Studies on Articular and General Toxicity of Orally Administered Ozenoxacin in Juvenile Rats and Dogs

Borroto, Jorge I. González; Awori, Malaika; Chouinard, Luc; Smith, Susan Y.; Tarragó, Cristina; Blazquez, Teresa; Gargallo-Viola, Domingo; Zsolt, Ilonka

doi:10.2217/fmb-2017-0291

Cited by 13 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ozenoxacin lacks a fluorine atom and have fewer side effects than other fluoroquinolones ( 33 ). Ofloxacin produced typical quinolone-induced lesions in the articular cartilage of three of 10 juvenile rats, while chondrotoxicity was unassociated with ozenoxacin ( 34 ). Oral administration of ozenoxacin in juvenile dogs demonstrated no chondrotoxicity or toxicologically in select target organs.…”

Section: Discussionmentioning

confidence: 98%

Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS)

Kong

Mao²,

Zhang³

et al. 2023

Front. Pediatr.

View full text Add to dashboard Cite

BackgroundQuinolones are widely prescribed for the treatment or prevention of infectious diseases in children. To gain further insight into quinolone-associated adverse event (AE) in children and better protect pediatric patients, continued surveillance of safety data is essential. The purpose of this study was to characterize the safety profiles of quinolone-associated AEs in children by mining the FDA adverse event reporting system (FAERS).MethodsFAERS reports from quarter 1 of 2004 to quarter 1 of 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify adverse events. Reporting odds ratios (ROR) corresponding 95% confidence intervals (CIs) and information component (IC) along with 95% CIs were calculated to detect drug–AE pairs with higher-than-expected reporting rates within the FAERS from System Organ Classes (SOCs) to Preferred Terms (PTs). Reports were considered as signals if the 95% conﬁdence interval did not contain the null value.ResultsAfter inclusion criteria were applied, a total of 4,704 reports associated with quinolones were considered. Most FAERS reports associated with ciprofloxacin (N = 2,706) followed by levofloxacin (N = 1,191), moxifloxacin (N = 375), oflaxacin (N = 245) and ozenoxacin (N = 187). The most common age group was 12–18 years. The median weight was 39.0 kilogram. The adverse effects of quinolones emerging for SOCs primarily included Infections and infestations, gastrointestinal symptoms, blood and lymphatic system disorders, cardiac disorders, nervous system disorders, musculoskeletal and connective tissue disorders and psychiatric disorders. The most frequently AE signals at the PT level were pyrexia (N = 236), febrile neutropenia (N = 120), off label use (N = 48), drug resistance (N = 18) and cardiac arrest (N = 22) following the use of ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, and ozenoxacin, respectively. Serious oznoxacin-associated AE signals were found and have not been documented in the package insert. They included cardiac arrest (N = 22; ROR = 19.83; IC = 3.68), overdose (N = 21; ROR = 4.98; IC = 2.07), seizure (N = 16; ROR = 6.01; IC = 2.29), small for dates baby (N = 9; ROR = 14.7; IC = 3.05), completed suicide (N = 15, ROR = 18.87; IC = 3.51), asthma (N = 9; ROR = 6.69; IC = 2.24;) and hypotension (N = 9; ROR = 3.83; IC = 1.68).ConclusionThis study provided additional evidence with respect to quinolones-related AEs for children. Generally, the findings of this study are compatible with AEs recorded in package inserts. The unexpected signals of ozenoxacin justify active vigilance by clinicians and timely monitoring by pharmacovigilance experts.

show abstract

Section: Discussionmentioning

confidence: 98%

Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS)

Kong

Mao²,

Zhang³

et al. 2023

Front. Pediatr.

View full text Add to dashboard Cite

show abstract

“…Ozenoxacin (OZE) is a novel non-fluorinated quinolone (). Like NEM, its non-fluorination grants a better safety profile than classical fluorinated quinolones, precluding the development of quinolone-induced chondrotoxicity and transdermal absorption [153]. Like DLX, OZE inhibits both gyrase and topoisomerase IV with equal affinity, conferring activity against CIP- and LVX-resistant S. aureus, S. pyogenes, Staphylococcus epidermidis and Streptococcus agalactiae [154, 155].…”

Section: Approved Anti-staphylococcal Antibiotics Since 2010mentioning

confidence: 99%

Staph wars: the antibiotic pipeline strikes back

Douglas,

Laabei

2023

Microbiology

View full text Add to dashboard Cite

Antibiotic chemotherapy is widely regarded as one of the most significant medical advancements in history. However, the continued misuse of antibiotics has contributed to the rapid rise of antimicrobial resistance (AMR) globally. Staphylococcus aureus , a major human pathogen, has become synonymous with multidrug resistance and is a leading antimicrobial-resistant pathogen causing significant morbidity and mortality worldwide. This review focuses on (1) the targets of current anti-staphylococcal antibiotics and the specific mechanisms that confirm resistance; (2) an in-depth analysis of recently licensed antibiotics approved for the treatment of S. aureus infections; and (3) an examination of the pre-clinical pipeline of anti-staphylococcal compounds. In addition, we examine the molecular mechanism of action of novel antimicrobials and derivatives of existing classes of antibiotics, collate data on the emergence of resistance to new compounds and provide an overview of key data from clinical trials evaluating anti-staphylococcal compounds. We present several successful cases in the development of alternative forms of existing antibiotics that have activity against multidrug-resistant S. aureus . Pre-clinical antimicrobials show promise, but more focus and funding are required to develop novel classes of compounds that can curtail the spread of and sustainably control antimicrobial-resistant S. aureus infections.

show abstract

“…Its dual inhibitory activity against bacterial replication avoids the development of resistance (Vila et al, 2019); ozenoxacin also has a high accumulation inside Grampositive bacterial cells, apparently due to its resistance to certain efflux pumps commonly found in S. aureus that affect other quinolones (López Cubillos et al, 2018). The absence of a fluorine atom in its molecular structure confers a better safety profile than other fluorinated quinolones, including a lack of quinolone-induced chondrotoxicity (González Borroto et al, 2018).…”

Section: Ozenoxacinmentioning

confidence: 99%

“…The practical clinical recommendations suggest topical antibiotic therapy for localized lesions and systemic therapy with oral antibiotics in cases of extensive injury, failure or inability to perform topical therapy (Yamakawa et al, 2002;European Medicines Agency, 2014;Health Canada, 2017;U.S. Food and Drug Administration, 2017;Canton et al, 2018;González Borroto et al, 2018;López Cubillos et al, 2018;Tarragó et al, 2018;Vila et al, 2019;Torrelo et al, 2020). The increase in multidrug resistance pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), mupirocin-resistant Staphylococcus aureus or quinoloneresistant Staphylococcus aureus, requires the development of new antibiotics against these agents.…”

Section: Introductionmentioning

confidence: 99%

The Use of Ozenoxacin in Pediatric Patients: Clinical Evidence, Efficacy and Safety

2020

View full text Add to dashboard Cite

Impetigo is the most common childhood skin infection in the world. There are two patterns of impetigo: nonbullous (or impetigo contagiosa) and bullous. The nonbullous type is due to Staphylococcus aureus and group A beta-haemolytic Streptococcus and occurs in 70% of impetigo cases. Impetigo is often a self-limited disease, but complications can sometimes occur. Therapy depends on the extent and site of the lesions and on the presence of systemic symptoms. The increase in multidrug resistance pathogens, such as methicillin-resistant Staphylococcus aureus, mupirocin-resistant Staphylococcus aureus or quinolone-resistant Staphylococcus aureus, requires the development of new antibiotics against these agents. The aim of this review is to evaluate the efficacy and safety of ozenoxacin in children compared to those of other approved topical antimicrobial therapies. The bactericidal activity against both susceptible and resistant organisms is a relevant feature of ozenoxacin because the bacterial strain and potential for resistance are generally not known at the beginning of therapy. Additionally, its minimal dermal absorption and its capability to reach high concentrations in the upper layers of the epidermidis agrees with the recommended practice aimed at avoiding the emergence of bacterial resistance in presence of a good safety profile. Further studies with real-life analyses and pharmacoeconomic evaluation are needed to confirm its role as first-line and second-line therapy in children with impetigo.

show abstract

Studies on Articular and General Toxicity of Orally Administered Ozenoxacin in Juvenile Rats and Dogs

Abstract: Ozenoxacin was generally well-tolerated in juvenile rats and dogs, with no evidence of quinolone-induced arthropathy.

Cited by 13 publications

References 21 publications

Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS)

Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS)

Staph wars: the antibiotic pipeline strikes back

The Use of Ozenoxacin in Pediatric Patients: Clinical Evidence, Efficacy and Safety

Contact Info

Product

Resources

About