In vitro selection of antibiotic resistance in the probiotic strain Lactobacillus rhamnosus GG ATCC 53103.

Antibiotic resistance in probiotic strains is a matter of interest due to the increase in consumption of probiotic products. Many studies have evaluated the antibiotic susceptibility of lactobacilli or the presence of resistance determinants, while knowledge on selection of resistance during exposure to antibiotics is still limited. Our aim was to evaluate the behavior of Lactobacillus rhamnosus GG ATCC 53103, a well-known probiotic microorganism, during exposure to erythromycin, tetracycline, amoxicillin/ clavulanate and ciprofloxacin. Our study demonstrated that prolonged exposure to erythromycin and ciprofloxacin could select mutants with reduced susceptibility, even if these modifications in susceptibility could not be attributed to known antibiotic resistance genes or genetic mutations.

Comparative evaluation of synergy of combinations of beta-lactams with fluoroquinolones or a macrolide in Streptococcus pneumoniae.

OBJECTIVES: Streptococcus pneumoniae has shown a great ability to develop efficacious mechanisms of resistance to the main drugs for the treatment of pneumonia, such as ß-lactams, macrolides and fluoroquinolones. The present study aimed to compare the antipneumococcal activity of combinations of respiratory fluoroquinolones with cephalosporins (either parenteral or oral) or protected penicillin versus the standard combinations (i.e. a macrolide with a protected penicillin or cephalosporin) against 100 isolates with different susceptibilities to macrolides and/or penicillin. METHODS: Chequerboard assays for all isolates and time-kill curves for nine isolates with different patterns of susceptibility were performed. Synergy between antibiotics at serum peak concentrations was also determined. RESULTS: The combination of levofloxacin with ceftriaxone produced the highest rate of synergy (54/100), mainly against macrolide-resistant strains (22/30). Antagonism was not observed for any tested combination apart from clarithromycin with amoxicillin/clavulanic acid (22/100 isolates). Although the killing activities of all antibiotics improved when they were tested in combination, synergy was observed only for some combinations after 12 and/or 24 h. Serum concentrations were effective in inhibiting the growth of the tested strains. CONCLUSIONS: Combinations of levofloxacin with parenteral cephalosporins were the most active among all the tested combinations, while antagonism occurred when clarithromycin and amoxicillin/clavulanic acid were tested.

Effects of Lactobacillus salivarius LS01 (DSM 22775) treatment on adult atopic dermatitis: a randomized placebo-controlled study.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by xerosis, pruritus and eczema. The role of probiotics in the prevention and the treatment of AD have been extensively studied in children with controversial results while there are few studies on an adult population. The aim of this randomized, double-blind, placebo-controlled study is to evaluate the clinical efficacy of the intake of a probiotic strain (Lactobacillus salivarius LS01) in the treatment of adult patients with AD. A group of 38 patients was treated with probiotics or placebo (maltodextrin) for 16 weeks. The study was performed from January (T0) to May, 2009 (T16). The assessment of efficacy was based on change in SCORAD (SCORing Atopic Dermatitis) index, dermatology life quality index (DLQI) improvement, cytokine production by PBMCs and ability to modify faecal microbial flora. No significant adverse events were recorded during the study. Patients treated with probiotics showed a statistically improvement of both clinical parameters (SCORAD p<0.0001 and DLQI p= 0.021) at the end of treatment (T16) compared with the placebo group. Furthermore, after four months of treatment there was a significant reduction of Th1 cytokines (IL-12+IFNgamma) (p= 0.03) and Th1/Th2 ratio (IL-12+IFNgamma/IL-4+IL-5) (p= 0.019) only in placebo-treated patients. A statistically relevant decrease of staphylococci in faeces of the probiotictreated group was also observed at the end of treatment. In our study, the administration of L. salivarius LS01 was well tolerated and was associated with a significant improvement of clinical manifestation and QoL. This probiotic strain could have an important role in modulating Th1/Th2 cytokine profiles and could be considered as an important adjunctive therapy in the treatment of adult AD.

Microbiological evaluation of commercial probiotic products available in the USA in 2009.

Probiotics are widely used to prevent and treat several diseases. Many commercial products are available worldwide. However, there is no clear international or local legislation about them and previous studies showed that most of the tested products are not in conformity with international guidelines. The aim of this study was to determine if products available in the USA market in 2009 were correctly labeled in terms of quantity of viable bacteria, identification of species and cross contamination by species not on the label. Disturbingly, we found that only 4 of 13 products (31%) were in accordance with label claims. Our results suggest the need for adequate control of probiotic production as well as periodical screenings by competent organizations to monitor the effect of storage on product quality.

Effects of liver disease on pharmacokinetics. An update.

Liver disease can modify the kinetics of drugs biotransformed by the liver. This review updates recent developments in this field, with particular emphasis on cytochrome P450 (CYP). CYP is a rapidly expanding area in clinical pharmacology. The information currently available on specific isoforms involved in drug metabolism has increased tremendously over the latest years, but knowledge remains incomplete. Studies on the effects of liver disease on specific isoenzymes of CYP have shown that some isoforms are more susceptible than others to liver disease. A detailed knowledge of the particular isoenzyme involved in the metabolism of a drug and the impact of liver disease on that enzyme can provide a rational basis for dosage adjustment in patients with hepatic impairment. The capacity of the liver to metabolise drugs depends on hepatic blood flow and liver enzyme activity, both of which can be affected by liver disease. In addition, liver failure can influence the binding of a drug to plasma proteins. These changes can occur alone or in combination; when they coexist their effect on drug kinetics is synergistic, not simply additive. The kinetics of drugs with a low hepatic extraction are sensitive to hepatic failure rather than to liver blood flow changes, but drugs having a significant first-pass effect are sensitive to alterations in hepatic blood flow. The drugs examined in this review are: cardiovascular agents (angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium antagonists, ketanserin, antiarrhythmics and hypolipidaemics), diuretics (torasemide), psychoactive and anticonvulsant agents (benzodiazepines, flumazenil, antidepressants and tiagabine), antiemetics (metoclopramide and serotonin antagonists), antiulcers (acid pump inhibitors), anti-infectives and antiretroviral agents (grepafloxacin, ornidazole, pefloxacin, stavudine and zidovudine), immunosuppressants (cyclosporin and tacrolimus), naltrexone, tolcapone and toremifene. According to the available data, the kinetics of many drugs are altered by liver disease to an extent that requires dosage adjustment; the problem is to quantify the required changes. Obviously, this requires the evaluation of the degree of hepatic impairment. At present there is no satisfactory test that gives a quantitative measure of liver function and its impairment. A critical evaluation of these methods is provided. Guidelines providing a rational basis for dosage adjustment are illustrated. Finally, it is important to consider that liver disease not only affects pharmacokinetics but also pharmacodynamics. This review also examines drugs with altered pharmacodynamics.

Effects of cardiovascular disease on pharmacokinetics.

The pathophysiologic changes occurring in cardiovascular disease can affect the kinetics of drugs in several different ways. The present review examines these modifications and the underlying mechanisms. The kinetics of specific agents, such as antiarrhythmic, antihypertensive, cardiotonic, and other drugs are considered, and the clinical implications are outlined. The clinician should be aware of these modifications, because they require an adjustment of the dosage regimen. A rational basis for a correct therapeutic choice can be provided by adequate knowledge of these modifications.

Therapeutic drug monitoring of cyclosporin. Practical applications and limitations.

Cyclosporin, a potent immunosuppressive agent used to prevent rejection of transplanted organs, has a narrow therapeutic range and various toxic effects, mostly concentration-dependent. The kinetics of this drug present a large intra- and interindividual variability due to many factors resulting in marked variations of blood cyclosporin concentrations, and in a poor correlation between administered dose and concentrations. The knowledge of cyclosporin peculiarities and of factors affecting blood concentrations can provide a rational basis for establishing an adequate therapy for the individual patient, in conjunction with other laboratory and clinical data. Cyclosporin monitoring is a method of evaluating whether the therapeutic choice is correct. Cyclosporin concentrations can be measured in blood, plasma and serum using radioimmunoassay or high performance liquid chromatography. Different results are obtained, depending on the technique and on biological fluids used. Cyclosporin measurement presents many problems and difficulties. There is a need for standardisation and for quality assessment programmes. The recent development of monoclonal antibodies may represent a significant advance for cyclosporin monitoring. The most important factors affecting blood concentrations are: type of transplant, bile deficit, gastrointestinal dysfunction, food, variations of lipoprotein concentrations, impairment of liver function, age, drug coadministration. Therapeutic drug monitoring should be undertaken on a regular basis after the initiation of therapy with cyclosporin. After discharge from the hospital the patient and the attending physician should be aware of the factors which may require changes in cyclosporin therapy.

Verapamil-induced changes in digoxin kinetics in cirrhosis.

The influence of a single low dose of verapamil (80 mg) on the serum levels of digoxin (single dose of 0.5 mg) was studied in 6 patients with hepatic cirrhosis and in 6 healthy volunteer controls. In the cirrhotic patients verapamil increased the peak serum level and the total AUC of digoxin by 98% and 32%, respectively. There was an associated 23% decrease in the renal digoxin clearance. In normal subjects only marginal alterations in digoxin kinetics were observed following verapamil administration. The results indicate that cirrhosis magnifies the influence of verapamil on digoxin kinetics.

[Dynamics of the production of staphylococcal enterotoxin and thermonuclease in foods responsible for outbreaks of food poisoning]. / Dinamica della produzione di enterotossine e termonucleasi stafilococciche in alimenti responsabili di episodi di tossinfezioni alimentari.

The behaviour of staphylococcal growth, thermonuclease and enterotoxin production in foods responsible of different food poisoning outbreaks is described. The significance of thermonuclease estimation, as a simple laboratory test for evaluating the hygienic status of foods in different steps of their commercial life, is discussed.