Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms

Koulenti, Despoina; Xu, Elena; Mok, Isaac Yin Sum; Song, Andrew; Karageorgopoulos, Drosos E.; Armaganidis, Apostolos; Lipman, Jeffrey; Tsiodras, Sotirios

doi:10.3390/microorganisms7080270

Cited by 84 publications

(54 citation statements)

References 111 publications

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“…was reported. On the other hand, ceftobiprole is active against Gram-positive and Gram-negative microorganisms [60][61][62].…”

Section: New Treatmentsmentioning

confidence: 99%

“…aureusandS. pyogenes [62].  Omadacycline(7) (Figure 3) is a tetracycline analog that inhibits protein synthesis by binding on the 30S ribosomal subunit.…”

Section: New Treatmentsmentioning

confidence: 99%

“…Besifloxacin is active against Gram-positive bacteria, especially S. aureus, Staphylococcus epidermidis, S. pneumoniae, and Haemophilus influenzae, and Gram-negative bacteria, while delafloxacin is active against S. aureus, S. pneumoniae, and fluoroquinolone-resistant strains except for enterococci. On the other hand, ozenoxacin is active against MRSA, MSSA, MRSE, and S. pyogenes and was approved by the FDA to treat impetigo caused by S. aureus and S. pyogenes [62]. Omadacycline (7) (Figure 3) is a tetracycline analog that inhibits protein synthesis by binding on the 30S ribosomal subunit.…”

Section: New Treatmentsmentioning

confidence: 99%

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Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

2020

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The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.

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“…was reported. On the other hand, ceftobiprole is active against Gram-positive and Gram-negative microorganisms [60][61][62].…”

Section: New Treatmentsmentioning

confidence: 99%

“…aureusandS. pyogenes [62].  Omadacycline(7) (Figure 3) is a tetracycline analog that inhibits protein synthesis by binding on the 30S ribosomal subunit.…”

Section: New Treatmentsmentioning

confidence: 99%

Section: New Treatmentsmentioning

confidence: 99%

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Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

2020

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“…Oral lefamulin has not been studied and is therefore not recommended in those patients with moderate or severe liver impairment (Child-Pugh Classes B and C). 34…”

Section: Dosage Drug Interactions and Special Populationmentioning

confidence: 99%

Lefamulin: novel pleuromutilin drug for community acquired bacterial pneumonia

Dubey

Maggo²,

Karan³

et al. 2019

Int J Basic Clin Pharmacol

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The advent and spread of antimicrobial resistance has led to a global public health emergency necessitating development of new antimicrobial drugs. Community acquired bacterial pneumonia (CABP) contributes a major portion of societal burden with increasing morbidity due to evolution of drug resistant strains. Lefamulin is a novel pleuromutilin antibiotic with unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50s bacterial ribosome. The drug displays activity against Gram positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumonia, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded Gram-positive spectrum including Staphylococcus aureus (i.e., methicillin-resistant, vancomycin-intermediate, and heterogeneous strains). Lefamulin is available in both intravenous (IV) and per oral (PO) formulation, exhibits high nonlinear plasma protein binding with low unbound concentrations, higher concentrations in lung epithelial lining fluid (ELF) than in plasma, and a half-life of approximately 10 hour. The recommended IV dose is 150 mg twice daily over 1 hour or a PO dose of 600 mg twice daily. Most common adverse drug reactions injection site reactions, hepatic enzyme elevation, nausea, diarrhoea, hypokalemia, insomnia, and headache. Clinical trials for lefamulin have been positive and Phase 3 data suggest similar efficacy when compared to moxifloxacin with or without linezolid in CABP. Also, the documented resistance and cross-resistance with other Gram-positive antibacterials remains low. With Nabrivia Pharmaceuticals having already received US FDA approval in August 2019, lefamulin may soon be a new addition to the mounting armoury of drugs against CABP.

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“…We will also briefly present alternative treatment approaches for Gram-positive microorganisms that are currently under clinical development. For novel, approved antibiotics against MDR Gram-positive microorganism, we refer the reader to other publications [4,5]. defensin mimetic S. aureus and S. epidermidis ABSSSI 1 Nemonoxacin has been approved for treating community-acquired pneumonia in adults in Taiwan and China.…”

Section: Introductionmentioning

confidence: 99%

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

Koulenti

Song

et al. 2020

Microorganisms

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Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

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Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms

Cited by 84 publications

References 111 publications

Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

Lefamulin: novel pleuromutilin drug for community acquired bacterial pneumonia

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

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