Treatment for T1DM patients by a neuro-fuzzy inverse optimal controller including multi-step prediction.

Diabetes Mellitus is a serious metabolic condition for global health associations. Recently, the number of adults, adolescents and children who have developed Type 1 Diabetes Mellitus (T1DM) has increased as well as the mortality statistics related to this disease. For this reason, the scientific community has directed research in developing technologies to reduce T1DM complications. This contribution is related to a feedback control strategy for blood glucose management in population samples of ten virtual adult subjects, adolescents and children. This scheme focuses on the development of an inverse optimal control (IOC) proposal which is integrated by neural identification, a multi-step prediction (MSP) strategy, and Takagi-Sugeno (T-S) fuzzy inference to shape the convenient insulin infusion in the treatment of T1DM patients. The MSP makes it possible to estimate the glucose dynamics 15 min in advance; therefore, this estimation allows the Neuro-Fuzzy-IOC (NF-IOC) controller to react in advance to prevent hypoglycemic and hyperglycemic events. The T-S fuzzy membership functions are defined in such a way that the respective inferences change basal infusion rates for each patient's condition. The results achieved for scenarios simulated in Uva/Padova virtual software illustrate that this proposal is suitable to maintain blood glucose levels within normoglycemic values (70-115 mg/dL); furthermore, this level remains less than 250 mg/dL during the postprandial event. A comparison between a simple neural IOC (NIOC) and the proposed NF-IOC is carried out using the analysis for control variability named CVGA chart included in the Uva/Padova software. This analysis highlights the improvement of the NF-IOC treatment, proposed in this article, on the NIOC approach because each subject is located inside safe zones for the entire duration of the simulation.

[Multicenter study of in vitro activity of tigecycline in clinical isolates from 30 centers in Spain]. / Estudio multicéntrico de la actividad in vitro de tigeciclina en aislados clínicos en 30 hospitales españoles.

INTRODUCTION: In the last years, the increase of antibiotic resistances of gram-positive and gram-negative bacteria is an important therapeutic problem. The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 750 bacterial isolates from 30 centers in Spain. METHODS: Multicenter and retrospective study. In 2005, thirty laboratories participated in this study. Data collected in this study included antimicrobial susceptibilities for S.aureus resistant to methicillin (MRSA), ESBL- E. coli or ESBL- K. pneumoniae, E. coli resistant to quinolons (E.coli- QR), Klebsiella spp and E. faecalis. Trains were obtained of the each Hospital s collection (5 strains of each microorganisms). The susceptibility determinations were performed locally by each laboratory following the standard method usually performed. The tigecycline susceptibility determinations were performed with E/test. RESULTS: Tigecycline was the most potent agent against MRSA, E. faecalis, E.coli-QR and ESBLs enterobacteriaceae; with MIC50-MIC90 values of: 0.125-0.25 g/ml; 0.125-0.5 g/ml; 0.25-0.75 g/ml and 0.38-1.5 g/ml; respectively. CONCLUSIONS: The results of this study confirm the excellent in vitro activity of tigecycline against gram-positive and gram-negative pathogens, including multirresistant microorganisms.

[Recommendations in the empiric anti-infective agents of intra-abdominal infection]. / Recomendaciones en el tratamiento antibiótico empírico de la infección intraabdominal.

A significant number of patients with abdominal infection develop advanced stages of infection and mortality is still above 20%. Failure is multifactorial and is associated with an increase of bacterial resistance, inappropriate empirical treatment, a higher comorbidity of patients and poor source control of infection. These guidelines discuss each of these problems and propose measures to avoid the failure based on the best current scientific evidence.

[Recommendations of antifungal treatment in patients with low grade immunosuppression]. / Recomendaciones de tratamiento antifúngico en pacientes con bajo grado de inmunodepresión.

Because of the relevance that the systemic mycoses has acquired in non-highly immunocompromised patients, the treatment difficulties they have due to the increase of the non-albicans Candida species and the need to have a better and more rational use of the new antifungal agents (voriconazole, posaconazole, caspofungin, anidulafungin and micafungin), an experts' panel on infectious diseases in representation of the Spanish Society of Chemotherapy, Spanish Society of Internal Medicine, and Spanish Society of Pneumology and Thoracic Surgery has met in order to make a few recommendations based on the scientific evidence in an effort to improve their efficiency.

The Meropenem Yearly Susceptibility Test Information Collection antimicrobial susceptibility program in Spain: a 5-year analysis.

The Meropenem Yearly Susceptibility Test Information Collection program is a global study providing in vitro surveillance data on antimicrobial susceptibility in centers prescribing meropenem. This study summarizes data on the activity of meropenem and 5 comparators against 4022 clinical isolates from 7 centers in Spain (1999-2003). Those bacteria intrinsically resistant to meropenem were excluded. Among Enterobacteriaceae, 100% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem. Escherichia coli and Klebsiella pneumoniae susceptibilities to carbapenems were 100% and > or =98%, respectively. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were 3.8% of isolates, and all of them were susceptible to meropenem. Ciprofloxacin resistance in E. coli was around 20%. Meropenem and piperacillin/tazobactam were the most active agents against Pseudomonas aeruginosa. Acinetobacter baumannii were 61-90% susceptible to carbapenems, but only 6-21% susceptible to ciprofloxacin. In this period, around 100% of oxacillin-susceptible staphylococci were susceptible to meropenem. There was no significant decrease in susceptibility to the carbapenems throughout the 5-year period. The clinical use of meropenem in 7 Spanish centers did not increase bacterial resistance to this agent in the microorganisms evaluated.

In vitro susceptibility of community-acquired urinary tract pathogens to commonly used antimicrobial agents in Spain: a comparative multicenter study (2002-2004).

The susceptibility patterns of 2724 uropathogens isolated in 9 Spanish regions during 2002, and 3013 obtained in 2004 were determined. The antibiotics tested were fosfomycin trometamol, amoxicillin, co-amoxiclav, cefixime, cefuroxime-axetil, pipemidic, ceprofloxacin, trimethoprim plus sulphamethoxazole and nitrofurantoin. Escherichia coli was the main pathogen in both studies (73% vs. 68.3%) followed by Proteus mirabilis 7.2% vs. 6.4%) and Klebsiella pneumoniae (5.4% vs. 5.2%). Enteroccocus spp. (4.7% vs. 6.8%), Streptoccocus agalactiae (1.7% vs. 3.1%) and Staphyloccocus saprophyticus (0.7% vs. 1.3%)were the most frequent Gram-positive pathogens. 31.3% of E. coli in 2002 and 32% in 2004 were susceptible to all antibiotics tested. Around 40% of E. coli were resistant to a single agent. 21.6-24.1% were resistant to two antibiotics. 35.4% of first period isolates, and 37.6% of second period ones were resistant to two or more classes of antibiotics. Fosfomycin (2.1- 2.8%) and nitrofurantoin (3.5-5.7%) had the lowest resistance rates for E. coli. Amoxicillin (58.2-58.7%), co-trimoxazole (30.8-33.8%) and ciprofloxacin (22.6-22.7%) showed the highest resistance rates, and their suitability as empiric treatments for UTI should probably be re-evaluated.

[National multicenter survey: the use of intravenous antimicrobial agents]. / Encuesta multicéntrica nacional sobre utilización de antibióticos intravenosos.

Infectious diseases are currently one of the major health problems worldwide. As a consequence, both nosocomial and community-acquired infections are responsible for a significant increase in workload and health costs for hospitals, particularly in Intensive Care Units (ICU), Internal Medicine and Surgery. The use of intravenous antimicrobial agents is common in hospitalized patients. In order to determine the use of antimicrobial agents and the most frequent procedures used for their administration in Spanish hospitals, a national multicenter survey was undertaken among ICU, Internal Medicine and Surgery health staff from 63 hospitals, in which data were collected on central and peripheral catheter manipulation and intravenous administration. Results showed that, in Spain, both catheter manipulation (insertion, maintenance and removal) and administration of antimicrobial agents are performed by the nursing staff following established protocols, particularly for central catheters. Moreover, the ICUs had the highest rates of catheter-bearing patients, as well as patients undergoing antimicrobial treatment, sometimes in combination. The use of intravenous antimicrobial agents in Spanish hospitals results in an increased workload for the nursing staff and higher health costs, not to mention the risk involved with the use of vascular catheters.

[Patterns of susceptibility to antibiotics of Enterobacteriaceae causing intra-abdominal infection in Spain: SMART 2003 study outcomes]. / Patrones de sensibilidad a antimicrobianos de Enterobacteriaceae causantes de infecciones intraabdominales en España: resultados del estudio SMART 2003.

SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections. The objective of this subanalysis was to assess antimicrobial susceptibility patterns among Entero-bacteriaceae recovered at 13 participating Spanish sites during 2003. Antimicrobial susceptibility testing was performed using broth microdilution techniques according to the CLSI (formerly NCCLS) guidelines for MIC testing. The presence of extended-spectrum beta-lactamases (ESBL) was confirmed in isolates with a MIC of ceftriaxone, ceftazidime, or cefepime>or=2 mg/l by comparing cefepime MICs with and with-out clavulanate. A total of 981 Enterobacteriaceae recovered from 840 patients were tested, of which 398 (41%) were community-acquired. Escherichia coli was the most common isolate (571 isolates; 58%), followed by Klebsiella spp. (153; 16% Enterobacter spp. (97; 10%), and Proteus spp. (63; 6%). A total of 191 isolates (19%) from 176 patients produced inducible beta-lactamases. The carbapenems and amikacin were the most consistently active agents against the Enterobacteriaceae (susceptibility>or=99%). Resistance rates for ceftazidime, cipro-floxacin, and levofloxacin exceeded 10%. ESBLs were detected phenotypically in 61 (6%) isolates, being the most common E. coli (61%), Klebsiella spp. (20%), and Enterobacter spp. (8%). Antimicrobial resistance among Enterobacteriaceae isolated from intra-abdominal infections is a problem in Spain. A significant proportion of inducible beta-lactamase and ESBL-producing Enterobacteriaceae causing intra-abdominal infection were acquired in the community. The carbapenems ertapenem, imipenem and meropenem and the aminoglycoside amikacin were highly active in vitro against Enterobacteriaceae isolated from intra-abdominal sites, including ESBL-producing organisms.

Molecular epidemiology of drug-resistant Salmonella Typhimurium in Spain.

One hundred and forty-seven Salmonella serotype Typhimurium strains isolated in three provinces in the midwest of Spain were studied. Of these, 93.6% were drug resistant. There were two predominant resistance phenotypes: 43 isolates (29.3%) were resistant to amoxicillin, tetracyclines, chloramphenicol, streptomycin and sulphamethoxazole and 27 isolates (18.4%) to amoxicillin, amoxicillin/clavulanic acid, tetracyclines, chloramphenicol, streptomycin and sulphamethoxazole. Randomly amplified polymorphic DNA (RAPD) analysis and pulsed field gel electrophoresis (PFGE) were performed for molecular typing. Thirty-six DNA band profiles were differentiated by RAPD, and 38 by PFGE. We found a high level of clonality; 27% of strains were identical by both methods. There were additional smaller clonal lines within every area. The highest discriminatory power was obtained with PFGE, but the greatest degree of genetic diversity was observed among Salmonella Typhimurium using both RAPD and PFGE.

[Prevalence of anti-Chlamydophila pneumoniae antibodies in patients with intrinsic asthma]. / Prevalencia de anticuerpos frente a Chlamydophila pneumoniae en pacientes con asma intrinseca.

Chlamydophila pneumoniae is a respiratory pathogen which has been involved in the pathogenesis of a number of chronic diseases. We studied the association between IgG antibodies against C. pneumoniae and intrinsic asthma in adults. C. pneumoniae IgG serum titers were determined by enzymatic immunoassay in 55 adult patients and 87 healthy controls. A significant association was found between anti-C. pneumoniae antibodies and intrinsic asthma, as compared to the control group (23.6% vs. 10.3%, p <0.05). C. pneumoniae may therefore be involved in the origin or in exacerbations of intrinsic asthma.

Detection of circulating antigens in the diagnosis of acute toxoplasmosis.

Using an enzyme-linked immunosorbent assay, we have found circulating antigens of Toxoplasma gondii in three models of murine toxoplasmosis: mice infected with trophozoites of the RH strain (acute toxoplasmosis), the Beverley strain (subacute toxoplasmosis), and the T626 strain (chronic toxoplasmosis). Circulating antigens were detected 48 hr after infection in the mice infected with the RH strain, and all mice had antigenemia by the fourth day. In those infected with the Beverley strain, circulating antigens were detected from the second day after inoculation until the end of the study, with a peak (71% of the infected mice) on day 10. Of those infected with the T626 strain, 40% had antigenemia at 13 days after infection. The detection of circulating antigens in serum is directly related to the presence of toxoplasmosis in the acute phase in the three models studied and, therefore, may prove very useful in the rapid diagnosis of this disease.

Current status of bacterial resistance to third-generation cephalosporins.

A review of the evolution of bacterial resistance to third-generation cephalosporins is presented, focusing mainly on the prototypical member of this group-cefotaxime. Third-generation cephalosporins generally remain highly active against most Enterobacteriaceae, staphylococci, streptococci, Haemophilus, and Neisseriaceae. Only enterobacteria with a high frequency of mutant derepressed strains that hyperproduce chromosomally mediated beta-lactamase, Pseudomonas spp., and some glucose nonfermenter Gram-negative bacilli have demonstrated increased levels of resistance. The significance of derepressed strains and of the recently described extended-spectrum, plasmid-mediated beta-lactamases to the usefulness of the third-generation cephalosporins is discussed.

Antibiotic susceptibility profile of Xanthomonas maltophilia. In vitro activity of beta-lactam/beta-lactamase inhibitor combinations.

The susceptibility of 42 strains of Xanthomonas (Pseudomonas) maltophilia to 37 antibiotics (mainly beta-lactams, aminoglycosides, and fluorinated quinolones) was tested. Xanthomonas maltophilia was resistant to most beta-lactams, with ceftazidime, moxalactam, and ICI-194008 being the most active ones. Aminoglycosides had a very modest activity, with quinolones showing only moderate activity against this species. Trimethoprim/sufamethoxazole was effective against all strains tested. We also tested the synergy of several beta-lactam/beta-lactamase inhibitors against X. maltophilia. Only aztreonam/clavulanic acid at 3:1, 1:1 and, mainly, 2:1 combinations had synergistic activity, decreasing the rate of resistance from 92.8% for aztreonam alone to 32.4% for aztreonam-clavulanic acid at 1:1 and 0% for aztreonam-clavulanic acid at 2:1.

Review of pulmonary brucellosis: a case report on brucellar pulmonary empyema.

In certain geographic areas, among which most South European countries are included, brucellosis continues to be an important health problem. Despite the disease's continued high prevalence, the advances made in its diagnosis and treatment have contributed to the rarity of different focal locations, such as the lung. Formerly, these occurrences were much more frequent. The present work offers a review of the literature on pulmonary brucellar affection and describes a case report of brucellar pulmonary empyema with isolation of Brucella melitensis from the pleural exudate. This constitutes an exceptional circumstance even in areas considered hyperendemic, such as a large part of Spain.

Results of two worldwide surveys into physician awareness and perceptions of extended-spectrum beta-lactamases.

An omnibus survey of microbiologists (n = 400) and a survey of participants (n = 49) in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme were conducted to determine the awareness and prevalence of extended-spectrum beta-lactamases (ESBLs), and the regularity and method of screening. Of the omnibus survey participants, 69% screened regularly for ESBLs, compared with 83% of MYSTIC participants. In both surveys, ESBLs were more common in Klebsiella pneumoniae (73% and 79%, respectively) and Escherichia coli (63% and 81%, respectively) than in other bacteria. The surveys demonstrated that awareness of, and testing for, ESBLs is inconsistent.

The role of fluoroquinolones in respiratory tract infections: community acquired pneumonia.

Newer fluoroquinolones may play an important role in the management of community acquired pneumonia. They retain activity similar to older fluoroquinolones against Gram-negative bacteria and are significantly more active against Gram-positive bacteria, especially pneumococci. They are also active against bacteria causing atypical pneumonia, penicillin-sensitive and -resistant and macrolide-sensitive and -resistant pneumococci and against beta-lactamase producing and non-producing Haemophilus influenzae. They have similar or slightly lower activity than ciprofloxacin against other Gram-negative organisms. They have rapid bactericidal activity and attain good lung tissue levels. Clinical studies show results similar or better than older treatments. Their impact on ecology and resistance remains to be elucidated but data on side effects and toxicity must be carefully evaluated.

Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors.

Psychotropic drugs have been shown to have antimicrobial activity against several groups of microorganisms. Some of these drugs, such as the new antidepressant agents sertraline, fluoxetine and paroxetine are known to act as efflux pump inhibitors in human cells. Their activity has been studied, alone and combined with antibiotics, against bacterial species, mainly in multiply resistant strains. These agents have surprising activity, mainly against Gram positive microorganisms. They also show synergistic activity when combined with some antibiotics against several bacteria, shown by a decrease in MICs, that converts strains previously resistant to the category of sensitive, and modify physiological aspects related with pathogenicity.

Oral cephalosporins: current perspectives.

Oral cephalosporins had been, for years, a small group of compounds belonging to the first or second-generation cephalosporins, with a limited antimicrobial spectrum. New oral first-generation cephalosporins include cefprozil and loracarbef, similar to cefadroxil and cefaclor, respectively, with activity similar to cefaclor but with pharmacokinetic improvements. Second-generation oral cephalosporins are esters of already available cephalosporins, and third-generation oral cephalosporins include a number of drugs whose activity is similar to available parenteral drugs, showing pharmacokinetic advantages and, some of them, better resistance to hydrolysis mediated by extended wide-spectrum beta-lactamases. They may be a good alternative against mild to moderate ENT infections, UTIs, STDs, lower respiratory tract and skin and soft tissue infections, mainly in the outpatient setting.

In vitro activity of linezolid, synercid and telithromycin against genetically defined high level fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus.

The in vitro activity of levofloxacin, moxifloxacin, gatifloxacin, erythromycin, telithromycin, linezolid, synercid and vancomycin was measured against 36 genetically defined, gyrA/grlA double mutant MRSA clinical strains with an MIC to ciprofloxacin > or = 8 mg/l. The three newer fluoroquinolones tested were more active than ciprofloxacin. Resistance rates for levofloxacin and gatifloxacin were high (44.5 and 36.1%, respectively). All the strains were moxifloxacin-susceptible, though most of them had MICs close to the break point. All the strains were intermediate or resistant to erythromycin and most were also resistant to telithromycin. No strains were resistant to linezolid, synercid or vancomycin (MIC(90): 2, 1 and 2 mg/l, respectively).