Sulfonamides complexed with metals as mycobacterial biofilms inhibitors.

Rapidly growing mycobacteria (RGM) are found in non-sterile water and often associated with severe post-surgical infections and affect immunocompromised patients. In addition, RGM can prevent the host's immune response and have the ability to adhere to and form biofilms on biological and synthetic substrates, making pharmacological treatment difficult because conventional antimicrobials are ineffective against biofilms. Thus, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this context, sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against various microorganisms. Considering the importance of combating RGM-associated infections, this study aimed to evaluate the activity of sulfonamide metal complexes against RGM biofilm. The sulfonamides were tested individually for their ability to inhibit mycobacterial formation and destroy the preformed biofilm of standard RGM strains, such as Mycobacterium abscessus, M. fortuitum, and M. massiliense. All sulfonamides complexed with metals could reduce, at subinhibitory concentrations, the adhesion and biofilm formation of three RGM species in polystyrene tubes. It is plausible that the anti-biofilm capacity of the compounds is due to the inhibition of c-di-GMP synthesis, which is an important signal for RGM biofilm formation. Hence, the impacts and scientific contribution of this study are based on the discovery of a potential new therapeutic option against RGM-associated biofilm infections. Sulfonamides complexed with metals have proven to be a useful and promising tool to reduce microbial adhesion on inert surfaces, stimulating the improvement of methodologies to insert compounds as new antibacterial and coating agents for medical and hospital materials.

Sulfamethoxazole derivatives complexed with metals: a new alternative against biofilms of rapidly growing mycobacteria.

Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with biofilm formation. In this context, this work aimed to evaluate the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on rapidly growing mycobacteria (RGM), as well as to evaluate their safety through cytotoxic assays. The results demonstrate potentiation of the novel compounds in antibiofilm activity, mainly in the complex with Au, which was able to completely inhibit biofilm formation and had the capacity to destroy the biofilm at all the concentrations tested. All cytotoxic data suggest that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives, as well as safe molecules, which could be used as potential therapeutic agents for bacterial and biofilm elimination.

The antibacterial and anti-biofilm activity of gold-complexed sulfonamides against methicillin-resistant Staphylococcus aureus.

The drug-resistant strains of Staphylococcus aureus have been considered as one of the serious health threats, which are related to high patient hospitalization rates. Besides, Staphylococcus aureus biofilm formation exhibits a drug-tolerant nature and shows nonspecific resistance against a broad-spectrum of antibiotics. The emergence of drug-resistant bacteria stimulated the development of novel medicines as a strategy to control infections. In this study, we evaluated the antibacterial and anti-biofilm activity of gold-complexed sulfonamides against Staphylococcus aureus strains such as methicillin-resistant S. aureus and clinical isolates. Our data showed that the exposure of gold-complexed sulfonamides promoted a remarkable reduction in the bacterial adhesion. Also, confocal microscopy displayed the effects of the compounds on in the bacterial cell biofilm, revealed that the compounds decreased the biofilm formation. Our results also demonstrated that gold-complexed sulfonamides exhibited potent antibacterial activity against Staphylococcus aureus strains. Besides, all compounds presented a synergic antibacterial activity when were associated with classical antibiotics. Gold-complexed sulfonamide compounds did not promote toxic effects on Caenorhabditis elegans. Thus, our results showed that the coordination of sulfonamide with gold is a promising alternative in the development of safe and active compounds against methicillin-resistant and clinical isolates S. aureus.

Anti-biofilm activity of A22 ((S-3,4-dichlorobenzyl) isothiourea hydrochloride) against Pseudomonas aeruginosa: Influence on biofilm formation, motility and bioadhesion.

Bacterial biofilms are involved in various medical infections and for this reason it is of great importance understanding adhesion mechanisms of involved microorganisms is essential to develop new strategies of prevention and control. Different approaches have been used for preventing biofilm related infections in health care settings, such as use of surface coatings agents in medical implants. In this context, is necessary to explore new compounds with anti-biofilm activity. Thus, this study evaluated for the first time the action of A22 against biofilms of Pseudomonas aeruginosa PAO1 strain and multi-resistant clinical isolates on biotic and abiotic surfaces. A22 acts as inhibitor of the MreB protein of the bacterial cell wall, causing the rods to change shape to the coccoid form. In this work, A22 at subinhibitory concentrations was able to prevent biofilm formation, and atomic force microscopy images showed that A22 was highly effective in inhibiting adhesion on polyethylene surfaces. Pseudomonas aeruginosa PAO1 exhibited a strong ability to adhere to HeLa cells, and A22 inhibited the aggregation after 4 h of exposure. Swarming and twitching motilities were significantly altered by A22 at subinhibitory concentrations. Thus, by changing the shape of the bacterial cell, many properties can be affected, such as motility, surface adhesion and biofilm formation. This work presents A22 as a promising novel antibacterial or surface coating agent of medical materials.

In vitro antimicrobial efficacy of a fixed-dose combination of RHZE against M. tuberculosis

ABSTRACT The use of drugs in fixed-dose combination (FDC) is now recommended by the World Health Organization (WHO) due to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis. FDC uses different drugs against tuberculosis (TB) in a single tablet for phase-intensive therapeutic intervention. This therapy aims to optimize treatment, to prevent inappropriate use of drugs, and to prevent the emergence of new resistant strains. This study aims to evaluate the susceptibility of clinical isolates of M. tuberculosis against rifampicin, isoniazid, ethambutol, and pyrazinamide. The antimicrobials were tested separately and in associations according to FDC. This was used for broth microdilution method, which was compared to the proportions method previously considered as the gold standard. In antimicrobials testing alone, several strains were resistant to one, two, or three drugs. However, when applied to association of drugs in FDC, there was no antimicrobial resistance. The results strengthen the FDC's concept, which aims to unite the four anti-TB drugs to combat bacterial resistance.

Antibiofilm effect of antimicrobials used in the therapy of mycobacteriosis.

Rapidly growing mycobacteria (RGM) are opportunistic pathogens found in the environment. When in biofilms, mycobacteria is highly resistant to antibacterial treatments. The purpose of this study is to evaluate the antibiofilm activity of antimicrobials commonly used in therapy against mycobacteria. The antimicrobial susceptibility of Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium massiliense was determined in planktonic and sessile populations. The antimicrobials amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole were tested. For each drug, it was evaluated the susceptibility of the pathogen, the ability to inhibit biofilm formation and the resistance of biofilms to antimicrobial activity. Results showed although, the antimicrobials tested are used as an alternative therapy for RGM, M. abscessus proved to be resistant to clarithromycin, beside that, M. massiliense showed a resistant profile to clarithromycin and sulfamethoxazole. Moreover, the inhibition of biofilm formation and its destruction have not been fully met. Considering that the biofilms are a known form of bacterial resistance, the failure of alternatives to inhibit or destroy biofilms can trigger the recurrence of infections. In RGM, besides causing treatment failures, biofilms are a factor of pathogenic risk, since these microorganisms are found in environmental sources and can cause infections easily.

Identification of antimicrobial activity among new sulfonamide metal complexes for combating rapidly growing mycobacteria.

Mycobacteriosis is a type of infection caused by rapidly growing mycobacteria (RGM), which can vary from localized illness, such as skin disease, to disseminated disease. Amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole are antimicrobial drugs chosen to treat such illnesses; however, not all patients obtain the cure. The reason why the treatment does not work for those patients is related to the fact that some clinical strains present resistance to the existing antimicrobial drugs; thereby, the research of new therapeutic approaches is extremely relevant. The coordination of antimicrobial drugs to metals is a promising alternative in the development of effective compounds against resistant microorganisms. Sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against a variety of microorganisms. Considering the importance of fighting against infections associated with RGM, the objective of this study is to evaluate the antimycobacterial activity of metal complexes of sulfonamides against RGM. Complexed sulfonamides activity were individually tested and in association with trimethoprim. The minimum inhibitory concentration (MIC) and time-kill curve of compounds against the standard strains of RGM [Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841) and Mycobacterium massiliense (ATCC 48898)] was determined. The interaction of sulfonamides with trimethoprim was defined by inhibitory concentration index fractional for each association. The results showed that sulfonamides complexed whit metals have outstanding antimicrobial activity when compared to free sulfamethoxazole, bactericidal activity and synergistic effect when combined with trimethoprim.

Detection of Staphylococcus aureus with an intermediate profile to vancomycin (VISA) isolate from Santa Maria, RS.

Twenty-three isolates of Staphylococcus aureus resistant to methicillin have been analyzed, being found a clinical isolate of VISA through microdilution technique. The others techniques were unable to detect such isolates. This is the first study that shows the presence of VISA in clinical isolates in the city of Santa Maria-RS.

Chlorhexidine activity against bacterial biofilms.

BACKGROUND: A biofilm is a complex microbiological ecosystem deposited on surfaces. Microorganisms in form of biofilms are of particular clinical concern because of the poor response to antimicrobial treatments. This study aimed to determine whether bacterial and fungal biofilms are able to resist the antimicrobial activity of chlorhexidine, a powerful antiseptic widely used in the hospital environment. METHODS: Disk diffusion and susceptibility tests were conducted in accordance with Clinical and Laboratory Standards Institute standards for the determination of biofilm inhibitory concentration. Chlorhexidine was tested first at a minimum inhibitory concentration and then at higher concentrations when it was not able to destroy the biofilm. The plates were developed with a solution of 0.1% crystal violet, and readings were made at an optical density of 570 nm. RESULTS: Chlorhexidine demonstrated excellent antimicrobial activity for most microorganisms tested in their free form, but was less effective against biofilms of Acinetobacter baumannii, Escherichia coli, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa. CONCLUSION: This study confirms that microorganisms in biofilms have greater resistance to chlorhexidine, likely owing to the mechanisms of resistance conferred to the structure of biofilms.

Identification of mycobacteria isolated at University Hospital of Santa Maria, Rio Grande do Sul, Brazil / Identificação de micobactérias isoladas no Hospital Universitário de Santa Maria, Rio Grande do Sul, Brasil

This study evaluated the prevalence of nontuberculous mycobacterium (NTM) in relation to the total number of cases of mycobacterial infections detected in patients admitted at the University Hospital of Santa Maria from 2008 to 2010. From the positive samples for the genus Mycobacterium, 67% belonged to the Mycobacterium tuberculosis complex (MTBC) and 33% of them were classified as NTM. This investigation aims to contribute to the epidemiology of mycobacterioses, inasmuch as patients infected by NTM require distinctive treatment and monitoring in comparison with those infected by MTBC.

Foi avaliada a prevalência de micobactérias não tuberculosas (MNT) em relação ao total de casos de micobacterioses identificadas em pacientes do Hospital Universitário de Santa Maria, entre os anos de 2008 e 2010. Entre as amostras positivas para o gênero Mycobacterium, 67% eram do complexo Mycobacterium tuberculosis (CMTB) e 33% foram classificadas como MNT. Este estudo procura contribuir com a epidemiologia das micobacterioses, uma vez que os pacientes infectados por MNT necessitam de tratamento e acompanhamento diferenciado dos infectados pelo CMTB.

Evaluation of antimycobacterial activity of a sulphonamide derivative.

Mycobacterial infections including Mycobacterium tuberculosis have been increasing globally. The additional prevalence of multidrug-resistant (MDR-TB) strains and extensively drug-resistant tuberculosis (XDR-TB) stimulate an urgent need for the development of new drugs for the treatment of mycobacterial infections. It is very important to test the antimicrobial activity of novel compounds because they can be used in new with antimycobacterial drug formulation. Studies have shown that Mycobacterium smegmatis can be used in Minimum Inhibitory Concentration (MIC) assays with the advantage of rapidly and safely screen anti-tubercular compounds. This paper presents an evaluation of potential mycobacteriological compounds derived from inorganic synthesis and their microbiological performance along and in conjunction with Trimethoprim. Antimicrobial activity experiments were carried out by using the microdilution technique in broth to evaluate the sensibility against M. smegmatis. MIC values were between 0.153 and 4.88 µg/ml for the compounds tested. Tests of interaction between drugs were made by the method of Fractional Inhibitory Concentration Index (FICI). The compound [Au (sulfatiazolato)(PPh3)] showed synergism FICI = 0.037 and was evaluated by isobols.

A simple and inexpensive automated technique for measurement of serum nitrite/nitrate.

OBJECTIVE: We described an automated technique for measurement of serum nitrite/nitrate (NO(x)) using the Cobas Mira clinical chemistry analyzer. DESIGN AND METHODS: NO(x) was measured by the modified Griess method. Precision, accuracy, linearity, instrument carry-over and lower limit of quantitation (LLOQ) were assessed. RESULTS: The automated technique for measurement of serum NO(x) was linear, precise, and accurate. It has a LLOQ of 2.0 µmol/L. CONCLUSION: Serum NO(x) measured by the modified Griess method can be applied easily to the Cobas Mira clinical chemistry analyzer.