Risks associated with the therapeutic use of fluoroquinolones

Stahlmann, Ralf; Lode, H.

doi:10.1517/14740338.2013.796362

Cited by 116 publications

(85 citation statements)

References 53 publications

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“…When considering broadening the therapeutic use of FQs beyond use as anti-microbials, it is important to bear in mind that these drugs can have significant toxic side effects and their application is restricted in certain groups, particularly children [69,70]; also, the dangers of promoting microbial resistance through wider use must be considered [71]. Thus, generating modified derivatives, or finding structurally-related alternatives to FQs that have reduced toxicity and anti-microbial activity but show enhanced anti-inflammatory activity, could provide a valuable source of novel anti-inflammatory agents.…”

Section: Discussionmentioning

confidence: 99%

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Todd

Negm

Reps

et al. 2017

Pharmacological Research

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2Abbreviations: BCA, bicinchoninic acid; CV, coefficient of variation; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBMCs, peripheral blood mononuclear cells; RPPA, reverse phase protein array; SSMD, strictly standardised mean difference; TNFR1, tumour necrosis factor receptor-1; TRAPS, TNF receptor associated periodic syndrome; WT, wild type. 3ABSTRACT: TNF Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disease caused by mutations in TNF Receptor 1 (TNFR1). Current therapies for TRAPS are limited and do not target the pro-inflammatory signalling pathways that are central to the disease mechanism. Our aim was to identify drugs for repurposing as anti-inflammatories based on their ability to down-regulate molecules associated with inflammatory signalling pathways that are activated in TRAPS. This was achieved using rigorously optimised, high through-put cell culture and reverse phase protein microarray systems to screen compounds for their effects on the TRAPS-associated inflammatory signalome. 1360 approved, publically available, pharmacologically active substances were investigated for their effects on 40 signalling molecules associated with pro-inflammatory signalling pathways that are constitutively upregulated in TRAPS. The drugs were screened at four ten-fold concentrations on cell lines expressing both wild-type (WT) TNFR1 and TRAPS-associated C33Y mutant TNFR1, or WT TNFR1 alone; signalling molecule levels were then determined in cell lysates by the reversephase protein microarray. A novel mathematical methodology was developed to rank the compounds for their ability to reduce the expression of signalling molecules in the C33Y-TNFR1 transfectants towards the level seen in the WT-TNFR1 transfectants. Seven high-ranking drugs were selected and tested by RPPA for effects on the same 40 signalling molecules in lysates of peripheral blood mononuclear cells (PBMCs) from C33Y-TRAPS patients compared to PBMCs from normal controls. The fluoroquinolone antibiotic lomefloxacin, as well as others from this class of compounds, showed the most significant effects on multiple pro-inflammatory signalling pathways that are constitutively activated in TRAPS; lomefloxacin dose-dependently significantly reduced expression of 7/40 signalling molecules across the Jak/Stat, MAPK, NF-kB and PI3K/AKT pathways. This study demonstrates the power of signalome screening for identifying candidates for drug repurposing.

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Section: Discussionmentioning

confidence: 99%

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Todd

Negm

Reps

et al. 2017

Pharmacological Research

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“…Still penicillins are among the safest drugs.. However neurotoxic, nephrotoxic, cation toxicity (hypokalemia) is likely to occur among susceptible patients (1,13,14,25) .…”

Section: Side-effectsmentioning

confidence: 99%

“…There is some disagreement in the medical literature regarding whether and to what extent levofloxacin and other fluoroquinolones produce serious adverse effects more frequently than other broad spectrum antibacterial drugs (12,13,14) .…”

Section: Introductionmentioning

confidence: 99%

Amoxicillin vs Levofloxacin in Treatment of Chronic Periodontitis: Review

Ali¹,

Zeiny²

2016

Iraqi dent. j.

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Background: Antibiotics Resistance can be the main problem faced by the specialists in the medical fields. The main reason of such resistance is the improper prescribing of antibiotics. In dentistry this problem must be in concern for 2 reasons, first, limited and outdated knowledge of many dentist in Iraq with recent modalities in the field of therapeutics, so they keep prescribing penicillins, for every odontogenic infection (rationale prescribing), second, the patient who keeps prescribing the same drug for himself every time (i.e. dealing with antibiotic as over-the-counter drug). Aim of the study: This review will clarifies the use of amoxicillin (most prescribed drug in Iraqi dental clinics) vs the use of third generation quinolones (levofloxacin) in an important field of dental practice which is periodontology, with focusing on levofloxacin as it took a privileged position in medical researches. Conclusion: levofloxacin was superior to amoxicillin since it is applied once daily, few nonhazardous side effects, nearly 100 % bioavailability in spite of different rout of administration, and can be applied topically as gels and intra-pocket films. Perhaps this can change a lot among practitioners' and non-practitioners' prescribing (habits).

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“…ADRs frequently involve the gastro-intestinal tract (GIT), musculoskeletal system, central nervous system (CNS), dermatological and the hepatic systems. 3,4 Rare and potentially fatal side effects, however, have resulted in the withdrawal from the U.S. market of lomefloxacin, sparfloxacin (phototoxicity, QTc prolongation), gatifloxacin, temafloxacin, trovafloxacin (hepatotoxicity), grepafloxacin (cardiotoxicity), and clinafloxacin (phototoxicity). In all these cases, the side effects were detected by post marketing surveillance.…”

Section: Introductionmentioning

confidence: 99%

Monitoring, evaluation and comparison of adverse effect profile of ciprofloxacin and ofloxacin in acute bacterial exacerbation of chronic bronchitis patients attending pulmonology department of tertiary care teaching hospital: a prospective observational study

Kurli

2018

Int J Basic Clin Pharmacol

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Background: In 2016, FDA recommended that "serious side effects associated with flouroquinolones generally outweigh the benefits for the patients with acute sinusitis, acute bronchitis and uncomplicated UTI". Throughout India the most commonly used flouroquinolones for above conditions are Ciprofloxacin, Ofloxacin, and Levofloxacin. In this scenario, the present study was undertaken to monitor, evaluate and compare the adverse effect profile of Ciprofloxacin and Ofloxacin in acute exacerbation of chronic bronchitis patients. Methods: Prospective, observational study done in 200 patients of tertiary care teaching hospital. The patients diagnosed with, acute bronchitis treated with Ciprofloxacin 500mg BD or Ofloxacin 400mg BD for 7 days were included in the study. The study duration was 6 months. ADR causality assessment was done with Naranjo algorithm. Statistical test applied was chi-square test. Results: 63 ADR were reported in Ofloxacin group and 19 ADR in Ciprofloxacin group. Insomnia was most frequent ADR (40%) in patients treated with Ofloxacin. There is high incidence of ADRs in ofloxacin group. chi square test showed this difference is statistically significant (p<0.05). Insomnia was significantly higher in ofloxacin group (p<0.05). Conclusions: In India frequently used and misused antimicrobials are fluoroquinolones. The present study concluded that no serious ADRs but ofloxacin group of patients have shown increased incidence of ADRs associated with CNS especially Insomnia. However, further large scale, multi-centric studies are needed to confirm these results.

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Risks associated with the therapeutic use of fluoroquinolones

Abstract: Changes in the resistance situation and newly recognized adverse reactions require a continuing adjustment of therapeutic recommendations and constant educational efforts in the field of antimicrobial therapy.

Cited by 116 publications

References 53 publications

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Amoxicillin vs Levofloxacin in Treatment of Chronic Periodontitis: Review

Monitoring, evaluation and comparison of adverse effect profile of ciprofloxacin and ofloxacin in acute bacterial exacerbation of chronic bronchitis patients attending pulmonology department of tertiary care teaching hospital: a prospective observational study

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