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Objective: To determine the risk factors associated with therapeutic failure of vancomycin in hospitalized adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Design: Case-control study. Setting: Conducted in a high complexity hospital in Cali, Colombia. Participants: Adult hospitalized from January 1, 2015, to December 31, 2021, with MRSA infections with confirmed microbiological isolation. Methods: Cases were patients with therapeutic failure of vancomycin (mortality, poor clinical improvement, change of antibiotic used, early relapse, or persistence of positive blood cultures) and control patients were those who did not present failure. Significant variables from the bivariate analysis were included in a multiple analysis with an asymmetric logistic regression model. Results: A total of 105 patients were included in the study, 28 in the treatment group and 77 in the control group. The median age was 49 years and 59 (56%) of participants were men. The following variables: age (OR 1.034; 95% CI 1.007-1.061, p=0.011), osteomyelitis/ septic arthritis (OR 6.035; 95% CI 2.282-15.956, p=0.000) and minimum inhibitory concentration (MIC) (OR 5.971; 95% CI 1.321-26.979, p=0.020) were found to be independent risk factors associated with therapeutic failure of vancomycin. Vancomycin trough levels were not different between cases and controls (OR 0.976; 95% CI 0.911-1.044, p=0.478). Conclusions: When a multiple analysis was performed to control for confounding factors, only 3 variables were found to be significant and were considered risk factors for therapeutic failure of vancomycin in adult patients with MRSA infection: age, MIC, and osteomyelitis/ septic arthritis.

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BACKGROUND: Kawasaki disease is a systemic vasculitis that affects small and medium-sized vessels, primarily the coronary arteries. First-line treatment includes intravenous immunoglobulin (IVIG) and acetylsalicylic acid; however, 20% do not respond adequately despite treatment. We describe a case treated with etanercept after initial IVIG failure, showing a good response. CASE REPORT: A 5-year-old female was diagnosed with classic Kawasaki disease. Echocardiography and angiotomography revealed giant and fusiform aneurysms in the coronary arteries. A first dose of IVIG therapy was administered without improvement; after the second dose, the fever persisted, so etanercept was administered, and the fever subsided. There were no new lesions in medium-caliber vessels and the previously identified coronary lesions did not progress. CONCLUSIONS: The use of etanercept in Kawasaki disease has demonstrated a clinically favorable response. Controlled clinical trials of this drug are needed to establish it as a formal therapy in cases of initial IVIG failure.

INTRODUCCIÓN: La enfermedad de Kawasaki es una vasculitis sistémica que afecta los vasos de pequeño y mediano calibre con predominio de las arterias coronarias. El tratamiento de primera línea incluye inmunoglobulina intravenosa (IGIV) y ácido acetilsalicílico; a pesar del tratamiento, el 20% de los pacientes no responden adecuadamente. Se presenta un caso tratado con etanercept debido a la falla inicial a IGIV, con buena respuesta. CASO CLÍNICO: Se trata de una paciente de 5 años de edad, a quien se diagnosticó con enfermedad de Kawasaki clásica. En ecocardiografía y angiotomografía se evidenciaron aneurismas gigantes y fusiformes en las coronarias. Se administró una primera dosis con IGIV, sin mejoría; después de la segunda dosis, la paciente persistió con fiebre, por lo que se administró etanercept, tras lo cual esta cesó. No aparecieron nuevas lesiones en vasos de mediano calibre y las lesiones coronarias previas no progresaron. CONCLUSIONES: Con el uso de etanercept se presentó una respuesta favorable clínicamente en la enfermedad de Kawasaki. Se requieren ensayos clínicos controlados con este fármaco para establecerlo como terapia formal en los casos de falla inicial a IGIV.

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Patients with cutaneous leishmaniasis (CL) present an exacerbated inflammatory response associated with tissue damage and ulcer development. In recent years, higher rates of failure to pentavalent antimoniate therapy have been observed, yet the underlying reason remains poorly understood. We hypothesize that the eicosanoid PGE2 favours the establishment of infection by L. braziliensis, which contributes to therapeutic failure. The aim of the present study was to investigate the influence of PGE2 on the survival of L. braziliensis in macrophages and rates of therapeutic failure in CL patients. PGE2, an eicosanoid derived from the metabolism of arachidonic acid by the COX-2 enzyme, plays several roles in immune response. We found that increased PGE2 decreases the microbicidal function of macrophages and is associated with disease severity and therapeutic failure. Additionally, the neutralization of COX-2 by NS398, a selective NSAID, increases the ability of macrophages to kill L. braziliensis and protects against the pathological inflammatory response. Our data suggest that NS398 may serve as an adjunct treatment for CL patients.

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Abstract Background: Kawasaki disease is a systemic vasculitis that affects small and medium-sized vessels, primarily the coronary arteries. First-line treatment includes intravenous immunoglobulin (IVIG) and acetylsalicylic acid; however, 20% do not respond adequately despite treatment. We describe a case treated with etanercept after initial IVIG failure, showing a good response. Case report: A 5-year-old female was diagnosed with classic Kawasaki disease. Echocardiography and angiotomography revealed giant and fusiform aneurysms in the coronary arteries. A first dose of IVIG therapy was administered without improvement; after the second dose, the fever persisted, so etanercept was administered, and the fever subsided. There were no new lesions in medium-caliber vessels and the previously identified coronary lesions did not progress. Conclusions: The use of etanercept in Kawasaki disease has demonstrated a clinically favorable response. Controlled clinical trials of this drug are needed to establish it as a formal therapy in cases of initial IVIG failure.

Resumen Introducción: La enfermedad de Kawasaki es una vasculitis sistémica que afecta los vasos de pequeño y mediano calibre con predominio de las arterias coronarias. El tratamiento de primera línea incluye inmunoglobulina intravenosa (IGIV) y ácido acetilsalicílico; a pesar del tratamiento, el 20% de los pacientes no responden adecuadamente. Se presenta un caso tratado con etanercept debido a la falla inicial a IGIV, con buena respuesta. Caso clínico: Se trata de una paciente de 5 años de edad, a quien se diagnosticó con enfermedad de Kawasaki clásica. En ecocardiografía y angiotomografía se evidenciaron aneurismas gigantes y fusiformes en las coronarias. Se administró una primera dosis con IGIV, sin mejoría; después de la segunda dosis, la paciente persistió con fiebre, por lo que se administró etanercept, tras lo cual esta cesó. No aparecieron nuevas lesiones en vasos de mediano calibre y las lesiones coronarias previas no progresaron. Conclusiones: Con el uso de etanercept se presentó una respuesta favorable clínicamente en la enfermedad de Kawasaki. Se requieren ensayos clínicos controlados con este fármaco para establecerlo como terapia formal en los casos de falla inicial a IGIV.

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Background: Intra-abdominal infection (IAI) results in prolonged in-hospital length-of-stay, critical care unit requirements, and multiple surgical procedures. Several antimicrobial agents are available for treatment of IAI. In Colombia, there are no data on the comparative effectiveness of the different regimens used. Patients and Methods: A multicenter retrospective cohort study was completed in four third-level hospitals by comparing treatment effectiveness of five different antibiotic protocols (ampicillin-sulbactam, clindamycin-amikacin, piperacillin-tazobactam, amikacin-metronidazole, and cefuroxime-metronidazole) in patients with a diagnosis of IAI. Analysis was based on a composed outcome of therapeutic failure (change of antibiotic because of no clinical improvement, requirement of surgical re-intervention, post-operative infection, change of antibiotic because of antimicrobial resistance, and in-hospital mortality). Association of each antibiotic protocol to therapeutic failure was assessed through logistic regression analysis. Results: Five hundred ninety-three individuals were included. Two hundred twenty-nine were prescribed ampicillin-sulbactam; 170, clindamycin-amikacin; 77, amikacin-metronidazole; 83, piperacillin-tazobactam; and 34, cefuroxime-metronidazole. Therapeutic failure rate was 22%. Multivariable analysis showed none of the evaluated antibiotic protocols had an association with the primary outcome. Variables having an association for higher risk were age >70 years old (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.04-4.18); complicated IAI (OR, 3.36; 95% CI, 1.4-8.07); and World Society of Emergency Surgery (WSES) Sepsis Severity Score (OR, 1.31; 95% CI, 1.18-1.45). Adequate source control (OR, 0.16; 95% CI, 0.05-0.45) and hospitalization at Health Center 2 (OR, 0.30; 95% CI, 0.14-0.63) were identified as protective factors. Conclusions: There are no differences between the rate of therapeutic failure among the different antibiotic protocols evaluated. This outcome depends heavily on risk factors related to disease severity when surgical intervention occurs.

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The western Amazon basin is an important endemic area for malaria by P. vivax. In recent years, several reports showed the treatment failure with chloroquine, which can be related to resistance. The assessment of chloroquine resistance requires the evaluation of drug exposure, and when possible, the estimation of the pharmacokinetic parameters. However, there is no data on the pharmacokinetics of chloroquine in this endemic area. Moreover, the influence of the early reappearance of parasites in blood on the exposure to the drug was low exploited in the literature. The present study described the pharmacokinetic parameters of chloroquine in whole blood of adult patients with P. vivax malaria from the western Brazilian Amazon basin and compared the area under the curve (AUC) with the parasitological outcome at day 28. A total of 19 patients with parasite recurrence within 28 days and 20 patients with no recurrence were included in the study. Chloroquine was measured by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters were estimated by non-compartmental modeling. The maximum concentration ranged from 1285 to 2030 ng/mL. The terminal half-life varied from 5.3 to 12.8 days. The volume of distribution from 1090 to 2340 L/kg, and the area under the curve to the last measurable concentration from 247 to 432 ng/mL.h. The pharmacokinetic parameters were similar in both groups, which suggests the lack of influence of early reappearance of parasites on chloroquine pharmacokinetics.

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BACKGROUND: Psoriasis is a chronic disease that seriously impacts quality of life. There are known genetic and environmental factors that influence its onset and progression. Even though there is no cure for it, there are a variety of treatments available today to control its symptoms, although many of them fail to do so substantially. OBJECTIVE: To identify the association of multiple sociodemographic, clinical, and pharmacological factors with therapeutic failure. METHODS: Observational, descriptive, cross-sectional, retrospective, and analytical study of therapeutic failure in patients with moderate or severe psoriasis between 2020 and 2021 was performed. RESULTS: In total 1051 patients with moderate or severe psoriasis were evaluated. Gender (ORa: 0.579 CI 95%: 0.382-0.878), type of therapy (biologic or non-biologic; ORa: 1.939 CI 95%: 1.242-3.027), age (ORa: 1.018 CI 95%: 1.003-1.034), days of treatment (ORa: 1 CI 95%: 0.999-1) and DLQI (ORa: 1.212 CI 95%: 1.172-1.253) are significantly associated with therapeutic failure. CONCLUSION: Being male and receiving biologic therapy are associated with a higher incidence of therapeutic failure in the treatment of moderate or severe psoriasis. The increase in DLQI increase in the probability of failure, and mayor age or days of treatment decrease in the probability of failure.

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Abstract Background: Undernutrition is frequent among children living with HIV in developing countries. An interaction between malnutrition and HIV pediatric infection remains incompletely characterized in Colombia. Methodology: Retrospective longitudinal study, descriptive in nature, in 28 patients with a diagnosis of HIV infection, less than 18 years of age and receiving anti retroviral therapy. Variables were retrieved from clinical records at start of antiretroviral therapy and after 12 months. Statistical analysis was exploratory. Results: 4 out of 28 patients were stunted (14,3%; 95%CI: 1,3 - 27,2), 2 out of 7 patients were wasted (28,6%; 95%CI: 0 - 62), 5 out of 17 patients were underweight (27,8%; 95%CI: 7,1 - 48,5) and 4 out of 28 patients had thinness (29,6%; 95%CI: 12,4 - 46,8). No clinically relevant anthropometric change was detected during follow-up. Anemia prevalence was 52% and 82% of patients had some degree of dyslipidemia. Both viral load (p=0,001) and CD4 count (p=0,01), significantly increased and the proportion of patients with therapeutic failure remained invariable during follow-up. Conclusion: Malnutrition is frequent and its prevalence might have decreased. HIV program improved medical control of the disease, with stable therapeutic failure rates that were comparable with previous reports. Nonetheless, anemia and dyslipidemia remain to be a paramount therapeutic challenge.

Resumen Introducción: La desnutrición es frecuente en niños con VIH en países en desarrollo. En Colombia, la interacción entre la desnutrición y la infección pediátrica por VIH se encuentra insuficientemente caracterizada. Metodología: Estudio longitudinal retrospectivo de carácter descriptivo, en 28 pacientes con diagnóstico de infección por VIH, edad menor a 18 años y con terapia antirretroviral en curso. Se extrajeron variables mediante revisión de historias clínicas en el momento de inicio de la terapia antirretroviral y 12 meses después. El análisis estadístico fue exploratorio. Resultados: 4 de 28 pacientes sufrían retraso del crecimiento (14,3%; IC95%: 1,3 - 27,2), 2 de 7 pacientes sufrían emaciación (28,6%; IC95%: 0 - 62), 5 de 17 pacientes sufrían insuficiencia ponderal (27,8%; IC95%: 7,1 - 48,5) y 4 de 28 pacientes se encontraban en delgadez (29,6%; IC95%: 12,4 - 46,8). No hubo cambios antropométricos clínicamente relevantes con el seguimiento. La prevalencia de anemia fue del 52% y 82% de los pacientes tenían algún grado de dislipidemia. Tanto la carga viral (p=0,001) como el conteo de CD4 (p=0,01), mejoraron significativamente y la proporción de pacientes con fallo terapéutico no cambió durante el seguimiento. Conclusión: La desnutrición es frecuente y su prevalencia podría haber disminuido. El programa de VIH mejoró el control médico de la enfermedad, con tasas de fallo terapéutico estables y comparables con reportes previos. No obstante, la anemia y la dislipidemia continúan siendo un gran reto terapéutico.

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BACKGROUND: Ocular toxoplasmosis is an infection caused by Toxoplasma gondii. In South America, the clinical course of ocular toxoplasmosis is more severe than in Europe and North America because virulent strains of the parasite are present. Ocular toxoplasmosis is the leading cause of posterior uveitis and retinochoroiditis in Colombia, requiring timely and appropriate treatment. However, there is no standardized therapy protocol based on economic studies for the country. PURPOSE: To compare the cost-effectiveness of four first-line treatment regimens for active ocular toxoplasmosis in immunocompetent adults in Colombia, using the number of averted therapeutic failures as the outcome. METHODS: We performed an economic and cost-effectiveness analysis to compare four first-line treatment regimens for ocular toxoplasmosis from the perspective of a third-party payer (Colombian General System of Social Security in Health). A decision analysis tree was used over a 24-week time horizon, considering only direct costs. Additionally, we performed a discrete sensitivity analysis and a probabilistic sensitivity analysis with 10,000 iterations in the Monte Carlo simulation. RESULTS: For the base case, trimethoprim/sulfamethoxazole showed 86% effectiveness at a cost of <57 United States Dollars, resulting in the most cost-effective first-line alternative. When performing the probabilistic sensitivity analysis and maintaining the willingness to pay 466.00 United States Dollars, the trimethoprim/sulfamethoxazole regimen remained the most cost-effective alternative. CONCLUSION: Ocular toxoplasmosis is a public health issue in Latin America. Despite severe visual consequences for affected patients, there are no standardized treatment guidelines in countries such as Colombia. Our evidence supports the use of trimethoprim/sulfamethoxazole as first-line treatment in Colombia because of its availability and optimal cost-effectiveness performance; it reduces recurrences and complications, while averting therapeutic failure. Furthermore, our evidence can be generalized to other Latin American countries with similar frequencies and severities of Toxoplasma gondii ocular infection and health systems similar to the Colombian system.