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In this paper, the effect of zero-valent iron (Fe0) activated persulfate (PDS) on the removal of enrofloxacin (ENR) was investigated, and the effect and mechanism were analyzed by exploring the effects of Fe0 concentration, PDS concentration, pH, and the influence of anion and aqueous matrix on the removal of ENR by the Fe0/PDS system. The results showed that when [ENR] = 20 µmol/L, [Fe0] = 0.15 g/L, [PDS] = 0.4 mmol/L, the removal rate of ENR was 85.3% at 90 min, the mainradicals were HO•, SO4•− and O2•−. At the same time, the system had a good mineralization effect (TOC removal rate > 40%), in addition, the system did not show obvious toxicity to soil microorganisms after the reaction, furthermore the Fe0/PDS system had a good removal effect on ENR in a wide pH range (4 ≤ pH ≤ 10). There is basically no difference in the removal rate of Fe0/PDS system in ultrapure water and river water. The results of this experiment could provide a reference for the removal of antibiotics based on advanced oxidation techniques based on SO4•−. [ABSTRACT FROM AUTHOR]

Coriolopsis gallica (Cga) is a white-rot fungus renowned for its ability to secrete ligninolytic enzymes that are capable of oxidizing phenolic compounds. This study aimed to investigate the biochemical characteristics of a dye-decolorizing peroxidase named CgaDyP1 and test its ability to biotransform antibiotics. CgaDyP1 was cloned and heterologously expressed in Escherichia coli. We fully characterized the biochemical properties of CgaDyP1 and evaluated its dye-decolorizing potential to confirm that it belongs to the DyP class of enzymes. We also tested its fluoroquinolone antibiotic biotransformation potential for possible biotechnological applications. Alignment of the primary amino acid sequence with DyP homolog sequences showed that CgaDyP1 has high similarity with other fungal DyPs. The recombinant CgaDyP1 exhibited activity on substrates such as ABTS and 2,6-dimethoxyphenol (DMP) with optimal performance at a pH of 3, although activity at pH 2.5, pH 4, and pH5 diminished over time. Thermostability tests indicated that the enzyme remains stable at temperatures between 30 °C and 50 °C and retains 70% of its initial activity after 180 min at 50 °C. Tests on the effect of hydrogen peroxide on CgaDyP1 activity found peak activity at 0.25 mM H2O2. CgaDyP1 decolorized five industrial dyes, and kinetics data confirmed that it belongs to the DyP class of enzymes. CgaDyP1 was shown to biotransform some of the 7 recalcitrant fluoroquinolone antibiotics tested here, including levofloxacin, moxifloxacin, and norfloxacin, and thus holds potential for biotechnological applications. [ABSTRACT FROM AUTHOR]

The work focuses on the development of a fluorimetric version of the fingerprint method based on conducting indicator reactions in the presence of a test sample. Observation of these reactions over time provides a more detailed information compared to batch methods, thereby improving sample recognition and enabling quantitative analysis. The proposed indicator reaction utilizes a commercial carbocyanine dye and 4-dimethylaminobenzaldehyde, whose interaction results in a decrease in fluorescence intensity and changes in absorbance over time. Three fluoroquinolones—moxifloxacin, levofloxacin, and ofloxacin—selectively change the signal in concentrations of 1 μM or higher, while other drugs, including different fluoroquinolones, do not interfere with the determination. Ofloxacin was detected in human urine samples at various times post-drug intake. A potential of using the same indicator reaction for sample recognition was demonstrated on examples of apple juices, soil extracts, and meat of varying freshness. Chemometric methods, including linear discriminant analysis, were used for data processing. The method achieved 97% accuracy in discriminating fifteen apple juice samples, 94% accuracy for ten apple juices from 2022 and 2023, 99% accuracy for ten soil samples, and successfully determined the freshness of five meat samples. [ABSTRACT FROM AUTHOR]

Fluoroquinolones (FQ), commonly prescribed antibiotics, may trigger aortic and carotid dissections. We report three successive cases of visceral artery dissection: one patient with celiac trunk dissection and two with dissection of the superior mesenteric artery. These events occurred up to 4 months after 7 to 14 days of FQ treatment (2 cases of ofloxacin, 1 of norfloxacin). There was no other apparent cause of dissection. These dissections were isolated, apart from a minimal aortic dissection separate from the visceral arterial dissection in one case. A case series cannot certify the relationship between dissection and FQ, but it can be hypothesized. The association between fluoroquinolone use and higher occurrence of aneurysm and dissection remains discussed in aortic syndrome. The potential link between FQ and visceral artery dissection is even less described but should be reported in the absence of previous cases in the literature. The pathophysiological theory is the induction of overexpression of some matrix metalloproteinases and a decrease of their inhibitors, provoking a dysregulation in collagen synthesis and degradation of the extracellular matrix. [ABSTRACT FROM AUTHOR]

A 3‐year‐old male neutered Golden Retriever with nasal swelling and lymphadenopathy was diagnosed with diffuse Mycobacterium avium infection. Treatment with 9 months of enrofloxacin, clarithromycin and rifampicin was successful, but relapsed 10 months later with lymphadenopathy, skin plaques and testicular involvement. Repeat treatment for 12 months was effective but 15 months later a second relapse responded to the same therapy which is ongoing with survival from diagnosis of 82 months. A 1‐year‐old male neutered Portuguese Podengo was diagnosed with polyarthritis and M. avium infection and treated with enrofloxacin, clarithromycin and rifampicin for 4 months but relapsed, subsequently responding to combined pradofloxacin, rifampicin, doxycycline and ethambutol. After 12 months of treatment, M. avium was detected and treatment extended to 17 months before stopping when no organism was detected. Relapse occurred after 6 weeks, responding to retreatment but relapsing (polyarthropathy, lymphadenomegaly) after 15 months, with euthanasia 38 months after diagnosis. Dogs with M. avium are challenging to treat with frequent relapse; however, long‐term survival is possible. [ABSTRACT FROM AUTHOR]

Improvement of selectivity and activity of imprinted photocatalysis is a major challenge for antibiotic photodegradation due to the functional monomers of imprinting hindering the photogenerated carrier migration. Here, an organic imprinted Ag-polyaniline/CoFe2O4/Carbon photocatalyst (IM-Ag-PANI/CoFe2O4/C) was successfully prepared by photo-initiated polymerization which achieved selective photodegradation of tetracycline (TC). The heterojunction formed by the functional monomer Ag@PANI and CoFe2O4/C not only facilitates the separation of photo-excited carriers and the exposure of active sites but also contributes to the selective adsorption capability by imprinted cavity on Ag@PANI, thereby improving the photocatalytic activity and selectivity simultaneously. In addition, the Corncob conversion carbon matrix method and iron-based magnetic character enable a more environmentally friendly and recyclable capability of IM-Ag-PANI/CoFe2O4/C. After using machine learning models to train and predict experimental parameters by changing experimental parameters, the IM-Ag-PANI/CoFe2O4/C can photodegrade 82.23% of TC within 2 h, and it has a selective degradation ability compared to enrofloxacin hydrochloride (EH). This research provides a new idea for the construction of imprinted photocatalytic materials that can improve photocatalytic activity. [ABSTRACT FROM AUTHOR]

Pharmaceuticals and personal care products (PPCPs) monitoring in surface water is crucial to address the escalating threat of antimicrobial resistance and safeguard public health. This study aimed to investigate the occurrence of 21 different PPCPs, including wastewater chemical markers, antibiotics, and parabens in the surface water of Chennai city using Ultra Performance Liquid Chromatography—Triple Quadrupole Mass Spectrometry (UPLC-MS/MS) analysis. It is noteworthy that chemical markers viz., carbamazepine (CBZ) and caffeine (CAF) were detected in all the sites and contributed to more than 95% of the total PPCPs load indicating a significant intrusion of wastewater. Among the antibiotics, fluoroquinolones were dominant in this study. Interestingly, a significant and strong correlation was seen between fluoroquinolones, CBZ and CAF (R2 = 0.880–0.928, p < 0.05), suggesting similarities in their sources. More than 50% of the sites exhibited a risk for antimicrobial resistance (RQAMR) with RQAMR > 1 for ciprofloxacin, indicating a significant public health concern. The ecotoxicological risk assessment of PPCPs showed no risk to any organisms, except for triclosan, which posed a risk to fish and daphnids at one site near an open drain in Buckingham canal. [ABSTRACT FROM AUTHOR]

Background: Fluoroquinolones are broad-spectrum antibiotics with significant antimicrobial activity. Despite their therapeutic benefits, they are associated with a range of adverse drug reactions (ADRs), particularly those affecting the central nervous system (CNS). This study aimed to analyze the psychiatric ADRs linked to fluoroquinolones using data from the FDA Adverse Event Reporting System (FAERS) database. Methods: A retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q4 2023. The data processing phase involved the FDArecommended deduplication method, and ADRs were classified according to Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was performed using the reporting odds ratio (ROR), and statistical significance was assessed using the Chi-square test or Fisher's exact test. Results: The study identified 84,777 reports associated with fluoroquinolones, with 359,480 Preferred Terms-annotated entries, 27,816 of these reports were psychiatric ADRs. Mood disorders were the most frequently reported, including anxiety, depression, and delirium, with some reports escalating to suicidal ideation and behaviors. The Standardized MedDRA Query classification system was used to categorize these ADRs into Depression, Suicide/self-injury, Psychosis and psychotic disorders, and Non-infectious encephalopathy/delirium. Ciprofloxacin was most frequently linked to depression and suicidal ideation, while moxifloxacin showed a robust correlation with delirium. The risk of psychiatric ADRs varied by age group, with affective disorders more prevalent in adults under 65 and psychosis and delirium in those over 65. Conclusion: Fluoroquinolones are associated with a range of psychiatric ADRs, with notable differences between the drugs in the class. The study highlights the need for caution in prescribing fluoroquinolones, particularly for patients with pre-existing mental health conditions or those in higher risk age groups. The findings also underscore the importance of considering age-specific preventive strategies when administering these antibiotics. [ABSTRACT FROM AUTHOR]

Development of new multi‐ratiometric fluorescence probes has been a popular research field. This approach provides richer and more accurate information for the recognition of different substances which have similar chemical and physical properties. In this work, a ratiometric fluorescence sensor UIO‐66⊃FL/RhB is successfully constructed by incorporating fluorescein (FL) and rhodamine B (RhB) to the UIO‐66. With the addition of fluoroquinolones (FQs), the prepared UIO‐66⊃FL/RhB sensor can be used for the 2D emission‐fingerprint map, the linear discriminant analysis (LDA) and hierarchical clustering analysis (HCA) in recognition the presence of each FQs. The fluorescence probe offers a broad linear range (0‐8 µM) and a low detection limit (3.7 nM) in sensing ofloxacin. In addition, a smartphone‐assisted portable sensing platform and a portable UIO‐66⊃FL/RhB hydrogel test material are constructed successfully for screening before fluorescence detection. This study proposes a novel multi‐ratiometric fluorescence probe, which can recognize different FQs. Besides, the UIO‐66⊃FL/RhB‐based hydrogel beads are construction for screening before the detection of FQs, which established a promising strategy for the simple and accurate discrimination of FQs. [ABSTRACT FROM AUTHOR]

Background In 2019, the World Health Organization called for operational research on all-oral shortened regimens for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We report safety and effectiveness of three 9-month all-oral regimens containing bedaquiline (Bdq), linezolid (Lzd), and levofloxacin (Lfx) and reinforced with cycloserine (Cs) and clofazimine (Cfz), delamanid (Dlm) and pyrazinamide (Z), or Dlm and Cfz. Methods We conducted a prospective cohort study of patients initiating treatment for pulmonary MDR/RR-TB under operational research conditions at public health facilities in Kazakhstan. Participants were screened monthly for adverse events. Participants with baseline resistance were excluded from the study and treated with a longer regimen. We analyzed clinically relevant adverse events of special interest in all participants and sputum culture conversion and end-of-treatment outcomes among individuals who were not excluded. Results Of 510 participants, 41% were women, the median age was 37 years (25th–75th percentile: 28–49), 18% had a body mass index <18.5 kg/m2, and 51% had cavitary disease. A total of 399 (78%) initiated Bdq-Lzd-Lfx-Cs-Cfz, 83 (16%) started Bdq-Lzd-Lfx-Dlm-Z, and 28 (5%) initiated Bdq-Lzd-Lfx-Dlm-Cfz. Fifty-eight individuals (11%) were excluded from the study, most commonly due to identification of baseline drug resistance (n = 52; 90%). Among the remaining 452 participants, treatment success frequencies were 92% (95% CI: 89–95%), 89% (95% CI: 80–94%), and 100% (95% CI: 86–100%) for regimens with Cs/Cfz, Dlm/Z, and Dlm/Cfz, respectively. Clinically relevant adverse events of special interest were uncommon. Conclusions All regimens demonstrated excellent safety and effectiveness, expanding the potential treatment options for patients, providers, and programs. [ABSTRACT FROM AUTHOR]

A new group of thiazolidine-2,4-dione derivatives of ciprofloxacin having butyryl linker 3a-l was synthesized via an alkylation of thiazolidine-2,4-diones with butyryl ciprofloxacin with yield range 48–77% andfully characterized by various spectroscopic and analytical tools. Anti-cancer screening outcomes indicated that 3a and 3i possess antiproliferative activities against human melanoma LOX IMVI cancer cell line with IC50 values of 26.7 ± 1.50 and 25.4 ± 1.43 µM, respectively, using doxorubicin and cisplatin as positive controls with an IC50 of 7.03 ± 0.40 and 5.07 ± 0.29 µM, respectively. Additionally, compound 3j showed promising anticancer activity against human renal cancer A498 cell line with IC50 value of 33.9 ± 1.91 µM while doxorubicin and cisplatin showed IC50 values of 3.59 ± 0.20 and 7.92 ± 0.45, respectively. On the other hand, compound 3i did not show considerable anti-bacterial activity against S. aureus, E. coli and P. aeruginosa, and only moderate activity against K. pneumoniae with only a tenth of the activity of ciprofloxacin, confirming the cytotoxicity observed. Mechanistically, compound 3i inhibited both topoisomerase I and II with IC50 of 4.77 ± 0.26 and 15 ± 0.81 µM. Furthermore, it induced cell cycle arrest at S phase in melanoma LOX IMVI cells. Moreover, 3i provoked substantial levels of early, late apoptosis and necrosis in melanoma LOX IMVI cell line comparable to that induced by doxorubicin. Furthermore, compound 3i increased the expression level of active caspase-3 by 49 folds higher in LOX IMVI cell, increased protein expression level of Bax more than the control by 3 folds and inhibited PARP-1by 33% in LOX IMVI. All results were supported by theoretical docking studies on both tested enzymes confirming potential cytotoxicity for the synthesized hybrids. [ABSTRACT FROM AUTHOR]

This study established novel and high-throughput strategies for the simultaneous analysis of 30 fluorinated emerging pollutants in different matrices from the shrimp aquaculture system in eastern China using UHPLC-MS/MS. The parameters of SPE for analysis of water samples and of QuEChERS methods for sediment and shrimp samples were optimized to allow the simultaneous detection and quantitation of 17 per- and polyfluoroalkyl substances (PFASs) and 13 fluoroquinolones (FQs). Under the optimal conditions, the limits of detection of 30 pollutants for water, sediment, and shrimp samples were 0.01–0.30 ng/L, 0.01–0.22 μg/kg, and 0.01–0.23 μg/kg, respectively, while the limits of quantification were 0.04–1.00 ng/L, 0.03–0.73 μg/kg, and 0.03–0.76 μg/kg, with satisfactory recoveries and intra-day precision. The developed methods were successfully applied to the analysis of multiple samples collected from aquaculture ponds in eastern China. PFASs were detected in all samples with concentration ranges of 0.18–0.77 μg/L in water, 0.13–1.41 μg/kg (dry weight) in sediment, and 0.09–0.96 μg/kg (wet weight) in shrimp, respectively. Only two FQs, ciprofloxacin and enrofloxacin, were found in the sediment and shrimp. In general, this study provides valuable insights into the prevalence of fluorinated emerging contaminants, assisting in the monitoring and control of emerging contaminants in aquatic foods. [ABSTRACT FROM AUTHOR]

Metal ions have important roles in supporting the catalytic activity of DNA-regulating enzymes such as topoisomerases (topos). Bacterial type II topos, gyrases and topo IV, are primary drug targets for fluoroquinolones, a class of clinically relevant antibacterials requiring metal ions for efficient drug binding. While the presence of metal ions in topos has been elucidated in biochemical studies, accurate location and assignment of metal ions in structural studies have historically posed significant challenges. Recent advances in X-ray crystallography address these limitations by extending the experimental capabilities into the long-wavelength range, exploiting the anomalous contrast from light elements of biological relevance. This breakthrough enables us to confirm experimentally the locations of Mg2+ in the fluoroquinolone-stabilized Streptococcus pneumoniae topo IV complex. Moreover, we can unambiguously identify the presence of K+ and Cl-ions in the complex with one pair of K+ ions functioning as an additional intersubunit bridge. Overall, our data extend current knowledge on the functional and structural roles of metal ions in type II topos. [ABSTRACT FROM AUTHOR]

Herein, the pharmacokinetic profiles, binding interactions, and molecular properties of fluoroquinolone derivatives as prospective antiviral drugs are examined using a combination of docking, ADME, and DFT simulations. The effectiveness of the ligands is compared with the clinically tested and FDA-authorized medicine remdesivir. The findings demonstrated encouraging binding energies, indicating possible inhibitory effectiveness against SARS-CoV-2 Mpro. The fluoroquinolone derivatives also exhibit promising ADME characteristics, although compounds 5, 6, 9, 12–20 possess poor values, suggesting that oral administration may be possible. The potential of the selected compounds as SARS-CoV-2 Mpro inhibitors is thoroughly understood because of the integrated analysis of DFT, with compound 11 demonstrating the highest energy gap of 0.2604 eV of, docking with viral targets with docking scores of −7.9 to −5.9 kcal/mol, with compound 18 demonstrating the highest docking score, which is at the 13th position in energy difference in the DFT data. Their favorable electrical properties, robust binding interactions with viral targets, and attractive pharmacokinetic profiles boost their potential as prospective study subjects. These substances have the potential to be transformed into cutting-edge antiviral therapies that specifically target SARS-CoV-2 Mpro and related coronaviruses. [ABSTRACT FROM AUTHOR]

This article discusses the recent regulatory restrictions on the use of fluoroquinolones and their impact on treating orthopaedic infections. We focus on the balance between the benefits and risks of fluoroquinolones in scenarios involving severe infections where alternative antibiotics may be less effective. The discussion includes a summary of recent evidence on adverse effects and the implications for clinical practice. [ABSTRACT FROM AUTHOR]

Background Over the years, reports have associated fluoroquinolones (FQ) with seizures. The incidence and whether FQ compared to non-epileptogenic antibiotic are associated with increased risk of seizures has yet to be examined. Methods A retrospective observational study of hospitalized patients treated with FQ (ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin) or macrolides (MA: azithromycin or roxithromycin) between January 2009 and January 2021 in a large tertiary academic medical centre. The outcome was the occurrence of a seizure during treatment. The Naranjo scale was used to assess causality between FQ treatment and seizures. Comparative analysis was conducted using propensity score matching to correct for possible bias due to non-random selection, followed by inverse probability weighting (IPW) to estimate the difference in seizure risk between FQ and MA. Results Overall, 52 722 patients were treated with FQ during a total of 178 982 days. Mean age was 65 (±19) years and 47% were females. Thirty-three patients (0.06%) experienced a seizure, yielding an incidence of 1:5422 treatment days. Causality was deemed probable and possible among 9/33 and 24/33, respectively. The MA group composed of 8522 patients treated during 17 954 treatment days. Mean age was 65 (±21) years, 49% were females. Six (0.07%) patients experienced each a single seizure. IPW estimated OR for seizures among the FQ versus MA group was 1.44 (95%CI 0.59–3.5, P  = 0.42). Discussion The incidence of FQ associated seizures among hospitalized patients is low and the risk did not significantly exceed that under macrolides. Our results provide evidence for clinicians and decision-makers when balancing fluoroquinolones risks and benefits. [ABSTRACT FROM AUTHOR]

Patients are sometimes mislabeled as having an immune-mediated antibiotic allergy in their medical records. Therefore, the aim of this study was to investigate the prevalence of subjects with non-immune mediated reactions to antibiotics using a standardized questionnaire. Subjects aged 18 years and older with a documented antibiotic allergy were identified and recruited from 2 outpatient clinics in the greater Chicago area. Subjects completed a standardized questionnaire during a single visit regarding their previous adverse reaction to an antibiotic. For subjects with multiple documented antibiotic allergies, 1 questionnaire was filled out for each antibiotic allergy. Investigators subsequently evaluated the questionnaire responses to determine whether the adverse reaction was a true immune-mediated allergic reaction or an adverse drug reaction. A total of 98 subjects were recruited with completion of 159 questionnaires. Eighteen subjects (18.37%, 95% CI: 10.7%, 26.3%) had antibiotic allergy labels with no corresponding immune-mediated reaction history. There were 35 allergy labels (22.0%, 95% CI: 14.7%, 29.4%) that were unlikely to be immune-mediated. Antibiotics with the highest percentage of clinical histories that were unlikely to be immune-mediated were macrolides (8 of 11 subjects), nitrofurantoin (1 of 2 subjects), and amoxicillin/clavulanate (2 of 8 subjects). The most common antibiotic allergy labels were penicillin (43 of 159 subjects), sulfonamides (25 of 159 subjects), and fluoroquinolones (21 of 159 subjects). Identification of adverse reactions to antibiotics that are unlikely to be immune-mediated can be accomplished using a standardized questionnaire in the outpatient setting. Improved identification of low-risk antibiotic allergy labels can guide de-labeling initiatives to improve antibiotic prescribing. [ABSTRACT FROM AUTHOR]

Purpose: To describe the incidence and management of delayed infections following frontalis sling suspension with polybutylate-coated polyester suture (Ethibond). Methods: Retrospective, interventional case series of 177 eyes of 150 patients, who underwent frontalis suspension surgery with Ethibond (Johnson and Johnson, USA), at L V Prasad Eye Institute, Hyderabad, India, between January 2016 and February 2022. Patients were assessed for chronic secondary sling infection, defined as infection/suture granuloma occurring beyond 6 weeks post-surgery. All patients received postoperative oral antibiotics. The clinical profile, microbiological evaluation, antibiotic sensitivity patterns, and management outcomes were analyzed. Results: Delayed infection following Ethibond sling suspension was noted in 14 eyes of 13 patients (7.9%). Of these, eight cases (61.5%) were females. The average time interval from surgery to presentation was 7.5 months (range: 2.5 months to 2.5 years). Eleven eyes underwent sling removal. Of the three who received initial antibiotic course, two eventually needed sling removal. Microbiological evaluation was available in seven eyes (50%), with Staphylococcus aureus as the most common organism. Of the six positive cultures, five (83.3%) were resistant to fluoroquinolones (FQs). Conclusion: Frontalis suspension with Ethibond has an 8% incidence of delayed infections, with Staphylococcus aureus as the most common organism. The authors recommend early sling removal in all patients with infection and recommend consideration of an alternative material in the event of future revision surgery. [ABSTRACT FROM AUTHOR]

Pantoea agglomerans is a gram-negative bacterium that usually lives in symbiosis in soil and plants. However, it may also lead to serious diseases in plants, animals and humans. We describe a case of aspiration from dysphagia associated with the isolation of P. agglomerans in a horse admitted to an Italian hospital. The patient was presented to the hospital for the onset of chronic cough after an acute episode of pulmonary hemorrhage during a race recorded two months before and was treated with dexamethasone and penicillin. The cough was accentuated during meals, leading to a suspicion of aspiration from dysphagia. A bronchoalveolar lavage was collected, and cytological examination showed the presence of vegetable fibers, rod bacteria, and a high macrophage population (89%). From the tracheal wash collected for bacteriological culture, P. agglomerans was isolated in monoculture, and the antimicrobial susceptibility test revealed that the isolate was susceptible to all tested antimicrobials except sulfonamide. The horse recovered well after 10 days of enrofloxacin treatment. The present report highlights the role of P. agglomerans as an opportunistic respiratory pathogen in horses, especially in the presence of plants or their parts. [ABSTRACT FROM AUTHOR]

Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes. [ABSTRACT FROM AUTHOR]

Antibiotics can affect the photosynthetic system of Microcystis, potentially altering the balance of carbon and nitrogen, which may influence the synthesis of different microcystin (MC) congeners. However, the regulatory mechanisms by which antibiotics affect the synthesis of various MC congeners in Microcystis remain unknown. In this study, the effects of ciprofloxacin (CIP) on the growth, carbon and nitrogen balance, amino acid composition, mcyB gene expression, and production of different MC congeners were investigated in two toxin-producing strains of Microcystis aeruginosa. The results show that CIP exposure significantly inhibited the growth of both strains, achieving an inhibition rate of 71.75% in FACHB-315 and 41.13% in FACHB-915 at 8 μg/L CIP by the end of the cultivation. The intracellular C:N ratio in FACHB-315 increased by 51.47%, while no significant change was observed in FACHB-915. The levels of leucine, tyrosine, and arginine, as identified and quantified by UPLC-MS/MS, were significantly altered at higher CIP concentrations, leading to a reduction in leucine percentage and a notable increase in tyrosine in both strains, which contributed to a reduction in MC-LR proportion and an increase in MC-RR and MC-YR proportion. Additionally, the expression of the mcyB gene was upregulated by as much as 5.57 times, indicating that antibiotic stress could enhance MC synthesis at the genetic level, contributing to the increased toxicity of cyanobacteria. These findings emphasize the significant role of CIP in the biochemical processes of M. aeruginosa, particularly in MC synthesis and composition, providing valuable insights into the ecological risks posed by antibiotics and harmful cyanobacteria. [ABSTRACT FROM AUTHOR]

Purpose: The evidence of the neuropsychiatric effects associated with fluoroquinolones is mainly supported by case reports. Population‐based evidence remains largely limited. We aimed to investigate the association between the use of fluoroquinolones and hospitalization or Accident & Emergency department visits for acute neuropsychiatric events using a self‐controlled case series (SCCS) and active comparator to reduce confounding. Methods: We conducted a SCCS with a recently described active comparator design using all public outpatient clinics, hospitalization, and Accident and Emergency department records from the Clinical Data Analysis and Reporting System, Hong Kong from 2001 to 2013. Among 166 325 people with an oral fluoroquinolone prescription, 4287 people who had an incident neuropsychiatric event were included. We then estimated the incidence rate ratio (IRR) of acute neuropsychiatric events during periods before and after fluoroquinolone prescription, versus baseline. We repeated the analysis for amoxicillin/clavulanic acid users as an active comparator. We then estimated the comparator‐adjusted estimates by dividing the IRR for fluoroquinolone by the IRR for amoxicillin/clavulanic acid. The primary outcome was neuropsychiatric events. Secondary outcomes were psychotic events and cognitive impairment. Results: An increased risk of neuropsychiatric events was observed in the current use of fluoroquinolone [IRR: 2.11 (95% confidence interval (CI): 1.58–2.83)] and 1–7 days after the end of fluoroquinolone prescription [IRR: 1.90 (95% CI: 1.30–2.75)] versus baseline. No increased risk was observed in other risk periods versus baseline. Similar patterns were observed in the current use of amoxicillin/clavulanic acid [IRR: 1.92 (95% CI: 1.19–3.11)] and 1–7 days after the end of fluoroquinolone prescription [IRR: 1.81 (95% CI: 1.11–2.97)] versus baseline. Similar results were found for secondary outcomes. Using the active comparator design, comparator‐adjusted estimates were 1.10 (95% CI: 0.63–1.93) in current use of fluoroquinolones and 1.05 (95% CI: 0.57–1.95) in 1–7 days postexposure to fluoroquinolones versus baseline. Conclusions: Although our study showed a higher incidence of neuropsychiatric events in the current use of fluoroquinolones and 7 days after the end of fluoroquinolones prescriptions compared with baseline, a similar temporal pattern was also found for amoxicillin/clavulanic acid users. Using amoxicillin/clavulanic acid as the active comparator, we found no difference in the risk of neuropsychiatric events associated with fluoroquinolone compared with baseline. Therefore, the risk of neuropsychiatric events may not need to influence the decision to prescribe either fluoroquinolones or amoxicillin/clavulanic acid based on the evidence in this study. [ABSTRACT FROM AUTHOR]

Purpose: To illustrate the interest in using interrupted time series (ITS) methods, this study evaluated the impact of the UK MHRA's March 2019 Risk Minimisation Measures (RMM) on fluoroquinolone usage. Methods: Monthly and quarterly fluoroquinolone use incidence rates from 2012 to 2022 were analysed across hospital care (Barts Health NHS Trust), primary care (Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD), and linked records from both settings (East Scotland). Rates were stratified by age (19–59 and ≥ 60 years old). Seasonality‐adjusted segmented regression and ARIMA models were employed to model quarterly and monthly rates, respectively. Results: Post‐RMM, with segmented regression, both age groups in Barts Health experienced nearly complete reductions (> 99%); CPRD Aurum saw 20.19% (19–59) and 19.29% (≥$$ \ge $$ 60) reductions; no significant changes in CPRD GOLD; East Scotland had 45.43% (19–59) and 41.47% (≥$$ \ge $$ 60) decreases. Slope analysis indicated increases for East Scotland (19–59) and both CPRD Aurum groups, but a decrease for CPRD GOLD's ≥$$ \ge $$ 60; ARIMA detected significant step changes in CPRD GOLD not identified by segmented regression and noted a significant slope increase in Barts Health's 19–59 group. Both models showed no post‐modelling autocorrelations across databases, yet Barts Health's residuals were non‐normally distributed with non‐constant variance. Conclusions: Both segmented regression and ARIMA confirmed the reduction of fluoroquinolones use after RMM across four different UK primary care and hospital databases. Model diagnostics showed good performance in eliminating residual autocorrelation for both methods. However, diagnostics for hospital databases with low incident use revealed the presence of heteroscedasticity and non‐normal white noise using both methods. [ABSTRACT FROM AUTHOR]

Herein, a novel UV spectrophotometric method coupled with chemometric tools was developed for the simultaneous determination of three fluoroquinolone antibiotics: ciprofloxacin, lomefloxacin, and enrofloxacin. Such integration of UV spectroscopy and chemometric analysis proved to be a simple, rapid, and cost-effective approach for the quantification of these clinically important pharmaceutical compounds and aid in their quality control analysis. The method employed firefly algorithm for variable selection and partial least squares (PLS) regression for model calibration. The developed method was validated by independent test set in addition the accuracy, intra and inter-day precision as per ICH guidelines which showed a satisfactory performance with mean recovery ranged between 98.18 and 101.83 with %RSD < 2. Besides, the developed method displayed ultrasensitive levels with LODs (0.0803, 0.1125, 0.1309 µg/mL) and LOQs (0.2434, 0.3409, 0.3968 µg/mL) for ciprofloxacin, lomefloxacin, and enrofloxacin, respectively. The greenness and blueness of the developed method were also evaluated using the recently proposed Analytical GREEnness metric approach (AGREE) and Blue applicability grade index (BAGI) tools, which showed a high AGREE score of 0.79 and a BAGI score of 77.5. These results indicate that the developed method provides an environmentally friendly alternative to the traditionally used chromatographic techniques, while maintaining high analytical practicability. Finally, the application of the developed methodology was demonstrated on real pharmaceutical and tap water samples, and the results were in good agreement with those obtained by the reference HPLC method indicating the reliability and suitability of the proposed spectrophotometric method for routine analysis of fluoroquinolone antibiotics. [ABSTRACT FROM AUTHOR]

The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma (β ), elimination of the drug from the colon (ϑ ), fifty percent sensitive bacteria (P. multocida) killing effect ( L s50 ), fifty percent of bacteria (E. coli) above ECOFF killing effect ( C r50 ), and net drug transfer rate in the lung (γ ) parameters. [ABSTRACT FROM AUTHOR]

There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics. The nuance of the decision to give or not give prophylaxis is discussed in the context of published evidence defining the risks and benefits of levofloxacin prophylaxis for pediatric leukemia patients at high risk for bacterial infection. Knowledge gaps are also identified to guide further investigations to optimize the use of fluoroquinolone prophylaxis in pediatric patients receiving chemotherapy for cancer or undergoing a hematopoietic cell transplantation. [ABSTRACT FROM AUTHOR]

In the present study, a total of 102 samples were collected from chickens of different flocks, died due to suspected colibacillosis. Bacteriological and PCR methods were applied to detect avian pathogenic Escherichia coli (APEC). Phenotypic antimicrobial resistance (AMR) was determined by disk diffusion method. Extended spectrum beta lactamases (ESBL) detection was carried out via PCR by targeting blaTEM, blaSHV, blaOXA, and blaCTX-M groups 1, 2, and 9. Genes of eight virulence factors and class I integrons were also detected by PCR using gene specific primers. Culture, microscopic, biochemical tests and PCR recognised 69/102 (67.64%) samples as E. coli. Phenotypic AST revealed higher resistance against fluoroquinolone antibiotics, i.e., enrofloxacin (72.46%), levofloxacin (69.56%) & ciprofloxacin (66.66%), followed by amoxyclav (63.77%) and tetracycline (59.42%). Six isolates were found as pan-drug-resistant E. coli. A total of 48 (69.56%) and 7 (10.14%) isolates were positive for the presence of blaTEM and blaCTX-M-G9 genes, respectively, whereas 2 (2.90%) isolates each were found positive for blaSHV, blaOXA, and blaCTX-M-G1 genes. Among APEC associated virulence genes, iss (79.71%) was the most predominant, followed by tsh (50.72%), ast (30.43%), cvaf (26.08%), pap (23.18%), vat (8.69%) and stx-1 (1.44%). Thirty-two isolates harboured class I integrons, either with or without ESBL genes. Conclusively, the isolates under study showed pan and multiple-drug resistance, specifically against fluoroquinolone drugs. ESBL production was mediated principally through blaTEM and blaCTX-M-G9. Multiple virulence factors, toxins, and carriage & spread factor render these as zoonotically potential pathogens for humans. [ABSTRACT FROM AUTHOR]

The majority of Klebsiella pneumonia isolates possess the extended-spectrum beta-lactamase (ESBL) enzymes. Therefore, K. pneumoniae can easily develop drug resistance. How to effectively overcome the problem of drug resistance in K. pneumoniae is still a research hotspot. This study aimed to compare the mutant prevention concentration (MPC) of ESBL-positive and ESBL-negative K. pneumoniae isolated from orthopedic patients, which may provide a basis for the effective use of drugs to control the enrichment of resistance mutants of K. pneumoniae. The MPC90 values of 55 isolates of ESBL-positive K. pneumoniae against 4 fluoroquinolones were 32 µg/mL for levofloxacin and gatifloxacin, 16 µg/mL for ciprofloxacin, and 4 µg/mL for gemifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin and 2 for gemifloxacin and gatifloxacin, respectively. For ESBL-negative K. pneumoniae isolates, the MPC90 values were 16 µg/mL for levofloxacin and ciprofloxacin, 4 µg/mL for gemifloxacin, and 32 µg/mL for gatifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin, 2 for gemifloxacin, and 4 for gatifloxacin. For the ESBL-positive K. pneumoniae, the %T>MIC90 order was gemifloxacin > levofloxacin > ciprofloxacin > gatifloxacin. For the ESBL-negative K. pneumoniae, the %T>MIC90 order was levofloxacin > gemifloxacin > ciprofloxacin > gatifloxacin. The mutant-preventing ability of gatifloxacin and gemifloxacin was the strongest among the 4 fluoroquinolones. So gemifloxacin may be the first choice of drug to treat K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Electron beam radiation is applied in wastewater treatment to destroy pollutants, including antibiotics. Standard solutions of oxytetracycline, enrofloxacin, erythromycin, and sulfamethoxazole (10–100 ppm) were irradiated at 10–50 kGy. Increasing irradiation dose and concentration increased and decreased degradation efficiency, respectively. Most antibiotic standard samples, irradiated at 25 kGy, showed destruction efficiency more than 90%. Erythromycin and enrofloxacin as target antibiotics, were identified in real pharmaceutical wastewater, with degradation efficiency of 100% and 90%, respectively, at 25 kGy. Byproducts found by LC/MS in irradiated samples had acceptable toxicity. Therefore, electron beam irradiation is an efficient way to eliminate antibiotics from pharmaceutical wastewater. [ABSTRACT FROM AUTHOR]

Objectives Antimicrobials can select for antimicrobial-resistant bacteria. After treatment the active compound is excreted through urine and faeces. As some antimicrobials are chemically stable, recirculation of subinhibitory concentrations of antimicrobials may occur due to coprophagic behaviour of animals such as chickens. Methods The persistence of three antimicrobials over time and their potential effects on antimicrobial resistance were determined in four groups of broilers. Groups were left untreated (control) or were treated with amoxicillin (unstable), doxycycline or enrofloxacin (stable). Antimicrobials were extracted from the faecal samples and were measured by LC-MS/MS. We determined the resistome genotypically using shotgun metagenomics and phenotypically by using Escherichia coli as indicator microorganism. Results Up to 37 days after treatment, doxycycline and enrofloxacin had concentrations in faeces equal to or higher than the minimal selective concentration (MSC), in contrast to the amoxicillin treatment. The amoxicillin treatment showed a significant difference (P  ≤ 0.01 and P  ≤ 0.0001) in the genotypic resistance only directly after treatment. On the other hand, the doxycycline treatment showed approximately 52% increase in phenotypic resistance and a significant difference (P  ≤ 0.05 and P  ≤ 0.0001) in genotypic resistance throughout the trial. Furthermore, enrofloxacin treatment resulted in a complete non-WT E. coli population but the quantity of resistance genes was similar to the control group, likely because resistance is mediated by point mutations. Conclusions Based on our findings, we suggest that persistence of antimicrobials should be taken into consideration in the assessment of priority classification of antimicrobials in livestock. [ABSTRACT FROM AUTHOR]

Ciprofloxacin (CFX) and ofloxacin (OFX) are commonly found as residual contaminants in aquatic environments, posing potential risks to various species. To ensure the safety of aquatic wildlife, it is essential to determine the toxicity of these antibiotics and establish appropriate concentration limits. Additionally, in (eco)toxicological studies, addressing the issue of multiple hypothesis testing through p-value adjustments is crucial for robust decision-making. In this study, we assessed the no observed adverse effect concentration (NOAEC) of CFX and OFX on Moina macrocopa across a concentration range of 0–400 µg L−1. Furthermore, we investigated multiple p-value adjustments to determine the NOAECs. Our analysis yielded consistent results across seven different p-value adjustments, indicating NOAECs of 100 µg CFX L−1 for age at first reproduction and 200 µg CFX L−1 for fertility. For OFX treatment, a NOAEC of 400 µg L−1 was observed for both biomarkers. However, further investigation is required to establish the NOAEC of OFX at higher concentrations with greater certainty. Our findings demonstrate that CFX exhibits higher toxicity compared to OFX, consistent with previous research. Moreover, this study highlights the differential performance of p-value adjustment methods in terms of maintaining statistical power while controlling the multiplicity problem, and their practical applicability. The study emphasizes the low NOAECs for these antibiotics in the zooplanktonic group, highlighting their significant risks to ecological and environmental safety. Additionally, our investigation of p-value adjustment approaches contributes to a deeper understanding of their performance characteristics, enabling (eco)toxicologists to select appropriate methods based on their specific needs and priorities. [ABSTRACT FROM AUTHOR]

To explore potential factors contributing to high fluoroquinolone resistance levels, it is essential to develop analytical methods capable of detecting residues and trace amounts of antibiotic use in broilers. The aim of the present study was to develop and in-house validate a sensitive UHPLC-MS/MS method capable of determining enrofloxacin (ENR) and flumequine (FLU) residues at slaughter age (day 45) when the animals were treated with these antimicrobials one day after hatching. Residue depletion of ENR and FLU in feathers was also assessed. Two experimental trials were performed, both consisting of 5 different treatment groups. In the first trial animals were treated with ENR and in the second one with FLU. The developed method was successfully validated and was found to be sensitive enough to detect residues of fluoroquinolones in the feathers up until slaughter age in all treatment groups. Average ENR concentration on day 45 was 10 ng g−1 feather after drinking water treatment, with all concentrations above the limit of quantification (LOQ) of 5 ng g−1 feather. For FLU average concentration on day 45 after drinking water administration was 4 ng g−1 feather, with an LOQ of 1 ng g−1 feather. Therefore, the method is suited for application to monitor fluoroquinolone use in broilers. [ABSTRACT FROM AUTHOR]

A sensor based on graphite nanosheets was fabricated through the electrochemical expansion of a graphite electrode in dimethyl sulfoxide for the sensitive electrochemical determination of enrofloxacin. The modified electrode surface exhibited a distinctive structure of nanoplates, characterized by layer thickness ranging from a few nanometers to ten nanometers. The developed electrode displayed notable electrochemical properties, including a faster charge transfer rate and a larger electrochemically active surface area, which was 1.3 times greater compared to the unmodified electrode. As a result, the sensor improved square wave voltammetric signals for enrofloxacin, exhibiting a 2.4-fold enhancement compared to the unmodified electrode. By optimizing the experimental parameters such as electrode fabrication conditions, pH of analytical solution, and adsorption time for enrofloxacin, the sensor demonstrated good reproducibility and a strong linear correlation over two ranges of enrofloxacin concentrations from 0.05–0.15 μM and 0.1–20 μM. The limit of detection was determined to be 0.002 μM. The sensor was successfully employed for the determination of enrofloxacin in spiked surface water samples before and after treating enrofloxacin by a photocatalytic method. The obtained results exhibited consistency with those obtained using a liquid chromatography-tandem mass spectrometry reference method, and a high recovery rate of 105.5% further confirmed the reliability of the proposed method for enrofloxacin detection. [ABSTRACT FROM AUTHOR]

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Oral bacterial infections are a great health concern worldwide especially in diabetic patients. Emergence of antimicrobial resistance with reference to biofilms in oral cavity is of great concern. We investigated antibiotics combination with proton pump inhibitors against oral clinical isolates. The strains were identified as Staphylococcus epidermidis and Staphylococcus aureus by the 16S rRNA gene sequencing. In molecular docking, ciprofloxacin, levofloxacin, and omeprazole best fit to active pockets of transcriptional regulators 4BXI and 3QP1. None of the proton pump inhibitors were active against S. epidermidis, whereas omeprazole showed significant inhibition (MIC 3.9 μg/ml). Fluoroquinolones were active against both S. epidermidis and S. aureus. In combination analysis, a marked decrease in minimum inhibitory concentration was noticed with omeprazole (MIC 0.12 μg/ml). In antiquorum sensing experiments, a significant inhibitory zone was shown for all fluoroquinolones (14–20 mm), whereas among proton pump inhibitors, only omeprazole (12 ± 0.12 mm) was active against Chromobacterium violaceum. In combination analysis, a moderate increase in antiquorum sensing activity was recorded for ciprofloxacin, ofloxacin, and proton pump inhibitors. Further, significant S. aureus biofilm eradication was recorded using of ciprofloxacin, levofloxacin, and omeprazole combination (78 ± 2.1%). The time-kill kinetic studies indicated a bactericidal effect by ciprofloxacin: levofloxacin: omeprazole combination over 24 hrs. It was concluded that fluoroquinolone combined with omeprazole could be an effective treatment option for eradicating oral bacterial biofilms. [ABSTRACT FROM AUTHOR]

Fluoroquinolone antibiotics are pseudo-persistence in aquatic environments as emerging contaminants. In this study, the Shitoukoumen Reservoir and its four inflow rivers were selected as a typical river-reservoir system. The factors, including river input, rainfall, flow regulation, population, antibiotic half-life, and antibiotic emission path were investigated to find out the reasons for antibiotic variations in the river-reservoir system during the reservoir discharge and filling periods. The results showed that ofloxacin was the most prevalent antibiotic in both the reservoir and inflow-river water, with median concentrations of 18.6 ± 2.4 and 39.7 ± 6.2 ng L−1, respectively. The concentrations of enrofloxacin, norfloxacin, and ofloxacin in the reservoir fluctuated during the reservoir discharge and filling periods. Enrofloxacin was only detected in the reservoir during the discharge period due to its input from the inflow rivers. Artificial reservoir discharge decreased the dissolved concentrations of norfloxacin and ofloxacin in the reservoir, whereas reservoir filling increased their accumulation. The Shuangyang, Yinma, and Chalu Rivers contributed relatively high individual antibiotic mass loads to the reservoir, ranging from 66.7% to 100%. Antibiotic-containing waste runoff during rainfall events increased input contributions of antibiotics from the Shuangyang and Chalu Rivers. The risk assessments indicated that norfloxacin posed a high risk to the most sensitive algae and therefore required greater attention. The study provides a comprehensive insight into fluoroquinolone antibiotic residues in the river-reservoir system during the periods of reservoir discharge and filling, and is of importance for their future monitoring and management. [ABSTRACT FROM AUTHOR]

Abstract A new group of thiazolidine-2,4-dione derivatives of ciprofloxacin having butyryl linker 3a-l was synthesized via an alkylation of thiazolidine-2,4-diones with butyryl ciprofloxacin with yield range 48–77% andfully characterized by various spectroscopic and analytical tools. Anti-cancer screening outcomes indicated that 3a and 3i possess antiproliferative activities against human melanoma LOX IMVI cancer cell line with IC50 values of 26.7 ± 1.50 and 25.4 ± 1.43 µM, respectively, using doxorubicin and cisplatin as positive controls with an IC50 of 7.03 ± 0.40 and 5.07 ± 0.29 µM, respectively. Additionally, compound 3j showed promising anticancer activity against human renal cancer A498 cell line with IC50 value of 33.9 ± 1.91 µM while doxorubicin and cisplatin showed IC50 values of 3.59 ± 0.20 and 7.92 ± 0.45, respectively. On the other hand, compound 3i did not show considerable anti-bacterial activity against S. aureus, E. coli and P. aeruginosa, and only moderate activity against K. pneumoniae with only a tenth of the activity of ciprofloxacin, confirming the cytotoxicity observed. Mechanistically, compound 3i inhibited both topoisomerase I and II with IC50 of 4.77 ± 0.26 and 15 ± 0.81 µM. Furthermore, it induced cell cycle arrest at S phase in melanoma LOX IMVI cells. Moreover, 3i provoked substantial levels of early, late apoptosis and necrosis in melanoma LOX IMVI cell line comparable to that induced by doxorubicin. Furthermore, compound 3i increased the expression level of active caspase-3 by 49 folds higher in LOX IMVI cell, increased protein expression level of Bax more than the control by 3 folds and inhibited PARP-1by 33% in LOX IMVI. All results were supported by theoretical docking studies on both tested enzymes confirming potential cytotoxicity for the synthesized hybrids.

For infectious and inflammatory eye lesions, the main methods of controlling pathogens include antibacterial agents of various classes and antiseptics. However, the use of these agents has a number of limitations: they are able to act primarily on the surface of the eye tissue, and in accordance with clinical recommendations, they should be used as an addition to antibacterial therapy.Antibacterial therapy remains the main recommendation for the treatment of bacterial eye infections, both in the anterior segment and in deeper lesions. In most countries, drugs from the group of fluoroquinolones and aminoglycosides are more often prescribed empirically, to which an acceptable level of sensitivity of microorganisms remains. Among aminoglycosides, the greatest sensitivity of eye infection pathogens is currently determined to netilmicin.The review examines the prospects and effectiveness of using netilmicin as monotherapy, as well as in combination with fluoroquinolones for topical treatment of bacterial infections in ophthalmology, and provides examples of the successful use of netilmicin.

Background Rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) is featured by challenges in the treatment, low cure rate, and high infectivity. Fluoroquinolones (FQs), as the core drugs for the treatment of RR/MDR-TB, have a severe trend of resistance. Analyzing influencing factors for FQs can help to increase the cure rate of RR/MDR-TB and to control the occurrence of the pre-extensive drug resistance (pre-XDR) and extensive drug resistance. Objective To analyze the drug resistance of FQs in hospitalized patients with pulmonary tuberculosis and the influencing factors, and to construct and validate a Nomogram prediction model for the risk factors of drug resistance of FQs. Methods A total of 583 patients with pulmonary tuberculosis who were hospitalized in Guiyang Public Health Clinical Center from January 2021 to February 2022 and tested for drug sensitivity were retrospectively selected as study subjects. They were divided into the initial treatment group (296 patients) and the retreatment group (287 patients) according to the history of previous treatment. Moreover, they were divided into the FQs-resistant group (63 patients) and FQs-sensitive group (520 patients) according to their FQs-resistance status. The distribution of total resistance to 13 antituberculosis drugs in 583 patients was analyzed, and the baseline characteristics of patients in the FQs-resistant group and FQs-sensitive group were compared. After screening the characteristic variables using least absolute shrinkage and selection operator (LASSO) regression model, multivariate Logistic regression was performed to analyze the independent risk factors for the resistance of FQs. A Nomogram prediction model was constructed, and its performance was validated by calculating the area under the curve (AUC) of receiver operating characteristic (ROC), and plotting the calibration curve. Results Among 583 patients, 520 cases were sensitive to FQs and 63 cases were resistant (resistance rate of 10.81%). The resistance rate of FQs was secondary to the total resistance rate of first-line antituberculosis drugs, including the isoniazid (36.36%), rifampicin (32.76%), streptomycin (21.61%), and ethambutol (12.86%). The resistance rates of rifampicin, isoniazid, ethambutol, streptomycin, levofloxacin, moxifloxacin and rifampicin resistance (RR), multidrug resistance (MDR), and pre-XDR were significantly higher in patients of the retreatment group than those of the initial treatment group (P

INTRODUCTION. Fluoroquinolones are antibacterial agents associated with adverse drug reactions (ARDs), including aortic lesions; this ARD risk limits the use of fluoroquinolones. Moreover, fluoroquinolones have been reported to induce lesions in other connective tissues (cartilage, tendons), associated with magnesium deficiency.AIM. The study aimed to analyse the effects of magnesium orotate on the thoracic aorta in laboratory rabbits treated with levofloxacin.MATERIALS AND METHODS. The study randomised laboratory rabbits into 3 groups of 10 animals each to receive oral doses of either the carrier solution (control group), or 150 mg/kg/day levofloxacin (levofloxacin group), or 150 mg/ kg/day levofloxacin and 140 mg/kg/day magnesium orotate (levofloxacin/magnesium group). After 14 days of treatment, venous blood samples were taken to determine the serum levels of magnesium, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), as well as MMP-9 to TIMP-1 ratios. The authors conducted morphological and mechanical characterisation of thoracic aorta samples; the mechanical characterisation involved uniaxial tensile testing. Data are presented as the mean and standard deviation values.RESULTS. The study did not detect any changes in the serum MMP-9, TIMP-1, and magnesium levels or in the MMP-9/TIMP-1 ratios. The authors identified foci of moderate elastic fibre fragmentation in the aortic media in 5 of 10 aortic samples from the levofloxacin group, in 1 of 10 samples from the levofloxacin/magnesium group, and in none from the control group (p=0.013). Rabbits from the levofloxacin group had significantly fewer medial elastic membranes than the others (p=0.015; vs the control group: p=0.022), and their elastic mem

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

The comparison of the efficiency of the removal process of two antibiotics, Ciprofloxacin and Moxifloxacin, from aqueous solutions, between an adsorption–photolysis and adsorption–photocatalysis processes, was studied. In the adsorption–photolysis process were used the inorganic supports activated carbon, silica and alumina, while in the adsorption–photocatalysis the titanium dioxide photocatalyst was used as adsorbent. The adsorption process of Ciprofloxacin and Moxifloxacin was carried out in a rotary shaker at 200 rpm, at a temperature of 30°, at a pH of 5.5 for a period of time of 3 h, using an initial concentration of both pharmaceutical compounds of 75 mg L−1. The degradation of antibiotics adsorbed on inorganic supports was carried out by direct photolisys with UV-C radiation of 180 mW cm−2, while to the photocatalitic process were irradiate with UV-A radiation with an irradiance of 0.45 mW cm−2. Results demonstrate that activated carbon and silica were the systems with the higher adsorption capacity, while the alumina and titanium dioxide obtained the lower adsorption values. The degradation of the adsorbed pharmaceutical compounds on inorganics supports by photolysis reached values higher than 88%, while in the case of the adsorbed–photocatalysis process the degradation values were higher than 91%. The most efficient systems for the removal of Ciprofloxacin or Moxifloxacin from water sources in the experimental conditions was the adsorption–photolysis process that used active carbon as support inorganic with a remotion factor value of 0.99. In the case of the adsorption–photocatalysis process, the remotion factor calculated was close to 0.52. [ABSTRACT FROM AUTHOR]

Introduction. Fluoroquinolones remain the key second-line anti-tuberculosis drugs. The aim of the study was the molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis strains from newly diagnosed tuberculosis patients in the Northwest of the Russian Federation. Materials and methods. The retrospective study collection included M. tuberculosis isolates isolated in 2015–2019 from previously untreated tuberculosis patients. Susceptibility to antituberculosis drugs (including the fluoroquinolone ofloxacin) was determined using the BACTEC MGIT960 or absolute concentration method. Mutations in the gyrA gene as a marker of resistance to fluoroquinolones, were detected by real-time PCR. Beijing genotype and its subtypes were detected by PCR and real-time PCR methods. Non-Beijing strains were spoligotyped. Results and discussion. Phenotypic resistance to ofloxacin was detected in 6.7% (40/599) of strains and in 17.4% (40/230) of MDR strains. 34 of 40 (85%) ofloxacin-resistant strains belonged to the Beijing genotype. 18 (45%) strains were assigned to the Russian epidemic subtype Beijing B0/W148 and 12 (30%) to Beijing Central Asian/Russian. The remaining 6 ofloxacin-resistant strains belonged to the Euro-American phylogenetic lineage. Mutations in the gyrA gene were found in 97.5% (39/40) of strains. The most common were mutations in codon 94 (69.2%, 27/39). The Asp94Gly substitution was identified in 57.5% (23/40) of ofloxacin-resistant strains and was dominant among Beijing (19/34) and non-Beijing (4/6) strains. The second most common substitution was Ala90Val (25%, 10/40). More than half of the ofloxacin-resistant strains, Beijing B0/W148 (10/18) and Central Asian/Russian (7/12), carried the Asp94Gly mutation. Conclusion. In the Northwest of Russia in 2016-2019, primary resistance of M. tuberculosis to fluoroquinolones was 6.7% in the total collection and 17.4% of MDR strains, and was mainly caused by the gyrA Asp94Gly and Ala90Val mutations. Beijing B0/W148 genotype was characterized by the largest proportion of fluoroquinolone-resistant strains.

Abstract Background The study aims to investigate the effect of combining silver nanoparticles (AGNPs) with different antibiotics on multi-drug resistant (MDR) and extensively drug resistant (XDR) isolates of Pseudomonas aeruginosa (P. aeruginosa) and to investigate the mechanism of action of AGNPs. Methods AGNPs were prepared by reduction of silver nitrate using trisodium citrate and were characterized by transmission electron microscope (TEM) in addition to an assessment of cytotoxicity. Clinical isolates of P. aeruginosa were collected, and antimicrobial susceptibility was conducted. Multiple Antibiotic Resistance (MAR) index was calculated, and bacteria were categorized as MDR or XDR. Minimum inhibitory concentration (MIC) of gentamicin, ciprofloxacin, ceftazidime, and AGNPs were determined. The mechanism of action of AGNPs was researched by evaluating their effect on biofilm formation, swarming motility, protease, gelatinase, and pyocyanin production. Real-time PCR was performed to investigate the effect on the expression of genes encoding various virulence factors. Results TEM revealed the spherical shape of AGNPs with an average particle size of 10.84 ± 4.64 nm. AGNPS were safe, as indicated by IC50 (42.5 µg /ml). The greatest incidence of resistance was shown against ciprofloxacin which accounted for 43% of the bacterial isolates. Heterogonous resistance patterns were shown in 63 isolates out of the tested 107. The MAR indices ranged from 0.077 to 0.84. Out of 63 P. aeruginosa isolates, 12 and 13 were MDR and XDR, respectively. The MIC values of AGNPs ranged from 2.65 to 21.25 µg /ml. Combination of AGNPs with antibiotics reduced their MIC by 5–9, 2–9, and 3-10Fold in the case of gentamicin, ceftazidime, and ciprofloxacin, respectively, with synergism being evident. AGNPs produced significant inhibition of biofilm formation and decreased swarming motility, protease, gelatinase and pyocyanin production. PCR confirmed the finding, as shown by decreased expression of genes encoding various virulence factors. Conclusion AGNPs augment gentamicin, ceftazidime, and ciprofloxacin against MDR and XDR Pseudomonas isolates. The efficacy of AGNPs can be attributed to their effect on the virulence factors of P. aeruginosa. The combination of AGNPs with antibiotics is a promising strategy to attack resistant isolates of P. aeruginosa.

Abstract Background The emergence of fluoroquinolone resistance in clinical isolates of Klebsiella pneumoniae is a growing concern. To investigate the mechanisms behind this resistance, we studied a total of 215 K. pneumoniae isolates from hospitals in Bushehr province, Iran, collected between 2017 and 2019. Antimicrobial susceptibility test for fluoroquinolones was determined. The presence of plasmid mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining region (QRDR) of gyrA and parC genes in ciprofloxacin-resistant K. pneumoniae isolates were identified by PCR and sequencing. Results Out of 215 K. pneumoniae isolates, 40 were resistant to ciprofloxacin as determined by E-test method. PCR analysis revealed that among these ciprofloxacin-resistant isolates, 13 (32.5%), 7 (17.5%), 40 (100%), and 25 (62.5%) isolates harbored qnrB, qnrS, oqxA and aac(6’)-Ib-cr genes, respectively. Mutation analysis of gyrA and parC genes showed that 35 (87.5%) and 34 (85%) of the ciprofloxacin-resistant isolates had mutations in these genes, respectively. The most frequent mutations were observed in codon 83 of gyrA and codon 80 of parC gene. Single gyrA substitution, Ser83→ Ile and Asp87→Gly, and double substitutions, Ser83→Phe plus Asp87→Ala, Ser83→Tyr plus Asp87→Ala, Ser83→Ile plus Asp87→Tyr, Ser83→Phe plus Asp87→Asn and Ser83→Ile plus Asp87→Gly were detected. In addition, Ser80→Ile and Glu84→Lys single substitution were found in parC gene. Conclusions Our results indicated that 90% of isolates have at least one mutation in QRDR of gyrA orparC genes, thus the frequency of mutations was very significant and alarming in our region.