• Candida Spp.
• Children
• Iran
• Malignancy
• Methicillin-resistant Staphylococcus aureus
• Staphylococcus aureus

• candidemia
• colonization index
• febrile episode
• lymphoreticular malignancy
• mannan antigen

There is a worldwide concern regarding the antimicrobial resistance and the inappropriate use of antifungal agents, which had led to an ever-increasing antifungal resistance. This study aimed to identify the antifungal susceptibility of colonized Candida species isolated from pediatric patients with cancer and evaluate the clinical impact of antifungal stewardship (AFS) interventions on the antifungal susceptibility of colonized Candida species. Candida species colonization was evaluated among hospitalized children with cancer in a tertiary teaching hospital, Shiraz 2017–2018. Samples were collected from the mouth, nose, urine, and stool of the patients admitted to our center and cultured on sabouraud dextrose agar. The isolated yeasts identified by polymerase chain reaction–restriction fragment length polymorphisms (PCR–RFLP). DNA Extracted and PCR amplification was performed using the ITS1 and ITS4 primer pairs and Msp I enzyme. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) for amphotericin B, caspofungin, and azoles. The prevalence of Candida albicans in the present study was significantly higher than other Candida species. Candida albicans species were completely susceptible to the azoles. The susceptibility rate of C. albicans to amphotericin B and caspofungin was 93.1% and 97.1%, respectively. The fluconazole MIC values of Candida albicans decreased significantly during the post-AFS period (P < 0.001; mean difference: 72.3; 95% CI of the difference: 47.36–98.62). We found that ‏52.5% (53/117) of the isolated C. albicans were azole-resistant before AFS implementation, while only 1.5% (2/102) of the isolates were resistant after implementation of the AFS program (P < 0.001). C. albicans fluconazole and caspofungin resistant rate also decreased significantly (P < 0.001) after implementation of the AFS program [26 (32.9%) versus 0 (0.0%) and 11 (10.9%) versus 1 (0.9%), respectively]. Besides, fluconazole use (p < 0.05) and fluconazole expenditure reduced significantly (about one thousand US$ per year) after the AFS program. Our results confirm the positive effect of optimized antifungal usage and bedside intervention on the susceptibility of Candida species after the implementation of the AFS program. C. albicans and C. glabrata exhibited a significant increase in susceptibility after the execution of the AFS program.

• Candida
• infection
• oesophagitis

• Antifungals
• Candida
• Cystic fibrosis
• saliva

Surveillance of current changes in the epidemiology of Invasive Fungal Diseases (IFDs) as an important component of the antifungal stewardship programs (ASP), requires careful regular monitoring, especially in high-risk settings such as oncology centers. This study aimed to examine Candida colonization status and corresponding current changes in children with malignancy during repeated admissions and also investigate the possible epidemiological shifts after the implementation of ASP.

In this prospective observational study, all eligible patients younger than 18 years were recruited during 2016–2017 at Amir Medical Oncology Center (AMOC) in Shiraz, Iran. Totally, 136 patients were enrolled and 482 samples were collected from different sites (oral/nasal discharges, urine and stool). Weekly regular sampling was carried out during hospitalization. Candida colonization status and epidemiological changes were monitored during repeated admissions. Samples were cultivated on Sabouraud Dextrose agar medium and identified by Polymerase Chain Reaction -Restriction Fragment Length Polymorphism (PCR-RFLP).

Estimated Candida colonization incidence was 59.9% (82/136) in our patients. Candida colonization was found to be higher in oral cavity and rectum than that in nasal cavity. Among those long-term follow ups and repetitive hospitalizations, a significant number of patients exhibited changes in their colonization patterns (37.7%). Candida colonization did not reveal any significant relationship with age, sex, oncologic diseases and degree of neutropenia. C. albicans (72.0%) was found as the most common Candida species in colonized patients, followed by C. krusei, C. kefyr, C. glabrata and C. parapsilosis.

Given the high incidence of Candida infections in children with cancers, close monitoring of epidemiologic changes is essential for judicious management, based on local surveillance data and improvement of overall quality of care in high risk patients.

• Candida albicans
• Fungal colonization
• Pediatric leukemia

• antifungal
• caspofungin
• epidemiology
• micafungin
• pediatrics

• Cystic fibrosis
• Epidemiology
• Fungal infection

AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.

METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: “gastrointestinal infection AND antineoplastic chemotherapy AND children”, “gastrointestinal infection AND oncology AND children”, “liver infection AND antineoplastic chemotherapy AND children”, “liver abscess AND chemotherapy AND child”, “neutropenic enterocolitis AND chemotherapy AND children”, “thyphlitis AND chemotherapy AND children”, “infectious diarrhea AND children AND oncology”, “abdominal pain AND infection AND children AND oncology”, “perianal sepsis AND children AND oncology”, “colonic pseudo-obstruction AND oncology AND child AND chemotherapy”, “microflora AND children AND malignancy”, “microbiota AND children AND malignancy”, “fungal flora AND children AND malignancy”. We also analysed evidence from several articles and book references.

RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infection in those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available.

CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented (also by further studies on new biomarkers) for a prompt and individualized therapy.

• Gastrointestinal tract
• Liver
• Microflora
• Infection
• Oncology
• Chemotherapy
• Children

• Adolescent
• Antineoplastic Agents/adverse effects
• Child
• Colonic Pseudo-Obstruction/etiology
• Colonic Pseudo-Obstruction/immunology
• Diarrhea/etiology
• Diarrhea/immunology
• Dysbiosis/etiology
• Dysbiosis/immunology
• Enterocolitis, Neutropenic/etiology
• Enterocolitis, Neutropenic/immunology
• Gastroenteritis/etiology
• Gastroenteritis/immunology
• Gastrointestinal Microbiome
• Hepatitis, Viral, Human/etiology
• Hepatitis, Viral, Human/immunology
• Humans
• Immunocompromised Host
• Liver Abscess/etiology
• Liver Abscess/immunology
• Liver Diseases/etiology
• Liver Diseases/immunology
• Mycoses/etiology
• Mycoses/immunology
• Neoplasms/drug therapy
• Sepsis/etiology
• Sepsis/immunology

• children
• diabetes mellitus type 1
• drug susceptibility
• duration of the disease
• metabolic control
• yeast-like fungi

• Candida spp.
• Caries-free and caries-active children
• Differentiation
• Prevalence

• Cystic fibrosis
• disease progression
• forced expiratory volume/physiology
• sputum/microbiology

• Candida albicans
• Cystic fibrosis
• colonisation
• inhaled antibiotics
• yeast

• Candida albicans
• RAPD
• antifungal
• cystic fibrosis
• susceptibility
• virulence factors

This study aimed to investigate the possible topical effect of a broad-spectrum antibiotic on dental biofilm formed in situ in the absence or presence of sucrose.

A crossover study was conducted in three phases of 14 days each, during which 11 volunteers wore palatal devices containing 6 enamel blocks covered with meshes to allow biofilm formation. Dental blocks were extraorally submitted to a 20% sucrose solution at three different frequencies of exposure (0, 3 and 8 times/day), and to a suspension of amoxicillin/clavulanate potassium (A/CP) or a placebo (P) suspension at an 8-hour time interval application regimen. On the 14^th day of each phase, biofilms were collected for microbiological (conventional culture) and molecular (Denaturing Gradient Gel Electrophoresis – DGGE) analyses.

In the absence of sucrose exposure (SE) and at the 3-time daily frequency, dental biofilms treated with A/CP showed lower total biofilm weight and lower counts of total microbiota than the ones treated with P (p>0.05). A/CP presented higher counts of Candida spp. when compared with P in the presence of SE, especially at the 8-time daily frequency (p<0.05). Considering the DGGE analysis, the mean number of bands was higher for P (p>0.05), regardless of SE. However, DGGE profiles demonstrated large interindividual variability.

Both conventional culture and DGGE have demonstrated some differences on total microbiota of dental biofilms when exposed to the A/CP or P suspensions, mainly in the absence of sucrose, which suggests a possible topical effect of the sugar-free A/CP suspension on dental biofilm.

• Administration, Topical
• Adult
• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/therapeutic use
• Biofilms/drug effects
• Colony Count, Microbial
• Cross-Over Studies
• Dental Plaque/drug therapy
• Dental Plaque/microbiology
• Female
• Humans
• Male
• Metagenome/genetics
• RNA, Ribosomal, 16S
• Sucrose/metabolism
• Young Adult

Given the polymicrobial nature of pulmonary infections in patients with cystic fibrosis (CF), it is essential to enhance our knowledge on the composition of the microbial community to improve patient management. In this study, we developed a pyrosequencing approach to extensively explore the diversity and dynamics of fungal and prokaryotic populations in CF lower airways.

Fungi and bacteria diversity in eight sputum samples collected from four adult CF patients was investigated using conventional microbiological culturing and high-throughput pyrosequencing approach targeting the ITS2 locus and the 16S rDNA gene. The unveiled microbial community structure was compared to the clinical profile of the CF patients. Pyrosequencing confirmed recently reported bacterial diversity and observed complex fungal communities, in which more than 60% of the species or genera were not detected by cultures. Strikingly, the diversity and species richness of fungal and bacterial communities was significantly lower in patients with decreased lung function and poor clinical status. Values of Chao1 richness estimator were statistically correlated with values of the Shwachman-Kulczycki score, body mass index, forced vital capacity, and forced expiratory volume in 1 s (p = 0.046, 0.047, 0.004, and 0.001, respectively for fungal Chao1 indices, and p = 0.010, 0.047, 0.002, and 0.0003, respectively for bacterial Chao1 values). Phylogenetic analysis showed high molecular diversities at the sub-species level for the main fungal and bacterial taxa identified in the present study. Anaerobes were isolated with Pseudomonas aeruginosa, which was more likely to be observed in association with Candida albicans than with Aspergillus fumigatus.

In light of the recent concept of CF lung microbiota, we viewed the microbial community as a unique pathogenic entity. We thus interpreted our results to highlight the potential interactions between microorganisms and the role of fungi in the context of improving survival in CF.

• Adult
• Bacteria/classification
• Bacteria/genetics
• Biodiversity
• Cystic Fibrosis/microbiology
• Cystic Fibrosis/therapy
• DNA, Bacterial/genetics
• DNA, Fungal/genetics
• DNA, Ribosomal Spacer/genetics
• Female
• Fungi/classification
• Fungi/genetics
• Humans
• Male
• Metagenome/genetics
• Respiratory System/microbiology
• Sequence Analysis, DNA