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Antimicrobial Agents and Chemotherapy May 2017The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing isolates were compared. Since quinolones...
Pharmacodynamics of Finafloxacin, Ciprofloxacin, and Levofloxacin in Serum and Urine against TEM- and SHV-Type Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections.
The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing isolates were compared. Since quinolones lose activity in acidic media, and particularly in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine. For this purpose, TEM- and SHV-type ESBL-producing and strains and their wild-type counterparts were exposed in a modified Grasso model to simulated concentrations of drugs in serum and urine following oral doses of either finafloxacin at 800 mg once a day (q.d.), immediate-release ciprofloxacin at 500 mg twice a day (b.i.d.), extended-release ciprofloxacin at 1,000 mg q.d., or levofloxacin at 500 or 750 mg q.d. The concentrations of the drugs in urine were fitted by compartmental modeling. Bacteria were cultivated in Mueller-Hinton broth (MHB) at pH 7.2 or 5.8 or in artificial urine at pH 5.8. Bacteria were counted every 2 h until 10 h and at 24 h; the areas under the bacterial-count-versus-time curves were calculated. It was found that finafloxacin eliminated all strains within 2 h under all the conditions studied. At all doses studied, ciprofloxacin and levofloxacin were highly active against wild-type strains in MHB at pH 7.2 but lost activity in MHB, and particularly in urine, at pH 5.8. Viable counts of ESBL producers were reduced for 6 to 8 h by 3 log titers, but the bacteria regrew thereafter. Ciprofloxacin and levofloxacin were almost inactive against the SHV producer grown in artificial urine. We conclude that pharmacodynamic models using artificial urine may mirror the physiology of urinary tract infections more closely than those using conventional media. In contrast to ciprofloxacin and levofloxacin, finafloxacin gained activity in this model at an acidic pH, maintained activity in artificial urine, and was active against TEM and SHV producers.
Topics: Anti-Bacterial Agents; Blood; Ciprofloxacin; Escherichia coli; Fluoroquinolones; Humans; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Urinary Tract Infections; Urine; beta-Lactamases
PubMed: 28193648
DOI: 10.1128/AAC.02446-16 -
MBio Oct 2023Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is...
Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.
Topics: Humans; Fosfomycin; Levofloxacin; Urinary Tract Infections; Anti-Bacterial Agents; Cystitis
PubMed: 37698412
DOI: 10.1128/mbio.01677-23 -
BMC Infectious Diseases Jun 2022The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply challenged in the last decade. The goal of this analysis was to identify the potential relevance between cagA and vacA genotypes with reported antibiotic resistance observed in clinical H. pylori isolates.
METHODS
This literature search was conducted in databases such as Clarivate analytics, PubMed, Scopus, EMBASE, DOAJ, and Google Scholar by April 2022, regardless of language restrictions and publication date. Quality of the included studies was assessed by the Newcastle-Ottawa scale. Statistical analysis of retrieved studies was fulfilled using Comprehensive Meta-Analysis software version 2.2. Following quality appraisal of eligible studies, potential association between the status of cagA and vacA genes with resistance to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was measured using odds ratio with 95% confidence interval. We also used sensitivity analyses and meta-regression to eliminate the source of heterogeneity from the overall estimates. Publication bias was assessed using funnel plot, Egger's test, Begg's test with the trim and fill procedure to assess the presence and magnitude of publication bias in the included studies.
RESULTS
Our findings suggested that a significant relationship between cagA status and increase resistance to metronidazole (OR: 2.69; 95% CI: 1.24-5.83). In subgroup analysis, we found that in the Western population, infection with cagA-positive strains could be led to increase in the resistance to metronidazole (OR: 1.59; 95% CI: 0.78-3.21), amoxicillin (OR: 19.68; 95% CI: 2.74-141.18), and levofloxacin (OR: 11.33; 95% CI: 1.39-91.85). After implementation of trim and fill method, the adjusted OR was not significantly differed from original estimates which in turn represented our subgroup analysis was statistically robust. On the other hand, vacA genotypes usually reduce the antibiotic resistance of this bacterium, so that vacA s1m1 significantly reduces the resistance to metronidazole (OR: 0.41; 95% CI: 0.20-0.86). Surprisingly, resistance of vacA s2m2 strains to antibiotics was low, the reason may be due to the non-inflammatory properties of strains containing vacA s2m2. The meta-regression and sensitivity analyses successfully reduced the effect of heterogeneity from the overall estimates. In addition, although the pooled OR is reduced after trim and fill adjustment but results do not change the conclusion regarding vacA genotypes and antibiotic resistance.
CONCLUSIONS
According to our findings, it was clearly demonstrated that cagA-positive strains are resistance to metronidazole, especially in Western countries. In Western countries, vacA s1m1 increases resistance to amoxicillin and levofloxacin. Based on the present findings, the vacA s1m1 genotype significantly increases resistance to metronidazole, while the vacA s1m2 decreases resistance to clarithromycin and metronidazole. Resistance to antibiotics in less virulent (vacA s2m2) strains is statistically significant lower than others.
Topics: Amoxicillin; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Proteins; Clarithromycin; Drug Resistance, Microbial; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole
PubMed: 35752757
DOI: 10.1186/s12879-022-07546-5 -
Frontiers in Cellular and Infection... 2020antibiotic resistance is increasing worldwide, emphasizing the urgent need for more rapid resistance detection prior to the administration of eradication regimens....
antibiotic resistance is increasing worldwide, emphasizing the urgent need for more rapid resistance detection prior to the administration of eradication regimens. Macrolides and fluoroquinolones are widely used to treat . In this study, we aimed to compare the diagnostic performance of A) 23SrDNA qPCR (with melting curve analysis) and an in-house developed qPCR followed by Sanger sequencing with a commercial IVD-marked hybridization probe assay (for 23SrDNA and ) using 142 gastric biopsies (skipping culturing) and B) the same two qPCR for 23SrDNA and (including Sanger sequencing) with whole-genome sequencing (WGS) and phenotypic characterization of clarithromycin and levofloxacin resistance using 76 cultured isolates. The sensitivity of both qPCRs was 100% compared to that of the commercial IVD-marked hybridization probe assay for the detection of in gastric biopsies (without resistance testing). The specificity of the qPCR followed by Sanger sequencing was 100%, indicating that the best sequence identity was always . The results show good agreement between molecular tests, especially between qPCR (inclusive Sanger sequencing) and WGS. Discrepancies (concerning mutated or wild type of positive gastric biopsies) were observed between Sanger sequencing of the gene and the corresponding commercial hybridization probe assay, mostly because the high sequence diversity of the gene even at positions adjacent to the relevant codons of 87 and 91 interfered with obtaining correct results from the hybridization probe assay. Interestingly, we found several mixed sequences, indicating mixed populations in the gastric biopsies (direct detection without culturing). There was a high percentage of both levofloxacin and clarithromycin resistance in gastric biopsies (both between 22% and 29%, direct detection in gastric biopsies). Therefore, we recommend analyzing both targets in parallel. We confirmed that phenotypic resistance is highly correlated with the associated mutations. We concluded that the two qPCR followed by Sanger sequencing of the gene is a fast, cost-effective and comprehensive method for resistance testing of directly in gastric biopsies.
Topics: Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Microbial Sensitivity Tests
PubMed: 33392106
DOI: 10.3389/fcimb.2020.596371 -
PeerJ 2023Efficacy of . ) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of in Fujian, China.
BACKGROUND AND AIM
Efficacy of . ) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of in Fujian, China.
METHODS
-infected patients in four centers were enrolled in the study from Oct 2019 to Jan 2022. The bacteria were isolated, cultured and identified from the biopsy of patients' gastric mucosa samples. Antimicrobial susceptibility testing was performed by a modified broth microdilution method for to seven guideline-recommended antibiotics and seven potential choices for eradication.
RESULTS
A total of 205 strains were isolated. The resistance rates of amoxicillin (AMX), amoxicillin and clavulanate potassium (AMC), cefixime (CFM), gentamicin (GEN), tetracycline (TET), doxycycline (DOX), azithromycin (AZM), clarithromycin (CLR), levofloxacin (LVFX), sparfloxacin (SPFX), metronidazole (MTZ), tinidazole (TID), rifampicin (RFP) and furazolidone (FZD) were 11.22%, 12.20%, 7.32%, 12.20%, 4.88%, 4.39%, 44.39%, 43.90%, 30.24%, 21.46%, 40.98%, 45.85%, 5.37% and 10.24%, respectively. The rates of pan-sensitivity, single, double, triple and multiple resistance for seven guideline-recommended antibiotics were 32.68%, 30.24%, 13.17%, 7.76%, and 14.15%, respectively. The main double-resistance patterns were CLR+MTZ (10/205, 5%) and CLR+LVFX (9/205, 4%). The main triple-resistance pattern was CLR+MTZ+ LVFX (15/205, 7%).
CONCLUSIONS
In Fujian, the prevalence of resistance to AZM, CLR, LVFX, SPFX, MTZ, and TID was high, whereas that to AMX, AMC, GEN, CFM, TET, DOX, RFP and FZD was relatively low. CFM and DOX are promising new choices for eradication.
Topics: Humans; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Microbial Sensitivity Tests; Metronidazole; Clarithromycin; Amoxicillin; Tetracycline; Drug Resistance, Bacterial; Furazolidone; Cefixime; Doxycycline; Levofloxacin
PubMed: 37456872
DOI: 10.7717/peerj.15611 -
United European Gastroenterology Journal Feb 2024Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful...
BACKGROUND
Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication.
AIM
To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg).
METHODS
Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022.
RESULTS
Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness.
CONCLUSIONS
We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.
Topics: Adult; Humans; Proton Pump Inhibitors; Helicobacter pylori; Metronidazole; Clarithromycin; Levofloxacin; Bismuth; Prospective Studies; Drug Therapy, Combination; Anti-Bacterial Agents; Helicobacter Infections; Amoxicillin; Tetracycline; Registries
PubMed: 38050339
DOI: 10.1002/ueg2.12476 -
Frontiers in Cellular and Infection... 2023Legionnaires' Disease is a pneumonia caused by spp., currently treated empirically with fluoroquinolones and macrolides. In this study, we aim to describe the...
INTRODUCTION
Legionnaires' Disease is a pneumonia caused by spp., currently treated empirically with fluoroquinolones and macrolides. In this study, we aim to describe the antibiotic susceptibility pattern of environmental recovered in the south of Portugal.
METHODS
Minimal inhibitory concentration (MIC) determination of 57 isolates (10 Lp sg 1, 32, Lp sg 2-14 15 L. spp) was achieved by broth microdilution, as described by EUCAST, for azithromycin, clarithromycin, ciprofloxacin, levofloxacin, and doxycycline.
RESULTS
Fluoroquinolones were the most active antibiotic, displaying the lowest MIC values in contrast to doxycycline which had the highest. MIC90 and epidemiological cut-off (ECOFF) values were, respectively, 0.5/1 mg/L for azithromycin, 0.125/0.25 mg/L for clarithromycin, 0.064/0.125 mg/L for ciprofloxacin, 0.125/0.125 mg/L for levofloxacin and 16/32 mg/L for doxycycline.
DISCUSSION
MIC distributions were higher than reported by EUCAST for all antibiotics. Interestingly, two phenotypically resistant isolates with high-level quinolone resistance were identified. This is the first time that MIC distributions, and tet56 genes have been investigated in Portuguese environmental isolates of .
Topics: Humans; Legionella; Levofloxacin; Portugal; Azithromycin; Clarithromycin; Doxycycline; Legionella pneumophila; Anti-Bacterial Agents; Fluoroquinolones; Legionnaires' Disease; Ciprofloxacin; Microbial Sensitivity Tests
PubMed: 37153155
DOI: 10.3389/fcimb.2023.1141115 -
International Journal of... 2020Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum...
BACKGROUND
Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum peak concentration (C) and total area under the concentration time curve (AUC). Pharmacokinetic exposures can be measured to personalize dosing to reach targets, but this practice requires venepuncture, chromatographic or mass spectrometry equipment, and technical expertise. We sought to demonstrate the accuracy of using urine colorimetry as a more feasible estimation of levofloxacin exposure.
METHOD
A colorimetric method using bromocresol green was tested on spiked urine samples with levofloxacin measured using a spectrophotometer. This method was tested in urine samples of healthy volunteers given one 750 mg dose of levofloxacin with urine collected at 0-4 h, 4-8 h, and 8-24 h intervals, and concomitant serum samples were collected and analyzed by high-performance liquid chromatography. Validation of this assay was done in a cohort of people living with human immunodeficiency virus (PLWH), initiating a levofloxacin containing MDR-TB regimen.
RESULTS
Urine colorimetry was reproducible in spiked samples and the calibration was curve linear for levofloxacin concentrations ranging from 7.8 μg/ml to 250 μg/ml, with r = 0.98. In healthy volunteers, correlation between urine absorbance values and serum AUC was highest in urine collected between 4 and 8 h (r = 0.91, P = 0.01), yet in PLWH, urine collected between 0 and 4 h had highest correlation (r = 0.66, P = 0.05). The area under the receiver operating characteristics curve was >0.8 in the derivation, as well as the validation cohort for the urine absorbance values identifying people with total serum exposure below target.
CONCLUSION
Urine colorimetry was highly sensitive in predicting target serum concentrations. Colorimetric methods to determine levofloxacin in urine may improve the feasibility of therapeutic drug monitoring and personalized dose adjustment in TB endemic settings.
Topics: Antitubercular Agents; Colorimetry; Drug Monitoring; Female; Humans; Levofloxacin; ROC Curve; Tuberculosis, Multidrug-Resistant
PubMed: 33323657
DOI: 10.4103/ijmy.ijmy_186_20 -
Antimicrobial Agents and Chemotherapy Mar 2017A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The...
A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The aim was to assess the population pharmacokinetics (popPK) and pharmacodynamics of levofloxacin among older patients. PopPK and Monte Carlo simulation were performed to define the permissible doses in older patients according to various degrees of renal function. Classification and regression tree (CART) analysis was used to detect the cutoff 24-hour area under the concentration-time curve (AUC)/MIC ratio that best correlated with the clinical outcome. The probability of target attainment (PTA) of this value was calculated against different pathogens. A total of 168 patients were included, and 330 trough and 239 peak concentrations were used for the popPK analysis. Creatinine clearance (CrCL) was the only covariate that improved the model fit (levofloxacin CL = 0.399 + 0.051 × CrCL [creatinine clearance estimated by means of the chronic kidney disease epidemiology]). Drug doses ranged between 500 mg every 48 h and 500 mg every 12 h in relation to different renal functions. The identified cutoff AUC/MIC ratio (≥95.7) was the only covariate that correlated with a favorable clinical outcome in multivariate regression analysis (odds ratio [OR], 20.85; 95% confidence interval [CI], 1.56 to 186.73). PTAs were optimal (>80%) against and , borderline against , and suboptimal against The levofloxacin doses defined in our study may be effective for the treatment of infections due to bacterial pathogens, with an MIC of ≤0.5 mg/liter in older patients with various degrees of renal function, while minimizing the toxicity risk. Conversely, the addition of another active antimicrobial should be considered whenever treating infections caused by less susceptible pathogens.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Biological Availability; Body Mass Index; Creatinine; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Escherichia coli; Female; Haemophilus influenzae; Hospitalization; Humans; Kidney Function Tests; Levofloxacin; Male; Microbial Sensitivity Tests; Models, Statistical; Pseudomonas aeruginosa; Retrospective Studies; Staphylococcus aureus
PubMed: 28031199
DOI: 10.1128/AAC.02134-16 -
BMC Infectious Diseases Jan 2023Helicobacter pylori (H. pylori) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Helicobacter pylori (H. pylori) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different gastric maliganacies. It has been also correlated to extraintestinal diseases, including refractory iron deficiency anaemia, vitamin B12 deficiency, and immune thrombocytopenic purpura. The misuse of antibiotics during the coronavirus diseases 2019 (COVID-19) pandemic time can affect H. pylori eradication rates. Our aim was to compare the efficacy of clarithromycin versus levofloxacin-based regimens for H. pylori treatment in naïve patients after the COVID-19 pandemic misuse of antibiotics.
METHODS
A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were recruited. Patients were randomized to receive either clarithromycin, esomeprazole, and amoxicillin, or levofloxacin, esomeprazole, and amoxicillin.
RESULTS
A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were included, 135 in each arm. In total, 19 patients in the clarithromycin group and 18 patients in the levofloxacin group stopped treatment after 2-4 days because of side effects or were lost for follow-up. Finally, 116 subjects in the clarithromycin group and 117 in the levofloxacin group were assessed. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: group I, 55.56% and 64.66%; and Group II, 64.44% and 74.36% respectively (p = 0.11).
CONCLUSION
As COVID-19 pandemic has moved forward fast, high resistance rates of H. pylori to both clarithromycin and levofloxacin were developed after less than two years from the start of the pandemic. Molecular & genetic testing is highly recommended to identify antimicrobial resistance patterns. Strategies to prevent antibiotic misuse in the treatment of COVID-19 are needed to prevent more antibiotic resistance.
TRIAL REGISTRATION
The trial was registered on Clinicaltrials.gov NCT05035186. Date of registration is 2-09-2021.
Topics: Humans; Levofloxacin; Clarithromycin; Helicobacter pylori; Esomeprazole; Helicobacter Infections; Pandemics; Proton Pump Inhibitors; Drug Therapy, Combination; COVID-19; Anti-Bacterial Agents; Amoxicillin; Treatment Outcome
PubMed: 36670359
DOI: 10.1186/s12879-023-07993-8