Efficient Antibacterial Agents: A Review of the Synthesis, Biological Evaluation and Mechanism of Pleuromutilin Derivatives

Shang, Ruofeng; Wang, Jiatu; Guo, Wanshou; Liang, Jianping

doi:10.2174/15680266113136660217

Cited by 51 publications

(35 citation statements)

References 77 publications

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“…Retapamulin is a pleuromutilin antibiotic derived from the fungus Clitopilus passeckerianus (Shang, Wang, Guo, & Liang, 2013). In 2007, the FDA approved retapmulin 1% ointment for skin infections associated with gram-positive bacteria such as Streptococcus pyogenes and S. aureus, which have been linked to HE severity (Haslund et al, 2009;Yan et al, 2006).…”

Section: Retapamulinmentioning

confidence: 99%

Current and emerging therapies for hand eczema

Lee

Maarouf

Hendricks

et al. 2019

Dermatologic Therapy

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Although hand eczema (HE) and chronic hand eczema (CHE) are common conditions with significant disease burden, they traditionally have had limited treatment options beyond topical and short‐term systemic corticosteroids. We reviewed published and preliminary evidence on the current and emerging topical and systemic therapeutic agents for HE and CHE. The etiologies of various HE subtypes are discussed, and remaining knowledge and practice gaps are highlighted to encourage further investigations. A comprehensive search of http://clinicaltrials.gov and PubMed was completed for clinical trials that utilized known and emerging treatment options for HE and CHE. Several agents that target IL‐4 and IL‐13 signaling, keratinocyte proliferation, inflammatory cytokine production, bacterial protein synthesis, and inflammatory mediator (TNF‐α, JAK1, JAK2, and JAK3) proliferation are shown to be involved in the pathogenesis of CHE. Systemic agents include dupilumab, alitretinoin, acitretin, cyclosporine, azathioprine, and probiotics. Topical agents include delgocitinib, retapamulin, halometasone/triclosan, calcipotriol/betamethasone, tacrolimus, and pimecrolimus. These modalities have demonstrated varying degrees of clinical efficacy, evaluated by subjective assessments and scoring indexes. Targeted therapies are emerging for HE, but options are still limited, partially due to our narrow understanding of this heterogeneous condition. Additional and targeted therapeutic options are needed to match the rising prevalence and burden of HE. Keypoints Hand eczema (HE) is a heterogenous dermatosis with limited therapeutic options due to a lack of international guidelines regarding classification of HE subtypes and treatment. This review discusses current and emerging topical and systemic agents and their efficacies in the treatment of different types of hand eczema.

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Section: Retapamulinmentioning

confidence: 99%

Current and emerging therapies for hand eczema

Lee

Maarouf

Hendricks

et al. 2019

Dermatologic Therapy

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“…Lefamulin belongs to the pleuromutilin class of antimicrobial agents, which inhibits bacterial protein synthesis by selectively binding to the peptidyl transferase center of the bacterial ribosome and prevents the correct positioning of the 3=-CCA ends of tRNAs for peptide transfer (5)(6)(7)(8)(9)(10). Lefamulin is the first pleuromutilin in development for intravenous and oral administration in humans (6), and it is currently in late-stage clinical development for the treatment of CABP and acute bacterial skin and skin structure infections (11)(12)(13).…”

mentioning

confidence: 99%

In Vitro Activity of Lefamulin Tested against Streptococcus pneumoniae with Defined Serotypes, Including Multidrug-Resistant Isolates Causing Lower Respiratory Tract Infections in the United States

Mendes

Farrell

Flamm

et al. 2016

Antimicrob Agents Chemother

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Lefamulin was evaluated against various Streptococcus pneumoniae serotypes that were collected from adults with lower respiratory tract infections. Lefamulin exhibited MIC 50 and MIC 90 values of 0.12 and 0.25 g/ml, respectively, against the entire collection (n ‫؍‬ 822). Similar results were obtained for lefamulin against each of the most common serotypes as well as against multidrug-resistant isolates and strains that are nonsusceptible to ceftriaxone or erythromycin. These data support the clinical development of lefamulin for the treatment of community-acquired respiratory tract infections.

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“…The antimicrobial class pleuromutilins includes tiamulin and valnemulin, which are semisynthetic derivatives (11, 12). In Denmark, they are registered for indications including porcine proliferative enteropathy (due to Lawsonia intracellularis ), swine dysentery (due to Brachyspira hyodysenteriae ), porcine colonic spirochetosis (due to Brachyspira pilosicoli ), enzootic pneumonia (due to Mycoplasma hyopneumoniae ), infections caused by Mycoplasma hyorhinis and M. hyosynoviae , and respiratory diseases caused by tiamulin-sensitive microorganisms (13).…”

Section: Resultsmentioning

confidence: 99%

Assessment of the Risk to Public Health due to Use of Antimicrobials in Pigs—An Example of Pleuromutilins in Denmark

Alban

Ellis‐Iversen

Andreasen³

et al. 2017

Front. Vet. Sci.

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Antibiotic consumption in pigs can be optimized by developing treatment guidelines, which encourage veterinarians to use effective drugs with low probability of developing resistance of importance for human health. In Denmark, treatment guidelines for use in swine production are currently under review at the Danish Veterinary and Food Administration. Use of pleuromutilins in swine has previously been associated with a very low risk for human health. However, recent international data and sporadic findings of novel resistance genes suggest a change of risk. Consequently, a reassessment was undertaken inspired by a risk assessment framework developed by the European Medicines Agency. Livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (MRSA CC398) and enterococci were identified as relevant hazards. The release assessment showed that the probability of development of pleuromutilin resistance was high in MRSA CC398 (medium uncertainty) and low in enterococci (high uncertainty). A relatively small proportion of Danes has an occupational exposure to pigs, and foodborne transmission was only considered of relevance for enterococci, resulting in an altogether low exposure risk. The human consequences of infection with pleuromutilin-resistant MRSA CC398 or enterococci were assessed as low for the public in general but high for vulnerable groups such as hospitalized and immunocompromised persons. For MRSA CC398, the total risk was estimated as low (low uncertainty), among other due to the current guidelines on prevention of MRSA in place at Danish hospitals, which include screening of patients with daily contact to pigs on admittance. Moreover, MRSA CC398 has a medium human–human transmission potential. For enterococci, the total risk was estimated as low due to low prevalence of resistance, low probability of spread to humans, low virulence, but no screening of hospitalized patients, high ability of acquiring resistance genes, and a limited number of alternative antimicrobials (high uncertainty). This assessment reflects the current situation and should be repeated if pleuromutilin consumption increases substantially, resulting in increased prevalence of mobile, easily transmissible resistance mechanisms. Continuous monitoring of pleuromutilin resistance in selected human pathogens should therefore be considered. This also includes monitoring of linezolid resistance, since resistance mechanisms for pleuromutilins and oxazolidones are often coupled.

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Efficient Antibacterial Agents: A Review of the Synthesis, Biological Evaluation and Mechanism of Pleuromutilin Derivatives

Cited by 51 publications

References 77 publications

Current and emerging therapies for hand eczema

Current and emerging therapies for hand eczema

In Vitro Activity of Lefamulin Tested against Streptococcus pneumoniae with Defined Serotypes, Including Multidrug-Resistant Isolates Causing Lower Respiratory Tract Infections in the United States

Assessment of the Risk to Public Health due to Use of Antimicrobials in Pigs—An Example of Pleuromutilins in Denmark

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