title: Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.
abstract: BACKGROUND
  Mortality and morbidity due to neonatal sepsis and necrotizing enterocolitis (NEC) is high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline, a phosphodiesterase inhibitor, is one such agent.
  
  
  OBJECTIVE
  The primary objectives were to assess the effect on mortality and the safety of intravenous pentoxifylline as an adjunct to antibiotic therapy in neonates with suspected or confirmed sepsis and NEC.
  
  
  METHODS
  The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE, EMBASE and CINAHL, Science Citation Index for articles referencing Lauterbach 1996, proceedings of the Pediatric Academic Societies (1990 to 2011), BIOSIS (1992 to 2011), conference proceedings (1992 to 2011), ongoing trials and reference lists of identified RCTs were searched in July 2011.
  
  
  METHODS
  Randomised or quasi-randomised trials assessing the efficacy of pentoxifylline as an adjunct to antibiotics for treatment of suspected or confirmed sepsis or NEC in neonates were eligible.
  
  
  METHODS
  Two review authors independently abstracted information for the outcomes of interest. Typical relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) using fixed effects model are reported for dichotomous outcomes and mean differences for continuous outcomes. NNT was calculated for outcomes for which there was a statistically significant reduction in RD.
  
  
  RESULTS
  In four randomised controlled trials, 227 neonates with suspected or confirmed sepsis were randomised to pentoxifylline or placebo. Pentoxifylline therapy significantly decreased "all cause mortality during hospital stay" in the overall population of infants with sepsis [typical RR 0.40 (95%CI 0.20 to 0.77); typical RD -0.15 (95%CI -0.26 to -0.05); NNT 7 (95%CI 4 to 20)]. Subgroup analyses revealed significant reduction in mortality in preterm infants, infants with confirmed sepsis and gram-negative sepsis. Pentoxifylline treatment significantly decreased length of hospital stay [mean difference -11.20 [95%CI -22.09 to -0.31] but not development of NEC in neonates with sepsis [typical RR 0.29 (95%CI 0.07 to 1.24); typical RD -0.20 (95%CI -0.41 to 0.01)]. No adverse effects due to pentoxifylline were noted. No completed trial of treatment with pentoxifylline for treatment of NEC was identified.
  
  
  CONCLUSIONS
  Current evidence from four small studies suggests that the use of pentoxifylline as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. Researchers are encouraged to undertake large well-designed multicenter trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and adverse outcomes in neonates with suspected or confirmed neonatal sepsis and NEC.
authors: Division of Neonatology, Department of Child Health, Queen Mary's Hospital for Children, Epsom & St Helier NHS Trust, Wrythe Lane, Carshalton, Surrey, UK, SM5 1AA.
authors: Khalid N
authors: KN
authors: Haque
authors: Mohan
authors: M
authors: Pammi
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D017024:Chemotherapy, Adjuvant; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline