In vitro antimicrobial activity of ozenoxacin against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Streptococcus pyogenes isolated from clinical cutaneous specimens in Japan

doi:10.1016/j.jiac.2016.03.006

Journal of Infection and Chemotherapy

Volume 22, Issue 10, October 2016, Pages 720-723

https://doi.org/10.1016/j.jiac.2016.03.006 Get rights and content

Abstract

Ozenoxacin, a novel non-fluorinated topical quinolone, was assessed for in vitro antimicrobial activity against each 50 isolates of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes according to the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. The isolates used in this study were recovered from cutaneous specimens of Japanese adult and pediatric patients who visited hospitals in 2014.

The MIC₉₀s of ozenoxacin against MSSA, MRSA and S. pyogenes isolates from adult patients were ≤0.06, 4 and ≤0.06 μg/mL, respectively. The MIC₉₀s of ozenoxacin against MSSA and S. pyogenes isolates from pediatric patients were equal to those against the adult isolates. On the other hand, the MIC₉₀s of ozenoxacin against the pediatric MRSA isolates was 0.12 μg/mL, and was 32 times lower than that against the adult isolates. The antimicrobial activity of ozenoxacin against MSSA, MRSA and S. pyogenes was equal to or greater than those of 7 reference antimicrobial agents had been used for the treatment of skin infections. The MICs of ozenoxacin was highly correlated with those of nadifloxacin and levofloxacin in the 50 MRSA isolates (r² = 0.906 and 0.833, respectively). However, ozenoxacin kept the potent antimicrobial activity with the MIC ranging from 1 to 4 μg/mL even against MRSA low susceptible (MIC: >64 μg/mL) to nadifloxacin or levofloxacin.

Ozenoxacin could represent the first-in-class non-fluorinated quinolone for the topical treatment of various superficial skin infections caused by MSSA, MRSA and S. pyogenes.

Section snippets

Conflict of interest

Shoji Kanayama, Fumiaki Ikeda, Kazuaki Okamoto, Akiko Nakajima, Tatsumi Matsumoto and Ritsuko Ishii are employees of Maruho Co., Ltd. Ayako Amano, Kaoru Matsuzaki and Satoru Matsumoto are employees of LSI Medience Co.

References (14)

R.N. Jones et al.
Influence of patient age on the susceptibility patterns of Streptococcus pneumoniae in North America (2000-2001): report from the SENTRY Antimicrobial Surveillance Program
Diagn Microbiol Infect Dis
(2003)
The JAID/JSC guide to clinical management of infectious disease
(2014)
Y. Liu et al.
Antimicrobial susceptibility of Staphylococcus aureus isolated from children with impetigo in China from 2003 to 2007 shows community-associated methicillin-resistant Staphylococcus aureus to be uncommon and heterogeneous
Br J Dermatol
(2009)
T. Yamakawa et al.
In vitro and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone
J Antimicrob Chemother
(2002)
M. Kawashima et al.
A comparative phase Ⅲ study of ozenoxacin lotion in patients with acne vulgaris
J Clin Ther Med
(2015)
M. Kawashima et al.
An open-label, phase Ⅲ study of ozenoxacin lotion in patients with superficial infection of the skin
J Clin Ther Med
(2015)
S. Gropper et al.
Ozenoxacin 1% cream in the treatment of impetigo: a multicenter, randomized, placebo- and retapamulin-controlled clinical trial
Future Microbiol
(2014)

There are more references available in the full text version of this article.

Cited by (13)

Phytochemical investigation and antibacterial activity of Curcuma longa against multi-drug resistant bacteria
2024, South African Journal of Botany
Emergence of antibiotic resistance in bacterial species is increasing at an alarming rate. This calls for an urge to search for new antimicrobial agents from natural sources. Curcuma longa rhizome is used in traditional medicine as a remedy for many infectious diseases. The rhizome extracted in different solvents is tested against hospital isolates of multidrug-resistant bacteria (Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa) using agar well diffusion and broth microdilution assays. Antioxidant activity was determined using DPPH radical scavenging and superoxide anion scavenging methods. GC–MS analysis was performed to identify biologically active compounds present in the plant. All the plant samples inhibited bacterial growth with varying degree of inhibition observed for different bacterial strains. In general MRSA was more sensitive to most of the extracts with larger zones of inhibition and high percentage inhibition while A. baumannii was the most resistant with smaller zones of inhibition and low percentage inhibition observed for different plant samples. n-Hexane fraction of C. longa was the most effective in inhibiting bacterial growth with lowest MIC values (2.5 mg/mL). Antioxidant activity assays indicated strong antioxidant potential of n-hexane fraction in DPPH assay and of methanol fraction in superoxide scavenging assay. GC–MS analysis indicated ar-turmerone as the most abundant component of the plant (34.63 %). The non-polar fractions of the plant were particularly more effective against multidrug-resistant bacteria. Further purification and characterization of bioactive compounds, from active fractions of this plant, for their applications as antibacterial leads in pharmaceutical industries is recommended.
Antimicrobial activity of ozenoxacin and other antimicrobials against Staphylococcus aureus strains isolated from clinical skin specimens in Japan in 2019 and 2020
2022, Journal of Infection and Chemotherapy
Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and the spread of antimicrobial resistance are a major problem in Japan. Here, we investigated the susceptibility of S. aureus clinical isolates to ozenoxacin (OZNX), a topical antimicrobial approved for superficial skin infection treatment in Japan. Susceptibility to OZNX was measured in 110 skin-derived methicillin-susceptible S. aureus (MSSA) and 130 MRSA strains isolated in 2019 and 2020 in Japan. The broth microdilution method was performed, and results were analyzed according to the Clinical and Laboratory Standard Institute (M07 and M100) guidelines. The results were compared with those of other antimicrobials used against S. aureus. The minimum inhibitory concentrations (MIC)₉₀ of OZNX for MSSA and MRSA were 0.12 and 0.25 μg/mL, respectively, indicating that OZNX exhibited the same or stronger antibacterial activity than that of the other antimicrobials tested, such as nadifloxacin, fucidic acid, and gentamicin. No strains exhibited reduced OZNX susceptibility. Notably, a low MIC of OZNX was observed even for strains with reduced susceptibility to nadifloxacin, a similar quinolone-based topical antimicrobial. OZNX is a highly potent antimicrobial used in Japan for superficial skin infections caused by S. aureus, such as impetigo contagiosa and related diseases.
Emerging Treatment Strategies for Impetigo in Endemic and Nonendemic Settings: A Systematic Review
2021, Clinical Therapeutics
Citation Excerpt :
Considering the significant burden of skin infections, such as impetigo, and the increase in antibiotic resistance, treatment choices are limited, especially in people with impetigo caused by MRSA. Ozenoxacin is highly effective against methicillin-susceptible S aureus, MRSA, and S pyogenes.44 Furthermore, it has a superior resistance profile when compared with quinolone antibiotics because of its ability to simultaneously inhibit bacterial DNA gyrase and intravenous topoisomerase, whereas most quinolones bind with only 1 of the 2.45
Impetigo affects approximately 162 million children worldwide at any given time. Lack of consensus on the most effective treatment strategy for impetigo and increasing antibiotic resistance continue to drive research into newer and alternative treatment options. We conducted a systematic review to assess the effectiveness of new treatments for impetigo in endemic and nonendemic settings.
We searched PubMed, MEDLINE, CINAHL, Web of Science, and Embase via Scopus for studies that explored treatments for bullous, nonbullous, primary, and secondary impetigo published between August 1, 2011, and February 29, 2020. We also searched online trial registries and hand-searched the reference lists of the included studies. We used the revised Cochrane risk of bias (version 2.0) tool for randomized trials and the National Heart, Lung, and Blood Institute for nonrandomized uncontrolled studies to assess the risk of bias.
We included 10 studies that involved 6651 participants and reported on 9 treatments in the final analysis. Most clinical trials targeted nonbullous impetigo or did not specify this. The risk of bias varied among the studies. In nonendemic settings, ozenoxacin 1% cream appeared to have the strongest evidence base compared with retapamulin and a new minocycline formulation. In endemic settings, oral co-trimoxazole and benzathine benzylpenicillin G injection were equally effective in the treatment of severe impetigo. Mass drug administration intervention emerged as a promising public health strategy to reduce the prevalence of impetigo in endemic settings.
This review highlights the limited research into new drugs used for the treatment of impetigo in endemic and nonendemic settings. Limited recent evidence supports the use of topical ozenoxacin or retapamulin for impetigo treatment in nonendemic settings, whereas systemic antibiotics and the mass drug administration strategy have evidence for use in endemic settings. Given the troubling increase in resistance to existing treatments, there is a clear need to ensure the judicious use of antibiotics and to develop new treatments and alternative strategies; this is particularly important in endemic settings. PROSPERO identifier: CRD42020173042.
Topical Antibacterial Agents
2020, Comprehensive Dermatologic Drug Therapy, Fourth Edition
The major advantage in the topical use of an antibacterial agent is the ability to achieve high local drug concentrations with minimal systemic absorption, thus minimizing the risk of systemic adverse effects. This chapter summarizes the current scientific information on commonly used topical antibacterial agents and their role in skin diseases. In addition, the potential of allergic contact sensitivity from several of the topical antibacterial agents is discussed. The chapter is divided into two broad categories of topical antibacterial agents: (1) drugs used primarily for wound care and minor topical bacterial infections, and (2) drugs used primarily for acne and rosacea. Popular topical antiseptic agents are briefly discussed at the end of the chapter.
Bactericidal activity and post-antibiotic effect of ozenoxacin against Propionibacterium acnes
2017, Journal of Infection and Chemotherapy
Citation Excerpt :
However, it has been concerned an expansion of antimicrobial-resistant P. acnes [7–11]. Ozenoxacin, a novel non-fluorinated quinolone, has demonstrated a broad antimicrobial spectrum against both Gram-positive and -negative organisms including major pathogenic bacteria of acne vulgaris and superficial skin infections such as P. acnes, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes [12–17]. Recently, 2% ozenoxacin-containing lotion (Zebiax® Lotion 2%, Maruho Co., Ltd., Osaka, Japan) has demonstrated a good therapeutic effect in patients with acne vulgaris and superficial skin infections in Japan [7,18].
Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic effect (PAE) of ozenoxacin against Propionibacterium acnes, a major causative bacterium of acne vulgaris. The minimum inhibitory concentrations (MICs) of ozenoxacin against 3 levofloxacin-susceptible strains (MIC of levofloxacin; ≤4 μg/mL) and 3 levofloxacin-resistant strains (MIC of levofloxacin; ≥8 μg/mL) ranged from 0.03 to 0.06 μg/mL and from 0.25 to 0.5 μg/mL, respectively. These MICs of ozenoxacin were almost the same or lower than nadifloxacin and clindamycin. The minimum bactericidal concentrations (MBCs) of ozenoxacin against the levofloxacin-susceptible and -resistant strains were from 0.06 to 8 μg/mL and from 0.5 to 4 μg/mL, respectively. These MBCs were lower than those of nadifloxacin and clindamycin. In time-kill assay, ozenoxacin at 1/4, 1 and 4 times the respective MIC against both levofloxacin-susceptible and -resistant strains showed a concentration-dependent bactericidal activity. Ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains showed more potent and more rapid onset of bactericidal activity compared to nadifloxacin and clindamycin at 4 times the respective MICs. The PAEs of ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains were from 3.3 to 17.1 h, which were almost the same or longer than nadifloxacin and clindamycin. In contrast, the PAEs were hardly induced by any antimicrobial agents against the levofloxacin-resistant strains.
The present findings suggest that ozenoxacin has a potent bactericidal activity against both levofloxacin-susceptible and -resistant P. acnes, and a long-lasting PAE against levofloxacin-susceptible P. acnes.
Investigation of Morchella esculenta and Morchella conica for their antibacterial potential against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes
2022, Archives of Microbiology

View all citing articles on Scopus

View full text

Article preview

Journal of Infection and Chemotherapy

Abstract

Section snippets

Conflict of interest

References (14)

Influence of patient age on the susceptibility patterns of Streptococcus pneumoniae in North America (2000-2001): report from the SENTRY Antimicrobial Surveillance Program

Diagn Microbiol Infect Dis

The JAID/JSC guide to clinical management of infectious disease

Antimicrobial susceptibility of Staphylococcus aureus isolated from children with impetigo in China from 2003 to 2007 shows community-associated methicillin-resistant Staphylococcus aureus to be uncommon and heterogeneous

Br J Dermatol

In vitro and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone

J Antimicrob Chemother

A comparative phase Ⅲ study of ozenoxacin lotion in patients with acne vulgaris

J Clin Ther Med

An open-label, phase Ⅲ study of ozenoxacin lotion in patients with superficial infection of the skin

J Clin Ther Med

Ozenoxacin 1% cream in the treatment of impetigo: a multicenter, randomized, placebo- and retapamulin-controlled clinical trial

Future Microbiol

Cited by (13)

Phytochemical investigation and antibacterial activity of Curcuma longa against multi-drug resistant bacteria

Antimicrobial activity of ozenoxacin and other antimicrobials against Staphylococcus aureus strains isolated from clinical skin specimens in Japan in 2019 and 2020

Emerging Treatment Strategies for Impetigo in Endemic and Nonendemic Settings: A Systematic Review

Topical Antibacterial Agents

Bactericidal activity and post-antibiotic effect of ozenoxacin against Propionibacterium acnes

Investigation of Morchella esculenta and Morchella conica for their antibacterial potential against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes

NoteIn vitro antimicrobial activity of ozenoxacin against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Streptococcus pyogenes isolated from clinical cutaneous specimens in Japan

Abstract

Section snippets

Conflict of interest

Diagn Microbiol Infect Dis

The JAID/JSC guide to clinical management of infectious disease

Antimicrobial susceptibility of Staphylococcus aureus isolated from children with impetigo in China from 2003 to 2007 shows community-associated methicillin-resistant Staphylococcus aureus to be uncommon and heterogeneous

Br J Dermatol

In vitro and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone

J Antimicrob Chemother

A comparative phase Ⅲ study of ozenoxacin lotion in patients with acne vulgaris

J Clin Ther Med

An open-label, phase Ⅲ study of ozenoxacin lotion in patients with superficial infection of the skin

J Clin Ther Med

Ozenoxacin 1% cream in the treatment of impetigo: a multicenter, randomized, placebo- and retapamulin-controlled clinical trial

Future Microbiol

Note
In vitro antimicrobial activity of ozenoxacin against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Streptococcus pyogenes isolated from clinical cutaneous specimens in Japan