Progressive Development Of Resistance Research Articles

Antifungal and Modulatory Activity of Lemon Balm (Lippia alba (MILL.) N. E. BROWN) Essential Oil

Fungal diseases and the progressive development of resistance are a challenge. In this context, Lippia alba (lemon balm) is a species used in folk medicine, being described with antimicrobial potential. The aim of this study was to determine the antifungal activity and modulating effect of the essential oil of Lippia alba (Mill.) N.E. Brown leaves (LaEO). The antifungal activity of LaEO on eight Candida strains was determined by minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC), minimum biofilm inhibition concentration (MBIC), minimum biofilm eradication concentration (MBEC) and time-kill. The checkerboard technique was used to determine the modulating effect of LaEO on antifungal activity. The results indicate the presence of 11 constituents, with a predominance of carvone (58.15%) and limonene (25.37%). LaEO was able to inhibit the growth of all tested microorganisms, with MIC and MLC ranging from 0.078 to 1.25 mg/mL and MBIC and MBEC ranging from 0.156 to 5 mg/mL. The time-kill assay showed that LaEO was able to eliminate the strains after two hours of exposure and the best association was observed for the combination of LaEO and ketoconazole. The results of the study indicate that LaEO has excellent antifungal activity with potential biotechnological application.

New approaches to developing antimicrobials for resistant bacteria.

Few medical advances in the twentieth century which we have just completed have had as much potential to change the health of the world’s population as the discovery and clinical application of antibacterial agents. These agents were truly “miracle drugs” and they made it possible to treat a whole series of diseases that formerly were universally fatal or produced a heavy toll of morbidity. The list of such infections that threatened the human race in the preantibiotic era included a variety of venereal diseases, such as syphilis and gonorrhea, as well as pneumococcal pneumonia, tuberculosis, typhoid fever, bubonic plague, and a host of other diseases. The initial antimicrobial agents were discovered by scientists in Germany (arsphenamine and the sulfonamides) and the United Kingdom (penicillin). Subsequently a great deal of work on the discovery of new antimicrobial agents was carried out in the United States and Japan. Indeed, the Japanese contribution to the discovery of new antimicrobial agents is truly remarkable. There are more than 117 useful antibiotics and related agents that have been discovered by Japanese scientists and, of these, 41 agents have been licensed for clinical use throughout the world. The luster of this discovery has been tarnished over the ensuing years by the progressive development of resistance in multiple species of bacteria. Because of this, as we enter the twenty-first century there is again a major need for new antibacterial agents. At the same time, the number of new agents being developed for clinical use has been progressively decreasing. There are several key reasons for the recent decline in the number of newly marketed antimicrobial agents. In the first place, most of the easy targets allowing selective toxicity for antimicrobials have been discovered. Moreover, it is increasingly costly to bring a new antimicrobial agent to the market. It is currently estimated that the average cost to develop a new prescription drug from the discovery phase to active marketing of the drug is

Antibiotic Choices in Surgical Intensive Care Unit Patients

Antibiotics have dramatically changed the care of the critically ill patient over the last 60 years. Patients with complex physiological conditions present with infectious processes requiring the effective use of antimicrobial drugs. In many situations, the inability to eradicate the infectious process is complicated by the progressive development of resistance among the causative organisms. Systemic antibiotic prophylaxis is warranted only for the prevention of wound infections. Regimens in these cases should use large doses of nontoxic antibiotics covering the spectrum of organisms likely to contaminate the wound. The duration of wound prophylaxis should be short, essentially covering only the period of active wound closure; this is usually less than 24 hours. Prevention of most other infections in the ICU depends on the recognition and correction of the various disturbances of host defenses. Topical antibiotic therapy may reduce the level of colonization for a few specific types of infection. Initial empiric antibiotic therapy should be started for clear indications. The antibiotics chosen should be those most likely to be effective against the probable organisms, those which have the lowest toxicity, and those with the smallest likelihood of inducing multiresistance. They must be adjusted promptly based on the microbiologic sensitivities observed. The realization that the physiology of critical illness may alter the normal relations between drug dosages and the tissue antibiotic levels obtained mandates a different approach to the treatment of these patients. The drug volumes of distribution are generally markedly expanded in these patients. Furthermore, these patients require high tissue antibiotic concentrations to improve the chances for successful therapy. Thus, the antibiotics selected must be capable of providing these levels without significant toxicity to the host. Therapy should be continued based on the clinical response observed. Premature cessation of effective therapy often results in relapse.

Emergence and development of resistance to antimicrobial chemicals and heat in spores of Bacillus subtilis.

The emergence and development of chemical and thermal resistance in spores of Bacillus subtilis was examined. The chemicals studied were of the disinfectant type: glutaraldehyde, hypochlorite, hypochlorite-methanol and povidone-iodine. Growth and sporulation were followed by electron microscopy and resistance assigned to specific stages in relation to 45Ca and DPA accumulation. A sequential development of resistance was observed with thermal resistance appearing first at early Stage V corresponding to maturation of cortex and deposition of rudimentary spore coat material. Chemical resistance coincided with middle to late Stage V dependent on the chemical concerned. A progressive development of resistance was observed on prolonged incubation in sporulation medium and was affected by inclusion of lysozyme in the spore washing sequence.