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International Journal of Antimicrobial... Dec 2023Data on protein binding are incomplete for first-line antituberculosis drugs, and lacking for second-line antituberculosis drugs that are used extensively for...
Data on protein binding are incomplete for first-line antituberculosis drugs, and lacking for second-line antituberculosis drugs that are used extensively for multi-drug-resistant tuberculosis (levofloxacin, linezolid and moxifloxacin). Thus, the main purposes of this study were to investigate: (i) the relationship between carrier protein concentration and drug binding; and (ii) the feasibility of predicting free drug concentration using in-vitro and in-vivo results. In-vitro experiments were performed on spiked plasma mimicking real-case samples (drug combinations from clinical practice). Median in-vivo protein binding was 1.5% for ethambutol, 9.7% for isoniazid, 0.7% for pyrazinamide and 88.2% for rifampicin; and median in-vitro protein binding was 26.2% for levofloxacin, 12.8% for linezolid and 46.3% for moxifloxacin. Albumin concentration (<30 g/L) had a moderate impact on moxifloxacin binding and a strong impact on levofloxacin, linezolid and rifampicin binding. Determination of the free drug concentration seems to be of little value for ethambutol, isoniazid, moxifloxacin and pyrazinamide; limited value for linezolid because of its low binding; and major value for rifampicin in hypoalbuminaemic patients with tuberculosis, and levofloxacin because total concentration was an inaccurate reflection of free concentration. The free concentration predicted by the mathematical model was suitable for levofloxacin and linezolid, whereas the real free concentration should be measured for rifampicin. Further investigations should be carried out to investigate the benefit of using free concentration for levofloxacin, linezolid and rifampicin, particularly in the critical period of active tuberculosis associated with hypoalbuminaemia.
Topics: Humans; Antitubercular Agents; Isoniazid; Linezolid; Rifampin; Ethambutol; Pyrazinamide; Levofloxacin; Moxifloxacin; Protein Binding; Tuberculosis
PubMed: 37838149
DOI: 10.1016/j.ijantimicag.2023.106999 -
Iranian Journal of Microbiology Apr 2024is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the...
BACKGROUND AND OBJECTIVES
is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates.
MATERIALS AND METHODS
Minimum inhibitory concentration was determined using broth microdilution method for levofloxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; , and genes and biofilm related genes , and without and with diclofenac and the combination.
RESULTS
Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac-showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed and showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm formation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations.
CONCLUSION
Diclofenac showed an antibacterial effect against The combination showed synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.
PubMed: 38854979
DOI: 10.18502/ijm.v16i2.15349 -
Chemosphere Dec 2023Microplastics can combine with pollutants such as antibiotics and pose a threat to the environment and organisms. At the same time, the inevitable aging behavior of...
Microplastics can combine with pollutants such as antibiotics and pose a threat to the environment and organisms. At the same time, the inevitable aging behavior of microplastics in the actual environment leads to changes in their physical and chemical properties, and thus changes the reaction mechanism between microplastics and other pollutants. In this study, we used three common microplastics PE/PS/PA to study the adsorption behavior of levofloxacin hydrochloride. Ultraviolet aging method was used to simulate the aging process of levofloxacin hydrochloride under sunlight, and compared with that of before aging. The results showed that the order of adsorption capacity was PS-UV > PA-UV > PE-UV > PA > PS > PE. Aging behavior can significantly enhance the adsorption capacity of microplastics to pollutants. Both Langmuir and Freundlich models can be used to fit the isothermal adsorption process well, indicating that the adsorption process was not a simple monolayer adsorption, but also a multi-molecular layer adsorption. The experiments showed that the adsorption process was affected by various mechanisms, including π-π conjugation, hydrogen bond, ion exchange and electrostatic interaction. This study elucidated the interaction mechanism between microplastics and levofloxacin hydrochloride, which has important significance for future control of microplastics and antibiotic pollution.
PubMed: 37717913
DOI: 10.1016/j.chemosphere.2023.140196 -
Journal of Cardiovascular Pharmacology Nov 2023A correlation is already established between fluoroquinolones (FQs) use and cardiovascular events (CVEs), such as QT prolongation; however, serious events such as aortic...
A correlation is already established between fluoroquinolones (FQs) use and cardiovascular events (CVEs), such as QT prolongation; however, serious events such as aortic aneurysm and valve regurgitation have also been reported with FQs. Several unstudied factors could contribute to the development of different CVEs that were not previously evaluated with FQ therapy. Therefore, we aimed to assess the incidence of different serious CVEs after completion of FQ therapy and potential associating factors. This was a retrospective case-control study of inpatients who received ciprofloxacin, levofloxacin, or moxifloxacin for ≥3 days. Patients' echocardiograms were evaluated for the development of aortic or valvular disease or worsening of an existing condition after completion of therapy. Of 373 included patients, 83 developed new valvular disease or worsening of an existing disease, where tricuspid valve regurgitation was the most common CVE (50/83; 60.2%), followed by mitral valve diseases (48/83; 57.8%). Aortic valve regurgitation occurred more commonly with moxifloxacin compared with ciprofloxacin and levofloxacin (17.8% vs. 6.7% and 10.7%, respectively; P = 0.01). Median time to CVE detection ranged 93-166 days for all FQs. The receipt of moxifloxacin and elevated baseline QT interval were associated with an increased CVEs risk (adjusted odds ratio 3.26; 95% confidence interval, 1.31-8.11 and adjusted odds ratio 1.02; 95% confidence interval, 1.00-1.04, respectively). Other factors did not show such association. The lack of association of different factors with the occurrence of CVEs indicates that all patients receiving FQ therapy, especially moxifloxacin, should be monitored during the first-year after therapy. Alternatively, other antibiotics with a better safety profile may be considered.
Topics: Humans; Fluoroquinolones; Levofloxacin; Moxifloxacin; Case-Control Studies; Retrospective Studies; Ciprofloxacin; Heart Valve Diseases
PubMed: 37506675
DOI: 10.1097/FJC.0000000000001459 -
Microbiology Spectrum Sep 2023To investigate the antibiotic resistance of () in outpatients and to explore the consistency between genotype and phenotype of antibiotic resistance. A retrospective...
To investigate the antibiotic resistance of () in outpatients and to explore the consistency between genotype and phenotype of antibiotic resistance. A retrospective study on outpatients screened with urea breath test for infection in Nanjing First Hospital from April 2018 to January 2022. Patients who tested positive underwent a consented upper endoscopy, and the infection was confirmed by rapid urease test (RUT) and culture. For antibiotic resistance phenotype analysis, the strains isolated from gastric biopsy were tested for antibiotic resistance phenotype by the Kirby-Bauer disk diffusion test. In addition, the antibiotic resistance genotype of isolated was tested with a real-time polymerase chain reaction. A total of 4,399 patients underwent infection screening, and 3,306 strains were isolated. The antibiotic resistance phenotype test revealed that the resistance rates of metronidazole (MTZ), clarithromycin (CLR), levofloxacin (LEV), amoxicillin (AMX), furazolidone (FR), and tetracycline (TE) were 74.58%, 48.61%, 34.83%, 0.76%, 0.27%, and 0.09%, respectively. Additionally, the antibiotic resistance genotype test revealed that rdxA gene mutation A610G (92.96%), A91G (92.95%), C92A (93.00%), and G392A (95.07%) were predominant in with MTZ resistance; 23S rRNA gene mutation A2143G (86.47%) occurred in most with CLR resistance; and gyrA gene mutation 87Ile/Lys/Tyr/Arg (97.32%) and 91Asn/Gly/Tyr (90.61%) were the most popular mutations in strains with LEV resistance. The phenotypic resistance and genotypic resistance to CLR (kappa value = 0.824) and LEV (kappa value = 0.895) were in good agreement. The history of eradication with MTZ, CLR, LEV, and AMX was correlated with resistance. In short, this study demonstrated that drug resistance of was mainly to MTZ, CLR, and LEV in local outpatients. Three drugs can be selected for increased MICs (Minimum Inhibitory Concentration) via single chromosomal mutations. In addition, the genotype could be used to predict the phenotypic resistance to CLR and LEV. IMPORTANCE is a key bacterium that causes stomach diseases. There was a high prevalence of in the Chinese population. We analyzed the resistance phenotype and genotype characteristics of in 4,399 outpatients at the First Hospital of Nanjing, China. We found a higher resistance rate to metronidazole (MTZ) , clarithromycin (CLR), and levofloxacin (LEV), and the genotype could be used to predict the phenotypic resistance to CLR and LEV. This study provides information on infection and also provides guidance for clinical doctors' drug treatment.
PubMed: 37732751
DOI: 10.1128/spectrum.00550-23 -
Frontiers in Microbiology 2023Fluoroquinolones are some of the most used antimicrobial agents for the treatment of . This study aimed at exploring the differential activity of ciprofloxacin and...
BACKGROUND
Fluoroquinolones are some of the most used antimicrobial agents for the treatment of . This study aimed at exploring the differential activity of ciprofloxacin and levofloxacin on the selection of resistance among isolates at our medical center.
METHODS
233 clinical isolates were included in this study. Antimicrobial susceptibility testing (AST) was done using disk diffusion and broth microdilution assays. Random Amplification of Polymorphic DNA (RAPD) was done to determine the genetic relatedness between the isolates. Induction of resistance against ciprofloxacin and levofloxacin was done on 19 isolates. Fitness cost assay was done on the 38 induced mutants and their parental isolates. Finally, whole genome sequencing was done on 16 induced mutants and their 8 parental isolates.
RESULTS
AST results showed that aztreonam had the highest non-susceptibility. RAPD results identified 18 clusters. The 19 isolates that were induced against ciprofloxacin and levofloxacin yielded MICs ranging between 16 and 256 μg/mL. Levofloxacin required fewer passages in 10 isolates and the same number of passages in 9 isolates as compared to ciprofloxacin to reach their breakpoints. Fitness cost results showed that 12 and 10 induced mutants against ciprofloxacin and levofloxacin, respectively, had higher fitness cost when compared to their parental isolates. Whole genome sequencing results showed that resistance to ciprofloxacin and levofloxacin in sequenced mutants were mainly associated with alterations in , and genes.
CONCLUSION
Understanding resistance patterns and risk factors associated with infections is crucial to decrease the emerging threat of antimicrobial resistance.
PubMed: 37744929
DOI: 10.3389/fmicb.2023.1209224 -
European Journal of Pediatrics Jul 2024Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a... (Review)
Review
UNLABELLED
Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on alternative treatment options, optimal dosage, and duration for treating severe, progressive, and systemic MP pneumonia after macrolide treatment failure. Macrolide-resistant MP pneumonia and refractory MP pneumonia are the two major complex conditions that are clinically encountered. Currently, the vast majority of MP isolates are resistant to macrolides in East Asia, especially China, whereas in Europe and North America, whereas in Europe and North America prevalence is substantially lower than in Asia, varying across countries. The severity of pneumonia and extrapulmonary presentations may reflect the intensity of the host's immune reaction or the dissemination of bacterial infection. Children infected with macrolide-resistant MP strains who receive macrolide treatment experience persistent fever with extended antibiotic therapy and minimal decrease in MP-DNA load. Alternative second-line agents such as tetracyclines (doxycycline or minocycline) and fluoroquinolones (ciprofloxacin or levofloxacin) may lead to clinical improvement after macrolide treatment failure in children. Refractory MP pneumonia reflects a deterioration of clinical and radiological findings due to excessive immune response against the infection. Immunomodulators such as corticosteroids and intravenous immunoglobulin (IVIG) have shown promising results in treatment of refractory MP pneumonia, particularly when combined with appropriate antimicrobials. Corticosteroid-resistant hyperinflammatory MP pneumonia represents a persistent or recrudescent fever despite corticosteroid therapy with intravenous methylprednisolone at standard dosage.
CONCLUSION
This report summarizes the clinical significance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drugs, with a stepwise approach to the management of MP pneumonia recommended from the viewpoint of clinical practice.
WHAT IS KNOWN
• Although MP pneumonia is usually a benign self-limited infection with response macrolides as first line therapy, severe life-threatening cases may develop if additional treatment strategies are not effectively implemented. • Macrolide-resistant and refractory MP pneumonia are two conditions that may complicate the clinical course of MP pneumonia, increasing the risk for exacerbation and even death.
WHAT IS NEW
• This report summarizes the clinical relevance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drug therapies. • A practical stepwise approach to the management of MP pneumonia is developed based on a comprehensive analysis of existing evidence and expert opinion.
Topics: Humans; Pneumonia, Mycoplasma; Anti-Bacterial Agents; Child; Macrolides; Mycoplasma pneumoniae; Drug Resistance, Bacterial; Community-Acquired Infections; Adolescent
PubMed: 38634891
DOI: 10.1007/s00431-024-05519-1 -
International Journal of Clinical... Dec 2023Quinolones can cause rhabdomyolysis, but rhabdomyolysis secondary to quinolone use is uncommon, and few reports associate rhabdomyolysis with levofloxacin use. We report...
Quinolones can cause rhabdomyolysis, but rhabdomyolysis secondary to quinolone use is uncommon, and few reports associate rhabdomyolysis with levofloxacin use. We report a case of acute rhabdomyolysis associated with levofloxacin use. A 58-year-old Chinese woman developed myalgia and difficulty walking ~ 4 days after taking levofloxacin for a respiratory infection. Blood biochemistry revealed elevated peripheral creatine kinase and liver enzyme levels, but the patient did not develop an acute kidney injury. Her symptoms resolved after discontinuation of levofloxacin. This case report highlights the need for monitoring of blood biochemistry in patients taking levofloxacin to enable early diagnosis and treatment of potentially life-threatening myositis.
Topics: Female; Humans; Middle Aged; Levofloxacin; Respiratory Tract Infections; Rhabdomyolysis; Acute Kidney Injury
PubMed: 37114513
DOI: 10.5414/CP204377 -
International Journal of Microbiology 2023Today, () is a major opportunistic pathogen among hospitalized or immunocompromised patients. Antibiotic-resistant clinical isolates are increasing in several parts of...
OBJECTIVES
Today, () is a major opportunistic pathogen among hospitalized or immunocompromised patients. Antibiotic-resistant clinical isolates are increasing in several parts of the world. Various antibiotic-resistance and biofilm-forming genes are identified in this bacterium. Its capacity to form biofilms is an important virulence factor that may impact antibiotic-resistance patterns. In the current study, we evaluated the biofilm-formation capacity, antibiotic-resistance profile, and prevalence of biofilm-forming genes as well as antibiotic resistance genes among isolates.
MATERIALS AND METHODS
In this cross-sectional study, 94 clinical isolates were recovered from four tertiary-care hospitals in Iran between 2021 and 2022. The presence of the selected antibiotic-resistance genes and biofilm-forming genes was examined by polymerase chain reaction (PCR). The ability of biofilm formation was examined by microtiter plate assay. The Kirby-Bauer disc diffusion method was used to evaluate the trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and minocycline resistance.
RESULTS
is mainly isolated from bloodstream infections. Notably, 98.93% of isolates were biofilm producers, of which 19.35%, 60.22%, and 20.43% produced strong, moderate, and weak biofilm, respectively. The frequency of biofilm genes was 100%, 97.88%, 96.80%, and 75.53% for -1, and , respectively. Isolates with the genotype of -1+/+/+/+ were mostly strong biofilm producers. Among the antibiotic-resistance genes, the had the highest prevalence (76.59%, 72.34%, and 64.89), respectively. Antimicrobial susceptibility evaluation showed 1.06%, 3.19%, and 6.3% resistance to minocycline, TMP-SMX, and levofloxacin.
CONCLUSION
The results of the current study demonstrated that isolates differ in biofilm-forming ability. Moreover, -1, , and genes were presented in all strong biofilm producers. Although the overall resistance rate to the evaluated antibiotics was high, there was no statistically significant relation between antibiotic resistance and the type of biofilm.
PubMed: 37692920
DOI: 10.1155/2023/8873948 -
Frontiers in Cellular and Infection... 2023The increasing prevalence of antibiotic resistance in cases of () infection has emerged as a significant global issue. This study offers a comprehensive examination of...
BACKGROUND
The increasing prevalence of antibiotic resistance in cases of () infection has emerged as a significant global issue. This study offers a comprehensive examination of the alterations in drug resistance exhibited by in the Nanjing region of China during the preceding five years. Another important objective is to investigate the influence of levofloxacin medication history on genotypic and phenotypic resistance.
METHODS
This research screened 4277 individuals diagnosed with infection between April 2018 and May 2023. The phenotype and genotypic resistance were evaluated using the Kirby-Bauer disk diffusion and PCR method.
RESULTS
The most recent primary resistance rates for metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone, and tetracycline were recorded at 77.23% (2385/3088), 37.24% (1150/3088), 27.72% (856/3088), 0.52% (16/3088), 0.19% (6/3088), and 0.06% (2/3088), respectively. For the recent five years, we observed a notable upsurge in the rate of metronidazole resistance and a slight elevation of clarithromycin and levofloxacin resistance. The documented resistance rates to single-drug, dual-drug, triple-drug, and quadruple-drug regimens were 35.39%, 28.32%, 25.72%, and 0.21%, respectively. The prevalence of multidrug-resistant strains escalated, rising from 37.96% in 2018 to 66.22% in 2023. The rate of phenotypic and genotypic resistance rate (57.10% and 65.57%) observed in strains obtained from patients without a levofloxacin treatment history was significantly lower than the rate in strains obtained from those with a history of levofloxacin treatment (88.73% and 94.74%). The prevailing mutations were primarily N87K (52.35%, 345/659), accompanied by D91N (13.96%, 92/659), and closely followed by D87G (10.77%, 71/659). For mutations, the 91-amino acid mutants exhibit a higher likelihood of discrepancies between phenotypic and genotypic resistance than the 87-amino acid mutants.
CONCLUSION
The extent of antibiotic resistance within remains substantial within the Nanjing region. If levofloxacin proves ineffective in eradicating during the initial treatment, its use in subsequent treatments is discouraged. The employment of levofloxacin resistance genotype testing can partially substitute conventional antibiotic sensitivity testing. Notably, predicting phenotypic resistance of levofloxacin through PCR requires more attention to the mutation type of to improve prediction accuracy.
Topics: Humans; Clarithromycin; Metronidazole; Helicobacter pylori; Levofloxacin; Anti-Bacterial Agents; Helicobacter Infections; Drug Resistance, Microbial; China; Amino Acids; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 38089809
DOI: 10.3389/fcimb.2023.1294379