Search Results (629)

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article

Polymicrobial biofilms involving fungal and bacterial species are increasingly recognized as contributors to persistent infections, particularly in the oral cavity. Candida albicans and Aggregatibacter actinomycetemcomitans are two commensals that can turn into opportunistic pathogens and are able to form robust biofilms. Objectives: This study aimed to assess the interaction dynamics between these two microorganisms and to evaluate their susceptibility to fluconazole and azithromycin in single- and mixed-species forms. Methods: Biofilm biomass was quantified using crystal violet assays, while biofilm cell viability was assessed through CFU enumeration (biofilm viability assay). To assess the resistance properties of single versus mixed-species coincubations, we applied the antimicrobial susceptibility test (AST) to each drug, and analysed spatial organization with confocal laser scanning microscopy, using PNA-FISH. Results: The results indicated that both species can coexist without significant mutual inhibition. However, a non-reciprocal synergism was also observed, whereby mixed-species biofilm conditions promoted the growth of A. actinomycetemcomitans, while C. albicans growth remained stable. As expected, antimicrobial tolerance was elevated in mixed cultures, likely due to enhanced extracellular matrix production and potential quorum-sensing interactions, contributing to increased resistance against azithromycin and fluconazole. Conclusions: This study provides novel insights into previously rarely explored interactions between C. albicans and A. actinomycetemcomitans. These findings underscore the importance of investigating interspecies interactions within polymicrobial biofilms, as understanding their mechanisms, such as quorum-sensing molecules and metabolic cooperation, can contribute to improved diagnostics and more effective targeted therapeutic strategies against polymicrobial infections. Full article

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen responsible for a range of severe infections and nosocomial outbreaks. Phage-based therapy and biocontrol represent effective strategies to combat the prevalence of A. baumannii. This study reports a novel phage, BUCT775, capable of specifically lysing A. baumannii, and investigates its physiological properties, genomic characteristics, in vivo therapeutic efficacy, and environmental disinfection performance. Phage BUCT775 is a podovirus that forms clear, well-defined plaques with an average diameter of 2.5 ± 0.52 mm. It exhibits a broad range of temperature stability (4–55 °C) and pH stability (pH 3–12). The optimal multiplicity of infection (MOI) for phage BUCT775 is 0.01. At an MOI of 0.01, it demonstrates a latent period of approximately 10 min and exhibits a high burst size. Genomic sequencing and bioinformatics analysis revealed that phage BUCT775 belongs to the order Caudoviricetes and the family Autographiviridae. Its genome has a G + C content of 39.3% and is not known to contain virulence genes or antibiotic resistance genes. Phage BUCT775 exhibited significant therapeutic effects on A. baumannii-infected G. mellonella larvae, increasing the 120 h survival rate of the larvae by 20%. Additionally, phage BUCT775 efficiently eliminated A. baumannii in the environment, with an average clearance rate exceeding 98% within 3 h. These studies suggest that phage BUCT775 holds significant potential for application in phage therapy and environmental disinfection. Full article

Weeksella virosa (W. virosa) is a rare, non-saccharolytic Gram-negative bacterium initially described in the 1970s, later proposed as a distinct genus in 1986. The genus Weeksella currently contains two species, namely W. virosa and W. massiliensis. Although primarily considered non-pathogenic, recent evidence has linked W. virosa to a limited number of clinical infections, mostly in immunocompromised patients. This review aims to consolidate the current body of knowledge on W. virosa, encompassing its microbiological and biochemical characteristics, involvement in human and animal infections, antimicrobial susceptibility profiles, and a critical evaluation of existing diagnostic methodologies. This review includes 13 case reports detailing 16 human cases retrieved from multiple databases, highlighting diagnostic inconsistencies and a lack of standardized antimicrobial susceptibility testing. Although W. virosa is generally susceptible to most antibiotics with the exception of aminoglycosides, recent reports seem to suggest a possible emerging resistance trend. The presence of this organism in hospital environments raises concerns about its potential transmission within healthcare settings. While biochemical testing appears to offer reasonably accurate identification of W. virosa, molecular confirmation may be warranted in some cases mainly due to the organism’s rarity. The reliability of MALDI-TOF MS for the identification of W. virosa remains currently uncertain. Further studies, including electron microscopy and genome-wide analysis, are urgently needed to clarify the pathogenic potential of this bacterium and guide clinical management. This review underscores the necessity for awareness among clinicians and microbiologists regarding this underrecognized pathogen. Full article

About a quarter of the world’s population is infected with Mycobacterium tuberculosis. Growing antibiotic resistance by this microorganism is a major problem in the therapy of the disease. M. avium-M. intracellulare that emerged as a major opportunistic infection of HIV/AIDS continues to afflict immunocompromised individuals. We describe the use of liposome-encapsulated antibiotics in the experimental and clinical therapy of mycobacterial infections, as well as recent experimental liposomal vaccines against tuberculosis. Liposome-mediated intravenous or inhalational delivery of antibiotics enhances the antibacterial effects of the drugs, particularly for infections of resident macrophages, where the liposomes are passively targeted. Despite experimental successes of liposomal antibiotics in the treatment of mycobacterial and other bacterial infections, applications of this method to the clinic have been lagging. This review underscores the significance of liposomes in the treatment of mycobacterial infections, encompassing their synthesis methods, limitations, and both preclinical and clinical studies, providing guidance for the development of future therapeutic approaches and innovative antimicrobial strategies. Full article

Staphylococcus saprophyticus (S. saprophyticus) is an opportunistic coagulase-negative staphylococcus (CoNS) known to cause urinary tract infections in humans and is increasingly recognized in veterinary medicine. The aim of this study was to provide an epidemiological characterization of S. saprophyticus strains and to identify potential virulence factors that may contribute to interspecies transmission. This research is particularly important, as companion animals represent an understudied reservoir of this microorganism, and their role in the spread of resistant pathogens remains insufficiently understood. A total of 61 S. saprophyticus strains isolated from humans, dogs, and cats were analyzed. Identification was performed using MALDI-TOF MS and confirmed by PCR targeting the hrcA gene. Antimicrobial susceptibility was assessed using the disk diffusion and broth microdilution methods, while resistance genes were detected by PCR. The blaZ and mecA genes were present in all strains; additionally, the majority harbored the resistance genes ermA, ermB, tetM, and tetK. Multidrug resistance (MDR) was identified in 21/61 strains (34.4%). Biofilm-forming capacity was temperature-dependent, with the strongest biofilm production observed at 37 °C (70.5%). At 38 °C and 39 °C, the proportion of strong biofilm producers decreased to 50.8% and 52.5%, respectively. All tested strains demonstrated pathogenic potential in the Galleria mellonella larvae infection model, with the highest mortality recorded for selected feline and canine strains. These findings indicate that S. saprophyticus strains from both humans and companion animals possess notable virulence and multidrug resistance. The detection of genotypically and phenotypically resistant strains in animals highlights their potential role as reservoir for zoonotic transmission. Full article

Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen with significant clinical relevance in both human and veterinary medicine. Despite its well-documented role in hospital-acquired infections in human healthcare settings, its persistence and transmission within veterinary clinics remain underexplored. This review highlights the overlooked status of veterinary facilities as environmental reservoirs and amplification points for multidrug-resistant (MDR) P. aeruginosa, emphasizing their relevance to One Health surveillance. We examine the bacterium’s environmental survival strategies, including biofilm formation, resistance to disinfectants, and tolerance to nutrient-poor conditions that facilitate the long-term colonization of moist surfaces, drains, medical equipment, and plumbing systems. Common transmission vectors are identified, including asymptomatic animal carriers, contaminated instruments, and the hands of veterinary staff. The review synthesizes current data on antimicrobial resistance in environmental isolates, revealing frequent expression of efflux pumps and mobile resistance genes, and documents the potential for zoonotic transmission to staff and pet owners. Key gaps in environmental monitoring, infection control protocols, and genomic surveillance are identified, with a call for standardized approaches tailored to the veterinary context. Control strategies, including mechanical biofilm disruption, disinfectant cycling, effluent monitoring, and staff hygiene training, are evaluated for feasibility and impact. The article concludes with a One Health framework outlining cross-species and environmental transmission pathways. It advocates for harmonized surveillance, infrastructure improvements, and intersectoral collaboration to reduce the risk posed by MDR P. aeruginosa within veterinary clinical environments and beyond. By addressing these blind spots, veterinary facilities can become proactive partners in antimicrobial stewardship and global resistance mitigation. Full article

Background: Exophiala spp. are dematiaceous fungi with opportunistic pathogenic potential and a widespread environmental presence. Clinical cases of Exophiala spp. fungemia are uncommon. Although rarely encountered in the general population, these organisms are increasingly reported in immunocompromised individuals or those with complex underlying health conditions. Objectives: This review seeks to examine all documented human cases of Exophiala spp. fungemia, with particular focus on aspects such as epidemiology, microbiological features, resistance patterns, therapeutic approaches and associated mortality rates. Methods: A narrative review was conducted using data sourced from the PubMed/MedLine and Scopus databases. Results: A total of 19 articles described infections in 32 patients involving Exophiala spp. fungemia. The mean patient age was 49.2 years, and 65.6% were male. Central venous catheters emerged as the leading predisposing factor (96.9%). Fever represented the most frequent clinical presentation (50%), followed by organ dysfunction (21.9%). The yeast generally demonstrated susceptibility to voriconazole and itraconazole. Voriconazole was also the most frequently administered antifungal (62.5%), followed by amphotericin (31.3%) and micafungin (28.1%). Overall mortality reached 34.4%, with 25% of deaths specifically caused by the infection. Conclusions: Given the potential of Exophiala spp. to cause severe fungemia, healthcare professionals, particularly clinicians and microbiologists, should consider this pathogen in the differential diagnosis when black yeast is detected in blood cultures, especially in patients with immunodeficiency or significant comorbidities, to ensure timely and accurate identification. Full article

Escherichia coli (E. coli) is an opportunistic pathogen widely distributed in nature, and multi-drug resistance (MDR) E. coli has been widely recognized as a critical reservoir of resistance genes, posing severe health threats to humans and animals. A total of 288 E. coli strains were isolated and purified from fresh fecal samples of forest musk deer collected from farms in Sichuan, Shaanxi, and Yunnan Provinces of China between 2013 and 2023. This study aimed to conduct antibiotic susceptibility testing and resistance gene detection on the isolated forest musk deer-derived E. coli, analyze the correlations between them, investigate the presence of CRISPR systems within the strains, and perform bioinformatics analysis on the CRISPR systems carried by the strains. Results showed that 138 out of 288 E. coli strains were MDR, with the highest resistance to tetracycline (48.3%), cefalexin (45.1%), and doxycycline (41.7%). Prevalent genes were tetA (41.0%), sul2 (30.2%), blaTEM (27.1%), with 29 gene–phenotype pairs correlated. CRISPR system-negative strains had higher resistance rates to 16 antibiotics and lower detection rates only for aac (6′)-Ib-cr, qnrA, and qnrB compared to CRISPR system-positive strains. Regional analysis showed that the problem of drug resistance in Sichuan and Shaanxi was more serious, and that the detection rate of antibiotic resistance genes was relatively high. This study guides E. coli infection control in forest musk deer and enriches resistance research data. Full article

Background/Objectives: Mycobacterium avium, a member of Mycobacterium avium complex (MAC), is an emerging opportunistic pathogen causing MAC-pulmonary disease (PD). Fluoroquinolones (FQs), along with ethambutol (EMB) and rifampicin, are recommended for macrolide-resistant MAC-PD; however, FQ-resistant M. avium have been reported worldwide. WQ-3810 is an FQ with high potency against FQ-resistant pathogens; however, its activity against M. avium has not yet been studied. Methods: In this study, we conducted a DNA supercoiling inhibitory assay to evaluate the inhibitory effect of WQ-3810 on recombinant wild-type (WT) and four mutant DNA gyrases of M. avium and compared the IC₅₀s of WQ-3810 with those of ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF). In addition, we examined WQ-3810’s antimicrobial activity against 11 M. avium clinical isolates, including FQ-resistant isolates, with that of other FQs. Furthermore, we assessed the synergistic action of WQ-3810 with the combination of either EMB or isoniazid (INH). Results: In a DNA supercoiling inhibitory assay, WQ-3810 showed 1.8 to 13.7-fold higher efficacy than LVX and CIP. In the MIC assay, WQ-3810 showed 4 to 8-fold, 2 to 16-fold, and 2 to 4-fold higher antimicrobial activity against FQ-resistant isolates than CIP, LVX, and MXF, respectively. The combination of WQ-3810 and INH exhibited a synergistic relationship. Conclusions: The overall characteristics of WQ-3810 demonstrated greater effectiveness than three other FQs, suggesting that it is a promising option for treating FQ-resistant M. avium infections. Full article

Staphylococcus aureus (S. aureus) is a major cause of opportunistic infections in humans and animals, leading to severe systemic diseases. The rise of MDR strains associated with animal carriage poses significant health challenges, underscoring the need to investigate animal-derived S. aureus. Objectives: This study examined the genotypic relatedness and phenotypic profiles of antimicrobial resistance in S. aureus, previously sampled from nostril swabs of healthy horses from two geographically distant Brazilian states (Northeast and South), separated by over 3700 km. The study also sought to confirm the presence of methicillin-resistant (MRSA) and borderline oxacillin-resistant (BORSA) strains and to characterize the isolates through molecular typing using PCR. Methods: Among 123 screened staphylococci, 21 isolates were confirmed as S. aureus via biochemical tests and PCR targeting species-specific genes (femA, nuc, coa). Results: REP-PCR analysis generated genotypic profiles, revealing four antimicrobial resistance patterns, with MDR observed in ten isolates. Six isolates exhibited cefoxitin resistance, suggesting methicillin resistance, despite the absence of the mecA gene. REP-PCR demonstrated high discriminatory power, grouping the isolates into five major clusters. Conclusions: The genotyping indicated no clustering by geographical origin, highlighting significant genetic diversity among S. aureus strains colonizing horses’ nostrils in Brazil. These findings highlight the widespread and varied nature of S. aureus among horses, contributing to a deeper understanding of its epidemiology and resistance profiles in animals across diverse regions. Ultimately, this genetic diversity can pose a public health risk that the epidemiological surveillance services must investigate. Full article

Pseudomonas aeruginosa is a major opportunistic pathogen with high levels of antibiotic resistance. Phage therapy represents a promising alternative for the treatment of difficult infections both alone and in combination with antibiotics. Here, we isolated and characterized three novel lytic myoviruses, Cisa, Nello, and Moonstruck. Genomic analysis revealed that Cisa and Nello belong to the Pbunavirus genus, while Moonstruck is a novel Pakpunavirus species. All lacked lysogeny, virulence, or resistance-associated genes, supporting their therapeutic suitability. Phage Nello and Moonstruck were active against P. aeruginosa Pa3GrPv, isolated from a patient with lung infection candidate for phage therapy. Moonstruck exhibited superior lytic activity with ciprofloxacin sub-MIC value (0.125 µg/mL), achieving bacterial suppression for 48 h. However, to improve the lytic efficacy of the phages on the clinical isolate, phage adaptation via serial passage was investigated. The killing efficacy of Nello was enhanced, whereas Moonstruck showed a less consistent improvement, suggesting phage-specific differences in evolutionary dynamics. Sequencing of the evolved phages revealed point mutations in tail-associated genes, potentially linked to a better phage–host interaction. These results support the use of phage–antibiotic combinations and directed evolution as strategies to enhance phage efficacy against drug-resistant infections. Overall, these findings support the therapeutic potential of the newly isolated phages in treating P. aeruginosa lung infections. Full article

Nocardia spp. is an environmental Gram-positive bacterium able to cause infections in humans, predominantly of an opportunistic nature. Nocardial brain abscesses are rare and result from dissemination from another primary lesion, mainly observed in immunocompromised hosts. The diagnosis of nocardiosis relies on direct examination and bacterial culture, but antimicrobial susceptibility testing (AST) remains controversial due to technical challenges, limited standardization, and a paucity of studies correlating in vitro susceptibility with clinical efficacy. Management is challenging and usually based on expert opinion, as robust evidence is limited. In this case report, we describe an immunocompromised patient with a Nocardia farcinica brain abscess who achieved clinical resolution following combination therapy that included ceftriaxone, despite in vitro resistance, illustrating the complexities in interpreting AST and guiding treatment decisions in rare infections. Full article

Acinetobacter baumannii is an opportunistic pathogen and a major cause of nosocomial infections worldwide. This study aimed to isolate and characterize phages with lytic activity against multidrug-resistant A. baumannii strains to enable antibacterial alternatives. Eight phages (AKO8a, PS118, B612, MCR, IDQ7, 89P13, CRL20, and CIM23) were isolated and subjected to genomic, phylogenetic, and functional analyses. Antibacterial activity was assessed in vitro against A. baumannii strain AbAK04 by measuring optical density over 17 h at multiplicities of infection (MOIs) of 0.1, 1, and 10, using a repeated-measures design with time as a crossed factor and MOI as a nested factor. Tukey’s post-hoc test identified significant bacterial growth reductions of 57–72% (p < 0.001). Specifically, phages PS118 and 89P13 reduced growth by 71% at MOI 10; CIM23, B612, and CRL20 achieved 68% reduction at MOI 1; and MCR reduced growth by 64% at MOIs 0.1 and 1. Notably, lytic phage MCR encodes a glycosyl hydrolase family 58 (GH58) enzyme, potentially contributing to its antibacterial activity. Genomic analyses confirmed absence of virulence and antibiotic resistance genes, with all phages classified as novel species within the Kagunavirus genus. These findings support the use of these phages as promising candidates for in vivo evaluation. Full article

Background: The opportunistic pathogen Staphylococcus aureus causes skin and soft tissue infections that are associated with biofilm formation, and in immunocompromised patients can progress to surgical site infections, pneumonia, bacteremia, sepsis, and even death. Most antibiotics actively damage living, dividing cells on the surface of the biofilm, where there is a high concentration of nutrients and oxygen, while in the depths, where these factors are scarce, slowly growing cells remain. Objectives: The aim of our study was to evaluate the antibiofilm potential of ethyl acetate roots (EtOAcR) and aerial parts (EtOAcAP) extracts from the perennial Bulgarian plant Geum urbanum L. against methicillin-resistant S. aureus (MRSA) NBIMCC 8327. Methods: The effects of both extracts on the expression of biofilm-related genes, icaA and icaD, were investigated. The cytotoxicity of EtOAcR and EtOAcAP on A-375 (human melanoma), A-431 (epidermoid skin cancer) and HaCaT (normal keratinocytes) cell lines, and the induction of apoptosis were determined. Finally, the in vivo skin irritation potential of the most active extract was studied. Results: Both tested extracts inhibited biofilm formation at concentrations that did not affect bacterial growth. Interestingly, the expression of icaA and icaD was upregulated, although the biofilm development was inhibited 72.4–90.5% by EtOAcAP and 18.9–20.4% by EtOAcR at sub-MICs. EtOAcAP extract showed a more favorable cytotoxic profile on non-tumorigenic cells and stronger antineoplastic activity (IC₅₀ = 6.7–14.68 µg/mL) as compared to EtOAcR extract (IC₅₀ = 8.73–23.67 µg/mL). Therefore, a skin irritation test was performed with the EtOAcAP extract at ten-times higher concentrations than the minimum inhibitory one, and, resultantly, the primary irritation index was equal to zero (no skin irritation observed). Conclusions: The EtOAcAP extract was proven to be an effective antistaphylococcal agent with favorable skin tolerance. The extract showed strong antineoplastic activity and antibiofilm effect at sub-MICs, which outlines new prospects for its development as a natural product for specific skin applications in medical practice. Full article