In vitro susceptibility and cross-resistance of South African isolates of Neisseria gonorrhoeae to 14 antimicrobial agents.

Abstract Objectives Novel antimicrobials for treatment of gonorrhoea are imperative. The first-in-class spiropyrimidinetrione zoliflodacin is promising and currently in an international Phase 3 randomized controlled clinical trial (RCT) for treatment of uncomplicated gonorrhoea. We evaluated the in vitro activity of and the genetic conservation of the target (GyrB) and other potential zoliflodacin resistance determinants among 1209 consecutive clinical Neisseria gonorrhoeae isolates obtained from 25 EU/European Economic Area (EEA) countries in 2018 and compared the activity of zoliflodacin with that of therapeutic antimicrobials currently used. Methods MICs of zoliflodacin, ceftriaxone, cefixime, azithromycin and ciprofloxacin were determined using an agar dilution technique for zoliflodacin or using MIC gradient strip tests or an agar dilution technique for the other antimicrobials. Genome sequences were available for 96.1% of isolates. Results Zoliflodacin modal MIC, MIC50, MIC90 and MIC range were 0.125, 0.125, 0.125 and ≤0.004–0.5 mg/L, respectively. The resistance was 49.9%, 6.7%, 1.6% and 0.2% to ciprofloxacin, azithromycin, cefixime and ceftriaxone, respectively. Zoliflodacin did not show any cross-resistance to other tested antimicrobials. GyrB was highly conserved and no zoliflodacin gyrB resistance mutations were found. No fluoroquinolone target GyrA or ParC resistance mutations or mutations causing overexpression of the MtrCDE efflux pump substantially affected the MICs of zoliflodacin. Conclusions The in vitro susceptibility to zoliflodacin was high and the zoliflodacin target GyrB was conserved among EU/EEA gonococcal isolates in 2018. This study supports further clinical development of zoliflodacin. However, additional zoliflodacin data regarding particularly the treatment of pharyngeal gonorrhoea, pharmacokinetics/pharmacodynamics and resistance selection, including suppression, would be valuable.

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High In Vitro Susceptibility to the First-in-Class Spiropyrimidinetrione Zoliflodacin among Consecutive Clinical Neisseria gonorrhoeae Isolates from Thailand and South Africa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01479-19 ◽

2019 ◽

Vol 63 (12) ◽

Cited By ~ 1

Author(s):

Susanne Jacobsson ◽

Ranmini Kularatne ◽

Rossaphorn Kittiyaowamarn ◽

Venessa Maseko ◽

Porntip Paopang ◽

...

Keyword(s):

South Africa ◽

Neisseria Gonorrhoeae ◽

Cross Resistance ◽

Controlled Clinical Trial ◽

Phase 3 ◽

In Vitro Susceptibility ◽

Content Type ◽

Randomized Controlled ◽

Highly Active

ABSTRACT We evaluated the in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among recent consecutive clinical Neisseria gonorrhoeae isolates cultured in Thailand (n = 99) (in 2018) and South Africa (n = 100) (in 2015 to 2017). Zoliflodacin was highly active in vitro against all tested isolates (MIC range, 0.004 to 0.25 μg/ml; MIC50, 0.064 μg/ml; MIC90, 0.125 μg/ml), with no cross-resistance to any of the seven comparator antimicrobials. Our data support the initiation of the global phase 3 randomized controlled clinical trial of zoliflodacin for uncomplicated gonorrhea.

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In vitro susceptibility of penicillianse-producing Neisseria gonorrhoeae to a select group of antimicrobial agents, alone and in combination

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/5.5.618 ◽

1979 ◽

Vol 5 (5) ◽

pp. 618-620

Author(s):

THOMAS T. YOSHIKAWA ◽

SHARON A. SHIBATA

Keyword(s):

Neisseria Gonorrhoeae ◽

Antimicrobial Agents ◽

In Vitro Susceptibility ◽

Select Group

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In Vitro Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00929-17 ◽

2017 ◽

Vol 61 (10) ◽

Cited By ~ 11

Author(s):

Victoria F. Miari ◽

Priya Solanki ◽

Yonek Hleba ◽

Richard A. Stabler ◽

John T. Heap

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Related Species ◽

Cross Resistance ◽

Drug Resistant ◽

In Vitro Susceptibility ◽

Content Type ◽

Reference Strains ◽

Species Cross

ABSTRACT Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

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In Vitro Susceptibility of Neisseria gonorrhoeae Strains to Mupirocin, an Antibiotic Reformulated for Parenteral Administration in Nanoliposomes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02377-17 ◽

2018 ◽

Vol 62 (4) ◽

Cited By ~ 1

Author(s):

Ahuva Cern ◽

Kristie L. Connolly ◽

Ann E. Jerse ◽

Yechezkel Barenholz

Keyword(s):

Neisseria Gonorrhoeae ◽

Topical Administration ◽

Parenteral Administration ◽

Cross Resistance ◽

Drug Resistant ◽

Potential Treatment ◽

In Vitro Susceptibility ◽

Antibiotic Resistant ◽

Content Type

ABSTRACT Neisseria gonorrhoeae is an urgent antibiotic-resistant threat. This study determined the MICs of mupirocin to be 0.0039 to 0.0625 μg/ml for 94 N. gonorrhoeae strains. Cross-resistance with other antibiotics was not detected. Mupirocin, which is currently limited to topical administration, demonstrated activity by injection when delivered in nanoliposomes. The nanoliposomal formulation of mupirocin is a potential treatment for drug-resistant N. gonorrhoeae .

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Molecular Epidemiology and Antifungal Susceptibility of Trichophyton Isolates in Greece: Emergence of Terbinafine-Resistant Trichophytonmentagrophytes Type VIII Locally and Globally

Journal of Fungi ◽

10.3390/jof7060419 ◽

2021 ◽

Vol 7 (6) ◽

pp. 419

Author(s):

Maria Siopi ◽

Ioanna Efstathiou ◽

Konstantinos Theodoropoulos ◽

Spyros Pournaras ◽

Joseph Meletiadis

Keyword(s):

Molecular Epidemiology ◽

Antifungal Susceptibility ◽

Reference Method ◽

Cross Resistance ◽

Squalene Epoxidase ◽

In Vitro Susceptibility ◽

Type Viii ◽

In Vitro Antifungal Susceptibility ◽

Resistance Rates

Trichophyton isolates with reduced susceptibility to antifungals are now increasingly reported worldwide. We therefore studied the molecular epidemiology and the in vitro antifungal susceptibility patterns of Greek Trichophyton isolates over the last 10 years with the newly released EUCAST reference method for dermatophytes. Literature was reviewed to assess the global burden of antifungal resistance in Trichophyton spp. The in vitro susceptibility of 112 Trichophyton spp. molecularly identified clinical isolates (70 T. rubrum, 24 T. mentagrophytes, 12 T. interdigitale and 6 T. tonsurans) was tested against terbinafine, itraconazole, voriconazole and amorolfine (EUCAST E.DEF 11.0). Isolates were genotyped based on the internal transcribed spacer (ITS) sequences and the target gene squalene epoxidase (SQLE) was sequenced for isolates with reduced susceptibility to terbinafine. All T. rubrum, T. interdigitale and T. tonsurans isolates were classified as wild-type (WT) to all antifungals, whereas 9/24 (37.5%) T. mentagrophytes strains displayed elevated terbinafine MICs (0.25–8 mg/L) but not to azoles and amorolfine. All T. interdigitale isolates belonged to ITS Type II, while T. mentagrophytes isolates belonged to ITS Type III* (n = 11), VIII (n = 9) and VII (n = 4). All non-WT T. mentagrophytes isolates belonged to Indian Genotype VIII and harbored Leu393Ser (n = 5) and Phe397Leu (n = 4) SQLE mutations. Terbinafine resistance rates ranged globally from 0–44% for T. rubrum and 0–76% for T. interdigitale/T. mentagrophytes with strong endemicity. High incidence (37.5%) of terbinafine non-WT T. mentagrophytes isolates (all belonging to ITS Type VIII) without cross-resistance to other antifungals was found for the first time in Greece. This finding must alarm for susceptibility testing of dermatophytes at a local scale particularly in non-responding dermatophytoses.

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