<i>In Vitro</i>
            Activity of Lefamulin against Sexually Transmitted Bacterial Pathogens

Paukner, Susanne; Gruss, Astrid; Jensen, Jørgen Skov

doi:10.1128/aac.02380-17

Cited by 51 publications

(39 citation statements)

References 27 publications

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“…In this study, where azithromycin was given only to macrolide-susceptible cases and sitafloxacin therapy was used for macrolide-resistant cases,>92% of M. genitalium infections were shown to be cured. 26 Our data highlight the significant public health challenges in the control of M. genitalium, including an urgent need for evidence-based third line treatments, such as pristinamycin, minocycline or new antimicrobials such as lefamulin, gepotidacin, solithromycin or zoliflodacin, [27][28][29][30] and the need for systematic national and international surveillance of AMR and treatment failure to inform treatment guidelines.…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population

et al. 2020

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BackgroundMycoplasma genitalium is a common sexually transmitted infection. Treatment guidelines focus on those with symptoms and sexual contacts, generally with regimens including doxycycline and/or azithromycin as first-line and moxifloxacin as second-line treatment. We investigated the prevalence of antimicrobial resistance (AMR)-conferring mutations in M. genitalium among the sexually-active British general population.MethodsThe third national survey of sexual attitudes and lifestyles (Natsal-3) is a probability sample survey of 15 162 men and women aged 16–74 years in Britain conducted during 2010–12. Urine test results for M. genitalium were available for 4507 participants aged 16–44 years reporting >1 lifetime sexual partner. In this study, we sequenced regions of the 23S rRNA and parC genes to detect known genotypic determinants for resistance to macrolides and fluoroquinolones respectively.Results94% (66/70) of specimens were re-confirmed as M. genitalium positive, with successful sequencing in 85% (56/66) for 23S rRNA and 92% (61/66) for parC genes. Mutations in 23S rRNA gene (position A2058/A2059) were detected in 16.1% (95%CI: 8.6% to 27.8%) and in parC (encoding ParC D87N/D87Y) in 3.3% (0.9%–11.2%). Macrolide resistance was more likely in participants reporting STI diagnoses (past 5 years) (44.4% (18.9%–73.3%) vs 10.6% (4.6%–22.6%); p=0.029) or sexual health clinic attendance (past year) (43.8% (23.1%–66.8%) vs 5.0% (1.4%–16.5%); p=0.001). All 11 participants with AMR-conferring mutations had attended sexual health clinics (past 5 years), but none reported recent symptoms.ConclusionsThis study highlights challenges in M. genitalium management and control. Macrolide resistance was present in one in six specimens from the general population in 2010–2012, but no participants with AMR M. genitalium reported symptoms. Given anticipated increases in diagnostic testing, new strategies including novel antimicrobials, AMR-guided therapy, and surveillance of AMR and treatment failure are recommended.

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Section: Resultsmentioning

confidence: 99%

Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population

et al. 2020

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“…8,111 Nevertheless, new antimicrobials for monotherapy and/or inclusion in a dual therapy, which should be considered for all novel antimicrobials, for urogenital and extragenital gonorrhoea is essential. Antimicrobials such as lefamulin, 112,113 SMT-571, 114 gepotidacin [115][116][117] and especially zoliflodacin 118-122 must be studied further. 123,124 In conclusion, gonococcal AMR remains a major global public health concern, which compromises treatment and control of gonorrhoea.…”

Section: Discussionmentioning

confidence: 99%

World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts

et al. 2019

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Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious public health problem, compromising the management and control of gonorrhoea globally. Resistance in N. gonorrhoeae to ceftriaxone, the last option for first-line empirical monotherapy of gonorrhoea, has been reported from many countries globally, and sporadic failures to cure especially pharyngeal gonorrhoea with ceftriaxone monotherapy and dual antimicrobial therapies (ceftriaxone plus azithromycin or doxycycline) have been confirmed in several countries. In 2018, the first gonococcal isolates with ceftriaxone resistance plus high-level azithromycin resistance were identified in England and Australia. The World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Program (GASP) is essential to monitor AMR trends, identify emerging AMR and provide evidence for refinements of treatment guidelines and public health policy globally. Herein we describe the WHO GASP data from 67 countries in 2015–16, confirmed gonorrhoea treatment failures with ceftriaxone with or without azithromycin or doxycycline, and international collaborative actions and research efforts essential for the effective management and control of gonorrhoea. In most countries, resistance to ciprofloxacin is exceedingly high, azithromycin resistance is present and decreased susceptibility or resistance to ceftriaxone has emerged. Enhanced global collaborative actions are crucial for the control of gonorrhoea, including improved prevention, early diagnosis, treatment of index patient and partner (including test-of-cure), improved and expanded AMR surveillance (including surveillance of antimicrobial use and treatment failures), increased knowledge of correct antimicrobial use and the pharmacokinetics and pharmacodynamics of antimicrobials and effective drug regulations and prescription policies (including antimicrobial stewardship). Ultimately, rapid, accurate and affordable point-of-care diagnostic tests (ideally also predicting AMR and/or susceptibility), new therapeutic antimicrobials and, the only sustainable solution, gonococcal vaccine(s) are imperative.

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“…The compound showed potent activity, an MIC range of 0.004–2 mg/L, against gonococcal isolates and no significant cross-resistance to other antimicrobials. Furthermore, this compound has also been proven to be active against the other most relevant bacterial pathogens causing sexually transmitted infections (STIs), Chlamydia trachomatis and Mycoplasma genitalium , proving to be a good candidate first-line antibiotic for the treatment of STIs [ 33 ]. However promising, further studies are required in order to consider the introduction of Lefamulin as a first-line treatment option.…”

Section: Future Perspectivesmentioning

confidence: 99%

Future Prospects for Neisseria gonorrhoeae Treatment

Suay-García

Pérez‐Gracia

2018

Antibiotics

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Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the World Health Organization (WHO) Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis, and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting of dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. The increase in the detection of resistant gonococci may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics; (2) development of new antibiotics; and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this superbug. This has led the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

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In Vitro Activity of Lefamulin against Sexually Transmitted Bacterial Pathogens

Cited by 51 publications

References 27 publications

Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population

Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population

World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts

Future Prospects for Neisseria gonorrhoeae Treatment

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