Identification of Yeast and Yeast-Like Fungi at a Tertiary Care Center: A Retrospective Study.

Background Fungal infections pose a significant global health challenge. Despite their substantial impact, these ubiquitous fungi can become pathogenic but have not received adequate attention in public health, leading to infections that are often underestimated by the general public and healthcare professionals. Candida species and Cryptococcus species play a key role in these infections, with emerging multidrug resistance in Candida species posing considerable challenges. This study aimed to understand the prevalence of yeast and yeast-like infections, particularly in the COVID-19 era, and to assess the antifungal susceptibility pattern. Methodology A retrospective observational study was conducted at a rural tertiary care medical college in Maharashtra, India. Retrospective records of samples processed for fungal culture were analyzed in the microbiology department. Yeast identification and antifungal susceptibility were performed using the VITEK-2 automated system. Results Among 95 fungal isolates, 86 (90.52%) were yeast isolates, primarily non-albicans Candida (NAC) species. Candida albicans accounted for 41 (47.67%) yeast isolates. In 14 isolates, NAC species were not identified by the VITEK-2 system up to the species level. Isolates from urine samples contributed the highest percentage of 61% (58) of yeast isolates. C. albicans showed high sensitivity to most antifungal agents. Other Candida species, such as Candida famata, Candida parapsilosis, and Candida guilliermondii, were sensitive to all antifungal agents. Candida auris showed complete resistance to amphotericin B and fluconazole but sensitivity to other agents. Mixed sensitivity patterns were observed in Candida ciferri and Candida lusitaniae, with some resistance to voriconazole, caspofungin, and micafungin. Conclusions This study shows the increasing prevalence of yeast and yeast-like infections, particularly NAC, during the COVID-19 era. Improved yeast identification and susceptibility testing are crucial for guiding the appropriate treatment and mitigating the impact of these infections, emphasizing the need for comprehensive future studies in this area.

A prospective observational study on species differentiation and antifungal susceptibility pattern in patients with genital candidiasis.

Background: Candidial balanitis, balanoposthitis and vulvovaginitis can be diagnosed by direct microscopy, culture and treated with antifungals. Resistance to antifungals is emerging. Hence, we conducted a study to identify the causative species and antifungal susceptibility. Aim: To observe the species differentiation and antifungal susceptibility pattern in patients with genital candidiasis. Materials and Methods: A prospective observational study was carried out that included 54 patients of age group (18-60 years) diagnosed clinically and direct microscopically (KOH) for genital candidiasis. Culture was done using Sabouraud dextrose agar. Species identification and antifungal susceptibility were tested. Descriptive data were expressed in the form of frequency and percentage. Results: Out of 54 patients, 41 had culture positive candidiasis. Among the isolated species, 68.3% were Candida albicans (28/41) and 31.7% were non- albicans Candida spp. Among non-albicans Candida species (13/41), Candida glabrata (19.5%), Candida tropicalis (7.3%), Candida guilliermondii (2.4%), Candida parapsilosis (2.4%) were identified. Antifungal susceptibility was tested for fluconazole (FLU), clotrimazole (CLTZ), itraconazole (ITZ), ketoconazole (KTZ), voriconazole (VOR), amphotericin-B (AMPH-B). Except C. glabrata and C.parapsilosis, all other species were sensitive to all tested antifungals. All isolated species were sensitive to KTZ, VOR, AMPH-B, and CLTZ. Nearly 22% of isolates were resistant to fluconazole. Conclusion: C. glabrata causes complicated, severe recurrent vulvovaginitis which is fluconazole resistant. Drug sensitivity prior prescribing antifungal agent identifies appropriate drug, decreases patient's disease morbidity and cross resistance.

Predominance of Candida glabrata in candidemia among patients with solid tumor cancer in Oman: A retrospective study.

Objectives: Candida species frequently cause bloodstream infections; however, there is a lack of epidemiological studies on candidemia in Oman. Methods: To address this, we conducted a retrospective study at Sultan Qaboos Comprehensive Cancer and Research Center from October 2021 to October 2023. Results: Our study identified 27 episodes of candidemia among 26 patients with cancer, with an incidence of 4.9 per 1000 admissions. Non-albicans Candida (NAC) prevailed over C. albicans (70.37% vs 29.62%), with C. glabrata as the predominant NAC species (n = 10; 37%). The 30-day mortality rate was 40.7%, showing no significant difference between NAC and C. albicans but was notably higher in critically ill patients (P = 0.03). Conclusion: In Oman, NAC surpasses C. albicans as a causative pathogen for candidemia with a high mortality rate.

Candida parapsilosis: A systematic review to inform the World Health Organization fungal priority pathogens list.

Candida parapsilosis is globally distributed and recognised for causing an increasing proportion of invasive Candida infections. It is associated with high crude mortality in all age groups. It has been particularly associated with nosocomial outbreaks, particularly in association with the use of invasive medical devices such as central venous catheters. Candida parapsilosis is one of the pathogens considered in the WHO priority pathogens list, and this review was conducted to inform the ranking of the pathogen in the list. In this systematic review, we searched PubMed and Web of Science to find studies between 2011 and 2021 reporting on the following criteria for C. parapsilosis infections: mortality, morbidity (hospitalisation and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. We identified 336 potentially relevant papers, of which 51 were included in the analyses. The included studies confirmed high mortality rates, ranging from 17.5% to 46.8%. Data on disability and sequelae were sparse. Many reports highlighted concerns with azole resistance, with resistance rates of >10% described in some regions. Annual incidence rates were relatively poorly described, although there was clear evidence that the proportion of candidaemia cases caused by C. parapsilosis increased over time. While this review summarises current data on C.parapsilosis, there remains an urgent need for ongoing research and surveillance to fully understand and manage this increasingly important pathogen.

Unveiling the antifungal mechanisms of CTP, a new copper(II)-theophylline/1,10-phenanthroline complex, on drug-resistant non-albicans Candida species.

Candida species undeniably rank as the most prevalent opportunistic human fungal pathogens worldwide, with Candida albicans as the predominant representative. However, the emergence of non-albicans Candida species (NACs) has marked a significant shift, accompanied by rising incidence rates and concerning trends of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our research group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as "CTP" - Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP demonstrated significant efficacy in inhibiting mitochondrial dehydrogenases, leading to heightened intracellular reactive oxygen species production. CTP treatment resulted in substantial damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and induced DNA fragmentation as revealed by the TUNEL assay. Scanning electron microscopy images of post-CTP treatment NACs further illustrated profound alterations in the fungal surface morphology, including invaginations, cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to a polystyrene surface and to form robust biofilm structures. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. In conclusion, CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.

Emerging trends of invasive yeast infections and azole resistance in Beijing intensive care units.

BACKGROUND: Invasive fungal infections pose a substantial threat to patients in healthcare settings globally. Recent changes in the prevalence of fungal species and challenges in conducting reference antifungal susceptibility testing emphasize the importance of monitoring fungi and their antifungal resistance. METHODS: A two-phase surveillance project was conducted in Beijing, China, involving 37 centres across 12 districts, from January 2012 to December 2013 and from January 2016 to December 2017. FINDINGS: We found that the proportion of Candida albicans in intensive care units (ICUs) during 2016-2017 exhibited a significant decline compared with the 2012-2013 period, although it remained the most predominant pathogen. In contrast, the prevalence of Nakaseomyces glabratus (formerly Candida glabrata) and Candida tropicalis notably increased during the two-phase surveillance. The high prevalence of C. tropicalis and its resistance to azole drugs posed a serious threat to patients in ICUs. The pathogens causing invasive fungal infections in Beijing were relatively sensitive to echinocandins. While C. albicans continued to exhibit susceptibility to azoles, the resistance and growth rates of C. tropicalis towards azoles were particularly prominent. Concerns were raised due to the emergence of multiple, short-term isolates of Clavispora lusitaniae and Candida parapsilosis complex in neonatal ICUs, given their similarity in antifungal susceptibilities. Such occurrences point towards the potential for transmission and persisting presence of these pathogens within the ICU environment. CONCLUSIONS: Our study complements existing data on the epidemiology of invasive fungal infections. It is imperative to exercise cautious medication management for ICU patients in Beijing, paying particular attention to azole resistance in C. tropicalis.

Treatment of vaginitis caused by non-albicans Candida species.

INTRODUCTION: In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs available. Drug selection is further handicapped by an absence of data of clinical efficacy of available antifungal drugs for these infections. AREAS COVERED: In this review, attention is directed at the cause of drug shortage as well as increased frequency of non-albicans Candida (NAC) vulvovaginitis. There is widespread recognition of reduced in vitro azole drug susceptibility in NAC species. Moreover, antifungal susceptibility tests have not been standardized or validated for NAC isolates, hence clinicians rely on an element of empiricism especially given the absence of randomized controlled comparative studies targeting NAC species. Clinical spectrum of NAC species isolates is highly variable with ongoing difficulty in determining a causal role in symptomatic patients. EXPERT OPINION: We have entered the era of demand for Candida species-specific therapy and although consensus treatment guidelines are emerging, new antifungal agents that target these multiple-azole resistant or relatively resistant vaginal NAC species are urgently needed.

Non-albicans Candida Infection as a Rare Cause of Emphysematous Pyelonephritis in an Uncontrolled Diabetic Patient: A Case Report.

The uncommon but dangerous condition known as emphysematous pyelonephritis (EPN) usually affects people with diabetes. This potentially fatal illness is characterized by gas-forming necrosis of the kidneys and surrounding tissues, typically brought on by urinary tract bacteria. Fungal EPN, less prevalent than bacterial EPN, has been reported in a few isolated cases. Cultures of the urine or blood often detect the infection. With an 18% fatality rate, EPN is still a serious illness despite advancements in therapy. High suspicion for EPN is critical in diabetic patients experiencing pyelonephritis. Interestingly, women with uncontrolled diabetes seem to be more susceptible. While Escherichia coli is the usual culprit, rare cases involve Candida species. This case report describes a pathogen that is rarely encountered and causes EPN. A diabetic woman in her sixties without prior hospitalizations presented with a sudden fever and excruciating abdominal pain. The patient also complained of abdominal distension with reduced urine output and breathlessness at rest. Investigations revealed left-sided EPN that was "WAN Type 1." We treated the patient according to culture sensitivity with systemic antifungals, percutaneous nephrostomy (PCN), and ureteral stenting (double J stent or DJ stent). Following successful treatment, the patient recovered and was discharged. This case highlights the importance of considering uncommon causes, even in seemingly typical presentations of EPN. Our case is unique as the patient had an infection with non-albicans Candida with a complication of anuric acute kidney injury and uncontrolled diabetes mellitus.

Photoactivated riboflavin inhibits planktonic and biofilm growth of Candida albicans and non-albicans Candida species.

Fungal infections caused by Candida species pose a serious threat to humankind. Antibiotics abuse and the ability of Candida species to form biofilm have escalated the emergence of drug resistance in clinical settings and hence, rendered it more difficult to treat Candida-related diseases. Lethal effects of Candida infection are often due to inefficacy of antimicrobial treatments and failure of host immune response to clear infections. Previous studies have shown that a combination of riboflavin with UVA (riboflavin/UVA) light demonstrate candidacidal activity albeit its mechanism of actions remain elusive. Thus, this study sought to investigate antifungal and antibiofilm properties by combining riboflavin with UVA against Candida albicans and non-albicans Candida species. The MIC20 for the fluconazole and riboflavin/UVA against the Candida species tested was within the range of 0.125-2 µg/mL while the SMIC50 was 32 µg/mL. Present findings indicate that the inhibitory activities exerted by riboflavin/UVA towards planktonic cells are slightly less effective as compared to controls. However, the efficacy of the combination towards Candida species biofilms showed otherwise. Inhibitory effects exerted by riboflavin/UVA towards most of the tested Candida species biofilms points towards a variation in mode of action that could make it an ideal alternative therapeutic for biofilm-related infections.

The impact of increasing non-albicans Candida trends on diagnostics in immunocompromised patients.

Invasive candidiasis (IC) represents a growing concern worldwide, with a considerable increase in non-albicans Candida (NAC) species. The study's primary goal was to determine if species identification by semi-nested PCR (sn-PCR) with primers for the five most prevalent Candida species is sufficient to deal with the current trends of Candida infections in cancer patients. Over one year, Candida isolates were collected from samples of patients with hematological and solid organ tumors in a single center. Species of Candida were identified by chromagar and multiplex sn-PCR using specific primers for Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, and the Candida parapsilosis complex. Most Candida infection episodes are caused by NAC species (70.5% of 105 isolates). Rare species (14 isolates) accounted for 13.3% of isolates and were not identified by sn-PCR using the five most common Candida species primers. More than half of these rare species caused candidemia in cancer patients (57.1%; p = 0.011). The risk factor for candidiasis was recent surgeries (p = 0.020) in adults and chemotherapy in pediatric patients (p = 0.006). Prolonged hospitalization and genitourinary tract cancer were significantly associated with invasive infections (p = 0.005 and 0.049, respectively). Recent surgery was a significant risk factor associated with C. parapsilosis and C. glabrata infections (P = 0.038 and 0.003, respectively), while C. tropicalis was significantly more common in patients with hematological malignancies (P = 0.012). Techniques with a broader identification spectrum than the major five Candida species are crucial for the optimal management of cancer patients.

Evaluation of Antifungal Selective Toxicity Using Candida glabrata ERG25 and Human SC4MOL Knock-In Strains.

With only four classes of antifungal drugs available for the treatment of invasive systemic fungal infections, the number of resistant fungi is increasing, highlighting the urgent need for novel antifungal drugs. Ergosterol, an essential component of cell membranes, and its synthetic pathway have been targeted for antifungal drug development. Sterol-C4-methyl monooxygenase (Erg25p), which is a greater essential target than that of existing drugs, represents a promising drug target. However, the development of antifungal drugs must consider potential side effects, emphasizing the importance of evaluating their selective toxicity against fungi. In this study, we knocked in ERG25 of Candida glabrata and its human ortholog, SC4MOL, in ERG25-deleted Saccharomyces cerevisiae. Utilizing these strains, we evaluated 1181-0519, an Erg25p inhibitor, that exhibited selective toxicity against the C. glabrata ERG25 knock-in strain. Furthermore, 1181-0519 demonstrated broad-spectrum antifungal activity against pathogenic Candida species, including Candida auris. The approach of utilizing a gene that is functionally conserved between yeast and humans and subsequently screening for molecular target drugs enables the identification of selective inhibitors for both species.

Pseudolaric Acid A: A Promising Antifungal Agent Against Prevalent Non-albicans Candida Species.

Purpose: The non-albicans Candida (NAC) species have recently gained great importance worldwide due to the increasing proportion in candida causing bloodstream infections. This investigation aimed to explore the efficacy of Pseudolaric acid A (PAA, a diterpenoid derived from Pseudolarix kaempferi) and its synergistic effect with fluconazole (FLC) against NAC species, including C. tropicalis, C. parapsilosis complex, and C. glabrata. Methods: The microdilution checkerboard assay and time-killing curves were performed to detect the antifungal efficiency. To examine the integrity of cell walls and membranes, calcofluor white stain and propidium iodide stain were used. The changes of intracellular ultrastructure in Candida cells after treatment were observed using transmission electron microscopy. Changes in cell viability with the autophagy inhibitor 3-MA were assessed by the XTT method. Results: It was revealed that PAA alone is effective on C. tropicalis, C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis (MIC 8-128 µg/mL). Strong synergism against FLC-resistant C. tropicalis was observed (FICI 0.07-0.281), when PAA and FLC were combined. PAA had dose-dependently detrimental effects on C. tropicalis cell membranes. Moreover, increased vacuoles and autophagosome formation were found in C. tropicalis exposed to PAA. And the inhibitory effect of PAA against C. tropicalis can be relieved by autophagy inhibitor 3-MA in a certain concentration range. Ultrastructural alterations of C. tropicalis were more pronounced under the combination of PAA and FLC, including separation of the cell membrane from the cell wall, increased number of vacuoles, and degradation of organelles. Conclusion: These observations indicated that PAA and its combination with FLC could be a promising therapeutic candidate for treating infections caused by NAC species.

Profile of neonatal candidiasis in tertiary neonatal intensive care unit: A report from a developing country.

BACKGROUND: Systemic candidiasis is an important nosocomial infection in neonatal intensive care units. The objective of this study was to identify the change in the profile of neonatal candidiasis in a tertiary neonatal intensive care unit (NICU) in eastern India in recent times. METHODS: It was a retrospective review of case records from 2014 to 2019 from a tertiary NICU of eastern India. Data of the fungal sepsis, demographic details, risk factors of fungal sepsis and mortality were collected from 103 neonates. RESULTS: One hundred and three neonates had blood culture positive for fungal species of which 91 (88.3%) infants weighed ≥1500 g and 66 (64%) infants were term. There was significant higher incidence of candidiasis among outborn (Relative risk of outborn 18.84, 95% CI 10.74-33.05). Prolonged antibiotic usage (>14 days), meropenem usage (>5 days), central catheterization (>5 days), invasive mechanical ventilation (>5 days), surgical intervention were found in 64 (62.1%), 46 (44.6%), 31(30.0%), 40 (38.8%) and 39 (37.8%) infants. Non albicans candida (NAC) was isolated as the predominant species (82/103, 79.6%). Resistance to both of fluconazole and amphotericin B were found in 19 (18.4%) babies. Presence of NAC infection and resistance to both amphotericin B and fluconazole were independent predictors of candida associated mortality in NICU. CONCLUSION: Neonatal candidiasis is found among outborn infants with higher birth weight and gestational age. NAC species are predominant organisms with resistance to common antifungal drugs.

Development of Echinocandin Resistance in Candida haemulonii: An Emergent, Widespread, and Opportunistic Fungal Pathogen.

Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant Candida species. Among these species, those belonging to the Candida haemulonii complex are rare multidrug-resistant (MDR) yeasts that are frequently misidentified but have emerged as significant healthcare-associated pathogens causing invasive infections. The objectives of this study were to investigate the evolutionary pathways of echinocandin resistance in C. haemulonii by identifying mutations in the FKS1 gene and evaluating the impact of resistance on fitness. After subjecting a MDR clinical isolate of C. haemulonii (named Ch4) to direct selection using increasing caspofungin concentrations, we successfully obtained an isolate (designated Ch4'r) that exhibited a high level of resistance, with MIC values exceeding 16 mg/L for all tested echinocandin drugs (caspofungin, micafungin, and anidulafungin). Sequence analysis revealed a specific mutation in the resistant Ch4'r strain, leading to an arginine-histidine amino acid substitution (R1354H), occurring at the G4061A position of the HS2 region of the FKS1 gene. Compared to the wild-type strain, Ch4'r exhibited significantly reduced growth proliferation, biofilm formation capability, and phagocytosis ratio, indicating a decrease in fitness. Transmission electron microscopy analysis revealed alterations in cell wall components, with a notable increase in cell wall thickness. The resistant strain also exhibited higher amounts (2.5-fold) of chitin, a cell wall-located molecule, compared to the wild-type strain. Furthermore, the resistant strain demonstrated attenuated virulence in the Galleria mellonella larval model. The evolved strain Ch4'r maintained its resistance profile in vivo since the treatment with either caspofungin or micafungin did not improve larval survival or reduce the fungal load. Taken together, our findings suggest that the acquisition of pan-echinocandin resistance occurred rapidly after drug exposure and was associated with a significant fitness cost in C. haemulonii. This is particularly concerning as echinocandins are often the first-line treatment option for MDR Candida species.

The Impact of COVID-19 on the Epidemiology and Outcomes of Candidemia: A Retrospective Study from a Tertiary Care Center in Lebanon.

Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19-associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4%, respectively). The mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported candidemia mortality rate observed in studies involving ICU patients. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs. 78.1%; p = 0.76). Performing ophthalmic examination (p = 0.002), CVC removal during the 48 h following the candidemia (p = 0.008) and speciation (p = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species such as C. auris.

Invasive Candida infection: epidemiology, clinical and therapeutic aspects of an evolving disease and the role of rezafungin.

INTRODUCTION: Invasive Candida Infections (ICIs) have undergone a series of significant epidemiological, pathophysiological, and clinical changes during the last decades, with a shift toward non-albicans species, an increase in the rate of exogenous infections and clinical manifestations ranging from candidemia to an array of highly invasive and life-threatening clinical syndromes. The long-acting echinocandin rezafungin exhibits potent in-vitro activity against most wild-type and azole-resistant Candida spp. including C.auris. AREAS COVERED: The following topics regarding candidemia only and ICIs were reviewed and addressed: i) pathogenesis; ii) epidemiology and temporal evolution of Candida species; iii) clinical approach; iv) potential role of the novel long-acting rezafungin in the treatment of ICIs. EXPERT OPINION: Authors' expert opinion focused on considering the potential role of rezafungin in the evolving context of ICIs. Rezafungin, which combines a potent in-vitro activity against Candida species, including azole-resistant strains and C.auris, with a low likelihood of drug-drug interactions and a good safety profile, may revolutionize the treatment of candidemia/ICI. Indeed, it may shorten the length of hospital stays when clinical conditions allow and extend outpatient access to treatment of invasive candidiasis, especially when prolonged treatment duration is expected.

Epidemiology of Invasive Candidiasis in Patients with Hematologic Malignancy on Antifungal Prophylaxis.

The landscape of invasive Candida infections in patients with hematologic malignancy has evolved due to the adoption of anti-fungal prophylaxis, advances in oncological therapies, and developments in antifungal therapies and diagnostics. Despite these scientific gains, the morbidity and mortality caused by these infections remain unchanged, highlighting the importance of an updated understanding of its epidemiology. Non-albicans Candida species are now the predominant cause of invasive candidiasis in patients with hematological malignancy. This epidemiological shift from Candida albicans to non-albicans Candida species is partially a consequence of selective pressure from extensive azole use. Further analysis of this trend suggests other contributing factors including immunocompromise caused by the underlying hematologic malignancy and the intensity of its associated treatments, oncological practices, and regional or institution specific variables. This review characterizes the changing distribution of Candida species in patients with hematologic malignancy, describes the causes driving this change, and discusses clinical considerations to optimize management in this high-risk patient population.

Retrospective analysis on distribution and antifungal susceptibility profile of Candida in clinical samples: a study from Southern India.

Introduction: Candida is one of the rising primary causes of infections connected with health care. However, their distribution and susceptibility patterns vary widely amongst different regions. Method: The study was carried out to retrospectively analyze the distribution of Candida in various clinical samples, their species types and susceptibility, in a tertiary care hospital, in India for 4 years using the Vitek-2 database. Results: Candida infection was identified in 751 clinical samples, and the major source of infection was found to be urine samples accounting for about 58.32%. A total of 18 different Candida species were recorded. Non-albicans Candida (NAC) 73.64% (n = 553) predominated Candida albicans 26.36% (n = 198). Candida tropicalis was found to be identified at a higher frequency followed by C. albicans, Candida glabrata and Candida parapsilosis. Candida tropicalis was the only species which were recovered from bile; Candida pelliculosa was recorded merely from blood and Candida lipolytica from urine and blood and not in any other samples. In vaginal swabs, C. albicans accounted for 63.64% (n = 14) compared to NAC 36.36% (n = 8). The susceptibility test revealed that 75.44% (n = 559) isolates were susceptible and 24.56% (n = 182) were resistant to one or more drugs tested. Major resistance was exhibited to flucytosine by C. tropicalis 77.46% (n = 55) compared to C. albicans 11.27% (n = 8). Apart from C. albicans, NAC-C. tropicalis, C. glabrata and Candida krusei showed resistance to echinocandins, and Candida haemulonii to amphotericin-B. Conclusion: The knowledge of the incidence, resistance and emergence of different species might guide clinicians to select an appropriate antifungal therapy and plan effective strategies to control invasive and systemic Candida infections.

Bloodstream Infections with Opportunistic Pathogens in COVID-19 Era: A Real Challenge Necessitates Stringent Infection Control.

Background : Bloodstream infections (BSI) due to opportunistic microbes in the coronavirus disease 2019 (COVID-19) pandemic lead to high morbidity and mortality among hospitalized patients. Thus, it is vital to find out the risk factors of BSI and to learn the ways to mitigate it. Aim : The aim of this study was to evaluate important risk factors of BSI due to opportunistic pathogens and to assess the role of the rigid infection control program to deal with this issue. Methods : A prospective, cross-sectional study was performed for 6 months on 150 patients admitted in both COVID-19 and non-COVID-19 intensive care units of our hospital. BSI was confirmed by the BACTEC and Vitek 2 compact system. Prospective surveillance and environmental sampling were carried out for source tracking along with rigorous infection control measures and the outcome was analyzed. Findings : Burkholderia cepacia, Elizabethkingia meningoseptica, Candida auris, vancomycin-resistant Enterococcus , and Achromobacter xylosoxidans were the common opportunistic pathogens isolated from a single or paired blood sample(s) in our study. Key risk factors were prolonged intensive care unit stay, central venous access, mechanical ventilation, immune-compromised condition, and use of biologics. Reverse osmosis water and used normal saline bottles were the common environmental source of infection. Following the implementation of precise infection control measures, there was a sharp decline in BSI cases, which was not attributed to the downfall of COVID-19 cases. Conclusion : Combined prospective surveillance and environmental sampling helped to find out the sources and implementation of an intensive and insistent infection control program that are needed to control opportunistic pathogens mediated BSI.

Inhibitory effect of lactobacilli supernatants on biofilm and filamentation of Candida albicans, Candida tropicalis, and Candida parapsilosis.

Introduction: Probiotic Lactobacillus strains had been investigated for the potential to protect against infection caused by the major fungal pathogen of human, Candida albicans. Besides antifungal activity, lactobacilli demonstrated a promising inhibitory effect on biofilm formation and filamentation of C. albicans. On the other hand, two commonly isolated non-albicans Candida species, C. tropicalis and C. parapsilosis, have similar characteristics in filamentation and biofilm formation with C. albicans. However, there is scant information of the effect of lactobacilli on the two species. Methods: In this study, biofilm inhibitory effects of L. rhamnosus ATCC 53103, L. plantarum ATCC 8014, and L. acidophilus ATCC 4356 were tested on the reference strain C. albicans SC5314 and six bloodstream isolated clinical strains, two each of C. albicans, C. tropicalis, and C. parapsilosis. Results and Discussion: Cell-free culture supernatants (CFSs) of L. rhamnosus and L. plantarum significantly inhibited in vitro biofilm growth of C. albicans and C. tropicalis. L. acidophilus, conversely, had little effect on C. albicans and C. tropicalis but was more effective on inhibiting C. parapsilosis biofilms. Neutralized L. rhamnosus CFS at pH 7 retained the inhibitory effect, suggesting that exometabolites other than lactic acid produced by the Lactobacillus strain might be accounted for the effect. Furthermore, we evaluated the inhibitory effects of L. rhamnosus and L. plantarum CFSs on the filamentation of C. albicans and C. tropicalis strains. Significantly less Candida filaments were observed after co-incubating with CFSs under hyphae-inducing conditions. Expressions of six biofilm-related genes (ALS1, ALS3, BCR1, EFG1, TEC1, and UME6 in C. albicans and corresponding orthologs in C. tropicalis) in biofilms co-incubated with CFSs were analyzed using quantitative real-time PCR. When compared to untreated control, the expressions of ALS1, ALS3, EFG1, and TEC1 genes were downregulated in C. albicans biofilm. In C. tropicalis biofilms, ALS3 and UME6 were downregulated while TEC1 was upregulated. Taken together, the L. rhamnosus and L. plantarum strains demonstrated an inhibitory effect, which is likely mediated by the metabolites secreted into culture medium, on filamentation and biofilm formation of C. albicans and C. tropicalis. Our finding suggested an alternative to antifungals for controlling Candida biofilm.