Search PubMed⌕ Search

Biomedical subjects

M Gobernado

Publications and source records attributed to M Gobernado.

At least 55 records · Page 3Linked to original sources

[The activity of systemic antimycotic drug combinations].

The treatment of deep mycoses is complex, especially in immunosuppressive patients, owing to several factors: the scarcity of antimycotic drugs, the difficulty of carrying out antimycotic susceptibility tests, the scarcity of in vitro/in vivo correlation studies, the lesser response to therapy in comparison to antibacterial treatment, etc. Aside from this, the adverse effects, therapeutic failure and the appearance of resistance are serious problems that may emerge with the use of antimycotic drugs. These problems can be partly avoided by using combinations of antimycotics. In this article, the results obtained by different authors when using systemic antimycotics in combined therapy are reviewed. The effect of the combination of amphotericin B and azoles varies according to the moment of administration: when the azole is administered before amphotericin B, antagonism between the two has been observed; however, when they are administered simultaneously the effect is synergistic with the hydrophylic azoles (fluconazole), antagonistic with lipophilic azoles (itraconazole) or indifferent. The combination of flucytosine with azoles has been demonstrated to be synergistic on Candida albicans (itraconazole, fluconazole) and on Cryptococcus neoformans (fluconazole). With the combinations of an equinocandine and amphotericin B or fluconazole, synergism has been observed on C. neoformans.

Amphotericin B↗

Epidemiological, microbiological, clinical, and prognostic factors of bacteremia caused by high-level vancomycin-resistant Enterococcus species.

A case-control study was performed between 1994 and 1996 in order to study the epidemiological, microbiological, clinical, and prognostic features of high-level vancomycin-resistant enterococcal bacteremia. Seventeen consecutive patients who had clinically significant bacteremia due to vancomycin-resistant enterococci (vanA genotype: 16 Enterococcus faecalis, 1 Enterococcus faecium) were compared with 169 who had vancomycin-susceptible enterococcal bacteremia. The following were selected by multivariate analysis as independent risk factors that influenced the development of high-level vancomycin-resistant enterococcal bacteremia: prior glycopeptide therapy (P=0.049); inclusion in a hemodialysis program (P=0.046); prior therapy with corticosteroids or antineoplastic agents (P=0.029); and prior surgical treatment (P=0.022). The following other factors were selected by univariate analysis: tracheostomy (P=0.002); prolonged hospitalization (P=0.01); and any kind of puncture (P=0.02). The crude associated-mortality rate was 13.4%. Gene amplification of vanA was positive for 17 strains of enterococci. Pulsed-field gel electrophoresis of genomic DNA after SmaI digestion of vanA isolates revealed that one strain predominated (10 isolates), though at least four similar banding patterns were identified (6 isolates). The 16 strains closely related to the outbreak were investigated further. The surgical intensive care unit was the first and most involved service. The hospital outbreak of vanA vancomycin-resistant enterococcal bacteremia occurred between 1994 and 1995 and was caused by Enterococcus faecalis. This is believed to be the first and only such outbreak described in a Spanish hospital thus far.

Adolescent↗

[Comparative analysis of viral load by bDNA HCV RNA-2.0 and amplicor HCV monitor in patients with hepatitis C infection].

BACKGROUND: Two standardized techniques, Quantiplex (bDNA-2.0) and Amplicor Monitor have been evaluated for the quantification of virus load of HCV with these objectives: a) determinate the relationship between virus load and genotype, and b) evaluate the virus load in serial serum samples and in patients with normal or slightly increased liver enzymes in an area with a high prevalence of genotype 1. RESULTS: A significant correlation of 0.7 (p < 0.0001) in virus load has been observed by both methods, but the virus load is smaller by Monitor than by Quantiplex and does not depend on genotype. The relationship Monitor/Quantiplex is smaller in patients with non-1 genotype than in patients with genotype 1a (p = 0.01) and 1b (p = 0.005). Virus characteristics are similar in patients with normal or slightly increased enzymes than in patients with high enzymes. Virus load by both methods is not related to the age, sex, know duration of the infection, transmission manner of the infection neither to the histologic activity index. CONCLUSION: The virus load not depends on genotype. The determination of virus load in a single serum sample adequately reflects the virus load are in several serum samples in patients with chronic HCV infection. The genotype and the virus load are similar in patients with normal enzymes than in patients with high enzymes.

Adult↗

[ROC curve analysis of factors predictive of non-response to interferon treatment in patients with chronic hepatitis C, genotype 1].

The objectives of this study included: 1) to identify pretreatment variables predictive of absence of response in 107 patients with chronic hepatitis C, genotype 1, treated with interferon-a (IFN-a) at a dose of 3 MU three times weekly for 3-12 months and classified into two groups: group A, nonresponders vs. patients with a complete response, and group B, nonresponding and relapsing patients vs. patients with a sustained response; and 2) to establish a prognostic index using ROC curve analysis. The rate of sustained response was 6. 5% at the 24-month follow-up. The pretreatment characteristics with predictive value using ROC curves were as follows: in group A, age, GGT, serum ferritin, viral load, and grade and stage of the histological lesion; and in group B, known duration of infection, GPT, GGT, serum ferritin, viral load, and grade and stage of the histological lesion. In both group A and group B the positive predictive value (the probability of predicting an absence of response when the variable is present) was greater than the negative predictive value (mean: 84.3% vs. 41.1%, 99% vs. 16.5%, respectively). In group A, based on the prognostic index, the positive predictive value when three variables were present was 96% and the sensitivity was 63.5%, with the test being unequivocal in 6.5%, whereas when four or five variables were present, the positive predictive value was 97% and 100% and the sensitivity was 40.5% and 18%, respectively. In group B, the positive predictive value when two variables were present was 100% and the sensitivity was 87%, whereas when three, four, five and six variables were present the sensitivity was between 73% and 28%. In group A, age, GGT and ferritin were the predictive variables independently associated with an absence of response, with a relative risk of 6.5, 4.8 and 3.1, respectively, whereas in group B we did not find variables independently associated with an absence of response. It was concluded that in patients with genotype 1, it is possible to predict the absence of response to IFN therapy with a high degree of reliability.

Adolescent↗

[ROC curve analysis of factors predictive of no response to interferon treatment in patients with chronic hepatitis C, genotype 1]

The objectives of this study included: 1) to identify pretreatment variables predictive of absence of response in 107 patients with chronic hepatitis C, genotype 1, treated with interferon-a (IFN-a) at a dose of 3 MU three times weekly for 3-12 months and classified into two groups: group A, nonresponders vs. patients with a complete response, and group B, nonresponding and relapsing patients vs. patients with a sustained response; and 2) to establish a prognostic index using ROC curve analysis. The rate of sustained response was 6.5% at the 24-month follow-up. The pretreatment characteristics with predictive value using ROC curves were as follows: in group A, age, GGT, serum ferritin, viral load, and grade and stage of the histological lesion; and in group B, known duration of infection, GPT, GGT, serum ferritin, viral load, and grade and stage of the histological lesion. In both group A and group B the positive predictive value (the probability of predicting an absence of response when the variable is present) was greater than the negative predictive value (mean: 84.3% vs. 41.1%, 99% vs. 16.5%, respectively). In group A, based on the prognostic index, the positive predictive value when three variables were present was 96% and the sensitivity was 63.5%, with the test being unequivocal in 6.5%, whereas when four or five variables were present, the positive predictive value was 97% and 100% and the sensitivity was 40.5% and 18%, respectively. In group B, the positive predictive value when two variables were present was 100% and the sensitivity was 87%, whereas when three, four, five and six variables were present the sensitivity was between 73% and 28%. In group A, age, GGT and ferritin were the predictive variables independently associated with an absence of response, with a relative risk of 6.5, 4.8 and 3.1, respectively, whereas in group B we did not find variables independently associated with an absence of response. It was concluded that in patients with genotype 1, it is possible to predict the absence of response to IFN therapy with a high degree of reliability.

Journal Article↗

Human intestinal infection due to coccidia in Mozambique: two cases.

A case of intestinal infection by Cryptosporidium parvum and another of intestinal Isospora belli infection, both in AIDS patients, are described. The two patients presented pulmonary tuberculosis symptoms and watery diarrhoea. Modified Ziehl-Neelsen stain of stools gave a definitive diagnosis in both cases. They are the first reports of intestinal coccidia infections in AIDS patients described in Mozambique.

AIDS-Related Opportunistic Infections↗

Antibiotic susceptibility among aerobic gram-negative bacilli in intensive care units in 5 European countries. French and Portuguese ICU Study Groups.

CONTEXT: Surveillance of antibiotic resistance is especially important in intensive care units (ICUs) because the infection rates are much higher there than in other hospital wards and most epidemics with multiresistant bacteria originate in ICUs. OBJECTIVE: To evaluate the incidence of decreased antibiotic susceptibility among aerobic gram-negative bacilli isolated from patients in ICUs. DESIGN: Consecutive specimens collected on clinical indications from ICU patients were cultured and tested. Minimum inhibitory concentrations for amikacin, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, piperacillin, and piperacillin-tazobactam were determined using E test. SETTING: Eighteen hospitals in Belgium, 40 in France, 20 in Portugal, 30 in Spain, and 10 in Sweden. SUBJECTS: A total of 9166 gram-negative strains were initially isolated from 7308 patients between June 1994 and June 1995. MAIN OUTCOME MEASURES: The incidence of decreased susceptibility, defined as the sum of resistant and intermediate categories with use of the minimum inhibitory concentration break points recommended by the National Committee for Clinical Laboratory Standards. RESULTS: The most frequently isolated organisms were Enterobacteriaceae (59%) followed by Pseudomonas aeruginosa (24%). The main sources were respiratory tract (42%), urine (26%), blood (14%), abdomen (11%), and skin and soft tissue (7%). Decreased antibiotic susceptibility across all species and drugs was highest in Portuguese ICUs followed by French, Spanish, Belgian, and Swedish ICUs. The highest incidence of resistance was seen in all countries among P aeruginosa (up to 37% resistant to ciprofloxacin in Portuguese ICUs and 46% resistant to gentamicin in French ICUs), Enterobacter species, Acinetobacter species, and Stenotrophomonas maltophilia, and in Portugal and France among Klebsiella species. CONCLUSION: The high incidence of reduced antibiotic susceptibility among gram-negative bacteria in these ICUs suggests that more effective strategies are needed to control the selection and spread of resistant organisms.

Belgium↗

High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes.

The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporine-based HCV-infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV-related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first-year liver biopsy findings. We studied 81 consecutive HCV-RNA-positive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporine-based immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow-up was 32 months (range, 12-60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV-related cirrhosis at a median time of 24 months (range, 12-48 months), with an actuarial rate of HCV-cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P =.02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P =.001). The degree of activity and fibrosis score in the first-year biopsy were higher in patients who developed cirrhosis than in those who did not (P =.008 and.18, respectively). In conclusion, HCV genotype 1b-infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes. First-year liver biopsies may help to sooner identify patients at the highest risk, improving further patient management.

Adult↗

Fluconazole susceptibilities of bloodstream Candida sp. isolates as determined by National Committee for Clinical Laboratory Standards method M27-A and two other methods.

The in vitro activity of fluconazole against 143 Candida spp. obtained from the bloodstreams of 143 hospitalized patients from 1995 to 1997 was studied. Susceptibility tests were carried out by two macrodilution methods, the M27-A and a modified M27-A method (0. 165 M, pH 7/morpholinepropanesulfonic acid-buffered RPMI 1640 medium supplemented with 20 g of D-dextrose per liter), and by the agar diffusion method (with 15-microg fluconazole [Neo-Sensitab] tablets). With 2 microg of fluconazole per ml, 96.92% of 65 C. albicans isolates, 86.2% of 58 C. parapsilosis isolates 7 of 8 C. tropicalis isolates, and 1 of 6 C. glabrata isolates were inhibited. Only one strain of C. albicans and one strain of C. tropicalis were resistant. The agreement between the two macrodilution methods was greater than 90% within +/-2 log2 dilutions for all strains except C. glabrata (83.3%) and C. tropicalis (87.5%). Generally, MICs were 1 log2 dilution lower in glucose-supplemented RPMI 1640 medium. No correlation between zone sizes and MICs was found. All strains susceptible by the diffusion test were susceptible by the dilution method, but the converse was not necessarily true. Interestingly, inhibition zones were smaller for C. albicans, for which the geometric mean MIC was 0.29 microg/ml and the mean inhibition zone diameter was 25.7 mm, while for C. parapsilosis the geometric mean MIC was 0.96 microg/ml and the mean inhibition zone diameter was 31. 52 mm. In conclusion, the two macrodilution methods give similar results. The modified M27-A method with 2% dextrose has the advantage of shortening the incubation time and simplifying the endpoint determination.

Antifungal Agents↗

Value of the polymerase chain reaction assay in noninvasive respiratory samples for diagnosis of community-acquired pneumonia.

We studied the causes of community-acquired pneumonia (CAP) in 184 patients. Microbiologic evaluation included sputum examination, blood culture, assessment of acute and convalescent antibody titers for Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Coxiella psitacci, Coxiella burnetii and respiratory viruses, polymerase chain reaction (PCR) assays for M. pneumoniae and C. pneumoniae in throat swab, and PCR assay based on the amplification of pneumolysin gene fragment in sera. The causative pathogen was identified in 78 patients (Streptococcus pneumoniae, 44; M. pneumoniae, 26; C. pneumoniae, 1; others, 7). S. pneumoniae was detected in serum by the PCR assay in 41 patients, five of whom also had a positive blood culture. PCR assay was negative in two patients with positive blood culture for S. pneumoniae. C. pneumoniae was detected by PCR in nine patients, but only one showed seroconversion. M. pneumoniae was detected by PCR in only three patients (two without seroconversion). The diagnosis of pneumonia caused by S. pneumoniae was five times greater using PCR in serum than with blood culture. Detection of C. pneumoniae by PCR without fulfilling criteria for acute infection may be considered a prior infection. The PCR assay for the diagnosis of M. pneumoniae has a lower sensitivity than serologic methods.

Adolescent↗

[Update on the pharmacological interactions of systemic antifungal agents].

The incidence of systemic fungal infections has increased considerably in the last few decades, however the number of available antifungal agents continues to be reduced. Furthermore, these infections tend to affect patients with severe underlying diseases who are treated with different types of medication which may interact with antifungal agents, thus reducing their therapeutic efficacy or increasing their toxicity. In this paper, we discuss the interactions of systemic antifungal agents with other medications and comment on their clinical consequences and the therapeutic approach to adopt in each case.

Amphotericin B↗