Molecular characterization and genotyping of isolates from cancer patients with Clostridioides difficile infection or asymptomatic colonization.

Introduction. Cancer patients with Clostridioides difficile infection (CDI) are at a higher risk for adverse outcomes. In addition, a high prevalence of Clostridioides difficile asymptomatic colonization (CDAC) has been reported in this vulnerable population.Gap Statement. The molecular characteristics and potential role of CDAC in healthcare-related transmission in the cancer population have been poorly explored.Aim. We aimed to compare the molecular and genotypic characteristics of C. difficile isolates from cancer patients with CDAC and CDI.Method. We conducted a prospective cohort study of cancer patients with CDAC or CDI from a referral centre. Molecular characterization, typification and tcdC gene expression of isolates were performed.Results. The hospital-onset and community-onset healthcare facility-associated CDI rates were 4.5 cases/10 000 patient-days and 1.4 cases/1 000 admissions during the study period. Fifty-one C. difficile strains were isolated: 37 (72 %) and 14 (28 %) from patients with CDI or CDAC, respectively. All isolates from symptomatic patients were tcdA+/tcdB+, and four (10 %) were ctdA+/ctdB+. In the CDAC group, 10 (71 %) isolates were toxigenic, and none were ctdA+/ctdB+. The Δ18 in-frame tcdC deletion and two transition mutations were found in five isolates. After bacterial typing, 60 % of toxigenic isolates from asymptomatic carriers were clonal to those from patients with C. difficile-associated diarrhoea. No NAP1/027/BI strains were detected.Conclusions. We found a clonal association between C. difficile isolates from patients with CDAC and CDI. Studies are needed to evaluate the potential role of asymptomatic carriers in the dynamics of nosocomial transmission to support infection control measures and reduce the burden of CDI in high-risk groups.

Active Surveillance of Antimicrobial Resistance and Carbapenemase-Encoding Genes According to Sites of Care and Age Groups in Mexico: Results from the INVIFAR Network.

We analyzed the antimicrobial resistance (AMR) data of 6519 clinical isolates of Escherichia coli (n = 3985), Klebsiella pneumoniae (n = 775), Acinetobacter baumannii (n = 163), Pseudomonas aeruginosa (n = 781), Enterococcus faecium (n = 124), and Staphylococcus aureus (n = 691) from 43 centers in Mexico. AMR assays were performed using commercial microdilution systems (37/43) and the disk diffusion susceptibility method (6/43). The presence of carbapenemase-encoding genes was assessed using PCR. Data from centers regarding site of care, patient age, and clinical specimen were collected. According to the site of care, the highest AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from ICU patients. In contrast, in A. baumannii, higher AMR was observed in isolates from hospitalized non-ICU patients. According to age group, the highest AMR was observed in the ≥60 years age group for E. coli, E. faecium, and S. aureus, and in the 19-59 years age group for A. baumannii and P. aeruginosa. According to clinical specimen type, a higher AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from blood specimens. The most frequently detected carbapenemase-encoding gene in E. coli was blaNDM (84%).

Genetic diversity of Mycobacterium bovis evaluated by spoligotyping and MIRU-VNTR in an intensive dairy cattle breeding area in Mexico.

Bovine tuberculosis (bTB) is mainly caused by Mycobacterium bovis. In Mexico, dairy cattle play an important role in the persistence and spread of the bacillus. In order to describe M. bovis genetic diversity, we genotyped a total of 132 strains isolated from slaughtered cattle with bTB suggestive lesions between 2009 and 2010 in Hidalgo, Mexico, using a panel of 9-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) and spoligotyping. We found 21 spoligotypes, and 124 isolates were grouped in 13 clusters. The most frequent spoligotypes were SB0121 (49, 37.1%) and SB0673 (27, 20.5%); three new spoligotypes were reported SB02703, SB02704 and SB02705. We observed 37 MIRU-VNTR patterns, 107 isolates were grouped in 12 clusters and 25 isolates were unique. Spoligotypes SB0121, SB0673, SB0140, SB0145 and SB0120 showed marked subdivision applying MIRU-VNTR method; meanwhile, spoligotypes SB0971 and SB0327 showed single MIRU-VNTR profiles. The Hunter-Gaston discriminatory index (HGDI) was 0.88, 0.78 and 0.90 for 9-loci MIRU-VNTR, spoligotyping and both methods, respectively. Additionally, allelic diversity (h) analysis showed high diversity for QUB3232, QUB26 and QUB11b with h = 0.79, 0.66 and 0.63, respectively. Overall, high genetic variability was observed among M. bovis isolates. Thus, the use of 9-loci MIRU-VNTR panel is enough to describe genetic diversity, evolution and distribution of M. bovis. This study supports the use of these tools for subsequent epidemiological studies in high incidence areas.

Outcomes in Temporary ICUs Versus Conventional ICUs: An Observational Cohort of Mechanically Ventilated Patients With COVID-19-Induced Acute Respiratory Distress Syndrome.

Throughout the COVID-19 pandemic, thousands of temporary ICUs have been established worldwide. The outcomes and management of mechanically ventilated patients in these areas remain unknown. OBJECTIVES: To investigate mortality and management of mechanically ventilated patients in temporary ICUs. DESIGN SETTING AND PARTICIPANTS: Observational cohort study in a single-institution academic center. We included all adult patients with severe COVID-19 hospitalized in temporary and conventional ICUs for invasive mechanical ventilation due to acute respiratory distress syndrome from March 23, 2020, to April 5, 2021. MAIN OUTCOMES AND MEASURES: To determine if management in temporary ICUs increased 30-day in-hospital mortality compared with conventional ICUs. Ventilator-free days, ICU-free days (both at 28 d), hospital length of stay, and ICU readmission were also assessed. RESULTS: We included 776 patients (326 conventional and 450 temporary ICUs). Thirty-day in-hospital unadjusted mortality (28.8% conventional vs 36.0% temporary, log-rank test p = 0.023) was higher in temporary ICUs. After controlling for potential confounders, hospitalization in temporary ICUs was an independent risk factor associated with mortality (hazard ratio, 1.4; CI, 1.06-1.83; p = 0.016).There were no differences in ICU-free days at 28 days (6; IQR, 0-16 vs 2; IQR, 0-15; p = 0.5) or ventilator-free days at 28 days (8; IQR, 0-16 vs 5; IQR, 0-15; p = 0.6). We observed higher reintubation (18% vs 12%; p = 0.029) and readmission (5% vs 1.6%; p = 0.004) rates in conventional ICUs despite higher use of postextubation noninvasive mechanical ventilation (13% vs 8%; p = 0.025). Use of lung-protective ventilation (87% vs 85%; p = 0.5), prone positioning (76% vs 79%; p = 0.4), neuromuscular blockade (96% vs 98%; p = 0.4), and COVID-19 pharmacologic treatment was similar. CONCLUSIONS AND RELEVANCE: We observed a higher 30-day in-hospital mortality in temporary ICUs. Although both areas had high adherence to evidence-based management, hospitalization in temporary ICUs was an independent risk factor associated with mortality.

Point Prevalence Survey of Antimicrobial Use in Four Tertiary Care Hospitals in Mexico.

PURPOSE: To describe the antimicrobial use in four tertiary care hospitals in Mexico. PATIENTS AND METHODS: Point prevalence surveys (PPSs) were conducted on medical records of hospitalized patients with prescribed antimicrobials (AMs) in four tertiary care hospitals in Mexico in 2019. Prevalence estimates and descriptive statistics were used to present the collected data on antimicrobial prescribing and microbiological studies. RESULTS: The prevalence of patients with prescribed AMs among the hospitals ranged from 47.1% to 91.3%. Antibiotics for systemic use (J01s) were the most prescribed (84.6%, [95% CI: 81.5-87.3]), mainly extended-spectrum J01s: third-generation cephalosporins 19.8% [95% CI: 16.8-23.1], and carbapenems 17.0% [95% CI: 14.2-20.2]. Antibiotic treatments were largely empirical, with no planned duration or review dates. The ceftriaxone use was excessive and prolonged. No formal reference guidelines for antimicrobial prescribing were available in the hospitals. Multidrug-resistant Escherichia coli and ESKAPE pathogens were identified in all hospitals. CONCLUSION: This study describes the extensive use of antimicrobials and broad-spectrum antibiotics for systemic use in Mexican hospitals, along with the presence of resistant pathogens to the antibiotics frequently used in the hospitals surveyed.

Adverse Effects Associated With the Use of Antimalarials During The COVID-19 Pandemic in a Tertiary Care Center in Mexico City.

Background: Antimalarial drugs were widely used as experimental therapies against COVID-19 in the initial stages of the pandemic. Despite multiple randomized controlled trials demonstrating unfavorable outcomes in both efficacy and adverse effects, antimalarial drugs are still prescribed in developing countries, especially in those experiencing recurrent COVID-19 crises (India and Brazil). Therefore, real-life experience and pharmacovigilance studies describing the use and side effects of antimalarials for COVID-19 in developing countries are still relevant. Objective: To describe the adverse effects associated with the use of antimalarial drugs in hospitalized patients with COVID-19 pneumonia at a reference center in Mexico City. Methods: We integrated a retrospective cohort with all adult patients hospitalized for COVID-19 pneumonia from March 13th, 2020, to May 17th, 2020. We compared the baseline characteristics (demographic and clinical) and the adverse effects between the groups of patients treated with and without antimalarial drugs. The mortality analysis was performed in 491 patients who received optimal care and were not transferred to other institutions (210 from the antimalarial group and 281 from the other group). Results: We included 626 patients from whom 38% (n = 235) received an antimalarial drug. The mean age was 51.2 ± 13.6 years, and 64% were males. At baseline, compared with the group treated with antimalarials, the group that did not receive antimalarials had more dyspnea (82 vs. 73%, p = 0.017) and cyanosis (5.3 vs. 0.9%, p = 0.009), higher respiratory rate (median of 28 vs. 24 bpm, p < 0.001), and lower oxygen saturation (median of 83 vs. 87%, p < 0.001). In the group treated with antimalarials, 120 patients had two EKG evaluations, from whom 12% (n = 16) prolonged their QTc from baseline in more than 50 ms, and six developed a ventricular arrhythmia. Regarding the trajectories of the liver function tests over time, no significant differences were found for the change in the mean value per day between the two groups. Among patients who received optimal care, the mortality was 16% (33/210) in those treated with antimalarials and 15% (41/281) in those not receiving antimalarials (RR 1.08, 95% 0.75-1.64, and adjusted RR 1.12, 95% CI 0.69-1.82). Conclusion: The adverse events in patients with COVID-19 treated with antimalarials were similar to those who did not receive antimalarials at institutions with rigorous pharmacological surveillance. However, they do not improve survival in patients who receive optimal medical care.

[Factors associated with Clostridium difficile disease in a tertiary-care medical institution in Mexico: a case-control study]. / Factores asociados con el desarrollo de la enfermedad por Clostridium difficile en un hospital de tercer nivel en México: estudio de casos y controles.

INTRODUCTION: Clostridium difficile-associated disease (CDAD) has been clearly associated with the use of broad-spectrum antibiotics worldwide. However, information about CDAD is scarce in Mexico and Latin America. MATERIAL AND METHODS: We studied clinical characteristics, associated factors and outcomes of all cases of CDAD diagnosed by toxin A fecal detection in a tertiary care hospital in Mexico City from 2003 to 2007. Cases were paired with controls by date of hospital discharge. RESULTS. A total of 3170 tests were performed; we evaluated 113 cases and 226 controls, with an incidence of 5.04 cases x 1000 hospital discharges during the study period. There was no difference in gender or primary diagnosis. After multivariate analysis, we found as significant risks the following: use of H2 blockers (OR 21.73, 95% CI 7.14-66.67, p < 0.001), age < 65 y (OR 10.21, IC95% 2.74-38.00, p < 0.001), prior hospitalization within 12 weeks of diagnosis (OR 4.39, IC95% 1.81-40.64, p < 0.001), prior use of cephalosporins (OR 3.41, CI 95% 1.56-7.46, p = 0.002), and fluoroquinolones (OR 3.11, IC95% 1.12-8.62, p = 0.029), stay at the intensive care unit (ICU) (OR 2.76, IC95% 1.38-5.49, p = 0.004); and, extended hospital stay (OR 1.10, IC95% 1.05-1.16, p < 0.001) or antimicrobial use before diagnosis (OR 1.05, IC95% 1.01-1.09, p = 0.010). We described an outbreak of 12 cases occurred in August of 2005 (29.5 cases per 1,000 discharges). We also observed a higher seasonal incidence of disease during the summer in the study period. CONCLUSIONS: The use of H2 blockers, age < 65 years, prior hospitalization or earlier use of cephalosporins or fluoroquinolones, as well as stay at the ICU were independent risk factor for CDAD.

Potential Effect of Statins on Mycobacterium tuberculosis Infection.

Tuberculosis is one of the 10 leading causes of death in the world. The current treatment is based on a combination of antimicrobials administered for six months. It is essential to find therapeutic agents with which the treatment time can be shortened and strengthen the host immune response against Mycobacterium tuberculosis. M. tuberculosis needs cholesterol to infect and survive inside the host, but the progression of the infection depends to a large extent on the capacity of the immune response to contain the infection. Statins inhibit the synthesis of cholesterol and have pleiotropic effects on the immune system, which have been associated with better results in the treatment of several infectious diseases. Recently, it has been reported that cells treated with statins are more resistant to M. tuberculosis infection, and they have even been proposed as adjuvants in the treatment of M. tuberculosis infection. The aim of this review is to summarize the immunopathogenesis of tuberculosis and its mechanisms of evasion and to compile the available scientific information on the effect of statins in the treatment of tuberculosis.

Factors associated with an outbreak of hospital-onset, healthcare facility-associated Clostridium difficile infection (HO-HCFA CDI) in a Mexican tertiary care hospital: A case-control study.

OBJECTIVE: To identify clinical and environmental factors associated with an outbreak of hospital-onset, healthcare facility-associated Clostridium difficile infection (HO-HCFA CDI). DESIGN: Case-control study. SETTING: Public, acute care, academic tertiary referral center in Mexico. PATIENTS: Adults hospitalized ≥48 hours between January 2015 and December 2016 were included. Cases were patients with a first episode of HO-HCFA CDI. Controls were patients with any other diagnosis; they were randomly selected from the hospital discharge database and matched in a 1:2 manner according to the date of diagnosis of case ± 10 days. Variables with p<0.1 were considered for multivariable analysis. RESULTS: One hundred and fifty-five cases and 310 controls were included. Variables independently associated with HO-HCFA CDI were: exposure to both ciprofloxacin and proton pump inhibitor (PPI) within the last 3 months (OR = 8.07, 95% CI = 1.70-38.16), febrile neutropenia (OR = 4.61, 95% CI = 1.37-15.46), intraabdominal infection (OR = 2.06, 95% CI = 0.95-4.46), referral from other hospitals (OR = 1.99, 95% CI = 0.98-4.05) and an increasing number of antibiotics previously used (OR = 1.28, 95% CI = 1.13-1.46). CONCLUSIONS: Multiple factors were found to be associated with the first episode of HO-HCFA CDI in the setting of an outbreak; of the modifiable risk factors, prior exposure to both ciprofloxacin and PPI was the most important. Referral from other hospitals was an environmental risk factor that deserves further study.

[Fluoroquinolone prophylaxis utility during chemotherapy-induced severe neutropenia in patients with acute leukemia, with fluoroquinolone resistance high prevalence, in a reference hospital in Mexico City]. / Utilidad de la profilaxis con fluoroquinolonas durante la neutropenia grave inducida por quimioterapia en pacientes con leucemia aguda, en un hospital de referencia de la Ciudad de México con alta prevalencia de resistencia a fluoroquinolonas.

BACKGROUND: The use of fluoroquinolone prophylaxis in patients with cancer and neutropenia has failed to show a significant impact on mortality, despite its usefulness in reducing the incidence of gramnegative bacteremia. However, an increase in grampositive bacteremia and the emergence of resistant colonizing bacteria have consistently been noticed. OBJECTIVE: To determine the impact of prophylaxis with fluoroquinolones on the incidence of bacteremia and mortality in a hospital with high fluorquinolone resistance in Mexico City. PATIENTS: We conducted a retrospective and comparative study of patients with acute mieloid (AML) and hybrid (HL) leukemia who received or not prophylaxis with fluoroquinolones and who were attended from January 2000 to December 2003. We reviewed all pertinent clinical and laboratory data of the hematologic malignancies and the febrile episodes. RESULTS: A total of 108 febrile episodes of severe neutropenia occurred in 69 patients, with an incidence of 6.5 events/1000 day-patient with neutropenia. The median age was 35 +/- 18.3 years and 58% were men; 51 patients had AML (71.8%) and 20 (28.1%) HL. Prophylaxis had been given since the beginning of granulocytopenia in 46 (42.6%) febrile episodes (group 1), where as in 62 no prophylaxis was given (group 2). Of the 46 episodes with prophylaxis, 27 received ciprofloxacin 500 mg qd p.o. and 19, ciprofloxacin 500 mg qd po plus fluconazol 100 mg qd po. The median duration of prophylaxis was 8.5 days (range 1-90 days). Twenty-nine bacteremias (26.8%) were documented, with an incidence of 16.4 bacteremias/1000 day-patient with neutropenia, 12 (26%) in group 1 and 17 (27.5%) in group 2. Bacteremia was most frequently caused by gram negative organisms (18/29), being Escherichia coli (14) the most commonly isolated pathogen, with 7 episodes in each group. Eight (29.6%) of the 21 isolates in which fluoroquinolone susceptibility was tested were ciprofloxacin resistant, 3 in group 1 and 5 in group 2 (p = 0.58). Median survival of patients was 38 days in group 1 and 40 days in group 2. (p = 0.2); mortality was similar in both groups, 34% and 27%, respectively. CONCLUSIONS: In a hospital with a high prevalence of fluoroquinolone-resistance, prophylaxis in patients with acute leukemia and severe neutropenia did not prevent febrile episodes and did not have any impact on mortality. However, there was no increase in infections caused by resistant bacteria.

High prevalence of Chlamydia pneumoniae seropositivity in Mexican patients with ischemic heart disease.

BACKGROUND: Risk factors for development of atherosclerosis, such as hyperlipidemia, high blood pressure, smoking habit, and diabetes mellitus, have been identified. The possibility that infectious agents may unchain biological and biochemical reactions related to inflammation, atherogenesis, and vascular thromboses events have recently been described. Chlamydia pneumoniae has been associated with coronary artery disease in some seroepidemiology studies. Reports of this association are limited in the Latin American population; therefore, we conducted a case-control study to explore this issue in the Mexican population. METHODS: Eighty nine patients with scintigraphic evidence of coronary artery disease compared with a control group of 105 individuals were analyzed. Serum levels of IgA, IgM, and IgG against Chlamydia pneumoniae were determined using enzyme immunoassay method in all subjects. Conventional risk factors were also analyzed. RESULTS: High seroprevalence of IgA and IgG with no significant difference between the two groups was found. Prevalence of antibodies was as follows: IgA 56.2% (50/89 patients); IgG 66.3% (59/ 89 patients) in coronary artery disease group; IgA 56.2% (59/105 patients), and IgG 70.5% (74/105 patients) in control group. Among common risk factors for coronary artery disease, significant differences were found in males, in patients with diabetes, and in habitual smokers. CONCLUSIONS: These results suggest a high prevalence of C. pneumoniae infection in the studied population. However, in this series seroprevalence was not evidently associated with coronary artery disease (CAD). To clarify the possible relation between C. pneumoniae and coronary atherosclerosis, additional studies must be performed.

Prevalence of latent and active tuberculosis among dairy farm workers exposed to cattle infected by Mycobacterium bovis.

BACKGROUND: Human tuberculosis caused by M. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. The disease in humans is mainly attributed to unpasteurized dairy products consumption. However, transmission due to exposure of humans to infected animals has been also recognized. The prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (DFW) exposed in settings with poor control of bovine tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Tuberculin skin test (TST) and Interferon-gamma release assay (IGRA) were administered to 311 dairy farm and abattoir workers and their household contacts linked to a dairy production and livestock facility in Mexico. Sputa of individuals with respiratory symptoms and samples from routine cattle necropsies were cultured for M. bovis and resulting spoligotypes were compared. The overall prevalence of latent tuberculosis infection (LTBI) was 76.2% (95% CI, 71.4-80.9%) by TST and 58.5% (95% CI, 53.0-64.0%) by IGRA. Occupational exposure was associated to TST (OR 2.72; 95% CI, 1.31-5.64) and IGRA (OR 2.38; 95% CI, 1.31-4.30) adjusting for relevant variables. Two subjects were diagnosed with pulmonary tuberculosis, both caused by M. bovis. In one case, the spoligotype was identical to a strain isolated from bovines. CONCLUSIONS: We documented a high prevalence of latent and pulmonary TB among workers exposed to cattle infected with M. bovis, and increased risk among those occupationally exposed in non-ventilated spaces. Interspecies transmission is frequent and represents an occupational hazard in this setting.