Search Results (119)

Background: Infections caused by the protozoan Trichomonas vaginalis affect millions of people worldwide and are responsible for one of the most common sexually transmitted diseases. Despite the efficacy of 5-nitroimidazoles like metronidazole, concerns regarding widespread resistance and the absence of viable alternatives for specific patient populations necessitate the development of structurally diverse pharmacological agents. In this study, we investigated the antiparasitic activity of 1,3-thiazolidin-4-one derivatives against T. vaginalis. Methods: Thiazolidines were synthesized via multicomponent reaction (MCR) using one-pot methodology and tested in vitro against the parasite and mammalian cell lines. Results: Seventy percent of the compounds showed more than 80% antiparasitic activity at 100 μM, with compounds 4a, 4b, and 4f exhibiting IC₅₀ ≤ 20 µM. None of the molecules exhibited cytotoxic against Vero CCL-81 and HeLa cells. Evaluation of the structure–activity relationship (SAR) indicates that the substituent at the nitrogen position of the heterocycle may be involved in the antiparasitic effect of these compounds. In silico studies also revealed that the three compounds possess adequate oral bioavailability and do not present mutagenic, tumorigenic or irritating risks. Finally, molecular docking predicted strong interactions of compounds 4a, 4b, and 4f with T. vaginalis enzymes lactate dehydrogenase and purine nucleoside phosphorylase; compound 4f also interacted with methionine Ƴ-lyase. Conclusions: These preliminary results suggest that 1,3-thiazolidin-4-ones are promising scaffolds for developing new trichomonacidal agents. Full article

Background/Objectives: Giardia lamblia is an intestinal protozoan responsible for giardiasis, a globally prevalent parasitic disease. Current therapeutic options, including nitroimidazoles and benzimidazoles, have increasing treatment failures due to resistance, adverse reactions, and patient non-compliance. Drug repositioning offers a cost-effective strategy for identifying new antigiardial agents. This study aimed to evaluate the in vitro antiparasitic effects and possible mechanisms of action of the tricyclic antidepressant imipramine against G. lamblia trophozoites. Methods: Trophozoites were exposed to increasing concentrations of imipramine (25–125 µM). Growth inhibition and adhesion capacity were quantified using cell counts. Apoptosis- or necrosis-like death was evaluated through Annexin V/PI staining. The expression and distribution of α-tubulin and lipid rafts were analyzed by immunofluorescence microscopy. Finally, the effect of the drug on encystment efficiency was assessed in vitro. Results: Imipramine inhibited G. lamblia trophozoite growth in a concentration-dependent manner, with an IC₅₀ of 42.31 µM at 48 h. The drug significantly reduced adhesion capacity (>90% at 125 µM) and induced apoptosis-like cell death, as evidenced by Annexin V positivity. Immunofluorescence revealed disruption of α-tubulin distribution and lipid raft organization, accompanied by morphological rounding. Moreover, encystment efficiency decreased in a concentration-dependent mode, suggesting interference in the differentiation process. Conclusions: This investigation describes, for the first time, the antigiardial potential of imipramine, which alters cytoskeletal organization, membrane microdomains, and differentiation pathways, ultimately leading to apoptosis-like cell death. These findings position this compound as a promising lead structure and support further exploration of tricyclic antidepressants as scaffolds for the development and optimization of new antiparasitic agents, as well as future studies on their molecular targets and in vivo efficacy. Full article

Trichomoniasis is the most common non-viral sexually transmitted infection in humans, with over 200 million people affected each year. This disease is associated with pre-term birth, low birth weight, and premature membrane rupture. Its causal pathogen, Trichomonas vaginalis (TV), is a prevalent sexually transmitted protozoan parasite that infects the urogenital tract through cytoadherence. TV infection alters TV gene expression and induces host immune responses, while TV-secreted exosomes carry RNA and protein cargoes that mediate extracellular signaling. This review summarizes recent discoveries of molecules that interact with host receptors involved in cytoadherence. We also discuss human innate and adaptive immune responses to TV infection via a variety of inflammatory mediators. Recent research on concurrent or endosymbiont relationships of TV with other urogenital microbes and cancers, is also examined. These studies not only highlight the necessity of understanding host–microbe interactions in TV pathogenesis but also provide a crucial insight into potential therapeutic targets of nitroimidazole-resistant TV strains. Full article

The emergence of bacterial infections as a critical public health challenge underscores the urgent need for innovative therapeutic strategies. We designed and synthesized a series of novel heteroaryl bishydrozono nitroimidazoles and their analogs by strategically hybridizing multiple molecular components through diverse linkers. Among the newly synthesized compounds, compound 4 displayed a broad-spectrum antibacterial profile with low cytotoxicity and hemolysis. It could inhibit the proliferation of methicillin-resistant Staphylococcus aureus and reduce its metabolic activity with low bacterial resistance. Further investigations revealed that the highly active compound 4 could not only disrupt cell membrane integrity and induce excessive reactive oxygen species within bacterial membranes, but also intercalate into DNA to form a supramolecular 4-DNA gyrase complex and cause cell death. These results demonstrated that compound 4 should have large potential as a promising candidate in the ongoing battle against resistant bacterial infections. Full article

Dermatophytes can cause infections of the skin, hair and nails. This study aims to investigate the thiosemicarbazides with nitroimidazole moiety against Trichophyton spp. The activity of fourteen thiosemicarbazide derivatives was evaluated against Trichophyton spp. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) showing 50% and 90% reduction in fungal growth after 4–7 days of incubation (MFC₅₀ and MFC₉₀) were used. The 6 and 11 (MICs ≤ 125 µg/mL), followed by the 3, 5 and 7 containing a fluorophenyl group (MIC = 125 µg/mL, MFC = 125–250 µg/mL) exhibited the best activity and specifically T. mentagrophytes, respectively. Fluorine-containing derivatives (5–9) demonstrated 2–4-fold higher activity (MIC = 31.25–1000 µg/mL) against T. rubrum than T. mentagrophytes, than their chlorinated counterparts (2–4) with MIC = 62.5–500 µg/mL. The position of the fluorine atom within the phenyl ring was important, as observed for derivatives with fluorine in the meta position (3, 6), while the para position was associated with enhanced selectivity. A methoxy group in the meta position of the phenyl ring exhibited the strongest, broadest-spectrum activity. Notably, the introduction of the trifluoromethylphenyl moiety (pharmacophore) led to the disappearance of antifungal properties. Full article

Background/Objectives: Understanding the medication prescribing patterns in pediatric primary care is essential for informing policy and clinical practice. In the Kingdom of Saudi Arabia (KSA), and following the 2018 antibiotic restriction policy, limited data exist on the patterns, types, and regimens of antibiotics prescribed during routine family medicine visits for children. This pharmacoepidemiological study aimed to describe the antibiotic prescribing patterns in a university-affiliated model primary healthcare center. Methods: A retrospective chart review was conducted for all the pediatric visits (<14 years) to general family medicine clinics between January and December 2024. Demographic characteristics, visit type, diagnosis, and antibiotic prescription details such as medication class, route, frequency, and duration were extracted from electronic medical records and analyzed descriptively. Results: Among the 2036 pediatric visits, 705 (34.63%) resulted in at least one prescription. Of these, 87 visits (12.34%) included an antibiotic. The most frequently prescribed antibiotic classes were nitroimidazoles (39.29%), penicillins (36.90%), and macrolides (10.71%). Penicillins were typically prescribed for 7 days twice daily as suspensions. Among the non-antibiotic prescriptions, vaccines, nutritional supplements, and analgesics were the most common. Follow-up consultations accounted for 34.09% of all the visits. Conclusions: A lower proportion of antibiotic prescriptions was found when compared to regional and international reports, which may reflect the impact of the antibiotic restriction policy in the country. The findings suggest a shift toward more cautious prescribing in primary care and align with the national efforts to regulate antimicrobial use. Ongoing surveillance of the prescribing trends is essential to evaluate the long-term effectiveness of these measures. Full article

Background: Pigs and cattle have been implicated as reservoirs of antimicrobial resistance genes (ARGs) that can spread to humans, and houseflies are considered potential carriers of bacteria with ARGs that could contribute to their spread to the environment, including food, animals, and humans. Methods: In this study, 107, 145, and 127 Escherichia coli strains were isolated from houseflies, pigs, and cattle, respectively, from a slaughterhouse in Lima, Peru. Antimicrobial susceptibility testing was performed using the Kirby–Bauer method, where thirteen antibiotics were used. Strains were also plated on CHROMagar COL-APSE agar, and colistin’s minimum inhibitory concentration (MIC) was determined. Colistin-resistant E. coli strains were subjected to whole genome sequencing. Results: 7.8% (8/107), 1.38% (2/145), and 0.79% (1/127) of E. coli strains isolated from houseflies, pigs, and cattle, respectively, were resistant to colistin (MIC ≥ 4 µg/mL). ARGs associated with resistance to more than 6 different antibiotic classes were identified, including tetracyclines, beta-lactams, fluoroquinolones, nitroimidazoles, trimethoprim and amphenicols. Conclusions: This study suggests that flies could contribute to the dissemination of ARG carrying bacteria and shows the potential risk of animals and meat production systems as reservoirs of ARG carrying bacteria. Full article

Background/Objectives: Antibiotic prophylaxis is a key component of infection prevention strategies. This study aimed to evaluate whether the duration of antibiotic prophylaxis influences the incidence of HAIs in patients undergoing elective colorectal surgery. Methods: This prospective cohort study included 278 adult patients who underwent elective colorectal surgery at a single tertiary care center. Patients were categorized into two groups based on the duration of antibiotic prophylaxis: one day or more than one day. Data on demographics, clinical characteristics, perioperative variables, and infection outcomes were collected. Results: The overall incidence of HAIs was 16.9%, with no significant difference between patients receiving one-day versus extended antibiotic prophylaxis. However, traditional multivariate analysis showed that prophylaxis lasting more than one day was independently associated with a significantly lower risk of HAI (RR = 0.30, 95% CI: 0.12–0.75, p = 0.010) and surgical site infections (RR = 0.24, 95% CI: 0.08–0.72, p = 0.011). After adjusting for confounders using propensity score matching, this association was no longer statistically significant. No significant association was found between prophylaxis duration and urinary tract infections. Regarding antibiotic selection, first-generation cephalosporins were the most commonly used agents, accounting for 78.8% of prophylactic prescriptions. This was followed by fluoroquinolones (14.4%) and third-generation cephalosporins (5.0%). All patients received metronidazole, a nitroimidazole-class antimicrobial, in combination with the above agents. Conclusions: One day of prophylactic antibiotics may be sufficient in SSI prevention in patients undergoing elective colorectal surgery. The use of extended antibiotic prophylaxis beyond one day should be considered for high-risk patients at high risk of infection, particularly those requiring ICU care. Full article

Background and Aims: Ornidazole, a nitroimidazole antibiotic, is widely used for protozoal and anaerobic infections and is generally considered safe. However, ornidazole-induced liver injury (OILI) is an underrecognized yet potentially severe adverse reaction. This multicenter study aims to characterize the clinical features, histopathology, and outcomes of OILI to improve the awareness and management of this rare entity worldwide. Methods: We conducted a retrospective analysis of 101 patients with OILI from eight tertiary centers between 2006 and 2023. Cases were included based on liver enzyme elevations temporally linked to ornidazole and the exclusion of other causes. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score. Clinical data, laboratory parameters, autoantibody profiles, histology, treatments, and outcomes were evaluated. Results: OILI was classified as highly probable in 42.6% of cases (n = 43), probable in 51.5% of cases (n = 52), and possible in 5.9% (n = 6) of cases. The predominant pattern was acute hepatocellular injury (83.2%) (n = 84). Autoimmune-like hepatitis occurred in 5% of cases (n = 5), with ANA positivity in 16.8% of cases (n = 17). Corticosteroids were used in 24.8% of cases (n = 25) and were associated with higher ANA positivity and a 20% (n = 5) relapse rate post-discontinuation. Recovery was achieved in 87.7% of cases (n = 88), while 7.9% of cases (n = 8) required liver transplantation and 4% (n = 4) died. Conclusions: Ornidazole can cause serious idiosyncratic liver injury, including autoimmune phenotypes, and should be considered in the differential diagnosis of acute hepatitis. Given the notable risk of liver failure and death, early recognition, drug discontinuation, and close monitoring are essential. In select cases, corticosteroids and plasmapheresis may be beneficial, though the evidence remains limited. Full article

Objectives: In the context of the global rise in antimicrobial resistance (AMR), this study aimed to investigate temporal trends in AMR among pathogens isolated from endometrial cultures of patients diagnosed with chronic endometritis (CE). Methods: This cross-sectional study included 244 women consecutively diagnosed with CE at the Gynecology Unit of the University of Bari, Italy, between January 2020 and June 2024. Exclusion criteria were (i) previous CE diagnosis or treatment; (ii) antimicrobial use in the month prior to hysteroscopy and biopsy; (iii) use of oral or vaginal prebiotics/probiotics or contraceptives in the three months prior; (iv) known immunosuppression; and (v) hypersensitivity to quinolones or macrolides. CE was diagnosed using hysteroscopy combined with endometrial histology and microbial culture. Specifically, in cases with hysteroscopic signs suggestive of CE, endometrial biopsies were obtained using a Novak curette and processed for histological and immunohistochemical analyses, as well as for microbial identification and antimicrobial susceptibility testing in accordance with EUCAST guidelines. The primary outcomes were the prevalence of CE-associated pathogens and their AMR profiles. Results: The median age at CE diagnosis was 33 years (range 26–44). The most frequently isolated pathogens were Enterococcus faecalis (26.2%), Escherichia coli (19.3%), and Ureaplasma urealyticum (16.4%). High AMR rates were observed, with increasing trends over time. Ampicillin resistance reached 98.5% (63/64), penicillin resistance 30.8% (16/52), and extended-spectrum beta-lactamase (ESBL) positivity 34.7% (25/72), all with statistically significant trends (p < 0.001). Resistance to commonly used first-line antimicrobials, such as tetracyclines, quinolones, and nitroimidazoles, was also substantial. Conclusions: This study highlights a significant increase in AMRs among microorganisms responsible for CE between 2020 and 2024. As a result, empirical first-line antimicrobial therapies commonly used to treat patients with CE may be increasingly ineffective in a growing number of cases. This underscores the need for improved and targeted diagnostic and therapeutic strategies to effectively manage CE and prevent treatment failures. Strengthening surveillance systems, implementing antimicrobial stewardship programs, and enhancing patient education may help counter the growing threat of AMR. Full article

Trichomonas vaginalis, a prevalent sexually transmitted protozoan parasite, is associated with adverse birth outcomes, increased risk of HIV and other sexually transmitted infections, infertility, and cervical cancer. Despite its widespread impact, trichomoniasis remains underdiagnosed and underreported globally. Trichomonas vaginalis virus (TVV), a double-stranded RNA (dsRNA) virus infecting T. vaginalis, could impact T. vaginalis pathogenicity. We provide an overview of TVV, including its genomic structure, transmission, impact on protein expression, role in 5-nitroimidazole drug susceptibility, and clinical significance. TVV is a ~5 kbp dsRNA virus enclosed within a viral capsid closely associated with the Golgi complex and plasma membrane of infected parasites. Hypothetical mechanisms of TVV transmission have been proposed. TVV affects protein expression in T. vaginalis, including cysteine proteases and surface antigens, thus impacting its virulence and ability to evade the immune system. Additionally, TVV may influence the sensitivity of T. vaginalis to treatment; clinical isolates of T. vaginalis not harboring TVV are more likely to be resistant to metronidazole. Clinically, TVV-positive T. vaginalis infections have been associated with a range in severity of genital signs and symptoms. Further research into interactions between T. vaginalis and TVV is essential in improving diagnosis, treatment, and the development of targeted interventions. Full article

Nitro-functionalized heterocycles, such as nitroimidazoles, are significant environmental contaminants and have been identified as components of secondary organic aerosols (SOA) and biomass-burning organic aerosols (BBOA). Their strong absorption in the near-UV (300–400 nm) makes photochemistry a critical aspect of their atmospheric processing. This study investigates both the direct near-UV photochemistry and hydroxyl radical (OH) oxidation of 4-nitroimidazole (4-NI). The atmospheric photolysis rate of 4-NI in the near-UV (300–400 nm) was found to be J_4-NI = 4.3 × 10⁻⁵ (±0.8) s⁻¹, corresponding to an atmospheric lifetime of 391 (±77) min under bulk aqueous conditions simulating aqueous aerosols and cloud water. Electrospray ionization mass spectrometry (ESI-MS) analysis following irradiation indicated loss of the nitro group, while NO elimination was observed as a more minor channel in direct photolysis. In addition, the rate constant for the reaction of 4-NI with OH radicals, k_NI+OH, was determined to be 2.9 × 10⁹ (±0.6) M⁻¹s⁻¹. Following OH oxidation, ESI-MS results show the emergence of a dominant peak at m/z = 130 amu, consistent with hydroxylation of 4-NI. Computational results indicate that OH radical addition occurs with the lowest barrier at the C2 and C5 positions of 4-NI. The combined results from direct photolysis and OH oxidation experiments suggest that OH-mediated degradation is likely to dominate under aerosol-phase conditions, where OH radical concentrations are elevated, while direct photolysis is expected to be the primary loss mechanism in high-humidity environments and bulk cloud water. Full article

Background/Objectives: Livestock species, particularly dairy animals, can serve as important reservoirs of E. coli, carrying antibiotic resistance and virulence genes under constant selective pressure and their spread in the environment. In this study, we performed the pathogenomic analysis of seven multidrug resistant (MDR) E. coli strains carrying efflux-associated and virulence genes from the dairy farm environment in Xinjiang Province, China. Methods: First, we processed the samples using standard microbiological techniques followed by species identification with MALDI-TOF MS. Then, we performed whole genome sequencing (WGS) on the Illumina NovaSeq PE150 platform and conducted pathogenomic analysis using multiple bioinformatics tools. Results: WGS analysis revealed that the E. coli strains harbored diverse antibiotic efflux-associated genes, including conferring resistance to fluoroquinolones, aminoglycosides, aminocoumarins, macrolides, peptides, phosphonic acid, nitroimidazole, tetracyclines, disinfectants/antiseptics, and multidrug resistance. The phylogenetic analysis classified seven E. coli strains into B1 (n = 4), C (n = 2), and F (n = 1) phylogroups. PathogenFinder predicted all E. coli strains as potential human pathogens belonging to distinct serotypes and carrying broad virulence genes (ranging from 12 to 27), including the Shiga toxin-producing gene (stx1, n = 1). However, we found that a few of the virulence genes were associated with prophages and genomic islands in the E. coli strains. Moreover, all E. coli strains carried a diverse bacterial secretion systems and biofilm-associated genes. Conclusions: The present study highlights the need for large-scale genomic surveillance of antibiotic-resistant bacteria in dairy farm environments to identify AMR reservoir spillover and pathogenic risks to humans and design targeted interventions to further stop their spread under a One Health framework. Full article

The increasing resistance of Trichomonas vaginalis to the only approved chemical family of drugs for treatment, the 5-nitroimidazoles, has prompted the exploration of new therapeutic agents against this prevalent non-viral sexually transmitted infection. Natural products have emerged as a significant source of novel treatments for trichomoniasis. The aim of this study was to evaluate the anti-T. vaginalis activity of citral (3,7-dimethyl-2,6-octadienal), the main constituent of the essential oil of Cymbopogon species, commonly known as lemongrass. Our findings indicate that citral exhibits a minimum inhibitory concentration (MIC) of 100 μM, effectively inhibiting the growth of T. vaginalis trophozoites within 12 h of exposure, and a 50% inhibitory concentration (IC₅₀) of approximately 40 μM after 24 h. Furthermore, the evaluation of nitric oxide (NO) levels suggests that citral possesses antioxidant properties. Molecular docking studies reveal a weak interaction with three parasite proteins: thioredoxin reductase (TvTrxR), purine nucleoside phosphorylase (TvPNP), and methionine gamma lyase (TvMGL). The present study highlights the potential of citral as a candidate for the development of no-nitroimidazole drugs, offering new avenues for trichomoniasis treatment and underscoring the importance of further investigation into citral’s mechanism of action. Full article

Giardiasis is a common intestinal infection caused by Giardia lamblia. The standard treatment for this parasitic infection involves the administration of nitroimidazoles, albendazoles, and nitrothiazoles. However, in recent years, Giardia lamblia strains resistant to these treatments have been reported. Additionally, the current therapies exhibit considerable side effects, highlighting the need for new compounds that specifically target this parasite. The aim of this study was to evaluate nitrothiazole analogs and assess their impact on the metabolic, redox, and structural gene expression of this parasite. First, the compounds CNZ-7, CNZ-8, FLP-2, FLP-6, and FLP-8 were tested at concentrations ranging from 0 to 50 µM to determine their IC₅₀ in G. lamblia cultures. Subsequently, gene expression changes and structural cell damage in trophozoites were analyzed following incubation with the IC₅₀ of each compound. The giardicidal activity of the compounds was also evaluated in a nitazoxanide-resistant strain. The results showed that FLP-2, FLP-6, and FLP-8 exhibited a stronger effect on trophozoite viability compared to nitazoxanide (NTZ) and metronidazole (MTZ). Both compounds induced an increase in the expression of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), pyruvate phosphate dikinase (PPDK), and pyruvate:ferredoxin oxidoreductase (PFOR). Additionally, FLP-2 caused ultrastructural alterations in trophozoites. Furthermore, FLP-2, FLP-6, and FLP-8 demonstrated efficacy against drug-resistant strains. These findings suggest that FLP-2, FLP-6, and FLP-8 are promising candidates for the treatment of giardiasis, as they effectively reduce parasite viability, modify gene expression, and exhibit activity against drug-resistant G. lamblia strains. Full article