Novel pharmaceutical molecules against emerging resistant gram-positive cocci

Abstract

Introduction: methicillin-and also vancomycin (glycopeptide)-resistant Gram-positive organisms have emerged as an increasingly problematic cause of hospital-acquired infections, also spreading into the community. Vancomycin (glycopeptide) resistance has emerged primarily among Enterococci, but the MIC values of vancomycin for the entire Staphylococcus species are also increasing worldwide. Material and Methods: the aim of our review is to evaluate the efficacy and tolerability of newer antibiotics with activity against methicillin-resistant and glycopeptide-resistant Gram-positive cocci, on the ground of our experience at a tertiary care metropolitan Hospital, and the most recent literature evidences in this field. Results: Quinupristin-dalfopristin, linezolid, daptomycin, and tigecycline show an excellent in vitro activity, comparable to the activity of vancomycin and teicoplanin for methicillin-resistant staphylococci, and superior to the one that vancomycin for vancomycin-resistant isolates. Dalbavancin, televancin, and oritavancin are new lipoglycopeptide agents with excellent activity against Gram-positive cocci, and have superior pharmacodynamics properties compared to vancomycin. We review the bacterial spectrum, clinical indications and practical use, pharmacologic properties, and expected adverse events and contraindications associated with each of these novel antimicrobial agents, compared with the present standard of care. Discussion: linezolid activity is substantially comparable to that of vancomycin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although its penetration into the respiratory tract is exceptionally elevated. Tigecycline has activity against both Enterococus species and MRSA; it is also active against a broad spectrum of Enterobacteriaceae and anaerobes, which allows for use intraabdominal, diabetic foot and surgical infections. Daptomycin has a rapid bactericidal activity for Staphylococcus aureus and it is approved in severe complications, such as bacteremia and right-sided endocarditis. It cannot be used to treat pneumonia and respiratory diseases, due to its inactivation in the presence of pulmonary surfactant.

Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

“…As the multiresistance spread is apparent among S. aureus strains in hospital settings, and becoming more evident in the community (so called community-aquired MRSA), several attempts are taken to develop strategies against these bacteria. The most popular and main-stream areas of research are new antimicrobial therapeutics [29]. However, alternative therapeutic options are also under investigation, to name: antimicrobial natural compounds [30,31], cationic antimicrobial peptides [32], the use of protection strategy to biofilm formation [33,34] or bacteriophage-based approaches [35,36].…”

Proteome Analyses of Cellular Proteins in Methicillin-Resistant Staphylococcus aureus Treated with Rhodomyrtone, a Novel Antibiotic Candidate

“…Several active researches have documented new antibiotics and semi-synthetic analogs with improved antimicrobial properties [6], [7], [8]. Various plants worldwide have been used in traditional medicine as alternative treatments of bacterial infections [9], [10], [11].…”

Newer antibacterials in therapy and clinical trial

“…Dalbavancin, a glycolipopeptide that requires only once-a-week dosing,[5] has been withdrawn from the market following feedback from regulatory authorities. Development of friulimicin, a lipopeptide was discontinued after a Phase I intravenous escalating-dose trial indicated that the pharmacokinetic profile of the drug was unfavourable.…”

“…equisimilis and Enterococcus faecalis (vancomycin-susceptible only). [10] It has also been approved for use in bacteremia and endocarditis[5] caused by MSSA or MRSA. It is inactivated by surfactant and is therefore contraindicated in pneumonia.…”

“…[5] Renal function should be monitored before, during and after telavancin therapy. Telavancin is not recommended in pregnancy.…”