Jesús Gaytán-Martínez

Microbiological findings in febrile neutropenia.

BACKGROUND This study was carried out to assess the isolation rate of bacterial and fungal causative agents in Mexican neutropenic adults with hematological neoplasia. METHODS A prospective observational survey involving 120 consecutive episodes of febrile neutropenia during 1 year was carried out. These episodes were observed in 630 patients discharged with diagnoses of leukemia or lymphoma, or after bone-marrow transplantation. RESULTS At least one pathogen was isolated in 42 of 120 episodes (35%), and was present in 39 patients with acute myeloid leukemia (AML) (43%), acute lymphoblastic leukemia (ALL) (23%), and in patients who underwent bone-marrow transplantation (20%). Primary bacteremia was the most frequent cause of fever (24 episodes, 57%), followed by intravascular device-related infections (5 episodes, 17%), and soft-tissue infections (5 episodes, 15%). Escherichia coli (33%) was the most frequently isolated agent of primary bacteremia, followed by coagulase-negative Staphylococcus (29%), and Klebsiella oxytoca (16%). Fungal infection was responsible for five events (4%): two episodes of pneumonia (Penicillium marneffei and Aspergillus fumigatus, one event each); two cases of fungemia, one due to Candida tropicalis and one to Rhodotorula gluttinis, and one cryptococcal meningitis event. CONCLUSIONS The isolation rate, approximately 30%, was in accordance with previous reports; similar percentages of Gram-positive and Gram-negative isolates were found. A remarkably low rate of viridans group streptococci and fungal agents was observed, despite the fact that neutropenia is the main risk factor for infection due to these agents. Studies reporting local microbiological findings are necessary because they support an antibiotic choice for prophylaxis or therapy more accurately than reports from other areas.

Correlation between HIV viral load and aminotransferases as liver damage markers in HIV infected naive patients: a concordance cross-sectional study.

Abnormalities in liver function tests could be produced exclusively by direct inflammation in hepatocytes, caused by the human immunodeficiency virus (HIV). Mechanisms by which HIV causes hepatic damage are still unknown. Our aim was to determine the correlation between HIV viral load, and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as markers of hepatic damage in HIV naive infected patients.We performed a concordance cross-sectional study. Patients with antiviral treatment experience, hepatotoxic drugs use or co-infection were excluded. We used a Pearsons correlation coefficient to calculate the correlation between aminotransferases serum levels with HIV viral load. We enrolled 59 patients, 50 men and 9 women seen from 2006 to 2008. The mean (± SD) age of our subjects was 34.24 ± 9.5, AST 37.73 ± 29.94 IU/mL, ALT 43.34 ± 42.41 IU/mL, HIV viral load 199,243 ± 292,905 copies/mL, and CD4+ cells count 361 ± 289 cells/mm3. There was a moderately strong, positive correlation between AST serum levels and HIV viral load (r = 0.439, P < 0.001); and a weak correlation between ALT serum levels and HIV viral load (r = 0.276, P = 0.034); after adjusting the confounders in lineal regression model the correlation remained significant. Our results suggest that there is an association between HIV viral load and aminotransferases as markers of hepatic damage; we should improved recognition, diagnosis and potential therapy of hepatic damage in HIV infected patients.

Risk factors and correlates for anemia in HIV treatment-naïve infected patients: a cross-sectional analytical study

BackgroundHematologic manifestations of the human immunodeficiency virus (HIV) infection are a well-recognized complication of the disease and may be clinically important. Our objective was to determine the risk factors for anemia and its correlation with HIV treatment-naïve infected patients without co-infection or opportunistic diseases.FindingsWe performed a cross-sectional comparative study in which HIV treatment-naïve infected patients with anemia were compared with a control group of HIV patients without anemia. The interrelationship between risk factors and anemia was determined. Odds ratio and 95% confidence intervals were calculated, to adjust for the effects of potential confounders and we used a logistic regression model. Pearsons correlation coefficient was obtained to calculate the correlation between risk factors and hemoglobin.We enrolled 54 men and 9 women. Anemia was found in 13 patients; prevalence .20 (CI 95% 0.12-0.32). Severe anemia was found in only one patient (1.5%). Only CD4+ Cells Count <200 cells/mm3 was associated with increased risk of anemia in the multivariate analysis. There was a moderately strong, positive correlation between WBC and hemoglobin (r = 0.49, P < 0.001) and between CD4+ cell count and hemoglobin (r = 0.595, P < 0.001) and a moderately strong, negative correlation between HIV RNA viral load and hemoglobin (r = - 0.433, P < 0.001).ConclusionsAnemia is a common manifestation in the Mexican population without antiretroviral therapy. In HIV naïve patients a CD4+ Cell Count < 200 cells/mm3 was associated with an increased risk of anemia. There is a positive correlation between hemoglobin and CD4+ cell count.

In169, A New Class 1 Integron that Encoded blaIMP-18 in a Multidrug-Resistant Pseudomonas aeruginosa Isolate from Mexico

BACKGROUND AND AIMS Carbapenem resistance in Pseudomonas aeruginosa may be due to the presence of metallo-beta-lactamases (MbetaL). The genes that encode these enzymes can be located in association with aminoglycoside-modifying enzymes on class 1 integrons. This study describes the bla(IMP-18) class 1 integron array (In169) from a carbapenem-resistant P. aeruginosa clinical isolate obtained at the Centro Medico Nacional La Raza (CMNR) in Mexico City and compares it to other bla(IMP)-type producers. METHODS Twenty six multiresistant P. aeruginosa clinical isolates were recovered between June and December 2004 and tested by MicroScan and CLSI agar dilution methods. The MbetaL production was screened by a disk approximation test and MbetaL Etest strips, whereas MbetaL genes and integrons were detected using PCR primers. DNA sequence analysis was carried out by BLAST, and epidemiological typing was performed by pulsed-field gel electrophoresis (PFGE). A Southern hybridization analysis was performed with a bla(IMP) specific DNA probe. RESULTS Nine of 26 P. aeruginosa isolates were imipenem-resistant with unique PFGE patterns (no clonal relation), and only one strain (5106) was positive for MbetaL production, corresponding to the IMP-type. The class 1 integron encoding the MbetaL was characterized: it contained the IMP-18, two copies of aadA2 and OXA-2 genes, corresponding to a new class 1 integron array, denoted In169. P. aeruginosa isolate 5106 is genetically related to bla(IMP-18) positive P. aeruginosa isolate from a distant hospital (Hospital Infantil de Morelia). CONCLUSION This report is the first to describe the bla(IMP-18) in two genetically related isolates from two different institutions.

Widespread of ESBL- and carbapenemase GES-type genes on carbapenem-resistant Pseudomonas aeruginosa clinical isolates: a multicenter study in Mexican hospitals

The present work describes a prevalence of 36.2% of carbapenemases IMP-, VIM-, and GES-type on 124 imipenem-resistant Pseudomonas aeruginosa clinical isolates. The ESBL GES-19 and carbapenemase GES-20 genes were the most prevalent (84.4%) β-lactamases among imipenem-resistant P. aeruginosa clinical isolates in Mexico. These genes are chromosomal encoded on embedded class 1 integron arrays.

Effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment-naïve infected patients.

The aim of this study was to evaluate the effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment‐naïve infected patients. This was a prospective cohort study in HIV treatment‐naïve infected patients. The patients were assigned to a untreated group or a treatment group according to the therapeutic strategy received. Patients in the treatment group received efavirenz or lopinavir/ritonavir, each given with zidovudine and lamivudine. HIV RNA, CD4+ cell count, and the levels of hsCRP, sCD40L, sICAM‐1, sVCAM‐1, and sE‐selectin were measured before and 12 weeks after treatment. Fifty patients were enrolled: 13 in the untreated group and 37 in the treatment group; 48 (96%) completed the follow‐up. The mean (±SD) age was 33 ± 9 years, and 38 (79%) were men. The median pretreatment CD4+ cell counts were 263 cells/ml (IQR 118–341) in the treatment group and 658 cells/ml (IQR 475–887) in the untreated group. In the treatment group, the median serum sVCAM‐1 and sICAM‐1 levels decreased by a small but significant amount (1,400 and 228 ng/ml, respectively, P < 0.05) from before to after the 12 weeks. These levels did not change in the untreated group. Antiretroviral therapy is associated with a decrease in sVCAM‐1 and sICAM‐1 levels after 12 weeks of treatment. J. Med. Virol. 85:1321–1326, 2013.

Responses to peginterferon alfa-2a vs alfa-2b plus ribavirin in a Mexican population with chronic hepatitis C

INTRODUCTION The WHO estimates that 180 million people are chronically infected with hepatitis C virus (HCV) throughout the world. Despite the emergence of new therapies, the combination of pegylated interferon and ribavirin remains the accepted standard of care in low-income countries, including Mexico. Two types of peginterferon are available (peginterferon alfa-2a and peginterferon alfa-2b), and both are recommended for the treatment of HCV, although there is controversy over which treatment option is most effective. METHODOLOGY This was a retrospective cohort study at a infectious disease center in Mexico City. Patients were included if they had received peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin. Age, sex, body mass index, AST platelet ratio index, HCV RNA viral load, levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, and hemoglobin, and platelet and leukocyte counts of the subjects were assessed before treatment and at weeks 4, 12, 24, 48, and 6 months post treatment. RESULTS Eighty-seven patients met the inclusion criteria. A sustained virological response (SVR) occurred in 33 (38%) of them, 11 (33%) given peginterferon alfa-2a and 22 (67%) given peginterferon alfa-2b (p = 0.17). Seventeen patients (20%) relapsed, 7 (41%) of those given peginterferon alfa-2a and 10 (59%) of those given peginterferon alfa-2b (p = 0.76); 27 (31%) patients were non-responders (p = 0.09). The rates of anemia, thrombocytopenia, and leukopenia were similar in both groups. CONCLUSIONS Similar SVR rates and frequencies of adverse events were observed. Either type of interferon can be used to treat HCV infection in the Mexican population.

Dyslipidemia and Fasting Glucose Impairment among HIV-InfectedPatients 48-Weeks after the First Antiretroviral Regimen

Background: People infected with human immunodeficiency virus (HIV) develop lipid and glucose metabolic alterations, which predisposes them to cardiovascular disease. The aim of this study was to evaluate the cumulative incidence of dyslipidemia and fasting glucose impairment after 48 weeks of initiating the first antiretroviral (ART) regimen and the association with the type of ART regimen. Method: Retrospective cohort of HIV-1 infected patients attending in the AIDS clinic of five centers of the country, between February 2009 and March 2013. Lipids (total cholesterol and triglycerides) and fasting glucose, were collected prior and 48 weeks after starting ART. We assessed risk factors for dyslipidemia and fasting glucose. To adjust for the effects of potential confounders of metabolic alterations we used logistic regression model. Results: During the study, 223 patients on ART were evaluated. Median age was 34 years [interquartile range (IQR): 28-43]. Of the total patients, 201 (90%) were men. Most common OBR regimens were tenofovir/emtricitabine (TDF/FTC), and efavirenz (EFV) in 42%, abacavir/lamivudine (ABC/3TC) +EFV in 16.6% and TDF/FTC+nevirapine (NVP) in 11.7% patients. Cumulative incidence per 1,000 patients/year of glucose ≥ 100 mg/dL was 233.1, total cholesterol >200 mg/dL was 273.5 and tryglicerides >200 mg/dL was 372.2. The proportion of patients with hypertriglyceridemia (>200 mg/dL) at 48 weeks of ART initiation was 37.2% (95% CI: 31.1-43.7%), hypercholesterolemia (>200 mg/dL) 32.3% (95% CI: 26.5-38.6%) and impairment of fasting glucose (IFG) (>100 mg/dL) 23.3% (95% CI: 18.2-29.2%), After adjustment in a logistic regression model for IFG, EFV-containing regimen OR 2.9 (95%CI 1.12-7.45); p=0.027; for hypertriglyceridemia, age >40 years old OR=1.9 (95% CI: 1.01-3.63); p=0.044, ABC/LAM-containing regimen OR=2.69 (95% CI: 1.42-5.09); p=0.002 and LPV/r-containing regimen OR=5.04 (95% CI 2.32-10.92); p=0.001 were significant; finally, for hypercholesterolemia age >40 years old OR=2.4 (95% CI: 1.15- 4.9); p=0.004 and ABC/3TC-containing regimen OR=1.87 (95% CI: 1.01-3.49); p=0.05 remain significant. Conclusion: These data show high risk of cumulative incidence of IFG and dyslipidemia after initiation of ART. Age >40 years old, ABC/3TC and LPV/r-containing regimens were independent factors to develop dyslipidemia and EFV-containing regimen for IFG in this cohort.

Case report: Identification of recombinant HCV genotype 1b–2b by viral sequencing in two patients with treatment failure, who responded to re-treatment with sofosbuvir and daclatasvir

Hepatitis C virus (HCV) infection is a global health problem. HCV has been classified into seven genotypes and >67 subtypes. Genotyping is necessary to enable selection of appropriate treatments. The commercial molecular techniques currently used do not identify some HCV subtypes, mixed infections and recombinant forms. In this study, the core-E1 and NS5B regions were sequenced and phylogenetically analysed to identify infections by HCV recombinant genotype 1b-2b in two patients who had initially been diagnosed with HCV genotype 2 infection by reverse hybridization with a Versant HCV Genotype 2.0 Assay. Response to treatment was monitored by viral kinetics. Therapeutic failure occurred with initial treatment with PEGylated interferon-α2b and ribavirin, but the use of sofosbuvir and daclatasvir on a re-treatment regimen after reclassification of the infecting virus resulted in a sustained virologic response. The use of a sequencing approach in treatment-naïve infected patients could enable physicians to select the optimal therapy and avoid possible relapses and adverse reactions associated with antiviral therapy.

Mexican patients with HIV have a high prevalence of vertebral fractures

Low bone mineral density (BMD) and fragility fractures are common in individuals infected with HIV, who are undergoing antiretroviral therapy (ART). In high-income countries, dual energy X-ray absorptiometrry is typically used to evaluate osteopenia or osteoporosis in HIV infected individuals. However, this technology is unavailable in low andmiddle income countries, so a different approach is needed. The aim of this study was to use X-ray scans of the spine to determine the prevalence of and associated risk factors for vertebral fractures in HIVinfected patients in a tertiary-care hospital in Mexico. We conducted a cross-sectional study of outpatients who were >40 years old and receiving ART at the Hospital de Infectología, La Raza National Medical Center in Mexico City, Mexico. We used semi-quantitative morphometric analysis of centrally digitized X-ray images to assess vertebral deformities in the spine. Anterior, middle and posterior vertebral heights were measured, and height ratios were calculated. For each vertebral body, fractures were graded on the basis of height ratio reductions, and a spine deformity index’ (SDI) value was calculated by summing the grades of the vertebral deformities: An SDI>1 was indicative of a vertebral fracture. We included 104 patients, 87% of whom were men. The median age was 49 years [interquartile range (IQR) 42-52]. The most common stage of HIV infection, as defined by the Centers for Disease Control, was B2 in 40 (39%) of patients. Forty seven (45%) patients were on ART regimens that included protease inhibitors (PIs) and 100 (96%) being treated with tenofovir. The median time of ART was 6.5 years (IQR 1.6-9.0). Of the 104 patients in our study, 83 (80%) had undetectable viral load, as assessed by HIV-1 RNA levels, 32 (31%) showed evidence of a previous fracture, 4 (4%) were co-infected with hepatitis C virus, and 57 (55%) had a history of corticosteroid treatment. The prevalence of vertebral fractures was 25%, 95% confidence interval 17-34%. We assessed whether gender, HCV co-infection, previous corticosteroid use, AIDS, total HIV viral load, and current and previous use of PIs were associated with fractures in our study group, but we did not observe a significant association between any of these factors and vertebral fractures. The prevalence of vertebral fractures was high among HIV-infected patients. We propose that screening for bone disease should be performed in HIV individuals who are at risk of fragility fractures. Furthermore, we suggest that X-ray based assessment of the spine should be considered in patients who are at increased risk of fragility fractures, irrespective of BMD levels, particularly in elderly patients in low and middle income countries.