Risk Factors for Invasive Pulmonary Aspergillosis and Hospital Mortality in Acute-On-Chronic Liver Failure Patients: A Retrospective-Cohort Study

Background: Invasive pulmonary aspergillosis (IPA) in acute-on-chronic liver failure (ACLF) patients is associated with a high mortality. But the clinical characteristics of and the risk factors for IPA among patients with ACLF remains unclear. This study was aimed at assessing clinical manifestation, the risk factors and antifungal medications for as well as the mortality due to IPA in ACLF patients at the First Affiliated Hospital, College of Medicine, Zhejiang University.Patients and Methods: Patients with ACLF who were diagnosed with proven or probable IPA by clinical and laboratory parameters from 1 December 2008 to 1 May 2012 were retrospectively evaluated to determine the risk factors for IPA and the clinical outcomes. The follow-up ended on 30 July 2012. Multivariate analysis was performed to identify the risk factors for mortality and the development of IPA.Results: In total, 787 patients with ACLF were enrolled, and 39 of these patients developed IPA. Thirty seven of these 39 patients died in spite of treatment with antifungal drugs. Controls included 48 patients who did not have a pulmonary infection. The survival rate of patients with IPA was significantly lower than that of those without IPA. IPA was found to be independently associated with age (p = 0.021), encephalopathy (p = 0.002), and steroid use (p = 0.000). There was significant difference in the prognosis between the patients treated with either voriconazole or itraconazole and those without antifungal treatment.Conclusions: Patients with ACLF and IPA have a high mortality rate. Patients with ACLF who present with encephalopathy should avoid steroids, as they increase the mortality rate. Azoles may prolong the survival time.     

Candidaemia in a Tertiary Care Centre of Developing Country: Monitoring Possible Change in Spectrum of Agents and Antifungal Susceptibility

Purpose: Candidaemia is a major cause of morbidity and mortality of hospitalised patients, especially in developing countries. This study was conducted to monitor any change in species distribution and antifungal susceptibility pattern of Candida species causing candidaemia over the last 20 years. Materials and Methods: The candidaemia cases reported during January 1999 and December 2018 at our centre were reviewed. The yeasts were identified by phenotypic characters (during 1999–2014) and matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) (during 2014–2018). Antifungal susceptibility testing (AFST) was performed in accordance with the Clinical and Laboratory Standards Institute guidelines. Results: A total of 602,963 blood samples from patients with suspected sepsis were processed. Candidaemia was diagnosed in 7927 (1.31%) cases. The frequency of cases rose significantly (P = 0.000) in the last quarter of the study. Candida tropicalis (40.1%) was the most common species, followed by Candida albicans (15.2%), Wickerhamomyces anomalus (13.1%), Candida krusei (6.6%), Candida parapsilosis (4.7%) and others. Rare species such as Candida auris, Candida lambica, Candida orthopsilosis, Candida vishwanathii were identified after the introduction of MALDI-TOF. The minimum inhibitory concentrations of amphotericin B rose significantly from the first to last quarter (0.5%–4.9%). Fluconazole resistance was fairly constant at 7.4%–8.8%. Conclusion: Local epidemiology of candidaemia at our centre was distinct regarding prevalence and change of spectrum of species. The identification of rare species was possible after the introduction of MALDI-TOF. With the emergence of multidrug-resistant C. auris and resistance in other species, routine AFST has become imperative.     

Antifungal susceptibility of clinical isolates of 25 genetically confirmed Aspergillus species collected from Taiwan and Mainland China

BackgroundTo investigate the in vitro antifungal susceptibilities of 25 genetically confirmed Aspergillus species collected from Taiwan and Mainland China.MethodsA total of 390 non-duplicate and consecutive Aspergillus isolates representing of 25 species recovered from clinical sources at two teaching hospitals in Taiwan and Mainland china were preserved for this study. In vitro antifungal susceptibility testing (AFST) of those Aspergillus isolates against seven antifungal agents was performed using Sensititre YeastOne (SYO) system. The susceptibility profiles of isolates were analyzed according to the general interpretation code drawn from the SYO instruction. The CYP51A gene sequencing analysis was performed for triazole-resistant Aspergillus fumigatus isolates.ResultsAmong the 390 Aspergillus isolates, 76.7% (n = 299) exhibited complete susceptibility to all the tested antifungals, and 23.3% (91/390) of different Aspergillus species isolates showed resistance to one or two classes of antifungal agents with higher minimum inhibitory concentrations (MICs) of >2 mg/L. Resistance to amphotericin B was found in 91.2% (83/91) of those less susceptible isolates and most of them focused on species being resistant to Amphotericin B innately. The total rate of triazole resistance in this study was low (3.3%, 13/390), and only 3 (2.8%) A. fumigatus isolates were resistant to at least one of the triazoles with mutations of TR₃₄/L98H or TR₄₆/Y121F/T289A in CYP51A gene. The echinocandins were highly potent to the tested Aspergillus isolates.ConclusionThe existence of triazole resistance among A. fumigatus isolates in Taiwan and Mainland China indicates the need for continuous monitoring from now on.     

Antifungal susceptibility,species distribution and risk factors associated with mortality of invasive candidiasis in children in Turkey: A six-year retrospective,single-centre study

Invasive candidiasis (IC) is a life-threatening fungal infection with high morbidity and mortality. In this study, we aimed to investigate the Candida species distribution and antifungal drug susceptibility and to identify the risk factors associated with IC mortality in children. We conducted a retrospective, single-centre study of paediatric IC in patients from a tertiary care hospital in Turkey between January 2013 and February 2019. A total of 56 Candida isolates underwent antifungal susceptibility testing performed by Sensititre YeastOne YO10 panel, and the demographic and clinical data of 65 patients were examined during the study period. The most commonly isolated species was Candida albicans in 30 patients (46%), followed by C. parapsilosis in 25 patients (38%) and C. tropicalis in three patients (5%). According to the antifungal drug susceptibility testing, C. albicans was fully susceptible to fluconazole and the other antifungal agents (100%). None of the isolates displayed resistance to anidulafungin, micafungin, flucytosine, posaconazole, voriconazole or itraconazole. There were low rates of resistance to fluconazole (1.8%), caspofungin (1.8%) and micafungin (1.8%). In addition, 5.3% of the Candida isolates were susceptible in a dose-dependent manner to itraconazole, 3.6% were susceptible to voriconazole and fluconazole and 1.8% were susceptible to anidulafungin. The mortality rate of IC was 15.4%. Thrombocytopenia after IC treatment was significantly associated with mortality in the multivariate analysis. These results, which help determine the species distribution, antifungal susceptibility patterns and risk factors for mortality, could make a significant contribution to the management of these challenging infections, including choosing appropriate empirical antifungal therapy.     

Evolution of fungemia in an Italian region

BackgroundFungemia represents a public health concern. Knowing aetiology and activity of the antifungals is critical for the management of bloodstream infections. Therefore, surveillance on local/international levels is desirable for a prompt administration of appropriate therapy.MethodsData on fungi responsible for fungemia and antifungal susceptibility profiles were collected from a laboratory-based surveillance over 2016–2017 in 12 hospitals located in Lombardia, Italy. The trend of this infection in twenty years was analysed.ResultsA total of 1024 episodes were evaluated. Rate of candiaemia progressively increased up to 1.46/1000 admissions. C.albicans was the most common species (52%), followed by C. parapsilosis (15%) and C glabrata (13%). As in the previous surveys the antifungal resistance is rare (echinocandins < 2%, fluconazole 6%, amphotericin B 0.6%). Fungi other than Candida were responsible for 18 episodes: Cryptococcus neoformans (5 cases), Fusarium spp. (4), Magnusiomyces clavatus (3), Saccharomyces cerevisiae (3), Rhodotorula spp. (2), Exophiala dermatitidis (1). All fungi, except S.cerevisiae, were intrinsically resistant to echinocandins. Some isolates showed also elevated azole MIC.ConclusionsNo particular changes in terms of species distribution and antifungal susceptibility patterns was noted. However, surveillance programs are needed to monitor trends in antifungal resistance, steer stewardship activities, orient empirical treatment.     

Isolated invasive Aspergillus tracheobronchitis: a clinical study of 19 cases

Isolated invasive Aspergillus tracheobronchitis (iIATB) is an uncommon clinical form of invasive Aspergillosis in which Aspergillus infection is limited entirely or predominantly to the tracheobronchial tree. In the present study, we retrospectively analyzed the medical records of 19 patients who had histological documented iIATB in the Department of Respiratory Medicine of Changhai Hospital between October 2000 and February 2008. Malignancy was the most common underlying disease, which existed in 14 patients (73.7%) in our series. Most patients had impaired airway structures or defence functions, whereas the systemic immune status was relatively normal. Only three patients (15.8%) had neutropenia. The clinical manifestations and chest radiograph were non-specific. We classified iIATB into four different forms according to the bronchoscopic features of intraluminal lesions: superficial infiltration type (Type I, n = 4), full-layer involvement type (Type II, n = 2), occlusion type (Type III, n = 6) and mixed type (Type IV, n = 7). Type IV was the largest group in our study, followed by Type III. All patients with iIATB of Type IV had definite airway occlusion. Fourteen patients (73.7%) had a good response to antifungal treatments and five (26.3%) died as a result of the progression of Aspergillosis, all of whom had full-layer invasion of the involved bronchi. In conclusion, we found that iIATB could occur in moderately or non-immunocompromised patients with impaired airway structures or defence functions and may be an early period of invasive pulmonary Aspergillosis. Most of the iIATB patients had a favourable prognosis with early diagnosis and effective antifungal treatment. The morphological features of intraluminal lesions might be of prognostic value.     

Cold-active antibacterial and antifungal activities and antibiotic resistance of bacteria isolated from an alpine hydrocarbon-contaminated industrial site

Selection pressure in hydrocarbon-contaminated soils may lead not only to increased microbial resistance to antibiotics, but also to increased capacity of the soil indigenous population to produce antimicrobial compounds. Therefore, we studied the antibiotic resistance pattern and antibacterial and/or antifungal activities of 47 bacterial strains isolated from an industrial alpine site heavily polluted with petroleum hydrocarbons. Resistance to penicillin was more widespread (49%) than resistance to chloramphenicol or rifampicin (28%) or streptomycin (26%). Only 9% of the strains were resistant to tetracycline. The ability to produce cold-active (10 °C) antimicrobial compounds was tested by using human pathogenic bacteria (Escherichia coli, Shigella flexneri, Salmonella enterica, Pseudomonas aeruginosa, Staphylococcus aureus) and yeasts (Candida albicans, Cryptococcus neoformans) as indicator microorganisms. About two-thirds of the 47 tested strains produced compounds that inhibited growth of at least one indicator microorganism. Six strains inhibited growth of both bacteria and yeast indicators; 12 and 16 strains showed either antibacterial or antifungal activity, respectively. The most versatile bacteria with regard to multiple antibiotic resistance and antimicrobial activity belonged to Actinobacteria or Gammaproteobacteria. The antimicrobial compounds produced by three Pseudomonas spp. and two Serratia spp. strains were characterized in more detail by TLC and HPLC. Depending on the sensitivity of growth inhibition to enzymes, the compounds produced by the three pseudomonads contained a proteinaceous component.     

Emerging antimicrobial resistance pattern of Helicobacter pylori in central Gujarat

Background: Antimicrobial resistance is a growing problem in H. pylori treatment. The study was intended to evaluate the prevalence of resistance amongst 80 H.pylori isolates cultured from biopsy taken during routine endoscopies in 2008-2011. Materials and Methods: 855 gastro duodenal biopsies were collected and cultured on H.pylori selective medium (containing Brucella agar and Columbia agar (Hi media), with Skirrow’s supplement (antibiotic supplement) and 7% human blood cells). H.pylori was isolated from 80 specimens. The antimicrobial susceptibility of H.pylori isolates was carried out by the Kirby Bauer technique against metronidazole (5 µg), clarithromycin (15 µg), ciprofloxacin (5 µg), amoxicillin (10 µg), tetracycline (30 µg), erythromycin (15 µg), levofloxacin (5 µg), and furazolidone (50 µg) (Sigma- Aldrich, MO). Results: 83.8% isolates were resistant to metronidazole, 58.8% were resistant to Clarithromycin 72.5% were resistant to Amoxicillin, 50% to Ciprofloxacin and 53.8% to tetracycline. furazolidone, erythromycin and Levofloxacin showed only 13.8% resistance to H.pylori. Multi drug resistance with metronidazole+ clarithromycin+ tetracycline was 85%. For all the drugs Antimicrobial resistance rate was found higher in males compare to females. Metronidazole and amoxicillin resistance was found noteworthy in patients with duodenal ulcer (p = 0.018), gastritis (P = 0.00), and in reflux esophagitis (P = 0.00). clarithromycin and tetracycline resistance was suggestively linked with duodenitis (P = 0.018), while furazolidone, erythromycin and levofloxacin showed excellent sensitivity in patients with duodenitis (P value- 0.018), gastritis (P= 0.00) and reflux esophagitis (P = 0.00). Resistance with metronidazole (P = 0.481), clarithromycin (P= 0.261), amoxicillin (P = 0.276), tetracycline (P = 0.356), ciprofloxacin (P = 0.164) was not correlated well with Age-group and Gender of the patients. Conclusion: A very high percentage of patients were infected with metronidazole and clarithromycin resistant strains. The use of antibiotics for other indications seems to be the major risk factor for the development of primary resistance. High incidence should alarm the gastroenterologist while prescribing the eradication regimen.     

Multicentre study to determine the Etest epidemiological cut-off values of antifungal drugs in Candida spp. and Aspergillus fumigatus species complex

ObjectivesTo determine the Etest-based epidemiological cut-off values (ECVs) for antifungal agents against the most frequent yeast and Aspergillus fumigatus species isolated in 12 French hospitals.MethodsFor each antifungal agent, the Etest MICs in yeast and A. fumigatus isolates from 12 French laboratories were retrospectively collected from 2004 to 2018. The ECVs were then calculated using the iterative statistical method with a 97.5% cut-off.ResultsForty-eight Etest ECVs were determined for amphotericin B, caspofungin, micafungin, anidulafungin, fluconazole, voriconazole, posaconazole and itraconazole, after pooling and analysing the MICs of 9654 Candida albicans, 2939 Candida glabrata SC, 1458 Candida parapsilosis SC, 1148 Candida tropicalis, 575 Candida krusei, 518 Candida kefyr, 241 Candida lusitaniae, 131 Candida guilliermondii and 1526 Aspergillus fumigatus species complex isolates. These ECVs were 100% concordant (identical or within one two-fold dilution) with the previously reported Etest-based ECVs (when available), and they were concordant in 76.1% of cases with the Clinical and Laboratory Standards Institute ECVs and in 81.6% of cases with the European Committee on Antimicrobial Susceptibility Testing ECVs.ConclusionsOn the basis of these and other previous results, we recommend the determination of method-dependent ECVs. Etest ECVs should not be used instead of breakpoints, but may be useful to identify non-wild-type isolates with potential resistance to antifungal agents, and to indicate that an isolate may not respond as expected to the standard treatment.     

Multiple colony antifungal susceptibility testing detects polyresistance in clinical Candida cultures: a European Confederation of Medical Mycology excellence centers study

ObjectivesMany factors influence the outcome of in vitro antifungal susceptibility testing (AFST), including endpoint definition, inoculum sizes, time and temperature of incubation, and growth medium used. This European Confederation of Medical Mycology (ECMM) Excellence center driven study investigated multiple colony testing (MCT) of five separate colonies to investigate the prevalence of polyresistance (PR), defined as heterogeneous MICs from a same-species Candida culture irrespective of the underlying resistance mechanism.MethodsCandida spp. MCT for fluconazole and anidulafungin was performed by Etest prospectively comprising 405 clinical samples. MCT results were compared to the real-life routine MIC data and PR was assessed. Candida colonies displaying strong PR were selected for genotyping using multilocus sequence typing and random amplified polymorphic DNA assays for C. lusitaniae.ResultsCandida PR was observed in 33 of 405 samples (8.1%), with higher rates for non-albicans species (26/186, 14%) than for C. albicans (7/219, 3.2%), and for fluconazole than for anidulafungin. MCT detected acquired resistance more often than routine AFST (18/405, 4.5%) and 9 of the 161 investigated blood cultures showed PR (5.6%). Multilocus sequence typing and random amplified polymorphic DNA did not reveal a uniform genetic correlate in strains studied.ConclusionsThis study shows that Candida single MIC-values obtained in routine diagnostics may be incidental, as they fail to detect PR and resistant subpopulations reliably. The reasons for PR seem to be manifold and should be regarded as a phenotypical expression of genomic variability irrespective of the underlying resistance mechanism, which may help to interpret ambiguous and non-reproducible AFST results.     

Species distribution and drug susceptibility of candida in clinical isolates from a tertiary care centre at Indore

Background: The incidence of fungal infections has increased significantly, contributing to morbidity and mortality. This is caused by an alarming increase in infections with multi-drug resistant bacteria leading to overuse of broad-spectrum antimicrobials, which lead to overgrowth of Candida, thus enhancing its opportunity to cause disease. Candida are major human fungal pathogens that cause both mucosal and deep tissue infections. Objective: The aim of our study was to identify the distribution of Candida species among clinical isolates and their sensitivity pattern for common antifungal drugs. Materials and Methods: Two hundred and thirty-seven different clinical isolates of Candida were collected from patients visiting to a tertiary care centre of Indore from 2010 to 2012. Identification of Candida species as well as antifungal sensitivity testing was performed with Vitek2 Compact (Biomerieux France) using vitek 2 cards for identification of yeast and yeast like organisms (ID-YST cards). Antifungal susceptibility testing was performed with Vitek2 “Fungal Susceptibility Card (AST YS01) kits respectively. Results: We found that the non-albicans Candida were more prevalent than Candida albicans in paediatric (<3 year) and older (>60 year) patients than other age group (4-18, 19-60 years) patients and also in intensive care unit (ICU) patients as compared to out patient department (OPD) patients. Resistance rates for amphotericin B, fluconazole, flucytosine, itraconazole, and voriconazole were 2.9%, 5.9%, 0.0%, 4.2% and 2.5%%, respectively. All the strains of C. krusei were found resistant to fluconazole with intermediate sensitivity to flucytosine. Conclusion: Species-level identification of Candida and their antifungal sensitivity testing should be performed to achieve better clinical results.     

Molecular identification,phylogenetic analysis and antifungal susceptibility patterns of Aspergillus nidulans complex and Aspergillus terreus complex isolated from clinical specimens

ObjectiveAspergillus sections Terrei and Nidulantes are the less common causes of invasive aspergillosis and pulmonary aspergillosis (PA) in immunocompromised patients when compared to A. fumigatus and A. flavus. Identifying these fungi as the infectious agent is crucial because of the resistance to amphotericin B (AMB) and increased lethality. The aim of this study was to identify the molecular status, evaluate the genetic diversity and examine the antifungal susceptibility profile of the uncommon Aspergillus species. Forty-five uncommon Aspergillus species were identified based on the microscopic and macroscopic criteria. Then, the molecular identification was performed using the sequencing beta tubulin (benA) gene. In vitro antifungal susceptibility to amphotericin B (AMB), itraconazole (ITC), ravuconazole (RAV), voriconazole (VRC), caspofungin (CFG) isavuconazole (ISA) and posaconazole (POS) test was performed according to the CLSI M38-A2 guidelines.ResultsA. terreus was the most species detected, followed by A. nidulans, A. latus, A. ochraceus, and A. citrinoterreus, respectively. The analysis of the benA gene showed the presence of 12 distinct genotypes among the A. terreus isolates. The other species did not show any intraspecies variation. CFG exhibited the lowest MEC₅₀/MIC₅₀ (0.007 μg/mL), followed by POS (0.125 μg/mL), VRC, ITC, ISA (0.25 μg/mL), RAV (0.5 μg/mL), and AMB (8 μg/mL). Among all the isolates, only 15.5% (7/45) were susceptible to AMB.ConclusionAntifungal susceptibility pattern of the uncommon Aspergillus species is useful to improve patient management and increase knowledge concerning the local epidemiology. Moreover, this information is necessary when an outbreak dealing with drug-resistant infections occurs.     

In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris

ObjectiveCandida auris has emerged as a health-care-associated and multidrug-resistant fungal pathogen of great clinical concern. As many as 50% of C. auris clinical isolates are reported to be resistant to amphotericin B, but no mechanisms contributing to this resistance have been identified. Here we describe a clinical case in which high-level amphotericin B resistance was acquired in vivo during therapy and undertake molecular and genetic studies to identify and characterize the genetic determinant of resistance.MethodsWhole-genome sequencing was performed on four C. auris isolates obtained from a single patient case. Cas9-mediated genetic manipulations were then used to generate mutant strains harbouring mutations of interest, and these strains were subsequently subjected to amphotericin B susceptibility testing and comprehensive sterol profiling.ResultsA novel mutation in the C. auris sterol-methyltransferase gene ERG6 was found to be associated with amphotericin B resistance, and this mutation alone conferred a >32-fold increase in amphotericin B resistance. Comprehensive sterol profiling revealed an abrogation of ergosterol biosynthesis and a corresponding accumulation of cholesta-type sterols in isolates and strains harbouring the clinically derived ERG6 mutation.ConclusionsTogether these findings definitively demonstrate mutations in C. auris ERG6 as the first identified mechanism of clinical amphotericin B resistance in C. auris and represent a significant step forward in the understanding of antifungal resistance in this emerging public health threat.     

The clinical significance of and the factors associated with macrolide resistance and poor macrolide response in pediatric Mycoplasma pneumoniae infection: A retrospective study

BackgroundMacrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain.MethodsThe data of the Laboratory Medicine Department of Chang Gung Memorial Hospital in northern Taiwan was searched for children with molecular confirmed macrolide-susceptible Mycoplasma pneumoniae (MSMP) and MRMP infections between January 2011 and December 2018. The clinical features, laboratory data, and chest image presentations were compared between patients with MRMP and MSMP infections and between patients with good and poor macrolide response, respectively.ResultsRecords from 158 patients were recovered. Of the enrolled patients 34 (22%) suffered MRMP infection, 27 (17%) had pleural effusions, and 47 (32%) had poor macrolide response. The macrolide resistance rate was 12% in 2011, 20% between 2015 and 2016, and 50% between 2017 and 2018, respectively. Other than a poor macrolide response, the MRMP and MSMP infections are clinically indistinguishable. The presence of pleural effusion and MRMP infections were found to be independently associated with a poor macrolide response, with odds ratios (95% confidence interval) of 14.3 (4.9–42.0) and 14.6 (5.4–40), respectively. The macrolide resistance rate of the patients with a poor macrolide response was 49% and 18% among all the patients enrolled and the patients with a pleural effusion, respectively.ConclusionThe macrolide resistance rate had possibly increased in recent years in Taiwan and should be continuously monitored. In addition, the macrolide response could be misleading in predicting a macrolide resistance especially for the patients with a pleural effusion.     

Clinical significance of chromosome 1p/19q loss of heterozygosity and Sox17 expression in oligodendrogliomas

Objective: To study chromosome 1p/19q loss of heterozygosity (LOH) and Sox17 protein expression in oligodendrogliomas and correlate this loss with clinicopathological features. Methods: This study included 100 cases of oligodendrogliomas at the First Affiliated Hospital of Xinjiang Medical University from 2003 to 2014. The cases included paraffin-embedded tissues from 50 low-grade oligodendrogliomas and 50 anaplastic oligodendrogliomas. Chromosome 1p/19q LOH was detected by fluorescence in situ hybridization (FISH) and Sox17 protein expression was analyzed by immunohistochemistry. Clinicopathological characteristics of the oligodendrogliomas were compared and prognosis analyzed using Cox regression and Kaplan-Meier analyses. Results: The LOH positivity rate of 1p/19q was 52% in 50 cases of low-grade oligodendrogliomas and 68% in 50 cases of anaplastic oligodendrogliomas (P = 0.102). The rates of Sox17 expression were significantly different in oligodendrogliomas (82%) and anaplastic oligodendrogliomas (62%, P = 0.026). Single factor analysis determined that 1p/19q LOH (P = 0.000), Sox17 protein expression (P = 0.000), location (P = 0.001), chemotherapy (P = 0.000), and radiation therapy (P = 0.001) were associated with oligodendroglioma patient prognosis. Cox multiple factors regression analysis determined that 1p/19q LOH and Sox17 expression were independent prognostic factors of oligodendrogliomas. Conclusion: In this study, oligodendroglioma patients with 1p/19q LOH and Sox17 protein expression had a better prognosis. Thus, analysis of 1p/19q LOH and Sox17 protein expression could significantly enhance diagnostic accuracy, guide treatment, and improve the prognosis.     

Clinical utility of antifungal susceptibility testing in patients with fungal rhinosinusitis

PurposeTo determine the association between antifungal susceptibility test (AFST) results and in vivo therapeutic response in Indian patients with fungal rhinosinusitis.MethodsThe clinicoradiological, fungal culture, AFST, histopathology results and outcomes of 48 patients with fungal rhinosinusitis seen between 20132015 were analysed. Minimum inhibitory concentration (MIC) determination was performed for amphotericin B, itraconazole, voriconazole and posaconazole.ResultsForty patients had invasive and 8 had non-invasive fungal sinusitis. Rhizopus and Aspergillus species which comprised 46.9% each of isolates were mostly associated with acute invasive fungal rhinosinusitis and chronic granulomatous fungal rhinosinusitis respectively. All patients with non-invasive fungal rhinosinusitis had Aspergillus isolates.The Geometric Mean (GM) MIC for R. arrhizus of amphotericin B and posaconazole was 0.51 mcg/mL and 3.08 mcg/mL respectively and for A. flavus species for amphotericin B and voriconazole values were 1.41mcg/mL and 0.35 mcg/mL respectively.In patients with Aspergillus infections, while there was no association of MICs for azoles and outcome (p = 1), a strong association was noted between azole therapy and a good outcome (p = 0.003). In patients with Rhizopus infections, no association was found between MICs for amphotericin B and outcome (p = 1) and because of therapeutic complications, no association was found between amphotericin B therapy and outcome (p = 1).ConclusionNo significant association exists between in vitro (AFST) and in vivo responses despite low GM MICs for the drugs used in Aspergillus and Rhizopus infections. Therapeutic complications following conventional amphotericin B therapy confounds analysis. Clinical responses suggest that azoles are the drug of choice for Aspergillus infections.     

Current scenario of the search for new antifungal agents to treat Candida auris infections: An integrative review

Candida auris emerges as an important causative agent of fungal infections, with worrisome mortality rates, mainly in immunocompromised individuals. This scenario is worsened by the limited availability of antifungal drugs and the increasing development of resistance to them. Due to the relevance of C. auris infections to public health, several studies aimed to discover new antifungal compounds capable of overcoming this fungus. Nonetheless, these information are decentralized, precluding the understandment of the current status of the search for new anti-C. auris compounds. Thus, this integrative review aimed to summarize information regarding anti-C. auris compounds reported in literature. After using predefined selection criteria, 71 articles were included in this review, and data from a total of 101 substances were extracted. Most of the studies tested synthetic substances, including several azoles. Moreover, drug repurposing emerges as a suitable strategy to discover new anti-C. auris agents. Few studies, however, assessed the mechanism of action and the in vivo antifungal activity of the compounds. Therefore, more studies must be performed to evaluate the usefulness of these substances as anti-C. auris therapies.     

Antifungal sensitivity and species of yeasts in oral mucosa of street mixed-breed dogs

The aim of this research is to verify the yeast species isolated from oral mucosa in street mixed-breed dogs and to determine the antifungal profiles. After capturing and sedating the animals, oral mucosa samples were collected from fifty dogs and the materials were inoculated on Sabouraud dextrose agar with chloramphenicol. Forty-three yeast strains were isolated and identified trough the API-20C AUX method. Thirty-seven (86.1%) of the yeasts belonged to genus Candida, five (11.6%) to genus Trichosporon and only one strain (2.3%) to genus Malassezia. The sensitivity profiles to anifungals (amphotericin B, itraconanole, ketoconazole, fluconazole and variconazole) were determined through Etest® method. This study found resistance of some yeasts to amphotericin B and a good susceptibility to voriconazole and ketoconazole. Some of these antifungals are used in veterinary medical practice. This research is the first investigation on street mixed-breed dogs regarding yeast identifications and antifungals profiles.