ABSTRACT Background: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in Western countries. Risk factors, mortality, and healthcare utilization for CDI in Latin America are poorly understood. This study assessed risk factors and burden associated with nosocomial CDI in four Latin American countries. Methods: This retrospective, case-control study used databases and medical records from 8 hospitals in Argentina, Brazil, Chile, and Mexico to identify nosocomial CDI cases from 2014 − 2017. Cases were patients aged ≥18 years with diarrhea and a positive CDI test ≥72 h after hospital admission. Two controls (without diarrhea; length of hospital stay [LOS] ≥3 days; admitted ±14 days from case patient; shared same ward) were matched to each case. CDI-associated risk factors were assessed by univariate and multivariable analyses. CDI burden (LOS, in-hospital mortality) was compared between cases and controls. Results: The study included 481 cases and 962 controls. Mean age and sex were similar between cases and controls, but mean Charlson comorbidity index (4.3 vs 3.6; p< 0.001) and recent hospital admission (35.3% vs 18.8%; p< 0.001) were higher among cases. By multivariable analyses, CDI risk was associated with prior hospital admission within 3 months (odds ratio [OR], 2.08; 95% CI: 1.45, 2.97), recent antibiotic use (ie, carbapenem; OR, 2.85; 95% CI: 1.75, 4.64), acid suppressive therapy use (OR, 1.71; 95% CI: 1.14, 2.58), and medical conditions (ie, renal disease; OR, 1.48; 95% CI: 1.19, 1.85). In-hospital mortality rate (18.7% vs 6.9%; p< 0.001) and mean overall LOS (33.5 vs 18.8 days; p< 0.001) were higher and longer, respectively, in cases versus controls. Conclusion: Antibiotic exposure, preexisting medical conditions, and recent hospital admission were major risk factors for CDI in Argentina, Brazil, Chile, and Mexico. CDI was associated with increased in-hospital risk of death and longer LOS. These findings are consistent with published literature in Western countries.

The intensive care units (ICUs) are often considered as the epicenters of antibiotic resistance. Therefore, the total antibiotic consumption is approximately ten fold greater in ICU wards than in general hospital wards. The aim of this study was to evaluate the current use of antibiotics in Latin American ICUs. Three cross-sectional (one-day point) prevalence studies were undertaken in 43 Latin American ICUs. Of 1644 patients admitted, 688 received antibiotic treatment on the days of the study (41.8 %) and, 392 cases (57 %) were due to nosocomial-acquired infections. Of all infections, 22 % (151/688) corresponded to septic shock; and 22 % (151/688) to nosocomial pneumonia (50/151 [33 %], ventilator-associated pneumonia). In 485 patients (70.5 %), cultures were performed before starting antibiotic treatment. The most common microorganisms isolated were extended-spectrum ß-lactamase Enterobacteriaceae, (30.5 %), and Pseudomonas aeruginosa (17 %). Carbapenems (imipenem or meropenem) were the antibiotics most frequently prescribed (151/688, 22 %), followed by vancomycin (103/688, 15 %), piperacillin-tazobactam (86/688, 12.5 %) and broad-spectrum cephalosporins (mainly cefepime) (83/688, 12 %). In summary, carbapenems were the most frequent antibiotics prescribed in Latin American ICUs. This practice seems justified for the high rates of ESBL-producing Gram-negatives found in our patients. Beyond this reason, the problem of bacterial resistance in LA requires that physicians improve the use of carbapenems. The high prevalence of carbapenem-resistant A. baumannii and P. aeruginosa in the region, along with the prevalence of carbapenem-resistant Enterobacteriaceae, have increased markedly. A comprehensive evidence-based stewardship program based on local antimicrobial use and resistance problems should be implemented in our clinical settings.

Prescripción de antibióticos en unidades de cuidados intensivos de Latinoamérica. Las unidades de cuidados intensivos (UCI) son a menudo consideradas el epicentro de la resistencia a los antibióticos. En este sentido, el consumo total de antibióticos es aproximadamente diez veces mayor en las UCI que en las salas de internación general. El objetivo de este estudio fue evaluar el hábito prescriptivo de antibióticos en las UCI de varios países de Latinoamérica. A tal fin, se realizó un estudio transversal con tres evaluaciones puntuales de un día de duración cada una, para determinar la prevalencia del uso de antibióticos en las 43 UCI ubicadas en distintos países del continente americano. De los 1644 pacientes admitidos, 688 estaban recibiendo tratamiento antibiótico en los días en que se realizó el relevamiento (41,8 %), en 392 casos (57 %), debido a infecciones nosocomiales. De todas las infecciones, 22 % (151/688) correspondieron a shock séptico y 22 % (151/688) a neumonía nosocomial (de estas últimas, el 33 % [50/151] fueron neumonías asociadas a ventilación mecánica). En 485 pacientes (70,5 %) se obtuvieron cultivos antes del inicio del tratamiento antibiótico. Entre los aislamientos, los microorganismos más comúnmente aislados fueron las enterobacterias productoras de ß-lactamasas de espectro extendido (BLEE) (30,5 %) y Pseudomonas aeruginosa (17 %). Los carbapenems (imipenem o meropenem) fueron los antibióticos prescriptos con mayor frecuencia (151/688, 22 %), seguidos por la vancomicina (103/688, 15 %), la piperacilina-tazobactama (86/688, 12,5 %) y las cefalosporinas de amplio espectro (principalmente cefepima) (83/688, 12 %). En conclusión, los carbapenems fueron los antibióticos más frecuentemente prescriptos en las UCI de los países latinoamericanos evaluados. Esta práctica podría estar justificada por las altas tasas de enterobacterias productoras de BLEE halladas en los pacientes de esas regiones. Más allá de esta razón, el problema de la resistencia bacteriana en muchos países del continente requiere que los médicos optimicen el uso de los carbapenems, ya que la prevalencia de aislamientos resistentes a este grupo de antimicrobianos se ha incrementado marcadamente, tanto en A. baumannii y P. aeruginosa como en enterobacterias. Frente a este panorama, en todos estos países se torna necesario implementar programas de optimización del uso de antibióticos, basados en la epidemiología y en las tasas de resistencia locales.

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 América (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity índex (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the región, 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 andpneumococcus 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 first versión of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II.

La neumonía adquirida por adultos en la comunidad (NAC) es, probablemente, una de las infecciones que afecta a los pacientes ambulatorios para la cual se ha escrito la mayor diversidad de lineamientos en todo el mundo. La mayoría de ellos concuerdan en que el tratamiento antimicrobiano debe ser ajustado inicialmente de acuerdo con la gravedad de la infección o con la presencia de co-morbilidades y el patógeno etiológico. Aun así, se puede notar una gran variabilidad entre los diferentes países en la selección de la elección primaria de los agentes antimicrobianos, incluso en los casos considerados como de bajo riesgo. Este hecho puede deberse a las múltiples causas microbianas de la NAC y las especialidades médicas involucradas, como así también los diferentes sistemas de asistencia de salud que afectan la disponibilidad o el costo de los antimicrobianos. No obstante, muchos países o regiones adoptan alguno de los lineamientos o diseñan sus propias recomendaciones independientemente de los datos locales, probablemente debido a la escasez de dichos datos. Por esta razón desarrollamos lineamientos para el tratamiento inicial de la NAC hacia el año 2002, sobre la base de varias evidencias locales en Sudamérica (ConsenSur I). Sin embargo, varios temas merecen discutirse nuevamente como sigue: ciertos puntajes clínicos además del índice Fisiológico de Severidad (IFS) se hicieron más populares en la práctica clínica (por ej. CURB-65, CRB-65); emergieron algunos patógenos en la región, tal como Staphylococcus aureus resistente adquirido en la comunidad (SAMR-AC) y Legionella spp; se reportaron nuevas evidencias sobre el desempeño de la prueba rápida para el diagnóstico etiológico de NAC (por ejemplo, Legionella urinaria y antígenos de Streptococcus pneumoniae); deben abordarse nuevas consideraciones terapéuticas (por ej.: reformulación de la dosis, duración del tratamiento, emergencia de antimicrobianos nuevos e impacto clínico del tratamiento combinado). Como en la primera versión del ConsenSur (ConsenSur I), los diversos lineamientos actuales ayudaron a organizar y estratificar la presente propuesta, ConsenSur II.

As a part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), Gram-positive and Gram-negative bacterial isolates were collected from 33 centers in Latin America (centers in Argentina, Brazil, Chile, Colombia, Guatemala, Honduras, Jamaica, Mexico, Panama, Puerto Rico, and Venezuela) from January 2004 to September 2007. Argentina and Mexico were the greatest contributors of isolates to this study. Susceptibilities were determined according to Clinical Laboratory Standards Institute guidelines. Resistance levels were high for most key organisms across Latin America: 48.3% of Staphylococcus aureus isolates were methicillin-resistant while 21.4% of Acinetobacter spp. isolates were imipenem-resistant. Extended-spectrum β-lactamase were reported in 36.7% of Klebsiella pneumoniae and 20.8% of E. coli isolates. Tigecycline was the most active agent against Gram-positive isolates. Tigecycline was also highly active against all Gram-negative organisms, with the exception of Pseuodomonas aeruginosa, against which piperacillin-tazobactam was the most active agent tested (79.3% of isolates susceptible). The in vitro activity of tigecycline against both Gram-positive and Gram-negative isolates indicates that it may be an useful tool for the treatment of nosocomial infections, even those caused by organisms that are resistant to other antibacterial agents.

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.

Tigecycline is a new class of antibiotics active against emerging nosocomial pathogens as methicillin-resistant Staphylococcus aureus, extended spectrum (3-lactamases-producing enterobacteria and multidrug-resistant Acinetobacter sp. It was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections, but its pharmacological and microbiological profile is attractive to physicians for using it in other pathologies caused by resistant pathogens. The aim of this study was to evaluate in which indications tigecycline was used in Argentinian usual clinical settings during the first months after its launch. We analyzed tigecycline prescriptions in 69 patients with severe infections in 15 institutions. Fifteen patients (21%) received tigecycline for approved indications, and 54 (79%) for off label indications (56%) with scientific support and 23%> with limited or without any scientific support). The most frequent off label use was ventilator associated pneumonia (VAP) (36 patients). The etiology of the infections was established in 61%> of the patients. In all cases the isolated bacteria were multi-drug resistant (MDR) Acinetobacter s/?.-carbapenems included. Our study shows that the off label use of tigecycline is frequent, specially in VAP. One of the reasons could be that for MDR-Acinetobacter sp. -VAP, there are few therapeutic options (for instance: colistin). Physicians must evaluate the benefits/risks to use this antibiotic for indications that lack rigorous scientific support

Tigeciclina es una nueva clase de antimicrobiano activo contra patógenos nosocomiales emergentes como Staphylococcus aureus resistente a meticilina, enterobacterias productoras de (3-lactamasas de espectro extendido y Acinetobacter sp multi-resistente. Hasta el momento, ha sido aprobado para el tratamiento de infecciones intra-abdominales complicadas e infecciones de piel y tejido celular subcutáneo complicadas, pero su perfil farmacológico y microbiológico resulta atractivo para prescribirlo en otras patologías, sobre todo aquellas causadas por patógenos resistentes. El objetivo de este estudio fue evaluar en qué indicaciones fue utilizada tigeciclina en Argentina durante el primer mes después de su lanzamiento. Para tal fin, fueron analizadas las prescripciones de tigeciclina en 69 pacientes con infecciones graves en 15 instituciones. Quince pacientes (21%) recibieron tigeciclina para indicaciones aprobadas y 54 (79%) para indicaciones no aprobadas -off label- (56% con respaldo científico y 23% con mínimo o nulo respaldo científico). La indicación más frecuente, dentro de las no aprobadas, fue la neumonía asociada a ventilación mecánica (NAVM) (36 pacientes). Se demostró la etiología de las infecciones en 61% de los pacientes. En todos ellos las bacterias aisladas fueron Acinetobacter sp multi-resistente (MR) incluidos los carbapenemes. Nuestro estudio muestra que la prescripción de tigeciclina para indicaciones no aprobadas es frecuente, especialmente en NAVM. Dentro de las razones que podrían explicar este fenómeno, se encuentra el escaso número de opciones terapéuticas para el tratamiento de infecciones graves por Acinetobacter sp (p. ej: colistín). Sin embargo, es aconsejable que los médicos evalúen el beneficio/riesgo de usar este antimicrobiano para indicaciones que carecen aún de respaldo científico consistente