Search Results (12)

Background: Antibiotics are commonly used in gynecology, yet only limited outpatient prescribing data are available in Germany. The aim of this study is to estimate the prevalence of antibiotic prescriptions in gynecological practices and to identify patient and diagnostic factors. Methods: A retrospective cross-sectional analysis was conducted using anonymized electronic records from the IQVIA Disease Analyzer, including 344,187 women aged ≥16 years who had at least one gynecological visit in 2024. The primary outcome of interest was the prescription of an antibiotic. Consequently, the prevalence of antibiotic prescriptions was calculated overall and stratified by age group. Associations between potential factors and antibiotic prescriptions were assessed using multivariable logistic regression. Results: The overall prescription prevalence was 8.4% (29,007/344,187). Regarding the age distribution within the prescribed sample, the highest percentages were observed among women aged 31–40 years (25.6%) and 16–30 years (25.4%), while those aged 51–60 and >60 made up 12.9% and 19.1%, respectively. The most commonly prescribed agents were fosfomycin trometamol (35.9%), clindamycin (17.6%), and pivmecillinam (10.7%). Mastitis (OR 63.54, 95% CI 55.79–72.38), acute cystitis (OR 43.67, 95% CI 41.63–45.80), and unspecified urinary tract infection (OR 31.58, 95% CI 20.11–33.12) were strongly positively associated with AB prescription. Positive associations were also observed for acute vaginitis (OR 3.44, 95% CI 3.30–3.58), chlamydial infection (OR 6.27, 95% CI 5.77–6.81), and pregnancy (OR 1.95, 95% CI 1.85–2.05). Negative associations were observed for dysmenorrhea (OR 0.52, 95% CI 0.48–0.56), irregular menstruation (OR 0.65, 95% CI 0.60–0.71), menopausal disorders (OR 0.51, 95% CI 0.48–0.53), and ovarian cysts (OR 0.78, 95% CI 0.72–0.84). Conclusions: Antibiotic use in gynecology is low and strongly diagnosis-driven, primarily for urogenital infections. Signals of inappropriate prescribing in patients with candidiasis suggest a need for improved diagnostic accuracy and guideline adherence. Full article

Programmed death-ligand 1 (PD-L1) is a crucial immune checkpoint protein that tumors often exploit to evade immune surveillance. This study systematically screened a library of 1031 FDA-approved drugs using a high-throughput molecular dynamics approach to identify potential inhibitors targeting PD-L1. From this screening, five promising compounds—vorapaxar, delafloxacin, tenofovir disoproxil, pivmecillinam, and fursultiamine—showed significant binding affinities to PD-L1 and demonstrated cytotoxic activity against A549 lung tumor cells. These candidates were further evaluated through extended molecular dynamics simulations lasting up to 150 ns to assess their structural stability, residue fluctuations, and binding free energy. Among the identified compounds, pivmecillinam demonstrated the most favorable results, exhibiting stable binding interactions and a binding free energy of −18.01 kcal/mol, comparable to that of the known PD-L1 inhibitor BMS-1. These findings suggest that pivmecillinam has promising immunomodulatory potential and could serve as a candidate for further development in cancer immunotherapy. Overall, this study underscores the value of integrating high-throughput MD and experimental approaches for drug repositioning to identify novel therapeutic agents. Full article

Urinary tract infections (UTIs) are one of the most common bacterial diseases both in communities and in hospitalized patients, and at the same, time they are one of the most common indications for the use of antibiotics. UTI guidelines are generally available nationally or internationally, but they do not address all aspects of UTI treatment for different patient cohorts, age, gender, or comorbidities. The aim of the study was to point out the importance of stratified cumulative antibiograms at the level of individual health care facilities and the significant differences between epidemiological data, not only at the national level, but also at the local level. Our study analyses data from 383 patients with UTIs from a hospital department, General University Hospital (GUH), and 272 patients from an outpatient medical facility, Urocentrum (UC). This analysis focuses on the most common UTI causative agent, Escherichia coli, its representation as the causative agent of UTI in patients with complicated acute cystitis (N30), and its representation in complicated acute cystitis in patients with prostate cancer (C61). In addition to the frequency of occurrence, a sub-analysis of the incidence of resistance of E. coli to commonly used antibiotics by age, gender, diagnosis, and medical facility was performed. Results: The most common causative agent of UTI was E. coli. In patients with N30, it was 70% in GUH and 54% in UC, but in oncological patients with UTI, it was only 39% and 35%, respectively. In patients with UTI in C61, there was a significant difference in susceptibility of E. coli between individual health care facilities. Lower resistance was found in UC opposite to GUH isolates in ampicillin, with 29.8% vs. 65%, p = 0.001; amoxicillin/clavulanic acid, with 8.5% vs. 30%, p = 0.01; with 2.1% vs. 17.5% in pivmecillinam, p = 0.01; with 10.6% vs. 37.5% in co-trimoxazole, p = 0.003; and ciprofloxacin, with 10.6% vs. 30%, p = 0.04. The study shows significant differences in the sensitivity of urinary E. coli isolates in patients in relation to age, gender, medical devices, and the presence of comorbidities. Full article

Background: The balance between antioxidants and pro-oxidants plays a significant role in the context of oxidative stress, influenced by both physiological and non-physiological factors. Objectives: In this study, 18 prescribed antibiotics (including doxycycline hydrochloride, tigecycline, rifampicin, tebipenem, cefuroxime, cefixime, potassium clavulanate, colistin, ampicillin, amoxicillin, amikacin, nalidixic acid, azithromycin, pipemidic acid trihydrate, pivmecillinam, aztreonam, fosfomycin sodium, and ciprofloxacin) were subjected to simultaneous determination of antioxidant and pro-oxidant potential to assess if pro-oxidant activity is a dominant co-mechanism of antibacterial activity or if any antibiotic exhibits a balanced effect. Methods: This study presents a recently developed approach for the simultaneous assessment of antioxidant and pro-oxidant potential on a single microplate in situ, applied to prescribed antibiotics. Results: Ten antibiotics from eighteen showed lower antioxidant or pro-oxidant potential, while five exhibited only mild potential with DPPH50 values over 0.5 mM. The pro-oxidant antioxidant balance index (PABI) was also calculated to determine whether antioxidant or pro-oxidant activity was dominant for each antibiotic. Surprisingly, three antibiotics—doxycycline hydrochloride, tigecycline, and rifampicin—showed significant measures of both antioxidant and pro-oxidant activities. Especially notable was tebipenem, a broad-spectrum, orally administered carbapenem, showed a positive PABI index ratio, indicating a dominant antioxidant over pro-oxidant effect. Conclusions: These findings could be significant for both therapy, where the antibacterial effect is enhanced by radical scavenging activity, and biotechnology, where substantial pro-oxidant activity might limit microbial viability in cultures and consequently affect yield. Full article

Urinary tract infections (UTIs) cause a significant infectious burden in the community and demand a coordinated approach from all first-line health professionals. Uncomplicated UTIs refer to infections in non-pregnant females without any underlying localized or generalized pathology, diagnosed through history by the presence of specific local symptoms and in the absence of systemic ones like fever. Uncomplicated UTIs are usually caused by Escherichia coli species; thus, empirical antibiotic treatment can be immediately initiated. A percentage of patients can experience a resolution of symptoms without therapy; however, this “wait and observe” approach is supported only by the relevant British guidelines. There are limited quality studies in the literature on adjuvant treatment options; these can include BNO 145, a phytotherapeutic medicine, and XHP, a medical technology product. Despite being licensed by the European Medicines Agency on the basis of traditional use, there is inadequate support in the medical literature for the use of cranberry extracts and Arctostaphylos uva-ursi extracts. The use of antibiotics is associated with higher response rates and urine culture sterilization as well as lower recurrence/relapse rates; on the other hand, side effect rates are also higher. In choosing the proper empirical antibiotic therapy, one has to take into account individual patient characteristics and community resistance patterns as well as the antimicrobial resistance pressure exerted by the wide use of a specific antibiotic. There is a need for a common framework through which all frontline health practitioners should operate when faced with a case of uncomplicated UTI. In Greece, there are three different guidelines for UTI treatment, developed by the Ministry of Health, the National Organization for Medicines, and the Hellenic Society for Infectious Diseases. The authors of the present study aim at synthesizing these guidelines as well as relevant guidelines from international scientific or other national regulatory organizations while taking into account local resistance patterns. The authors propose the first-line use of either fosfomycin, nitrofurantoin, or pivmecillinam. The use of trimethoprim/sulfamethoxazole is discouraged due to increased resistance of Greek community E. coli isolates. Fluoroquinolone use should be avoided due to high E. coli community resistance (exceeding 20% for Greece), along with their unfavorable benefit/side effect balance in uncomplicated UTIs, as well as the overall community resistance pressure exerted by their use. A 5-day regimen remains superior to a 3-day one; the latter may be suitable for certain, not yet adequately characterized, patients. Full article

Isovaleric aciduria (IVA) is a rare disorder of leucine metabolism and part of newborn screening (NBS) programs worldwide. However, NBS for IVA is hampered by, first, the increased birth prevalence due to the identification of individuals with an attenuated disease variant (so-called “mild” IVA) and, second, an increasing number of false positive screening results due to the use of pivmecillinam contained in the medication. Recently, machine learning (ML) methods have been analyzed, analogous to new biomarkers or second-tier methods, in the context of NBS. In this study, we investigated the application of machine learning classification methods to improve IVA classification using an NBS data set containing 2,106,090 newborns screened in Heidelberg, Germany. Therefore, we propose to combine two methods, linear discriminant analysis, and ridge logistic regression as an additional step, a digital-tier, to traditional NBS. Our results show that this reduces the false positive rate by $69.9\%$ from 103 to 31 while maintaining $100\%$ sensitivity in cross-validation. The ML methods were able to classify mild and classic IVA from normal newborns solely based on the NBS data and revealed that besides isovalerylcarnitine (C5), the metabolite concentration of tryptophan (Trp) is important for improved classification. Overall, applying ML methods to improve the specificity of IVA could have a major impact on newborns, as it could reduce the newborns’ and families’ burden of false positives or over-treatment. Full article

Shigella sonnei remains the second most common cause of shigellosis in young children and is now increasingly dominant across developing countries. The global emergence of drug resistance has become a main burden in the treatment of S. sonnei infections and β-lactam antibiotics, such as pivmecillinam and ceftriaxone, are recommended to be used as second-line treatment. They work by inhibiting the biosynthesis of the peptidoglycan layer of bacterial cell walls, in which the final transpeptidation step is facilitated by penicillin-binding proteins (PBPs). In this study, using protein homology modelling, we modelled the structure of PBP6 from S. sonnei and comprehensively examined the molecular interactions between PBP6 and its pentapeptide substrate and two antibiotic inhibitors. The docked complex of S. sonnei PBP6 with pentapeptides showed that the substrate bound to the active site groove of the DD-carboxypeptidase domain, via hydrogen bonding interactions with the residues S79, V80, Q101, G144, D146 and R240, in close proximity to the catalytic nucleophile S36 for the nucleophilic attack. Two residues, R240 and T208, were found to be important in ligand recognition and binding, where they formed strong hydrogen bonds with the substrate and β-lactams, respectively. Our results provide valuable information on the molecular interactions essential for ligand recognition and catalysis by PBP6. Understanding these interactions will be helpful in the development of effective drugs to treat S. sonnei infections. Full article

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Escherichia coli is by far the leading cause of community-acquired UTIs. Pivmecillinam, the oral prodrug of the penicillin derivative mecillinam (amdinocillin), was re-introduced in Germany in March 2016 for first-line treatment of acute uncomplicated cystitis. This study aimed to evaluate the prevalence of resistance to mecillinam in comparison to nine other antibiotics used for oral treatment in E. coli urine isolates after the re-introduction of pivmecillinam. A total of 460 isolates were collected at 23 laboratories of clinical microbiology between October 2019 and March 2020. Forty-six isolates (10.0%) produced an extended-spectrum β-lactamase (ESBL) of the CTX-M family. Resistance to amoxicillin (43.3%) was most widespread, followed by resistance to trimethoprim-sulfamethoxazole (27.0%), amoxicillin-clavulanic acid (18.0%), cefuroxime (11.3%), and ciprofloxacin (11.1%). Twenty-four E. coli isolates (5.2%) were resistant to mecillinam. The concentrations of mecillinam needed to inhibit 50/90% of the ESBL-producing isolates and the remaining isolates were 1/4 mg/L and 0.5/4 mg/L, respectively. The findings support the recommendation to regard pivmecillinam as a first-line option for the treatment of uncomplicated lower UTIs. Full article

In the context of increasing antimicrobial resistance in Enterobacterales, the management of these UTIs has become challenging. We retrospectively assess the prevalence of antimicrobial resistance in Enterobacterales isolates recovered from urinary tract samples in France, between 1 September 2017, to 31 August 2018. Twenty-six French clinical laboratories provided the susceptibility of 134,162 Enterobacterales isolates to 17 antimicrobials. The most frequent species were E. coli (72.0%), Klebsiella pneumoniae (9.7%), Proteus mirabilis (5.8%), and Enterobacter cloacae complex (2.9%). The overall rate of ESBL-producing Enterobacterales was 6.7%, and ranged from 1.0% in P. mirabilis to 19.5% in K. pneumoniae, and from 3.1% in outpatients to 13.6% in long-term care facilities. Overall, 4.1%, 9.3% and 10.5% of the isolates were resistant to cefoxitin, temocillin and pivmecillinam. Cotrimoxazole was the less active compound with 23.4% resistance. Conversely, 4.4%, 12.9%, and 14.3% of the strains were resistant to fosfomycin, nitrofurantoin, and ciprofloxacin. However, less than 1% of E. coli was resistant to fosfomycin and nitrofurantoin. We identified several trends in antibiotics resistances among Enterobacterales isolates recovered from the urinary tract samples in France. Carbapenem-sparing drugs, such as temocillin, mecillinam, fosfomycin, cefoxitin, and nitrofurantoin, remained highly active, including towards ESBL-E. Full article

Background: Antibiotics are commonly prescribed for outpatient management of cystitis. Previous evidence suggests that certain factors likely beyond the infection seem to influence the choice of antimicrobial treatment. However, studies on the specific antibiotic treatments for cystitis are lacking. This study aimed to explore the antibiotic treatments for cystitis using nationwide primary healthcare data and investigate if factors beyond the infection could be associated with fluoroquinolone treatment. Methods: This nationwide follow-up cohort study consisted of 352,507 women with cystitis. The primary aim was to investigate what specific classes of antibiotics were redeemed by patients within five days from the cystitis diagnosis. Each patient could only be included once. Logistic regression models were also used to examine the relationship between fluoroquinolone (FQ) treatment, parity, and sociodemographic factors. Results: In total, 192,065 antibiotic prescriptions were redeemed. Pivmecillinam (58.4%) followed by nitrofurantoin (22.2%), trimethoprim (12.0%), fluoroquinolone (5.6%), and cephalosporins (1.5%) were the most redeemed antibiotics. Sociodemographic factors were weakly associated with fluoroquinolone treatment; young age was inversely associated with fluoroquinolone treatment. Parity and cervical cancer history were not associated with fluoroquinolone treatment. The proportion of fluoroquinolone and trimethoprim treatments decreased over time, while pivmecillinam and nitrofurantoin increased. Conclusions: The treatment trends of antibiotics redeemed within five days from a cystitis diagnosis were similar to the national surveillance program of these antibiotics (not diagnosis linked). Fluoroquinolones were weakly associated with sociodemographic factors, which likely is only of historical relevance. Full article

Given the increasing antimicrobial resistance in urinary tract infections (UTI), alternative strategies need to be investigated. Determination of minimal inhibitory and bactericidal concentrations of essential oils from cajeput, lemongrass, tea tree, and thyme in artificial urine, revealed bactericidal activity of all four tested essential oils against seven uropathogenic species with values ranging between 0.78–50 mg/mL. Tea tree and thyme essential oils were more efficient than lemongrass and cajeput. In addition, antibiotic-resistant strains showed similar susceptibility as antibiotic-sensitive strains, suggesting no cross-resistance between antibiotics and these essential oils. Checkerboard assays revealed a synergistic activity of the combination of thyme and tea tree. Furthermore, the combination with thyme and tea tree essential oils increased the activity of fosfomycin and pivmecillinam, but not nitrofurantoin, against Escherichia coli. This study provides a basis for further investigation of the potential of thyme and tea tree oil as an alternative or additional treatment of UTI. Full article

Objectives: To investigate pivmecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivmecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect—symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect—elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ≥10³ bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18–55 years) were empirically treated with pivmecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: Pivmecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised. Full article