Incidence Of Fungal Colonization Research Articles

Efficacy and safety of fluconazole in prophylaxis of invasive fungal infections in very low birth weight infants: a Meta analysis

To assess the efficacy and safety of fluconazole in the prophylaxis of invasive fungal infection in very low birth weight (VLBW) infants. Databases including PubMed, Embase, the Cochrane Library, Wanfang Data, Weipu, and CNKI were searched for randomized controlled trials (RCTs) of prophylactic fluconazole in VLBW infants. Review Manager 5.3 software was used to perform a Meta analysis of the included studies. A total of 12 RCTs were included, involving 1 679 VLBW infants. The Meta analysis showed that prophylactic fluconazole significantly reduced the incidence of invasive fungal infection (RR=0.44, 95%CI: 0.27-0.71, P<0.001), the incidence of fungal colonization (RR=0.31, 95%CI: 0.24-0.40, P<0.001), and the mortality during hospitalization (RR=0.74, 95%CI: 0.58-0.94, P=0.01) compared with the control group. There were no significant differences between VLBW infants using different doses of fluconazole in the incidence of invasive fungal infection and fungal colonization (P>0.05). No significant differences were found in the incidence of fluconazole resistance and complications between the fluconazole and control groups (P>0.05). Prophylactic fluconazole can effectively and safely prevent invasive fungal infection in VLBW infants, even at a small dose.

Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial

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.

Fungal Prophylaxis and Chronic Lung Allograft Dysfunction

Prior studies demonstrate that lung transplant recipients (LTRs) experience the highest rate of invasive mold infections amongst all transplant recipients. Aspergillosis is the most common offender, and aspergillus colonization and invasive disease have been linked to chronic lung allograft dysfunction (CLAD). There are no standardized guidelines regarding fungal prophylaxis strategy or agent selection. This study examined the relationship between post-transplant antifungal prophylaxis and freedom from CLAD. This single-center retrospective analysis evaluated 566 adult LTRs from July 2, 2005 to December 28, 2015. Fungal prophylaxis practices evolved during the study period from targeted antifungal prophylaxis (TAP) to universal antifungal prophylaxis (UAP) for the first 6 months post-transplant with either voriconazole or posaconazole. A Kaplan-Meir analysis and Cox regression were performed to estimate freedom from CLAD at 3 years for TAP versus UAP patients. A similar approach was used to examine the relationship between freedom from CLAD and discharge antifungal selection (none, voriconazole, or posaconazole). Freedom from CLAD at 3 years post-transplant in the TAP versus UAP cohorts was 65% and 68%, respectively (P=0.35). The relative risk of CLAD was not significantly reduced in the UAP cohort even when adjusting for pre-transplant disease, transplant type, and induction therapy (hazard ratio 0.83; 95% confidence interval 0.63-1.13; P=0.24). Freedom from CLAD at 3 years post-transplant with patients grouped by discharge antifungal regimen was as follows: no prophylaxis 67%, voriconazole 68%, and posaconazole 70% (P=0.65). There was also no significant difference in risk of CLAD across patients grouped by discharge antifungal regimen following multivariable adjustment. There was no significant difference in freedom from CLAD at 3 years post-transplant for LTRs managed under a TAP versus UAP strategy or for these patients when grouped by discharge antifungal regimen. These results, while unexpected, pique interest in further investigation, particularly elucidating the relationship between prophylaxis and incidence of fungal colonization and invasive disease. Pursuing these avenues of study will advance our understanding of the utility and benefit of fungal prophylaxis in the LTR population.

VIRULENT PROPERTIES OF GENUS CANDIDA IN PATIENTS WITH PERSISTENT BRONCHIAL ASTHMA AND LONG-TERM TREATMENT WITH INHALED STEROIDS

Aim. The aim of this study was to investigate virulent properties of the genus Candida spp. in patients with persistent bronchial asthma and long-term treatment with inhaled steroids. Methods. In this study, virulent properties of the genus Candida spp. were investigated in oropharyngeal smears of 30 patients with persistent asthma treated with moderate-to-high dose inhaled corticosteroids (ICS) for at least 1 year. A control group included 15 steroid-naive asthmatic patients. Fungi were identified by conventional methods (morphology, presence of germination tubes, chlamydospores, fermentation of carbohydrates). Sensitivity to antibiotics was determined by disk method on the Saburo agar medium. Adhesion was assessed in a model with nitrocellulose film and immobilized hemoglobin. Proteinase activity was measured by the ELISA method in supernatant at two pH values: acidic (pH = 4.5) or weakly alkaline (pH = 7.8). CD cell leukocyte receptor proteolysis was evaluated by the cytofluorometrics method. Results. An incidence of fungal colonization of the pharynx in ICS-treated patients with bronchial asthma was 76.7 %. Most strains were highly virulent as they had significantly higher adhesive and enzymatic activity and multi-drug resistance to antifungals compared to control group. Conclusion. The ability of these strains to secrete proteolytic enzymes against CD4+ T-lymphocyte surface receptors could provide an additional immunomodulatory mechanism in Candida albicans invasion.

Effects of Chlorhexidine Oral Decontamination on Respiratory Colonization during Mechanical Ventilation in Intensive Care Unit Patients

We conducted a retrospective cohort study to assess respiratory colonization before and after the use of chlorhexidine oral decontamination among a cohort of intensive care unit patients who received mechanical ventilation. We observed a decrease in the prevalence of Enterobacteriaceae and an increase in the incidence of fungal colonization. Chlorhexidine oral decontamination might have a differential effect on respiratory colonization.

Bovine Lactoferrin Prevents Invasive Fungal Infections in Very Low Birth Weight Infants: A Randomized Controlled Trial

Lactoferrin is a mammalian milk glycoprotein involved in innate immunity. Recent data show that bovine lactoferrin (bLF) prevents late-onset sepsis in preterm very low birth weight (VLBW) neonates. This is a secondary analysis of data from a multicenter randomized controlled trial where preterm VLBW neonates randomly received bLF (100 mg/day; group A1), bLF + Lactobacillus rhamnosus GG (10(6) colony-forming units per day; group A2), or placebo (group B) for 6 weeks. Here we analyze the incidence rates of fungal colonization, invasive fungal infection (IFI), and rate of progression from colonization to infection in all groups. This study included 472 neonates whose clinical, nutritional, and demographical characteristics were similar. Overall, the incidence of fungal colonization was comparable (17.6%, 16.6%, and 18.5% in A1, A2, and B, respectively; P = .89 [A1] and .77 [A2]). In contrast, IFIs were significantly decreased in A1 and A2 (0.7% and 2.0%, respectively) compared with B (7.7%; P = .002 [A1] and .02 [A2]), and this was significantly true both in <1000 g (0.9% [A1] and 5.6% [A2], vs 15.0%) and in 1001 to 1500 g infants (0% and 0% vs 3.7%). The progression rate colonization-infection was significantly lower in the bLF groups: 3.7% (A1) and 12% (A2), vs 41.9%; P < .001 (A1) and P = .02 (A2). No IFI-attributable deaths occurred in the treatment groups, versus 2 in placebo. No adverse effects or intolerances occurred. Prophylactic oral administration of bLF reduces the incidence of IFI in preterm VLBW neonates. No effect is seen on colonization. The protective effect on IFI is likely due to limitation of ability of fungal colonies to progress toward invasion and systemic disease in colonized infants.

A Review of Candida Prophylaxis in the Neonatal Intensive Care Population

To review the efficacy and safety of antifungal prophylaxis in the neonatal intensive care setting. English-language literature was accessed using MEDLINE (January 1988- December 2010). The following Medical Subject Heading (MeSH) search terms were used: "amphotericin B," "fluconazole," "nystatin," "itraconazole," "caspofungin," "voriconazole," "Candida," "prevention and control," and "critically ill." Literature was further limited to studies focusing on patient birth to 6 months of age. Abstracts and original research articles were included. Preference was given to published controlled trials. Articles providing descriptions of the safety and effectiveness of antifungal prophylaxis in neonatal intensive care patients were also used in this review. Twenty-two studies have evaluated the impact of antifungal prophylaxis on Candida colonization or invasive infections in the Neonatal Intensive Care Unit (NICU). The two antifungal agents most commonly studied were nystatin and fluconazole. All of the nystatin studies demonstrated that nystatin is effective at reducing fungal colonization and invasive fungal infections. All of the studies designed to evaluate the impact of fluconazole prophylaxis on fungal colonization demonstrated a reduction in the incidence of fungal colonization with fluconazole prophylaxis. A total of 12 of 16 studies that evaluated the impact of fluconazole prophylaxis on the incidence of invasive fungal infections demonstrated a reduction in invasive fungal infections with fluconazole prophylaxis. Two studies found no difference between fluconazole and nystatin when used for prophylaxis. Antifungal prophylaxis appears to be effective in reducing the incidence of Candida colonization and invasive Candida infections in the NICU. Antifungal prophylaxis also appears to be safe in the NICU population. The impact of antifungal prophylaxis on resistance patterns could be significant and needs to be evaluated long term before widespread prophylaxis can be recommended.

Prophylactic Fluconazole Is Effective in Preventing Fungal Colonization and Fungal Systemic Infections in Preterm Neonates: A Single-Center, 6-Year, Retrospective Cohort Study

Despite the promising preliminary results observed in extremely low birth weight (ELBW) populations, the use of fluconazole to prevent fungal colonization and infection in preterm neonates in the NICU is still an open question and not yet recommended as a standard of care. We have reviewed our 6-year series to assess the effectiveness and safety of this form of prophylaxis. This retrospective study consisted of 465 neonates who weighed < 1500 g at birth and were admitted to our NICU in the period 1998-2003. Those who were born between 1998 and 2000 and did not receive fluconazole prophylaxis (group A, n = 240) were compared with those who were born between 2001 and 2003 and treated with fluconazole until the 30th day of life (45th for neonates < 1000 g at birth; group B, n = 225). Weekly surveillance cultures were obtained from all patients. Incidence of fungal colonization, incidence of systemic fungal infection (SFI), rate of progression from colonization to infection, and mortality rates attributable to fungi were calculated for both groups and separately for neonates who were < 1000 g (ELBW) and were 1001 to 1500 g (NE-VLBW) at birth. Overall fungal colonization was significantly lower in group B (24.0%) than in group A (43.8%; relative risk [RR]: 0.406; 95% confidence interval [CI]: 0.273-0.605). The same was true of neonates with colonization in multiple sites (2.6% vs 5.8%) and of those with colonization from high-risk sites (5.8% vs 19.2%). SFI incidence was significantly lower in group B (10 of 225 cases; 4.4%) than in group A (40 of 240 cases; 16.7%; RR: 0.233; 95% CI: 0.113-0.447). Reduction of both colonization and SFI in group B was greater in the ELBW neonates and also significant in the NE-VLBW neonates. Rate of progression from colonization to infection was significantly lower in group B (0.17 vs 0.38; RR: 0.369; 95% CI: 0.159-0.815). Crude mortality rate attributable to Candida species was 1.7% (4 of 240) in group A vs 0% (0 of 225) in group B. Overall mortality rate (any cause before hospital discharge) was similar in the two groups (11.2% vs 10.6%), but in colonized infants (n = 159), it was significantly lower in group B (3.7% vs 18.1%; RR: 0.174; 95% CI: 0.039-0.778). The incidence of natively fluconazole-resistant fungal species did not increase over the years, and patterns of sensitivity to fluconazole remained the same. No adverse reaction related to fluconazole occurred. Prophylactic fluconazole significantly reduces the incidence of colonization and systemic infection by Candida species in both ELBW and NE-VLBW neonates and decreases the rates of progression from initial colonization to massive colonization and to systemic infection. All VLBW neonates may benefit from fluconazole prophylaxis.

176 Early-Onset Neutropenia is Associated with Heavy Fungal Colonization In The 1st Month of Life in Very Low Birth Weight Neonates

Background: Fungal Colonization (FC), mostly by Candida spp., and subsequent invasive fungal infection are increasingly frequent features in preterm neonates in NICUs, and several risk factors have been found associated to them. The objective of this study was to evaluate the role of Early-Onset Neutropenia (EON) in the development of FC in preterm very low birth weight (VLBW) neonates in NICU. Methods: Medical records of all <1500 g birth weight neonates admitted to our 3rd level Facility between 1997 and 2003 and survived more than 1 week were reviewed. Neonates with baseline fungal colonization were excluded, thus final number of considered neonates was n=424. For all neonates we recorded: a) the presence of neutropenia in the first week of life (EON), diagnosed with Manroe (J Pediatr 1979) and Mouzinho (Pediatrics 1994) reference values (n=52, 12.2%); b) the presence of FC (at least one site), the number and the type of sites colonized during the first month of life. In 25 on 52 neutropenic infants, a 3-days course of Filgrastim (10 mg/kg/die) was performed during the 1st week of life with normalization of the neutrophil count always before the 8th day of life. In neutropenic not treated neonates neutrophil count became spontaneously normal before the beginning of 3rd week of life. Statistical analysis was performed by Chi-square, ANOVA and T-test using SPSS 8.0 for Windows. Results: Statistical analysis did not show significant differences between neutropenic and not neutropenic neonates as for mean gestational age and birth weight, sex, race, outcome and presence of the most common risk factors associated with FC. Incidence of FC in the 2nd, 3rd and 4th week of life was significantly higher in neutropenic (n=32/52, 61.5%) than in not neutropenic patients (n=134/372, 36%) (Chi-square 14.288, OR 0.32; p<0.001). Intensity (as number of different sites affected) and severity (as number of risk sites affected) of FC were as well higher in the neutropenic patients (p<0.002 and p<0.001 respectively). Treatment with Filgrastim did not change the relative risk for colonization: FC was present in 60% of neutropenic treated neonates and 64% of not treated (p<0.28, NS). Conclusion: EON in VLBW neonates significantly influences the rate of colonization by fungal spp. in the first month of life, causing a higher risk that cannot be corrected by filgrastim therapy. VLBW neonates with EON should be carefully monitored for fungal colonization during their stay in NICU, and should undergo prophylactic measures to prevent it.