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Data about short courses of antibiotic therapy for Gram-negative bacilli (GNB) bacteremia in immunosuppressed patients are limited. This is a prospective observational study performed on adult patients with cancer and hematopoietic stem cell transplant (HSCT) who developed GNB bacteremia and received appropriate empirical antibiotic therapy (EAT), had a clinical response within 7 days and survived 48 h after the end of therapy. They received antibiotic therapy in the range of 7-15 days and were divided into short course, with a median of 7 days (SC), or long course, with a median of 14 days (LC). Seventy-four patients were included (SC: 36 and LC: 38). No differences were observed in baseline characteristics or in the presence of neutropenia: 58.3% vs. 60.5% (p = 0.84). Clinical presentation and microbiological characteristics were similar in SC and LC, respectively: clinical source of bacteremia 72.2% vs. 76.3% (p = 0.68); shock 2.8% vs. 10.5% (p = 0.35) and multidrug-resistant GNB 27.8% vs. 21.1% (p = 0.50). Overall, mortality was 2.8% vs. 7.9% (p = 0.61), and bacteremia relapse was 2.8% vs. 0 (p = 0.30). The length of hospitalization since bacteremia was 7 days (interquartile range (IQR), 6-15) for SC and 12 days (IQR, 7-19) (p = 0.021) for LC. In the case of patients with cancer or HSCT and GNB bacteremia who receive appropriate EAT with clinical response, 7 days of antibiotic therapy might be adequate.

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In spite of the low frequency of COVID-19 associated bacterial coinfections, the rate of empiric antibiotic use varies between 70% and 90%. The primary objective of this study was to evaluate the impact of an antimicrobial stewardship program (ASP) on COVID-19 patients. The study design was an interrupted time series, assessing prevalence of antibiotic use, adequacy of treatment and antimicrobial consumption in adult patients hospitalized with COVID before the COVID-ASP implementation in June 2020, and on three subsequent periods (P2 in August 2020, P3 in October 2020 and P4 in June 2021). One hundred and one patients were included. Moderate and severe disease was more frequent in P2, P3, and P4 periods (p < 0.001). After the implementation we observed a significant reduction on ATM use (61% vs. 41% vs. 31.1% vs. 8.1%, p < 0.001), and macrolid combination therapy (17.3% vs. 19.2% vs. 10.8% vs. 1.4%, p = 0.03), and an increase of adequate use (37.5% vs. 46.9% vs. 69.9% vs. 66.6%, p = 0.039). Antimicrobial consumption by period in days of therapy (DOT)/1000 patient-day was 347.9 vs. 272.8 vs. 134.29 vs. 43.6 (p <0.001). We did not find any difference in intensive care unit transfer or mortality. COVID-ASP implementation was an effective strategy to reduce antimicrobial consumption and optimize antibiotic indications without affecting morbidity or mortality.

A pesar de la baja frecuencia de coinfecciones bacterianas asociadas al COVID-19, la tasa de uso de antibióticos (ATB) empíricos varía entre 70 y 90%. El objetivo primario del estudio fue evaluar el impacto de la implementación de un programa de optimización de antimicrobianos en pacientes con COVID-19 (PROA-COVID). Se realizó un estudio prospectivo de serie de tiempo interrumpida. Se evaluó la prevalencia, adecuación y consumo de ATB en adultos internados con COVID previo a la implementación del PROA-COVID (P1, junio 2020) y en tres períodos posteriores (P2 en agosto 2020, P3 en octubre 2020 y P4 en junio 2021). Se incluyeron 301 pacientes. Las formas clínicas moderadas-graves fueron más frecuentes en los P2, 3 y 4 (p < 0.001). La implementación del programa mostró una disminución significativa del uso de ATB (61% vs. 41% vs. 31.1% vs. 8.1%, p < 0.001), de la indicación de tratamiento combinado con macrólidos (17.3% vs. 19.2% vs. 10.8% vs. 1.4%, p = 0.03) y aumento del uso adecuado (37.5% vs. 46.9% vs. 69.9% vs. 66.6%, p = 0.039). El consumo de ATB en DDT (días de tratamiento) totales/1000 días paciente fue: 347.9 vs. 272.8 vs. 134.3 vs. 43.6 (p < 0.001). No hubo diferencias significativas en el pase a unidades de cuidados críticos ni en la mortalidad. La implementación del PROA-COVID fue una estrategia efectiva para reducir el uso de antibióticos y optimizar sus indicaciones sin impacto en la morbimortalidad.

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Resumen A pesar de la baja frecuencia de coinfecciones bacterianas asociadas al COVID-19, la tasa de uso de antibióticos (ATB) empíricos varía entre 70 y 90%. El objetivo primario del estudio fue evaluar el impacto de la implementación de un programa de optimización de antimicrobianos en pacientes con COVID-19 (PROA-COVID). Se realizó un estudio prospectivo de serie de tiempo interrumpida. Se evaluó la prevalencia, adecuación y consumo de ATB en adultos internados con COVID previo a la implementación del PROA-COVID (P1, junio 2020) y en tres períodos posteriores (P2 en agosto 2020, P3 en octubre 2020 y P4 en junio 2021). Se incluyeron 301 pacientes. Las formas clínicas moderadas-graves fueron más frecuentes en los P2, 3 y 4 (p < 0.001). La implementación del programa mostró una disminución significativa del uso de ATB (61% vs. 41% vs. 31.1% vs. 8.1%, p < 0.001), de la indicación de tratamiento combinado con macrólidos (17.3% vs. 19.2% vs. 10.8% vs. 1.4%, p = 0.03) y aumento del uso adecuado (37.5% vs. 46.9% vs. 69.9% vs. 66.6%, p = 0.039). El consumo de ATB en DDT (días de tratamiento) totales/1000 días paciente fue: 347.9 vs. 272.8 vs. 134.3 vs. 43.6 (p < 0.001). No hubo diferencias significativas en el pase a unidades de cuidados críticos ni en la mortalidad. La implementación del PROA-COVID fue una estrategia efectiva para reducir el uso de antibióticos y optimizar sus indicaciones sin impacto en la morbimortalidad.

Abstract In spite of the low frequency of COVID-19 associated bacterial coinfections, the rate of empiric an tibiotic use varies between 70% and 90%. The primary objective of this study was to evaluate the impact of an antimicrobial stewardship program (ASP) on COVID-19 patients. The study design was an interrupted time series, assessing prevalence of antibiotic use, adequacy of treatment and antimicrobial consumption in adult patients hospitalized with COVID before the COVID-ASP implementation in June 2020, and on three subsequent periods (P2 in August 2020, P3 in October 2020 and P4 in June 2021). One hundred and one patients were included. Moderate and severe disease was more frequent in P2, P3, and P4 periods (p < 0.001). After the implementation we observed a significant reduction on ATM use (61% vs. 41% vs. 31.1% vs. 8.1%, p < 0.001), and macrolid combination therapy (17.3% vs. 19.2% vs. 10.8% vs. 1.4%, p = 0.03), and an increase of adequate use (37.5% vs. 46.9% vs. 69.9% vs. 66.6%, p = 0.039). Antimicrobial consumption by period in days of therapy (DOT)/1000 patient-day was 347.9 vs. 272.8 vs. 134.29 vs. 43.6 (p<0.001). We did not find any difference in intensive care unit transfer or mortality. COVID-ASP implementation was an effective strategy to reduce antimicrobial consump tion and optimize antibiotic indications without affecting morbidity or mortality.

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Clostridioides difficile infection (CDi) is one of the foremost hospital-acquired infections. We present an observational study aimed to describe the incidence, epidemiology, and clinical outcome of CDi in a tertiary university hospital in Buenos Aires. The episodes, diagnosed in 117 consecutive adult patients in the period 01/01/2017 to 01/04/2020, were distributed in three groups: 63 (53.9%) were classified as hospital-acquired infections (HA), 25 (21.4%) as community onset-health care-associated infections (CO-HCA) and 29 (24.8%) as community-associated infections (CA). The incidence of HA CDi infections was 3.1, 5. 2 and 2.8 every 10 000 patient days in 2017, 2018 and 2019, respectively. The microbiological diagnosis was made by immunochromatography with antigen GDH and C. difficile toxin positive in 51 episodes (43.6%) and by GDH positive, toxin negative and PCR positive in 66 episodes (56.4%). Older age (p = 0.018), chronic kidney disease (p = 0.013), immunosuppression (p = 0.021), and higher comorbidity Charlson score (p = 0.001) were observed in patients with IH and CA-HCA infections. No significant differences in clinical features were found among groups. During the hospital st ay, 13 patients (11.1%) required admission to the intensive care unit. Ten recurrences occurred, representing 8.5% of CDI episodes. The 90-day mortality was 19.8%, being significantly higher in HA and CO-HCA infections (p = 0.014). Our findings highlight both the local burden of CDi morbidity and mortality and the need for the implementation of preventive strategies.

La infección por Clostridioides difficile (ICD) es una de las más importantes infecciones intrahospitalarias. Se realizó un estudio observacional que describe la incidencia, las características epidemiológicas y la evolución clínica de la ICD en un hospital universitario de la Ciudad de Buenos Aires. Los episodios, diagnosticados en 117 pacientes adultos consecutivos entre el 01/01/2017 y el 01/04/2020, fueron clasificados en ICD intrahospitalaria (IH) en 63 (53.9%), de inicio comunitario y asociada al ámbito de la salud (ICAAS) en 25 (21.4%) y comunitaria (CO) en 29 (24.8%) pacientes. La incidencia de ICD IH fue 3.1, 5.2 y 2.8 cada 10 000 días paciente en 2017, 2018 y 2019, respectivamente. El diagnóstico microbiológico se realizó mediante inmunocromatografía con glutamato deshidrogenasa y toxina positivas en 51 (43.6%) y mediante glutamato deshidrogenasa positiva, toxina negativa y PCR positiva en 66 (56.4%). Los pacientes con ICD IH e ICAAS presentaron mayor edad (p = 0.018), mayor frecuencia de insuficiencia renal crónica (p = 0.013) e inmunosupresión (p = 0.021) y mayor puntaje en índice Charlson de comorbilidad (p = 0.001). No hubo diferencia significativa en la forma de presentación clínica entre los tres grupos. Durante la evolución de la ICD, 13 (11.1%) pacientes requirieron internación en terapia intensiva. Se registraron 10 recurrencias, que correspondieron al 8.5% de los episodios de ICD. La mortalidad a los 90 días fue 19.8%, significativamente mayor en los pacientes con ICD IH e ICAAS (p = 0.014). Estos hallazgos destacan la considerable carga de morbilidad de la ICD y la necesidad de implementar estrategias preventivas.

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Resumen La infección por Clostridioides difficile (ICD) es una de las más importantes infecciones intrahospitalarias. Se realizó un estudio observacional que describe la incidencia, las características epi demiológicas y la evolución clínica de la ICD en un hospital universitario de la Ciudad de Buenos Aires. Los episodios, diagnosticados en 117 pacientes adultos consecutivos entre el 01/01/2017 y el 01/04/2020, fueron clasificados en ICD intrahospitalaria (IH) en 63 (53.9%), de inicio comunitario y asociada al ámbito de la salud (ICAAS) en 25 (21.4%) y comunitaria (CO) en 29 (24.8%) pacientes. La incidencia de ICD IH fue 3.1, 5.2 y 2.8 cada 10 000 días paciente en 2017, 2018 y 2019, respectivamente. El diagnóstico microbiológico se realizó mediante inmunocromatografía con glutamato deshidrogenasa y toxina positivas en 51 (43.6%) y mediante glutamato deshidrogenasa positiva, toxina negativa y PCR positiva en 66 (56.4%). Los pacientes con ICD IH e ICAAS presentaron mayor edad (p = 0.018), mayor frecuencia de insuficiencia renal crónica (p = 0.013) e inmu nosupresión (p = 0.021) y mayor puntaje en índice Charlson de comorbilidad (p = 0.001). No hubo diferencia significativa en la forma de presentación clínica entre los tres grupos. Durante la evolución de la ICD, 13 (11.1%) pacientes requirieron internación en terapia intensiva. Se registraron 10 recurrencias, que correspondieron al 8.5% de los episodios de ICD. La mortalidad a los 90 días fue 19.8%, significativamente mayor en los pacientes con ICD IH e ICAAS (p = 0.014). Estos hallazgos destacan la considerable carga de morbilidad de la ICD y la necesidad de implementar estrategias preventivas.

Abstract Clostridioides difficile infection (CDi) is one of the foremost hospital-acquired infections. We present an observa tional study aimed to describe the incidence, epidemiology, and clinical outcome of CDi in a tertiary university hospital in Buenos Aires. The episodes, diagnosed in 117 consecutive adult patients in the period 01/01/2017 to 01/04/2020, were distributed in three groups: 63 (53.9%) were classified as hospital-acquired infections (HA), 25 (21.4%) as community onset-health care-associated infections (CO-HCA) and 29 (24.8%) as community-associated infections (CA). The incidence of HA CDi infections was 3.1, 5. 2 and 2.8 every 10 000 patient days in 2017, 2018 and 2019, respectively. The microbiological diagnosis was made by immunochromatography with antigen GDH and C. difficile toxin positive in 51 episodes (43.6%) and by GDH positive, toxin negative and PCR positive in 66 episodes (56.4%). Older age (p = 0.018), chronic kidney disease (p = 0.013), immunosuppression (p = 0.021), and higher comorbidity Charlson score (p = 0.001) were observed in patients with IH and CA-HCA infections. No significant differences in clinical features were found among groups. During the hospital st ay, 13 patients (11.1%) required admission to the intensive care unit. Ten recurrences occurred, representing 8.5% of CDI episodes. The 90-day mortality was 19.8%, being significantly higher in HA and CO-HCA infections (p = 0.014). Our findings highlight both the local burden of CDi morbidity and mortality and the need for the implementation of preventive strategies.

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INTRODUCTION: Pulmonary complications are frequent in patients with hematologic malignancies and stem cell transplantation. Regardless of the microbiological usefulness of bronchoalveolar lavage (BAL), little information exists on both its benefits as a guide for therapeutic decisions and its impact on patients' clinical outcome. METHODS: A prospective observational single-center study was performed between July 2011 and July 2016. Consecutive episodes of pulmonary infiltrates were analyzed in subjects over 18 years of age who presented hematologic malignancies and underwent chemotherapy or stem cell transplantation. RESULTS: Ninety-six episodes of pulmonary infiltrates were analyzed. Acute leukemia was the most frequent underlying condition. Thirty-seven patients (38.5%) received a stem cell transplant. Sixty-one (62.9%) were neutropenic at the moment of inclusion in the study. A definitive etiologic diagnosis was obtained in 41 cases (42.7%), where infection accounted for the vast majority of cases (33 cases, 80.5%). Definitive diagnosis was reached by non-invasive methods in 13 cases (13.5%). BAL was performed in 47 cases and led to a diagnosis in 40.4% of the cases. BAL results led to therapeutic changes in 27 cases (57.4%), including the addition of new antimicrobials to empiric treatments in 10. Regarding BAL's safety, two patients experienced minor adverse events and one a severe adverse event; no procedure-related deaths were observed. CONCLUSIONS: Infection was the leading cause of pulmonary infiltrates in patients with hematologic malignancies and stem cell transplantation. BAL was a useful decision-making diagnostic tool, with minor adverse events.

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Introducción: No obstante la baja frecuencia de infecciones bacterianas asociadas al COVID-19, la prevalencia del uso de antibióticos empíricos es de 70 a 90%. El objetivo primario del estudio fue evaluar el impacto de la implementación de un programa de optimización de antimicrobianos dirigido a pacientes con COVID-19 (PROA-COVID).Material y métodos: Estudio antes y después, retrospectivo, descriptivo y analítico. Se evaluó prevalencia y adecuación del uso de antibióticos antes y después de implementación del PROA-COVID en pacientes internados. Se estimó consumo mensual de antibióticos en DDD/100 pacientes-día y costos por uso inadecuado.Resultados: Se incluyeron 153 pacientes, 75 antes y 78 después de la intervención, sin diferencias significativas en las características poblacionales entre ambos períodos. Las formas clínicas moderadas-severas fueron más frecuentes postintervención (p=0,03). La implementación mostró una disminución significativa en prevalencia de uso (64% vs 41%, p=0,004), con aumento de uso adecuado (37,5% vs. 46,8%, p=NS). La indicación innecesaria fue mayor antes del PROA (80% vs 50%, p=0,03) y la duración del tratamiento postintervención (13,3% vs. 43,7%%, p=0,02). La implementación redujo el consumo de betalactámicos + IBL y azitromicina.No se observaron diferencias significativas en mortalidad, frecuencia de pase a UCC ni uso de antibioticoterapia combinada con macrólidos entre ambos períodos ajustando por severidad. Conclusiones: La implementación del PROA-COVID fue una estrategia efectiva para reducir el uso de antibióticos y optimizar sus indicaciones, lo que destaca la importancia de su aplicación rápida y oportuna.

ntroduction: Despite the low frequency of Covid-19-associated bacterial infections, empirical antibacterial treatment is as high as 70 to 90%. The primary goal of this study was to determine the impact of the implementation of an antimicrobial stewardship program to target Covid-19 patients (ASP-COVID).Materials and methods: Retrospective, descriptive, and analytic pre and post intervention study. Prevalence and adequacy of antibacterial treatment in hospitalized patients prior and after ASP-COVID implementation were assessed. Monthly antibiotic consumption in DDD/100 patients-day and costs related with inadequate usage were estimated. Results: One hundred and fifty three patients, 75 prior and 78 after ASP-COVID implementation, were included. No significant difference in population characteristics between both periods was observed. Moderate and severe clinical presentations were more frequent after the intervention (p=0,03). ASP implementation showed a significant reduction of antimicrobial treatment (64% vs 41%, p=0,004), with an increment of adequate usage (37,5% vs 46,8%, p=NS). Unnecessary usage was higher prior to ASP (80% vs 50%, p =0,03) and length of treatment post intervention (13,3% vs 43,7%%, p=0,02). Program implementation decreased beta lactam antibiotics + IBL and azithromycin consumption. After adjusting for severity, no significant difference was found in mortality, incidence of ICU admission nor combined antibacterial therapy with macrolides between both periods.Conclusions: ASP-COVID implementation was an effective strategy in reducing antimicrobial usage and in optimizing antibacterial treatment indications, highlighting the importance of its rapid and timely application.

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Uncomplicated urinary tract infections rank among the most frequent bacterial infections in women in the outpatient setting and represent a major cause of antimicrobial prescription. The aims of this study were to assess frequencies and antimicrobial resistance of current uropathogens causing uncomplicated urinary tract infection. In a prospective multicenter study, patients were recruited in ambulatory settings of four participating hospitals between June 2011 and December 2013. We analyzed 138 patients that met clinical and bacteriological diagnostic criteria. The mean age was 28 years. Cystitis was defined in 70% (n: 97) and pyelonephritis in 30% (n: 41). Frequencies of isolated microorganisms were: Escherichia coli 70% (n: 97), Staphylococcus saprophyticus 17% (n: 24), Proteus spp. 7% (n: 10), Klebsiella spp. 4% (n: 5), Enterococcus spp. and Pseudomonas aeruginosa 1 (0.7%) each. The antimicrobial resistance was: ampicillin-sulbactam 37% (n: 51) cephalexin 28% (n: 39), trimethoprim/sulfamethoxazole 22% (n: 31), nitrofurantoin 12% (n: 17), gentamicin 7% (n: 10) and ciprofloxacin 5% (n: 7). The levels of resistance found for ampicillin-sulbactam, trimethoprim/sulfamethoxazole and cephalexin were higher than those previously reported in Argentina. A better knowledge of the etiology and local antimicrobial susceptibility allows the design of more adequate guidelines for empirical treatment.

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La infección urinaria no complicada en mujeres es un motivo frecuente de consulta e indicación de antimicrobianos. El objetivo de este estudio fue definir etiología y resistencia a antimicrobianos en episodios de infección urinaria no complicada. Este estudio prospectivo incluyó mujeres premenopáusicas no embarazadas, con infección urinaria no complicada, que consultaron en un hospital público y tres centros privados de las ciudades de Buenos Aires y La Plata (2011-2013). La edad media de 138 pacientes con infección confirmada por urocultivo fue 28 años. El diagnóstico fue cistitis en 97 (70%) y pielonefritis en 41 (30%). Las frecuencias de los microorganismos aislados fueron: Escherichia coli 97 (70%), Staphylococcus saprophyticus 24 (17%), Proteus spp. 10 (7%), Klebsiella spp. 5 (4%), Enterococcus spp. 1 (0.7%) y Pseudomonas aeruginosa 1 (0.7%). Las frecuencias de resistencia a antimicrobianos fueron: ampicilina-sulbactam 51 (37%), cefalexina 39 (28%), trimetoprima/sulfametoxazol 31 (22%), nitrofurantoína 17 (12%), gentamicina 10 (7%) y ciprofloxacina 7 (5%). La frecuencia de resistencia a ampicilina-sulbactam, trimetoprima/sulfametoxazol y cefalexina es mayor que las previamente publicadas en Argentina, lo que limita su recomendación para el tratamiento empírico. Una mejor comprensión de la etiología y la susceptibilidad antimicrobiana local permite el diseño de pautas más adecuadas para el tratamiento empírico.

Uncomplicated urinary tract infections rank among the most frequent bacterial infections in women in the outpatient setting and represent a major cause of antimicrobial prescription. The aims of this study were to assess frequencies and antimicrobial resistance of current uropathogens causing uncomplicated urinary tract infection. In a prospective multicenter study, patients were recruited in ambulatory settings of four participating hospitals between June 2011 and December 2013. We analyzed 138 patients that met clinical and bacteriological diagnostic criteria. The mean age was 28 years. Cystitis was defined in 70% (n: 97) and pyelonephritis in 30% (n: 41). Frequencies of isolated microorganisms were: Escherichia coli 70% (n: 97), Staphylococcus saprophyticus 17% (n: 24), Proteus spp. 7% (n: 10), Klebsiella spp. 4% (n: 5), Enterococcus spp. and Pseudomonas aeruginosa 1 (0.7%) each. The antimicrobial resistance was: ampicillin-sulbactam 37% (n: 51) cephalexin 28% (n: 39), trimethoprim/sulfamethoxazole 22% (n: 31), nitrofurantoin 12% (n: 17), gentamicin 7% (n: 10) and ciprofloxacin 5% (n: 7). The levels of resistance found for ampicillin-sulbactam, trimethoprim/sulfamethoxazole and cephalexin were higher than those previously reported in Argentina. A better knowledge of the etiology and local antimicrobial susceptibility allows the design of more adequate guidelines for empirical treatment.

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Fluorquinolone-prophylaxis has proven useful in preventing infections in high risk neutropenic patients. The objective of this study was to describe the clinical, microbiological and therapeutic characteristics, and outcome of patients in the first episode of febrile neutropenia, comparing those who received levofloxacin prophylaxis with those who didn't. It was a prospective observational study that included all the episodes of inpatients with febrile neutropenia (February 1997- November 2014), also including the first episode in a same patient in different hospitalizations. Of 946 episodes here included, 821 presented high risk febrile neutropenia. A total of 264 cases (27.9%) received levofloxacin prophylaxis. This group consisted of a higher proportion of high risk febrile neutropenia (99.2% vs. 82.3%, p = 0.0001) and patients that had received an hematopoietic stem cell transplant (67.8% vs. 29.3%, p = 0.0001) compared to those who didn't receive prophylaxis. Those who received levofloxacin prophylaxis presented a similar frequency of clinically diagnosed but a lower proportion of microbiologically documented infections (28.8% vs. 37.5%, p = 0.012) than those who didn't receive prophylaxis. The episodes of bacteremia that occurred in the first group were more frequently caused by multidrug resistant bacteria (MDRB) (34.5% vs. 17.3%, p = 0.007) and by extended spectrum beta lactamase producing Enterobacteriaceae (19% vs. 3.8%, p = 0.0001). The group that received prophylaxis had a lower proportion of adequate empirical antibiotic treatment (69.7% vs. 83.7%, p = 0.009), with similar outcomes in both groups. We suggest that levofloxacin prophylaxis should be stopped whenever there is a rise in the frequency of MDRB infections in this population.

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