Search Results (129)

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A₁ via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application. Full article

Background: Bordetella pertussis causes pertussis, a respiratory infection with whooping cough. Despite a high vaccine coverage, pertussis resurged post-COVID-19 pandemic. Meanwhile, isolates resistant to macrolides—the first-line therapy—have increased in several countries, including Japan. Culturing B. pertussis and detecting resistance are difficult; reports remain limited in Japan. Methods: From March to August 2025, we collected nasopharyngeal samples from children aged 0–15 years with suspected pertussis at six Japanese clinics. Pediatricians obtained swabs and tested them using gene-amplification kits (e.g., BioFire^® SpotFire^® in four clinics, LAMP Pertussis Detection^® in two clinics). B. pertussis was confirmed by PCR; isolates were sequenced to identify macrolide-resistant mutations. Results: Samples were taken from 54 children, the number of boys and girls was 34 and 20, and their median age was 12 years old. Among 54 B. pertussis isolates, 43/52 (82.7%) sequenced strains harbored the A2047G mutation associated with macrolide resistance. Resistance rates at each clinic varied from 40% to 96%. Conclusions: These findings indicate a post-pandemic rise in macrolide-resistant B. pertussis in Japan. Ongoing resistance surveillance is essential, and repurposing residual clinical samples after routine testing is useful given culture and detection challenges. Full article

Pneumonia caused by the facultative intracellular pathogen Rhodococcus equi stands out as one of the most significant infections associated with a notably high mortality rate in foals worldwide. Limited therapeutic options and inadequate control and prevention measures result in substantial economic losses, underscoring the need for enhanced interventions. A cross-sectional, multi-province study was conducted on racehorse-breeding farms in Türkiye to estimate prevalence and index virulence, assess relatedness, and summarize antimicrobial susceptibility within a farm management context. Nasal and fecal swabs and environmental samples (soil and water) were cultured and confirmed; virulence was assessed with vapA-specific PCR, genetic relationship determined with PFGE, and antimicrobial susceptibility using disk diffusion. R. equi was detected in 10% of nasal swabs, 22.9% of fecal swabs, 29.4% of soil samples, and 5.9% of water samples; 46.2% of confirmed isolates were vapA-positive. Susceptibility patterns were favorable overall, with frequent ampicillin resistance, infrequent resistance to macrolides and rifampin, rare multidrug resistance, and no vancomycin resistance was detected. PFGE demonstrated substantial genotypic diversity, with 12 clusters and 29 distinct pulsotypes. Farm-level observations were exploratory. More frequent mechanical paddock cleaning coincided with the absence of foal deaths, and vapA-positive isolates were observed on farms with prior infection. Taken together, these findings support routine paddock hygiene, prompt isolation of clinically affected foals, culture-guided therapy, and continued surveillance, and they indicate a need for longitudinal and genomic studies to evaluate the impact. Full article

Background: Canine skin and ear infections are common in small-animal practice and increasingly complicated by multidrug resistance (MDR), yet data from Serbia are limited. This study aimed to describe the bacterial etiology and antimicrobial resistance patterns in canine otitis externa and pyoderma. Methods: We retrospectively reviewed laboratory records from the Clinical Bacteriology and Mycology Laboratory, Faculty of Veterinary Medicine, University of Belgrade (January 2017–August 2024). A total of 422 non-invasive swabs from clinically ill dogs were included (ears: n = 210; skin: n = 212). Bacterial identification used conventional methods and commercial systems, and disk-diffusion susceptibility testing followed CLSI/EUCAST guidance. Methicillin resistance in staphylococci was assessed by cefoxitin/oxacillin screening; MRSA was confirmed by PCR and PBP2a detection. Resistance trends were compared between 2017–2020 and 2021–2024. Results: The leading pathogens were Staphylococcus pseudintermedius (ears 48.1%; skin 79.7%) and Pseudomonas aeruginosa (ears 29.1%; skin 7.6%). Staphylococci showed high resistance to macrolides, clindamycin, tetracycline, and first-line β-lactams (amoxicillin–clavulanate, cephalexin), with the highest susceptibilities to amikacin, florfenicol, and rifampicin. P. aeruginosa remained most susceptible to amikacin, polymyxin B, and imipenem. Between the two periods, S. pseudintermedius resistance increased to amikacin, fusidic acid, and cephalexin, while resistance to florfenicol decreased. P. aeruginosa resistance to imipenem increased. The prevalence of methicillin-resistant S. pseudintermedius (MRSP) was 27.4% (74/270). MDR S. pseudintermedius and MDR P. aeruginosa were identified in 38.5% and 53.3% of isolates, respectively. One isolate of each species was resistant to all tested drugs. Conclusions: These findings confirm high levels of antimicrobial resistance in major canine skin and ear pathogens and emphasize the need for susceptibility-based therapy, rational antimicrobial use, and ongoing surveillance in small-animal practice. Full article

Background: Legionella pneumophila is frequently acquired in the community and generally linked to contaminated domestic hot water systems, hotels, or other environmental sources or of unknown origin. L. pneumophila is a leading cause of pneumonia, especially in high-risk patients such as those over 50 who are immunocompromised or people with pre-existing illnesses. This study examines the factors linked to L. pneumophila acquired in the community in adult patients with hospitalization due to pneumonitis. Methods: This case-control study included 140 hospitalized adult patients admitted to the University Hospital Paolo Giaccone of Palermo between January 2019 and December 2024. Demographic, laboratory, clinical, and microbiological data were collected electronically. Urinary antigen testing and the BioFire FilmArray Pneumonia Panel were used to detect L. pneumophila and were performed within 48 h upon admission. Results: Of 140 pneumonia patients, 70 were positive (SG) and 70 were negative (CG) for L. pneumophila. Comorbidities were significantly associated with the presence of L. pneumophila (p = 0.0046). The most frequent comorbidity was only heart failure (p < 0.0015) and, similarly, for smoke (p = 0.0487). There was no difference in mortality between the two groups (SG). Levofloxacin was the most frequent therapy used in SG (p < 0.0001). Additionally, SG showed significantly lower blood sodium, phosphate, and platelet levels (all p < 0.0001) compared to the CG. In contrast, blood parameters such as LDH, CRP, AST, and ALT were significantly higher (all p < 0.0001). Conclusions: Our research highlights the critical need for early detection of L. pneumophila infections, especially in patients with high CRP levels, moderate hypophosphatemia, or heart failure. In these patients with L. pneumophila, early treatment with macrolide and fluoroquinolone is mandatory to reduce mortality. Full article

The incidence and prevalence of nontuberculous mycobacterial (NTM) disease are rising. This narrative review examines the evolution of NTM disease trends over the past four decades, in Canada and globally, encompassing changing epidemiology, shifting treatment paradigms, and emerging antimicrobial resistance patterns. Challenges to NTM treatment are explored, and novel and investigational therapies are summarized. Key themes include a significant increase in NTM disease incidence, temporal shifts in the dominant species causing human infections, evolution from single-drug to multi-drug treatment approaches, and growing concerns regarding macrolide resistance. The substantial challenges with treatment tolerability, effectiveness, and access are outlined. This review synthesizes data from multiple sources, including peer-reviewed literature, clinical trials, and public health databases, to provide a comprehensive understanding of the changing NTM disease landscape in Canada and more broadly. There is a need for expanded surveillance, continued innovation, and a multidisciplinary approach to NTM management. Full article

Background and Objectives: Antimicrobial stewardship plays a key role in the surgical setting by reducing the incidence of healthcare-associated infections and limiting the emergence of antimicrobial resistance. Clinical Decision Support Systems (CDSSs), when integrated into routine practice, are valuable tools for optimizing antimicrobial prescribing. However, evidence regarding their impact on surgical patients, particularly across different specialties, remains limited. Materials and Methods: We conducted a quasi-experimental time series study in surgical patients at a primary-level hospital, evaluating the effect of a CDSS on postoperative antimicrobial therapy. The pre-intervention period included patients admitted from April 2017 to September 2020, and the post-intervention period included those admitted from October 2020 to March 2024. Antimicrobial consumption and expenditures were measured as defined daily doses (DDDs) per 1000 patient-days and euros (€) per 1000 patient-days, respectively. Subgroup analyses were performed by the surgical service. Clinical outcomes included mortality and length of stay (LOS). Results: Following CDSS implementation, overall antimicrobial consumption decreased by 4.4%. Significant reductions were observed in aminoglycosides (−52.0%), macrolides, lincosamides and streptogramins (−40.6%), and fluoroquinolones (−32.3%). Reductions were heterogeneous across surgical services, with significant reductions in Traumatology (−21.3%) and Urology (−14.3%). Expenditures decreased from 3185.4 to 2733.9€/1000 patient-days (−14.2%; p = 0.17). Mortality remained stable, whereas significant reductions in LOS were observed in Urology (5 to 4 days, p = 0.03) and traumatology (16 to 8.5 days, p < 0.01). During the post-intervention period, 476 stewardship recommendations were issued for 330 patients, with an acceptance rate of 76.1%. The most frequent interventions were discontinuation of antimicrobials (25.8%), transition to oral therapy (21.0%), and de-escalation (18.7%). Conclusions: Implementation of a CDSS in the surgical setting was associated with reduced antimicrobial consumption, a downward trend in expenditures, and high acceptance of stewardship recommendations. Mortality remained unchanged, while reductions in LOS in selected services support the safety and potential efficiency of this approach. Full article

Background and Objectives: Odontogenic infections are common emergencies in oral and maxillofacial surgery. They are typically polymicrobial, with aerobes guiding initial empirical therapy. However, regional data on their microbiology and resistance patterns in Romania are limited. This study aimed to characterize the aerobic microbial profile of odontogenic infections in Southwestern Romania and assess the antimicrobial susceptibility of isolated pathogens. Materials and Methods: A prospective observational study was conducted over 12 months at a tertiary referral hospital. Pus samples collected intraoperatively were cultured aerobically. Bacterial identification used biochemical methods and the VITEK 2 system. Antimicrobial susceptibility was determined by disk diffusion and automated MIC testing, interpreted according to EUCAST v13.0 (2023). Results: Of 110 patients, 96 (87.3%) yielded positive aerobic cultures, producing 97 isolates. Streptococcus spp. were predominant (49.5%), followed by coagulase-negative staphylococci (24.7%), Staphylococcus aureus (14.4%), Enterobacterales (7.2%), and Pseudomonas aeruginosa (3.1%). Streptococcus spp. remained susceptible to penicillin G (82.3%), amoxicillin–clavulanate (76.4%), and clindamycin (70.5%), but only 55.0% to erythromycin. Most S. aureus isolates were methicillin-susceptible (92.9%), while coagulase-negative staphylococci showed high methicillin resistance (59.3%) yet full susceptibility to linezolid, vancomycin, and teicoplanin. Enterobacterales were resistant to ampicillin (90%) and amoxicillin–clavulanate (65%) but remained susceptible to ceftriaxone (80%) and ciprofloxacin (85%). P. aeruginosa isolates were fully susceptible to piperacillin–tazobactam, ceftazidime, cefepime, and meropenem. Conclusions: This study provides regional data on aerobic pathogens in odontogenic infections. High resistance to penicillin and macrolides limits empirical use. Amoxicillin–clavulanate and clindamycin retain moderate activity, while glycopeptides, linezolid, and carbapenems preserved full efficacy. Surgical drainage remains central to management, and antibiotic therapy should be guided by local susceptibility patterns. These data provide baseline information to inform empirical therapy and stewardship efforts and highlight the need for multicenter studies including anaerobic and molecular analyses. Full article

Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that plays a central role in extracellular matrix (ECM) remodeling, angiogenesis, immune cell trafficking, and cytokine activation. Dysregulated MMP-9 activity has been implicated in the pathogenesis of diverse conditions, including atherosclerosis, aneurysm formation, chronic obstructive pulmonary disease (COPD), asthma, neurodegeneration, and malignancy. Although broad-spectrum synthetic MMP inhibitors were initially developed as therapeutic agents, clinical trials failed due to lack of selectivity, poor tolerability, and impairment with physiological tissue repair. This outcome has shifted attention toward indirect pharmacological modulation of MMP-9 using drugs that are already approved for other indications. In this paper, we review the evidence supporting MMP-9 modulation by established therapeutics and adjunctive strategies. Cardiometabolic agents such as statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), metformin, and pioglitazone reduce MMP-9 expression and enzymatic activity, contributing to vascular protection, improved insulin sensitivity, and attenuation of aneurysm progression. Anti-inflammatory and respiratory drugs, including glucocorticoids, phosphodiesterase-4 (PDE4) inhibitors, macrolide antibiotics, montelukast, and nonsteroidal anti-inflammatory drugs (NSAIDs), suppress MMP-9-driven airway inflammation and pathological tissue remodeling in asthma, COPD, and acute lung injury. Tetracycline derivatives, particularly sub-antimicrobial dose doxycycline, directly inhibit MMP-9 activity and are clinically validated in the treatment of periodontal disease and vascular remodeling. Hormone-related therapies such as rapamycin, estradiol, and tamoxifen exert tissue- and disease-specific effects on MMP-9 within endocrine and oncologic pathways. In parallel, nutritional interventions—most notably omega-3 polyunsaturated fatty acids and antioxidant vitamins—provide adjunctive strategies for mitigating MMP-9 activity in chronic inflammatory states. Taken together, these findings position MMP-9 as a modifiable and clinically relevant therapeutic target. The systematic integration of approved pharmacologic agents with lifestyle and nutritional interventions into disease-specific treatment paradigms may facilitate safer, context-specific modulation of MMP-9 activity and unveil novel opportunities for therapeutic repurposing. Full article

This case describes an outbreak of salmonellosis caused by Salmonella enterica subspecies enterica serotype Agona in a Rottweiler breeding kennel, associated with raw meat-based diet (RMBD) of unlicensed origin. The report presents the clinical, epidemiological, and microbiological characteristics of the outbreak, as well as the control and preventive measures undertaken. Methods: Samples of faeces, vomit, raw food, and environmental surfaces were collected and examined. The isolated pathogen was identified using bacteriological culture, biochemical testing, MALDI-TOF mass spectrometry, and serotyping according to the White–Kauffmann–Le Minor scheme. Antimicrobial susceptibility was determined by the broth microdilution method in accordance with standards of Clinical and Laboratory Standards Institute (CLSI). Results: Clinical signs included vomiting, diarrhoea, lethargy, and dehydration without fever, with disease exacerbation observed in post-partum animals. Extensive carriage and faecal shedding of S. Agona were detected in affected dogs, along with widespread contamination of food and the kennel environment. The isolate was susceptible to some antimicrobial agents but resistant to cephalexin, aminoglycosides, lincosamides, macrolides, and fusidic acid, and showed intermediate susceptibility to polymyxin B. Following discontinuation of raw meat feeding, targeted antimicrobial therapy, and environmental disinfection, all dogs recovered, and subsequent tests for Salmonella spp., were negative. All human contacts also tested negative. Conclusions: This represents the first documented outbreak of S. Agona infection in dogs in Bulgaria linked to a RMBD. The findings emphasise the importance of feed safety, biosecurity, and traceability of feed sources in kennels, as well as the potential zoonotic risk associated with raw feeding practices. The diagnostic and therapeutic measures implemented in this case provide an effective model for managing similar epidemiological events within the One Health framework. Full article

Background/Objectives: Staphylococcus sciuri, traditionally regarded as a commensal organism in animals and the environment, is increasingly recognized as a potential opportunistic pathogen with zoonotic significance. Its genomic reservoir of methicillin resistance homologues further raises concern regarding its role in antimicrobial resistance dissemination. This study describes the first documented case of S. sciuri isolated from the urinary bladder of a domestic rabbit (Oryctolagus cuniculus) in Romania, emphasizing its clinical relevance and antimicrobial profile. Methods: A seven-year-old intact female rabbit presenting with apathy, dysuria, and hematuria underwent clinical evaluation, ultrasonography, and cystocentesis. The aspirated intravesical content was subjected to bacterial culture, MALDI-TOF MS identification, and antimicrobial susceptibility testing via the VITEK 2 system. Results: Pure colonies of Gram-positive cocci were identified as S. sciuri with high confidence. Antimicrobial susceptibility testing revealed susceptibility to β-lactams, aminoglycosides, glycopeptides, linezolid, rifampicin, fusidic acid, tigecycline, and trimethoprim-sulfamethoxazole, while resistance was observed against fluoroquinolones, macrolides, lincosamides, and tetracycline, indicating a multidrug-resistant phenotype. Treatment with trimethoprim-sulfamethoxazole combined with ultrasound-guided bladder lavage and supportive therapy resulted in complete clinical recovery within 10 days. Conclusions: This case highlights the pathogenic potential of S. sciuri in domestic rabbits and its capacity to exhibit multidrug resistance. The findings underscore the necessity of including rabbits in antimicrobial resistance surveillance programs and reinforce the importance of culture and sensitivity testing in guiding the therapeutic management of exotic companion animals. Full article

Candida spp. are common components of normal microbiota in the oral cavity. However, Candida albicans can be a primary cause of superficial infections in the oral cavity and esophagus, especially in immunocompromised individuals. While these infections are rarely life-threatening, they can significantly impair quality of life and, in severe cases, progress to hematogenous dissemination. Oral candidiasis often exhibits as pseudomembranous, erythematous (atrophic), chronic hyperplastic, denture stomatitis, or angular cheilitis. Esophageal candidiasis is typically diagnosed by upper endoscopy, which involves histological examination and brushing. Clinical guidelines recommend topical antifungal agents for mild oral candidiasis, and systemic agents for moderate-to-severe disease or when topical therapy fails. However, azole antifungals pose a substantial risk of drug–drug interactions, primarily due to the inhibition of cytochrome P450 enzymes and drug transporters, which dramatically alters the pharmacokinetics of co-administered drugs. Additionally, amphotericin B, a polyene macrolide antibiotic, may cause nephrotoxicity and electrolyte disturbances (e.g., hypokalemia and hypomagnesemia). Moreover, the co-administration of nephrotoxic drugs may augment the toxicity associated with amphotericin B. Therefore, this review aimed to provide a comprehensive overview of the management of oral and esophageal candidiasis from the viewpoint of clinical pharmacology, with a particular focus on drug–drug interactions and adverse effect profiles. Full article

Macrolides—especially azithromycin—have been increasingly investigated in chronic respiratory diseases for their combined antimicrobial, anti-inflammatory, and immunomodulatory properties. Randomized controlled trials have demonstrated significant reductions in exacerbation frequency in selected patient populations with bronchiectasis, COPD, and asthma, although benefits on lung function and quality of life are variable. Beyond these advantages, concerns remain regarding antimicrobial resistance and uncertainties about long-term safety. Different guidelines across various diseases therefore recommend cautious and selective use of macrolides, with attention to phenotype selection, while alternative or emerging options such as biologics and novel anti-inflammatory agents are reshaping the therapeutic landscape. In this narrative review, we analyze the evidence for macrolide therapy across major chronic respiratory diseases, highlighting both the enduring clinical relevance and the limitations of long-term macrolide therapy, and discussing whether these drugs are approaching their therapeutic dusk or could still open a new dawn for selected patients. To this end we researched EMBASE and PubMed for articles published in English between 2000 and 2020 with restrictions to original articles, and freely between 2021 and 2025. Full article

Objective: The high frequency of prescribing oral antimicrobial agents, such as third-generation cephalosporins, macrolides, and fluoroquinolones, in local clinics is a major issue that can lead to the emergence of antimicrobial-resistant bacteria in the community. Hospitals have recently adopted the days of antibiotic spectrum coverage (DASC), which considers the antibacterial spectrum as a novel indicator of appropriate antimicrobial use. Although it has been used in inpatient settings, its applicability in community pharmacy settings remains unclear. Materials and Methods: The aim of this study was to determine whether the DASC is a valuable indicator of appropriate antimicrobial use in community pharmacies. We tabulated the use of antimicrobials dispensed at one of our pharmacies in Tokyo from 1 January 2018, to 31 December 2023. The DASC/100 prescriptions were calculated using the Antibiotic Spectrum Coverage score, which quantifies the extent of antimicrobial activity against key organisms. Higher scores indicate broader-spectrum agents, whereas lower scores indicate narrower-spectrum agents. Additionally, the days of therapy (DOT) value was calculated, along with the DOT/100 prescriptions, based on the dispensed prescriptions. Subgroup analyses were conducted for pediatric children aged < 6 years and the elderly (≥65 years). Results: The DASC/DOT was used to assess the appropriate use of antimicrobials. The DOT/100 and DASC/100 prescriptions in 2021–2023 were 50.1% and 51.5% lower, respectively, than those before 2020 (p < 0.05). During the same period, the DASC/DOT decreased by 0.7%, indicating that, despite the decrease in the number of antimicrobial prescriptions, the antimicrobial spectrum did not become narrower. In children < 6 years of age, DOT and DASC values declined significantly, possibly indicating a decrease in the number of antibiotic prescriptions for viral upper respiratory tract infections. In the elderly (≥65 years), the DASC/DOT remained relatively high, indicating their continued reliance on broad-spectrum agents, such as fluoroquinolones and macrolides. Conclusions: This study demonstrates the feasibility and benefits of the DASC/DOT as a spectrum-based indicator for appropriate antimicrobial use in community pharmacies. Therefore, the DASC/DOT serves as a practical and spectrum-sensitive indicator of outpatient antimicrobial use to guide antimicrobial stewardship in community settings. Furthermore, age-specific analyses highlighted the importance of targeted interventions to promote the judicious use of broad-spectrum antimicrobials, particularly among the elderly (≥65 years old). Full article

Recurrent erysipelas is a common and clinically significant condition that poses challenges for both patients and healthcare systems. Each episode may damage lymphatic vessels, leading to chronic lymphedema, which perpetuates the risk of further relapses. Recurrence rates remain high, ranging from 11% in outpatients during the first year to up to 46% of hospitalized patients within three years. The lower limbs are the most frequent site, although recurrences may also occur in other regions, such as the upper limb after mastectomy with lymph node dissection. This review summarizes current knowledge on risk factors, preventive measures, and chemoprophylaxis in recurrent erysipelas. Modifiable risk factors such as obesity, diabetes, venous insufficiency, tinea pedis, and poor hygiene play an important role, while non-modifiable factors include age, sex, and a history of prior episodes. Non-pharmacological strategies—weight reduction, glycemic control, smoking cessation, compression therapy, and meticulous skin care—form the cornerstone of prevention and may reduce the need for long-term antibiotics. Antibiotic prophylaxis, most commonly with oral penicillin V or intramuscular benzathine penicillin, has been shown to lower recurrence rates. However, efficacy may be reduced in patients with chronic edema or severe obesity. Macrolides serve as alternatives in penicillin-allergic patients, but concerns remain about resistance, adverse effects, and drug–drug interactions. In conclusion, recurrent erysipelas requires a multifaceted approach. While antibiotic prophylaxis is effective, its long-term success depends on simultaneous management of underlying conditions. Further studies are needed to define optimal regimens, treatment duration, and non-antibiotic alternatives. Full article