Search Results (22)

Background/Objectives: Q fever, caused by Coxiella burnetii, is a zoonotic disease usually treated with doxycycline, but alternative options are needed when doxycycline is unsuitable. This study evaluated inhaled liposomal ciprofloxacin (Apulmiq^®) as a post-exposure prophylaxis (PEP) compared with oral doxycycline in a common marmoset model. Methods: Marmosets were exposed to aerosolised C. burnetii and treated 24 h later with Apulmiq (0.8 mg/kg inhaled), doxycycline (6 mg/kg oral), or placebo for 7 days. Outcomes included fever, weight loss, bacterial burden, histopathology, liver enzymes, and immune responses. Results: Both treatments delayed fever onset and reduced disease severity versus placebo. Doxycycline prevented fever during treatment and significantly reduced bacterial loads in the lungs and spleen by Day 28. Apulmiq slightly delayed the onset of fever and reduced early bacteraemia but was less effective at bacterial clearance. Immune analyses showed macrophage activation and elevation of IFN-γ during acute infection, and adaptive immune responses by Day 28. Conclusions: Inhaled Apulmiq provided partial prophylactic protection but did not achieve bacterial clearance. Doxycycline reduced bacterial burden but did not completely eliminate disease. Inhaled antibiotics may have potential for use as an alternative approach for PEP treatment, although further optimisation and investigation are needed. Full article

Background/Objectives: Reducing antibiotic use in the dairy sector is a critical objective. This study aimed to assess whether Danish farmers were able to achieve this objective appropriately without affecting animal health. Methods: Participants chose from three options—antibiotics (ABs), no treatment (NO), and non-steroidal anti-inflammatory drugs (NSAIDs)—and their decisions were compared against a laboratory-defined ‘gold standard’. Results: The results indicated that farmers’ professional judgment was unreliable; they frequently misallocated antibiotic treatments, often failing to treat cows that needed them while treating those that did not. Overall, producers administered significantly fewer antibiotics than laboratory results suggested were necessary. Although veterinarians achieved better results via in-clinic bacteriological examinations, their ability to identify specific bacterial species was insufficient. Consequently, cows remain at a significant risk of persistent infection following a clinical episode, regardless of the farmer’s chosen treatment. Conclusions: The study concludes that significant progress needs to be made both on farms and in veterinary clinics to ensure that the use of antibiotics is as little as possible, but as much as necessary. Until such reliability improves, unsuitable treatment will continue to compromise animal health. Full article

Background: Fixed-dose combination drugs (FDCs) are combinations of two or more active ingredients in a single dosage form. These formulations have proven effective in combating the development of resistance in diseases such as tuberculosis and malaria. Despite the benefits observed in the aforementioned cases, fixed-dose antibiotics combinations (FDACs) are increasingly raising questions about their rationality. This is the case for several FDACs listed in the AWaRe classification as not recommended, which unfortunately remain available on the pharmaceutical market, particularly in low- and middle-income countries like the Democratic Republic of Congo (DRC). Objectives: To identify the essential medicines available in pharmacies open to the public in the city of Kinshasa and to assess their inclusion in the DRC’s National List of Essential Medicines (NLEM) and in the World Health Organization’s (WHO) List of Essential Medicines (LEM). The rationality of the FDACs circulating in the city of Kinshasa were also evaluated based on the 2023 AWaRe classification. Methods: A cross-sectional and descriptive study was conducted between February and October 2025 in Kinshasa. For this purpose, fifty registered pharmacies open to the public were selected by systematic random sampling as the research sample. Data collection consisted of completing a data collection form after we had provided the pharmacies’ owners with the necessary explanations regarding the importance of the study and guaranteed their anonymity. Results: The controlled FDACs encountered comprised 27 specialties across 15 different formulations. Out of 15 formulations, 12 (80%) were included on the WHO list of non-recommended antibiotics and were not included in the DRC’s NLEM nor in the WHO’s LEM. Some had been withdrawn from the market in their countries of manufacture. Of the 15 FDACs evaluated for their rationality and compliance, the injectable FDACs presented problems related to the relevance and completeness of information contained on their packaging. On their primary packaging, there was a significant difference in the expiration dates of the powder and sterile water for injection contained in the combination pack, ranging from 6 to 36 months. Furthermore, the secondary packaging lacked data related to the sterile water for injection contained in the combination pack. In addition, several medications contained the same therapeutic combination. For injectable FDAC, for example, the combination Ceftriaxone-Sulbactam was represented by eight medications. For oral FDACs, the combination Sulfamethoxazole-Trimethoprim was represented by seven medications. Globally, 100% of these drug combinations originated from India. Conclusions: Fifteen varieties of FDACs were available in Kinshasa, most of which (80%) were unsuitable. It is important that public health authorities address this situation and develop stricter guidelines for granting marketing authorizations, particularly for FDACs. Full article

Background: Therapeutic drug monitoring (TDM) is essential for ensuring safe, effective, and individualized anti-infective therapy, particularly in patients with complex clinical needs. Variability in pharmacokinetics, challenges in drug administration, and high-dose regimens can compromise adherence and increase the risk of therapeutic failure or resistance. Swallowing difficulties, a common barrier to oral therapy, often necessitate alternative administration routes or customized formulations. However, interventions such as pharmaceutical compounding or manipulation of solid dosage forms may significantly alter drug bioavailability and pharmacokinetic profiles, making TDM indispensable for guiding dose adjustments and maintaining therapeutic targets. Objectives: This review not only emphasizes the clinical relevance of TDM but also addresses practical strategies that enable therapy when standard formulations are unsuitable or unavailable, while minimizing risks that could compromise treatment efficacy and safety. Special focus is given to anti-infective agents, such as antibiotics, antivirals, and antifungals, illustrating how TDM, combined with tailored pharmaceutical approaches, supports precision dosing and informed decision-making. Conclusions: Through clinical examples and pharmacokinetic considerations, we demonstrated that TDM is a cornerstone of personalized medicine, improving outcomes, and reducing adverse effects in anti-infective treatment. Full article

Background and Objectives: Helicobacter pylori (H. pylori) infection remains one of the most common chronic bacterial infections worldwide and is associated with a wide range of gastrointestinal disorders, including gastritis, peptic ulcer disease, and gastric cancer. Increasing rates of antibiotic resistance, particularly to clarithromycin and fluoroquinolones, represent a major therapeutic challenge. The objective of this study was to determine the prevalence of resistance-associated mutations in H. pylori-positive gastric biopsy samples from western Romania. Materials and Methods: We conducted a prospective study from January to December 2024, enrolling 138 patients undergoing gastroscopy. Biopsies were collected from the gastric antrum, and H. pylori infection was confirmed using the rapid urease test (RUT). Positive samples were further analyzed with the GenoType HelicoDR assay to detect mutations in the 23S rRNA gene (clarithromycin resistance) and gyrA gene (fluoroquinolone resistance). Clinical, demographic, and endoscopic data were also collected. Results:H. pylori infection was confirmed in 41.3% of the patients (57), of whom 63.2% (36) were treatment-naïve and 36.8% (21) had prior eradication therapy. Among treatment-naïve patients, clarithromycin resistance was identified in 19.4%, whereas previously treated patients showed a markedly higher resistance rate of 47.6% (p = 0.018). All clarithromycin-resistant cases carried the A2147G (23S MUT3) mutation. Fluoroquinolone resistance was present in 13.9% of naïve patients and increased to 23.8% in those with prior eradication therapy, with resistance linked to gyrA mutations at codons 87 (N87K) and 91 (D91 variants). Combined resistance to both antibiotics was observed only in a subset of previously treated patients. Conclusions: Primary resistance to clarithromycin in western Romania exceeds the 15% threshold defined by international guidelines, making clarithromycin-based triple therapy unsuitable as an empirical first-line option. The findings support the use of bismuth quadruple therapy as the preferred empirical regimen in this region. Also, molecular testing proved effective for rapid identification of resistance-associated mutations. Full article

Background: AMR causes a large global health burden, with approximately 4.95 million deaths linked to bacterial AMR in 2019, 1.27 million due to AMR directly. Although Brazil mandated prescriptions for systemic antibiotics in 2010/2011, self-medication and access without prescriptions continue, with community pharmacists playing a vital part in antimicrobial stewardship (AMS). This study examined antibiotic misuse and AMR in Brazil through community pharmacists’ perspectives, emphasising their dual role as professional actors and frontline observers of public behaviour. Methods: We conducted 20 semi-structured interviews with community pharmacists and performed reflexive thematic analysis of their accounts, repeating five independent analytic cycles to confirm thematic robustness. Results: Six themes were consistently identified as recounted by pharmacists in their practice contexts: Access and Self-Medication; Relationships with Healthcare Professionals; Knowledge and Beliefs about Antibiotics; Use and Adherence; Healthcare System Barriers; and Regulation and Enforcement. Pharmacists mentioned regular requests for antibiotics without prescriptions, drug reuse, and significant impact from community, i.e., from relatives, and peers. The common misunderstanding was that antibiotics treat viral illnesses. Structural issues, for instance GP appointment costs and long waits, made patients seek help from pharmacies. Due to regulation being applied inconsistently, pharmacies struggled to refuse unsuitable requests. Conclusions: Framed through pharmacists’ dual vantage as professionals and frontline observers, the findings highlight intertwined factors underpinning inappropriate antibiotic use in Brazil and support a multi-pronged intervention spanning health system strengthening, professional education, economic considerations, and community engagement. Full article

This review aims to increase attention on present water quality issues on Central Asia, finding gaps in the literature on ways to address treatment needs, and help ensure future use of Central Asia surface waters and groundwater for all beneficial uses. Central Asia is a landlocked region known for its harsh climatic conditions and scarce water resources, despite being home to some of the world’s largest internal drainage basins. The available literature suggests that increasing salinity has rendered water unsuitable for irrigation and consumption; hazardous trace elements are found throughout Central Asia, most often associated with mining and industrial sources; and that legacy pesticides influence water quality, particularly in agriculturally influenced basins. This study also focuses on the effects of municipal and industrial wastewater discharge. Additionally, the impact of inadequately treated wastewater on water resources is analyzed through a review of available data and reports regarding surface and groundwater quantity and quality. Given the challenges of water scarcity and accessibility, the reuse of treated wastewater is becoming increasingly important, offering a valuable alternative that necessitates careful oversight to ensure public health, environmental sustainability, and water security. However, due to insufficient financial and technical resources, along with underdeveloped regulatory frameworks, many urban areas lack adequate wastewater treatment facilities, significantly constraining their safe and sustainable reuse. Proper management of wastewater effluent is critical, as it directly influences the quality of both surface and groundwater, which serve as key sources for drinking water and irrigation. Due to their persistent and biologically active nature even at trace levels, we discuss contaminants of emerging concern such as antibiotics, pharmaceuticals, and modern agrochemicals. This review thus highlights gaps in the literature reporting on impacts of wastewater inputs to water quality in Central Asia. It is recommended that future research and efforts should focus on exploring sustainable solutions for water quality management and pollution control to assure environmental sustainability and public health. Full article

Perianal complications of Crohn’s disease are one of the significant reasons for abdominoperineal resection in patients with medically refractory perianal Crohn’s disease. A 35-year-old man with Crohn’s disease with colostomy presented to our clinic due to perianal fistulas. Complete stricture of the anus was observed, and the patient was found unsuitable for the stoma closure. The Turnbull–Cutait procedure was performed and he was discharged on the fifth postoperative day. In the second month after surgery, rectoscopy revealed a 2 cm long pouch on the neorectum. Then, the patient was treated with antibiotics and infliximab. Following the treatment, the symptoms of the patient were regressed. In the 10th postoperative month, a perianal abscess was seen, and the patient was treated with antibiotics. His ileostomy was reversed in the 18th postoperative month without any complications. In the 42nd postoperative month, no complications were reported. This case report presents the index perianal Crohn’s disease case successfully treated with the Turnbull–Cutait procedure. Full article

Feedstock plants for biofuel production can be cultivated on polluted sites that are unsuitable for edible crop production. This approach combines environmental restoration and renewable energy production, therefore enhancing the economic viability of plant-derived biofuels. Previous studies have indicated that exposure to environmental pollutants may elevate lignin levels in exposed plants, potentially impacting the biomass digestibility and the efficiency of bioethanol conversion. In this study, we investigated the impact of the antimicrobial agent chlortetracycline on lignin biosynthesis in the reference organism Arabidopsis thaliana. Toxicity testing showed that exposure to chlortetracycline significantly reduced plant growth at concentrations above 2.5 mg L⁻¹. Using Fourier-transform infrared spectroscopy (FTIR) analysis, we observed a significant increase in the lignin signature, ranging from 16 to 40%, in plants exposed to chlortetracycline as compared to non-exposed control plants. Transcriptomic analysis (RNA sequencing) was conducted to determine the molecular basis of plant response to chlortetracycline, revealing significant enrichment of several genes involved in lignin biosynthesis and the phenylpropanoid pathway, including cinnamyl alcohol dehydrogenase and peroxidases. Exposure to chlortetracycline also resulted in the overexpression of genes involved in the metabolism of xenobiotic compounds, including cytochrome P450 monooxygenases, glutathione S-transferases, and glycosyltransferases. Chlortetracycline also induced several genes involved in plant response to stress and defense mechanisms, including transcription factors (e.g., WRKY, MYB, AP2/ERF families), pathogenesis-related proteins, and genes involved in stress signaling. These results suggest that the antibiotic chlortetracycline triggers multiple stress responses in A. thaliana, which may cause changes in lignin biosynthesis, reductions in plant growth, increases in the lignin content, and induction of defense metabolic pathways. Full article

Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of neonatal sepsis in high-income countries. While intrapartum antibiotic screening reduces this risk, increasing resistance to macrolides and lincosamides in Europe since the 1990s has limited therapeutic options for penicillin-allergic patients. Reports of reduced beta-lactam susceptibility in GBS further emphasise the need for robust antimicrobial resistance (AMR) surveillance. However, broth microdilution (BMD) methods are unsuitable for large-scale antimicrobial susceptibility testing (AST). Objective: To demonstrate that agar-dilution AST provides equivalent results to broth dilution methods, with superior capacity for high-throughput screening. Methods: Agar-dilution and microdilution AST methods were compared using a panel of 24 characterised susceptible and resistant GBS strains for benzylpenicillin, chloramphenicol, clindamycin, erythromycin, gentamicin, levofloxacin, tetracycline, and vancomycin. Minimum inhibitory concentration (MIC) agreements were evaluated, and resistance profile correlations were assessed using Cohen’s kappa values. Results: Agar-dilution demonstrated >90% agreement with BMD MIC for most antimicrobials, except vancomycin (87.5%), erythromycin (83.33%), and tetracycline (52.78%). Cohen’s kappa values indicated strong agreement (0.88–1.00) for resistance determination. Agar-dilution avoided “trailing growth” issues associated with BMD and facilitated easier detection of non-GBS contaminants. Conclusions: Agar-dilution is a valid method for high-throughput AMR surveillance of retrospective cohorts (96 isolates per plate) and is critical for identifying emerging GBS resistance trends and informing therapeutic guidelines. However, due to the large number of plates required per antimicrobial, it is impractical for routine clinical diagnostics. Full article

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10–147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment. Full article

Bacterial multidrug resistance poses a growing hazard to public health worldwide. Pseudomonas aeruginosa is a ubiquitous bacterial species that has been identified as the second most critical pathogen on the list of drug-resistant bacteria posing a huge threat to human health. P. aeruginosa is an opportunistic Gram-negative bacterium that rapidly produces multiple virulence factors that promote adhesion, host cell penetration, and pathogenicity. It possesses inherent resistance to multiple classes of antibiotics, evading antibiotic treatment by triggering the persister phenotype. Traditional approaches for detecting pathogens in laboratory and clinical settings primarily involve microbiological, nucleic acid-based, immunological, and sequencing techniques, among others. These procedures are time-consuming, necessitate advanced laboratory equipment and skilled staff, and incur large setup costs, rendering them unsuitable for on-the-spot detection of bacterial infections in settings with limited resources. Aptasensors utilize nucleic acid aptamers as bio-receptors to detect pathogens. They circumvent the existing limitations of conventional detection systems due to their sensitivity, versatility for modification, cost-efficiency, and ability to enable real-time detection. So far, as per the literature, three aptamers have been developed against P. aeruginosa using whole bacterial cells but with unreported binding sites. This study aims to identify highly specific aptamers that can bind specifically to P. aeruginosa using whole-bacterium SELEX at any stage of growth with an extensive study of binding site interaction and identification. The objective is to develop an aptamer-based kit enabling rapid point-of-care detection of P. aeruginosa in clinical and environmental samples. Full article

In arid regions, starchy agricultural products such as wheat and rice provide essential carbohydrates, minerals, fibers and vitamins. However, drought, desiccation, high salinity, potentially toxic metals and hydrocarbon accumulation are among the most notable stresses affecting soil quality and cereal production in arid environments. Certain soil bacteria, referred to as Plant Growth-Promoting Rhizobacteria (PGPR), colonize the plant root environment, providing beneficial advantages for both soil and plants. Beyond their ability to improve plant growth under non-stressed conditions, PGPR can establish symbiotic and non-symbiotic interactions with plants growing under stress conditions, participating in soil bioremediation, stress alleviation and plant growth restoration. Moreover, the PGPR ability to fix nitrogen, to solubilize insoluble forms of nutrients and to produce other metabolites such as siderophores, phytohormones, antibiotics and hydrolytic enzymes makes them ecofriendly alternatives to the excessive use of unsuitable and cost-effective chemicals in agriculture. The most remarkable PGPR belong to the genera Arthrobacter, Azospirillum, Azotobacter, Bacillus, Enterobacter, Klebsiella, Pseudomonas, etc. Therefore, high cereal production in arid environments can be ensured using PGPR. Herein, the potential role of such bacteria in promoting wheat and rice production under both normal and derelict soils is reviewed and highlighted. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction, mainly due to bone-modifying agents (BMA), and it is a potentially painful and debilitating condition. To date, the literature has reported a 90% rate of successful outcomes for MRONJ patients undergoing surgical treatment. Particularly for patients with advanced disease stages who are unsuitable for surgery, prolonged medical treatment is required, with a consequent risk of the overuse of antibiotics and antibiotic resistance. The aim of this study is to evaluate the efficiency and safety of ozone, via oral mucosal infiltrations, in seven cancer patients with MRONJ, who are not eligible for surgery. The protocol (OZOPROMAF) consists of intratissue injections of an oxygen ozone (O₂O₃) mixture, which is applied until formation of a sequestrum and clinical healing. Follow-up was scheduled to confirm the healing of MRONJ and radiological evaluations by CBCT were planned. In order to assess the level of pain, a questionnaire including the Numeric Rating Scale for Pain (NRS Pain) was administered on the first visit, one day after treatment, and one week after treatment. After an application of OZOPROMAF, all patients reported discomfort for some hours, probably due to soft tissue pressure around the infiltration site. Thereafter, the discomfort subsided within 6–8 h. Complete mucosal healing of MRONJ occurred within a number of cycles ranging from 7 to 16. Complete resolution with an improvement in bone condition was observed in all patients. The MRONJ lesions of all patients healed after 18–24 months. The authors of this study contend that these preliminary results suggest the efficiency and safety of the O₂O₃ mixture. However, further research is required to confirm the efficacy of the O₂O₃ mixtures in MRONJ treatment, at least for patients who are unsuitable for surgery. Full article

To disclose the effect of crystal plane on the adsorption-photocatalytic activity of MnS, octahedral MnS was prepared via the hydrothermal route to enhance the adsorption and photocatalytic efficiencies of tetracycline hydrochloride (TCH) in visible light region. The optimal MnS treated at 433 K for 16 h could remove 94.83% TCH solution of 260 mg L⁻¹ within 180 min, and its adsorption-photocatalytic efficiency declined to 89.68% after five cycles. Its excellent adsorption-photocatalytic activity and durability were ascribed to the sufficient vacant sites of octahedral structure for TCH adsorption and the feasible band-gap structure for visible-light response. In addition, the band gap structure (1.37 eV) of MnS with a conduction band value of −0.58 eV and a valence band value of 0.79 eV was favorable for the generation of O²⁻, while unsuitable for the formation of OH. Hence, octahedral MnS was a potential material for the removal of antibiotics from wastewater. Full article