Antistaphylococcal Activity of the FtsZ Inhibitor C109

Staphylococcus aureus infections represent a great concern due to their versatility and involvement in different types of diseases. The shortage of available clinical options, especially to treat multiresistant strains, makes the discovery of new effective compounds essential. Here we describe the activity of the previously described cell division inhibitor C109 against methicillin-sensitive and -resistant S. aureus strains. Antibiofilm activity was assessed using microtiter plates, confocal microscopy, and in an in vitro biofilm wound model. The ability of C109 to block FtsZ GTPase activity and polymerization was tested in vitro. Altogether, the results show that the FtsZ inhibitor C109 has activity against a wide range of S. aureus strains and support its use as an antistaphylococcal compound.

Perioperative antibiotic prophylaxis in surgery

Infectious complications in surgery occupy a significant place among the causes of death and increase in the cost of medical care for various pathologies. Antibiotic prophylaxis takes one of the first places in the perioperative period, in addition to surgical treatment and compliance with the rules of asepsis and antiseptics. Laxers is a new drug in the cephalosporin group, consisting of a combination of cefoperazone and sulbactam. It has a wide range of action on gram(-) and anaerobic flora and antistaphylococcal activity, which is not inferior to cefoperazone. Due to sulbactam, it has antimicrobial activity against Pseudomonas aeruginosa and Acinetobacter spp. This article describes the main properties and advantages of Laxers over other cephalosporins in this group as the drug of choice in the treatment of surgical pathologies and alternative antibiotic prophylaxis in the perioperative period in severe patients at risk of contamination of the operating field with hospital flora.

Development of a Broth Microdilution Method for Exebacase Susceptibility Testing

Exebacase (CF-301) belongs to a new class of protein-based antibacterial agents, known as lysins (peptidoglycan hydrolases). Exebacase, a novel lysin with antistaphylococcal activity, is in Phase 3 of clinical development. To advance into the clinic, it was necessary to develop an accurate and reproducible method for exebacase MIC determination. The Clinical Laboratory Standards Institute (CLSI) reference broth microdilution (BMD) method using cation-adjusted Mueller-Hinton broth (CAMHB) produced trailing MIC end points and exebacase activity was diminished when frozen BMD panels were used. A modified BMD method was developed using CAMHB supplemented with 25% horse serum and 0.5 mM DL-dithiothreitol (CAMHB-HSD). Preliminary quality control (QC) ranges for Staphylococcus aureus ATCC 29213 of 0.25-1 μg/ml and Enterococcus faecalis ATCC 29212 of 16-64 μg/ml were determined based on the results of a CLSI M23-defined MIC QC tier 1 study. These preliminary QC ranges validated the MIC data generated from a systematic study testing a discrete S. aureus strain collection using CAMHB-HSD to investigate the impact of parameters known to influence susceptibility test results and to evaluate the exebacase MIC distribution against clinical S. aureus isolates. Presentation of these data led to the CLSI Subcommittee on Antimicrobial Susceptibility Testing (AST) approval of the use of CAMHB-HSD to determine exebacase susceptibility and commencement of a multi-laboratory (tier 2) QC study. Use of a standard BMD method and concomitant QC testing provides confidence in the assessment of test performance to generate accurate and reproducible susceptibility data during antibacterial drug development.

Could Supercritical Extracts from the Aerial Parts of Helianthus salicifolius A. Dietr. and Helianthus tuberosus L. Be Regarded as Potential Raw Materials for Biocidal Purposes?

Extracts from the June collection of aerial parts of Helianthus salicifolius A. Dietr and Helianthus tuberosus L. were obtained using carbon dioxide supercritical fluid extraction with water as co-solvent. The antimicrobial effect in vitro of these extracts was then determined against reference species of bacteria, as well as against fungi (represented by Candida spp.). Both extracts were found to possess antimicrobial activity, with MIC = 0.62–5 mg mL−1 for bacteria and MIC = 5–10 mg mL−1 for yeasts, and both extracts demonstrated suitable bactericidal and fungicidal effect. The highest activity was observed against S. aureus ATCC 29213 (MIC = 0.62 mg mL−1 for H. salicifolius extract; MIC = 2.5 mg mL−1 for H. tuberosus extract) as confirmed by time–kill assay. Higher antioxidant activity was found for H. tuberosus extract (EC50 = 0.332 mg mL−1) as compared to that of H. salicifolius (EC50 = 0.609 mg mL−1). The total polyphenol content (TPC) expressed as gallic acid equivalents (GAE) was 13.75 ± 0.50 mg GAE g−1 of H. salicifolius extract and 33.06 ± 0.80 mg GAE g−1 of H. tuberosus extract. There was a relationship between the antioxidant potential of both extracts and TPC, but not between antistaphylococcal activity and TPC. The ATIR–FTIR spectra of both extracts showed similar main vibrations of the functional groups typical for phytoconstituents possessing bioactivity. The obtained data suggest potential application of these extracts as natural antioxidants and preparations with biocidal activity. Additionally, both extracts may be regarded as potential natural conservants in cosmetics, as well as natural preservatives in food.

A Review on Antistaphylococcal Secondary Metabolites from Basidiomycetes

Fungi are a rich source of secondary metabolites with several pharmacological activities such as antifungal, antioxidant, antibacterial and anticancer to name a few. Due to the large number of diverse structured chemical compounds they produce, fungi from the phyla Ascomycota, Basidiomycota and Muccoromycota have been intensively studied for isolation of bioactive compounds. Basidiomycetes-derived secondary metabolites are known as a promising source of antibacterial compounds with activity against Gram-positive bacteria. The continued emergence of antimicrobial resistance (AMR) poses a major challenge to patient health as it leads to higher morbidity and mortality, higher hospital-stay duration and substantial economic burden in global healthcare sector. One of the key culprits for AMR crisis is Staphylococcus aureus causing community-acquired infections as the pathogen develops resistance towards multiple antibiotics. The recent emergence of community strains of S. aureus harbouring methicillin-resistant (MRSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) genes associated with increased virulence is challenging. Despite the few significant developments in antibiotic research, successful MRSA therapeutic options are still needed to reduce the use of scanty and expensive second-line treatments. This paper provides an overview of findings from various studies on antibacterial secondary metabolites from basidiomycetes, with a special focus on antistaphylococcal activity.

In vivo Antistaphylococcal Activity Evaluation of Ocimum gratissimum Linn. (Lamiaceae) Ophthalmic Ointment

The goal of this study is to evaluate the antistaphylococcal potential of ophthalmic ointment obtained from the leaves of Ocimum gratissimum. Cutaneous and ocular tolerances of methanolic extract of O. gratissimum leaves were evaluated according to the Organisation for Economic Co-operation and Development (OECD) 404 and 405 Guidelines. Gentamicin ophthalmic ointment 0.3 % was used as antibiotic reference. In vivo antibacterial activity evaluation of the phytomedicine was carried out in rabbits infected by S. aureus CIP 4.83. During 15 days, three groups of 6 animals were treated as follows: the excipient (vaseline + liquid paraffin), gentamicin ointment and Ocimum gratissimum ophthalmic ointment (OGO). 0, 5% Good cutaneous and ocular tolerances of methanolic extract were observed. The microbial contamination control carried out on the 5th and 240th days showed that the prepared formulation is consistent with the preparation of cleanliness standards for topical application to the European Pharmacopoeia. The subconjunctival injection of S. aureus suspension caused mucopurulent acute keratoconjunctivitis with edema, and sometimes eyelid erythema. It is therefore on these ocular observations that therapeutic efficacy of the phytomedicine was evaluated. The treated rabbits without anti-infective agent have developed leucoma, eyelids swelling and conjunctiva hyperemia. Only one panophthalmitis case was observed. From the 1st to 5th days, we observed significant and gradual regression on ocular damages in animals treated with gentamicin. On the 15th day, the eye became normal; the rabbits showed no lesion on cornea. The batch treated with OGO is experiencing a similar trend. The in vivo therapeutic activity of the OGO was similar to that of gentamicin.

Whether Supercritical Extracts from the Aerial Parts of Helianthus salicifolius and Helianthus tuberosus May be Regarded as a Potential Raw Materials for Non-bioenergy Purposes?

The extracts from the aerial parts of Helianthus salicifolius A. Dietr and Helianthus tuberosus L. collected in June were obtained using carbon dioxide supercritical fluid extraction with water as co-solvent. The antimicrobial activity in vitro of these extracts were determined against the reference species of Gram-positive and Gram-negative bacteria as well as fungi, representing by the yeast species of Candida spp. The following parameters were estimated: minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC). Both extracts were found to possess antimicrobial activity with MIC = 0.62-5 mg mL-1 for bacteria and MIC = 5-10 mg mL-1 for yeasts, showing bactericidal (MBC/MIC = 2-4) or fungicidal effect (MFC/MIC = 1-2 ). The highest activity was observed against S. aureus ATCC 29213 (MIC = 0.62 mg mL-1 for H. salicifolius extract; MIC = 2.5 mg mL-1 for H. tuberosus extract). Bactericidal effect of both extracts against S. aureus ATCC 29213 was confirmed by time-kill assay. Higher antioxidant activity was found for H. tuberosus extract (EC50 = 0.332 mg mL-1) as compared to that of H. salicifolius (EC50 = 0.609 mg mL-1). The total polyphenol content (TPC) expressed as gallic acid equivalents (GAE) was 13.75 ± 0.50 mg GAE (g of H. salicifolius extract)-1 and 33.06 ± 0.80 mg GAE (g of H. tuberosus extract)-1. There was a correlation between the antioxidant potential of both extracts and TPC but not between antistaphylococcal activity and TPC. The obtained data suggest potential application of these extracts as the natural preparations with the biocidal activity, including those with antistaphylococcal activity. Besides, both extracts may be regarded as potential natural conservants in cosmetics as well as natural preservatives in food.

Comparative antibiotic resistance of S. aureus strains isolated in surgical and therapeutic departments of hospitals

Objectives - to identify the characteristics of resistance of clinical isolates of S. aureus, obtained in hospitals of various specialization, to beta-lactam antibiotics, and to improve recommendations for empirical etiotropic therapy prescribed to patients with staphylococcal infections. Materials and methods. The subject of the study is the clinical isolates of S. aureus received from patients hospitalized to Vitebsk Regional Clinical Infectious Diseases Hospital "therapeutic" isolates, n=117) and purulent surgery departments and intensive care units of Vitebsk Regional Clinical Hospital ("surgical" isolates, n=111) in 2016-2017 years. Methods for the study of antibiotic resistance of clinical isolates of S. aureus: disk diffusion method, method for determining the beta-lactamase activity of bacterial suspension using the "BioLactam" test system. Results. It was found, that 80.6% of the therapeutic isolates and 73.2% of the surgical isolates were resistant to the 1st generation penicillins. 5.4% of therapeutic isolates and 34% of surgical isolates were resistant to inhibitor-protected beta-lactams. 36.8% of surgical isolates and no therapeutic isolates were resistant to cephalosporins of the 3rd generation. No MRSA were detected among the therapeutic isolates, and among the surgical isolates the prevalence of MRSA was 30.5%. 93.3% of therapeutic isolates of S. aureus did not show any beta-lactamase activity. Among surgical isolates there were only 34.4% of such isolates. Direct Spearman's correlations of moderate strength were revealed between the levels of beta-lactamase activity of S. aureus isolates, the duration of hospitalization and febrile period, as well as between the isolation of MRSA and the duration of hospitalization, fever and diarrheal syndrome. Conclusion. The use of inhibitor-protected penicillins and 3rd generation cephalosporins is recommended for empirical antibiotic therapy of "therapeutic" infections caused by S. aureus. Reserve antibiotics with selective antistaphylococcal activity (such as glycopeptides or oxazolidinones) are required for empirical antibacterial therapy of staphylococcal infections in surgical departments and resuscitation units