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Microbial Pathogenesis Feb 2022The purpose of this article is to study the isolated and combined effect of the peptides Synoeca-MP and IDR-1018 against multi-resistant clinical isolates of K....
The purpose of this article is to study the isolated and combined effect of the peptides Synoeca-MP and IDR-1018 against multi-resistant clinical isolates of K. pneumoniae (Kp2177569 - LACEN) in vitro. The bactericidal activity of the peptide Synoeca-MP in combination with three different classes of commercial antimicrobials and its immunomodulatory potential was also evaluated. Synoeca-MP showed better antimicrobial activity than IDR-1018 and presented synergistic action combined with levofloxacin. Therefore, Synoeca-MP and levofloxacin, and the combination of both, were used in subsequent analyses. In the presence of heat-killed antigens, cellular viability and TNF-α levels was maintained, the production of NO increased and a reduction in IL-10 production was observed. The synergistic antibacterial effect between Synoeca-MP and levofloxacin was effective against multidrug-resistant strains of K. pneumoniae. The association of Synoeca-MP and levofloxacin may present a low modulating action of pro and anti-inflammatory mediators, based on these results.
Topics: Anti-Bacterial Agents; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests
PubMed: 35033636
DOI: 10.1016/j.micpath.2022.105403 -
Microbiology Spectrum Aug 2022Fluoroquinolones have become a popular treatment option for Stenotrophomonas maltophilia infections. Although levofloxacin is most commonly used, delafloxacin...
Fluoroquinolones have become a popular treatment option for Stenotrophomonas maltophilia infections. Although levofloxacin is most commonly used, delafloxacin demonstrates comparable activity when evaluated under standard susceptibility testing conditions at neutral pH. At acidic pH, the activity of the anionic delafloxacin is improved, while the activity of the zwitterionic levofloxacin is reduced. Because the human respiratory tract has a pH of ~6.6 and is the most common site of S. maltophilia infection, it is vital to understand the activity of these agents in this environment. Therefore, levofloxacin and delafloxacin were tested against clinical S. maltophilia isolates via broth microdilution testing ( = 37) and time-kill analysis ( = 5) in neutral cation-adjusted Mueller-Hinton broth (CAMHB) (pH 7.3) and acidic CAMHB (aCAMHB) (pH 6.5). In CAMHB, MIC values were similar between levofloxacin and delafloxacin (8 mg/L versus 8 mg/L). In aCAMHB, levofloxacin MICs did not change, while delafloxacin MICs decreased by a median of 4 log dilutions (MIC values of 8 mg/L versus 0.25 mg/L). In time-kill analyses, levofloxacin and delafloxacin at the maximum drug concentration for the free drug () were bactericidal against 3 and 2 isolates in CAMHB, respectively. In aCAMHB, levofloxacin was not bactericidal against any isolate, while delafloxacin was bactericidal against the same 2 isolates. Relative to CAMHB, levofloxacin activity was reduced by 2.5 log CFU/mL in aCAMHB, whereas delafloxacin activity was increased 2.7 log CFU/mL. Although the bactericidal activity of levofloxacin against S. maltophilia was attenuated in an acidic environment in this study, the increased potency of delafloxacin at pH 6.5 did not translate into improved bactericidal activity in time-kill analyses, compared to pH 7.3. Stenotrophomonas maltophilia most often infects the lungs, where the physiologic environment is naturally slightly acidic (pH ~6.6), compared to most parts of the body (such as the bloodstream), which have neutral pH values (~7.4). Pneumonia due to S. maltophilia is often treated with the antibiotic levofloxacin, despite the activity of levofloxacin being known to be impaired at acidic pH. Unfortunately, currently available methods for susceptibility testing of levofloxacin against S. maltophilia are performed at a neutral pH and therefore may not accurately represent the activity of levofloxacin at the site of infection in the lungs. A similar but newer antibiotic in the same class as levofloxacin, namely, delafloxacin, is not affected by being in an acidic environment and may actually work better at lower pH values. Therefore, the purpose of this study was to investigate whether one drug might be better than the other in this setting by testing each agent's ability to kill S. maltophilia at pH 7.3 and pH 6.5. These findings could then be used to design confirmatory studies that may ultimately impact which drug is given to patients with lung infections due to S. maltophilia.
Topics: Anti-Bacterial Agents; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Hydrogen-Ion Concentration; Levofloxacin; Microbial Sensitivity Tests; Stenotrophomonas maltophilia
PubMed: 35862943
DOI: 10.1128/spectrum.02705-21 -
Antimicrobial Agents and Chemotherapy Apr 2022Pathogenic bacteria experience diverse stresses induced by host cells during infection and have developed intricate systems to trigger appropriate responses. Bacterial...
Pathogenic bacteria experience diverse stresses induced by host cells during infection and have developed intricate systems to trigger appropriate responses. Bacterial stress responses have been reported to defend against these stresses and cross-protect bacteria from antibiotic attack. In this study, we aimed to assess whether oxidative stress affects bacterial susceptibility to fluoroquinolone (FQ) and the underlying mechanism. Stenotrophomonas maltophilia, a species with high genetic diversity, is distributed ubiquitously and is an emerging multidrug-resistant opportunistic pathogen. FQs are among the limited antibiotic treatment options for S. maltophilia infection. The minimum inhibitory concentrations (MICs) of 103 S. maltophilia clinical isolates against ciprofloxacin (CIP) and levofloxacin (LVX) were determined using the agar dilution method in Mueller-Hinton plates with or without menadione (MD), a superoxide generator. The resistance rates for ciprofloxacin and levofloxacin were 40% and 18% in the MD-null group and increased to 91% and 23%, respectively, in the MD-treated group. Of the 103 isolates tested, 54% and 27% had elevated MICs against ciprofloxacin and levofloxacin, respectively, in the presence of MD. The involvement of oxidative stress responses in the MD-mediated FQ resistance was further assessed by mutants construction and viability assay. Among the 16 oxidative stress alleviation systems evaluated, and contributed to MD-mediated FQ resistance. The antibiotic susceptibility test is an accredited clinical method to evaluate bacterial susceptibility to antibiotics in clinical practice. However, oxidative stress-mediated antibiotic resistance was not detected using this test, which may lead to treatment failure.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Oxidative Stress; Stenotrophomonas maltophilia
PubMed: 35285252
DOI: 10.1128/aac.02043-21 -
International Journal of Clinical... May 2021Levofloxacin and ciprofloxacin are more commonly used amongst fluoroquinolone class and the question of cardiac safety and glucose hemostasis of this class has been... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Levofloxacin and ciprofloxacin are more commonly used amongst fluoroquinolone class and the question of cardiac safety and glucose hemostasis of this class has been raised.
OBJECTIVE
To compare intravenous levofloxacin and ciprofloxacin regarding their risk on QTc prolongation and dysglycemia in diabetic and non-diabetic patients.
METHODS
A randomised prospective study at Beni-Suef university hospital was conducted on 200 adult patients over 6 months. The patients received intravenous levofloxacin 750mg once daily or ciprofloxacin 400mg twice daily. Electrocardiogram and fasting blood glucose were obtained from each patient before starting the antibiotic, 24 hours, 72 hours after the first dose, and 72 hours after antibiotics cessation.
RESULTS
The results of the current study showed the relative risk for QTc prolongation with levofloxacin was more than ciprofloxacin by about 4 and 1.5 times in diabetic and non-diabetic patients, respectively. The relative risk for dysglycemia with levofloxacin was 2.28 and 1.39 times more than ciprofloxacin in diabetic and non-diabetic patients, respectively.
CONCLUSION
The present study showed that the risk for QTc prolongation and hyperglycemia was greater with levofloxacin than ciprofloxacin in diabetic and non-diabetic patients. In addition, the risk for hypoglycemia was greater with levofloxacin than ciprofloxacin in non-diabetic patients.
Topics: Adult; Ciprofloxacin; Diabetes Mellitus; Fluoroquinolones; Humans; Levofloxacin; Prospective Studies
PubMed: 33559294
DOI: 10.1111/ijcp.14072 -
American Journal of Therapeutics 2015Drug-induced hepatotoxicity is a major cause of hepatocellular injury in patients admitting to emergency services with acute liver failure. Hepatic necrosis may be at...
Drug-induced hepatotoxicity is a major cause of hepatocellular injury in patients admitting to emergency services with acute liver failure. Hepatic necrosis may be at varying degrees from mild elevations in transaminases to fulminant hepatitis, and even death. The case of a 53-year-old female patient with toxic hepatitis due to levofloxacin and multiple organ failure secondary to toxic hepatitis is presented. Patient suffered itching, redness, and rash after receiving a single dose of 750 mg of levofloxacin tablets for pulmonary infection 10 days ago. Skin lesions had regressed within 3 days, but desquamation formed all over the body. After the fifth day of drug intake, complaints of abdominal pain, vomiting, and yellowing in skin color had started. The patient was referred to our emergency department with these complaints 10 days after drug intake. Patient was thought as a candidate for liver transplant, but cardiopulmonary arrest occurred, and the patient died before she could be referred to a transplant center. This case is important because hepatotoxicity and death due to levofloxacin is uncommon in the literature.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Fatal Outcome; Female; Humans; Levofloxacin; Middle Aged
PubMed: 24067876
DOI: 10.1097/MJT.0b013e3182a44055 -
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 -
Journal of Clinical Pharmacy and... Jun 2021In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in...
WHAT IS KNOWN AND OBJECTIVE
In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in carrying out the diagnosis and treatment of refractory Mycoplasma pneumoniae pneumonia in children. Levofloxacin is suitable for treating infectious diseases in various systems but limited in children due to arthropathy issues in weight-bearing joints. This study aimed to evaluate the efficacy and safety of levofloxacin in children with macrolide-resistant Mycoplasma pneumoniae pneumonia.
METHODS
We retrospectively enrolled six confirmed cases of refractory Mycoplasma pneumoniae pneumonia who were admitted in the paediatric respiratory ward of Shandong provincial hospital Affiliated to Shandong first Medical University between 1st January 2020 and 29th February 2020. Levofloxacin was given to the patients through the intravenous or oral route as per the following dosages :<5 years, 8-10 mg/kg q12 h; >5 years, 8-10 mg/kg, qd for 10 days. The clinical data were collected and analysed.
RESULTS AND DISCUSSION
The average age of the enrolled cases was six years and nine months (range, four years, and seven months to eleven years and seven months). All cases were found to be drug-resistant and were treated with azithromycin combined with antibacterial drugs. Levofloxacin was used in the patient's refractory to macrolide antibiotics. The temperature of five cases returned to normal 1-2 days after treatment with levofloxacin, and the imaging of the four cases showed expected improvements. The gastrointestinal symptoms, neurological manifestations, joint symptoms, blood parameters, liver and kidney functions, and exercise conditions of the children were closely monitored. The follow-up time of the patients ranged from one week to five months. No drug-related adverse reactions were observed in patients during treatment or during follow-up.
WHAT IS NEW AND CONCLUSION
The clinical symptoms and imaging significantly improved after treatment with levofloxacin, and no drug-related adverse reactions were observed. Levofloxacin proved to be an effective and safe drug in the treatment of children with macrolide-resistant mycoplasma pneumonia. This study will provide a reference for evaluating the efficacy and safety of levofloxacin in the paediatric population.
Topics: Anti-Bacterial Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Female; Humans; Levofloxacin; Macrolides; Male; Pneumonia, Mycoplasma; Retrospective Studies
PubMed: 33403672
DOI: 10.1111/jcpt.13331 -
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 -
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 Materials Chemistry. B Sep 2023Carbon dot (CD)-based nanozymes have great potential in antibacterial applications. In order to achieve enhanced broad-spectrum antibacterial capacity, we synthesized...
Carbon dot (CD)-based nanozymes have great potential in antibacterial applications. In order to achieve enhanced broad-spectrum antibacterial capacity, we synthesized Co-doped drug-based CDs (Co-Lvx-CDs) using levofloxacin and vitamin B12 as precursors by mimicking the catalysis of antibacterial activity of natural enzymes. The Co-Lvx-CDs retained not only the effective functional groups of the traditional antibiotic levofloxacin but also achieved oxidase-like and peroxidase-like activities to generate reactive oxygen species (ROS) through Co doping. Additionally, the Co-Lvx-CDs had superb fluorescence properties and could be applied in information encryption. The CDs were validated to have a broad-spectrum bactericidal effect against Gram-positive and -negative bacteria, compensating for the limitations of levofloxacin while also having enhanced sterilization ability. Importantly, the proposed Co-Lvx-CDs provide a new idea for the design of multifunctional CD-based nanozymes with preconceived outcomes.
Topics: Levofloxacin; Carbon; Anti-Bacterial Agents; Catalysis
PubMed: 37545365
DOI: 10.1039/d3tb01376f