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Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants.

ABSTRACT: BACKGROUND:Invasive fungal infection is an important cause of mortality and morbidity in very preterm and very low birth weight infants. Early diagnosis is difficult and treatment is often delayed. Systemically absorbed antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection in this population. OBJECTIVES:To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS:We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 8), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews. SELECTION CRITERIA:Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very low birth weight infants. DATA COLLECTION AND ANALYSIS:We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS:We identified 15 eligible trials enrolling a total of 1690 infants. Ten trials (1371 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio (RR) 0.43, 95% confidence interval (CI) 0.31 to 0.59; risk difference (RD) -0.09, 95% CI -0.12 to -0.06). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies. Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.79, 95% CI 0.61 to 1.02; typical RD -0.04, 95% CI -0.07 to 0.00). Very limited data on long-term neurodevelopmental outcomes were available. Three trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. AUTHORS' CONCLUSIONS:Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very preterm or very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of many of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.

SUBMITTER: Cleminson J

PROVIDER: S-EPMC7156892 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSystemic fungal infection (SFI) is one of leading causes of morbidity and mortality in very low birth weight (VLBW) preterm infants. Because early diagnosis of SFI is challenging due to nonspecific manifestations, prophylaxis becomes crucial. This study aimed to assess effectiveness of oral nystatin as an antifungal prophylaxis to prevent SFI in VLBW preterm infants.MethodsA prospective, open-labelled, randomized controlled trial was performed in a neonatal intensive care unit (NICU) of an academic hospital in Indonesia. Infants with a gestational age ≤ 32 weeks and/or birth weight of ≤ 1500 g with risk factors for fungal infection were assessed for eligibility and randomized to either an intervention group (nystatin) or control group. The intervention group received 1 ml of oral nystatin three times a day, and the control group received a dose of 1 ml of sterile water three times a day. The incidence of fungal colonization and SFI were observed and evaluated during the six-week study period. Overall mortality rates and nystatin-related adverse drug reactions during the study period were also documented.ResultsA total of 95 patients were enrolled. The incidence of fungal colonization was lower among infants in nystatin group compared to those in control group (29.8 and 56.3%, respectively; relative risk 0.559; 95% confidence interval 0.357-0.899; p-value = 0.009). There were five cases of SFI, all of which were found in the control group (p-value = 0.056). There was no difference in overall mortality between the two groups. No adverse drug reactions were noted during the study period.ConclusionsNystatin is effective and safe as an antifungal prophylactic medication in reducing colonization rates in the study population. Whilst the use of nystatin showed a potential protective effect against SFI among VLBW preterm infants, there was no statistical significant difference in SFI rates between groups.Trial registrationNCT03390374. Registered 4 January 2018 - Retrospectively registered.

Project description:ObjectiveCan a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities?Study designProspectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always employ this therapy for VLBW infants, (2) never use this therapy, (3) employ this questionable therapy thoughtfully, only in certain circumstances and (4) this therapy has insufficient evidence of efficacy and safety. Extensive staff education emphasized evidence-based potentially better practice (PBP) selection with compliance checks, appreciation of intertwined co-morbidities and prioritizing infant risk reduction strategies.ResultsControl included 221 infants, mean (s.d.) age 29 (2.6) weeks, birth weight 1129 (257)?g and Study included 197 infants, 29 (2.7) weeks, 1093 (292)?g. One hundred and four distinct therapies were placed into categories 1 to 4, with 32 specific compliance checks. Overall mean compliance with the process checks during the second era was 70%, high: 100% (exclusive breast milk use), low: 24% (correct pulse oximetry alarm settings). Morbidity and mortality rates did not significantly change during the second era.ConclusionsIn our NICU with favorable morbidity rates, an expanded effort using a comprehensive therapy guideline for VLBW infants did not further improve outcomes. We need deeper understanding of continuous quality improvement (CQI) fundamentals, therapy compliance, co-morbidity relationships and enhanced sensitivity of risk assessment. Our innovative Antifragility PBP guideline could be useful to other NICUs seeking improvement in VLBW infant morbidities, as we offer a reasoned and concise template of a broad array of therapies categorized efficiently for transparency and review, designed to enhance responsible CQI decision-making.

Project description:IMPORTANCE:Thrombocytopenia and intraventricular hemorrhage (IVH) are common among very-low-birth-weight (VLBW) infants. Survey results suggest that US neonatologists frequently administer platelet transfusions to VLBW infants with mild to moderate thrombocytopenia. OBJECTIVES:To characterize platelet transfusion practices in US neonatal intensive care units (NICUs), to determine whether severity of illness influences platelet transfusion decisions, and to examine the association between platelet count (PCT) and the risk for IVH in the first 7 days of life. DESIGN, SETTING, AND PARTICIPANTS:This multicenter, retrospective cohort study included 972 VLBW infants treated in 6 US NICUs, with admission dates from January 1, 2006, to December 31, 2007. Data were collected from all infants until NICU discharge or death (last day of data collected, December 4, 2008). Data were entered into the central database, cleaned, and analyzed from May 1, 2009, to February 11, 2016. INTERVENTION:Platelet transfusion. MAIN OUTCOMES AND MEASURES:Number of platelet transfusions and incidence of IVH. RESULTS:Among the 972 VLBW infants (520 [53.5%] male; mean [SD] gestational age, 28.2 [2.9] weeks), 231 received 1002 platelet transfusions (mean [SD], 4.3 [6.0] per infant; range, 1-63 per infant). The pretransfusion PCT was at least 50?000/?L for 653 of 998 transfusions (65.4%) with this information. Two hundred eighty-one transfusions (28.0%) were given during the first 7 days of life. During that period, platelet transfusions were given on 35 of 53 days (66.0%) when the patient had a PCT less than 50?000/?L and on 203 of 436 days (46.6%) when the patient had a PCT of 50?000/?L to 99?000/?L. At least 1 marker of severe illness was present on 198 of 212 patient-days (93.4%) with thrombocytopenia (PCT, <100?000/?L) when a platelet transfusion was given compared with 113 of 190 patient-days (59.5%) with thrombocytopenia when no platelet transfusion was given. Thrombocytopenia was a risk factor for intraventricular hemorrhage during the first 7 days of life (hazard ratio, 2.17; 95% CI, 1.53-3.08; P?<?.001). However, no correlation was found between severity of thrombocytopenia and risk for IVH. After controlling for significant clinical factors and thrombocytopenia, platelet transfusions did not have a significant effect on the incidence of IVH (hazard ratio, 0.92; 95% CI, 0.49-1.73; P?=?.80). CONCLUSIONS AND RELEVANCE:A large proportion of platelet transfusions were given to VLBW infants with PCT greater than 50?000/?L. Severity of illness influenced transfusion decisions. However, the severity of thrombocytopenia did not correlate with the risk for IVH, and platelet transfusions did not reduce this risk.

Project description:ImportanceReduced death and neurodevelopmental impairment among infants is a goal of perinatal medicine.ObjectiveTo assess the association between surgery during the initial hospitalization and death or neurodevelopmental impairment of very low-birth-weight infants.Design, setting, and participantsA retrospective cohort analysis was conducted of patients enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998 through 2009 and evaluated at 18 to 22 months' corrected age. Twenty-two academic neonatal intensive care units participated. Inclusion criteria were birth weight 401 to 1500 g, survival to 12 hours, and availability for follow-up. A total of 12 111 infants were included in analyses.ExposuresSurgical procedures; surgery also was classified by expected anesthesia type as major (general anesthesia) or minor (nongeneral anesthesia).Main outcomes and measuresMultivariable logistic regression analyses planned a priori were performed for the primary outcome of death or neurodevelopmental impairment and for the secondary outcome of neurodevelopmental impairment among survivors. Multivariable linear regression analyses were performed as planned for the adjusted mean scores of the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development, Second Edition, for patients born before 2006.ResultsA total of 2186 infants underwent major surgery, 784 had minor surgery, and 9141 infants did not undergo surgery. The risk-adjusted odds ratio of death or neurodevelopmental impairment for all surgery patients compared with those who had no surgery was 1.29 (95% CI, 1.08-1.55). For patients who had major surgery compared with those who had no surgery, the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52 (95% CI, 1.24-1.87). Patients classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who had no surgery, the adjusted risk of neurodevelopmental impairment was greater and the adjusted mean Bayley scores were lower.Conclusions and relevanceMajor surgery in very low-birth-weight infants is independently associated with a greater than 50% increased risk of death or neurodevelopmental impairment and of neurodevelopmental impairment at 18 to 22 months' corrected age. The role of general anesthesia is implicated but remains unproven.

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Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants.

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