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Journal of Global Antimicrobial... Mar 2024Mycoplasma and Ureaplasma spp. especially M. hominis, U. parvum, and U. urealyticum recognized as an important cause of urogenital infections. Sake of the presence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mycoplasma and Ureaplasma spp. especially M. hominis, U. parvum, and U. urealyticum recognized as an important cause of urogenital infections. Sake of the presence of antibiotic resistance and a continuous rise in resistance, the treatment options are limited, and treatment has become more challenging and costlier.
OBJECTIVES
Therefore, this meta-analysis aimed to estimate worldwide resistance rates of genital Mycoplasmas and Ureaplasma to fluoroquinolones (ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin) agents.
METHODS
We searched the relevant published studies in PubMed, Scopus, and Embase from until 3, March 2022. All statistical analyses were carried out using the statistical package R.
RESULTS
The 30 studies included in the analysis were performed in 16 countries. In the metadata, the proportions of ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 59.8% (95% CI 49.6, 69.1), 31.2% (95% CI 23, 40), 7.3% (95% CI 1, 31), and 5.3% (95% CI 1, 2), respectively. According to the meta-regression, the ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin rate increased over time. There was a statistically significant difference in the fluoroquinolones resistance rates between different continents/countries (P < 0.05).
CONCLUSIONS
Based on the results obtained in this systematic review and meta-analysis we recommend the use of the newer group of fluoroquinolones especially levofloxacin as the first choice for the treatment of genital mycoplasmosis, as well as ofloxacin for the treatment of genital infections caused by U. parvum.
Topics: Humans; Ureaplasma; Mycoplasma; Fluoroquinolones; Levofloxacin; Ureaplasma urealyticum; Moxifloxacin; Mycoplasma hominis; Microbial Sensitivity Tests; Ureaplasma Infections; Urinary Tract Infections; Ciprofloxacin
PubMed: 38016593
DOI: 10.1016/j.jgar.2023.11.007 -
World Journal of Gastroenterology Feb 2014Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly... (Review)
Review
Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and third-line treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.
Topics: Anti-Bacterial Agents; Bismuth; Drug Resistance, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Moxifloxacin; Ofloxacin; Rifabutin; Rifamycins; Rifaximin; Salvage Therapy; Virulence Factors
PubMed: 24587627
DOI: 10.3748/wjg.v20.i6.1517 -
Antimicrobial Agents and Chemotherapy Dec 1994The pharmacodynamic properties of levofloxacin (an optically active isomer of ofloxacin), ofloxacin, and ciprofloxacin, alone and in combination with rifampin, were...
Pharmacodynamics of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with rifampin, against methicillin-susceptible and -resistant Staphylococcus aureus in an in vitro infection model.
The pharmacodynamic properties of levofloxacin (an optically active isomer of ofloxacin), ofloxacin, and ciprofloxacin, alone and in combination with rifampin, were evaluated over 24 to 48 h against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA 1199 and MRSA 494, respectively) in an in vitro infection model. The incidence of the emergence of resistance among the test strains was also determined. The fluoroquinolones were administered to simulate dosage regimens of 200 mg, 400 mg given intravenously (i.v.) every 12 h (q12h), and 400 and 800 mg given i.v. q24h. Rifampin was dosed at 600 mg i.v. q24h. Although the MICs and MBCs of the quinolones were similar (< or = 0.49 microgram/ml), levofloxacin was the most potent agent in time-kill studies on the basis of the time required to achieve a 99.9% reduction in the number of log10 CFU per milliliter (e.g., with the regimen of levofloxacin [400 mg q24h, 6.5 h] versus ofloxacin [12.5 h], P < 0.024, and levofloxacin versus ciprofloxacin [6.5 versus 9.0 h], P < 0.0017) against MSSA 1199. The killing activity of levofloxacin was similar to that of ofloxacin against MRSA 494 (time to achieve a 99.9% reduction in the number of log10 CFU per milliliter, 11.1 versus 13.8 h, respectively). Levofloxacin and ofloxacin dosed once daily demonstrated greater bactericidal activity than when they were dosed twice daily against MSSA 1199. Resistance to levofloxacin or ofloxacin was not observed with any dosage regimen. Furthermore, resistance to ofloxacin was not detected when the half-life was reduced from 6 to 3 h. Regrowth and stable resistance (65-fold increase in the MIC for MSSA 1199; 16-fold increase in the MIC for MRSA 494) were noted within 24 h of exposure to ciprofloxacin at 200 mg q12h. Combination therapy with rifampin prevented the emergence of resistance to ciprofloxacin. Neither DNA gyrase alteration nor an energy-dependent efflux process mediated by the norA gene appeared to be responsible for the resistance observed. Our data suggest that with levofloxacin there is a more rapid onset of bactericidal activity than with ofloxacin or ciprofloxacin against MSSA 1199 and that the activity of levofloxacin is similar to that of ofloxacin but better than that of ciprofloxacin against MRSA 494. Resistance was noted only after exposure to the low dose of ciprofloxacin. Resistance to ofloxacin did not develop even when the pharmacokinetics of the drug were set to equal those of ciprofloxacin, suggesting that ofloxacin differs from ciprofloxacin irrespective of time of exposure. The resistance to ciprofloxacin that developed in our vitro model may be mediated by the cfx-ofx locus, which has been shown to be associated with low-level fluoroquinolone resistance. Overall, levofloxacin demonstrated potent bactericidal activity against S. aureus, without the emergence of resistance in our infection model. Quinolones dosed once daily were more effective than equivalent dosages administered twice daily. The addition of rifampin was not synergistic but prevented the emergence of ciprofloxacin resistance.
Topics: Ciprofloxacin; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Levofloxacin; Methicillin Resistance; Microbial Sensitivity Tests; Ofloxacin; Rifampin; Staphylococcus aureus; Stereoisomerism
PubMed: 7695250
DOI: 10.1128/AAC.38.12.2702 -
Antimicrobial Agents and Chemotherapy May 2014Limited data on fluoroquinolone pharmacokinetics and cardiac effects in children exist. Among 22 children receiving drug-resistant tuberculosis prophylaxis or treatment,...
Limited data on fluoroquinolone pharmacokinetics and cardiac effects in children exist. Among 22 children receiving drug-resistant tuberculosis prophylaxis or treatment, serum concentrations following oral doses of levofloxacin (15 mg/kg of body weight) and ofloxacin (20 mg/kg) were lower than those expected from existing pediatric data, possibly due to differences in the formulations (crushed tablets). Drug exposures were lower than those in adults following standard doses and below the proposed pharmacodynamic targets, likely due to more rapid elimination in children. No QT prolongation was observed.
Topics: Adolescent; Antitubercular Agents; Child; Child, Preschool; Female; Humans; Infant; Levofloxacin; Male; Ofloxacin; Prospective Studies; Tuberculosis, Multidrug-Resistant
PubMed: 24550337
DOI: 10.1128/AAC.02755-13 -
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 -
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 -
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 -
Minerva Urology and Nephrology Jun 2023On March 11 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on... (Review)
Review
BACKGROUND
On March 11 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on musculoskeletal and nervous system, with quinolone (QN) and fluoroquinolone (FQ) antibiotics. Aim of this study was to evaluate the effect of the EMA warning on the rate of AEs after QN and FQ treatments, reported in the EudraVigilance (EV) database.
METHODS
EV database is the system for managing and analyzing information on suspected AEs to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We retrospectively explored the effect of FQs and QNs on musculoskeletal and nervous system from the EMA warning up to now (21 months) and compared these results with the 21 months before the EMA warning.
RESULTS
Main part of AEs in EV database were reported for ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin. Ciprofloxacin total AEs before 21 months till 12 months of EMA warning were 2763. 12 months before EMA Warning they were 2935. Twelve months after EMA Warning they were 3419. Between 12 months till 21 months they were 3174. Musculoskeletal disorders were respectively 574 (21% of the total) 21 months before, 558 (19%) 12 months before, 1048 (31%) after 12 months, 540 (17%) after 21 months of EMA Warning. Nervous system disorders were respectively 606 (22% of the total) 21 months before, 517 (18%) 12 months before, 680 (20%) after 12 months, 560 (18%) after 21 months of EMA Warning (respectively OR 1,16 95%CI 1,10 -1,22, P 0,12 ; OR 0,76 95%CI 0,69-0,83, P 0,27 ; OR 1,01 95%CI 0,96-1,06 P 0,05).
CONCLUSIONS
Our analysis clearly showed no significant differences before and after EMA warning, opening new insights in the role of the EMA warning in clinical practice.
Topics: Fluoroquinolones; Quinolones; Retrospective Studies; Ciprofloxacin; Levofloxacin
PubMed: 36940165
DOI: 10.23736/S2724-6051.23.05169-8 -
Antimicrobial Agents and Chemotherapy May 1997A total of 101 Acinetobacter genospecies (77 Acinetobacter baumannii strains and 24 non-A. baumannii strains) were tested for their susceptibilities to levofloxacin,... (Comparative Study)
Comparative Study
Activities of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with amikacin, against acinetobacters as determined by checkerboard and time-kill studies.
A total of 101 Acinetobacter genospecies (77 Acinetobacter baumannii strains and 24 non-A. baumannii strains) were tested for their susceptibilities to levofloxacin, ofloxacin, and ciprofloxacin and for synergy between the quinolones and amikacin by checkerboard titration and time-kill analyses. The MICs at which 50% of the isolates are inhibited (MIC50)/MIC90s for the 101 strains were as follows (in micrograms per milliliter): levofloxacin, 0.25/16.0; ofloxacin, 0.5/32.0; ciprofloxacin, 0.25/> 64.0; and amikacin, 1.0/> 32.0. At empiric breakpoints of < or = 2.0 microg/ml, 61% of the strains were susceptible to all three quinolones. At a breakpoint of < or = 16.0 microg/ml, 84% of the strains were susceptible to amikacin. Checkerboard titrations yielded synergistic fractional inhibitory concentration (FIC) indices (< or = 0.5) for one strain with levofloxacin and amikacin and for two strains with ofloxacin and amikacin. Indices of > 0.5 to 1.0 were seen for 57, 54, and 55 strains with levofloxacin plus amikacin, ofloxacin plus amikacin, and ciprofloxacin plus amikacin, respectively, and indices of > 1.0 in 43, 45, and 46 strains, respectively, were found with the above three combinations. No strains yielded antagonistic FIC indices (> 4.0). Most FIC results of > 1.0 occurred in strains for which the quinolone MICs were > 2.0 microg/ml and for which the amikacin MICs were > or = 32.0 microg/ml. By contrast, synergy (defined as > or = 2 log10 decrease compared to the more active compound alone by time-kill analysis) was found in all seven strains tested for which the quinolone MICs were < or = 2.0 microg/ml. For eight other strains for which the quinolone MICs were > 2.0 microg/ml as determined by time-kill analysis, quinolone and amikacin concentrations in combination were usually too high to permit clinical use. Time-kill analysis was found to be more sensitive in detecting synergy than was the checkerboard method.
Topics: Acinetobacter; Amikacin; Anti-Infective Agents; Ciprofloxacin; Drug Combinations; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin
PubMed: 9145872
DOI: 10.1128/AAC.41.5.1073 -
The Cochrane Database of Systematic... Jul 2006Uncomplicated acute cystitis is one of the most common bacterial infections in adults. The percentage of women who have at least one episode of acute cystitis is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uncomplicated acute cystitis is one of the most common bacterial infections in adults. The percentage of women who have at least one episode of acute cystitis is estimated to be between 40% to 50%. Quinolones are recommended for acute cystitis in regions where the level of resistance to other antimicrobials namely co-trimoxazole is high. However the efficacy, safety and tolerance of quinolones needs investigation.
OBJECTIVES
To compare the efficacy, safety and tolerance of different quinolones in women with uncomplicated acute cystitis.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library Issue 3, 2003), MEDLINE (1966 - September 2003), EMBASE (1988 - September 2003), reference lists of articles and abstracts from conference proceedings without language restriction. Reference lists of urology, infectious diseases and nephrology textbooks, review articles and relevant studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing two or more different quinolones in women (>/= 16 years) with uncomplicated acute cystitis were selected.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI).
MAIN RESULTS
We identified 11 studies enrolling 7535 women. There were no significant differences in clinical or microbiological efficacy between quinolones. Photosensitivity reactions were more frequently observed for sparfloxacin when compared to ofloxacin. Any adverse event, adverse events causing withdrawal, skin adverse events, photosensitivity reactions were more common for lomefloxacin when compared to norfloxacin. Any adverse event, adverse drug reactions, CNS adverse events were more common for ofloxacin when compared to ciprofloxacin. CNS adverse events and insomnia were more often reported for rufloxacin when compared to pefloxacin. Adverse drug reactions occurred frequently for ofloxacin than levofloxacin. Insomnia was reported more frequently for enoxacin than ciprofloxacin.
AUTHORS' CONCLUSIONS
We found no significant differences in clinical or microbiological efficacy between quinolones but some differences in occurrence and spectrum of quinolone safety.
Topics: Acute Disease; Adult; Anti-Infective Agents, Urinary; Ciprofloxacin; Cystitis; Female; Fluoroquinolones; Humans; Levofloxacin; Norfloxacin; Ofloxacin; Pefloxacin; Quinolones; Randomized Controlled Trials as Topic
PubMed: 16856014
DOI: 10.1002/14651858.CD003597.pub2