Based on molecular docking and real-time PCR technology, the two-component system Bae SR was investigated on the mechanism of drug resistance in CRAB.

This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain reaction (PCR). The two-component system Bae SR of Acinetobacter baumannii was subjected to molecular docking with imipenem, meropenem, and levofloxacin. Antibacterial assays and fluorescence quantitative PCR were used to explore protein-ligand interactions and molecular biological resistance mechanisms related to CRAB. The analysis of the two-component system in A. baumannii revealed that imipenem exhibited the highest docking energy in Bae S at - 5.81 kcal/mol, while the docking energy for meropenem was - 4.92 kcal/mol. For Bae R, imipenem had a maximum docking energy of - 4.28 kcal/mol, compared with - 4.60 kcal/mol for meropenem. The highest binding energies for Bae S-levofloxacin and Bae R-levofloxacin were - 3.60 and - 3.65 kcal/mol, respectively. All imipenem-resistant strains had minimum inhibitory concentration (MIC) values of 16 µg/mL, whereas levofloxacin-resistant strains had MIC values of 8 µg/mL. The time-sterilization curve showed a significant decrease in bacterial colony numbers at 2 h under the action of 8 µg/mL imipenem, indicating antibacterial effects. In contrast, levofloxacin did not exhibit any antibacterial activity. Fluorescence quantitative PCR results revealed significantly increased relative expression levels of bae S and bae R genes in the CRAB group, which were 2 and 1.5 times higher than those in the CSAB group, respectively, with statistically significant differences. Molecular docking in this study found that the combination of Bae SR and carbapenem antibiotics (imipenem, meropenem) exhibited stronger affinity and stability compared with levofloxacin. Moreover, the overexpression of the two-component system genes in carbapenem-resistant A. baumannii enhanced its resistance to carbapenem, providing theoretical and practical insights into carbapenem resistance in respiratory tract infections caused by A. baumannii.

Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.

OBJECTIVE: To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. METHODS: The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27. RESULTS: Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B. CONCLUSIONS: Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration. Clinical Trial Number: Iranian Registry of Clinical Trials: IRCT20221207056738N1.

Refractoriness to anti-Helicobacter pylori treatment attributed to phenotypic resistance patterns in patients with gastroduodenopathy in Guayaquil-Ecuador.

BACKGROUND: Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador. METHODS: A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied. RESULTS: All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin-amoxicillin was 43.4%, to tetracycline-metronidazole 30.3%, to amoxicillin-levofloxacin 27.6%, and to clarithromycin-metronidazole 59.2%. CONCLUSIONS: In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.

A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection.

BACKGROUND: Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin. METHODS: A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated. RESULTS: The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin. CONCLUSIONS: The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates.

Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity.

BACKGROUND: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. METHODS: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. RESULTS: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. CONCLUSION: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

Clinical Experience of Using a Combination of Dexamethasone and Levofloxacin After Cataract Surgery.

Background: Where routine prophylactic antibiotics have been adopted following cataract surgery, rates of endophthalmitis have been decreasing. Intracameral and topical antibiotics are currently used to prevent endophthalmitis after cataract surgery. When applying topical antibiotics, there are different recommendations on the frequency and duration of therapy. The development of bacterial resistance to the excessive and long-term use of antibiotics is a growing problem worldwide. The goal is to achieve a good antibiotic effect with the shortest possible use of antibiotics. Objective: The aim of this study was to compare the effectiveness of a new combination therapy of dexamethasone and levofloxacin for seven days after cataract surgery with the previous regimen of dexamethasone, neomycin sulfate, and polymyxin B, which was given for 21 days. Methods: A retrospective analysis of medical records and administered a questionnaire was conducted to assess the effectiveness of postoperative therapy in our cataract surgery patients. The study involved 52 patients who underwent surgery within the last year, performed by a single surgeon at our institution. The findings can help us improve the quality of care we provide and optimize our patients' overall quality of life. Results: We conducted an in-depth study on 52 individuals who underwent cataract surgery at our institution. The prescribed therapeutic regimen for the participants included administering Ducressa solution four times daily for the first seven days and Maxidex solution three times daily for the subsequent 14 days. The study found that none of the participants experienced complications after surgery, and all found it easy to instill the medication. The prescribed regimen effectively managed the postoperative recovery of the participants, and the medication was well-tolerated. Conclusion: Our research found that a new combination of levofloxacin and dexamethasone, when used topically, may require a shorter treatment period, reducing the risk of antibiotic resistance and providing a safe alternative for endophthalmitis prevention.

Insight into the catalytic performances of Fe0@chitosan/cellulose green hybrid structure for enhanced photo-Fenton's oxidation of levofloxacin toxic residuals: Pathway and toxicity.

A green hybridized structure of Fe0 painted chitosan/cellulose base (Fe0@CS/CF) has been developed using cellulose extracted from sugarcane bagasse along with reduction agents sourced from Khaya senegalensis leaves. The composite was assessed as an affordable, powerful, and multifunctional catalyst for enhancing the degradation of Levofloxacin (LVX) remnants within water supplies via photo-Fenton's interactions. Using a dosage of 0.5 g/L, the Fe0@CS/CF blend demonstrated noteworthy catalytic qualities, resulting in the complete photo-Fenton's degradation of LVX at a level of 25 mg/L after 40 min. However, the complete diminution of organic carbon (TOC) occurred only after 100 min, suggesting the presence of significant intermediate residues. The identified intermediate chemicals and confirmed hydroxyl radicals as the main oxidizer suggest that the degradation pathway involves carboxylation/decarboxylation, hydroxylation, demethylation, and oxidation of quinolone rings. The toxicity properties of untreated LVX solutions and their subsequent oxidized byproducts were assessed by evaluating their inhibiting impact on Vibrio fischeri over various durations. The samples that experienced partial oxidation at initial testing demonstrated a higher level of toxicity in comparison to the parent LVX. However, the sample that was treated for 100 min demonstrated substantial biological safety and a non-toxic nature. The blend of ingredients has a synergistic impact that enhances the uptake, Fenton's, photocatalytic, and photo-Fenton's characteristics of the hosted Fe0 nanoparticles.

High antibiotic resistance rates in Helicobacter pylori strains in Turkey over 20 years: implications for gastric disease treatment.

OBJECTIVE: Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics. BASIC METHODS: Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates. MAIN RESULTS: In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021. PRINCIPAL CONCLUSION: Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.

Spider chart, greenness and whiteness assessment of experimentally designed multivariate models for simultaneous determination of three drugs used as a combinatory antibiotic regimen in critical care units: Comparative study.

In this study, five earth-friendly spectrophotometric methods using multivariate techniques were developed to analyze levofloxacin, linezolid, and meropenem, which are utilized in critical care units as combination therapies. These techniques were used to determine the mentioned medications in laboratory-prepared mixtures, pharmaceutical products and spiked human plasma that had not been separated before handling. These methods were named classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), genetic algorithm partial least squares (GA-PLS), and artificial neural network (ANN). The methods used a five-level, three-factor experimental design to make different concentrations of the antibiotics mentioned (based on how much of them are found in the plasma of critical care patients and their linearity ranges). The approaches used for levofloxacin, linezolid, and meropenem were in the ranges of 3-15, 8-20, and 5-25 µg/mL, respectively. Several analytical tools were used to test the proposed methods' performance. These included the root mean square error of prediction, the root mean square error of cross-validation, percentage recoveries, standard deviations, and correlation coefficients. The outcome was highly satisfactory. The study found that the root mean square errors of prediction for levofloxacin were 0.090, 0.079, 0.065, 0.027, and 0.001 for the CLS, PCR, PLS, GA-PLS, and ANN models, respectively. The corresponding values for linezolid were 0.127, 0.122, 0.108, 0.05, and 0.114, respectively. For meropenem, the values were 0.230, 0.222, 0.179, 0.097, and 0.099 for the same models, respectively. These results indicate that the developed models were highly accurate and precise. This study compared the efficiency of artificial neural networks and classical chemometric models in enhancing spectral data selectivity for quickly identifying three antimicrobials. The results from these five models were subjected to statistical analysis and compared with each other and with the previously published ones. Finally, the whiteness of the methods was assessed by the recently published white analytical chemistry (WAC) RGB 12, and the greenness of the proposed methods was assessed using AGREE, GAPI, NEMI, Raynie and Driver, and eco-scale, which showed that the suggested approaches had the least negative environmental impact. Furthermore, to demonstrate solvent sustainability, a greenness index using a spider chart methodology was employed.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Insights into levofloxacin adsorption with machine learning models using nano-composite hydrochars.

Hydrothermal carbonization was applied to taro peel wastes to produce hydrochars using a facile and environmentally friendly process. Four different entities were prepared: hydrochar (TPh), phosphoric-activated hydrochar (P-TPh), and silver@hydrochars (Ag@TPh, Ag@P-TPh). The elemental compositions of the single and composite hydrochars were confirmed by EDX. Among the produced hydrochars, the morphology of the Ag@hydrochar composites demonstrated more wrinkled structure, and Ag nanoparticles decorated the surface. The optimal experimental conditions for levofloxacin adsorption were determined to be a contact time of 45 min, hydrochar dose of 0.15 g L-1, and pH of 7. The best adsorption performances were assigned to Ag@hydrochars. Two machine learning models were applied to predict the levofloxacin adsorption efficiency of the Ag@hydrochars. A central composite design (CCD) and a 3-10-1 artificial neural network (ANN) model were developed to estimate the removal performance of levofloxacin using Levenberg-Marquardt backpropagation algorithm based on correlation and error analysis of the adopted training functions. Furthermore, the ANN sensitivity analysis revealed the order of the relative importance variable as initial concentration> hydrochar dose> pH. The predicted values of the CCD and ANN models fitted the experimental results with R2> 0.989. Therefore, the applied models were effective in predicting levofloxacin removal under different operating conditions. This work provides an open option for the sustainable management of food industry wastes and the possibility of waste valorization to effective hydrochar composites to be applied in water treatment processes.

Mechanistic study of the electrochemical oxidation of fluoroquinolones: Ciprofloxacin, danofloxacin, enoxacin, levofloxacin and lomefloxacin.

The fluoroquinolones ciprofloxacin, danofloxacin, enoxacin, levofloxacin and lomefloxacin, occur in water bodies worldwide and therefore pose a threat to the aquatic environment. Advanced purification procedures, such as electrochemical oxidation, may act as a remedy since they contribute to eliminating contaminants and prevent micropollutants from entering open water bodies. By electrochemical treatment in a micro-flow reactor equipped with a boron-doped diamond (BDD) electrode, the fluoroquinolones were efficiently degraded. A total of 15 new products were identified using high-performance high-resolution chromatography coupled with high-resolution multifragmentation mass spectrometry. The ecotoxicity of the emerging transformation products was estimated through in silico quantitative structure activity relationship analysis. Almost all transformation products were predicted less ecotoxic than the initial compounds. The fluoroquinolone degradation followed three major mechanisms depending on the voltage during the electrochemical oxidation. At approximately 1 V, the reactions started with the elimination of molecular hydrogen from the piperazine moiety. At approx. 1.25 V, methyl and methylene groups were eliminated. At 1.5 V, hydroxyl radicals, generated at the BDD electrode, led to substitution at the piperazine ring. This novel finding of the three reactions depending on voltage contributes to the mechanistic understanding of electrochemical oxidation as potential remedy against fluoroquinolones in the aquatic environment.

Effects of Nanobubbles on Photochemical Processes of Levofloxacin Photosensitizer.

Photodynamic therapy (PDT) stands as an efficacious modality for the treatment of cancer and various diseases, in which optimization of the electron transfer and augmentation of the production of lethal reactive oxygen species (ROS) represent pivotal challenges to enhance its therapeutic efficacy. Empirical investigations have established that the spontaneous initiation of redox reactions associated with electron transfer is feasible and is located in the gas-liquid interfaces. Meanwhile, nanobubbles (NBs) are emerging as entities capable of furnishing a plethora of such interfaces, attributed to their stability and large surface/volume ratio in bulk water. Thus, NBs provide a chance to expedite the electron-transfer kinetics within the context of PDT in an ambient environment. In this paper, we present a pioneering exploration into the impact of nitrogen nanobubbles (N2-NBs) on the electron transfer of the photosensitizer levofloxacin (LEV). Transient absorption spectra and time-resolved decay spectra, as determined through laser flash photolysis, unequivocally reveal that N2-NBs exhibit a mitigating effect on the decay of the LEV excitation triplet state, thereby facilitating subsequent processes. Of paramount significance is the observation that the presence of N2-NBs markedly accelerates the electron transfer of LEV, albeit with a marginal inhibitory influence on its energy-transfer reaction. This observation is corroborated through absorbance measurements and offers compelling evidence substantiating the role of NBs in expediting electron transfer within the ambit of PDT. The mechanism elucidated herein sheds light on how N2-NBs intricately influence both electron-transfer and energy-transfer reactions in the photosensitizer LEV. These findings not only contribute to a nuanced understanding of the underlying processes but also furnish novel insights that may inform the application of NBs in the realm of photodynamic therapy.

How Should We Activate Ferrate(VI)? Fe(IV) and Fe(V) Tell Different Stories about Fluoroquinolone Transformation and Toxicity Changes.

Many studies have investigated activation of ferrate (Fe(VI)) to produce reactive high-valent iron intermediates to enhance the oxidation of micropollutants. However, the differences in the risk of pollutant transformation caused by Fe(IV) and Fe(V) have not been taken seriously. In this study, Fe(VI)-alone, Fe3+/Fe(VI), and NaHCO3/Fe(VI) processes were used to oxidize fluoroquinolone antibiotics to explore the different effects of Fe(IV) and Fe(V) on product accumulation and toxicity changes. The contribution of Fe(IV) to levofloxacin degradation was 99.9% in the Fe3+/Fe(VI) process, and that of Fe(V) was 89.4% in the NaHCO3/Fe(VI) process. The cytotoxicity equivalents of levofloxacin decreased by 1.9 mg phenol/L in the Fe(IV)-dominant process while they significantly (p < 0.05) increased by 4.7 mg phenol/L in the Fe(V)-dominant process. The acute toxicity toward luminescent bacteria and the results for other fluoroquinolone antibiotics also showed that Fe(IV) reduced the toxicity and Fe(V) increased the toxicity. Density functional theory calculations showed that Fe(V) induced quinolone ring opening, which would increase the toxicity. Fe(IV) tended to oxidize the piperazine group, which reduced the toxicity. These results show the different-pollutant transformation caused by Fe(IV) and Fe(V). In future, the different risk outcomes during Fe(VI) activation should be taken seriously.

First reported human case of isolation of Vagococcus fluvialis from the urine of a former zoo clerk in Japan: a case report.

BACKGROUND: Vagococcal infections are extremely rare in humans. There are limited studies on the optimal methods for identification, antimicrobial susceptibility testing, and clinical manifestations of vagococcal infections. Herein, we report a patient with a urinary tract infection who had Vagococcus fluvialis in the urine. CASE PRESENTATION: An 84-year-old man presented to our urology department with a fever that had persisted for several days. He previously worked as a zoo clerk. The patient underwent a left nephroureterectomy for ureteral cancer 5 years ago, and total cystectomy and right cutaneous ureterostomy for muscle-invasive bladder cancer 1 year prior. He was empirically treated with 500 mg of levofloxacin intravenously every 24 h for the urinary tract infection. V. fluvialis was detected in his urine samples and Pseudomonas aeruginosa was detected in his urine and blood samples. Two bacterial species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. He was administered intravenous levofloxacin for approximately 1 week, followed by oral levofloxacin for another week, after which the infections were eradicated. CONCLUSIONS: To the best of our knowledge, this is the first report of V. fluvialis detected in human urine in Japan. Vagococcus spp. is commonly isolated from fish or animals, and based on the patient's work history, it is possible that the patient was a carrier because of transmission from animals.

[Contamination Characteristics and Ecological Risk Assessment of Pharmaceuticals and Personal Care Products in Drains Flowing into the Yellow River of Ningxia].

Pharmaceuticals and personal care products (PPCPs) are a group of emerging contaminants causing detrimental effects on aquatic living organisms even at low doses. To investigate the contamination characteristics and ecological risks of PPCPs in drains flowing into the Yellow River of Ningxia, 21 PPCPs were detected and analyzed using solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry in this study. All 21 targeted compounds were detected in the drains, with total concentrations ranging from 47.52 to 1 700.96 ng·L-1. Ciprofloxacin, acetaminophen, benzophenone-3, and diethyltoluamide were the more commonly detected compounds, with detection frequencies exceeding 80%. The five highest-concentration PPCPs were acetaminophen, diethyltoluamide, caffeine, benzophenone-3, and levofloxacin, with the maximum concentrations of 597.21, 563.23, 559.00, 477.28, and 473.07 ng·L-1, respectively. Spatial analysis showed that the pollution levels of PPCPs in the drains of the four cities were different, with average concentrations of ∑PPCPs in the order of Yinchuan>Shizuishan>Wuzhong>Zhongwei. The total concentration of PPCPs before flowing into the Yellow River ranged from 124.82 to 1 046.61 ng·L-1. Source analysis showed that livestock and poultry breeding wastewater was the primary source for sulfadiazine and oxytetracycline, whereas medical wastewater was the primary source for levofloxacin and ciprofloxacin. The primary sources of triclocarban and triclosan were domestic sewage and industrial wastewater, whereas the primary source of caffeine and diethyltoluamide was domestic sewage. The pollution of diciofenac, cimetidine, triclocarban, and triclosan in the drains was positively correlated with the regional population and economic development level. The ecological risk assessment indicated that levofloxacin, diclofenac, gemfibrozil, benzophenone-3, and triclocarban posed high risks to aquatic organisms in drains flowing into the Yellow River. It is worthwhile to consider the mixture risk of the PPCPs that exhibited high risk at most sampling sites.

Zinc oxide resveratrol nanoparticles ameliorate testicular dysfunction due to levofloxacin-induced oxidative stress in rats.

The present work is aimed to assess the protective influence of zinc oxide resveratrol nanoparticles against oxidative stress-associated testicular dysfunction. The number of 50 male albino rats were randomly separated into five groups (n = 10): Group I, control: rats gavage distilled water orally; Group II, Levofloxacin: rats that administered Levofloxacin (LFX) softened in distilled water at a dosage of 40 mg/kg-1 BW orally every other day; Group III, Zn-RSV: rats administered with Zn-RSV (zinc oxide resveratrol in distilled water at a dose 20 mg/kg-1 BW orally every other day; Group IV, (LFX + Zn-RSV): rats that were administered with Levofloxacin along with Zn-RSV nPs; Group V, Levofloxacin + Zn: rats were administered with Levofloxacin and Zno at a dose of 20 mg/kg-1 BW orally every other day as mentioned before. This study lasted for 2 months. Sera were collected to assess luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone values. Testicular tissues were utilized to evaluate levels of superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA), and catalase (CAT). Semen samples were utilized to measure their quality (motility, concentration, and vitality). Histopathological and immune histochemical techniques investigated the morphological changes in the testis. Rats treated with Levofloxacin showed significantly lower levels of serum LH, testosterone, FSH, testicular enzymatic NO, catalase, SOD, BAX, and BCL-2 immune reactivity and sperm quality but significantly greater testicular malondialdehyde and caspase-3 immuno-reactivity Compared to both control and zinc oxide resveratrol treatment. Zinc oxide resveratrol nanoparticles ameliorated the harmful side effects of Levofloxacin. Improvements were more pronounced in the co-treatment (LFX + Zn-RSV) Zinc oxide resveratrol group than in the co-treatment (LFX + Zno) Zinc oxide group. Zinc oxide resveratrol nanoparticles could be a possible solution for levofloxacin oxidative stress-induced fertility problems.

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates.

BACKGROUND: Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. AIM: To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. METHODS: We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. RESULTS: A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. CONCLUSION: H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection.

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.