Mycobacterium tuberculosis lineage 4 associated with cavitations and treatment failure.

BACKGROUND: Mycobacterium tuberculosis genotyping has been crucial to determining the distribution and impact of different families on disease clinical presentation. The aim of the study was to evaluate the associations among sociodemographic and clinical characteristics and M. tuberculosis lineages from patients with pulmonary tuberculosis in Orizaba, Veracruz, Mexico. METHODS: We analyzed data from 755 patients whose isolates were typified by 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR). The associations among patient characteristics and sublineages found were evaluated using logistic regression analysis. RESULTS: Among M. tuberculosis isolates, 730/755 (96.6%) were assigned to eight sublineages of lineage 4 (Euro-American). Alcohol consumption (adjusted odds ratio [aOR] 1.528, 95% confidence interval (CI) 1.041-2.243; p = 0.030), diabetes mellitus type 2 (aOR 1.625, 95% CI 1.130-2.337; p = 0.009), sputum smear positivity grade (3+) (aOR 2.198, 95% CI 1.524-3.168; p < 0.001) and LAM sublineage isolates (aOR 1.023, 95% CI 1.023-2.333; p = 0.039) were associated with the presence of cavitations. Resistance to at least one drug (aOR 25.763, 95% CI 7.096-93.543; p < 0.001) and having isolates other than Haarlem and LAM sublineages (aOR 6.740, 95% CI 1.704-26.661; p = 0.007) were associated with treatment failure. In a second model, multidrug resistance was associated with treatment failure (aOR 31.497, 95% CI 5.119-193.815; p < 0.001). Having more than 6 years of formal education was not associated with treatment failure. CONCLUSIONS: Knowing M. tuberculosis genetic diversity plays an essential role in disease development and outcomes, and could have important implications for guiding treatment and improving tuberculosis control.

Espacios cardioprotegidos en México: acciones para prevenir la muerte súbita cardiaca. Una postura de profesionales de la salud.

La muerte súbita cardiaca es un problema de salud pública a nivel mundial. Aunque su incidencia no es conocida, se estima que causa hasta 50% de la mortalidad de origen cardíaco y hasta 20% de la mortalidad total en los adultos. En México, estimaciones previas sugieren que causa en promedio 33 000 muertes al año; sin embargo, los datos no son precisos. La  mitad de los eventos por muerte súbita cardiaca se deben a un paro cardiaco súbito extrahospitalario que, de no ser atendido oportunamente, deriva en una muerte súbita cardiaca. Por tanto, la capacidad de responder pronta y adecuadamente a estos eventos con las maniobras y equipos necesarios mejora la sobrevida de las víctimas. Para atender este problema, en algunos estados del país se han creado espacios cardioprotegidos que permiten realizar maniobras de reanimación cardiopulmonar y desfibrilación cardiaca de acceso público oportunamente. Como objetivo, los profesionales de la salud establecen la importancia de implementar espacios cardioprotegidos y crear políticas públicas al respecto en todo el país.

The cholesteryl-ester transfer protein isoform (CETPI) and derived peptides: new targets in the study of Gram-negative sepsis.

BACKGROUND: Sepsis is a syndrome where the dysregulated host response to infection threatens the life of the patient. The isoform of the cholesteryl-ester transfer protein (CETPI) is synthesized in the small intestine, and it is present in human plasma. CETPI and peptides derived from its C-terminal sequence present the ability to bind and deactivate bacterial lipopolysaccharides (LPS). The present study establishes the relationship between the plasma levels of CETPI and disease severity of sepsis due to Gram-negative bacteria. METHODS: Plasma samples from healthy subjects and patients with positive blood culture for Gram-negative bacteria were collected at the Intensive Care Unit (ICU) of INCMNSZ (Mexico City). 47 healthy subjects, 50 patients with infection, and 55 patients with sepsis and septic shock, were enrolled in this study. CETPI plasma levels were measured by an enzyme-linked immunosorbent assay and its expression confirmed by Western Blot analysis. Plasma cytokines (IL-1ß, TNFα, IL-6, IL-8, IL-12p70, IFNγ, and IL-10) were measured in both, healthy subjects, and patients, and directly correlated with their CETPI plasma levels and severity of clinical parameters. Sequential Organ Failure Assessment (SOFA) scores were evaluated at ICU admission and within 24 h of admission. Plasma LPS and CETPI levels were also measured and studied in patients  with liver dysfunction. RESULTS: The level of CETPI in plasma was found to be higher in patients with positive blood culture for Gram-negative bacteria that in control subjects, showing a direct correlation with their SOFA values. Accordingly, septic shock patients showing a high CETPI plasma concentration, presented a negative correlation with cytokines IL-8, IL-1ß, and IL-10. Also, in patients  with liver dysfunction, since higher CETPI levels correlated with a high plasma LPS concentration, LPS neutralization carried out by CETPI might be considered a physiological response that will have to be studied in detail. CONCLUSIONS: Elevated levels of plasma CETPI were associated with disease severity and organ failure in patients  with Gram-negative bacteraemia, defining CETPI as a protein implicated in the systemic response to LPS.

Epicardial adipose tissue thickness is associated with increased COVID-19 severity and mortality.

BACKGROUND: Increased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes. METHODS: We included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes. RESULTS: EAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95% CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4 C severity score, independent of obesity. EAT mediated 13.1% (95% CI 3.67-28.0%) and 5.1% (95% CI 0.19-14.0%) of the effect of age and 19.4% (95% CI 4.67-63.0%) and 12.8% (95% CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19. CONCLUSION: EAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.

Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID).

BACKGROUND: Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated. OBJECTIVE: To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19. DESIGN: We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial. PARTICIPANTS: We recruited 116 hospitalized patients with severe COVID-19 in Mexico. INTERVENTIONS: Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment. MAIN MEASURES: The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients. KEY RESULTS: Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35-1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66-3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A. CONCLUSIONS: Colchicine is safe but not effective in the treatment of severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04367168.

Incidence of Cytomegalovirus disease and viral replication kinetics in seropositive liver transplant recipients managed under preemptive therapy in a tertiary-care center in Mexico City: a retrospective cohort study.

BACKGROUND: In the absence of an adequate prevention strategy, up to 20% of CMV IgG+ liver transplant recipients (LTR) will develop CMV disease. Despite improved reporting in CMV-DNAemia, there is no consensus as to what the ideal CMV-DNAemia cutoff for a successful preemptive strategy is. Each transplant centre establishes their own threshold. We aimed to determine the effectiveness of our preventive strategy in CMV IgG+ LTR, and evaluate CMV replication kinetics. METHODS: In this retrospective study we determined the incidence of CMV disease in the first 6 months following transplantation in CMV seropositive LTR in a tertiary-care centre in Mexico. Secondary outcomes were determining the number of patients who required preemptive therapy (treatment cutoff ≥ 4000 UI/ml), adherence to the centre's prevention protocol and calculation of viral replication kinetics. RESULTS: One-hundred and twenty-four patients met inclusion criteria. Four patients (3.2%) developed CMV disease. Ninety-six (85%) had detectable DNAemia and 25 (22%) asymptomatic patients received preemptive therapy, none of them developed CMV disease. The highest viral loads were observed on the second posttransplant month. The number of viral load measurements decreased over time. Patients with DNAemia ≥ 4000 UI/ml had a faster viral load growth rate, shorter viral load duplication time, and higher basic reproductive number. Viral load growth rate and autoimmune hepatitis were associated with development of DNAemia ≥ 4000 UI/ml. CONCLUSION: Cytomegalovirus disease occurred in 3.2% of the study subjects. Preemptive therapy using a threshold of CMV ≥ 4000 UI/ml was effective in reducing the incidence of end-organ disease. The viral replication parameters described in this population highlight the importance of frequent monitoring, a challenging feat for transplant programs in low- and middle-income countries.

Predictors of Poor Outcomes in Young Non-Comorbid Patients with COVID-19.

Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objectives: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV. (Rev Invest Clin. 2022;74(5):268-75).

Effect of Tocilizumab in Mortality among Patients with Severe and Critical Covid-19: Experience in a Third-Level Medical Center.

BACKGROUND: Trials evaluating safety and efficacy of tocilizumab in coronavirus disease 19 (COVID-19) show contradictory results. OBJECTIVE: The objective of the study was to evaluate the effect of tocilizumab in hospital mortality among patients with severe COVID-19 in a third-level medical center. METHODS: This prospective cohort study included patients with severe and critical COVID-19. Primary outcome was death during hospitalization. Secondary outcomes included invasive mechanical ventilation (IMV), days on IMV, ventilator-free days (VFDs), length of hospital stay (LOS), and development of hospitalacquired infections (HAIs). Bivariate, multivariate, and propensity score matching analysis were performed. RESULTS: During the study period, 99/794 (12%) patients received tocilizumab. Male patients, health care workers, and patients with increased inflammatory markers received tocilizumab more frequently. No difference in hospital mortality was observed between groups (34% vs. 34%, p = 0.98). Tocilizumab was not independently associated with mortality. No significant treatment effects were observed in propensity score analysis. IMV was more frequent (46% vs. 11%, p < 0.01) and LOS was longer (12 vs. 7 days, p < 0.01) in the tocilizumab group, reflecting increased severity. Although HAIs were more frequent in the tocilizumab group (22% vs. 10%, p < 0.01), no difference was seen after adjusting for IMV (38% vs. 40%, p = 0.86). CONCLUSIONS: In our study, tocilizumab was not associated with decreased hospital mortality among patients with severe COVID-19.

Significant Rise in SARS-CoV-2 Reinfection Rate in Vaccinated Hospital Workers during the Omicron Wave: A Prospective Cohort Study.

Background: Relatively low SARS-CoV-2 reinfection rates have been reported in vaccinated individuals, but updates considering the Omicron variant are lacking. Objectives: The objective of the study was to provide a current estimate of the SARS-CoV-2 reinfection rate in a highly immunized population. Methods: A prospective cohort of Mexican hospital workers was followed (March 2020-February 2022). Reinfection was defined as the occurrence of two or more episodes of COVID-19 separated by a period of ≥ 90 days without symptoms. The reinfection rate was calculated as the number of reinfection episodes per 100,000 persons per day. Results: A total of 3732 medical consultations were provided to 2700 workers, of whom 1388 (51.4%) were confirmed COVID-19 cases. A total of 73 reinfection cases were identified, of whom 71 (97.3%) had completed their primary vaccination series and 22 (30.1%) had had a booster dose before the second episode. The overall reinfection rate was 23.1 per 100,000 persons per day (as compared to a rate of 1.9 per 100,000 persons per day before the Omicron wave). Conclusions: The SARS-CoV-2 reinfection rate rose significantly during the Omicron wave despite a high primary vaccination coverage rate. Almost one-third of reinfected workers had a vaccine booster ≥ 14 days before the last COVID-19 episode.

Prevention of COVID-19 superspreading events in buses boarded by presymptomatic cases.

INTRODUCTION: COVID-19 superspreader events have occurred when symptomatic individuals without wearing face masks boarded buses. OBJECTIVE: To report the risk of superspreader events when presymptomatic individuals boarded buses to-gether with unvaccinated passengers, but with non-pharmacological preventive interventions being maintained. METHODS: Prospec-tive study of health personnel transported in buses to a COVID-19 vaccination center for two weeks. Open windows, correct use of face masks and exclusion of symptomatic individuals were mandatory. Prospective surveillance identified workers with COVID-19 within 14 days after vaccination. Each asymptomatic passenger of buses where cases were identified was monitored for a similar time period. Voluntary screening results were available for workers who were tested in the month before or after vaccination. RESULTS: 1,879 workers boarded 65 buses. On-board time ranged from three to eight hours. Twenty-nine cases of COVID-19 and four asymptomatic cases were identified among 613 passengers of 21 buses. Median time between vaccina-tion and COVID-19 symptoms onset was six days. One case of suspected transmission on a bus was identi-fied. CONCLUSIONS: Strict nonpharmacological preventive interventions substantially reduced the risk of COVID-19 super-spreader events in buses boarded by presymptomatic individuals.

ANTECEDENTES: Ha ocurrido superpropagación de COVID-19 cuando individuos sintomáticos sin uso de cubrebocas abordaron autobuses. OBJETIVO: Reportar el riesgo de superpropagación cuando individuos presintomáticos abordaron autobuses junto con pasajeros no vacunados pero se mantuvieron intervenciones preventivas no farmacológicas. MATERIAL Y MÉTODOS: Estudio prospec­tivo de personal de salud transportado durante dos semanas en autobuses a un centro de vacunación contra COVID-19. Fue obligatorio llevar ventanas abiertas, uso correcto de cubrebocas y exclusión de personas con síntomas. La vigilancia prospectiva identificó a trabajadores con COVID-19 los 14 días siguientes a la vacunación. Cada pasajero asintomático de autobuses donde se detectaron casos fue vigilado durante un periodo de tiempo similar. Los resultados de tamizaje voluntario estuvieron disponibles para los trabajadores que se realizaron prueba el mes previo o el siguiente a la vacunación. RESULTADOS: 1879 trabajadores abordaron 65 autobuses. El tiempo a bordo varió de tres a ocho horas. Veintinueve casos de COVID-19 y 4 casos asintomáticos fueron identificados entre 613 pasajeros de 21 autobuses. La mediana de tiempo entre la vacunación y el inicio de síntomas en casos de COVID-19 fue de seis días. Fue identificado un caso de transmisión sospechada en autobús. CONCLUSIONES: Las intervenciones preventivas no farmacológicas estrictas redujeron sustancialmente el riesgo de superpropagación de COVID-19 en autobuses ocupados por individuos presintomáticos.

Accuracy of galactomannan testing on tracheal aspirates in COVID-19-associated pulmonary aspergillosis.

OBJECTIVE: Our aim was to evaluate the performance of two galactomannan (GM) assays (Platelia Aspergillus EIA, Bio-Rad® , and Aspergillus GM LFA, IMMY® ) in tracheal aspirate (TA) samples of consecutive critically ill patients with COVID-19. METHODS: We included critically ill patients, performed GM-EIA and GM-Lateral Flow Assay (GM-LFA) in TA and followed them until development of COVID-19-associated pulmonary aspergillosis (CAPA) or alternate diagnosis. CAPA was defined according to the modified AspICU criteria in patients with SARS-CoV-2 infection. We estimated sensitivity, specificity, positive and negative predictive values for GM-EIA, GM-LFA, the combination of both or either positive results for GM-EIA and GM-LFA. We explored accuracy using different breakpoints, through ROC analysis and Youden index to identify the optimal cut-offs. We described antifungal treatment and 30-day mortality. RESULTS: We identified 14/144 (9.7%) patients with CAPA, mean age was 50.35 (SD 11.9), the median time from admission to CAPA was 8 days; 28.5% received tocilizumab and 30-day mortality was 57%. ROC analysis and Youden index identified 2.0 OD as the best cut-off, resulting in sensitivity and specificity of 57.1% and 81.5% for GM-EIA and 60% and 72.6% for GM-LFA, respectively. CONCLUSIONS: The diagnostic performance of GM in tracheal aspirates improved after using a cut-off of 2 OD. Although bronchoalveolar lavage testing is the ideal test, centres with limited access to bronchoscopy may consider this approach to identify or rule out CAPA.

Surge in Ventilator-Associated Pneumonias and Bloodstream Infections in An Academic Referral Center Converted to Treat COVID-19 Patients.

BACKGROUND: Healthcare-associated infections (HAIs) are important adverse events that must be prevented. OBJECTIVE: The objective of the study was to report and study possible changes in HAI rates as well as their causes after the COVID-19 hospital surge capacity response (HSCR) in an academic referral center. METHODS: This was a before-after observational study. The Infection Prevention and Control (IPC) program (prospective surveillance, prevention bundles, antibiotic stewardship, continuing education, and feedback) was transiently disrupted after the start of HSCR (March 2020). HAI rates were compared before (January 2019-February 2020) and after (April-July 2020) HSCR, and plausible predisposing factors in affected patients were compared. RESULTS: An increase in the HAI rate from 6.2 to 11.8 cases/1000 patient-days was noted between periods due to increases in ventilator-associated pneumonia and bloodstream infection (BSI) rates. More critically ill patients were admitted during HSCR, and use of invasive devices increased. Prone positioning and infusion of muscle relaxants became commonplace. The nurse-to-patient ratio in the intensive care unit decreased, and 4 h shifts were introduced to avoid fatigue. The BSI rate decreased after the IPC program with additional measures was reintroduced in May 2020. CONCLUSIONS: The strain on the workforce and modifications to the IPC program very possibly underlay the findings. IPC programs continue to be essential during the pandemic.

Factors Associated with COVID-19 and Asymptomatic Carriage in Healthcare Workers of a COVID-19 Hospital.

BACKGROUND: Risk factors for coronavirus disease (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) asymptomatic carriage (AC) in healthcare workers (HCWs) have been scarcely characterized. OBJECTIVE: The objective of the study was to study factors associated with COVID-19 and AC in HCWs of a COVID-19 academic medical center. METHODS: This is a case-control study. Cases were either symptomatic or asymptomatic HCWs with a positive SARS-CoV-2 polymerase chain reaction (PCR) test result between March 16 and May 21 of 2020. Adjusted odds ratios (aOR) were calculated by means of multivariable logistic regression. In addition, each subject was followed for 14 days to inform outcomes. RESULTS: One hundred thirty of 249 (52.2%) symptomatic HCWs had COVID-19; 10 were hospitalized but none died. Of 987 asymptomatic HCWs,37 (3.7%) were AC; 6 of the remaining 950 asymptomatic HCWs with a negative PCR test result were found to be presymptomatic COVID-19 cases the following 14 days. Nurses were more frequently present in the COVID-19 group (51.5% vs. 37.0%), but multivariable analysis rendered non-significant results. After adjustment for age, comorbidities, and working place, factors found to be associated with AC were: working in wards as a nurse (aOR = 9.19, 95% confidence interval [CI] = 1.05-80.22, p = 0.045), kitchen personnel (aOR = 4.09, 95% CI = 1.55-10.83, p = 0.005), and being a physician (aOR = 0.12, 95% CI = 0.03-0.54, p = 0.006). CONCLUSIONS: HCW category was the predominant factor associated with AC of SARS-CoV-2 in this study.

Latent Tuberculosis in Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Strategies to Prevent Disease Activation in an Endemic Population.

Latent tuberculosis infection (LTBI) affects one-fourth of the world´s population. Hematopoietic stem cell transplantation (HSCT) recipients are at an elevated risk of developing active tuberculosis infection (ATBI). In this retrospective study of donors and HSCT recipients who underwent transplantation between February 2000 and June 2018, our aim was to determine the prevalence of LTBI and ATBI and to describe diagnostic and therapeutic strategies in an HSCT population in an endemic region. The cohort of 409 participants included 125 allogeneic HSCT (allo-HSCT) recipients, 165 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Patients were evaluated pre-HSCT with tuberculin skin test and thoracic imaging. LTBI was diagnosed in 26.2% of the cohort. Cases represented 20% of the auto-HSCT population, 20% of the allo-HSCT population, and 41.2% of the donor population. Pre-HSCT evaluation to rule out ATBI was performed in 62.6% of the cohort; all results were negative. Isoniazid was administered to 73.3% of those with LTBI. Within subgroups, 91.7% of HSCT recipients and 51% of donors received treatment. The median duration of therapy pre-HSCT was 70 days in recipients and 48 days in donors. The incidence of post-HSCT ATBI was 0 at 1-year follow-up. The incidence of LTBI in our population was higher than expected and still might have been underestimated owing to diagnostic test limitations. The absence of incident ATBI suggests that recipients, as opposed to donors, must receive LTBI treatment. Prevention of infectious complications in the HSCT population should be prioritized to improve clinical outcomes. Prospective data from collaborative working groups is needed to determine the best diagnostic and therapeutic approaches in this vulnerable patient population.

Perioperative fosfomycin disodium prophylaxis against urinary tract infection in renal transplant recipients: a randomized clinical trial.

BACKGROUND: Symptomatic urinary tract infection (UTI) is the most common infectious complication in renal transplant recipients (RTRs). Fosfomycin (FOS) is an attractive alternative for prophylaxis because it does not interact with immunosuppressants; although 90% is excreted unchanged in the urine, it does not require adjustment for renal function for single dose prophylaxis. METHODS: RTRs were recruited into this randomized, double-blind, placebo-controlled trial. Participants were randomized (1:1) to receive one 4 g dose of FOS disodium intravenously 3 h (FOS group) or placebo (placebo group) before placement and removal of a urinary catheter and before removal of a double-J ureteral stent. All participants received prophylaxis with trimethoprim/sulfamethoxazole. The main outcome was a comparison of the mean number of symptomatic UTI and asymptomatic bacteriuria (AB) episodes per patient during a 7-week follow-up period. The study was registered at ClinicalTrials.gov, NTC03235947. RESULTS: Eighty-two participants were included (41 in the FOS group and 41 in placebo group). The mean number of AB or symptomatic UTI episodes per patient was lower in the FOS group [intention-to-treat (ITT) 0.29 versus 0.60, P = 0.04]. The incidence of symptomatic UTI was lower in the FOS group (ITT, 7.3% versus 36.6%, P = 0.001), and there was no difference in the incidence of AB between both groups. The incidence of adverse events was similar in both groups. CONCLUSIONS: FOS addition is an effective and safe strategy to reduce the number of symptomatic UTIs during the first 7 weeks after renal transplant.

High prevalence of MDR gram-negative bacteria in feces of healthy blood donors in Mexico.

During the initial stage of a study to recruit universal intestinal microbiota donors in Mexico City, we found multiple "healthy" subjects that colonized with MDRO (Multidrug-resistant organisms). We aimed to describe clinical and demographic characteristics of these individuals. This was a prospective observational study. Participants were consecutively recruited among blood donors. A fecal sample was collected from each subject and analyzed at the same day in search of MDRO through chromographic culture media and, if growth observed, later confirmed by MALDI-TOF and susceptibility testing in Vitek 2 system. From July 2018 to March 2019, 85 individuals were screened for fecal colonization. Median age was 35 years (IQR 27-46 years), and 48/85 (56.4%) were males. Seventy-two (84.7%) subjects harbored at least one MDRO. ESBL-producing microorganisms were found in 72/85 (84.3%) subjects, and E. coli was the most frequent (63/85, 74.1%). Four samples (2 E. coli, 2 P. aeruginosa, 2.4% each) harbored carbapenem-resistant Enterobacteriaceae (CRE), together with an ESBL-producing microorganism. Antibiotic use (p = 0.06) and PPIs or H2-blockers intake (p = 0.03) were more common in the colonized subjects during the previous 6-month period. We report a high incidence of enteric colonization of healthy subjects with MDRO, a condition that may be related to antibiotics or PPIs/H2-blockers consumption. This surprisingly high MDRO colonization rate in potential FMT donors emphasizes the need for careful screening of donors to avoid possible transmission to FMT recipients.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF PATIENTS DIAGNOSED WITH COVID-19 IN A TERTIARY CARE CENTER IN MEXICO CITY: A PROSPECTIVE COHORT STUDY.

BACKGROUND: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. OBJECTIVE: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). METHODS: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. RESULTS: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. CONCLUSIONS: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.

Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients.

Loss to follow-up (LFU) of ≥2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU.We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan-Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU.Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3-11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36-50 years (HR 1.3, 95% CI 1.0-1.6; p=0.04) compared with age 0-25 years, being HIV positive (HR 1.8, 95% CI 1.2-2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6-1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4-0.6; p<0.01) compared with no serious adverse event.Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months.

Azole resistance and cyp51A mutation screening in Aspergillus fumigatus in Mexico.

BACKGROUND: Fungicide exposure in the environment has driven the emergence of azole-resistant Aspergillus fumigatus worldwide. A screening test allows identification of resistant isolates. OBJECTIVES: We screened clinical samples for azole-resistant Aspergillus through azole-containing agar plates and identified mutations in the cyp51A gene of A. fumigatus. METHODS: Aspergillus isolates from clinical samples collected in a tertiary care centre from 2014 to 2017 were screened for azole resistance. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subject to DNA extraction, DNA amplification and sequencing of the cyp51A gene (coding and promoter regions). Clinical data were obtained from medical records. RESULTS: We screened 43 Aspergillus isolates from 39 patients for azole resistance. Three isolates from three patients grew on azole-containing agar plates: two A. fumigatus and one Aspergillus flavus. PCR analysis and cyp51A sequencing identified the TR34/L98H mutation in both A. fumigatus isolates. The prevalence of cyp51A mutations among A. fumigatus was 8.3% (2/24). Both patients with TR34/L98H mutants were azole naive and presented with invasive aspergillosis; one had multiple myeloma and the other was a liver retransplant recipient. They suffered progressive disease and failed voriconazole therapy. CONCLUSIONS: To the best of our knowledge, this is the first report of azole-resistant A. fumigatus with the TR34/L98H mutation in two azole-naive patients with refractory invasive aspergillosis in Mexico.

Enfermedad granulomatosa hepática.

Granulomas are circumscribed lesions mainly composed of mononuclear cells that arise in response to poorly degradable antigenic stimuli. They are found in 2-15 % of liver biopsies and the meaning of their finding can range from an incidental phenomenon to the manifestation of a systemic disease of infectious, autoimmune or neoplastic origin. Clinical presentation usually points at the underlying pathology; however, the list of associated conditions is extensive, and differs based on patient epidemiological history and baseline characteristics. The most useful element for their study is a thorough medical history, with an emphasis on recent trips, exposures and consumption of drugs or raw or exotic foods. Detailed histopathological analysis may help identify the etiology. For example, the presence of epithelioid granulomas with caseous necrosis indicates tuberculosis and, its absence, sarcoidosis; eosinophil abundance can be associated with drug reactions or parasitic infections; and the presence of foreign bodies can be the cause of granulomatous liver disease (GLD). In this article, we describe the basic clinical-pathological aspects of GLD, and provide a brief summary of the most common etiologies, with an emphasis on the Latin-American region.

Los granulomas son lesiones circunscritas compuestas principalmente por células mononucleares que surgen en respuesta a estímulos antigénicos pobremente degradables. Se encuentran en 2 a 15 % de las biopsias hepáticas; su hallazgo puede significar desde un fenómeno incidental, hasta la manifestación de una enfermedad sistémica de origen infeccioso, autoinmune o neoplásico. El cuadro clínico suele apuntar a la patología subyacente, sin embargo, la lista de condiciones asociadas es amplia y difiere con base en los antecedentes epidemiológicos y a las características basales del paciente. El elemento de mayor utilidad para su estudio es la historia clínica exhaustiva, con énfasis en viajes recientes, exposición de riesgo y consumo de fármacos o alimentos crudos o exóticos. El análisis histopatológico detallado puede auxiliar en la identificación de la etiología, por ejemplo, la presencia de granulomas epitelioides con necrosis caseosa indica tuberculosis y su ausencia, sarcoidosis; la abundancia de eosinófilos es señal de reacciones farmacológicas o infecciones parasitarias; la presencia de cuerpos extraños puede ser la causa de la enfermedad granulomatosa hepática. En este artículo describimos los aspectos clínico-patológicos básicos de esta enfermedad y proveemos un breve resumen de las etiologías más comunes, principalmente en la región de Latinoamérica.