Neonatal Fungal Infections Research Articles

Fluconazole Doses Used for Prophylaxis of Invasive Fungal Infection in Neonatal Intensive Care Units: A Network Meta-Analysis

To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates. A systematic search was conducted with PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted. Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6?mg/kg. When the incidence of invasive Candida and invasive Candida-related mortality were considered as outcomes, the 3 and 6?mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 [95% credible interval, 1.81-18.94] and 2.63 [1.18-7.02], respectively, and 15.32 [1.54-54.31] and 9.14 [1.26-142.7], respectively), but data for the 3 doses were not statistically significantly different. Use of the lowest fluconazole dose (3?mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.

Profile of fungal septicaemia in new born at a tertiary care hospital in North India

Background: Advances in neonatal management have led to considerable improvement in new-born survival. The objective of this study was to determine the predominant organisms, antifungal sensitivity patterns and clinical risk factors in neonatal fungal blood stream infection cases (BSI) admitted to our hospital.Methods: This is a retrospective study of all neonatal fungal BSI cases between January 2015 to December 2015.Results: Fungal sepsis was found in 50/360 (13.6%) of cases. Non Albicans candida (NAC)species were responsible for 88% of cases with Candida. glabrata (54%)as the most predominant species. Other species isolated were C. tropicalis 9 (18%). C. albicans 6 (12%). C. paraspinolosis 5 (10%), C. Krusei 2 (4%) and C. Kodo1 (2%). Antifungal sensitivity results revealed that most of the NAC isolates especially candida glabrata,candida paraspinolosis were resistant to flucanazole, than Candida albicans. Amphoterician B had greater sensitivity than FLK over NAC species Among the risk factor observed for candidemia were low birth weight (62%), prematurity (60%,), broad spectrum antibiotic use (60%), ventilater support (56%) and total parentral nutrition (50%).Conclusions: The increase in neonatal fungal BSI and resistant organisms highlights the need to review use of strict infection control strategies, appropriate preventive and therapeutic measures such as prophylactic antifungal use and a restrictive policy of antibiotic use.

Generalized erythroderma in a neonate: Rare presentation of nosocomial candidemia with Candida tropicalis

Candida species are currently one of the most common causes of nosocomial infection in neonatal intensive care units with Candida tropicalis emerging as a frequent offending agent. Colonization precedes systemic invasive fungal infections in neonates. It generally manifests with lethargy, increased apneic episodes, feeding intolerance, late-onset thrombocytopenia, hypoglycemia, unexplained hyperglycemia, poor perfusion, and need for increased ventilator requirement. We report a 10-day-old neonate, with late-onset sepsis by C. tropicalis, presenting as generalized erythroderma. We present this case to highlight that nosocomial candidemia with C. tropicalis can present as generalized erythroderma in neonates. Maintaining adequate oral or parenteral fluidintake with monitoring of serum electrolytes is mandatory.

Retrospective analysis of 76 neonates with invasive fungal infection in 2004-2014

Objective To investigate the clinical features of neonatal invasive fungal infection(IFI)so as to guide diagnosis, prevention and treatment of IFI. Methods Seventy-six neonates with IFI admitted to the Neonatal Intensive Care Unit (NICU) at Children's Hospital of Fudan University from 2004 to 2014 were included in the study. Pathogens, clinical manifestation, risk factor exposure, laboratory findings, complications, and clinical outcome of neonatal IFI were analyzed. Results Seventy-six cases were diagnosed as IFI between 2004 and 2014, with an yearly increasing trend. Sixty-eight patients were premature infants (89.5%). Of the 76 cases, except one with unknown birth weight, 11(14.7%), 34(45.3%), 20(26.7%)and 10 (13.3%) cases had birth weight < 1 000 g, (≥1 000-<1 500) g, (≥1 500-<2 500) g and ≥2 500 g, respectively. The pathogens were mainly Candida (74/76, 97.4%), including 26 cases of Candida albicans (34.2%). However, the incidence of non-Candida albicans infection was increasing. Candida guilliermondii was the most common in non-Candida albicans, accounting for 29.2% (14/48). All Candida albicans were sensitive to fluconazole. One strain of Candida glabrata was resistant to fluconazole. The most common risk factors included use of broad-spectrum antibiotics(93.3%, 56/60), parenteral nutrition(70.0%, 42/60), central vein catheterization(53.3%, 32/60), invasive ventilation(40.0%, 24/60) and history of abdominal surgery(21.7%,13/60). Clinical manifestations of IFI included temperature instability, frequent apnea, increased requirement of respiratory support and feeding intolerance. Among all cases, six were diagnosed as central nervous system infection. Of the patients who received cranial MRI, 46.8%(22/47) showed multiple abnormal signals in cerebral parenchyma. Fifty-two patients were cured and seven patients died before discharge, including one death due to fungal infection. Conclusions There is an increasing trend of IFI cases in NICU, especially in premature infants. Non-Candida albicans has become the main pathogenic fungus. There are no specific clinical manifestations in neonatal IFI. Use of broad-spectrum antibiotics, parenteral nutrition and central venous catheterization are common risk factors, and preventive measures should be taken in high-risk infants. In addition, IFI in neonates may affect important organs such as central nervous system, thus early treatment is necessary in suspected patients. Key words: Candidiasis, invasive; Intensive care units, neonatal; Retrospective studies

Clinical characteristics of invasive fungal infection in neonates

Objective To analyze the clinical features of invasive fungal infection in neonates, in order to raise the level of diagnosis and treatment of this disease. Methods We collected the clinical data of 66 cases who were admitted to our neonatal ward between January 2012 and March 2012, and confirmed invasive fungal infection.The data which included general situation, onset time, the first symptoms, laboratory examination results, blood culture results, treatment and outcomes, prognosis and follow-up status were analyzed retrospectively. Results The average onset age of invasive fungal infection was(18.6±9.1) day-old.The clinical manifestations of the children patients were atypical, with the first clinical presentation of apnea, feeding intolerance, fever, poor response and less activity.The laboratory examination results were thrombocytopenia, elevated C-reactive protein and(1, 3) -β-D-glucan.The blood culture results mainly were Candida.And fluconazole treated was effective. Conclusion Fungal infection in neonate is lack of specific clinical manifestations.We should be on high alert for the neonate who has high risk factors of fungal infections.Early diagnosis and prompt treatment is the key to successful treatment. Key words: Neonate; Invasive fungal infection; Clinical characteristics

Research progress on the invasive fungal infections in neonates

Invasive fungal infections(IFI) is significantly increasing in the neonatal intensive care unit recent years.The characteristics of IFI are low diagnosis rate, high mortality and being prone to involve in the nervous system.In this paper, the epidemiology, pathogens, risk factors, diagnosis, treatment and prevention of neonatal IFI are reviewed to improve the understanding of this disease. Key words: Infant, newborn; Fungal infections; Diagnosis; Treatment; Prevention

A case presentation of Voriconazole therapy in a brochopulmonary dysplasia

Premature infants may be more vulnerable to fungal infections because of their immature immune system, poorly developed epithelial skin and mucosal barriers, and the high rate of invasive procedures, such as central venous catheters and intubation, which compromise host defenses (eg, skin integrity).Voriconazole is a newer systemic antifungal agent effective against Candida and Aspergillus. There are few reports of its safe use in newborns. We report the first case report - a 29 gestational age-900 gram baby girl of safe Voriconazole use in a critically ill with profound pancytopenia –huge hepatosplenomegaly due to fungal infection resistant to amphotericin B.With beginning oral Voriconazole all liver functions tests what were severely abnormal returned normal with normalizing of the size of liver and spleen. It was noted to be safe and well tolerated by the newborn. Because of oral administration of it, voriconazole is a very good choice for fungal infections in neonates.

A case of disseminated Candida dubliniensis in a preterm infant: The importance of early detection and management of invasive fungal infections in neonates

This case report highlights the importance of timely diagnosis of disseminated fungal infections in neonates, as well as the increased incidence of infection with non- albicans Candida , and the association with surgical conditions such as necrotising enterocolitis.

Update on the management of Candida infections in preterm neonates

Invasive fungal infections in preterm neonates in the neonatal intensive care unit are predominantly caused by Candida spp, and have a high burden of morbidity and mortality. Effective prophylactic strategies...

Erythema multiforme: A rare presentation of neonatal fungal urinary tract infection

Erythema multiforme (EM) is an acute, self-limiting, mucocutaneous hypersensitivity reaction characterized by distinctive target lesions. Most cases have been attributed to infection. EM occurs mainly in young adults and is extremely rare during the neonatal period. We report an 11-day-old boy who presented with target skin lesions on upper limbs and lower limbs with no other associated symptoms. He had no remarkable maternal, birth, or past medical history. Complete blood count, chest radiography, and herpes simplex virus 1 and 2 immunoglobulin G titers revealed no abnormalities. Urine analysis showed fungal hyphae and culture grew candida albicans. Lesions disappeared after starting antifungal. Pathologic examination showed vacuolar interface change and dyskeratotic cells in the epidermis consistent with EM. This unusual case emphasizes the importance of recognizing diagnostic clues in examining patients.

Recommendations for diagnosis, treatment and prevention of fungal infections in newborns

The article presents the epidemiology and clinical manifestations of neonatal fungal infections. We propose to introduce in neonatal practice guidelines for the diagnosis, treatment and prevention of fungal infections in newborns.

Monitoring neonatal fungal infection with metabolomics

The objective of our study was to evaluate the capability of the metabolomics approach to identify the variations of urine metabolites over time related to the neonatal fungal septic condition. The study population included a clinical case of a preterm neonate with invasive fungal infection and 13 healthy preterm controls. This study showed a unique urine metabolic profile of the patient affected by fungal sepsis compared to urine of controls and it was also possible to evaluate the efficacy of therapy in improving patient health.

Neonatal invasive fungal infection in England 2004–2010

Rates of invasive fungal infection are highest among neonates, especially those of low birthweight. This study aimed to describe the current epidemiology of invasive neonatal fungal infections in a UK neonatal infection surveillance network. From 2004 to 2010 prospective multicentre surveillance was conducted by 14 neonatal units using a web-based database. Clinicians then completed a standardized pro forma for each positive fungal blood and/or cerebrospinal fluid culture. The overall incidence was 2.4/1000 neonatal unit admissions and was highest among babies <1000 g (extreme low birthweight, 18.8/1000). Only five infants (6%) were >1500 g. The majority of infections were caused by Candida albicans (59; 69%) and Candida parapsilosis (17; 20%); 33% of infants had received antifungal prophylaxis. Known risk factors (use of central venous catheter, parenteral nutrition, previous antibiotic use) were common among cases. The attributable case fatality rate was 21% (18/84). Extreme low birthweight infants remain at highest risk of invasive fungal infection and prophylaxis should be particularly considered for this group. The number needing to receive prophylaxis to prevent one case varies significantly among units, hence unit-specific decisions are required. Further research is still needed into the optimal empiric and therapeutic strategies.

Cutaneous Fungal Infection in a Neonatal Intensive Care Unit Patient: A Case Report and Literature Review

Fungal skin infections are not uncommon in healthy, premature or immunocompromised newborns. Healthy neonates usually develop fungal skin infections caused by dermatophytes, Candida and Malassezia species, whereas immunocompromised neonates are more susceptible to skin infections with opportunistic pathogens (Aspergilus, Zygomycetes). Therefore neonatal fungal skin infections can range from generally benign superficial lesions to potentially fatal, deep, necrotic forms with dissemination. We present the case of a premature neonate twin with cutaneous fungal infection in a neonatal intensive care unit. Because there were doubts concerning the correspondence of the clinical features with the cultured species in the newborn, a literature review was performed searching for similar clinical cases.

A prospective study of the patterns and dynamics of colonization with Candida spp. in very low birth weight neonates

Knowledge of fungal colonization patterns in very low birth weight infants (VLBWI) admitted to the neonatal intensive care unit (NICU) is essential in understanding the process of fungal infections in neonates. We analyzed prospectively, during 2009-2010, the patterns and dynamics of fungal colonization in VLBWI, including timing, colonization sites, and species involved. Weekly skin, oropharynx, and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU. None received antifungal prophylaxis. Overall, 118 VLBWI provided 1723 samples; 34 (29%) had 104 positive samples at least once during the first 10 hospitalization weeks. Thirty-nine (33%) weighed < 1000 g; 68 were delivered by cesarean section. Candida albicans (57/104, 55%) and Candida parapsilosis (26/104, 25%) were the main fungi isolated. Eight (24%) VLBWI were colonized during the first week and 23 (68%) during the second week. No differences in colonization were recorded between cesarean section and vaginally delivered VLBWI. The colonization risk at least once during the first 10 weeks was 23% for skin, 14% for oropharynx, 27% for rectum/stool, and 38% for any anatomic site sampled. Persistent colonization was recorded in 5/34 (15%), while transient colonization was found in 14/34 (41%) VLBWI; 16/34 (47%) were discharged or died colonized with Candida spp. Candidemia was diagnosed in 4 (3%) VLBWI and previous/simultaneous colonization was found in 3/4. The cumulative risk of colonization, at any sampled site and at least once during follow-up, was high. Initial colonization occurred most often during the first 2 weeks of life. Colonization dynamics were characterized by various persistence, disappearance, and recolonization patterns. Candidemia was rare.

Mortality related to neonatal and pediatric fungal infections

Thanks to the recent advances in the treatment of neonatal fungal infections, the burden of mortality has been decreasing. However a widely accepted definition is yet to be found, since different thresholds of survival are used in the published trials, and therefore mortality is assumed as occurring 7, 20, 30, or 90 days after treatment, according to the different studies. Regardless of the uncertainty of the definitions, it is more important to know if the patient died with the fungal infection or because of the fungal infection. The new antifungal drugs currently available for neonatal patients were able to increase the survival rates: the attention should, therefore, be focused on the long-term seque­lae, which, on the contrary, still affect a big amount of patients. In particular, neurobehavioral and neurosensorial disorders become often evident with age.

Pediatric and Neonatal Fungal Infections. The Academy project

Pediatric and Neonatal Fungal Infections. The Academy project

Background changing patterns of neonatal fungal sepsis in a developing country

Candida albicans is the predominant isolate in many neonatal fungal bloodstream infections (BSIs), so fluconazole is used as empiric antifungal therapy. To determine the predominant organisms, antifungal sensitivity patterns, clinical and demographic risk factors and crude mortality rate in neonatal fungal BSI cases. This is a review of all neonatal fungal BSI cases between January 2007 and December 2011. Fifty-nine patients were included in the study. Candida parapsilosis (54.2%) was isolated in majority of the cases, followed by C. albicans (27.1%). Fluconazole resistance was present in 16 of 32 cases of C. parapsilosis versus 1 of 16 cases of C. albicans (P = 0.003). Mortality rate was 45.8%. Surgical problems were present in 55.9%. Death was significantly associated with lower birth weight (P = 0.046) and necrotizing enterocolitis (P = 0.034). The increase in neonatal fungal BSI and resistant organisms highlights the need to review use of routine empiric fluconazole and to implement preventive measures.

Pichia fabianii blood infection in a premature infant in China: case report

BackgroundInvasive fungal infections caused by uncommon fungi have increased in recent years. Hospitalized low-birth-weight infants are at high risk for neonatal fungal infections. Pichia fabianii is a rare pathogen causing blood infection, which has reportedly caused only 4 cases of fungemia and 1 case of endocarditis worldwide. Here, we describe the first case of a P. fabianii blood infection in a premature infant in China.Case presentationOn July 28th, a low-birth-weight (LBW, 1760 g) female infant born at 33+4 weeks of gestation was admitted to the pediatric intensive care unit with mild neonatal asphyxia. Until August 2nd, a mechanical respirator was used to assist respiration under the Continuous Positive Airway Pressure (CPAP) model. The baby had an increased body temperature and a fever. To prevent infection, Ceftriaxone Sodium (CS) was administered intravenously for three days, after which Cefepime was administered until August 13th. Chest X-rays showed suspected plaque-like shadows in the right lung. Blood cultures twice tested positive for fungal infection caused by Candida pelliculosa (recognized as Pichia fabianii later), which is first mis-identified by commercial kit. Hence, intravenous fluconazole was administered. However, cultures of other body fluids (e.g., urine, feces and sputum) tested negative for fungal infection. Routine tests and biochemistry of cerebrospinal fluid (CSF) were normal. Latex agglutination of Cryptococcus neoformans and fungi cultures in the CSF were also negative. After 14 days of intravenous fluconazole, blood was re-cultured, the result of which was negative. On August 30th, intravenous fluconazole was suspended. On Sep 3rd, the infant left the hospital in good health.ConclusionsThis is the first case of a blood infection caused by P. fabianii in a LBW premature female infant in China. Risk factors for fungal infection include premature birth, as well as mechanical invasive operation and antibacterial drug usage. Whether such risk factors necessitate prophylactic use of antifungal drugs is an important question that has yet to be fully addressed. Additionally, the pathogen P. fabianii collected in this study was resistant to amphotericin B (AMB) and itraconazole (ITR). With the exception of the azole-resistant endocarditis case, all other cases have not demonstrated such a resistance. Finally, commercial biochemical methods used in routine practice are limited in their ability to identify P. fabianii. Molecular genetic based methods are imperative for identification of uncommon fungal species from disseminated infections.

Effect of Routine Lactobacillus reuteri DSM 17938 use on Rates of Late-onset infection in Extremely-low-birth-weight Infants

Background: Preterm infants are at high risk for late-onset infections due to gram-negative or fungal organisms. Evidence supports that a common source for these organisms may be the gastrointestinal tract. One theoretical way to change the infection rate is to alter the bacterial flora inhabiting the newborn gastrointestinal tract using probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of late-onset gram-negative and fungal infection in neonates with birth weight ≤ 1000 grams. Methods: This is a retrospective cohort study comparing the rates of gram-negative bacterial and fungal infections in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri, and neonates born July 2009 through July 2012 who received routine L. reuteri prophylaxis. Neonates were excluded if they died or were transferred within the fi rst week of life. The remainder were included in the study and recorded as either having late onset infection related to gram negative organisms or fungi, or not having late onset infection. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of infection were compared using Chi square analysis with Fisher exact t-test. Results: Medical records for 354 neonates were reviewed, 232 before- and 122 after-introduction of L. reuteri prophylaxis. Despite a marked reduction in necrotizing enterocolitis and mortality, the incidence of late-onset infection varied from year-to-year, but was not signifi cantly altered by the introduction of routine L. reuteri. No adverse events related to use of L. reuteri were noted. Conclusions: Prophylactic initiation of L. reuteri as a probiotic does not decrease late-onset infection.