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There is an ongoing effort to optimize and revise antifungal susceptibility testing (AFST) methods due to the rising number of fungal infections and drug-resistant fungi. The rising antifungal resistance within Candida and Aspergillus species, which are common contributors to invasive fungal infections (IFIs), is a cause for concern, prompting an expanding integration of in vitro AFST to guide clinical decisions. To improve the relevance of in vitro AFST results to therapy outcomes, influential factors should be taken into account. The tested medium is one of several factors that could affect the results of AFST. The present study evaluated the effect of two complex media (Sabouraud dextrose and Columbia) versus the standard defined medium (RPMI 1640) on the AFST results of amphotericin B, posaconazole, and voriconazole against Candida spp. and Aspergillus spp. representatives, utilizing the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Etest methods. Overall, Candida species exhibited higher variability in minimum inhibitory concentration (MIC) across different media (more than three log2 dilutions) comparing to Aspergillus spp., while quality control isolates showed consistency regardless of tested media, antifungals, and methods. When comparing tested methods, MIC variation was mostly detected using EUCAST than it was using Etest. [ABSTRACT FROM AUTHOR]

Candida auris has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.7%) and 52 controls (C. albicans, 21.6%; C. parapsilosis, 21.6%; C. tropicalis, 21.6%; C. glabrata, 1.4%) were included and analysed in this study. Risk factors, clinical and microbiological characteristics and outcomes of patients with C. auris and non-auris Candida species (NACS) candidemia were compared. Previous fluconazole exposure was significantly higher in C. auris candidemia patients (OR 3.3; 1.15–9.5). Most C. auris isolates were resistant to fluconazole (86.3%) and amphotericin B (59%) whilst NACS isolates were generally susceptible. No isolates resistant to echinocandins were detected. The average time to start antifungal therapy was 3.6 days. Sixty-three (85.1%) patients received adequate antifungal therapy, without significant differences between the two groups. The crude mortality at 30 and 90 days of candidemia was up to 37.8% and 40.5%, respectively. However, there was no difference in mortality both at 30 and 90 days between the group with candidemia by C. auris (31.8%) and by NACS (42.3%) (OR 0.6; 95% IC 0.24–1.97) and 36.4% and 42.3% (0.77; 0.27–2.1), respectively. In this study, mortality due to candidemia between C. auris and NACS was similar. Appropriate antifungal therapy in both groups may have contributed to finding no differences in outcomes. [ABSTRACT FROM AUTHOR]

Background: Although uncommon, there is increasing interest and public health concerns of the pathogen Prototheca spp, a ubiquitous achlorophilic microalgae that can affect both humans and animals. High mortality rates have been reported in immunocompromised patients with disseminated infection, but no data is available in the immunocompetent population. Case Presentation: We present the case of a 59-year-old man from rural area of Colombia who was admitted to the intensive care unit due to decompensated heart failure that was difficult to medically manage, with development of septic shock and isolation of Prototheca wickerhamii from blood culture. Fluconazole and Amphotericin B were given with successful outcome. Conclusions: To date, protothecosis and its virulence factors and pathogenesis remain to be fully understood, in our case the isolation of this microalga and its implication of exacerbating chronic conditions such as heart failure is unclear. The medical-scientific community is invited to study this microorganism to determine effective management strategies, as well as its timely identification, treatment, and control, to avoid fatal outcomes. [ABSTRACT FROM AUTHOR]

Background: Since the first report of Candida auris in 2016, the Colombian Instituto Nacional de Salud (INS) has implemented a national surveillance of the emerging multidrug‐resistant fungus. Objectives: This report summarises the findings of this laboratory‐based surveillance from March 2016 to December 2020. Results: A total of 1720 C. auris cases were identified, including 393 (23%) colonisation cases and 1327 (77%) clinical cases. Cases were reported in 20 of 32 (62%) departments of Colombia and involved hospitals from 33 cities. The median age of patients was 34 years; 317 (18%) cases were children under 16 years, 54% were male. The peak number of cases was observed in 2019 (n = 541). In 2020, 379 (94%) of 404 cases reported were clinical cases, including 225 bloodstream infections (BSI) and 154 non‐BSI. Among the 404 cases reported in 2020, severe COVID‐19 was reported in 122 (30%). Antifungal susceptibility was tested in 379 isolates. Using CDC tentative breakpoints for resistance, 35% of isolates were fluconazole resistant, 33% were amphotericin B resistant, and 0.3% isolates were anidulafungin resistant, 12% were multidrug resistant, and no pan‐resistant isolates were identified. Conclusion: For five years of surveillance, we observed an increase in the number and geographic spread of clinical cases and an increase in fluconazole resistance. These observations emphasise the need for improved measures to mitigate spread. [ABSTRACT FROM AUTHOR]

Histoplasmosis presents a substantial clinical challenge globally, with a particular prevalence in South America, especially among patients with concurrent Human Immunodeficiency Virus (HIV) infection. Despite itraconazole's established efficacy, investigating alternative therapeutic approaches remains imperative. This is the largest study in our region to date, assessing the effectiveness of the less explored posaconazole treatment. This observational study, conducted at Fundación Valle del Lili (FVL) from 2016 to 2022, encompassed adults with disseminated histoplasmosis. Patients (n = 31) were treated with liposomal amphotericin B as an initial treatment, followed by consolidation treatment with posaconazole or itraconazole. Patients with single-organ cases, those lacking microbiological diagnosis, those who received initial treatment with antifungals other than liposomal Amphotericin B and those with < 6 months follow-up were excluded (Figure 1). Analyses considered population characteristics, treatments, and outcomes. Patients (average age: 45.6; 58.1% female) had common comorbidities (HIV 38.7%, solid organ transplantation 29% and oncologic disease 12.9%). Lungs (48.4%) and lymph nodes (16.1%) were commonly affected. Biopsy (64.5%) was the primary diagnostic method. Initial treatment with liposomal amphotericin B (100%) was given for 14 days on average. Follow-up indicated 71% completion with 19.4% requiring treatment modifications. Notably, 70.9% completed a posaconazole consolidation regimen over 350 days on average. Drug interactions during consolidation (80.6%) were common. No relapses occurred, and three deaths unrelated to histoplasmosis were reported. Traditionally, itraconazole has been the prevalent initial treatment; however, in our cohort, 55.9% of patients received posaconazole as the primary option. Encouragingly, posaconazole showed favorable tolerance and infection resolution, suggesting its potential as an effective and well-tolerated alternative for consolidation treatment. This finding prompts further exploration of posaconazole, potentially leading to more effective patient care and better outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background Globally, Candida auris is an emerging pathogen that poses an essential threat in healthcare settings presenting as outbreaks requiring significant allocation of infection control interventions to curb transmission. This fungal pathogen was initially identified in 2009 in Japan, but it has spread to all continents. Candida auris poses significant diagnostic and treatment challenges. Conventional microbiology laboratories often misidentify this pathogen as Candida haemulonii or as other Candida spp. Rhodoturola glutinis, and even with some bacterial pathogens, including Neisseria meningitidis serogroup A. Furthermore, C. auris displays distinct mechanisms of antifungal resistance to azoles and amphotericin B formulations. Most of the case series and outbreak reports have included invasive infections in adult populations. Methods Herein, we present a cluster of neonatal infections caused by Candida auris at a large referral center in Colombia. Results We report a case series of 8 neonates and infant patients who were seen at a large referral center in Colombia and who develop invasive infections caused by C. haemulonii and C. auris. Discussion Our report highlights the diagnostic challenges in identifying this fungal pathogen correctly, its clinical spectrum of disease, recommendations for empiric antifungal therapy, and it is not always associated with a high case fatality rate. [ABSTRACT FROM AUTHOR]

Background: Candida auris is an emerging yeast frequently reported as resistant to multiple antifungal drugs commonly used to treat Candida infections. This specie can colonize the patient's skin and has great ability for producing outbreaks in hospitals. C. auris is phylogenetically related to other Candida species, can be misidentified using conventional biochemical or commercial methods and requires specific technology for its identification. Case report: We report the first isolate of C. auris in Cali, Colombia, from a central venous catheter in a 37-year-old patient with rheumatoid arthritis and endocarditis who did not have symptoms of sepsis. The yeast was initially misidentified as C. haemulonii using the Phoenix system and subsequently identified as C. auris by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The broth microdilution method was used to determine the minimum inhibitory concentration; the isolate was susceptible to fluconazole, itraconazole, voriconazole and amphotericin B. Conclusions: This report contributes to knowledge of the epidemiology of C. auris infections in individuals with underlying disease and describes an isolate with a behavior different from what is usually reported. [ABSTRACT FROM AUTHOR]

Since 2016, in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster ( N = 166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these, 85% ( N = 22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% ( N = 38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates. This work describes molecular mechanisms associated with C. auris antifungal resistance in Colombia. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia., Importance: Candida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread., Competing Interests: The authors declare no conflict of interest.

Background and Objectives: Helicobacter pylori is a Gram-negative spiral-shaped bacterium that contaminates more than half of the world's inhabitants, and infection with this bacterium is associated with some gastric disorders. Also, 5% to 10% of H. pylori genes are specific to this bacterium and many bacterial virulence factors fall into this group. The cagA, vacA, sodB and hsp60 are among important virulence factors of H. pylori. Materials and Methods: A gastric biopsy specimen was taken from 341 gastric patients and cultivated on a Colombia agar plate, containing various antibiotics, such as vancomycin, amphotericin B, and trimethoprim & polymyxin B, and incubated for 3 to 10 days under microaerophilic conditions at 37°C. PCR was used to detect the ureC, cagA, vacA, sodB and hsp60 genes. Results: In this study, 131 isolates were identified as H. pylori. The prevalence of cagA, vacA, sodB and hsp60 were 74%, 100%, 92.4% and 96.2%, respectively. The correlation between the clinical forms of the disease and the virulence genes were analyzed by statistical tests and no significant correlation was found. Conclusion: The obtained results are similar to some studies conducted in different parts of the world and is different in other cases. This discrepancy is due to the difference in the type of gastric disorders, sample size and methodology. [ABSTRACT FROM AUTHOR]

Background Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015–2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods We sampled patients, patient contacts, healthcare workers, and the environment in 4 hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into 4 zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results Seven of the 17 (41%) people swabbed were found to be colonized. Candida auris was isolated from 37 of 322 (11%) environmental samples. These were collected from a variety of items in all 4 zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel nonsynonymous mutations were found to be significantly associated with AmB resistance. Conclusions Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility. [ABSTRACT FROM AUTHOR]

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Leishmaniasis is an infectious disease caused by species of the genus Leishmania. Among its main clinical manifestations, cutaneous leishmaniasis (CL) is the most prevalent in Colombia and is produced by endemic species such as Leishmania (V.) panamensis, L. (V.) braziliensis, and L. (V.) guyanensis. Although leishmaniasis is treatable, treatment failure to second-line therapy, such as amphotericin B (AmB), has been reported in recent years. Therefore, it is essential to understand the parasite molecular mechanisms that may explain differences in susceptibility to currently available drugs. In trypanosomatid parasites, lathosterol oxidase (LOS) and vesicleassociated membrane protein (VAMP) have been described as factors whose negative regulation decreases sensitivity to AmB. In addition, our previous findings evidenced that L. (V.) braziliensis clones with induced resistance to Miltefosine and low sensitivity to AmB had lower mRNA levels for these genes compared to the uninduced control. However, the involvement of both genes in increased AmB tolerance in L. (V.) braziliensis is still unclear. Hence, we aimed to evaluate the role of LOS and VAMP in increased tolerance to AmB in L. (V.) braziliensis by comparing their gene structure among clinical isolates with different susceptibility to AmB, as well as the in silico design of a CRISPR-Cas9 system for eventual functional validation. For this purpose, the sequence of LOS and VAMP genes of 13 clinical isolates of L. braziliensis with different sensitivity to AmB were identified using genomic data produced by Illumina sequencing and mapped against the L. braziliensis MHOM/BR/75/M2904 genome. Multiple alignments of LbLOS and LbVAMP genes among isolates revealed the presence of polymorphisms (Single nucleotide polymorphisms -SNPs-, insertions/deletions) mainly in the 5' and 3' untranslated regions (UTRs) of both genes, most frequently in LOS UTRs. Preliminary analyses have shown non-specific polymorphisms in LbLOS and LbVAMP UTRs of clinical isolates with higher AmB tolerance that can be related to a particular regulation of LbLOS and LbVAMP expression. Therefore, it is crucial to validate changes in the expression of both genes among the different clinical isolates. Finally, a CRISPR-cas9 strategy for LOS and VAMP knockout in L. braziliensis M2903 was designed in silico using the EuPaGDT and LeishGEdit platforms. From these analyses, two sets of sgRNAs were designed for partial or total excision of LOS and VAMP ORFs, sgRNAs specificity was verified by off-target absence in the L. braziliensis MHOM/BR/75/M2903 genome. These studies will allow us to determine whether the gain of AmB tolerance is certainly related to LbLOS and LbVAMP depletion, suggesting this mechanism as a factor associated with AmB tolerance in L. braziliensis. [ABSTRACT FROM AUTHOR]

Human leishmaniasis is a disease caused by infection with protozoan parasites of the genus Leishmania, presenting tegumentary (TL) or visceral manifestations. In Colombia, TL is predominant and is associated with Leishmania species of the subgenus Viannia such as Leishmania (V.) panamensis, L. (V.) braziliensis, and L. (V.) guyanensis. As the first line of treatment, pentavalent antimony salts are used and as the second line miltefosine, pentamidine, or amphotericin are prescribed. There is a variable percentage of therapeutic failure in TL for each of these drugs, and it is not well known the role of the parasite genetics regarding the treatment failure. The potential loss of susceptibility to amphotericin B (AmB) is a major issue since it is generally the last treatment option and natural resistance has not been described to AmB in Leishmania (Viannia) species. The present work aims to establish whether there is genomic variation between clinical isolates of L. (V.) braziliensis with different degrees of AmB susceptibility. For this purpose, phenotypic and genetic features of thirteen clinical isolates of L. (V.) braziliensis from the Colombian Orinoco and Amazon regions were analyzed. The isolates were evaluated in early culture stages (<10 passages) and two of them in late culture stages (>20). The strain MHOM/BR/75/M2904 was included as the reference genome. The in vitro doubling time of these isolates in their promastigote stage grown in Schneider medium ranged from 8.099h to 17.87h (median=9.352 h, IQR=3.983). Susceptibility to AmB, calculated as the IC50, ranged from 0.016 to 0.207 μg/mL (median= 0.071 μg/mL, IQR= 0.058) in promastigotes and from 0.008 to 0.244 μg/mL (median= 0.017 μg/mL, IQR= 0.012) in amastigotes. The in vitro infectivity to human macrophages, calculated as the percentage of infection to U937 derived macrophages, ranged from 26% to 64% (median= 42%, IQR= 15.5). These data correspond with a heterogeneous sample and groups with similar behavior for the evaluated variables were identified - e.g., isolates particularly sensitive or tolerant to AmB. Subsequently, a ploidy analysis was performed observing that the 13 isolates of L. (V) braziliensis were found to be predominantly diploid with exception of chromosome 31 which is tetraploid. Some isolates showed chromosome 33 aneuploidy and there it was found that chromosome 34, from all isolates, presents an increase in read depth of a 60Kb region (13 genes) and an LD1 amplification of 140Kb (38 genes) was found in one specific isolate. These observations constitute a preliminary analysis and once the genomic profiling is complete, a correlation between it and the parasite phenotype will be assessed. [ABSTRACT FROM AUTHOR]

Laryngeal histoplasmosis usually occurs in immunocompromised patients through the dissemination of the fungus from the lungs to other organs. Histoplasmosis isolated laryngeal (primary) is rare. If a patient presents with a history of renal transplant immunosuppression, primary histoplasmosis with laryngeal supraglottic granulomatous inflammation that was treated with amphotericin B and itraconazole, with complete resolution of laryngeal lesions. [ABSTRACT FROM AUTHOR]

Paracoccidioides brasiliensis is the ethiological agent of one of the most prevalent systemic mycosis in Latin America, where around ten-million individuals are affected. Brazil has the highest incidence but in Venezuela, Colombia, Ecuador, and Argentina cases have also been reported. We describe a 56-year-old male with a one year history of lip, oral mucosa, and lung lesions. Granulomas and multinucleated giant cells were observed in histopathological evaluation with haematoxilyn-eosin stain. Mycologic studies (KOH and Gomori Grocott stain) showed blastoconidias with multiple budding. Serologic tests for paracoccidioidine were reactive. A diagnosis of chronic multifocal paracoccidioidomycosis was made. Initially, amphotericin B 0.7 mg/kg per day was started for fifteen days and consecutively itraconazole (400 mg/day) was administered orally with improvement of skin and lung lesions; however, an important residual fibrosis was observed. The patient was lost to follow up. We highlight the importance of an early diagnosis and adequate treatment to decrease sequelae in patient quality of life. [ABSTRACT FROM AUTHOR]