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Scientific Reports Feb 2024Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori...
Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.
Topics: Humans; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Retrospective Studies; Gastritis, Atrophic; Amoxicillin; Clarithromycin; Stomach Diseases; Levofloxacin; Proton Pump Inhibitors; Furazolidone; Drug Resistance, Bacterial; Metronidazole
PubMed: 38418852
DOI: 10.1038/s41598-024-55589-2 -
SAGE Open Medicine 2023infection is very common worldwide, and about 10%-16% of these patients develop peptic ulcer disease. However, there is limited research on the impact of eradication...
BACKGROUND
infection is very common worldwide, and about 10%-16% of these patients develop peptic ulcer disease. However, there is limited research on the impact of eradication and peptic ulcer disease treatment sequencing.
METHODS
We conducted a retrospective study of adult patients diagnosed with infection and peptic ulcer disease between October 2020 and April 2021 at our center. Data on primary treatment outcomes, including eradication and peptic ulcer disease healing, were collected, and factors that may influence treatment outcomes were analyzed.
RESULTS
A total of 306 patients were included in this study. The sequence of eradication and peptic ulcer disease treatment did not significantly affect the outcomes of eradication and peptic ulcer disease healing. In addition, patient age, peptic ulcer disease type, clinic type and treatment regimen (including choice of proton pump inhibitor) had no significant impact on eradication. However, patient gender and the choice of antibiotic combination proved to be key factors, as eradication rates were lower in female patients compared to males, and the combination of levofloxacin and clarithromycin was the least effective in eradicating . Regarding peptic ulcer disease healing, the peptic ulcer disease type was an important influencing factor, since gastric ulcers being more likely to get cured completely compared to duodenal ulcers.
CONCLUSIONS
The sequence of eradication and peptic ulcer disease treatment does not significantly affect the primary outcomes. Patient gender and the choice of antibiotic combination are important factors in eradication, whereas peptic ulcer disease type plays a key role in ulcer healing.
PubMed: 38144880
DOI: 10.1177/20503121231220809 -
RSC Advances Jul 2023The investigation of the micellization of a mixture of cetylpyridinium bromide (CPB) and levofloxacin hemihydrate (LFH) was carried out by a conductivity technique in...
The investigation of the micellization of a mixture of cetylpyridinium bromide (CPB) and levofloxacin hemihydrate (LFH) was carried out by a conductivity technique in aqueous and aq. additive mixtures, including NaCl, NaOAc, NaBenz, 4-ABA, and urea. The aggregation behavior of the CPB + LFH mixture was studied considering the variation in additive contents and the change in experimental temperature. The micelle formation of the CPB + LFH mixture was examined from the breakpoint observed in the specific conductivity surfactant concentration plots. Different micellar characteristics, such as the critical micelle concentration (CMC) and the extent of counter ion bound (), were evaluated for the CPB + LFH mixture. The CMC and were found to undergo a change with the types of solvents, composition of solvents, and working temperatures. The Δ values of the CPB + LFH system in aqueous and aq. additive solutions were found to be negative, which denotes a spontaneous aggregation phenomenon of the CPB + LFH system. The changes in Δ and Δ for the CPB + LFH mixture were also detected with the alteration in the solvent nature and solution temperature. The Δ and Δ values obtained for the association of the CPB + LFH mixture reveal that the characteristic interaction forces may possibly be ion-dipole, dipole-dipole, and hydrophobic between CPB and LFH. The thermodynamics of transfer and Δ-Δ compensation variables were also determined. All the parameters computed in the present investigation are illustrated with proper logic.
PubMed: 37441036
DOI: 10.1039/d3ra02621c -
Journal of Diabetes and Metabolic... Dec 2023The present study was designed to determine the effect of levofloxacin (LVX) treatment on the blood glucose level, insulin sensitivity, anxiety level, nitrite and MDA...
PURPOSE
The present study was designed to determine the effect of levofloxacin (LVX) treatment on the blood glucose level, insulin sensitivity, anxiety level, nitrite and MDA level of STZ induced diabetic rats.
METHODS
Wistar rats were used in the present study. The rats were made diabetic by the administration of single dose of STZ (45 mg/kg, i.p.) and NAD (50 mg/kg, i.p.). The rats with the blood glucose level greater than 200 mg/dl were considered as diabetic (confirmed at day-3 of STZ-NAD administration). The non-diabetic rats were considered as control and received saline.Diabetic rats received metformin (50 mg/kg, p.o.) and LVX (20, 25, 30 and 35 mg/kg, i.p.) daily for 14 days (starting from the day at which STZ was injected). Following administration on 14th day,the blood sample was collected and the rats were subjected to behavioral assays for the determination of locomotor activity and anxiety level. Plasma was separated and used for the estimation ofnitrite and malondialdehyde (MDA)level. On 15th day OGTT was performed in the overnight fasted rats for the assessment of insulin sensitivity.
RESULTS
The results obtained suggested that the administration of STZ-NAD induced the hyperglycemia at day-3 of administration. Diabetic rats displayed the significant increase in blood glucose, anxiety related behavior, MDA level while significant decrease in the insulin sensitivity and plasma nitrite level. Daily administration of metformin to the diabetic rats decreased the blood glucose level, increased the time spent at the center of open field, reversed the anxiety related behavior in LDT and EPM, did not affect the plasma nitrite level, decreased the plasma MDA level, decreased the fasting glucose level and AUC in OGTT assay. LVX (30 and 35 mg/kg) treatment significantly decreased the blood glucose level of diabetic rats. LVX (20, 25 and 30 mg/kg) treatment significantly decreased the number of square crossing while LVX (20, 25, 30 and 35) treatment significantly increased the time spent at the center of the field by the diabetic rats. LVX (20 and 35 mg/kg) treatment significantly reversed the STZ induced anxiety in LDT while LVX (20, 30 and 35 mg/kg) treatment significantly reversed the STZ induced anxiety in EPM test. LVX (20, 25 and 35 mg/kg) treatment significantly increased the plasma nitrite level and LVX (20-35 mg/kg) treatment significantly decreased the MDA level of diabetic rats. Further only LVX (35 mg/kg) treatment significantly decreased the fasting glucose level and increased the AUC of diabetic rats.
CONCLUSION
In conclusion, STZ-NAD administration increased the blood glucose level, anxiety related behavior, decreased the plasma nitrite and increased the MDA level. LVX administration potentiated the diabetogenic effects of STZ-NAD in rats. Daily administration of LVX decreased the blood glucose level of diabetic rats. LVX administration alleviated the STZ induced anxiety in OFT, LDT and EPM test. LVX administration increased the plasma nitrite level and decreased the lipid peroxidation in diabetic rats.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01234-0.
PubMed: 37975146
DOI: 10.1007/s40200-023-01234-0 -
Infection and Drug Resistance 2023, a multidrug-resistant pathogen can cause hospital-acquired infections such as pneumonia, or bloodstream infection. infection is associated with high mortality rates....
The Activities of Antimicrobials Against Isolates and Evaluation of Clinical Outcomes Among Treatment Regimens in Patients with Infections: A Retrospective Multicenter Cohort Study.
PURPOSE
, a multidrug-resistant pathogen can cause hospital-acquired infections such as pneumonia, or bloodstream infection. infection is associated with high mortality rates. This retrospective study examined the antimicrobial susceptibility profile of clinical isolates and evaluated clinical outcomes, treatment regimens, and risk factors associated with 30-day mortality or treatment failure of infections at three tertiary care hospitals in Central Thailand.
PATIENTS AND METHODS
The characteristics, microbiological data, and clinical treatment outcomes were derived from medical records obtained from three tertiary care hospitals in Central Thailand from January 2017 to October 2022. The primary outcomes were treatment failure and 30-day mortality. The antimicrobial susceptibility rates of trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and ceftazidime were determined by minimum inhibitory concentration (MIC), which were based on broth microdilution and clear zone diameters using the disk diffusion method. However, we also report the susceptibility of minocycline and tigecycline in some clinical strains (n = 149) and determined by MIC with E-test method.
RESULTS
The antimicrobial susceptibility rates to TMP-SMX, levofloxacin, and ceftazidime were 97.1%, 93%, and 55.3%, respectively. The treatment failure rate and 30-day mortality were 66.3% and 49%, respectively. Significant factors associated with treatment failure included APACHE II score ≥15 (OR 3.37, 95% confidence interval (CI) 1.46-7.76), polymicrobial infections (OR 3.20, 95% CI 1.35-7.55). The significant factors associated with reduced treatment failure was treatment with TMP-SMX-based regimen (OR 0.29, 95% CI 0.11-0.76). The 30-day mortality rate was associated with APACHE II score ≥15 (OR 3.27, 95% CI 1.45-7.39) and septic shock (OR 2.53, 95% CI 1.36-4.69).
CONCLUSION
The results indicate a high mortality rate for infection. The predictive factors for an unfavourable outcome were severity of illness, septic shock, and non-use of TMP-SMX. Therefore, a TMP-SMX-based regimen is recommended for the treatment of infections.
PubMed: 37581163
DOI: 10.2147/IDR.S416678 -
Archives of Biochemistry and Biophysics Jan 2024Lysozyme complexes with amikacin and levofloxacin were studied by spectroscopy approaches as well as using a tritium probe. Tritium was used as a labeling agent to trace...
Lysozyme complexes with amikacin and levofloxacin were studied by spectroscopy approaches as well as using a tritium probe. Tritium was used as a labeling agent to trace labeled compound concentration in a system of two immiscible liquids and in the atomic form to determine the possible position of the binding site. Co-adsorption of protein and drug at the liquid-liquid interface was analyzed by scintillation phase method that allowed us to directly determine the amount of protein and drug in the mixed adsorption layer. Also, tensiometric measuring of the interfacial tension was used for calculation of binding parameters accordingly to Fainerman model. The treatment of complexes with atomic tritium followed by trypsinolysis and analysis of tritium distribution in the lysozyme peptides reveals the binding sites, binding energies in which were analyzed using molecular docking. Formation of complexes with amikacin and levofloxacin preserves secondar structure of protein. However, the formation of complex with amikacin leads to the almost total loss of the enzymatic activity of lysozyme and the redshift of the maximum on the lysozyme fluorescence band. A slight decrease in the distribution coefficient of lysozyme in the presence of amikacin assumes that the complex has higher hydrophilicity in comparison to lysozyme without additives. The most favorable for binding were the positions of the active centers that included amino acids Asp52 and Glu35, as well as in the vicinity of peptide His15-Arg21, with the participation of amino acids Tyr20, Arg14. In the case of levofloxacin, the formation of lysozyme-ligand complex in aqueous solution is possible without changing the microenvironment of the active center of the protein. Binding of levofloxacin to the active center of the enzyme was the most favorable, but Asp52 and Glu35 that are responsible for the enzymatic activity of lysozyme, were not affected.
Topics: Molecular Docking Simulation; Muramidase; Tritium; Amikacin; Levofloxacin; Spectrometry, Fluorescence; Peptides; Amino Acids
PubMed: 38065249
DOI: 10.1016/j.abb.2023.109848 -
Clinical Infectious Diseases : An... Jun 2024The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment...
BACKGROUND
The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations.
METHODS
We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier).
RESULTS
The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid.
CONCLUSIONS
Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy.
Topics: Humans; Bacillus anthracis; Anthrax; Meningitis, Bacterial; Anti-Bacterial Agents; Monte Carlo Method; Microbial Sensitivity Tests
PubMed: 38412060
DOI: 10.1093/cid/ciae093 -
Transplant Infectious Disease : An... Nov 2023The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial... (Review)
Review
BACKGROUND
The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications.
DISCUSSION
Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection-related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result.
CONCLUSIONS
The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk-benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT.
Topics: Adult; Child; Humans; Fluoroquinolones; Anti-Bacterial Agents; Antibiotic Prophylaxis; Neutropenia; Neoplasms
PubMed: 37746769
DOI: 10.1111/tid.14152 -
Antibiotics (Basel, Switzerland) Aug 2023Drain-associated intracerebral infections are life-threatening emergencies. Their treatment is challenging due to the limited penetration of antibiotics to the site of... (Review)
Review
Drain-associated intracerebral infections are life-threatening emergencies. Their treatment is challenging due to the limited penetration of antibiotics to the site of infection, resulting in potentially inadequate exposure. The emergence of multidrug-resistant pathogens might force the use of off-label intrathecal (IT) doses of antibiotics. We reviewed the literature on general aspects determining intrathecal dosing regimen, using pharmacometric knowledge. We summarised clinical experience with IT doses of antibiotics that are usually not used intrathecally, as well as the outcome of the cases and concentrations reached in the cerebrospinal fluid (CSF). Factors determining the IT regimen are the size of the ventricle system and the CSF drainage volume. With regard to pharmacometrics, pharmacokinetic/pharmacodynamic indices are likely similar to those in non-cerebral infections. The following number (N) of cases were described: benzylpenicillin (>50), ampicillin (1), ceftazidime (2), cephaloridine (56), ceftriaxone (1), cefotiam (1), meropenem (57), linezolid (1), tigecycline (15), rifampicin (3), levofloxacin (2), chloramphenicol (3) and daptomycin (8). Many side effects were reported for benzylpenicillin in the 1940-50s, but for the other antibiotics, when administered correctly, all side effects were minor and reversible. These data might help when choosing an IT dosing regimen in case there is no alternative option due to antimicrobial resistance.
PubMed: 37627711
DOI: 10.3390/antibiotics12081291 -
Molecular Pharmaceutics Jun 2024Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone drug that exists in both hydrated and anhydrous/dehydrated forms. Due to the complexity of such a compound,...
Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone drug that exists in both hydrated and anhydrous/dehydrated forms. Due to the complexity of such a compound, the primary aim of this study was to investigate the amorphization capabilities and solid-state transformations of LVXh when exposed to mechanical treatment using ball milling. Spray drying was utilized as a comparative method for investigating the capabilities of complete LVX amorphous (LVXam) formation. The solid states of the samples produced were comprehensively characterized by powder X-ray diffraction, thermal analysis, infrared spectroscopy, Rietveld method, and dynamic vapor sorption. The kinetics of the process and the quantification of phases at different time points were conducted by Rietveld refinement. The impact of the different mills, milling conditions, and parameters on the composition of the resulting powders was examined. A kinetic investigation of samples produced using both mills disclosed that it was in fact possible to partially amorphize LVXh upon mechanical treatment. It was discovered that LVXh first transformed to the anhydrous/dehydrated form γ (LVXγ), as an intermediate phase, before converting to LVXam. The mechanism of LVXam formation by ball milling was successfully revealed, and a new method of forming LVXγ and LVXam by mechanical forces was developed. Spray drying from water depicted that complete amorphization of LVXh was possible. The amorphous form of LVX had a glass transition temperature of 80 °C. The comparison of methods highlighted that the formation of LVXam is thus both mechanism- and process-dependent. Dynamic vapor sorption studies of both LVXam samples showed comparable stability properties and crystallized to the most stable hemihydrate form upon analysis. In summary, this work contributed to the detailed understanding of solid-state transformations of essential fluoroquinolones while employing greener and more sustainable manufacturing methods.
Topics: Levofloxacin; X-Ray Diffraction; Powders; Kinetics; Drug Compounding; Anti-Bacterial Agents; Calorimetry, Differential Scanning; Crystallization; Chemistry, Pharmaceutical
PubMed: 38662637
DOI: 10.1021/acs.molpharmaceut.4c00008