorcontrib><creatorcontrib>Haque, Khalid N</creatorcontrib><collection>Wiley-Blackwell Cochrane Library</collection><collection>Cochrane Library</collection><collection>Cochrane Library (Open Aceess)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cochrane database of systematic reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pammi, Mohan</au><au>Pammi, Mohan</au><au>Haque, Khalid N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates</atitle><jtitle>Cochrane database of systematic reviews</jtitle><addtitle>Cochrane Database Syst Rev</addtitle><date>2023-06-20</date><risdate>2023</risdate><volume>2023</volume><issue>6</issue><spage>CD004205</spage><pages>CD004205-</pages><issn>1465-1858</issn><issn>1469-493X</issn><eissn>1465-1858</eissn><eissn>1469-493X</eissn><abstract>Background
Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.
Objectives
To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference s.
Selection criteria
We included randomised controlled trials (RCTs) or quasi‐RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M‐enriched intravenous immunoglobulin (IgM‐enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM‐enriched IVIG with antibiotics.
Data collection and analysis
We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed‐effect model of meta‐analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD.
Main results
We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain.
Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all‐cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD −0.08, 95% CI −0.14 to −0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low‐certainty evidence) and may decrease length of hospital stay (LOS) (MD −7.74, 95% CI −11.72 to −3.76; 2 studies, 157 participants, low‐certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low‐certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low‐certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low‐certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low‐certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low‐certainty evidence) in neonates with sepsis.
Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM‐enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low‐certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low‐certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported.
Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM‐enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low‐certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low‐certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported.
All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons.
Authors' conclusions
Low‐certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM‐enriched IVIG, or PTX with antibiotics compared to IgM‐enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well‐designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>37338074</pmid><doi>10.1002/14651858.CD004205.pub4</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1465-1858 |
| ispartof | Cochrane database of systematic reviews, 2023-06, Vol.2023 (6), p.CD004205 |
| issn | 1465-1858 1469-493X 1465-1858 1469-493X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10282162 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Cochrane Library |
| subjects | Anti-Bacterial Agents Anti-Bacterial Agents - adverse effects Child health Enterocolitis, Necrotizing Enterocolitis, Necrotizing - drug therapy Gastrointestinal Tract Disorders Humans Immunoglobulin M Immunoglobulins, Intravenous Immunoglobulins, Intravenous - therapeutic use Infant, Newborn Infant, Premature Infections in newborns Infections in newborns: sepsis Infectious disease Lung Diseases Medicine General & Introductory Medical Sciences Necrotizing Enterocolitis Neonatal care Neonatal infections Neonatal infections: nosocomial sepsis Neonatal Sepsis Neonatal Sepsis - drug therapy Nosocomial sepsis Pentoxifylline Pentoxifylline - adverse effects Retinopathy of Prematurity Sepsis Sepsis - drug therapy |
| title | Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T09%3A41%3A39IST&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=Pentoxifylline%20for%20treatment%20of%20sepsis%20and%20necrotising%20enterocolitis%20in%20neonates&rft.jtitle=Cochrane%20database%20of%20systematic%20reviews&rft.au=Pammi,%20Mohan&rft.date=2023-06-20&rft.volume=2023&rft.issue=6&rft.spage=CD004205&rft.pages=CD004205-&rft.issn=1465-1858&rft.eissn=1465-1858&rft_id=info:doi/10.1002/14651858.CD004205.pub4&rft_dat=%3Cproquest_pubme%3E2827923399%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=2827923399&rft_id=info:pmid/37338074&rfr_iscdi=true |