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Antimicrobial Agents and Chemotherapy Jun 2023Biofilm-forming bacterial infections result in clinical failure, recurring infections, and high health care costs. The antibiotic concentrations needed to eradicate...
Biofilm-forming bacterial infections result in clinical failure, recurring infections, and high health care costs. The antibiotic concentrations needed to eradicate biofilm require further research. We aimed to model an prosthetic joint infection (PJI) to elucidate the activity of traditional systemic concentrations versus supratherapeutic concentrations to eradicate a Staphylococcus epidermidis biofilm PJI. We evaluated S. epidermidis high-biofilm-forming (ATCC 35984) and low-biofilm-forming (ATCC 12228) isolates in an pharmacodynamic biofilm reactor model with chromium cobalt coupons to simulate prosthetic joint infection. Vancomycin, daptomycin, levofloxacin, and minocycline were used alone and combined with rifampin to evaluate the effect of biofilm eradication. We simulated three exposures: (i) humanized systemic dosing alone, (ii) supratherapeutic doses (1,000× MIC), and (iii) and dosing in combination with rifampin. Resistance development was monitored throughout the study. Simulated humanized systemic doses of a lipoglycopeptide (daptomycin), a fluoroquinolone (levofloxacin), a tetracycline (minocycline), and a glycopeptide (vancomycin) alone failed to eradicate a formed S. epidermidis biofilm. Supratherapeutic doses of vancomycin (2,000 μg/mL) and minocycline (15 μg/mL) with or without rifampin (15 μg/mL) failed to eradicate biofilms. However, a levofloxacin supratherapeutic dose (125 μg/mL) with rifampin eradicated the high-biofilm-producing isolate by 48 h. Interestingly, supratherapeutic-dose exposures of daptomycin (500 μg/mL) alone eradicated high- and low-biofilm-forming isolates in established biofilms. The concentrations needed to eradicate biofilms on foreign materials are not obtained with systemic dosing regimens. The failure of systemic dosing regimens to eradicate biofilms validates clinical findings with recurring infections. The addition of rifampin to supratherapeutic dosing regimens does not result in synergy. Supratherapeutic daptomycin dosing may be effective at the site of action to eradicate biofilms. Further studies are needed.
Topics: Anti-Bacterial Agents; Daptomycin; Staphylococcus epidermidis; Vancomycin; Minocycline; Rifampin; Levofloxacin; Biofilms; Microbial Sensitivity Tests
PubMed: 37154699
DOI: 10.1128/aac.00108-23 -
The Turkish Journal of Gastroenterology... Apr 2023The purpose of this study was to determine the antimicrobial status of stocked clinical Helicobacter pylori isolates by using antibiotic gradient test and subsequently...
BACKGROUND
The purpose of this study was to determine the antimicrobial status of stocked clinical Helicobacter pylori isolates by using antibiotic gradient test and subsequently identify the mutations that cause clarithromycin resistance by DNA sequencing. Turkey is a transition zone between Europe and Asia; therefore, we also aimed to show both continents' mutations in Turkish isolates.
METHODS
One hundred forty-seven H. pylori isolates that had been stocked at -80°C between 1998 and 2008 were randomly selected and included in the study. Antibiotic susceptibility tests were performed using antibiotic gradient test for clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin. A polymerase chain reaction targeting the region of 23S rRNA gene domain V of H. pylori was performed and the mutations responsible for resistance against clarithromycin were defined by sequencing.
RESULTS
All of the tested isolates were found susceptible to amoxicillin and tetracycline. However, clarithromycin, metronidazole, and levofloxacin resistance were detected in 28.5% (42/147), 44.8% (66/147), and 23.1% (34/147) of the isolates, respectively. Point mutations were detected in 46 isolates (46/147, 31.2%). The majority of mutations were defined as A2143G (19/46, 41.3%), A2142G (14/46, 30.4%), and A2142C (7/46, 15.2%), respectively. T2188C, T2182C, G1949A, G1940A, and C1944T mutations were also identified in the isolates.
CONCLUSION
In conclusion, the most common mutations associated with clarithromycin resistance in H. pylori have been identified as A2143G, A2142G, and A2142C which are the most frequently detected mutations in European countries. Same mutations and other mutations like T2182C have also been detected frequently in north-eastern countries and China. Since Turkey is a transition zone between Europe and Asia, Turkey might have strains that carry mutations found in both continents.
Topics: Humans; Clarithromycin; Helicobacter pylori; Metronidazole; Levofloxacin; Helicobacter Infections; Drug Resistance, Bacterial; Anti-Bacterial Agents; Amoxicillin; Tetracycline; RNA, Ribosomal, 23S; Microbial Sensitivity Tests
PubMed: 36789980
DOI: 10.5152/tjg.2023.21954 -
Spectrochimica Acta. Part A, Molecular... Jan 2022Lipophilicity plays a significant role in the permeability of the drugs through cell membranes and impacts the drug activity in the human body. In this paper, the...
Lipophilicity plays a significant role in the permeability of the drugs through cell membranes and impacts the drug activity in the human body. In this paper, the spectrophotometric method was used to determine the apparent partition coefficients of two amphoteric drugs: ciprofloxacin and levofloxacin. The apparent partition coefficient was determined with the classic shake-flask method with n-octanol according to OECD guidelines. The lipophilicity profiles in a wide range of pH were determined and described quantitatively with the quadratic function. Basing on the macro- and microdissociation constants, the true partition coefficient for both drugs was calculated. Both levofloxacin and ciprofloxacin were lipophilic. The neutral forms, i.e., zwitterionic and uncharged, dominate in the pH relevant to the one in the intestines, the place from which they are absorbed.
Topics: 1-Octanol; Ciprofloxacin; Humans; Hydrogen-Ion Concentration; Levofloxacin; Permeability; Solubility; Water
PubMed: 34500409
DOI: 10.1016/j.saa.2021.120343 -
Trials Jun 2023New treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain...
BACKGROUND
New treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain reaction-based methods for antibiotic susceptibility testing are available for detecting H. pylori-specific mutations that confer resistance to clarithromycin and levofloxacin. Several meta-analyses have compared eradication rates for susceptibility-guided versus empirical therapy for H. pylori treatment; however, all have significant limitations and high heterogeneity, and the results are contradictory. The main objective of this trial is to assess whether a sequential strategy based on molecular susceptibility testing-guided therapy for H. pylori has a better eradication rate than empirical therapy.
METHODS
This trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. Men and women who are H. pylori-positive, naïve to treatment, and aged 18-65 years will be recruited. A total of 500 participants will be randomised to receive either empirical therapy or a susceptibility-guided sequential strategy. Bismuth quadruple therapy will be the empirical first-line therapy, and in case of failure, high-dose dual (proton-pump inhibitor + amoxicillin) treatment will be the rescue therapy. For the susceptibility-guided sequential strategy, regimen selection will be based on H. pylori susceptibility to clarithromycin (first-line) and levofloxacin (rescue). A first-line treatment of clarithromycin triple therapy will be selected for clarithromycin-sensitive strains. For clarithromycin resistance, a high-dose dual therapy will be selected. During the rescue treatment, a levofloxacin quadruple regimen will be selected for levofloxacin-sensitive strains, and a furazolidone quadruple regimen will be selected for others. The primary outcome is the first-line eradication rate in both groups, and the overall (including first and rescue therapies) H. pylori eradication rate in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis, and per-protocol analysis.
DISCUSSION
This randomised controlled trial will provide objective and valid evidence about the value of polymerase chain reaction-based molecular methods for antibiotic susceptibility testing in guiding H. pylori eradication.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05549115. Released on 18 September 2022. First posted on 22 September 2022. Enrolment of the first participant on 20 September 2022. The study is retrospectively registered.
Topics: Male; Humans; Female; Helicobacter Infections; Clarithromycin; Helicobacter pylori; Levofloxacin; Prospective Studies; Drug Therapy, Combination; Anti-Bacterial Agents; Proton Pump Inhibitors; Metronidazole; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37337241
DOI: 10.1186/s13063-023-07457-z -
Journal of Microbiology, Immunology,... Feb 2022The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious...
Emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole-resistant Stenotrophomonas maltophilia: Risk factors and antimicrobial sensitivity pattern analysis from a single medical center in Taiwan.
BACKGROUND
The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious problem, but clinical data analysis on this has not been reported.
METHODS
A matched case-control-control study was conducted to investigate risk factors for LTSRSM occurrence in hospitalized patients. For patients with LTSRSM infection/colonization (the case group), two matched control groups were used: control group A with levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) and control group B without S. maltophilia. Besides, tigecycline, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and colistin susceptibilities in collected LTSRSM and levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) isolates were compared.
RESULTS
From January 2014 to June 2016, 129 LTSRSM from cultured 1213 S. maltophilia isolates (10.6%) were identified. A total of 107 LTSRSM infected patients paired with 107 LTSSSM-, and 107 non-S. maltophilia-infected ones were included. When compared with control group A, previous fluoroquinolone and TMP/SMX use was found to be independently associated with LTSRSM occurrence. When compared with control group B, mechanical ventilation, cerebrovascular disease, and previous fluoroquinolone use were risk factors for LTSRSM occurrence. Eighty-five LTSRSM and 85 LTSSSM isolates were compared for antibiotic susceptibilities; the resistance rates and minimum inhibitory concentrations of tigecycline and ceftazidime were significantly higher for LTSRSM than for LTSSSM isolates.
CONCLUSION
The emergence of LTSRSM showing cross resistance to tigecycline and ceftazidime would further limit current therapeutic options. Cautious fluoroquinolone and TMP/SMX use may be helpful to limit such high-level resistant strains of S. maltophilia occurrence.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Risk Factors; Stenotrophomonas maltophilia; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33500210
DOI: 10.1016/j.jmii.2020.12.012 -
Molecules (Basel, Switzerland) Jun 2017The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus,...
The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R₄W₄] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 µg/mL against Methicillin-resistant (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R₄W₄] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of [R₄W₄K]-levofloxacin-Q and [R₄W₄K]-levofloxacin. The carboxylic acid group of levofloxacin or levofloxacin-Q was conjugated with the amino group of β-alanine attached to lysine in the presence of 2-(1-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and ,-diisopropylethylamine (DIPEA) for 3 h to afford the products. Antibacterial assays were conducted to determine the potency of conjugates [R₄W₄K]-levofloxacin-Q and [R₄W₄K]-levofloxacin against MRSA and . Although levofloxacin-Q was inactive even at a concentration of 128 µg/mL, [R₄W₄K]-levofloxacin-Q conjugate and the corresponding physical mixture showed MIC values of 8 µg/mL and 32 µg/mL against MRSA and , respectively, possibly due to the activity of the peptide. On the other hand, [R₄W₄K]-levofloxacin conjugate (MIC = 32 µg/mL and MIC = 128 µg/mL) and the physical mixture (MIC = 8 µg/mL and 32 µg/mL) was less active than levofloxacin (MIC = 2 µg/mL and 4 = µg/mL) against MRSA and , respectively. The data showed that the conjugation of levofloxacin with [R₄W₄K] significantly reduced the antibacterial activity compared to the parent analogs, while [R₄W₄K]-levofloxacin-Q conjugate was more significantly potent than levofloxacin-Q alone.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Bacterial; Ethylamines; Humans; Klebsiella pneumoniae; Levofloxacin; Methicillin-Resistant Staphylococcus aureus; Peptides, Cyclic; Triazoles; Urea
PubMed: 28594345
DOI: 10.3390/molecules22060957 -
The Lancet. Microbe Jun 2024
Multicentre, cross-sectional surveillance of Helicobacter pylori prevalence and antibiotic resistance to clarithromycin and levofloxacin in urban China using the string test coupled with quantitative PCR.
Topics: Humans; Clarithromycin; Levofloxacin; China; Helicobacter pylori; Helicobacter Infections; Cross-Sectional Studies; Anti-Bacterial Agents; Prevalence; Drug Resistance, Bacterial; Male; Female; Middle Aged; Adult; Microbial Sensitivity Tests; Aged; Urban Population; Real-Time Polymerase Chain Reaction
PubMed: 38437848
DOI: 10.1016/S2666-5247(24)00027-2 -
Annals of Palliative Medicine Sep 2021The efficacy of levofloxacin and ciprofloxacin in the treatment of urinary tract infection is not clear yet. This study perform a meta-analysis to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of levofloxacin and ciprofloxacin in the treatment of urinary tract infection is not clear yet. This study perform a meta-analysis to explore the differences between the two against urinary tract infection (UTI).
METHODS
A computerized literature search was conducted of the databases of PubMed, Medline, Embase, and the Cochrane Library. All the retrieved literatures were randomized comparative studies of levofloxacin and ciprofloxacin. The included studies were screened according to the standard of nanofiltration. The risk of bias was assessed with RevMan 5.3.5 software. The treatment effect index and incidence of adverse reactions index were established and compared via meta-analysis.
RESULTS
A total of 5 studies were included, involving 2,877 patients overall. The results showed that levofloxacin was more effective than ciprofloxacin, but the difference between the 2 drugs was not statistically significant [odds ratio (OR) =1.18, 95% confidence interval (CI): 0.94 to 1.46, P=0.15]. There was also no statistical significance in the rate of adverse reactions between the 2 drugs (OR =0.91, 95% CI: 0.78 to 1.07, P=0.27).
DISCUSSION
In the treatment of UTI, the efficacy and safety of levofloxacin and ciprofloxacin are similar statistically. If bacterial resistance is discovered after the treatment of one of the drugs, the other drug might become an alternative.
Topics: Ciprofloxacin; Humans; Levofloxacin; Urinary Tract Infections
PubMed: 34628902
DOI: 10.21037/apm-21-2042 -
Journal of Biomedical Science Oct 2018In the face of rising prevalence of antibiotic resistance, susceptibility testing to provide personalized treatment is recommended prior to eradication therapy for... (Review)
Review
In the face of rising prevalence of antibiotic resistance, susceptibility testing to provide personalized treatment is recommended prior to eradication therapy for Helicobacter pylori (H. pylori). Yet, population specific treatment according to the local prevalence of antibiotic resistance may be an alternative if susceptibility testing is not available. In this article, we reviewed the global prevalence of primary antibiotic resistance and the efficacies of commonly used regimens in antibiotic susceptible and resistance strains. We then constructed a model to predict the efficacies of these regimens and proposed an algorithm to choose the optimal first-line and rescue therapies according to the prevalence of antibiotic resistance. Clarithromycin-based therapy (triple, sequential, concomitant, and hybrid therapies) for 14 days remains the treatment of choice in regions with low clarithromycin resistance (≤15%) and bismuth quadruple therapy may be an alternative therapy. In regions with high clarithromycin resistance (> 15%), bismuth quadruple therapy is the treatment of choice and non-bismuth quadruple therapy may be an alternative. Either levofloxacin-based therapy or bismuth quadruple therapy may be used as second-line rescue therapy for patients fail after clarithromycin-based therapies, whereas levofloxacin-based therapy may be used for patients fail after bismuth quadruple therapy. Susceptibility testing or genotypic resistance should be determined after two or more eradication failures. However, empirical therapy according to prior medication history to avoid the empirical reuse of levofloxacin and clarithromycin may be an acceptable alternative after consideration of cost, patient preference, and accessibility. Rifabutin-based therapy for 14 days may serve as the fourth-line therapy. New antibiotics specific for H. pylori are highly anticipated.
Topics: Algorithms; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Resistance, Microbial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Models, Theoretical
PubMed: 30285834
DOI: 10.1186/s12929-018-0471-z -
PloS One 2023Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics...
Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli O157:H7). Results indicated that L. enzymogenes CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to E. coli (O157:H7). The combination of L. enzymogenes CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with L. enzymogenes CFS restored its antibacterial activity against MRSA. The MTT assay revealed that L. enzymogenes CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, L. enzymogenes bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Levofloxacin; Peptide Hydrolases; Cefixime; Escherichia coli; Virulence; Anti-Bacterial Agents; Methicillin; Staphylococcus aureus; Gentamicins; Microbial Sensitivity Tests
PubMed: 36893145
DOI: 10.1371/journal.pone.0282705