Gloria Royo

In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis

The in vitro activity of moxifloxacin, gatifloxacin, levofloxacin and linezolid was evaluated against 234 strains of Mycobacterium tuberculosis isolated in the Southeast of Spain. All drugs tested showed good activity, with an MIC(90) of less than 1 mg/l, and were active against isociacide and rifampicin resistant strains. Three strains were resistant to isoniazid and to the fluoroquinolones, which suggested the existence of mechanisms of resistance not yet described. These new compounds may prove to be therapeutic alternatives for treatment of multi-resistant tuberculosis and further studies should be done to demonstrate their true usefulness.

Importance of the Efflux Pump Systems in the Resistance of Mycobacterium tuberculosis to Fluoroquinolones and Linezolid

Objective: Our aim was to study the influence of efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid. Methods: We studied the mutations in gyrA and gyrB genes and the influence of efflux pump systems with 2 inhibitors (reserpine and MC 207.110). Results: The effect of the active efflux system on the decrease in sensitivity to ciprofloxacin, moxifloxacin, levofloxacin, ofloxacin, gatifloxacin and linezolid was studied by investigating the variation in the in vitro activity of these compounds when assayed in association with reserpine and MC 207.110. These inhibitors exhibit activity both in strains that are resistant and in strains that are susceptible to these antibiotics. However, they are seen to be most active in resistant strains, since the minimum inhibitory concentration of the antibiotics studied in these strains was reduced between 2- and 6-fold. Conclusions: Therefore, these mechanisms are involved in the resistance to both compounds. It would be of interest to carry out further studies to determine to what extent these active efflux systems influence resistance to the different groups of drugs used in the treatment of tuberculosis, with a view to the possibility of using the inhibitors of these systems in future therapeutic applications.

Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain

ABSTRACT This study presents data from a prospective study of adult patients with community-acquired pneumonia (CAP). Of 493 patients included in the study, 223 (45.2%) were aged ≥ 65 years, and 265 (53.7%) had one or more underlying diseases, mostly chronic obstructive pulmonary disease, diabetes mellitus or dementia. In total, 281 microorganisms were identified in 250 (50.7%) patients, with two or more pathogens detected in 28 (5.7%) cases. Microbial diagnosis varied according to age, severity, co-morbidity and site-of-care, but there was much overlap among groups. Streptococcus pneumoniae was the single most prevalent organism in outpatients, patients admitted to hospital, and patients who died, either as a single pathogen or combined with another organism. Infections caused by ‘atypical’ pathogens were seen across all groups, including the elderly and patients with co-morbidities. Mortality varied according to the pneumonia severity index (PSI) of the pneumonia patient outcomes research team. Shock (OR 34.48), an age of > 65 years (OR 25) and altered mental status (OR 9.92) were factors associated independently with 30-day mortality. Key findings from this study were the advanced age of the population with CAP, and the high prevalence of dementia as an underlying disease. The study also revealed that microbiological diagnosis of CAP remains problematic. Although certain epidemiological features may help to predict the microbial aetiology, the overlap among groups reduces the usefulness of this information in guiding therapeutic decisions. Greater effort should be made to improve identification methods for microbial pathogens causing CAP.

In vitro activity of four fluoroquinolones against Mycobacterium tuberculosis.

The in vitro activity of ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin against strains of Mycobacterium tuberculosis was studied. Moxifloxacin and levofloxacin showed the greatest activity having an MIC(90) of 1 mg/l. The MIC(90) for ofloxacin was 2 mg/l and for ciprofloxacin 4 mg/l. Further studies should be made to determine the role played by these compounds in the treatment of tuberculosis.

Examen de salud en la población inmigrante: prevalencia de infección tuberculosa latente, hepatitis B, hepatitis C, infección por el VIH y sífilis

Introduccion Describir la prevalencia de las enfermedades infecciosas en inmigrantes. Metodos Se practico intradermorreaccion de Mantoux, serologia de hepatitis B, hepatitis C, VIH y sifilis a 488 inmigrantes. Resultados El 19,1% de los que provenian de Africa tenian la prueba de Mantoux positiva, el 9,6% de Europa del Este y el 5,8% de Sudamerica (p Conclusiones La prevalencia de las enfermedades infecciosas en los inmigrantes difiere segun el area geografica del pais de origen.

Real-Time PCR for Diagnosing Helicobacter pylori Infection in Patients with Upper Gastrointestinal Bleeding: Comparison with Other Classical Diagnostic Methods

ABSTRACT The aim of this study was to determine the diagnostic usefulness of quantification of the H. pylori genome in detection of infection in patients with upper gastrointestinal bleeding (UGB). A total of 158 consecutive patients with digestive disorders, 80 of whom had clinical presentation of UGB, were studied. The number of microorganisms was quantified using a real-time PCR system which amplifies the urease gene with an internal control for eliminating the false negatives. A biopsy sample from the antrum and corpus of each patient was processed. The rapid urease test, culture, histological study, stool antigen test, and breath test were done. The gold standard was a positive culture or positive results in at least two of the other techniques. When a positive result was defined as any number of microorganisms/human cell, the sensitivity of real-time PCR was greater in bleeding patients, especially in the gastric corpus: 68.4% (95% confidence interval [CI], 52.3 to 84.5%) in non-UGB patients versus 91.5% (95% CI, 79.6 to 97.6%) in UGB patients. When a positive result was defined as a number of microorganisms/human cell above the optimal value that maximizes the Youden index (>3.56 microorganisms/human cell in the antrum and >2.69 in the corpus), the sensitivity and specificity in UGB patients were over 80% in both antrum and corpus. Our findings suggest that some bleeding patients with infection caused by H. pylori may not be correctly diagnosed by classical methods, and such patients could benefit from the improved diagnosis provided by real-time PCR. However, the clinical significance of a small number of microorganisms in patients with negative results in classical tests should be evaluated.

Comparison of the bactericidal activity of various fluoroquinolones against Mycobacterium tuberculosis in an in vitro experimental model

OBJECTIVES To compare the bactericidal activity of various fluoroquinolones against Mycobacterium tuberculosis in the latent and exponential growth phases. METHODS Ciprofloxacin, levofloxacin and moxifloxacin were tested against 16 M. tuberculosis clinical isolates (4 resistant and 12 susceptible to fluoroquinolones) from Elche, Spain, isolated between 1992 and 2009. To study bactericidal activity, an inoculum of approximately 10(5) cfu of each isolate was cultured in Middlebrook 7H9 broth. The broth was previously acidified to pH 4.6 to obtain the microorganism in the stationary phase. Cultures with different concentrations (0.1 to 50 mg/L) of antibiotic and antibiotic-free controls were incubated for 48 h then plated onto Middlebrook 7H11 to detect bacterial killing. In all stages of the process the M. tuberculosis strain ATCC 41323 was included as a quality control to ensure reproducible results. RESULTS Moxifloxacin and levofloxacin were found to exhibit bactericidal activity at lower concentrations and against more strains in both the latent and the exponential growth phases compared with ciprofloxacin. The bactericidal activity of moxifloxacin was greater than that of levofloxacin against microorganisms in the exponential growth phase, but the opposite was true in the latent phase. CONCLUSIONS Our data confirm the usefulness of moxifloxacin in the treatment of tuberculosis and suggest that levofloxacin may be used as an alternative drug in the treatment of latent tuberculosis when it is not possible to use isoniazid. Based on the results presented, ciprofloxacin appears to be a poor choice.

Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors

The aim of this study was to characterise community-acquired pneumonia (CAP) caused by atypical pathogens by combining distinctive clinical and epidemiological features and novel biological markers. A population-based prospective study of consecutive patients with CAP included investigation of biomarkers of bacterial infection, e.g., procalcitonin, C-reactive protein and lipopolysaccharide-binding protein (LBP) levels. Clinical, radiological and laboratory data for patients with CAP caused by atypical pathogens were compared by univariate and multivariate analysis with data for patients with typical pathogens and patients from whom no organisms were identified. Two predictive scoring models were developed with the most discriminatory variables from multivariate analysis. Of 493 patients, 94 had CAP caused by atypical pathogens. According to multivariate analysis, patients with atypical pneumonia were more likely to have normal white blood cell counts, have repetitive air-conditioning exposure, be aged <65 years, have elevated aspartate aminotransferase levels, have been exposed to birds, and have lower serum levels of LBP. Two different scoring systems were developed that predicted atypical pathogens with sensitivities of 35.2% and 48.8%, and specificities of 93% and 91%, respectively. The combination of selected patient characteristics and laboratory data identified up to half of the cases of atypical pneumonia with high specificity, which should help clinicians to optimise initial empirical therapy for CAP.

Available options in the management of non-typhi Salmonella.

Gastroenteritis, caused by Salmonella spp. is usually a self-limiting infection and does not require treatment. However, in some immunosuppressed patients (such as the newborn, the elderly, those with AIDS or neoplasms), there is a greater risk of developing a severe systemic infection, and in these cases, antibiotic treatment is recommended. Third-generation cephalosporins and fluoroquinolones are the most useful antibiotics in the treatment of these infections, although resistant strains are sometimes isolated. Therapeutic failures have been reported with fluoroquinolones in extra-intestinal infections caused by nalidixic acid resistant strains.

Mycobacterium abscessus from respiratory isolates: activities of drug combinations

Mycobacterium abscessus is the most resistant of rapidly growing pathogenic mycobacteria. We performed a screening of the in vitro sterilizing capacity of various antibiotic combinations against two strains isolated from respiratory samples (in vitro activity of each antibiotic: 51 combinations of two drugs and 47 of three drugs). Our findings confirm that clarithromycin is the most useful drug. The combination of this drug with linezolid exhibits good activity. In addition, the fluoroquinolones and rifabutin in association with clarithromycin may have clinical utility because they are administered orally. Therapeutic alternatives in this type of infections should be evaluated in greater depth.