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Biology of Blood and Marrow... Apr 2020Antibiotic-induced gut dysbiosis has been associated with poor outcomes after intensive therapy. We evaluated the effect of levofloxacin (LEVO), the most commonly used...
Antibiotic-induced gut dysbiosis has been associated with poor outcomes after intensive therapy. We evaluated the effect of levofloxacin (LEVO), the most commonly used prophylactic antibacterial antibiotic during intensive chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT), on the gut microbiota in 2 cohorts of patients, 1 cohort comprising 20 patients with acute leukemia receiving intensive chemotherapy and the other cohort comprising 20 allo-HCT recipients. 16S rRNA gene sequencing of thrice-weekly collected stool samples permitted a comparison between intervals with no antibacterial antibiotic exposure and those with only LEVO exposure. In mixed-effects modeling, the only variables influenced by LEVO were the relative abundances of Parabacteroides (regression coefficient, -.063; 99% confidence interval [CI], -.102 to -.024) and Blautia (regression coefficient, .050; 99% CI, .004 to .095). Other taxa and microbiota diversity were unaffected. Overall, the effect of LEVO on the gut microbiota in these cohorts was mild.
Topics: Dysbiosis; Gastrointestinal Microbiome; Hematopoietic Stem Cell Transplantation; Humans; Levofloxacin; RNA, Ribosomal, 16S
PubMed: 31870930
DOI: 10.1016/j.bbmt.2019.12.722 -
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 -
Antimicrobial Agents and Chemotherapy Jul 2022Fluoroquinolones are potentially effective against Elizabethkingia anophelis. We investigated the MIC, mutant prevention concentration (MPC), and target gene mutations...
Fluoroquinolones are potentially effective against Elizabethkingia anophelis. We investigated the MIC, mutant prevention concentration (MPC), and target gene mutations of fluoroquinolones in . Eighty-five s isolates were collected from five hospitals in Taiwan. The MIC and MPC of ciprofloxacin and levofloxacin were examined for all s except 17 isolates, in which ciprofloxacin MPC could not be determined due to drug precipitation caused by overly high drug concentration. Mutations in the quinolone resistance-determining regions of DNA gyrase (GyrA and GyrB) and topoisomerase IV (ParC and ParE) in the clinical isolates and fluoroquinolone-selected mutants were examined. Overall, 23.5% and 71.8% of the isolates tested were susceptible to ciprofloxacin and levofloxacin, respectively. The MPC of ciprofloxacin was 128 mg/L, and the MPC of levofloxacin was 51.2 mg/L. The MPC/MIC ratio for ciprofloxacin was 64, whereas that for levofloxacin was 25.6. The coefficient of determination between the MPC and MIC for ciprofloxacin and levofloxacin was 0.72 and 0.56, respectively, in the linear regression analysis. Preexisting mutations in GyrA (S83I, S83R, and D87Y) were identified in 18 clinical isolates, all of which were resistant to both ciprofloxacin and levofloxacin. Additional amino acid substitutions in GyrA were identified in all ciprofloxacin- and levofloxacin-selected mutants. Furthermore, GyrB alterations (D431N or D431H) were found in nine levofloxacin-treated isolates. Given that maintaining the serum concentrations of fluoroquinolones above MPCs is impossible under presently recommended doses, the selection of mutant strains seems inevitable.
Topics: Anti-Bacterial Agents; Ciprofloxacin; DNA Gyrase; DNA Topoisomerase IV; Drug Resistance, Bacterial; Flavobacteriaceae; Fluoroquinolones; Levofloxacin; Microbial Sensitivity Tests; Mutation
PubMed: 35708332
DOI: 10.1128/aac.00301-22 -
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 -
The American Journal of Tropical... Oct 2022Snakebite is a common occurrence in Hangzhou, and identifying bacteria in wounds is very important for snakebite treatment. To define the pattern of wound bacterial... (Review)
Review
Snakebite is a common occurrence in Hangzhou, and identifying bacteria in wounds is very important for snakebite treatment. To define the pattern of wound bacterial flora of venomous snakebites and their susceptibility to common antibiotics, we reviewed the medical charts of patients admitted with snakebite at Hangzhou TCM Hospital from January 2019 to December 2020. A total of 311 patients were enrolled in this study. Among them, bacteria culture was positive in 40 patients, and 80 organisms were isolated. The most frequent pathogens were Morganella morganii and Staphylococcus aureus. According to the results of susceptibility testing, a majority of the isolates were resistant to some common first-line antibiotics, such as ampicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, cefoxitin, and cephazolin. Quinolones, however, have shown a better antibacterial effect. In conclusion, snakebite wounds involve a wide range of bacteria. Fluoroquinolones, such as levofloxacin and ciprofloxacin, could be an alternative for empirical treatment in patients with snakebite when the effect of other antibiotics is poor.
Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; Bacteria; Cefazolin; Cefoxitin; Ciprofloxacin; Clavulanic Acid; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Snake Bites; Sulbactam; Venoms
PubMed: 36067984
DOI: 10.4269/ajtmh.21-1314 -
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 -
Transplantation and Cellular Therapy Mar 2022Levofloxacin has been widely used for bacteremia prophylaxis in the pre-engraftment setting for patients undergoing hematopoietic stem cell transplantation (HSCT), but...
Levofloxacin has been widely used for bacteremia prophylaxis in the pre-engraftment setting for patients undergoing hematopoietic stem cell transplantation (HSCT), but data supporting this practice are inconsistent. In addition to concern for lack of benefit, there are also concerns that this practice could increase the rates of Clostridioides difficile (C diff) infections, the incidence of multidrug-resistant organisms (MDRO) or lead to increased incidence of acute graft-versus-host disease (aGVHD) by disrupting the gut microbiome. This study aimed to assess the safety and efficacy of levofloxacin as bacterial prophylaxis in pediatric and young adult patients undergoing allogeneic or autologous HSCT at a single pediatric center. We conducted a retrospective chart review evaluating patients age ≥6 months who underwent HSCT at our center between January 1, 2016, and July 31, 2020. Patients who underwent transplantation before March 2018 did not receive levofloxacin prophylaxis, whereas those who underwent transplantation after April 2018 did receive levofloxacin prophylaxis. Each transplantation was included as a separate episode if the patient underwent more than 1 transplantation during the inclusion time. The primary outcome of this study was the proportion of patients who experienced at least 1 bacterial bloodstream infection (BSI) in the first 100 days post-transplantation. Secondary outcomes included the number of non-levofloxacin antibiotic days post-transplantation, the incidence of aGVHD, the occurrence of C diff infections, and development of MDRO. A total of 370 HSCT recipients with a median age of 6.7 years (range, 0.5 to 39 years) were included in this study. Seventy-two patients had undergone more than 1 transplantation, and thus we had 443 transplantations to observe. Of these, 216 did not include levofloxacin prophylaxis and 227 included levofloxacin prophylaxis. There were no differences in baseline characteristics between the 2 groups except for age; patients in the non-levofloxacin prophylaxis group were younger (8.1 years vs 9.6 years; P = .05). There were no between-group differences in rates of death at 100 days, antibiotic use, fungal infections, or MDRO infections. Patients in the non-prophylaxis group developed more bacterial BSI in the first 100 days post-HSCT (27% versus 17%; P = .004) and more C diff infections (20% versus 9%; P = .003) than patients who received levofloxacin prophylaxis. In addition, more aGVHD was seen in the patients without levofloxacin prophylaxis (P = .014). Levofloxacin prophylaxis given from day -2 of HSCT through engraftment was significantly associated with decreased bacterial BSI in the first 100 days post-transplantation and was not associated with increased risks of C diff, aGVHD, or MDRO. Our study supports the use of levofloxacin prophylaxis in the peritransplantation period. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Child; Child, Preschool; Clostridium Infections; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infant; Levofloxacin; Retrospective Studies; Young Adult
PubMed: 34875405
DOI: 10.1016/j.jtct.2021.11.017 -
PloS One 2023Helicobacter pylori treatment failure remains a challenging problem. This study aimed to identify predictive factors for successful eradication in patients following... (Clinical Trial)
Clinical Trial
BACKGROUND
Helicobacter pylori treatment failure remains a challenging problem. This study aimed to identify predictive factors for successful eradication in patients following treatment failures.
METHODS
This was a retrospective cohort study. This study included 1,050 dyspeptic patients diagnosed with H. pylori infection at tertiary care center in Thailand between March 2014 and October 2021. Patients' demographic data, endoscopic findings, H. pylori culture, antimicrobial susceptibility testing (AST), treatment regimens and outcomes were analysed.
RESULTS
Of 1,050 patients with H. pylori infections, 302 (28.7%) experienced treatment failure (mean age 58.4 years; 44.7% males). AST was performed in 192. Resistance was observed for metronidazole (43.2%), levofloxacin (33.9%), clarithromycin (24%), and amoxicillin (2.1%). There was no tetracycline resistance. Multidrug-resistance (MDR) was significantly more common following treatment failure (45.5% vs. 15.7%, p<0.001). Baseline characteristics were similar between treatment successes and failures. Eradication rates after first-line and second-line regimens were 71.2% and 54.5%, respectively. Medication nonadherence [OR 36.6 (95%CI 8.65-155.03, p<0.001)] and MDR [OR 4.49 (95%CI 2.29-8.81, p<0.001)] were associated with treatment failure. Over time, resistance increased for metronidazole, levofloxacin, and clarithromycin, while eradication rates with triple therapy declined. Tailored antibiotic therapy [OR 4.92 (95%CI 1.61-14.99, p = 0.005)] and a regimen including 4-times-daily dosing of amoxicillin (2 grams/day) [OR 3.05 (95%CI 1.10-8.41, p = 0.032)] were significantly associated with treatment success after first-line failure. Eradication rates when using tailored therapy and 4-times-daily dosing of amoxicillin (2 grams/day) were 91.1% and 89.4%, respectively. Performing AST before first-line therapy resulted in the highest cure rates. AST performed after multiple treatment failures was also associated with higher eradication rates compared with the group without AST (94.4% vs. 50%,p = 0.008).
CONCLUSIONS
AST either before or after treatment failure correlated with a higher proportion of successful eradication. Nonadherence and the MDR infections predicted treatment failure. Tailored therapy and 4-times-daily dosing of amoxicillin after treatment failure were likely to be successful.
Topics: Female; Humans; Male; Middle Aged; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Levofloxacin; Metronidazole; Retrospective Studies; Treatment Failure
PubMed: 38033026
DOI: 10.1371/journal.pone.0294403 -
BMJ Case Reports Jul 2019
Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Coitus; Conjunctivitis, Bacterial; Gonorrhea; Humans; Levofloxacin; Male; Neisseria gonorrhoeae; Orbital Cellulitis; Photophobia; Treatment Outcome
PubMed: 31340941
DOI: 10.1136/bcr-2018-227787