Search Results (300)

Yeasts of the genus Candida (C.) and the bacterium Staphylococcus aureus (S. aureus) are among the most common pathogens responsible for infections that are difficult to treat, including those resistant to standard therapy. In recent decades, this has become an increasing clinical problem. In response to the limitations of traditional procedures, antimicrobial photodynamic therapy (aPDT), which combines light, a photosensitizer, and oxygen, is gaining growing interest. The aim of this study was to evaluate the in vitro effectiveness of aPDT using a 635 nm diode laser in combination with toluidine blue O (TBO) against Candida spp. and S. aureus. Reference strains of C. albicans, C. glabrata, C. krusei, and S. aureus were subjected to aPDT. In phase I of this study, the optimal TBO incubation time was assessed with constant laser parameters. In phase II, the impact of the physical parameters of the laser, irradiation time, and output power, was analyzed, with the TBO incubation time set based on the phase I results, to evaluate the degree of microbial reduction (CFU/mL). Statistical analyses were then conducted to assess significance. TBO-mediated aPDT significantly reduced microbial viability, depending on incubation time and laser settings. The minimal effective incubation times were 10 min for Candida spp. and 5 min for S. aureus. The highest pathogen inactivation efficacy was observed at an output power of 400 mW and an irradiation time of 120 s. The use of the photosensitizer or laser alone did not result in significant antimicrobial effects. TBO-mediated aPDT may serve as an effective complement to conventional antimicrobial therapy and, in selected cases (e.g., drug resistance), has the potential to partially or fully replace it. The observed minimal effective incubation times provide a practical baseline, but further statistical comparisons are required to determine whether these durations are truly optimal. Full article

Background: Periprosthetic joint infection (PJI) is one of the most serious complications following total joint arthroplasty. The debridement, antibiotics, irrigation, and implant retention (DAIR) procedure is commonly employed to treat acute, early-stage infections, but its success is highly variable, influenced by factors such as pathogen virulence and antibiotic susceptibility profiles. This study aimed to evaluate the impact of pathogens responsible for these infections on the outcome of DAIR. Methods: This retrospective, single-center study analyzed the microbiological profiles of 116 patients (66 hips and 50 knees) treated for acute periprosthetic joint infections (PJIs) with DAIR between 2018 and 2022. Acute PJI was defined as a duration of symptom less than three weeks, according to the criteria established by the Tsukayama and Izakovicova classification. Preoperative joint aspirations, intraoperatively collected tissue samples, and sonication of the exchanged mobile parts were analyzed for each case. We differentiated between monomicrobial PJI, polymicrobial PJI (defined as the identification of more than one microorganism from preoperative joint fluid aspiration or intraoperative samples), and difficult-to-treat (DTT) pathogens. Results: In this cohort, the following pathogen profiles were identified: culture-negative cases accounted for 11.1% of infections, while 64.2% were attributed to Gram-positive bacteria, 19.8% to Gram-negative bacteria, and 4.9% to fungal pathogens. Among the identified microorganisms, coagulase-negative staphylococci (CNS) were the most frequently detected, exhibiting a notable oxacillin resistance rate of 52.9% and rifampicin resistance rate of 28.7%. Additionally, no significant difference in revision-free implant survival was found between patients with DTT pathogens and/or polymicrobial PJI and those without such infections. Conclusions: This study highlights that pathogens in prosthetic joint infections (PJIs) do not solely determine outcomes, as patient-specific factors (comorbidities, implant type) may also play a key role. Regional variations in pathogens and antibiotic resistance patterns should guide empirical therapy. For instance, this study found a high reliance on vancomycin due to high oxacillin resistance in CNS, the most frequent causative pathogen. Full article

Tritrichomonas foetus is an anaerobic flagellated protozoan that infects multiple animal hosts, primarily cattle and cats, with occasional isolation from pigs. It causes bovine trichomonosis, a venereal disease associated with infertility, abortion, and economic losses in cattle herd. In cats, T. foetus infects the gastrointestinal tract, causing chronic diarrhea which can be difficult to treat. Despite its broad impact, the pathogen is difficult to control because it evades immune responses and persists in host tissues. Recent advances in omics technologies, including genomics, transcriptomics, and proteomics, have contributed to a better understanding of the parasite’s genetic structure, virulence, drug resistance mechanisms, and metabolic pathways. These findings have identified potential drug targets and paved the way for targeted therapies. However, the biology, pathogenicity, and host interactions with T. foetus are still not fully understood, and many aspects of its life cycle and molecular mechanisms remain to be elucidated. This review summarizes the latest omics research on T. foetus, highlighting its genetic diversity and host-specific adaptations, and outlines the gaps in our understanding. Full article

Foodborne illness caused by bacterial pathogens is a global health concern and results in millions of infections annually. Therefore, food products typically undergo several processing stages, including sanitation steps, before being distributed in an attempt to remove pathogens. However, many sanitation methods have compounding effects on the color, texture, flavor, and nutritional quality of the product or do not effectively reduce the pathogens that food can be exposed to. Some bacterial pathogens particularly possess traits and tactics that make them even more difficult to mitigate such as biofilm formation. Non-thermal plasma sanitation techniques, including plasma-treated water (PTW), have proven to be promising methods that significantly reduce pathogenic bacteria that food is exposed to. Published work reveals that PTW can effectively mitigate both gram-positive and gram-negative bacterial biofilms. This study presents a novel analysis of the differences in antimicrobial effects of PTW treatment between biofilm-forming gram-positive bacteria, commonly associated with foodborne illness, that are sporulating (Bacillus cereus) and non-sporulating (Listeria monocytogenes). After treatment with PTW, the results suggest the following hypotheses: (1) that the non-sporulating species experiences less membrane damage but a greater reduction in metabolic activity, leading to a possible viable but non-culturable (VBNC) state, and (2) that the sporulating species undergoes spore formation, which may subsequently convert into vegetative cells over time. PTW treatment on gram-positive bacterial biofilms that persist in food processing environments proves to be effective in reducing the proliferating abilities of the bacteria. However, the variance in PTW’s effects on metabolic activity and cell vitality between sporulating and non-sporulating species suggest that other survival tactics might be induced. This analysis further informs the application of PTW in food processing as an effective sanitation method. Full article

The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve satisfactory results. Plants induce defense responses to natural elicitors by interpreting multiple genes that encode proteins, including enzymes, secondary metabolites, and pathogenesis-related (PR) proteins. These responses characterize systemic acquired resistance. Humic substances trigger positive local and systemic physiological responses through a complex network of hormone-like signaling pathways and can be used to induce biotic and abiotic stress resistance. This study aimed to assess the effect of humic substances on the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POX), and β-1,3-glucanase (GLU) used as a resistance marker in various plant species, including orange, coffee, sugarcane, soybeans, maize, and tomato. Seedlings were treated with a dilute aqueous suspension of humic substances (4 mM C L⁻¹) as a foliar spray or left untreated (control). Leaf tissues were collected for enzyme assessment two days later. Humic substances significantly promoted the systemic acquired resistance marker activities compared to the control in all independent assays. Overall, all enzymes studied in this work, PAL, GLUC, and POX, showed an increase in activity by 133%, 181%, and 149%, respectively. Among the crops studied, citrus and coffee achieved the highest activity increase in all enzymes, except for POX in coffee, which showed a decrease of 29% compared to the control. GLUC exhibited the highest response to HS treatment, the enzyme most prominently involved in increasing enzymatic activity in all crops. Plants can improve their resistance to pathogens through the exogenous application of HSs as this promotes the activity of enzymes related to plant resistance. Finally, we consider the potential use of humic substances as a natural chemical priming agent to boost plant resistance in agriculture Full article

Resistance of various bacterial pathogens to the activity of clinically approved drugs currently leads to serious infections, rapid spread of difficult-to-treat diseases, and even death. Taking the threats for human health in mind, researchers are focused on the isolation and characterization of novel natural products, including plant secondary metabolites. These molecules serve as inspiration and a suitable structural platform in the design and development of novel semi-synthetic and synthetic derivatives. All considered compounds have to be adequately evaluated in silico, in vitro, and in vivo using relevant approaches. The current review paper briefly focuses on the chemical and metabolic properties of resveratrol (1), as well as its oligomeric structures, viniferins, and viniferin-based molecules. The core scaffolds of these compounds contain so-called privileged structures, which are also present in many clinically approved drugs, indicating that those natural, properly substituted semi-synthetic, and synthetic molecules can provide a notably broad spectrum of beneficial pharmacological activities, including very impressive antimicrobial efficiency. Except for spectral verification of their structures, these compounds suffer from the determination or prediction of other structural and physicochemical characteristics. Therefore, the structure–activity relationships for specific dihydrodimeric and dimeric viniferins, their bioisosteres, and derivatives with notable efficacy in vitro, especially against chosen Gram-positive bacterial strains, are summarized. In addition, a set of descriptors related to their structural, physicochemical, pharmacokinetic, and toxicological properties is generated using various computational tools. The obtained values are compared to those of clinically approved drugs. The particular relationships between these in silico parameters are also explored. Full article

Background: Periprosthetic joint infections (PJIs) are considered as one of the most serious complications after total joint arthroplasty. Aim of this study was to evaluate the prevalence of PJI caused by difficult-to-treat (DTT) pathogens as well as PJIs with a superinfection with a DTT pathogen in the course of the infection and assess the risk factors leading to this emergence. Methods: Data of 169 consecutive patients with a PJI was analyzed in this retrospective observational single-center study, and cases were categorized into PJIs with initial DTT pathogens, PJIs with DTT pathogen superinfection, non-DTT PJIs, and PJIs with superinfection. Recorded parameters comprised age, gender, side, body mass index (BMI), preoperative anticoagulation, and serum level of C-reactive protein (CRP) at admission, as well as preoperative patient status using the ASA (American Society of Anesthesiologists) score and the age-adjusted form of the Charlson comorbidity index (CCI). Furthermore, the infecting microorganism and the type of infection as well as the chosen operative treatment regime, duration of the antibiotics interval, and the outcome were recorded. Results: In total, 46.2% of cases were DTT PJIs, and 30.8% of them were superinfections. Elevated serum CRP levels at admission (≥92.1 mg/L) were linked to a nearly 7-fold increased likelihood of a DTT PJI (OR 6.981, CI [1.367–35.63], p = 0.001), compared to patients with a non-DTT PJI. Hip joint involvement was also associated with a 3.5-fold higher risk compared to knee joints (OR 3.478, CI [0.361–33.538], p = 0.0225). Furthermore, patients undergoing ≥3 revision surgeries demonstrated a significantly 1.3-fold increased risk of developing a DTT superinfection (OR 1.288, CI [1.100–1.508], p < 0.0001). Chronic PJIs were similarly associated with a markedly 3.5-fold higher likelihood of superinfection by DTT pathogens (OR 3.449, CI [1.159–10.262], p = 0.0387). Remaining parameters did not significantly affect the rate of a DTT PJI or a PJI with DTT superinfection. Conclusions: These findings underscore the importance of early identification of high-risk patients and highlight the need for tailored preventive and therapeutic strategies in managing DTT PJIs. Full article

Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article

Central nervous system (CNS) tumor with BCL6 corepressor gene BCOR/BCORL1 fusion is an extremely rare tumor entity, with fewer than 40 cases reported. These tumors are distinct from the WHO 2021-defined CNS tumor with BCOR internal tandem duplication. Even rarer are CNS tumors that match to the methylation class of CNS tumors with BCOR/BCORL1 fusion, but lack fusions and instead harbor truncating small nucleotide variants in BCOR. To our knowledge, only two other cases of this scenario have been previously reported. Due to their scarcity and morphological features that mimic oligodendrogliomas and ependymomas, the diagnosis of CNS tumor with BCOR/BCORL1 fusion can be challenging, and misdiagnoses are not uncommon. Histologic findings of Olig2 positivity with focal to absent GFAP warrant further evaluation for this tumor entity. Moreover, no standard of care therapy exists for these tumors, making treatment selection difficult. We present a case of a 37-year-old woman with a midline CNS tumor with BCOR/BCORL1 fusion, harboring a pathogenic BCOR c.626del (p.S209Cfs*7) (Exon 4) variant, who was successfully treated with definitive radiation therapy and adjuvant temozolomide. Notably, EMA showed focal strong dot-like perinuclear immunoreactivity, which has not been previously reported in these tumors. This case adds to the limited but growing body of evidence supporting the use of radiation and temozolomide in treating tumors matching the methylation class of CNS tumors with BCOR/BCORL1 fusion without a detectable fusion. Full article

Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective–prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (≥18 years) treated with I/R for ≥48 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22/29 patients (75.9%), while 30-day mortality was 24.1% (7/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem–relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies. 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

Fungal prosthetic joint infection (fPJI) is one of the orthopaedic pathologies where there is no clear evidence, guidelines or algorithm to guide the surgeon in its management. This is in addition to the difficulty with which these infections are diagnosed, isolated and treated. Fungi form notorious biofilms that are difficult to eradicate once formed and that display resistance to antimicrobial agents. These biofilms have been shown to act synergistically with biofilms of bacteria, further adding to medical treatment resistance. We have reviewed the literature for reports that describe the results of different methods in surgically treating fPJI. We found that surgical management with two stages remains the gold standard for treatment of fPJI, as is the case for bacterial PJI (bPJI). We have investigated medical treatment, debridement with implant retention (DAIR) and staged revisions and whether a reasonable recommendation can be made based on the best knowledge and practice available. From the data on bPJI, there exists a role for conservative management of acute PJI with debridement, antibiotics and implant retention (DAIR). While fPJI and bPJI both represent infections, the differences in our ability to detect these infections clinically, culture the pathogens and treat them with proper antimicrobial agents, along with the difference in the reported results of the surgical treatment, make us believe that these two types of infections should not be treated in the same manner. With all this in mind, we reviewed several reports in the literature on fPJI to determine the efficacy of current treatment modalities, including DAIR, which followed current guidelines for PJI. Data show an overall treatment success rate of 64.4% [range 17.4–100%]. Subgroup analysis revealed a success rate of 11.6% [range 0–28.7%] in patients treated with DAIR. There is no doubt that DAIR should not be encouraged as it consistently has a bad record. Although there are not enough studies or numbers of patients to show an evidence-based preference over one- or two-staged revisions, the two-stage revision of fPJI consistently shows better results and should be considered as the gold standard of management in cases of revision fPJI. This should also be coupled with proper expertise, follow-ups and recommended lengths of medical treatment, which should not be less than six months. From the review of these data, we have developed reasonable recommendations for the management of fPJI. These recommendations center on staged surgical debridement along with medical management. Medical treatment should be for at least 6 months under the guidance of an infectious disease team and based on intraoperative cultures. In the case of local antimicrobial treatment reported in the literature, many patients with fPJI were found to have a polymicrobial infection. As a result, it is our recommendation that antifungals as well as antibacterials should be incorporated into the cement spacer mix of these cases. Fungal PJI remains an exceedingly difficult pathology to treat and should be managed by experienced surgeons in a well-equipped institution. Full article

Multidrug-resistant (MDR) Mycoplasma genitalium (M. genitalium) presents a significant risk of treatment failure in many sexually transmitted infections (STIs) and can result in persistent and recurrent urethritis or cervicitis. This case report describes a recurrent M. genitalium urethritis resistant to sulfamethoxazole-trimethoprim (TMP-SMX), doxycycline, and moxifloxacin. The infection was ultimately cured after both the removal of a nidus of infection and through the use of Lefamulin. Lefamulin is a novel agent approved for use in community-acquired bacterial pneumonia and bacterial skin infections that may be useful in difficult sexually transmitted infections. Background/Objectives: Deciding whether or not to treat M. genitalium can be challenging as it can be a colonizer, or present with a symptomatic pathogen, and even if it is causing symptoms, it can be drug-resistant. Our objective here is to highlight important considerations on whether or not to treat and, if so, what options exist. Conclusions: In a world of increasing drug-resistant STIs, this case highlights the challenges of managing MDR M. genitalium and how foreign bodies can allow reoccurrence. Also highlighted in this case, Lefamulin appears to be a viable alternative line of treatment of MDR M. genitalium that defies other first-line antibiotics. Full article

Background/Objectives: Antimicrobial resistance (AMR) has become a serious public health threat worldwide. Among the various surveillance domains, hospital wastewater (HWW) has been overlooked, and it is the major reason for the threats posed by AMR. Therefore, the HWW domain is of paramount importance for tackling the AMR. In this regard, the present study investigated the occurrence of Gram-negative bacteria from HWW and evaluated the isolates’ multi-drug-resistant (MDR) pattern in the study environment. Methods: This descriptive study involves HWW samples (n = 24) consecutively collected across 6 months. The samples were cultured for bacteria, identified, and subjected to antimicrobial susceptibility testing via Kirby–Bauer. PCR confirmed the presence of drug-resistance genes in Gram-negative bacterial isolates. Results: High rates of Enterobacterales resistant to carbapenems and cephalosporins observed in isolates from final treated effluent. The molecular screening showed tetD, tetE, tetG, catA1, catA2, bla_NDM-1, quinolones, qnrA, qnrB, qnrS, and qepa. Conclusions: Overall, our results suggest that microbiological surveillance and identification of resistance genes of clinically important pathogens in HWW can be a general screening method for early determination of under-detected antimicrobial resistance profiles in hospitals and early warning of outbreaks and difficult-to-treat infections. Full article

Mycobacterium abscessus complex (MABc) poses a major therapeutic challenge due to its intrinsic multidrug resistance and ability to form biofilms. This study evaluated the in vitro activity of three antimycobacterial agents—bedaquiline, delamanid, and clofazimine—on 20 clinical MABc isolates, including M. abscessus subsp. abscessus, massiliense, and bolletii, with a focus on biofilm-forming phenotypes. Biofilm analysis showed that the rough colony morphotypes were mostly weak biofilm formers, while the smooth and mixed morphotypes were predominantly moderate or strong biofilm formers. A statistically significant association was observed between the mixed colony morphology and strong biofilm formation (p = 0.032). Importantly, bedaquiline exhibited potent and consistent activity across all isolates, regardless of the biofilm-forming ability, with MIC values ranging from 0.125 to 1 µg/mL. In contrast, delamanid and clofazimine showed limited efficacy, with MIC values exceeding 16 µg/mL and 8 µg/mL, respectively. These findings strongly support the role of bedaquiline as a promising core agent for future combination therapies targeting drug-resistant MABc infections, including biofilm-associated infections. Our results, among the first from Poland, highlight the critical need for incorporating novel agents such as bedaquiline into therapeutic strategies against this difficult-to-treat pathogen. Full article