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

Abstract

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.

Green and Red Brazilian Propolis: Antimicrobial Potential and Anti‐Virulence against ATCC and Clinically Isolated Multidrug‐Resistant Bacteria

“…For the last few decades, infectious diseases caused by multidrug resistance bacteria (MDRB) has become a growing concern in human and veterinary medicine and a global public health problem [1–4] . Recent clinical data indicate that a significant number of antibacterial agents currently employed have become useless in the face of increasing resistance rates, [1–4] thus enhancing the rate of morbidity and mortality and the healthcare cost related to the prevention and treatment of infections caused by MDRB [3,4] . In this context, discovering new antibiotics and encouraging scientific investigations concerning novel approaches for clinical treatment options are an urgent need [2,4] …”

The search for novel treatment strategies forStreptococcus pneumoniaeinfections

“…describes in depth all antibacterial agents against Gram-positive bacteria currently in clinical trials (phase I to phase III) (Koulenti et al . 2020 ). Table 1 lists all evaluated compound libraries based on in-use antibiotics since 2010.…”

“…Gepotidacin is currently recruiting for phase III trials, evaluating efficacy, safety and applicability of the drug (Kolarič, Anderluh and Minovski 2020 ; Koulenti et al . 2020 ). Other classes of bacterial topoisomerase II inhibitors are the pyrrolamides, tetrahydropyrans, tricyclics, pyrimidines and quinolines.…”

Simultaneous and sequential influence of metabolite complexes of Lactobacillus rhamnosus and Saccharomyces boulardii and antibiotics against poly-resistant Gram-negative bacteria

“…Complications during the treatment of simple infectious diseases occur more and more often due to significant increase in the resistance of etiologically significant pathogens to antibacterial preparations (Andrzejczuk et al, 2019;Elbediwi et al, 2019;Palchykov et al, 2019;Perdikouri et al, 2019;Koulenti, 2020). Increase in the amount of antibiotic-resistant strains of different species of microorganisms raises concerns in many countries and stimulates scientists to develop alternative preparations (Chaudhary, 2016;Richardson, 2017;Pizzolato-Cezar et al, 2019).…”