In vitro antimicrobial effects of aztreonam, colistin, and the 3-drug combination of aztreonam, ceftazidime and amikacin on metallo-β-lactamase-producing Pseudomonas aeruginosa

<p>Abstract</p> <p>Background</p> <p>There are limited choice of antimicrobial agents to treat infection with metallo-<it>β</it>-lactamase-producing <it>Pseudomonas aeruginosa</it>. We evaluate the antimicrobial effects of aztreonam alone, colistin alone and the 3-drug combination of aztreonam, ceftazidime and amikacin on 23 strains of metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>by time-killing tests.</p> <p>Methods</p> <p>Strains used were from different hospitals in Japan and had different pulse-field gel electrophoresis patterns by restriction with <it>Spe</it>I. The minimum inhibitory concentrations of 11 antimicrobial agents (piperacillin, piperacillin/tazobactam, imipenem, meropenem, aztreonam, ceftazidime, amikacin, tobramycin, arbekacin, ciprofloxacin and colistin) were determined using the agar dilution test. The effects of aztreonam, colistin and the combination of aztreonam, ceftazidime and amikacin were determined by time-killing studies.</p> <p>Results</p> <p>Bacteriostatic effects after 6 hours of drug exposure were observed in 12 strains (52.2%) of 23 strains of metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>with 48 mg/l aztreonam, in 19 strains (82.6%) with the 3-drug combination of 16 mg/l aztreonam, 16 mg/l ceftazidime, and 4 mg/l amikacin, and in 23 strains (100%) with 2 mg/l colistin. Bactericidal effects after 6 h drug exposure were observed in 1 strain (4.3%) with 48 mg/l aztreonam, in 8 strains (30.4%) with the 3-drug combination and in all 23 strains (100%) with 2 mg/l colistin.</p> <p>Conclusion</p> <p>Evaluation of <it>in vitro </it>antimicrobial effects on metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>revealed relatively good effects of the 3-drug combination of aztreonam, ceftazidime and amikacin and marked effects of colistin.</p

The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms

Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive “non-producing” cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.National Institutes of Health (U.S.). National Institute of Environmental Health Sciences (Training Grant in Toxicology 5 T32 ES7020-37

Preparados estándar de nutrición parenteral en situaciones clínicas complejas Standard parenteral nutrition preparations in complex clinical situations

Objetivo: Los preparados binarios y ternarios de nutrición parenteral, en determinados casos pueden ver su utilidad limitada. El objetivo de este estudio es establecer situaciones de difícil manejo nutricional y analizar el tipo de fórmula utilizada en estas situaciones. Material y métodos: Se incluyen pacientes tratados con nutrición parenteral durante 9 meses. Se definen tres situaciones clínicamente complejas: larga duración, con más de 25 días; insuficiencia renal, uremia > 20 mmol/L o creatinina sérica > 200 µmol/L; e insuficiencia hepática, bilirrubina total > 30 mmol/L o ALT > 2 µkat/L y fosfatasa alcalina > 3 µkat/L o GGT > 3 µkat/L. Se estudian la mortalidad e hipoalbuminemia (Goal: Binary and ternary parenteral nutrition preparations may be of limited use in certain cases. The goal of this study is to establish difficult nutritional situations to handle and analyze the type of formula used in these situations. Material and methods: The study included patients treated with parenteral nutrition over 9 months. Three clinically complex situations were defined: long duration, lasting more than 25 days; kidney failure, uraemia > 20 mmol/L or serum creatinine > 200 µmol/L; and live failure, total bilirubin > 30 mmol/L or ALT > µkat/L and alkaline phosphatase > 3 µkat/L or GGT > 3 µkat/L. Mortality and hypoalbuminaemia (< 35 g/L) were studied and compared by means of a chi squared test (p < 0.05) against the rest of the patients. The use of individualized formulas was studied using a multiple logarithmic regression model, the dependent variable being the administration or not of an individualized formula and the independent variables being the 3 groups of patients in clinical situations defined as complex. The Odds Ratio (OR) was studied as the measure of risk. Results: A total of 511 patients receiving 8,015 feeds with parenteral nutrition were studied. Of these, 283 were included in one or more of the 3 complex clinical situations. All three groups presented higher levels of mortality and hypoalbuminaemia with statistically significant differences when compared to the group in a non-complex clinical situation. The use of individualized formulas was greater in the three groups defined, with statistically significant differences resulting: OR=6.7 (CI 95%; 3.78-11.91) with long duration; OR=3.66 (CI 95%; 2.68-5.68) in kidney failure; and OR=1.5 (CI 95%;1.01-2.35) in liver failure. Conclusions: Patients in complex clinical situations present greater visceral malnutrition, a worse clinical evolution and, at our hospital, their nutritional treatment by parenteral means is based on a greater use of individualized formulas