José Luis Gómez-Garcés

Antimicrobial polymethacrylates based on quaternized 1,3-thiazole and 1,2,3-triazole side-chain groups

Polymers containing quaternary ammonium cations (QUATS) are well-known antimicrobial and disinfectant agents. Mono- and bis-heterocyclic methacrylate monomers (MTAs) and their corresponding polymers (PMTAs) bearing 1,3-thiazole and 1,2,3-triazole groups with different spacer groups were designed, inspired by azole heterocycles found in nature. PMTAs were obtained by a simple synthetic approach from alkynyl alcohols and a thiazole azide derivative, followed by conventional radical polymerization. The N-alkylation of azole rings allowed the preparation of mono and dicationic polyelectrolytes (PMTAs-RI) with different amphiphilic natures. The resulting antimicrobial properties towards different microorganisms, bacteria and fungi, which are the cause of healthcare-associated infections, as well as their hemotoxic action using human blood red cells (RBCs) are reported. The results demonstrate that methyl and butyl quaternized PMTAs present a highly selective toxicity against microorganisms because they are non-hemolytic (some of them with selectivity values higher than 1000). In contrast, longer N-alkyl analogs lead to a reduction in antimicrobial activity, showing a general structure–activity relationship that depends on the amphiphilic balance of the polycation. These polymeric families may provide a scope for developing a new class of versatile antimicrobial QUATS with promising biomedical applications.

High Efficiency Antimicrobial Thiazolium and Triazolium Side-Chain Polymethacrylates Obtained by Controlled Alkylation of the Corresponding Azole Derivatives

Two series of antimicrobial polymethacrylates (PMTAs) bearing mono and bis-cationic quaternary ammonium cations (QUATs) were prepared by controlled N-alkylation of 1,3-thiazole and 1,2,3-triazole pendant groups with butyl iodide (PMTAs-BuI). The degree of quaternization (DQ) of the azole heterocycles was monitored by (1)H NMR spectroscopy over a wide range of reaction times. Spectra analysis of the (1)H NMR aromatic region allowed to characterize and quantify the different species involved and, therefore, to control the chemical composition distribution of the amphiphilic polycations. The polymer charge density and the hydrodynamic sizes were measured by zeta potential and dynamic light scattering (DLS), respectively. Consequently, the relationship between structure and antibacterial properties and toxicity was studied. Interestingly, these polyelectrolytes present excellent selective toxicity against bacteria being nonhemolytic even at low values of DQ. Furthermore, they were also evaluated for their microbial time-killing efficiency, presenting a 3 log-reduction in only 15 min. Additionally, the bacteria cell morphology treated with PMTAs-BuI was analyzed.

Effect of glycounits on the antimicrobial properties and toxicity behavior of polymers based on quaternized DMAEMA

Polymers with quaternary ammonium groups such as quaternized poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMAQ) have been used as antimicrobial agents because of their demonstrated good antimicrobial activities against a huge number and types of microbes, although their cytotoxicity is also well-known. In this work block copolymers based on PDMAEMAQ were synthesized containing hydrophobic segments of poly(butyl methacrylate) to improve the antimicrobial activity and glycomonomer units with the aim of decreasing the cytotoxicity of the polymers. Hydrophobic butyl methacrylate (BMA) blocks were chain extended by statistical and block copolymers of DMAEMA and 2-{[(d-glucosamin-2-N-yl)carbonylethyl methacrylate (HEMAGl) glycomonomer of different compositions. In order to find the balance between antimicrobial activity and cytotoxicity, the selectivity index of each polymer was obtained from minimum inhibitory concentrations (MIC) and white and red blood cells toxicity measurements.

Recurrent Episodes of Candidemia Due to Candida glabrata with a Mutation in Hot Spot 1 of the FKS2 Gene Developed after Prolonged Therapy with Caspofungin

ABSTRACT We report two episodes of recurrent candidemia caused by echinocandin-resistant Candida glabrata in a 69-year-old patient who underwent repeated abdominal surgery. In the first episode of candidemia, an echinocandin-susceptible Candida glabrata strain was isolated, and the patient was treated with caspofungin. The isolates from the later episodes showed resistance to echinocandins. Analysis of the HS1 region of the FKS2 gene showed the amino acid substitution S663P. Microsatellite analysis demonstrated a strong genetic relationship between the isolates.

Bacteremia by Dermabacter hominis, a Rare Pathogen

ABSTRACT Dermabacter hominis is a gram-positive, catalase-positive, glucose-fermenting rod, which, as it grows forms small greyish-white colonies with a characteristic pungent odor. Previously known as coryneform Centers for Disease Control and Prevention groups 3 and 5, it was catalogued as D. hominisin 1994. Various strains isolated in blood cultures, abscesses, or wounds in the 1970s were retrospectively characterized in referral centers as D. hominis. In this report we describe two patients with severe underlying pathology who developed bacteremias byD. hominis within the context of their clinical pictures.

Soft Tissue Infections Caused by Actinomyces neuii, a Rare Pathogen

Actinomyces neuii rarely causes disease in humans. First described in 1985 in two patients with postcataract endophthalmitis ([4][1]), A. neuii represents 17% of all clinical Actinomyces isolates ([8][2]), with some 132 cases of infection caused by this microorganism reported to date. The

Antimicrobial films obtained from latex particles functionalized with quaternized block copolymers.

New amphiphilic block copolymers with antimicrobial properties were obtained by atom transfer radical polymerization (ATRP) and copper catalyzed cycloaddition following two approaches, a simultaneous strategy or a two-step synthesis, which were proven to be very effective methods. These copolymers were subsequently quaternized using two alkyl chains, methyl and butyl, to amplify their antimicrobial properties and to investigate the effect of alkyl length. Antimicrobial experiments in solution were performed with three types of bacteria, two gram-positive and one gram-negative, and a fungus. Those copolymers quaternized with methyl iodide showed better selectivities on gram-positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, against red blood cells, demonstrating the importance of the quaternizing agent chosen. Once the solution studies were performed, we prepared poly(butyl methacrylate) latex particles functionalized with the antimicrobial copolymers by emulsion polymerization of butyl methacrylate using such copolymers as surfactants. The characterization by various techniques served to test their effectiveness as surfactants. Finally, films were prepared from these emulsions, and their antimicrobial activity was studied against the gram-positive bacteria. The results indicate that the antimicrobial efficiency of the films depends not only on the copolymer activity but also on other factors such as the surface segregation of the antimicrobial agent to the interface.

Bacteriemias significativas por Corynebacterium amycolatum: un patógeno emergente

Fundamentos Corynebacterium spp. es un genero muy dispar que engloba especies poco conocidas y en el que solo diphteriae, urealyticum y jeikeum son considerados patogenos indiscutibles. Otras especies como amycolatum estan en la actualidad reivindicando su papel como agentes causales de patologia infecciosa, en parte por su mejor conocimiento e identificacion, y en parte por el aumento de pacientes inmunocomprometidos en los cuales suelen desarrollar todo su poder patogeno. Presentamos 3 casos de bacteriemia presumiblemente significativa por C. amycolatum. M ETodos Los aislamientos bacterianos a partir de hemocultivos se llevaron a cabo utilizando un sistema vital. La identificacion se realizo mediante tincion de Gram, morfologia de la colonia, los resultados de numerosas pruebas bioquimicas (incluido el sistema Api Coryne), el comportamiento de aislados frente al agente vibriostatico O\129 y el patron de sensibilidad antibiotica obtenido mediante E-test. Resultados Los tres aislamientos de C. amycolatum pertenecian a pacientes hospitalizados largo tiempo, multi-instrumentados y con patologia grave de base. Los tres tuvieron otros aislamientos concomitantes por C. amycolatum en otra localizacion: esputo, escara y cateter, respectivamente, lo cual podria explicar la procedencia de la bacteriemia. La morfologia de la colonia, los patrones de sensibilidad antibiotica, su resistencia frente al agente vibriostatico O\129 y las pruebas bioquimicas utilizadas fueron semejantes en los tres casos y a los descritos previamente en la literatura. Conclusiones C.amycolatum debe ser tenido en cuenta como agente responsable de patologia grave y significativa en este tipo de pacientes. Ademas posee ciertas caracteristicas especificas que facilitan su sospecha en el trabajo habitual del laboratorio de microbiologia.

Functional surfaces obtained from emulsion polymerization using antimicrobial glycosylated block copolymers as surfactants

In this work, antimicrobial glycosylated block copolymers were successfully immobilized onto polymeric surfaces by using them as surfactants in butyl methacrylate emulsion polymerization. In particular several amphiphilic block copolymers of various compositions were employed, all consisting of a poly(butyl methacrylate) hydrophobic segment and a statistical copolymer containing quaternized trimethylaminoethyl methacrylate and 2-(D-glucosamin-2-N-yl)carbonylethyl methacrylate glycomonomer as a hydrophilic block. The influence of the antimicrobial polymeric surfactant structure and solid content on the emulsion polymerization was investigated in detail. It was demonstrated that the efficiency of the surfactant is highly dependent on the hydrophilic/hydrophobic balance; in general the surface-active properties get worse with an excess of hydrophilicity. Monodisperse and stable latexes stabilized with an antimicrobial polymeric surfactant were successfully obtained and then employed to form active films. The film formation process under thermal treatments was followed and confirmed by AFM. The surface functionality of the films was tested by analyzing the interaction of glycounits of the surface with Concanavalin A lectin by fluorescence spectroscopy. In addition, the antimicrobial capability of these films against Gram-positive bacteria and yeast was demonstrated whereas the leaching of the surfactants to the media was discarded.

Cuadros clínicos asociados a bacteriemia causada por las nuevas especies incluidas en el antiguo grupo Streptococcus bovis

OBJECTIVE We sought to identify possible diseases associated with bloodstream infections caused by new species of S. bovis group isolated in blood cultures and by studying patient records METHODS Forty-four consecutive blood culture isolates initially designated S. bovis were further characterised using phenotypic methods Patient records were examined. RESULTS We identified 15 Streptococcus gallolyticus subsp. gallolyticus, 24 Streptococcus gallolyticus subsp. pasteurianus, and 5 Streptococcus infantarius isolates in 44 BSI episodes. CONCLUSIONS The association between S. bovis bacteraemia and endocarditis and/or colon carcinoma is highly dependent on the causative species. Streptococcus gallolyticus subsp. gallolyticus is a surrogate for endocarditis and/or bowel disease, whereas Streptococcus gallolyticus subsp. pasteurianus is a surrogate for hepato-biliary disease.