IMPORTANCE Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. OBJECTIVE To determine whether ivermectin is an efficacious treatment for mild COVID-19. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. INTERVENTION Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). MAIN OUTCOMES AND MEASURES Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. RESULTS Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). CONCLUSION AND RELEVANCE Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout Latin America, a region swept by multiple previous and ongoing epidemics. There are significant concerns that the arrival of COVID-19 is currently overlapping with other viruses,
Community-acquired pneumonia (CAP) in adults is probably one of the infections affecting ambulatory patients for which the highest diversity of guidelines has been written worldwide. Most of them agree in that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of comorbidities and the etiologic pathogen. Nevertheless, a great variability may be noted among the different countries in the selection of the primary choice in the antimicrobial agents, even for the cases considered as at a low-risk class. This fact may be due to the many microbial causes of CAP and specialties involved, as well as the different health-care systems effecting on the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations regardless of the local data, probably because of the scarcity of such data. This is the reason why we have developed a guideline for the initial treatment of CAP by 2002 upon the basis of several local evidences in South America (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity Index (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the region, such as community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and Legionella spp; new evidences on the performance of the rapid test for the etiologic diagnosis in CAP have been reported (eg. urinary Legionella and pneumococcus antigens); new therapeutic considerations needs to be approached (i.e. dosage reformulation, duration of treatment, emergence of novel antibiotics and clinical impact of combined therapy). Like in the fi rst version of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II.
CTX-M-15-producing Escherichia coli has emerged worldwide as an important pathogen associated with community-onset infections, but in South America reports are scarce. We document the presence of CTX-M-15-producing E. coli of the international ST131 and ST405 clones in Colombia and present the first molecular characterization of these isolates in South America.Since the end of the 1990s, a new family of extended-spectrum -lactamases (ESBL), the CTX-M type, has spread among continents, becoming the most prevalent in the world (1). Within this family, Escherichia coli strains producing CTX-M-15 have emerged as an important causative agent of community-onset infections (COI), predominantly urinary tract infections (UTI) (1). Moreover, the successful dispersion of CTX-M-15 has been associated with specific clones, such as ST131 and ST405, which belong to virulent phylogenetic groups B2 and D, respectively (4, 14). Other genes normally present on the same plasmid carrying bla CTX-M-15 , like bla TEM and bla OXA , as well as aac-(6Ј)-Ib-cr and qnr determinants, explain the multiresistant phenotype of CTX-M-15-producing bacteria (6,14).In South America, CTX-M-2, CTX-M-9, and CTX-M-12 have been reported previously among Enterobacteriaceae (15). However, reports of CTX-M-15-producing Enterobacteriaceae remain scarce in this region, and only recently a single report from Brazil of the clone ST131 was presented in an abstract lacking clinical data or further molecular characterization (9).In this study, we present the first molecular characterization of CTX-M-15-producing Escherichia coli isolates belonging to the clones ST131 and ST405 associated with COI in Colombia and South America, describing demographic and clinical data of patients from which these isolates were cultured.(Part of this work was presented at the 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy [ICAAC], Boston, MA, 12 to 15 September 2010).From January 2010 to May 2010, ESBL-positive E. coli isolates were sent from three Colombian hospitals to our reference laboratory at CIDEIM in Cali, Colombia. All isolates were obtained from patients who presented to the emergency room with community-onset infections, defined by the patient's having no history of being in a hospital, long-term-care facility, or nursing home, receiving home care, or having an invasive procedure done in the last 3 months. Bacterial identification was confirmed using the Vitek 2 automatic system (bioMérieux, Marcy l'Etoile, France). Detection of bla TEM , bla SHV , bla CTX-M , and -lactamase genes was performed by PCR, and all isolates in which cluster 1 bla CTX-M was detected were sequenced.CTX-M-15-producing E. coli isolates were further characterized. Susceptibility testing was performed using the broth microdilution method (Sensititre panels; TREK Diagnostic Systems, Westlake, OH), and the results were interpreted according to the CLSI breakpoints (3). Multiplex PCR for qnr determinants (qnrA, qnrB, qnrS) was carried out as previously described (13). ...
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