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Biomedical subjects

M Gobernado

Publications and source records attributed to M Gobernado.

At least 73 records · Page 4Linked to original sources

[Effect of antiinflammatory agents on the accumulation of ofloxacin in human polymorphonuclear leukocytes].

The uptake of quinolones is a recently defined pharmacokinetic parameter which is increasing in importance in clinical practice, especially for immunocompromised patients whose polymorphonuclear leukocytes (PMNLs) have their bactericidal systems impaired, or in infections due to bacteria able to survive in the phagocytes. In both situations, antibiotics able to penetrate and be active in the phagocytes are required. The simultaneous administration of an antibiotic and an antiinflammatory drug is frequent, and previous studies have described interactions between the intracellular activity of the quinolones and the presence of phenylbutazone. We studied the effect of the presence of and the pretreatment (37 C for 30 and 60 min) of human PMNLs with the antiinflammatory drugs betamethasone (1 mg/l), hydrocortisone (1 mg/l), phenylbutazone (10 mg/ml), and acetylsalicylic acid (200 mg/l) on the uptake of ofloxacin (10 mg/l) by the PMNLs using a fluorometric method to measure the intra-PMNL concentration of ofloxacin. The presence of betamethasone did not modify the uptake of ofloxacin by PMNLs. Pretreatment of PMNLs with hydrocortisone, phenylbutazone and acetylsalicylic acid produced a significant decrease in the maximum intracellular concentration/extracellular concentration ratios compared with the maximum reached without pretreatment. These results suggest that hydrocortisone, phenylbutazone and acetylsalicylic acid interfere with the uptake of ofloxacin by PMNLs and increase the efflux of ofloxacin from PMNLs.

Anti-Infective Agents↗

[Neonatal colonization by Ureaplasma urealyticum and the development of bronchopulmonary dysplasia].

OBJECTIVE: The study purpose was to investigate the association between neonatal Ureaplasma urealyticum isolation, and bronchopulmonary dysplasia (BDP), in infants who had birth weights < 1,500 g, admitted in the Pediatric Intensive Care Unit, La Fe Hospital, Valencia, Spain. METHODS: A cohort study was designed, since March 1996 until April 1998, with a cohort of exposed and no exposed, determined by isolation of U. urealyticum in tracheal aspirate or pharyngeal cultures. 137 infants were admitted to the intensive care unit in this period, and 101 of them were enrolled in this study. RESULTS: U. urealyticum was isolated in 27 (26.7%) patients. The infants with U. urealyticum positive culture had a significantly lower gestational age (mean 28.1, SD 2.4 vs 29.2, SD 2.4; p = 0.048) than negative culture infants. BDP occurred in 30 infants (29.7%), and was significantly associated with decreasing gestational age (mean 26.9, SD 1.7 vs 29.7, SD 2.2; p < 0.001) and lower birth weight (mean 965.8, SD 166.7 vs 1121.4, SD 232.1; p < 0.001). However, after correction for gestational age by logistic regression analysis, DBP was significantly related to decreasing gestational age, but not to the presence of a positive U. urealyticum culture. In the cohort of U. urealyticum positive infants, BPD occurred in 9 (33%) vs 21 (28%) in the not colonized cohort. The odds ratio associated with colonization was 1.3 (CI 95% 0.5-3.2; p = 0.63). CONCLUSIONS: BPD was significantly associated with decreasing gestational age, independently of birth weight and U. urealyticum colonization.

Bronchopulmonary Dysplasia↗

[Early prediction of lack of response to treatment with interferon and interferon plus ribavirin using biochemical and virological criteria in patients with chronic hepatitis C].

The objectives of this study were the following: 1) to evaluate the predictive value of the detection of RNA-HVC compared to GPT in the third month of treatment in patients with chronic hepatitis C treated with IFN, and at the first and third month in patients treated with IFN and ribavirin for 6 and 12 months. The study included: A) 80/132 patients treated with IFN (3 MU/3 times a week for 6-12 months), and B) 70/110 patients who had previously not responded to IFN, and who were treated with combination therapy (IFN: standard dose, ribavirin: 1200 mg/day) for 6 months (n = 40) and 12 months (n = 30). In group A, the positive predictive value (the probability of predicting the lack of response if the RNA-HVC was positive or if the GPT was elevated at the third month) was greater for RNA-HVC than for GPT (97.9% vs. 94.4%), although the response was not unequivocal (2.3% vs. 10.5%). The negative predictive value was 48.6% vs. 36.2%, respectively. The prediction level (odds ratio) of RNA-HVC and of GPT was 39.7 vs. 8.78 (p <0.000001 vs. p <0.002). The positive predictive value was 97.6% in patients with genotype 1, 4 and 5, and 100% in those with genotype 2 and 3. In group B, the positive predictive value was also greater for RNA-HVC than for GPT at the first month (100% vs. 94.4%) following six months of therapy, the odds ratio being infinite vs. 7.6. The positive predictive value was greater for RNA-HVC at the third month than at the first (100% vs. 91%), whereas it was similar for GPT (100%) with 12 months of therapy, the odds ratio being greater for GPT than for RNA-HVC at the first month (infinite and 7.27). The following was concluded: 1) detection of RNA-HVC at the third month of treatment with IFN predicts in advance a lack of response in patients, with a minimum risk of error; 2) in patients with six months of combined therapy, the detection of RNA-HVC at the first month is extremely reliable in the prediction of a lack of response, whereas after 12 months of combined therapy, elevated GPT values at the first month and the detection of RNA-HVC at the third are highly predictive of a lack of response.

Adolescent↗

[Invasive fungal infections in patients with blood disorders].

BACKGROUND: Invasive fungal infections (IFI) are severe infectious complications frequently observed in patients with hematological disorders. The aims of this study were to analyse the characteristics of this particular type of infection in a large series of a single institution and to determine the factors associated with the outcome and therapeutic response. PATIENTS AND METHODS: This study reviews the clinical and microbiological features of 155 IFI occurred among 144 patients with hematologic disorders throughout a period of 17 years in a single institution. RESULTS: In 118 cases (82%) the diagnosis was acute leukemia. The main risk factors for developing IFI included a persistent and profound granulocytopenia, the use of broad-spectrum antibacterial agents, indwelling central venous catheters and the damage of normal host barriers following intensive cytotoxic chemotherapy. Candida (65 cases [44%]) and Aspergillus (38 cases [26%]) species were the most common fungal species isolated. An increasing number of IFI were caused by fungi previously considered as contaminants or harmless colonizers. The outcome of IFI was favourable in 78 cases (50%). The most important prognostic factors for the outcome of the IFI were the phase of cytotoxic chemotherapy (p = 0.005), the response of the underlying disease to the cytotoxic chemotherapy (p < 0.00001), and the recovery of neutropenia during the infection course (p < 0.00001). An earlier use of empirical antifungal therapy was also associated with a better outcome. CONCLUSIONS: In spite of earlier treatment and regardless the development of new antifungal agents, the prognosis of IFI in patients with hematological malignancies remains poor. The use of hematopoietic growth factors, through their impact in the duration and severity of neutropenia, may prove valuable the management of IFI in this setting.

Acute Disease↗

Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection.

BACKGROUND/AIMS: We retrospectively studied 63 consecutive patients (mean age 54+/-8) with hepatitis C virus genotype 1b recurrence after liver transplantation and with a minimum histological follow-up of 1 year, in order to determine whether an early severe recurrence, defined as the development of chronic active hepatitis within the first 2 years post-liver transplantation, was associated with increased immunosuppression. METHODS: The 1st year immunosuppression data (rejection episodes, boluses of methyl-prednisolone, cumulative doses of prednisone and azathioprine, OKT3 use) were recorded, and evaluated as predictive of severe recurrence at 1 and 2 years post-liver transplantation. Chronic active hepatitis and rejection were defined by histological criteria. Immunosuppression consisted of cyclosporine, azathioprine and prednisone. The treatment of rejection was based on a "bolus" of 1 g methyl-prednisolone/3 days. RESULTS: At 1 year, 64% (40/63) of the patients had chronic active hepatitis, whereas of the 40 patients who had a 2nd year biopsy available, 75% had chronic active hepatitis at 2 years. At 1 year post-liver transplantation, no significant association was observed between immunosuppression and the development of chronic active hepatitis. In contrast, at 2 years, rejection (p=0.006), treatment of rejection (p=0.05), methyl-prednisolone boluses (p=0.013) and the number of rejection episodes (p=0.0034) occurring during the 1st year post-liver transplantation were significantly more common in patients with chronic active hepatitis. There was also a trend towards higher cumulative steroids (9447+/-3176.5 vs 7891.5+/-2111 mg) and higher cumulative azathioprine doses (13472+/-11154 vs 6233.5+/-5937 mg) in patients with chronic active hepatitis as compared to those who did not develop chronic active hepatitis. CONCLUSIONS: Rejection and/or its treatment may accelerate the natural history of hepatitis C virus genotype 1b infection post-liver transplantation.

Alanine Transaminase↗

Repeated pulmonary infection by Nocardia asteroides complex in a patient with bronchiectasis.

A rare case of pulmonary nocardiosis was presented in a nonimmunocompromised patient who had chronic airway obstruction and bronchiectasis without corticoid treatment. The microbial diagnosis was established after isolating Nocardia in bronchial aspirate and sputum samples. An in vitro study showed sensitivity only to imipenem, netilmicine, amikacin and ofloxacin. The evolution was chronic, with multiple clinical recurrences in spite of prolonged antibiotic treatment. Finally, the eradication of Nocardia was achieved with the combination of imipenem and amikacin.

Amikacin↗

[Evolution of resistance in the genus Enterococcus in strains isolated from blood].

The objective of this study was to determine the evolution of the species distribution and the prevalence of resistance to the Enterococcus genus. We studied 281 strains of enterococcus isolated from blood samples: 90 throughout 1984 and 791 from the years 1994 to 1996. identification was made using PosCombo 4Y Microscan-Baxter dehydrated panels and the Rapid ID 32 Strep system (bioMerieux). The MICs were calculated using the agar dilution method according to recommendations of the NCCLS for the following antibiotics: ampicillin, vancomycin, teicoplanin, gentamicin, kanamycin and streptomycin. The production of betalactamases were evaluated using a paper disk with nitrocefin for all the strains. The genotypes with resistance to glycopeptides were determined using PCR. The percentage of E. faecalis for 1984-1986/1994-1996 was 82.2/79.4; of E. faecium 4.4/16.4; and other species 12.214.3. The resistance to ampicillin went from 1.1% to 5.8%; high level resistance to glycopeptides went from 0% to 9.9%; for low level from 7.7% to 2.6%; resistance to a high charge of gentamicin went from 27.7% to 40.8%; and that for kanamycin from 45.5% to 62.8%. Resistance to streptomycin remained constant (45.5%). No strains produced betalactamases. For the species E. faecium, a statistically significant increase was detected for global resistance to ampicillin, gentamicin and kanamycin, with resistance to streptomycin remaining at similar percentages. No high level resistance to glycopeptides was detected in the first time period, but the low level resistance was greater.

Ampicillin Resistance↗

[In vitro activity of fluconazole against Candida albicans isolated from blood culture].

The in vitro activity of fluconazole against 65 Candida albicans isolated from blood culture in 1995, 1996 and 1997 was studied by macrodilution and disk diffusion methods. The MIC ranged from 0.03 to 64 microg/ml, with 93.6% of strains being inhibited with 1 microg/ml fluconazole; the mode MIC was 0.25 microg/ml. Using this method, only one strain was resistant and another was susceptible depending on the dose. By diffusion, eight strains were susceptible, 53 intermediate, and four resistant. The strains susceptible by dilution were also susceptible by diffusion, but the strains resistant by diffusion were not always resistant by dilution. We find it therefore useful to determine the MIC of fluconazole to the C. albicans resistant by diffusion.

Antifungal Agents↗

[A national multicenter study of the in-vitro activity of piperacillin-tazobactam. The Spanish Piperacillin-Tazobactam Group].

The action of piperacillin-tazobactam on 4,137 of the 4,364 strains collected in a Spanish multicenter study involving 46 participating hospitals was studied. The samples were from the following: 41% urine, 18% exuded from wound abscesses, 13% respiratory, 9% blood, 3% peritoneal liquid, and the remainder from other various sources. The gram-negative bacteria included 2,778 strains from 13 genera: Escherichia (1,289), Pseudomonas (451), Proteus (230), Klebsiella (203), Haemophilus (172), Enterobacter (145), Acinetobacter (88), Salmonella (60), Bacteroides (57), Morganella (53), Serratia (46), Citrobacter (46), Stenotrophonomas (23) and Moraxella (21). The gram-positive bacteria were S. aureus (316), E. faecalis (239), S. epidermis (130), S. pneumoniae (115) and Clostridium spp. (12). The global susceptibility of the gram-negatives to piperacillin-tazobactam was 94%: E. coli 98%, P. aeruginosa 92%, and P. mirabilis, Morganella, K. pneumoniae, Serratia and Salmonella spp. all greater than 94%. The susceptibility of other bacteria was as follows: 91% Citrobacter, 77% E. cloacae, 42% A. baumannii, 61% S. maltophilia, 97% E. faecalis, 93% S. epidermidis, 100% M. catarrhalis, 99% H. influenzae and 100% anaerobic bacteria. The action on S. pneumoniae and S. aureus varied according to the susceptibility or lack there of to penicillin or methicillin. In comparison to other antibiotics (piperacillin, cefoxitin, cefotaxime, ceftazidime, cefepime, imipenem and ciprofloxacin), piperacillin-tazobactam was far better than piperacillin alone and better or similar to the others.

Bacteria↗

[Human immunodeficiency virus and resistance].

It has been demonstrated that following prolonged treatment with reverse transcriptase inhibitors, especially with nucleoside analogs, resistant viral strains appear that show mutations in the nucleotides of the gene that codifies reverse transcriptase. These mutations cause changes in amino acids, which gradually increases resistance. In this study we evaluated the applicability af the LiPA HIV-1 RT test in determining the presence of mutations in this gene that can lead to resistance to antiretroviral treatments.Twenty-one samples were studied without previous knowledge of the antiviral treatments that the patients had received. No mutations in the HIV-1 stains from untreated patients were found. In the other patients who had undergone various treatment regimens, the results obtained With the LiPA HIV-1 RT made in possible to retrospectively identify the different nucleoside analogs they had been treated with. The most frequently found mutations were those that lead to a certain degree of resistance to AZT, followed by those related to resistance to ddl, which in effect in this order were the drugs used in the treatment of the patients. However, the LiPA HIV-1 RT test has certain limitations. It can only detect mutations that can be recognized by its sequences. As such, including sequences that would make it possible to study the possible genotypic variations in the gene that codifies the protease of HIV-1 would be helpful, given the importance of the protease inhibitors in clinical practice. In any case, direct sequencing continues to be standard method as it allows us to obtain full information on the genes that need to be studied.

Anti-HIV Agents↗

[Bacteremia caused by Stenotrophomonas maltophilia: a clinical-epidemiological study and resistance profile].

Over a 7-year period (1990-1996), the causal disease, predisposing factors, focus infection, clinical manifestations, complications and evolution of patients presenting bacteremia from Stenotrophomonas maltophilia were analyzed retrospectively in a university hospital. A microbiological study was carried out to determine the percentage of positive blood cultures per episode and the characteristics of bacteremia and to evaluate the antibiotic susceptibility of the isolated strains. Twenty-seven episodes of bacteremia from S. maltophilia were identified in 26 patients, half of whom were women, and the median age was 40 years. A total of 48% of the patients had blood malignancy (12 cases), with acute myeloid leukemia (5 cases) being the most frequent. Seven patients (27%) needed to be admitted to an intensive care unit for some type of vital support and/or intensive treatment. The previous administration of large spectrum antimicrobials (21/26) and the presence of a catheter or central catheter (19/26) were the most frequently found predisposing factors (81% and 73%, respectively). One-quarter of the patients had received treatment with carbapenems. Immunodepression caused by chemotherapy or corticosteroids occurred in 65% of the cases. Half of the patients had undergone a major surgical procedure or had been intubated and submitted to mechanical ventilation. One-third presented granulocytopenia on the detection of bacteremia and 6 of the 12 patients with blood malignancy showed severe neutropenia (<500 neutrophils/mm3). The bacteremia was acquired in hospital in 78% of the cases (21/27). In 26% of these cases, S. maltophilia was diagnosed as the probable cause of bacteremia; in 34% this was just a possibility. The origin of the bacteremia was unknown in 11 cases (40%). Infection from the vascular catheter was the most frequent focus infection (7 cases). An average of 3.6 blood cultures were performed per patient, out of a total of 92, and 54% showed positive. The average time of growth for S. maltophilia in the blood culture bottles was 30 hours. One-third of the bacteremia episodes from S. maltophilia were polymicrobial (9/27). Clinical evolution was favorable in 18 patients, while 8 died (31%), 5 cases (20%) from causes directly related to the bacteremia (4 from septic shock). The mortality associated with the polymicrobial bacteremia was not significantly different from that for single microbial bacteremia from S. maltophilia. Ninety percent of the isolated strains showed susceptibility to co-trimoxazole, 77% to ticarcillin-clavulanic acid, 60% to ciprofloxacin, 62% to ceftazidime, 20% to amikacin and just 18% to imipenem.

Adolescent↗