Animal Health Protection - Assessing Antimicrobial Activity of Veterinary Disinfectants and Antiseptics and Their Compliance with European Standards: A Narrative Review.

Disinfectants and antiseptics lead in reducing the number of microorganisms, including pathogenic ones, thus limiting the number of infections. In the veterinary field, disinfection prevents the transfer of pathogenic microorganisms from animals to humans and , as well as among animals. Several assays of disinfectant antimicrobial activity testing, often not standardized, without appropriate controls, and not validated, have been used and published.

In Vitro Resistance-Predicting Studies and In Vitro Resistance-Related Parameters-A Hit-to-Lead Perspective.

Despite the urgent need for new antibiotics, very few innovative antibiotics have recently entered clinics or clinical trials. To provide a constant supply of new drug candidates optimized in terms of their potential to select for resistance in natural settings, in vitro resistance-predicting studies need to be improved and scaled up. In this review, the following in vitro parameters are presented: frequency of spontaneous mutant selection (FSMS), mutant prevention concentration (MPC), dominant mutant prevention concentration (MPC-D), inferior-mutant prevention concentration (MPC-F), and minimal selective concentration (MSC).

Exploiting thiol-functionalized benzosiloxaboroles for achieving diverse substitution patterns - synthesis, characterization and biological evaluation of promising antibacterial agents.

Benzosiloxaboroles are an emerging class of medicinal agents possessing promising antimicrobial activity. Herein, the expedient synthesis of two novel thiol-functionalized benzosiloxaboroles 1e and 2e is reported. The presence of the SH group allowed for diverse structural modifications involving the thiol-Michael addition, oxidation, as well as nucleophilic substitution giving rise to a series of 27 new benzosiloxaboroles containing various polar functional groups, , carbonyl, ester, amide, imide, nitrile, sulfonyl and sulfonamide, and pendant heterocyclic rings.

Aromatic Diboronic Acids as Effective KPC/AmpC Inhibitors.

Over 30 compounds, including -, -, and -phenylenediboronic acids, -substituted phenylboronic acids, benzenetriboronic acids, di- and triboronated thiophenes, and pyridine derivatives were investigated as potential β-lactamase inhibitors. The highest activity against KPC-type carbapenemases was found for -phenylenediboronic acid , which at the concentration of 8/4 mg/L reduced carbapenems' MICs up to 16/8-fold, respectively. Checkerboard assays revealed strong synergy between carbapenems and with the fractional inhibitory concentrations indices of 0.

Efflux-Related Carbapenem Resistance in Is Associated with Two-Component Regulatory Efflux Systems' Alteration and Insertion of ΔAbaR25-Type Island Fragment.

The efflux pumps, beside the class D carbapenem-hydrolysing enzymes (CHLDs), are being increasingly investigated as a mechanism of carbapenem resistance in . This study investigates the contribution of efflux mechanism to carbapenem resistance in 61 acquired -genes-carrying clinical strains isolated in Warsaw, Poland. Studies were conducted using phenotypic (susceptibility testing to carbapenems ± efflux pump inhibitors (EPIs)) and molecular (determining expression levels of efflux operon with regulatory-gene and whole genome sequencing (WGS)) methods.

Mutant Prevention Concentration, Frequency of Spontaneous Mutant Selection, and Mutant Selection Window-a New Approach to the Determination of the Antimicrobial Potency of Compounds.

The analysis of antimicrobial activity is usually MIC- and minimal bactericidal concentration (MBC)-focused, though also crucial are resistance-related parameters, e.g., the frequency of spontaneous mutant selection (FSMS), the mutant prevention concentration (MPC), and the mutant selection window (MSW).

The Contribution of Efflux Systems to Levofloxacin Resistance in Clinical Strains Isolated in Warsaw, Poland.

Levofloxacin is considered an alternative treatment option of infections to trimethoprim/sulfamethoxazole. The fluoroquinolone resistance in is usually caused by an overproduction of efflux pumps. In this study, the contribution of efflux systems to levofloxacin resistance in clinical isolates was demonstrated using phenotypic (minimal inhibitory concentrations, MICs, of antibiotics determination ± efflux pump inhibitors, EPIs) and molecular (real-time polymerase-chain-reaction and sequencing) methods.

Oxazoline scaffold in synthesis of benzosiloxaboroles and related ring-expanded heterocycles: diverse reactivity, structural peculiarities and antimicrobial activity.

Two isomeric benzosiloxaborole derivatives 3a and 5a bearing fluorine and 4,4-dimethyl-2-oxazolin-2-yl substituents attached to the aromatic rings were obtained. Both compounds were prone to hydrolytic cleavage of the oxazoline ring after initial protonation or methylation of the nitrogen atom. The derivative 3c featuring -methylammoniumalkyl ester functionality was successfully subjected to -sulfonylation and -acylation reactions to give respective derivatives which demonstrates its potential for modular synthesis of structurally extended benzosiloxaboroles.

Phenotypic and Molecular Characteristics of the MDR Efflux Pump Gene-Carrying Strains Isolated in Warsaw, Poland.

An increase of nosocomial infections caused by strains has recently been observed all over the world. The isolation of these bacteria from the blood is of particular concern. In this study we performed the phenotypic and genotypic characterization of 94 isolates, including isolates from patients hospitalized in a tertiary Warsaw hospital ( = 79) and from outpatients ( = 15).

Antimicrobial and KPC/AmpC inhibitory activity of functionalized benzosiloxaboroles.

A series of 22 benzosiloxaboroles, silicon analogues of strong antimicrobial agents - benzoxaboroles, have been synthesized and tested against β-lactamases KPC- and pAmpC-producing strains of Gram-negative rods. Comprehensive structural-property relationship studies supported by molecular modelling as well as biological studies reveal that 6-B(OH)-substituted derivative 27 strongly inhibits the activity of cephalosporinases (chromosomally encoded AmpC and plasmid encoded CMY-2) and KPC carbapenemases. It also shows strong ability to inhibit growth of the strains producing KPC-3 when combined with meropenem.

Non-antibiotics, Efflux Pumps and Drug Resistance of Gram-negative Rods.

Non-antibiotic medicinal products consist of drugs with diverse activity against bacteria. Many non-antibiotics demonstrate direct anti-bacterial activity against Gram-positive cocci. The activity observed against Gram-negative rods is much lower and non-antibiotics primarily from the following groups: non-steroidal anti-inflammatory drugs, cardiovascular and antidepressant medicinal products demonstrate this activity.

Identification of proteins, drying oils, waxes and resins in the works of art micro-samples by chromatographic and mass spectrometric techniques.

Simplified method for simultaneous identification of proteins, drying oils, waxes, and resins in the works-of-art samples was developed. Liquid chromatography with mass spectrometry and gas chromatography with mass spectrometry were used to identify natural materials most frequently encountered in historical paintings. Protein binders were extracted with ammonia and purified using miniaturized solid-phase microextraction (Omix tips) to efficiently suppress matrix interferences.

Prevalence of ESBL-producing Pseudomonas aeruginosa isolates in Warsaw, Poland, detected by various phenotypic and genotypic methods.

Knowledge of the prevalence of ESBL enzymes among P. aeruginosa strains compared to the Enterobacteraiceae family is limited. The phenotypic tests recommended by EUCAST for the detection of ESBL-producing Enterobacteriaceae are not always suited for P.

The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria.

The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO₄.

The Influence of Efflux Pump Inhibitors on the Activity of Non-Antibiotic NSAIDS against Gram-Negative Rods.

Background: Most patients with bacterial infections suffer from fever and various pains that require complex treatments with antibiotics, antipyretics, and analgaesics. The most common drugs used to relieve these symptoms are non-steroidal anti-inflammatory drugs (NSAIDs), which are not typically considered antibiotics. Here, we investigate the effects of NSAIDs on bacterial susceptibility to antibiotics and the modulation of bacterial efflux pumps.

CHEMICAL COMPOSITION AND ANTIBACTERIAL ACTIVITY OF SOME MEDICINAL PLANTS FROM LAMIACEAE FAMILY.

Chemical composition and antibacterial activity of aqueous (ethanolic and methanolic) extracts from herbs often used in Polish cuisine and traditional herbal medicine including thyme (Thymus vulgaris L.), rosemary (Rosmarinus officinalis L.), oregano (Origanum vulgare L.

Modification of the susceptibility of gram-negative rods producing ESβLS to β-lactams by the efflux phenomenon.

The production of β-lactamases is the most important mechanism of Gram-negative rod resistance to β-lactams. Resistance to ceftazidime and cefepime in clinical isolates of Enterobacteriaceae (especially ESβL-positive E. coli and K.

Synthesis and antimicrobial and nitric oxide synthase inhibitory activities of novel isothiourea derivatives.

The reaction of substituted benzylhalides, or of halomethyl derivatives of thiophene or furane, with thiourea or its derivatives yielded the respective isothioureas as hydrohalide salts. The products (a total of 17, including 16 novel compounds) were tested for activity against five Gram-positive and nine Gram-negative bacterial strains, six yeast species and two protozoan species. The most active against Gram-positive bacteria were S-(2,4-dinitrobenzyl)isothiourea hydrochloride (MIC range for four out of five strains tested: 12.

Defect in dolichol-dependent glycosylation increases sensitivity of Saccharomyces cerevisiae towards anti-fungal drugs.

Two temperature-sensitive Saccharomyces cerevisiae mutants, sec59-1 and dpm1-6, impaired, respectively, in dolichol kinase (Sec59p) and dolichyl phosphate mannose (DolPMan) synthase (Dpm1p), have an aberrant cell wall structure and composition. We tested their sensitivity to four classes of antifungal drugs used in clinical practice: 5-fluorocytosine, amphotericin B, caspofungin and itraconasole. The strains were resistant to itraconazole and sensitive to the other drugs used.

A novel isoquinoline alkaloid, DD-carboxypeptidase inhibitor, with antibacterial activity isolated from Streptomyces sp. 8812. Part I: Taxonomy, fermentation, isolation and biological activities.

A novel isoquinoline alkaloid of molecular formula C10H9NO4, labeled JS-1, was isolated from the culture broth of Streptomyces sp. 8812. It was purified by acetone protein precipitation from the culture supernatant, followed by anion exchange and C18 RP HPLC columns.

Synthesis of 1-{4-[4-(adamant-1-yl)phenoxymethyl]-2-(4-bromophenyl)- 1,3-dioxolan-2-ylmethyl}imidazole with expected antifungal and antibacterial activity.

A multistep synthesis of a new analogue of ketoconazole, which was expected to show antifungal and antibacterial activity, has been described.

Synthesis and antibacterial activity of 5-adamantan-1-yl-methyl analogues of trimethoprim.

A series of new trimethoprim [5-(3,4,5-trimethoxy-benzyl)-pyrimidine-2,4- diamine] analogues were prepared by condensation of adamantane-1-carbaldehyde with 3-methoxypropionitrile, followed by reaction of resulting mixture of 2-adamantan-1-ylmethyl-3-methoxy-acrylonitrile and 3-adamantan-1-yl-2-methoxymethyl-acrylonitrile with guanidine, acetamidine and thiourea, respectively. The activity of compounds obtained and sulfamethoxazole, alone and in combination, against several bacterial strains, as well as fungi was investigated.

[Synantropic cockroaches (Blattella germanica L.) in hospital environment--microbiological hazard for patients and hospital infections risk assessment].

Objective: The aim of our study was to determine what a hazard for patients creates the presence of cockroaches in hospital environment.

Material And Methods: The probable hospital infections cases in 9 hospitals in Warsaw were found in database of the Country Hospital Morbidity Register for the year 2004 and correlation between such factors as: drug resistance of bacteria isolated from external part of cockroach's bodies, their ability to biofilm building, adherence, resistance to disinfectants, resistance of cockroaches to insecticides, infestation level vs. infections of several body systems was examined.

Glycoprotein hypersecretion alters the cell wall in Trichoderma reesei strains expressing the Saccharomyces cerevisiae dolichylphosphate mannose synthase gene.

Expression of the Saccharomyces cerevisiae DPM1 gene (coding for dolichylphosphate mannose synthase) in Trichoderma reesei (Hypocrea jecorina) increases the intensity of protein glycosylation and secretion and causes ultrastructural changes in the fungal cell wall. In the present work, we undertook further biochemical and morphological characterization of the DPM1-expressing T. reesei strains.