Antifungal susceptibility testing and the correlation with clinical outcome in neonatal candidemia.

The objective of this article is to assess the distribution of minimal inhibition concentrations (MIC) for candidal isolates from bloodstreams in neonates and to assess the correlation of clinical outcome with antifungal susceptibility testing. Of the 62 episodes of neonatal candidemia in a Children's Hospital between January 1994 and July 1998, 38 stocked isolates from 38 infants' bloodstreams were available and underwent antifungal susceptibility test according to National Committee for Clinical Laboratory Standards M27-A document. Correlation of clinical response with in vitro results was assessed in 37 patient-episode-isolate events. No less than 90% of these isolates tested were susceptible to amphotericin B, flucytosin, and fluconazole. The ranges of amphotericin B MICs and flucytosin MICs were narrow, ranging from 0.25 to 2 microg/mL, respectively. The range of fluconazole MICs was broad, ranging from 0.25 to >64 microg/mL. Successful therapy was achieved in 18 (62%) of 29 amphotericin B-treated patient-episode-susceptible isolate (MIC < or =1 microg/mL) events and 9 (64%) of 14 fluconazole-treated patient-episode-susceptible isolate events, respectively. Most isolates from the bloodstreams of neonates with candidemia were susceptible to antifungal agents tested but a low MIC of the antifungal agent did not predict successful therapy in this study. Correlating MICs with clinical outcome in neonatal candidemia requires complex evaluation of other factors.     

Disseminated candidemia refractory to caspofungin therapy in an infant with extremely low birth weight

Systemic fungal infections have high morbidity and mortality rates in neonates, especially neonates with an extremely low birth weight (ELBW). Here, we describe a 21-day-old ELBW female infant with an amphotericin B-unresponsive congenital Candida albicans infection that was treated with caspofungin. Blood sterilization was performed during the first episode, but a second episode of candidemia occurred after the discontinuation of caspofungin. Blood sterilization was again performed during the second round of caspofungin treatment, but fungal endocarditis and renal fungal balls still developed during the second episode. Caspofungin can be considered for invasive candidiasis in premature infants, especially in life-threatening situations. As for the focal lesions, more aggressive treatments other than just parenteral antibiotics should be considered. The literature regarding caspofungin therapy for neonatal candidiasis is also reviewed.     

The use of antifungal therapy in neonatal intensive care

Invasive fungal infections remain a significant cause of infection-related mortality and morbidity in preterm infants. Central nervous system involvement is the hallmark of neonatal candidiasis, differentiating the disease's impact on young infants from that among all other patient populations. Over the past decade, the number of antifungal agents in development has grown, but most are not labeled for use in newborns. We summarize the findings of several antifungal studies that have been completed to date, emphasizing those including infant populations. We conclude that more studies are required for antifungals to be used safely and effectively in infants.     

Surfactant therapy for neonatal respiratory distress syndrome in 2013

Abstract

Surfactant whether given prophylactically in the delivery room or to babies with established respiratory distress syndrome (RDS) reduces the severity of RDS, incidence of air leaks and pneumothorax and, most importantly, neonatal death. Despite being the most intensively studied intervention in neonatal medicine, there is still debate among neonatologists regarding the best preparations, the optimal dose and mode of administration and when best to intervene with surfactant. European Consensus Guidelines on the management of RDS have been developed and updated twice since 2007 reflecting changes in practice as new evidence emerges and in this article we summarize current opinion regarding optimal surfactant use in the present era of non-invasive respiratory support.     

Antenatal therapy to minimize neonatal intraventricular hemorrhage

Periventricular-intraventricular hemorrhage is an important problem, resulting in significant mortality and morbidity. Attempts to reduce this complication require an understanding of its pathogenesis. In this chapter a model was proposed, consisting of a series of events resulting in rapid changes of cerebral blood flow and intracranial pressure and leading to rupture of the unique fragile vessels of the germinal matrix and intraventricular regions. Understanding the beneficial physiologic changes induced by such agents such as phenobarbital and vitamin K and that such pharmacologic therapy must be started during the antenatal period has resulted in significant reductions of severe grades of IVH. Further prospective studies are needed to confirm these results using these two drugs alone and in combination. Other potentially beneficial drugs such as indomethacin should be investigated. Although the benefits of such therapy may improve perinatal outcome, the emphasis in our discipline should be the continued attempt to prevent the delivery of these VLBW infants.     

Intravenous gammaglobulin therapy for neonatal alloimmune thrombocytopenia

A clinical experience with the combined use of intravenous gammaglobulin and platelet transfusions in a neonate with alloimmune thrombocytopenia secondary to PLA1 incompatibility is described and compared to a previously affected sibling treated with a conventional regimen of corticosteroids, random donor platelet transfusions, and exchange transfusion for neonatal alloimmune thrombocytopenia.     

Fluconazole:a valuable fungistatic

Fluconazole (Diflucan) is an important drug in obstetrics and gynecology in treating vaginal yeast infections. It is fungistatic and indicated for the treatment of oropharyngeal, esophageal, vaginal, and systemic candidiasis; urinary tract infections; peritonitis; cryptococcal meningitis; and as prophylaxis for bone marrow transplant recipients. It is preferred by many patients for treatment of vaginal candidiasis because it is easier to use than topical medications. It has proven to be as effective as the standard intravaginal creams, mainly because of its ability to penetrate well into body fluids and tissues. Fluconazole’s side effects are mild to moderate in nature. They include gastrointestinal disturbances and headaches. Fluconazole also may interact with many drugs. It is contraindicated in patients taking cisapride and terfenadine. It potentiates oral hypoglycemic agents and may cause patients to have symptomatic hypoglycemia. It also increases the prothrombin time in patients on oral anticoagulants. A single 150-mg dose costs approximately $12.00.     

Evidence-based neonatal drug therapy for prevention of bronchopulmonary dysplasia in very-low-birth-weight infants

Corticosteroids, intramuscular vitamin A and caffeine reduce the risk of bronchopulmonary dysplasia (BPD) in very-low-birth-weight infants. We compared the size of the beneficial drug effects on BPD and evaluated long-term drug safety by estimating the number needed to treat (NNT) and the number needed to harm (NNH) for the outcome of cerebral palsy (CP). When given prophylactically during the first 4 days of life, corticosteroids increase the risk of CP (NNH 22; 95% CI: 12-133). When prescribed between days 7 and 14, corticosteroids reduce the 28-day mortality rate in addition to reducing BPD. Their effect on CP remains uncertain: the limited data available are consistent with a best-case scenario (NNT 15) and a worst-case scenario (NNH 14). Although repeated intramuscular injections of vitamin A during the 1st month of life reduce BPD (NNT 12; 95% CI: 6-94), estimates for CP range from an NNT of 11 to an NNH of 33. Early use of caffeine reduces both BPD and CP. The NNT for BPD is 10 (95% CI: 7-16), while the NNT for CP is 34 (95% CI: 20-132). We conclude that caffeine is the drug of choice for the prevention of BPD in very-low-birth-weight infants. Corticosteroids should be avoided during the first few days of life. However, when given during the 2nd week of life to infants at high risk of BPD corticosteroids may have important short- and long-term benefits. These should be urgently confirmed or refuted in well-designed controlled trials.     

The effect of glucocorticoid therapy in preventing early neonatal complications in preterm delivery

AIM: Premature birth is the single largest cause of perinatal mortality and morbidity in non-anomalous infants in all developed nations. The aim of this study is to survey the role of glucocorticoid therapy in decreasing early neonatal complications in preterm delivery. METHODS: A case control study was carried out on 300 preterm labors. Half the women received one to four 6 mg doses of dexamethasone every 6 hours, depending on the interval between admission and delivery. Neonatal complications were compared between the two groups. RESULTS: Corticosteroid therapy was observed to have the greatest effect in preventing respiratory distress and neonatal mortality between 29-34 gestational weeks. There was a significant relationship between antenatal corticosteroid therapy interval and mortality of preterm neonates. Complications such as respiratory distress, sepsis, pneumonia, and hyperbilirubinemia were significantly lower in the case group than in the control. CONCLUSION: It is recommended that all women at high risk for preterm labor before 35 gestational weeks be given glucocorticoid at least 24 hours before delivery in order to markedly reduce neonatal mortality and morbidity.     

Dexpanthenol therapy reduces lung damage in a hyperoxic lung injury in neonatal rats

Objective: Dexpanthenol (Dxp) plays a major role in cellular defense and in repair systems against oxidative stress and inflammatory response and it has not yet been evaluated in treatment of bronchopulmonary dysplasia (BPD). We tested the hypothesis that proposes whether Dxp decreases the severity of lung injury in an animal model of BPD.

Methods: Forty rat pups were divided into four groups: control, control?+?Dxp, hyperoxia and hyperoxia?+?Dxp. All animals were processed for lung histology and tissue analysis. The degree of lung inflammation, oxidative and antioxidant capacity was assessed from lung homogenates.

Results: Lung injury score and alveol diameter increased in the hyperoxia group (p?<?0.001). Median level of malondialdehyde, total oxidant status and oxidative stress indexes was significantly higher in the hyperoxia group compared to the other groups. The median superoxide dismutase activity in the hyperoxia group was notably less than those of control?+?Dxp and hyperoxia?+?Dxp groups (p?<?0.01). Similarly, lung catalase, glutathione (GSH) peroxidase and reduced GSH activities in the hyperoxia group were significantly lower than other groups. Furthermore, the hyperoxia?+?Dxp group had lower tumor necrosis factor-α and interleukin-1β median levels compared to the hyperoxia group (p?=?0.007).

Conclusion: Dxp treatment results in less emphysematous change as well as decrease in inflammation and oxidative stress markers in an animal model of BPD.     

Rational principles for immunoglobulin prophylaxis and therapy of neonatal infections

Immunotherapy was a common method of treating infectious diseases in the preantibiotic era. Serotherapy was a popular approach to serious infections and employed hyperimmune globulins harvested from various large animals. Such antisera needed to be administered early in the course of the disease and unfortunately was associated with significant risks of anaphylaxis and serum sickness. Because of the allergic risks associated with animal immunoglobulin preparations, the development of methods to isolate human immunoglobulins heralded a new era in immunotherapy. This article examines the uses of immunotherapy in the treatment of neonatal infections.     

Fetal and neonatal cardiovascular complications from beta-sympathomimetic therapy for tocolysis

beta-Sympathomimetic drugs cross the placenta freely. Just as these agents cause serious cardiovascular changes in the mother, they may cause severe cardiovascular complications in the fetus. beta-Sympathomimetic agents for tocolysis have been associated with fetal heart rate and rhythm disturbances, hydrops, stillbirth, neonatal cardiac failure, myocardial ischemia and infarction, and neonatal death. Prospective studies have documented changes in interventricular septa of babies exposed to these drugs. Histologic changes have been reproduced in animal models and in vitro similar to those seen in infants with myocardial disease caused by beta-mimetic therapy. The mechanism of beta-mimetic toxicity appears to be increased myocardial intracellular calcium leading to overexcitation and cell necrosis. Since serious fetal cardiovascular effects may occur with beta-mimetic use, benefits should clearly outweigh risks before these drugs are administered.     

Early discharge with home antibiotic therapy in the treatment of neonatal infection.

OBJECTIVE: To determine the feasibility and cost of home antibiotic therapy for a select group of neonates. METHODS: A cohort of neonates at a university hospital who met criteria for home antibiotic therapy at discharge were prospectively followed (November 1995 to October 1997) for type and duration of antibiotic therapy as well as for hospital readmission. RESULTS: During the study period, 95 infants diagnosed with sepsis, presumed sepsis, pneumonia, or uncomplicated meningitis (having received > 10 days of in-hospital therapy) met prior, established, criteria for home antibiotic therapy. The mean +/- SD birth weight of the cohort was 3160 +/- 526 gm, with a mean gestational age of 38.4 +/- 2.1 weeks. A total of 59 infants (62%) received antimicrobial therapy for a clinical presentation consistent with sepsis or presumed sepsis, and 24 infants (25%) were treated for pneumonia. Ampicillin and gentamicin were prescribed for 56% of the cohort, and ceftriaxone was prescribed for 21% of the cohort. Four of those infants were switched from intravascular ampicillin/gentamicin therapy to intramuscular ceftriaxone after discharge due to loss of intravascular access. With a bilirubin level of > 8, four additional infants were changed from ceftriaxone back to ampicillin and gentamicin to complete coverage. The mean age at discharge was 5.2 days, with a mean hospitalization cost of $6121 for that period. There were no rehospitalizations or emergency department visits secondary to a worsening clinical course. CONCLUSION: In this cohort of neonates who met early discharge and defined home antibiotic therapy criteria, there were no serious complications or treatment failures reported; in addition, there were fewer costs compared with continued inpatient treatment.