The colonization with Candida species is more harmful in the second trimester of pregnancy.

PURPOSE: Vaginal colonization with Candida species (spp.) during pregnancy has been associated with impaired pregnancy outcomes. There is a reduction in spontaneous preterm birth among women with recurrent asymptomatic colonization of Candida who were treated with clotrimazole. This study aimed to evaluate the impact of the trimester of vulvovaginal colonization with Candida species. METHODS: Data from all women, who were tested positive for the vaginal colonization with Candida spp. during the first or second trimester of pregnancy, and who registered for a planned birth at our tertiary referral center between 2005 and 2014 were retrospectively analyzed. Their preterm birth rate served as the primary outcome variable. Secondary outcome variables were neonatal birthweight and Apgar score. RESULTS: Overall, 1066 women were eligible for the study. In 673 women (63%), who were diagnosed with Candida spp. during the first trimester of pregnancy, the rate of preterm birth was 10% (N = 64). In 393 women (37%), who were diagnosed with candidosis during the second trimester, the preterm birth rate was 18% (N = 71; p = 0.0002). Neonates of women, who presented with vulvovaginal candidosis during the first trimester, had a mean birthweight of 3243 g, compared to 2989 g in the group with a second trimester colonization (p < 0.0001). CONCLUSION: Women who are colonized with Candida spp. during the second trimester of pregnancy have higher rates of preterm birth and lower neonatal birthweight than those who are colonized during the first trimester of their pregnancy. Screening programs for asymptomatic Candida colonization should take this information into account.

Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, P<.001 in propensity score-matched subgroups). Administration of antifungal agents was not associated with A. baumannii VAP (29% vs. 21%, P=.153) but with higher in-hospital mortality (53% vs. 39%, P=.037). Candida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP.

Effect of norfloxacin therapy for acute, uncomplicated lower urinary tract infection on vaginal Candida prevalence.

INTRODUCTION AND HYPOTHESIS: Acute uncomplicated lower urinary tract infections (UTI) and vulvovaginal candidiasis (VVC) both occur frequently in women. Although VVC is believed to commonly occur after antibiotic therapy, few studies have demonstrated this association. Thus, the aim of the study was to estimate the prevalence of colonization by Candida spp. and VVC after norfloxacin (NOR) use for UTI and the effects on the vaginal microbiota and inflammatory process. METHODS: This was a prospective cohort study of women with culture-proven UTI who were treated with NOR (antibiotic group). The control group consisted of women with noninfectious diseases or in preventive care. Candida vaginal infections were monitored both clinically and mycologically at baseline and at the follow-up evaluation. RESULTS: All women showed UTI remission after NOR treatment, and no woman in either group, antibiotic and control, showed symptoms of VVC. Both groups showed similar ratios of a positive Candida culture at baseline (6.7 % and 12.8 %, respectively) and at follow-up (3.3 % and 8.5 %, respectively) (p = 0.2768 and p = 0.5035, respectively). The antibiotic group showed no increased risk of Candida colonization or VVC after NOR treatment compared with the control group [odds ratio (OR) 0.556, 95 % confidence interval (CI) 0.2407-10.05]. CONCLUSIONS: NOR was effective for UTI treatment, did not increase the risk of vaginal colonization by Candida or VVC, and did not lead to major disturbances of the vaginal microbiota.

The Correlation Between Candida Colonization of Distinct Body Sites and Invasive Candidiasis in Emergency Intensive Care Units: Statistical and Molecular Biological Analysis.

Both statistical and molecular biological methods were used to evaluate the association between Candida colonization of different body sites and invasive candidiasis (IC) and analyse the potential infection sources of IC. Candida surveillance cultures from the urine, sputum, rectum and skin were performed on patients admitted to an emergency intensive care units (EICU) of a tertiary care hospital in Shanghai, China, from February 2014 to January 2015. Specimens were collected once a week at admission and thereafter. The patients' clinical data were collected, and Candida isolates were genotyped using polymorphic microsatellite markers. A total of 111 patients were enrolled. Patients with positive urine (23.3 vs. 2.5 %, p = 0.001) and rectal swab (13.6 vs. 0 %, p = 0.010) cultures were more likely to develop IC. However, the risk for IC was not significantly different among patients with and without respiratory (10.0 vs. 5.8 %, p = 0.503) and skin (33.3 vs. 6.5 %, p = 0.056) colonization. Gene microevolution frequently occurred at rectal swab and urine sites, and IC with possible source of infection was caused by rectal isolates (2/7), urine isolates (4/7) and sputum isolate (1/7).The colonization of gut and urinary tract maybe more relevant indicators of IC, which should be taken into consideration when selecting practical body sites for Candida surveillance cultures.

Multifocal candidiasis can be considered a form of invasive candidiasis in critically non-neutropenic patients.

Candida infections can be serious in intensive care unit (ICU) patients, as Candida is an organism that specially colonizes the digestive system. In immunocompromised patients, treatment is protocolized, but in non-neutropenic patients, it is not well established. On the other hand, the treatment of this type of infection is not absent of adverse effects. The prevalence of fungal infections, especially candidiasis, and its mortality in the ICU is high, mainly due to the lack of diagnosis and absence of treatment criteria, because they are often detected in the disseminated candidiasis phase, such as candidemia. One of the indicators of the progression of the disease is the presence of Candida in more than two different foci, named Candida multifocality, within the concept of invasive candidiasis. In fact, the invasive fungal diseases in adult patients i intensive care unit (FUNDICU) project was created to optimize the management of candidiasis. The management of candidiasis in ICU patients first requires the identification of patients at high risk of candidiasis, which must be performed based on the evidence of immune dysregulation, higher severity index (acute physiologic assessment and chronic health evaluation and multiple organ dysfunction syndrome), long ICU stays or other factors such as mechanical ventilation or us of broad-spectrum antibiotics. To increase detection and dispense the appropriate antifungal at an early stage, it is necessary to include the concept of multifocality in invasive candidiasis with screening of different foci. Antifungal treatment reduces mortality both overall and attributable to Candida. Detecting a high invasive candidiasis risk is a patient safety concept and should be treated as such. Identifying patients (critically non-neutropenic adult patients with severe multiple organ dysfunction syndrome and the first isolation of Candida spp. in a study sample of possible secondary infection) and demonstrating invasive candidiasis (multifocal or disseminated) require urgent initiation of antifungal treatment to minimize mortality attributable to invasive candidiasis in the ICU and eliminate mortality rates above 50%.

White-opaque switching in Candida albicans: cell biology, regulation, and function.

SUMMARYCandida albicans remains a major fungal pathogen colonizing humans and opportunistically invading tissue when conditions are predisposing. Part of the success of C. albicans was attributed to its capacity to form hyphae that facilitate tissue invasion. However, in 1987, a second developmental program was discovered, the "white-opaque transition," a high-frequency reversible switching system that impacted most aspects of the physiology, cell architecture, virulence, and gene expression of C. albicans. For the 15 years following the discovery of white-opaque switching, its role in the biology of C. albicans remained elusive. Then in 2002, it was discovered that in order to mate, C. albicans had to switch from white to opaque, a unique step in a yeast mating program. In 2006, three laboratories simultaneously identified a putative master switch gene, which led to a major quest to elucidate the underlying mechanisms that regulate white-opaque switching. Here, the evolving discoveries related to this complicated phenotypic transition are reviewed in a quasi-chronological order not only to provide a historical perspective but also to highlight several unique characteristics of white-opaque switching, which are fascinating and may be important to the life history and virulence of this persistent pathogen. Many of these characteristics have not been fully investigated, in many cases, leaving intriguing questions unresolved. Some of these include the function of unique channeled pimples on the opaque cell wall, the capacity to form opaque cells in the absence of the master switch gene WOR1, the formation of separate "pathogenic" and "sexual" biofilms, and the possibility that a significant portion of natural strains colonizing the lower gastrointestinal tract may be in the opaque phase. This review addresses many of these characteristics with the intent of engendering interest in resolving questions that remain unanswered.

Evaluation of Candida colonization index, molecular identification, and antifungal susceptibility pattern of Candida species isolated from critically ill pediatric patients: A single-center study in Iran.

Background and Purpose: Given the high mortality rate of invasive candidiasis in hospitalized pediatric patients, it is crucial to establish a predictive system to achieve early diagnosis and treatment of patients who are likely to benefit from early antifungal treatment. This study aimed to assess the Candida colonization index, species distribution, and antifungal susceptibility pattern of Candida strains isolated from pediatric patients with high Candida colonization index (CI). Materials and Methods: This study was carried out at the Children's Medical Center in Tehran-Iran. In total, 661 samples were collected from 83 patients. The Candida CI was calculated according to the descriptions of previous studies. The isolates were identified using polymerase chain reaction-based techniques. The Clinical and Laboratory Standard Institute protocol M60 was used to conduct the antifungal susceptibility test. Results: A colonization index greater than 0.5 was confirmed in 29 cases (58% of positive samples) with two children developing candidemia. Candida albicans (n=53, 49.5%) was the most common Candida species in patients with CI > 0.5. Except for acute lymphoblastic leukemia, no risk factors were linked to a high index in colonized children (P > 0.05). Twelve isolates (7.01%) were multi-azole resistant with high MICs against both isavuconazole and ravuconazole and seven strains (4.09%) were echinocandins resistant. Conclusion: In pediatric intensive care units, patients are at risk of fungal infection, particularly candidemia. In this study, more than half of the children with positive yeast cultures had CI > 0.5, and 6.8% developed candidemia.

Epidemiology and Prevalence of Oral Candidiasis in HIV Patients From Chad in the Post-HAART Era.

Oral candidiasis remains a common problem in HIV-infected individuals, especially in sub-Saharan Africa. Here, we performed the first study in Chad on the prevalence of oral yeasts carriage and oral candidiasis in HIV-positive subjects from southern Chad and analyzed the influence of HAART, CD4+ T-cell numbers, and antimycotics in 589 patients. These patients were recruited from a specialized medical center for HIV patients in Sarh and from a rural medical health dispensary in the vicinity, including a total of 384 HIV-positive and 205 HIV-negative individuals. Yeasts obtained from oral specimen were identified by MALDI-TOF MS and their antifungal susceptibility profiles determined. The overall prevalence of yeast colonization and symptomatic oral candidiasis in HIV-infected patients was 25.1%. The prevalence of oral candidiasis was higher in untreated than in HAART-treated HIV-positive patients (16% vs. 2%; p < 0.01). Oral candidiasis was furthermore associated with high fungal burdens of Candida albicans and a CD4+ T-cell number <200/µl. A shift toward non-albicans Candida species was observed under nucleoside-based HAART therapy. Azole antifungal drug resistance was only observed for the intrinsically resistant species Candida krusei and Candida glabrata. Prevalence of oral candidiasis in the studied area was very low. The species distribution was similar to other countries around the world, with C. albicans being dominant. Candida dubliniensis was not isolated. Nucleoside-based HAART therapy significantly reduced oral colonization as well as occurrence of oral candidiasis caused by C. albicans and led to a species shift toward non-albicans species. Antifungal resistance was not yet a concern in Chad.

High frequency of Candida krusei colonization in critically ill pediatrics: A cross-sectional study in children's medical center, Tehran, Iran.

Background and Purpose: This study aimed to evaluate the species distribution and susceptibility pattern of the strains isolated from Candida colonization in pediatric patients staying at pediatric intensive care unit (ICU) and infant ICU of Children's Medical Center in Tehran, Iran. Materials and Methods: This study was conducted in the Children's Medical Center in Tehran, Iran. In total, 440 samples from 56 patients with oral cavity, skin surrounded catheters, and ear, throat, nasal, and urine cultures were collected. All patients were evaluated in terms of Candida colonization on the admission day as well as the days 7, 14, and 28 according to the previous studies. CHROMagar Candida medium was applied for primary/multiple species identification and the isolates were identified by using polymerase chain reaction-based methods to the species-specific complex level. The antifungal susceptibility test was performed according to the Clinical and Laboratory Standards protocol published as M27-A3 and M60 documents. Results: In total, 136 yeast samples from 26 individuals (30.9%) out of 440 samples were considered colonization. The most prevalent species in IICU was C. albicans (27%, n=20) followed by C. krusei (24 %, n=18) and C. parapsilosis (16%, n=12). In PICU, the predominant species was C. krusei (40%, n=24) followed by C. parapsilosis (18%, n=11) and C. dubliniensis (16%, n=10). Among the 40 tested isolates from both units, fluconazole-resistant isolates (n=11, 8.15%) were determined according to the new breakpoints. In the case of echinocandins, 2 isolates, including C. albicans (n=1) and C. krusei (n=1) were resistant against both caspofungin and anidulafungin (totally 1.48%). Conclusion: In the present study, since C. krusei is intrinsically-resistance against fluconazole, emphasizing the importance of species-level identification of Candida isolates is outstanding. However, according to the antifungal susceptibility testing results, only 7.2% of the strains were resistant to fluconazole. It would be beneficial to monitor the ICU patients who are at high risk of invasive Candida infection.

Candida colonization index in patients admitted to an ICU.

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.

Candida colonization as a predictor of invasive candidiasis in non-neutropenic ICU patients with sepsis: A systematic review and meta-analysis.

BACKGROUND: Candida colonization is a risk factor for the development of invasive candidiasis. This study sought to estimate the magnitude of this association, and determine if this information can be used to guide empirical antifungal therapy initiation in critically ill septic patients. METHODS: PubMed/MEDLINE and Embase were systematically reviewed for all published studies evaluating predictors of invasive candidiasis in ICU patients with sepsis. Meta-analysis was used to determine the pooled odds ratio for invasive candidiasis among colonized versus non-colonized patients. Sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV), and positive and negative likelihood ratios (+LR, -LR) were then calculated by considering the presence/absence of Candida colonization as the diagnostic test, and the presence/absence of invasive candidiasis as the disease of interest. RESULTS: Out of 9825 patients in the 10 eligible studies, 3886 (40%) were colonized with Candida and 462 patients (4.7%) developed invasive candidiasis. Meta-analysis indicated that critically ill patients with sepsis who are colonized with candida are more likely to develop invasive candidiasis (odds ratio 3.32; 95% CI 1.68-6.58) compared with non-colonized patients. The pooled SN was 75.2% (95% CI 59.6-86.2%), while the pooled SP was 49.2% (95% CI 33.2-65.3%).The NPV of Candida colonization was high (96.9%; 95% CI 92.0-98.9%), but the PPV was low (9.1%; 95% CI 5.5-14.6%). CONCLUSION: Candida colonization is strongly associated with the likelihood of invasive candidiasis among ICU patients with sepsis. Available data argue against initiating empirical antifungal treatment in non-neutropenic septic patients without prior documented Candida colonization.

Candida colonization of the esophagus and gastric mucosa; a comparison of patients taking proton pump inhibitors and those taking histamine receptor antagonist drugs.

AIM: Investigation of Candida colonization of the esophagus and gastric mucosa in patients taking proton pump inhibitors in comparison with those taking histamine-2 receptor antagonists. BACKGROUND: Candida species are normal flora of alimentary tract that can cause infection of the esophagus and gastro-intestinal tract in immunocompromised patients. Consumption of proton pump inhibitors and histamine-2 receptor antagonists has been shown to alter the gastric pH, which may predispose the esophagus and stomach to floral transmission and colonization. METHODS: Two hundred and forty-five clinical specimens were obtained from 91 patients who underwent endoscopy from September 2019 to February 2020. Direct microscopy with KOH 10% and subculture on sabouraud dextrose agar containing chloramphenicol was used as primary screening. PCR with ITS primers was performed to amplify the ITS1-5.8SrDNA-ITS2 region, and the MspI restriction enzyme was used for RFLP to identify clinical isolates. RESULTS: Seventy cultures out of 245 specimens were positive for Candida colonization (28.5%). Colonization of Candida species in gastric acid and gastric tissue biopsies of patients who took PPIs and H2 blockers was significantly higher than in those in the control group (p= 0.001). The use of ranitidine, pantoprazole, and omeprazole increased the risk of gastric candidiasis by 10.60, 9.20, and 12.99 times, respectively (p< 0.05). CONCLUSION: The use of PPIs and H2 blockers, ageing, and consumption of vegetables were main risk factors for gastric colonization in the present survey; other variables, such as Candida species, cigarette smoking, and alcohol consumption, were not implicated in the development of gastroesophageal lesions. Further investigations are necessary to understand how these predisposing factors change the host's defense mechanisms and increase colonization of fungi at mucosal surfaces.

First Case of Candida auris Colonization in a Preterm, Extremely Low-Birth-Weight Newborn after Vaginal Delivery.

Candida auris is a multidrug-resistant, difficult-to-eradicate pathogen that can colonize patients and health-care environments and cause severe infections and nosocomial outbreaks, especially in intensive care units. We observed an extremely low-birth-weight (800 g), preterm neonate born from vaginal delivery from a C. auris colonized mother, who was colonized by C. auris within a few hours after birth. We could not discriminate whether the colonization route was the birth canal or the intensive care unit environment. The infant died on her third day of life because of complications related to prematurity, without signs or symptoms of infections. In contexts with high rates of C.auris colonization, antifungal prophylaxis in low-birth-weight, preterm neonates with micafungin should be considered over fluconazole due to the C. auris resistance profile, at least until its presence is excluded.

Asymptomatic vaginal Candida colonization and adverse pregnancy outcomes including preterm birth: a systematic review and meta-analysis.

OBJECTIVE: During pregnancy, vaginal colonization by Candida spp is common. Some studies suggest an association between asymptomatic vaginal Candida colonization and adverse pregnancy outcomes, but the evidence is inconsistent. This review aimed to systematically review the association between asymptomatic vaginal colonization by Candida spp and adverse pregnancy outcomes, including preterm birth. DATA SOURCES: We searched Ovid MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials from inception to May 6, 2020 for published studies on vaginal Candida/yeast and pregnancy outcomes. STUDY ELIGIBILITY CRITERIA: Cohort studies, case-control studies, and randomized controlled trials that included pregnant women who were tested for asymptomatic vaginal Candida colonization and reported on adverse pregnancy outcomes were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently selected and extracted the data. Critical appraisal was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies and the revised Cochrane risk-of-bias tool for randomized controlled trials. RESULTS: We found no significant difference in preterm birth rate between Candida-positive and Candida-negative women (odds ratio, 1.10; 95% confidence interval, 0.99-1.22; I2, 0%) in 15 studies among 33,321 women for either spontaneous preterm birth only (odds ratio, 1.13, 95% confidence interval, 0.97-1.31; I2, 0%) or all preterm birth (odds ratio, 1.04; 95% confidence interval, 0.79-1.35; I2, 21%). Subgroup analyses for a treatment strategy including only studies reporting on spontaneous preterm birth did not reveal any statistically significant associations either, although the odds ratio was increased for the untreated Candida-positive women (odds ratio, 1.28; 95% confidence interval, 0.90-1.81; I2, 13%) in 3 studies among 5175 women. Asymptomatic vaginal Candida colonization was not associated with small for gestational age, perinatal mortality, or any other adverse pregnancy outcome. CONCLUSION: Asymptomatic vaginal Candida colonization is not associated with preterm birth and other adverse pregnancy outcomes. Previous studies reported that treatment of this microorganism reduces preterm birth rate. Our results suggest that this effect is unlikely to rely on treatment of vaginal Candida.

Clinical Significance of Candida in an Intraoperative Peritoneal Specimen with Perforation Peritonitis: An Institutional Perspective.

Introduction Fungal infection of the peritoneum has become more common in recent years, the most common cause of which is Candida. Candida peritonitis is considered as a severe disease and is regarded as an independent risk factor for mortality in postoperative peritonitis. This study was planned to find out the clinical significance of Candida isolation on the outcome of the patients with peritonitis in terms of morbidity and mortality. Methods This prospective study included consecutive patients admitted and operated for secondary peritonitis over a two-year period in a tertiary care hospital in South India. The time delay was assessed from the onset of symptoms to surgery. The intraoperative peritoneal fluid aspirate was analyzed for culture sensitivity (fungal and bacterial). Patients were followed until their discharge from the hospital or death. This study analyzed the clinico-microbiological profile in patients with perforation peritonitis with special reference to Candida isolation. The analysis also looked the results of antifungal therapy (fluconazole) in patients positive for Candida isolation. Results The study included 407 consecutive patients with hollow viscus perforation diagnosed intraoperatively. Fungal organisms were identified in 153 patients (37.6%). Old age (> 50 years), high lag period (≥ 48 hours), peritoneal contamination, length of hospital stay, the presence of co-morbidities, shock at presentation, and postoperative complications were found to be significantly associated with fungal infection (p < 0.05). The study noted a significant decrease in the perioperative complications in patients who were started on antifungal treatment early (within 72 hours after surgery). There were significant reductions in the length of hospital stay, intensive care unit (ICU) stay, ventilator support, and inotropic support in the postoperative period. However, we did not find any difference in mortality due to early treatment with fluconazole. Conclusion Candida peritonitis was associated with an increase in the mortality and morbidity, especially when associated with diabetes mellitus and fungemia. Early antifungal therapy (within 72 hours after surgery) reduced the morbidity due to Candida peritonitis but did not affect the mortality.

Probiotics Prevent Candida Colonization and Invasive Fungal Sepsis in Preterm Neonates: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To investigate whether probiotic supplementation could reduce the risk of fungal infection in preterm neonates in neonatal intensive care units (NICUs), we systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) focusing on the effect of probiotics on fungal infection in preterm neonates. The outcomes of interest were Candida colonization and invasive fungal sepsis. Seven trials involving 1371 preterm neonates were included. Meta-analysis (fixed-effects model) showed that probiotic supplementation was significantly associated with a lower risk of Candida colonization (2 RCTs, n = 329; relative risk (RR), 0.43; 95% confidence interval (CI), 0.27-0.67; p = 0.0002; I2 = 0%), and invasive fungal sepsis (7 RCTs, n = 1371; RR, 0.64; 95% CI, 0.46-0.88; p = 0.006; I2 = 13%). After excluding one study with a high baseline incidence (75%) of fungal sepsis, the effect of probiotics on invasive fungal sepsis became statistically insignificant (RR, 0.88; 95% CI, 0.44-1.78; p = 0.72; I2 = 15%). When using the random-effects model, the effect of probiotics remained favorable for Candida colonization (RR, 0.43; 95% CI 0.27-0.68; p = 0.0002; I2 = 0%) but not for fungal sepsis (RR, 0.64; 95% CI 0.38-1.08; p = 0.10; I2 = 13%). Current evidence indicates that probiotics can reduce the risk of Candida colonization in preterm neonates in NICUs. Limited data support that probiotic supplementation prevents invasive fungal sepsis in preterm neonates. High-quality and adequately powered RCTs are warranted.

Oral candidiasis among African human immunodeficiency virus-infected individuals: 10 years of systematic review and meta-analysis from sub-Saharan Africa.

Oral candidiasis (OC) is the most common opportunistic fungal infection among immunocompromised individuals. This systematic review and meta-analysis reports on the contribution of non-albicans Candida species in causing OC among human immunodeficiency virus (HIV)-infected individuals in sub-Saharan Africa between 2005 and 2015. Thirteen original research articles on oral Candida infection/colonization among HIV-infected African populations were reviewed. The prevalence of OC ranged from 7.6% to 75.3%. Pseudomembranous candidiasis was found to range from 12.1% to 66.7%. The prevalence of non-albicans Candida species causing OC was 33.5% [95% confidence interval (CI) 30.9-36.39%]. Of 458 non-albicans Candida species detected, C. glabrata (23.8%; 109/458) was the most common, followed by C. tropicalis (22%; 101/458) and C. krusei (10.7%; 49/458). The overall fluconazole resistance was 39.3% (95% CI 34.4-44.1%). Candida albicans was significantly more resistant than non-albicans Candida species to fluconazole (44.7% vs 21.9%; p < 0.001). One-quarter of the cases of OC among HIV-infected individuals in sub-Saharan Africa were due to non-albicans Candida species. Candida albicans isolates were more resistant than the non-albicans Candida species to fluconazole and voriconazole. Strengthening the capacity for fungal diagnosis and antifungal susceptibility testing in sub-Saharan Africa is mandatory in order to track the azole resistance trend.

Probiotics in critically ill children.

Gut microflora contribute greatly to immune and nutritive functions and act as a physical barrier against pathogenic organisms across the gut mucosa. Critical illness disrupts the balance between host and gut microflora, facilitating colonization, overgrowth, and translocation of pathogens and microbial products across intestinal mucosal barrier and causing systemic inflammatory response syndrome and sepsis. Commonly used probiotics, which have been developed from organisms that form gut microbiota, singly or in combination, can restore gut microflora and offer the benefits similar to those offered by normal gut flora, namely immune enhancement, improved barrier function of the gastrointestinal tract (GIT), and prevention of bacterial translocation. Enteral supplementation of probiotic strains containing either Lactobacillus alone or in combination with Bifidobacterium reduced the incidence and severity of necrotizing enterocolitis and all-cause mortality in preterm infants. Orally administered Lactobacillus casei subspecies rhamnosus, Lactobacillus reuteri, and Lactobacillus rhamnosus were effective in the prevention of late-onset sepsis and GIT colonization by Candida in preterm very low birth weight infants. In critically ill children, probiotics are effective in the prevention and treatment of antibiotic-associated diarrhea. Oral administration of a mix of probiotics for 1 week to children on broad-spectrum antibiotics in a pediatric intensive care unit decreased GIT colonization by Candida, led to a 50% reduction in candiduria, and showed a trend toward decreased incidence of candidemia. However, routine use of probiotics cannot be supported on the basis of current scientific evidence. Safety of probiotics is also a concern; rarely, probiotics may cause bacteremia, fungemia, and sepsis in immunocompromised critically ill children. More studies are needed to answer questions on the effectiveness of a mix versus single-strain probiotics, optimum dosage regimens and duration of treatment, cost effectiveness, and risk-benefit potential for the prevention and treatment of various critical illnesses.

Management of candidemia in patients with Clostridium difficile infection.

INTRODUCTION: Patients with C. difficile infection (CDI) experience intestinal microflora changes that can promote the overgrowth and subsequent translocation of gut resident pathogens into the blood. Consistently, CDI due to PCR-ribotype 027 strain, severe or relapsing CDI, and treatment with high-dosage vancomycin are independent risk factors for candidemia. AREAS COVERED: We review the role played by the gut microbiota during CDI and its treatment, as well as the clinical profile of CDI patients who are at risk of developing candidemia. Also, we discuss the management of these patients by focusing on pre-emptive strategies aimed at reducing the risk of candidemia, and on innovative anti-C. difficile therapies that may mitigate CDI-related effects such as the altered gut microbiota composition and prolonged intestinal mucosa damage. Expert commentary: A closer clinical and diagnostic monitoring of patients with CDI should help to limit the CDI-associated long-term consequences, including Candida infections, which worsen the outcome of hospitalized patients.

Prevalence and immediate outcome of candida colonized preterm neonates admitted to Special Care Unit of Mulago Hospital, Kampala Uganda.

BACKGROUND: Candida species is the third commonest cause of sepsis among neonates. Colonization by Candida is a predictor for candidemia among preterm neonates. OBJECTIVES: To determine prevalence of early Candida colonization and early outcome among colonized preterm neonates admitted to Mulago hospital Special Care Unit. METHODS: A prospective observational cohort was conducted between December 2008 and April 2009. Preterm neonates aged >72 hours and less than one week were screened for Candida colonization of the groin, oral pharynx and rectum using CHROMagar. Colonized neonates were followed up for 14 days. Blood cultures were done for those with signs of septicaemia. The Fisher's exact tests and logistic regression were conducted for factors associated with colonization and mortality among colonized neonates. P values of < 0.05 were considered significant and confidence interval of 95% was used. RESULTS: Candida colonization occurred in 50/213 (23.5%) neonates. Gestational age ≤ 30 weeks was the only factor independently associated with colonization (p = 0.005). Of the colonized 14/46 (30.4%) died and 13/46 (28.3%) developed mucocutaneous candidiasis. No candidemia was identified. Multiple site colonization was independently associated with mortality (p=0.035). CONCLUSION: The consequence of high colonization observed in this study needs to be further elucidated in Uganda.