Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases.

BACKGROUND: Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB. METHODS: We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends. RESULTS: A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) -1.5%, P < 0.001] and a -8.170 (-16.064 to -0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC -3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC -0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae. CONCLUSIONS: In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.

Antiretroviral therapy partially improves the abnormalities of dendritic cells and lymphoid and myeloid regulatory populations in recently infected HIV patients.

This study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIV-infected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load -10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin -IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals.

Differential characteristics of Acinetobacter baumannii colonization and infection: risk factors, clinical picture, and mortality.

OBJECTIVES: The objectives of this study were to detect those characteristics that were specifically associated with infection or colonization by Acinetobacter baumannii, describe the clinical manifestations of those patients in whom the infection was detected in intensive care unit (ICU) or non-ICU wards, and analyze the prognosis-associated factors in patients from whom A. baumannii was isolated. PATIENTS AND METHODS: A sample of 122 patients from whom A. baumannii was recovered during an endemic period in a teaching hospital was included. Only those cases in which A. baumannii was recovered as the unique microbe were considered. Demographic data; ward of admission; intrinsic and extrinsic risk factors for infection or colonization; chronic underlying condition severity, as evaluated by the McCabe classification or Charlson index and Acute Physiology and Chronic Health Evaluation (APACHE) II score; and clinical manifestations were analyzed to differentiate specific characteristics of colonized or infected patients. Factors independently associated with the mortality at 30 days were also analyzed by Cox regression. RESULTS: A total of 73 (60%) patients were colonized and 49 (40%) individuals were infected with A. baumannii. A non-fatal McCabe class (when compared to ultimately and rapidly fatal), days of hospitalization prior to isolation of A. baumannii, and present ICU admission were associated with the diagnosis of infection. The more frequent clinical picture was respiratory infection (tracheobronchitis, 16 [33%] cases; pneumonia, 27 [55%] cases). Mortality at 30 days was 24% (n=29). A non-fatal McCabe class (Exp[B] 2.44, 95% confidence interval [CI] 1.05-5.66, p=0.039) and the absence of infection (Exp[B] 2.75, 95% CI 1.18-6.38, p=0.019) were independently associated with survival. CONCLUSION: Parameters associated with infection by A. baumannii in an endemic situation are the admission at ICU and the number of days of hospitalization. Mortality of patients from whom A. baumannii was isolated was independently influenced by the chronic underlying basal state and the presence of infection by A. baumannii.

[Use of an empirical antiretroviral treatment depends on the primary resistance rate of the human immunodeficiency virus]. / La práctica de un tratamiento antirretroviral empírico es dependiente del porcentaje de resistencias primarias del virus de la inmunodeficiencia humana.

OBJECTIVE: The objective of this study was the analysis of the prevalence and type of primary resistance to antiretroviral drugs in patients diagnosed with HIV infection, and to determine the most appropriate empirical treatment to obtain a virological and immunological response. PATIENTS AND METHODS: An observational analysis of patients with a de novo diagnosis of HIV infection during the period 2008-2010. Clinical, immunological and virological characteristics, including genotype analysis of resistance to antiretrovirals, were considered as independent variables. The dependent variable was an undetectable HIV viral load after six months of treatment. Data are provided as median (interquartile range) and absolute number (percentage). RESULTS: Seventy-three patients with a de novo diagnosis of HIV infection were included [53 males (73%); 36 (30-46) years-old; prior use of intravenous drugs: 5 patients (7%); hepatitis C virus co-infection: 13 individuals (18%)]. Ten patients (14%) showed symptoms attributable to acute HIV infection. A CD4+ T cell count lower than 350 mm(3) was detected in a 37% (n=27) of all patients. The initiation of antiretroviral therapy followed the GESIDA recommendations (no therapy: 20 patients; tenofovir+emtricitabine+efavirenz: 28 patients; abacavir+lamivudine+efavirenz: 1 patient; tenofovir+emtricitabine+protease inhibitors: 5 patients; abacavir+lamivudine+protease inhibitors: 1 patient; 18 patients were lost in the follow-up). After starting antiretroviral therapy, the resistance analyses detected the existence of primary resistance to antiretrovirals in 12.7% (confidence interval 95%: 3-22) of the patients, distributed as follows: isolated resistance to, nucleosides was detected in 2% (M184V), to nevirapine/efavirenz in 9% (K103N), and combined resistance to nucleosides and non-nucleosides in 2%; there were no cases of resistance to protease inhibitors. Consequently, antiretroviral therapy was changed in 5 (14%) out of 35 patients, attaining an undetectable HIV viral load at 6 months in all of them. The primary resistance to antiretrovirals was not related with epidemiological, virological (including infection by non B subtype) or immunological variables. CONCLUSIONS: In the present study, a change in the epidemiological pattern of de novo diagnosis of HIV infection in our area has been observed. The existence of resistance mutations in more than 5% of the new cases is noteworthy. This finding must be considered in order to establish the rules of empirical treatment in our area.

Análisis descriptivo de las enfermedades asociadas a bacteriemia por Streptococcus bovis / Descriptive analysis of diseases associated with Streptococcus bovis bacteremia

Fundamento y objetivo: Aunque se conoce la relación entre la bacteriemia por Streptococcus bovis (S. bovis) y el cáncer de colon, cirrosis hepática u otras neoplasias, no se ha establecido un protocolo de estudio para descartar estas enfermedades subyacentes a la bacteriemia. Nuestro objetivo fue describir la bacteriemia por S. bovis y las enfermedades asociadas.Pacientes y método: Estudio multicéntrico, retrospectivo de cohortes. Se incluyeron las bacteriemias por S. bovis entre 2001 y 2009. Las variables principales fueron: neoplasia colónica, neoplasias en otras localizaciones o cirrosis hepática. Se recogieron variables epidemiológicas, relacionadas con la bacteriemia, antecedentes personales, familiares, datos clínicos y analíticos. Resultados: Se incluyeron 93 pacientes. Un 25% de los individuos tuvo neoplasia de colon. Un 57% de ellos fueron casos concomitantes con la bacteriemia y 6 fueron diagnósticos posteriores a ella (mediana [Q1-Q3] de tiempo bacteriemia-diagnóstico neoplasia de 2,6 meses [1-11]), con un máximo de 15,4 meses. Catorce (15%) pacientes padecían alguna neoplasia no colónica (mayoritariamente biliopancreática [6 casos] y esofagogástrica [3 casos]). Hubo 3 (21%) casos concomitantes con la bacteriemia y 2 posteriores a ella (a 1,2 y 10,4 meses). Veintiún (23%) enfermos tenían cirrosis hepática.Conclusiones: A los pacientes con bacteriemia por S. bovis es necesario realizarles un estudio encaminado a descartar enfermedades subyacentes. Sugerimos que se incluyan, al menos: una prueba de imagen colónica, preferentemente colonoscopia; un estudio hepático mediante analítica, ecografía abdominal o un método de medición de fibrosis hepática; una endoscopia digestiva alta; y una prueba de imagen del área biliopancreática como la colangiorresonancia magnética

Background and objective: It is well-known the relationship between Streptococcus bovis (S. bovis) bacteremia and colon cancer, liver cirrhosis and others neoplasms. However, a study protocol to rule out these underlying diseases has not been carried out yet. Our objective was to describe S. bovis bacteremia and associated diseases. Patients and method: Multicenter, retrospective cohort study. S. bovis bacteremias episodes between 2001 and 2009 were included. Mean variables: colon neoplasm, non-colonic neoplasm or liver cirrhosis. Epidemiologist aspects, bacteremia related variables, personal and familiar history and clinical and analytical data were collected.Results: Ninety three patients were included. One out of four individuals had a colon neoplasm. Fifty seven per cent were concomitant cases with bacteremia and six cases were diagnosed after bacteremia (time bacteremia-diagnosis of neoplasm [months], median [Q1-Q3], 2.6 [1-11]). Fourteen (15%) patients were diagnosed with any non-colonic neoplasm (mainly biliary and pancreatic [6 cases] or esophagus-gastric [3 cases]). There were three patients (21%) with concomitant bacteremia non-colonic neoplasm and two after it (1.2 and 10.4 months). Twenty-one (23%) patients suffered from liver cirrhosis. Conclusions: Patients with S. bovis bacteremia must undergo a study designed to rule out underlying diseases. We suggest that this study should include: a colonic evaluation, ideally by colonoscopy, a liver evaluation by serum chemistry, an abdominal ultrasound scan or a method of liver fibrosis assessment, a gastroscopy and an evaluation of biliary and pancreatic areas by magnetic resonance imaging

[Descriptive analysis of diseases associated with Streptococcus bovis bacteremia]. / Análisis descriptivo de las enfermedades asociadas a bacteriemia por Streptococcus bovis.

BACKGROUND AND OBJECTIVE: It is well-known the relationship between Streptococcus bovis (S. bovis) bacteremia and colon cancer, liver cirrhosis and others neoplasms. However, a study protocol to rule out these underlying diseases has not been carried out yet. Our objective was to describe S. bovis bacteremia and associated diseases. PATIENTS AND METHOD: Multicenter, retrospective cohort study. S. bovis bacteremias episodes between 2001 and 2009 were included. Mean variables: colon neoplasm, non-colonic neoplasm or liver cirrhosis. Epidemiologist aspects, bacteremia related variables, personal and familiar history and clinical and analytical data were collected. RESULTS: Ninety three patients were included. One out of four individuals had a colon neoplasm. Fifty seven per cent were concomitant cases with bacteremia and six cases were diagnosed after bacteremia (time bacteremia-diagnosis of neoplasm [months], median [Q1-Q3], 2.6 [1-11]). Fourteen (15%) patients were diagnosed with any non-colonic neoplasm (mainly biliary and pancreatic [6 cases] or esophagus-gastric [3 cases]). There were three patients (21%) with concomitant bacteremia non-colonic neoplasm and two after it (1.2 and 10.4 months). Twenty-one (23%) patients suffered from liver cirrhosis. CONCLUSIONS: Patients with S. bovis bacteremia must undergo a study designed to rule out underlying diseases. We suggest that this study should include: a colonic evaluation, ideally by colonoscopy, a liver evaluation by serum chemistry, an abdominal ultrasound scan or a method of liver fibrosis assessment, a gastroscopy and an evaluation of biliary and pancreatic areas by magnetic resonance imaging.

Candidemias: análisis multicéntrico en 16 hospitales andaluces / Candidemias: multicentre analysis in 16 hospitals in Andalusia (Spain)

Introducción La candidemia es una infección nosocomial con elevada mortalidad. Los cambios clínicos y microbiológicos descritos en otras áreas y las novedades terapéuticas de los últimos años hacen preciso conocer si la epidemiología clínica de las candidemias en nuestro medio ha cambiado. Material y métodos Estudio prospectivo, multicéntrico y observacional de todos los episodios de candidemia en pacientes adultos atendidos entre el 1 octubre 2005 y el 30 septiembre 2006 en 17 hospitales de Andalucía. Resultados El número total de episodios fue de 220, la incidencia de 0,58 episodios/por cada 1.000 altas. Candida albicans fue la etiología más frecuente (53%). El 89% de las cepas fueron sensibles a fluconazol. La sepsis fue la presentación clínica más frecuente (65,7%). El tratamiento empírico fue inapropiado en el 38,7%. La mortalidad global (..) (AU)

Introduction: Candidemia is a nosocomial infection with high associated mortality. There have been changes in microbiology, epidemiology and treatment over the last few years, which has led us to analyse our own situation. Material and methods: Prospective, multicentre and observational study. All episodes of candidemia in adult patients seen in 17 Andalusian hospitals from 1 October 2005 to 30 September 2006 were included. Results: Were detected 220 cases, the incidence was 0.58 cases/1,000 hospital discharges. Candida albicans was the most frequent species (53% of cases). The majority of isolates (89%) was susceptibility to fluconazole. Sepsis was the most frequent clinical manifestation (65.7%). The treatment was inadequate in b38.7% of cases. Overall mortality was 40%.On univarite analysis (..) (AU)

[Candidemias: multicentre analysis in 16 hospitals in Andalusia (Spain)]. / Candidemias: análisis multicéntrico en 16 hospitales andaluces.

INTRODUCTION: Candidemia is a nosocomial infection with high associated mortality. There have been changes in microbiology, epidemiology and treatment over the last few years, which has led us to analyse our own situation. MATERIAL AND METHODS: Prospective, multicentre and observational study. All episodes of candidemia in adult patients seen in 17 Andalusian hospitals from 1 October 2005 to 30 September 2006 were included. RESULTS: Were detected 220 cases, the incidence was 0.58 cases/1,000 hospital discharges. Candida albicans was the most frecuent species (53% of cases). The majority of isolates (89%) was susceptibility to fluconazole. Sepsis was the most frequent clinical manifestation (65.7%). The treatment was inadequate in 38.7% of cases. Overall mortality was 40%. On univarite analysis death was found to be significantly associated with: aged > 60 years, unknown candidemia focus, Pitt score ≥ 2, APACHE II, shock at onset, persistents positive second blood cultures, non-removal of the central venous catheter and Candida species different of C. parasilopsis, among others. In the multivariate analysis death was found to be significantly associated with: aged > 60 years, Pitt score ≥ 2, Candida species different of C.parasilopsis and inadequate treatment. CONCLUSIONS: The candidemia clinical epidemiology in our region is similar to other areas and receiving inadequate treatment is the only modifiable risk factor associated with higher odds of mortality. Therefore, this modifiable factor needs to be improved to reduce the mortality.