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.

Clinical, molecular, and histological characteristics of severely necrotic and fatal mpox in HIV-infected patients.

BACKGROUND: This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. CASE PRESENTATIONS: Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. CONCLUSIONS: Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.

Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial.

BACKGROUND: Voriconazole has been recommended as primary treatment for patients with invasive aspergillosis. Intravenous and tablet formulations of posaconazole that have improved systemic absorption could be an effective alternative to voriconazole. We aimed to assess non-inferiority of posaconazole to voriconazole for the primary treatment of invasive aspergillosis. METHODS: We did a randomised, prospective, double-blind, double-dummy, controlled trial comparing posaconazole (intravenous or oral posaconazole 300 mg twice on day 1, followed by 300 mg once a day for days 2-84) with voriconazole (6 mg/kg intravenous or 300 mg oral twice on day 1 followed by 4 mg/kg intravenously or 200 mg orally twice a day for days 2-84) for 12 weeks or less in the primary treatment of invasive aspergillosis. Participants were from 91 study sites in 26 countries, were aged 13 years or older, weighed at least 40 kg, and met criteria for proven, probable, or possible fungal disease. Participants were randomly assigned (1:1) via a computer-generated randomisation schedule with stratification by risk status. The primary endpoint was cumulative all-cause mortality up until day 42 in the intention-to-treat (ITT) population (defined as randomly assigned participants who received ≥1 dose of study drug), with a 10% non-inferiority margin. The ITT population was also evaluated for safety. This study is registered with ClinicalTrials.gov, NCT01782131, and EudraCT, 2011-003938-14. FINDINGS: Between Oct 25, 2013, and Sept 10, 2019, of 653 individuals assessed for eligibility, 575 ITT participants were randomly assigned and received one or more doses of study drug (n=288 [50%] posaconazole, n=287 [50%] voriconazole). Mortality up until day 42 was 15% (44 of 288) in the posaconazole group and 21% (59 of 287) in the voriconazole group (treatment difference -5·3% [95% CI -11·6 to 1·0]; p<0·0001). Mortality up until day 42 in the full-analysis-set subpopulation (ITT participants with proven or probable invasive aspergillosis) supported this conclusion: 31 (19%) of 163 participants in the posaconazole group and 32 (19%) of 171 participants in the voriconazole group (treatment difference 0·3% [95% CI -8·2 to 8·8]). The most frequently reported treatment-related adverse events (incidence >3%) were increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT), nausea, hypokalaemia, and vomiting in the posaconazole group and increased ALT, AST, or alkaline phosphatase, hallucination, increased γ-glutamyltransferase peptidase, nausea, and blurred vision in the voriconazole group. The overall incidence of treatment-related adverse event rates in the ITT population was 30% for posaconazole and 40% for voriconazole (treatment difference -10·2% [95% CI -17·9 to -2·4]). INTERPRETATION: Posaconazole was non-inferior to voriconazole for all-cause mortality up until day 42 in participants with invasive aspergillosis. Posaconazole was well tolerated, and participants had fewer treatment-related adverse events than in the voriconazole group. This study supports the use of posaconazole as a first-line treatment for the condition. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.

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.

Geotrichum spp: An overlooked and fatal etiologic agent in immunocompromised patients. A case series from a referral center in Mexico.

Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.

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.

COVID-19: WHAT'S NEXT?

Since December 2019, when severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China, this virus and the resulting disease, coronavirus disease (COVID-19), has spread worldwide. What has occurred in this year and a half goes beyond anything we have dealt with, as humankind, in the past two centuries, perhaps obscured only by war. An incredible number of articles, whether scientific or in the press, have been published, making it impossible to discern between what is biological and what is social in nature. Here, we aim to reflect on the basic structure of the virus and associate its behavior to that of determining factors of the human condition that may be modifiable soon. Needless to say, we find our effort clearly incomplete, and that both scientific and social aspects regarding COVID-19 or any other pandemic encountered in the future, will be constantly changing, from their beginning to their end.

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.

In vitro activity of ceftazidime/avibactam and comparators against Gram-negative bacterial isolates collected from Latin American centres between 2015 and 2017.

OBJECTIVES: We report the in vitro activity of ceftazidime/avibactam and comparators against 7729 Enterobacterales isolates and 2053 Pseudomonas aeruginosa isolates collected from six Latin American countries between 2015 and 2017. METHODS: A central reference laboratory performed antimicrobial susceptibility testing using broth microdilution panels according to CLSI guidelines. The presence of ß-lactamases was confirmed using multiplex PCR assays. RESULTS: Susceptibility rates among Enterobacterales were highest for ceftazidime/avibactam (99.3%, MIC90 = 0.5 mg/L), meropenem (95.4%, MIC90 = 0.12 mg/L) and amikacin (93.5%, MIC90 = 8 mg/L). High susceptibility rates were observed for ceftazidime/avibactam in all six countries. The majority of carbapenemase-positive isolates among Enterobacterales (N = 366, 4.7%) were susceptible to ceftazidime/avibactam (86.9%), colistin (76.8%) and amikacin (60.9%); MBL-positive isolates (N = 49, 0.6%) were susceptible only to colistin (79.6%), with a minority susceptible to amikacin (49.0%), aztreonam and levofloxacin (both 30.6%). Highest rates of susceptibility among P. aeruginosa isolates were for colistin (99.2%) and ceftazidime/avibactam (86.6%), with rates of susceptibility to all other agents being <80.0%. MDR P. aeruginosa isolates (N = 712, 34.7%) had a high rate of susceptibility to colistin (98.9%); the rate of susceptibility to ceftazidime/avibactam was 61.4% and <50.0% to all other comparator agents. A total of 235 (11.4%) isolates of P. aeruginosa were carbapenemase positive and 148 (7.2%) were MBL positive; both subsets had high rates of susceptibility to colistin (98.3% and 100%, respectively). CONCLUSIONS: Ceftazidime/avibactam susceptibility rates in Latin American countries are stable and high; ceftazidime/avibactam can be an appropriate treatment for patients with infections caused by Enterobacterales or P. aeruginosa and for whom treatment options may be limited.

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.

Pseudomonas infections among hospitalized adults in Latin America: a systematic review and meta-analysis.

BACKGROUND: Treatment of resistant Pseudomonas aeruginosa infection continues to be a challenge in Latin American countries (LATAM). We synthesize the literature on the use of appropriate initial antibiotic therapy (AIAT) and inappropriate initial antibiotic therapy (IIAT) in P. aeruginosa infections, and the literature on risk factors for acquisition of resistant P. aeruginosa among hospitalized adult patients in LATAM. METHODS: MEDLINE, EMBASE, Cochrane, and LILAC were searched between 2000 and August 2019. Abstracts and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when studies were sufficiently similar. RESULTS: The screening of 165 citations identified through literature search yielded 98 full-text articles that were retrieved and assessed for eligibility, and 19 articles conducted in Brazil (14 articles), Colombia (4 articles), and Cuba (1 article) met the inclusion criteria. Of 19 eligible articles, six articles (840 subjects) examined AIAT compared to IIAT in P. aeruginosa infections; 17 articles (3203 total subjects) examined risk factors for acquisition of resistant P. aeruginosa; and four articles evaluated both. Four of 19 articles were rated low risk of bias and the remaining were deemed unclear or high risk of bias. In meta-analysis, AIAT was associated with lower mortality for P. aeruginosa infections (unadjusted summary OR 0.48, 95% CI 0.28-0.81; I2 = 59%), compared to IIAT and the association with mortality persisted in subgroup meta-analysis by low risk of bias (3 articles; unadjusted summary OR 0.46, 95% CI 0.28-0.81; I2 = 0%). No meta-analysis was performed for studies evaluating risk factors for acquisition of resistant P. aeruginosa as they were not sufficiently similar. Significant risk factors for acquisition of resistant P. aeruginosa included: prior use of antibiotics (11 articles), stay in the intensive care unit (ICU) (3 articles), and comorbidity score (3 articles). Outcomes were graded to be of low strength of evidence owing to unclear or high risk of bias and imprecise estimates. CONCLUSION: Our study highlights the association of AIAT with lower mortality and prior use of antibiotics significantly predicts acquiring resistant P. aeruginosa infections. This review reinforces the need for rigorous and structured antimicrobial stewardship programs in the LATAM region.

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.

Mycobacterium obuense Bacteremia in a Patient with Pneumonia.

Mycobacterium obuense is a pigmented, rapidly growing mycobacterium. Because it has been considered nonpathogenic, M. obuense is being investigated in clinical trials of cancer immunotherapy and bioremediation. We report a case of bacteremia caused by M. obuense in a patient with pneumonia, showing its potential pathogenicity.

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.