Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

[Comparative analysis of clinical characteristics, evolution and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID Study)]. / Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (Registro ECCOVID).

INTRODUCTION: Clinical features and outcomes of SARSCoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. METHODS: Multicenter and prospective registry of patients =18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. RESULTS: A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized patients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hospitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hospitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. CONCLUSION: Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 during the second wave in Argentina were more seriously ill and had a higher mortality.

Introducción: Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos: Registro multicéntrico y prospectivo de pacientes = 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolución a 30 días. Resultados: Se incluyeron un total de 1691 pacientes (primera ola n = 809, segunda ola n = 882). Los pacientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospitalización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p < 0,001) y presentaron mayor mortalidad (11% vs. 26%, p < 0.001). Comparando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión: Comparados con los pacientes internados durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

[Clinical and epidemiological study of an outbreak of KPC-producing Klebsiella pneumoniae infection in Buenos Aires, Argentina]. / Descripción clínica y epidemiológica de un brote nosocomial por Klebsiella pneumoniae productora de KPC en Buenos Aires, Argentina.

INTRODUCTION: KPC-producing Klebsiella pneumoniae (Kpn-KPC) is an emerging pathogen, with a high capacity of nosocomial spread. The aim of this study was to describe the clinical and epidemiological characteristics of a nosocomial outbreak of Kpn-KPC in Buenos Aires, Argentina. METHODS: Prospective and descriptive study. We recorded clinical and epidemiological characteristics of patients with Kpn-KPC infection (august 2009 to july 2010). Antimicrobial susceptibility was performed by disk-diffusion antibiogram and an automated method (bioMerieux Vitek(®) 2C). Screening for K. pneumoniae carbapenemase (KPC) was performed with the 3-aminophenyl-boronic acid (APB) test inhibition and its presence was confirmed by PCR. Molecular typing of isolates was performed by pulsed field gel electrophoresis (PFGE). RESULTS: Twenty seven patients were infected by KPC producing K. pneumoniae (surgical care unit: n=8; medical care unit: n=6; intensive care unit [ICU]): n=5; emergency care unit: n=4; and other: n=4). All Kpn-KPC isolates belonged to a single clonal type (ST258). Site of infection: urinary tract (63%), respiratory tract (15%), intra-abdominal (15%), bloodstream (7%) and bone (4%). All Kpn-KPC isolates were only susceptible to tigecycline and colistin. Inappropriate empirical treatment: 63%. Specific treatment for Kpn-KPC infection: colistin (74%), tigecycline (4%) and tigecycline+colistin (22%).Global mortality: 59% (attributable mortality: 26%). Positive surveillance cultures (swabs): 7/70 (10%). CONCLUSIONS: We described the emergence of a nosocomial outbreak of Kpn-KPC in Buenos Aires, with a high capacity for dissemination and a high mortality rate. The implementation of infection control measures is essential to reduce the nosocomial spread of Kpn-KPC.

[Assessment of the humoral immunity induced by Sputnik V COVID-19 vaccine (Gam-COVID-Vac) in healthcare workers]. / Evaluación de la respuesta de los anticuerpos IGG específicos contra SARS-CoV-2 en el personal de salud con el esquema completo de la vacuna Sputnik V (Gam-COVID-Vac).

Background: Vaccination for COVID-19 in healthcare workers (HCW) is essential to protect one of the populations most exposed to this disease. However, data on the humoral response rate to the vaccine and the factors associated with it in this population are limited. Therefore, we aimed to evaluate the antibody response against SARS-CoV-2 in HCWs with complete Sputnik V vaccine scheme and factors associated with an increased antibody response. Material and methods: Prospective study to evaluate the anti-SARS-CoV-2 humoral response in HCWs vaccinated with two doses of the Sputnik V vaccine (April-July 2021). The assessment of anti-Spike IgG antibodies in plasma was performed using the COVIDAR IgG enzyme-linked immunosorbent assay. A logistic regression was performed to identify independent factors associated with a positive IgG serology test and an elevated antibody response. Results: A total of 630 HCWs were enrolled. Median age (IQR): 47 years (35-56). Female sex: 462 (73.33%). Previous COVID-19: 158 (25%). The median interval time between vaccine doses was 3 (3-4) weeks. Positive serology was observed in 607 (96.35%) HCWs. In the multivariate analysis, a history of systemic reactogenicity was identified as an independent variable associated with a positive serology; and history of systemic reactogenicity, COVID-19, interval between doses ≥ 4 weeks and time to serology < 14 weeks were associated with an elevated antibody response. Conclusions: This study provides data on the humoral response to the Sputnik V vaccine in a real-life setting. These initial data can contribute to the development of future immunization strategies in HCWs.

Molecular epidemiology of Mycobacterium tuberculosis, Buenos Aires, Argentina.

To analyze the molecular epidemiology of Mycobacterium tuberculosis strains at a hospital in Buenos Aires, Argentina, and mutations related to multidrug-resistant and extensively drug-resistant tuberculosis, we conducted a prospective case-control study. Our findings reinforce the value of incorporating already standardized molecular methods for rapidly detecting resistance.

Predicted susceptibility of etravirine in HIV patients experiencing virological failure secondary to non-nucleoside reverse transcriptase inhibitor resistance in Argentina.

INTRODUCTION: Virological response to etravirine (ETR) is dependent on the type and number of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs). METHODS: Data on NNRTI used in HAART at the time of failure and the number of NNRTI-RAMs were collected and retrospectively analyzed. ETR-RAMs were defined as V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S, and M230L, and were analyzed according to the weighted mutation score to predict susceptibility (Vingerhoets 2008). RESULTS: N=150. Efavirenz (EFV) containing regimen: 76.7%; nevirapine (NVP): 23.3%. Frequency of ETR-RAMs acquired after NNRTI failure: zero=38.7%, one=39.3%, two=17.3%, three=3.3%, four=1.3%. Most frequent ETR-RAMs after failure with EFV: G190A (28.1%), K101E (14.9%), L100I (10.5%); and with NVP: Y181C (41.7%), G190A (30.6%) and A98G (13.9%). Global predicted susceptibility of ETR: highest response: 69.3%, intermediate response: 24.7%, reduced response: 6%. Comparing maximal response with duration of virological failure: EFV-containing regimen: 94.4% (< 24-weeks) vs. 69.8% (>24-weeks) (p=0.02); NVP-containing regimen: 42.9% (< 24-weeks) vs. 56.5% (>24-weeks) (p=0.41). The presence of lamivudine regimen was associated with a better predicted susceptibility (highest response) to ETR (79% vs. 25%; P=.001). DISCUSSION: The majority of patients maintained susceptibility to ETR after the acquisition of NNRTI resistance. Failing with an EFV-containing regimen had a better predicted susceptibility to ETR than with NVP, especially after short-term virological failure.

Severe hyperkalaemia due to a potential drug-drug interaction between eplerenone and antiretrovirals in a HIV-positive patient after a myocardial infarction.

We present a case of a 48-year-old white HIV-1 positive man who presented an acute myocardial infarction. The patient was on ART for the last ten years with emtricitabine/tenofovir and ritonavir-boosted fosamprenavir. Eplerenone 25 mg/day was also initiated due to a left ventricular dysfunction. A week after discharge a routine laboratory examination revealed severe hyperkalaemia. Due to suspicion of a potential drug-drug interaction, both eplerenone and ARVs were interrupted. Despite daily treatment for hyperkalaemia, serum potassium levels normalized after two weeks. Eplerenone is metabolized by the hepatic P450 cytochrome isoenzyme CYP3A4; therefore, concomitant administration with CYP3A4 inhibitors, like ritonavir, may increase plasma levels of eplerenone and, therefore, the risk of side effects, mainly hyperkalaemia. Based on this case, it is important to alert the medical community of this possible life-threatening drug-drug interaction between eplerenone and ritonavir-boosted protease inhibitor.

Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study.

BACKGROUND: Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina. METHODS: Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). RESULTS: A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27). CONCLUSIONS: This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (REGISTRO ECCOVID) / Comparative analysis of clinical characteristics, evolu tion and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID STUDY)

Resumen Introducción : Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos : Registro multicéntrico y prospectivo de pacientes ≥ 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolu ción a 30 días. Resultados : Se incluyeron un total de 1691 pacien tes (primera ola n = 809, segunda ola n = 882). Los pa cientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospi talización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p <0,001) y presen taron mayor mortalidad (11% vs. 26%, p < 0.001). Compa rando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión : Comparados con los pacientes interna dos durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Abstract Introduction : Clinical features and outcomes of SARS-CoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. Methods : Multicenter and prospective registry of patients ≥18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. Results : A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized pa tients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hos pitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hos pitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. Conclusion : Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 dur ing the second wave in Argentina were more seriously ill and had a higher mortality.

Possible Drug-Herb Interaction between Herbal Supplement Containing Horsetail ( Equisetum arvense) and Antiretroviral Drugs.

The use of alternative medicines, including herbs, is common among HIV-positive patients, even in those on antiretroviral treatment. Equisetum arvense, known as "horsetail," is mainly used for its diuretic properties. There are limited data about the pharmacological properties of this compound and the potential drug-herb interactions. The authors report 2 cases in which a possible drug-herb interaction may have led to virological breakthrough in patients who were maintained on the same regimen for many years, including lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV) and emtricitabine (FTC)/tenofovir (TDF)/EFV, respectively. Therefore, a drug-herb interaction may be expected when these agents are taken concurrently. Until additional data are available, the authors advise clinicians to avoid this combination when possible.

Severe hypokalemia due to a possible drug-drug interaction between vinblastine and antiretrovirals in a HIV-infected patient with Hodgkin's lymphoma.

A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug--drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir. In the subsequent ABVD cycles, no neutropenia or hypokalemia were observed. Vinblastine is metabolized by the hepatic P450 cytochrome isoenzyme CYP3A4, therefore, concomitant administration with protease inhibitors may increase plasma levels of vinblastine. Vinblastine is also a substrate and inhibitor of multidrug resistance-associated protein 2 (MRP2) transporter in the proximal renal tubule. Inhibition of this renal transporter could increase tenofovir renal toxicity. Our hypothesis is that the hypokalemia could be a result of a tenofovir-mediated tubular damage triggered by the increased vinblastine serum levels secondary to a CYP3A4 inhibition by ritonavir. To the best of our knowledge, this is the first report of severe hypokalemia and proximal tubular renal dysfunction as a result of a possible drug-drug interaction between vinblastine, tenofovir and ritonavir-boosted atazanavir.

Impacto del aislamiento por la pandemia de COVID-19 en la realización de pruebas rápidas de VIH en un hospital general de agudos de CABA / Impact of isolation measures due to the COVID-19 pandemic on rapid HIV tests in an Acute General Hospital in Buenos Aires City

Introducción: La infección por VIH continúa siendo un problema de salud pública a nivel mundial. Las restricciones tomadas durante la pandemia por COVID-19 podrían afectar el alcance de las metas 95-95-95 propuestas por ONUSIDA. El objetivo de este trabajo fue determinar el impacto de la pandemia por COVID-19 en la realización de pruebas rápidas de VIH en un hospital general de agudos.Métodos: Análisis retrospectivo de los datos de pacientes mayores de 16 años, de ambos sexos, que se realizaron una prueba rápida de VIH durante la pandemia por COVID-19 vs. el período previo.Resultados: De 611 tests, 473 (77,4%) corresponden al período prepandémico y 138 (22,6%) al pandémico. La mediana de edad (rango intercuartílico) fue 32 años (24-40); sexo masculino 386 (63,2%), sin diferencias significativas. Durante el período prepandémico los motivos de testeo fueron control de salud 47,6% (n=225) y situaciones de riesgo/síntomas 52,4% (n=248), mientras que en el período pandémico fueron control de salud 27,5% (n=38) y situaciones de riesgo/síntomas 72,5% (n=100) respectivamente, p=0.0001. Tests positivos: 5,7% (n=27) vs. 8,7% (n=12), p=0.28. Las medianas de recuento de linfocitos T CD4+ y carga viral fueron: 327 cel/uL (135-718) y 66300 copias/mL (5260-192000), sin diferencias significativas.Conclusiones: La cantidad de testeos realizados durante la pandemia corresponde a un tercio de los realizados durante el período previo, con un descenso en aquellos motivados por controles de salud, evidenciando el impacto de la pandemia en el diagnóstico de VIH

INTRODUCTION: HIV infection remains as a public health worldwide problem. The restrictions taken during the COVID-19 pandemic could have affected the scope of the 95-95-95 goals proposed by UNAIDS. The aim of this work is to determine the impact of the COVID-19 pandemic on the performance of rapid HIV tests in an Acute General Hospital.METHODS: Retrospective analysis of data from patients over 16 years old, of both sexes, who underwent a rapid HIV test during the COVID-19 pandemic vs. the previous period.RESULTS: Of 611 tests, 473 (77.4%) correspond to the pre-pandemic period and 138 (22.6%) to the pandemic. The median age (interquartile range) was 32 years old (24-40); male sex 386 (63.2%), without significant differences. During the pre-pandemic vs pandemic period, the reasons for testing were: health control 47.6% (n=225) and risk situations/symptoms 52.4% (n=248), vs 27.5% (n= 38) and 72.5% (n=100) respectively, p=0.0001. Positive tests: 5.7% (n=27) vs 8.7% (n=12), p=0.28. The median CD4+ T lymphocyte count and viral load were: 327 cells/uL (135-718) and 66,300 copies/mL (5,260-192,000), with no significant differences.CONCLUSIONS: The number of tests carried out during the pandemic equals to a third of those performed during the previous period, with a decrease in those motivated by health controls; evidencing the impact of the pandemic on the diagnosis of HIV

[Prevalence of potential drug-drug interactions involving antiretroviral drugs in Buenos Aires, Argentina]. / Prevalencia de interacciones medicamentosas con fármacos anti-retrovirales en Buenos Aires, Argentina.

INTRODUCTION: Antiretroviral agents (ARVs) have a high potential for drug interactions. However, the prevalence and risk factors for clinically significant drug-drug interactions (CSDDIs) with ARVs from Latin American countries is unknown. AIM: To evaluate the prevalence and risk factors for CSDDIs in HIV outpatients attending at two centers in Buenos Aires, Argentina. METHODS: Descriptive cross-sectional study (september to november 2012). HIV-1 infected patients under ARV treatment at the time of the study were randomly assessed for concomitant medication. CSDDIs were screened using the University of Liverpool Drug Interactions Program (www.hiv-druginteractions.org). RESULTS: A total of 217 patients were included. Male sex: 64% (CI 95: 57-70). Median age (IQR): 41 (36-48). Presence of comorbidities: 19%. ARV regimen: NNRTI-based: 48%, PI-based: 50% and NNRTI plus PI: 2%. Median of CD4 T-cell count (IQR): 402 cells/mL (235-588). Viral load < 50 copies/mL: 78%. Overall, 64% (CI 95: 57-70) of patients had > 1 co-medication of whom a 49% had at least one CSDDI. Two patients had a CSDDI between ARVs. The most frequent co-medications observed were antimicrobial (40%), cardiovascular (25%) and gastrointestinal agents (22%). In the multivariate analysis the number of co-medications and use of CNS agents were associated with the presence of CSDDIs. CONCLUSIONS: Co-medications and CSDDIs were common in our setting. In this context, training of HIV physicians in drug interactions is of major importance for adequate management of these patients.

Potential drug-drug interactions in HIV-perinatally infected adolescents on antiretroviral therapy in Buenos Aires, Argentina.

INTRODUCTION: An increasing number of treatment-experienced perinatally HIV-infected adolescents (PHA) are being transitioned from paediatric centres to adult HIV-care [1]. Most of them had been heavily exposed to antiretroviral drugs (ARVs), harbour drug-resistant viruses and require non-antiretroviral medication due to comorbidities [2]. This may predispose for clinically significant drug-drug interactions (CSDDIs) [3]. There are no studies concerning CSDDIs in PHA. We aimed to evaluate the prevalence of concomitant medications and CSDDIs in PHA who were transitioned for adult HIV-care to the Infectious Diseases Unit, Cosme Argerich Hospital, Buenos Aires City, Argentina. MATERIALS AND METHODS: Descriptive pilot cross-sectional study (March to June 2014). PHA under ARVs at the time of the study were assessed for concomitant medication. CSDDIs were screened and categorized using the University of Liverpool Drug Interactions Program (www.hiv-druginteractions.org) [4]. RESULTS: Forty-five patients were included. Female sex: 53%. Median (IQR) age: 20 years (18-22). CDC-stage C was observed in 27 (79%); 50% had ≥1 comorbidities including 3 with HCV co-infection. Drug abuse was observed in 6 (13%). The median of prior ARV regimens was 3 (3-5). Current ARV regimen included: PI: 87%, NNRTI: 27%, INSTI: 20%, enfuvirtide: 7% and CCR5 inhibitor: 4%. Median CD4 T-cell count: 568 cells/mL (279-771). Viral load <50 copies/mL: 80%. Sixty percent (27/45) had ≥1 co-medications (median 1). The most frequent co-medications were NSAIDs (40%), hormonal therapy (19%) and antimicrobials (19%). Use of herbal supplements was observed in 10 (22%). Overall, 23 (51%) had ≥ 1 CSDDIs: 19/27 (70%) with co-medication (orange flag=18 and red flag=1); and 2/10 (20%) with herbal supplements. ARV-ARV interactions were observed in 4/45 (9%): unboosted atazanavir+tenofovir (n=2), unboosted atazanavir+efavirenz (n=1) and lopinavir/ritonavir+efavirenz (n=1) (all orange flag). Considering patients with CSDDIs, 6 (26%) had a CSDDI that could reduce ARV levels. CONCLUSIONS: In this pilot study, a high prevalence of comorbidities, co-medications and CSDDIs was observed in PHA. A considerable proportion of patients had CSDDIs with a potential to cause sub-therapeutic ARV levels, what could be a concern in patients harbouring drug-resistance viruses. Therefore, clinicians should be aware of comorbid conditions pharmacologic management in order to avoid CSDDIs with ARVs agents.

La era de los microorganismos multirresistentes: impacto en pacientes neutropénicos febriles / he era of multidrug-resistant microorganisms: impact on febrile neutropenic patients

Introducción: El tratamiento antimicrobiano para los pacientes neutropénicos febriles (NF) se ha convertido en un desafío debido a la emergencia de microorganismos multirresistentes (MOR). El objetivo de este trabajo es analizar las características de estos pacientes y la incidencia de MOR. Materiales y métodos: Estudio retrospectivo, observacional y descriptivo desde junio de 2015 hasta agosto de 2017 en adultos neutropénicos febriles hospitalizados en un hospital público de la ciudad de Buenos Aires. Se analizaron características demográficas, clínicas y microbiológicas, incluyendo los siguientes MOR: enterobacterias productoras de carbapenemasas (EPC) y beta-lactamasas de espectro extendido (BLEE), Acinetobacter baumannii complex, Enterococcus vancomicina resistente (EVR) y Stenotrophomonas maltophilia. Resultados: Fueron incluidos 32 pacientes, 56% mujeres con 84% de neoplasias hematológicas. Hubo colonización por EPC o EVR en el 59% de los pacientes. Se registraron 148 episodios infecciosos con 41% de documentación microbiológica. Los MOR fueron responsables del 25% de los episodios, siendo los más frecuentes Klebsiella pneumoniae productora de carbapenemasa y BLEE; los focos más frecuentes fueron bacteriemias e infecciones urinarias. Los pacientes con leucemias agudas (67%) presentaron colonización por EPC o EVR en el 80%. El tratamiento fue inadecuado en el 63% de las infecciones RESUMENARTÍCULO ORIGINALpor MOR y en el 12% por microorganismos sensibles (MS) (p<0,01). La mortalidad global fue 53% con MOR y del 27% con MS (p=ns). Conclusión: las infecciones por MOR fueron frecuentes con predominio de bacteriemias, especialmente EPC y BLEE. Por ello los MOR deben ser tenidos en cuenta para el tratamiento empírico en pacientes neutropénicos febriles

Background: Antimicrobial treatment for febrile neutropenic (FN) patients has become a challenge due to the growing emergence of multidrug-resistant microorganisms (MDR-MO). The objective of this study was to analyze the characteristics of these population and the incidence of MDR-MO. Methods & Materials: Retrospective, observational and descriptive study from June 2015 to August 2017 in FN adults hospitalized at a public hospital in Buenos Aires city, Argentina. Demographic, clinical and microbiological characteristics were analyzed. We included the following MDR-MO: extended spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae (CPE), Acinetobacter baumannii complex, vancomycin resistant Enterococcus (VRE) and Stenotrophomonas maltophilia. Results: Thirty-two patients were included; 56% were women, with 84% haematological diseases. Colonization by CPE or VRE was observed in a 59% of the patients. There were 148 infectious episodes. Of them 41% had microbiological documentation. MDR-MO were responsible for 25% of the episodes and the most frequent were carbapenemase-producing Klebsiella pneumoniae and ESBL producing Enterobacteriaceae. MDR-MO were isolated mainly from bacteremia and urinary infections, patients had acute leukemia in a 67% and colonization CPKP or VRE in 80%. Inadequate treatment for MDR-MO was observed in 63% of the cases and 12% for susceptible microorganisms (p<0,01). The mortality was 53% for MDR-MO and 27% for susceptible microorganisms (p=ns). Conclusion: MDR-MO infections were frequent with predominance of bacteremia especially CPE and ESBL producing Enterobacteriaceae. According to these results MDR-MO should be taken into account for the empiric antimicrobial treatment in febrile neutropenic patients

Evaluación infectológica inicial y seguimiento prospectivo de una cohorte de pacientes sometidos a inmunosupresión inducida / Initial assessment and prospective follow-up of a cohort of patients with immunosuppressive therapy by an infectious diseases physician

El uso de inmunosupresores generó una población creciente de pacientes con defectos en el sistema inmune. Creamos un consultorio especializado en la atención infectológica de dichos pacientes. Objetivos: Describir los antecedentes clínicos y la prevalencia de infecciones latentes, evaluar el estado de vacunación, determinar la necesidad de profilaxis antimicrobiana. Describir la frecuencia de aparición infecciones oportunistas (IO). Materiales y métodos: estudio descriptivo, prospectivo de pacientes atendidos en un consultorio que estuvieran bajo tratamiento inmunosupresor (noviembre 2015-enero 2017). Se recolectaron datos demográficos, clínicos y factores de riesgo para IO. Se realizó pesquisa de tuberculosis (TB), serologías para HIV, hepatitis A, B y C, sífilis, toxoplasmosis, Chagas, búsqueda de Strongyloides spp. Se indicaron vacunas de acuerdo con las recomendaciones actuales. Se realizó seguimiento para detección de IO. Resultados: n=197, media de edad 50,7 años (DE 14), mujeres 79,7%. Enfermedades de base: artritis reumatoidea 52%, lupus 12%. Drogas inmunosupresoras: metotrexato 45%, corticoides 16%, biológicos anti-TNF 15%, micofenolato 10%, ciclofosfamida 4%. Se diagnosticaron 49 (25%) infecciones: 15 Chagas, 15 anti-HBc positivo aislado, 7 sífilis, 4 HIV, 4 TB latentes, 2 HBV, 1 HCV, 1 estrongiloidiosis. Se indicó profilaxis antimicrobiana en 27 (14%) pacientes. En todos se intervino indicando o completando los esquemas de vacunación. Se detectaron 7 IO. Conclusiones: En el 39% de los pacientes, la evaluación sistematizada arrojó hallazgos que motivaron intervenciones, ya sea terapéuticas o de monitoreo. En el 100% fue necesaria la prescripción de vacunas. Esto pone en evidencia la importancia de evaluar sistemáticamente en consultorios especializados a estos pacientes

Introduction: The extensive use of immunosuppressive drugs resulted in a growing population of patients with defects in the immune system. We opened an infectious diseases practice focused on the attention of these patients. Our objectives were to describe the clinical history and prevalence of latent infections, evaluate the vaccination status, determine the need for antimicrobial prophylaxis and describe the frequency of opportunistic infections (OI). Methods: We performed a descriptive and prospective study of patients seen at a medical practice who were under immunosuppressive therapy (November 2015-January 2017). Demographic and clinical history, as well as risk factors for OI were collected. Tuberculosis (TB) screening, serologies for HIV, hepatitis A, B and C, syphilis, toxoplasmosis, Chagas and Strongyloides spp. screening were performed. Vaccines were indicated according to current recommendations. Follow-up was performed for IO detection. Results: n=197. Mean age: 50.7 years (SD 14). Female 79.7%. Underlying diseases: rheumatoid arthritis 52%, 12% lupus. Immunosuppressive drugs: methotrexate 45%, corticoids 16%, biological anti-TNF agents 15%, mycophenolate 10%, cyclophosphamide 4%. Forty-nine (25%) infections were diagnosed: 15 Chagas, 15 anti-HBc positive isolated, 7 syphilis, 4 HIV, 4 latent TB, 2 HBV, 1 HCV, 1 strongyloidiosis. Antimicrobial prophylaxis was indicated in 27 (14%) patients. In all cases, vaccination schemes were indicated or completed. Seven IO were detected. Conclusions: In 39% of the patients, the systematized evaluation revealed findings that motivated interventions, either therapeutic or monitoring. In 100% the prescription of vaccines was necessary. These findings highlight the importance of a systematically evaluation of these patients in specialized care centers.

Prevalencia de interacciones medicamentosas con fármacos anti-retrovirales en Buenos Aires, Argentina / Prevalence of potential drug-drug interactions involving antiretroviral drugs in Buenos Aires, Argentina

Introduction: Antiretroviral agents (ARVs) have a high potential for drug interactions. However, the prevalence and risk factors for clinically significant drug-drug interactions (CSDDIs) with ARVs from Latin American countries is unknown. Aim: To evaluate the prevalence and risk factors for CSDDIs in HIV outpatients attending at two centers in Buenos Aires, Argentina. Methods: Descriptive cross-sectional study (september to november 2012). HIV-1 infected patients under ARV treatment at the time of the study were randomly assessed for concomitant medication. CSDDIs were screened using the University of Liverpool Drug Interactions Program (www.hiv-druginteractions.org). Results: A total of 217 patients were included. Male sex: 64% (CI 95: 57-70). Median age (IQR): 41 (36-48). Presence of comorbidities: 19%. ARV regimen: NNRTI-based: 48%, PI-based: 50% and NNRTI plus PI: 2%. Median of CD4 T-cell count (IQR): 402 cells/mL (235-588). Viral load < 50 copies/mL: 78%. Overall, 64% (CI 95: 57-70) of patients had > 1 co-medication of whom a 49% had at least one CSDDI. Two patients had a CSDDI between ARVs. The most frequent co-medications observed were antimicrobial (40%), cardiovascular (25%) and gastrointestinal agents (22%). In the multivariate analysis the number of co-medications and use of CNS agents were associated with the presence of CSDDIs. Conclusions: Co-medications and CSDDIs were common in our setting. In this context, training of HIV physicians in drug interactions is of major importance for adequate management of these patients.

Introducción: Los fármacos anti-retrovirales (ARVs) tienen un alto potencial de interaccionar farmacológicamente con otros medicamentos. Sin embargo, los datos sobre la prevalencia y los factores de riesgo para la presencia de interacciones medicamentosas clínicamente significativas (IMCS) con ARVs en países latinoamericanos son limitados. Objetivo: Evaluar la prevalencia y los factores de riesgo para estas IMCS en dos centros de atención ambulatoria en Buenos Aires, Argentina. Métodos: Estudio transversal y descriptivo (septiembre-noviembre de 2012). Se evaluó la presencia de medicación concomitante en pacientes infectados por VIH bajo tratamiento ARV. Para evaluar la presencia de IMCS se utilizó la base de datos de interacciones de la Universidad de Liverpool (www.hiv-druginteractions.org). Resultados: Se incluyeron 217 pacientes. Sexo masculino: 64% (IC 95: 57-70). Mediana de edad (IQR): 41 (36-48). Presencia de co-morbilidades: 19%. Tratamiento ARV basado en INNTI: 48%, basado en IP: 50% y basado en INNTI más IP: 2%. Mediana de linfocitos T-CD4 (IQR): 402 céls/ml (235-588). Carga viral < 50 copias/ml: 78%. El 64% (IC 95: 57-70) de los pacientes tenían > 1 medicación concomitante: antimicrobianos (40%), fármacos cardiovasculares (25%) y gastrointestinales (22%). De los pacientes que presentaban medicación concomitante 68 (49%) tenían > 1 IMCS y sólo tres (2%) presentaban una asociación contraindicada. Además, dos pacientes tenían una IMCS entre ARVs. En el análisis multivariado, el número de medicamentos concomitantes y el uso psicofármacos se asociaron con una mayor chance de presentar IMCS. Conclusiones: La presencia de medicación concomitante e IMCS fue común en nuestra población. En este contexto, la formación de profesionales de la salud en la detección de interacciones medicamentosas es de suma importancia para un manejo adecuado de pacientes con infección por VIH que reciban tratamiento ARV.

Neurological manifestations of Chagas' disease.

OBJECTIVES: To review the neurological manifestations of Chagas' disease, including its clinical presentation, diagnosis, management, treatment and follow-up. METHODS: A systematic review of the literature found in MEDLINE, EMBASE, LILACS and SCIELO was performed to search for relevant references on Chagas' disease and neurological manifestations. RESULTS: The involvement of the nervous system in Chagas' disease is well established. The acute phase is described as a meningoencephalitis that more frequently affects children under 2 years old and is almost always fatal in those with coexistent myocarditis and cardiac insufficiency. In the chronic phase, it presents as neuritis that results in altered tendon reflexes and sensory impairment, and is reported in up to 10% of the patients. Isolated cases of central nervous system involvement can also include dementia, confusion, chronic encephalopathy and sensitive and motor deficits. Concurrent immunosuppression, such as that related to human immunodeficiency virus and organ transplantation, can result in the reactivation of the Trypanosoma cruzi infection. In these patients meningoencephalitis and brain abscesses may occur with a high mortality rate despite specific treatment. DISCUSSION: Although neurological involvement is infrequent, it has a high mortality and morbidity rate when is not well diagnosed and treated on time.