Role of previous systemic antibiotic therapy on the probability of recurrence after an initial episode of Clostridioides difficile infection treated with vancomycin.

Objectives: To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin. Methods: Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8 weeks were included. Previous antibiotic exposure up to 90 days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed. Results: Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); P = 0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); P = 0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving ≥5 days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06-0.29; P < 0.0001] whereas exposure for ≥5 days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4-27.1; P < 0.0001). Conclusions: Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.

High Incidence of Asymptomatic Phase I IgG Seroconversion After an Acute Q Fever Episode: Implications for Chronic Q Fever Diagnosis.

BACKGROUND: The aim of this study was to describe the natural history of acute Q fever, including its clinical and serological evolution and progression to chronic Q fever. METHODS: Observational cohort study (January 2011-September 2020) performed at Valme University Hospital (Seville, Spain). Inclusion criteria: (1) patients aged ≥18 years; (2) acute Q fever diagnosis, defined as suggestive symptoms in the presence of phase II immunoglobulin G (IgG) titer >1:256; (3) at least 6 months' follow-up after the acute Q fever episode. The incidence of seroconversion to a chronic Q fever serological pattern, defined as phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis, was assessed. RESULTS: During the study period, 117 patients were included. Thirty-four (29%) patients showed phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis. All patients with classic serological criteria for chronic Q fever diagnosis remained asymptomatic despite no specific treatment, with a median (quartile 1-quartile 3 [Q1-Q3]) follow-up of 26.5 (14-44) months in this subgroup. No cases of Q fever endocarditis nor other persistent focalized infection forms were observed during the study period. CONCLUSIONS: A significant proportion of acute Q fever patients develop classic serological criteria for chronic Q fever diagnosis in the absence of additional data of chronic Q fever. Consequently, phase I IgG cutoff titers >1:800 should not be used as a criterion to consider such a diagnosis. The incidence of persistent focalized infection forms after acute Q fever is extremely low and does not justify the use of prophylaxis strategies.

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

Impact of De-escalation on Prognosis of Patients With Bacteremia due to Enterobacteriaceae: A Post Hoc Analysis From a Multicenter Prospective Cohort.

BACKGROUND: More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. The aims of this study were to investigate predictors of de-escalation and its impact on the outcome of patients with bloodstream infection due to Enterobacteriaceae (BSI-E). METHODS: A post hoc analysis was performed on a prospective, multicenter cohort of patients with BSI-E initially treated with ertapenem or antipseudomonal ß-lactams. Logistic regression was used to analyze factors associated with early de-escalation (EDE) and Cox regression for the impact of EDE and late de-escalation (LDE) on 30-day all-cause mortality. A propensity score (PS) for EDE vs no de-escalation (NDE) was calculated. Failure at end of treatment and length of hospital stay were also analyzed. RESULTS: Overall, 516 patients were included. EDE was performed in 241 patients (46%), LDE in 95 (18%), and NDE in 180 (35%). Variables independently associated with a lower probability of EDE were multidrug-resistant isolates (odds ratio [OR], 0.50 [95% confidence interval {CI}, .30-.83]) and nosocomial infection empirically treated with imipenem or meropenem (OR, 0.35 [95% CI, .14-.87]). After controlling for confounders, EDE was not associated with increased risk of mortality; hazard ratios (HR) (95% CIs) were as follows: general model, 0.58 (.25-1.31); model with PS, 0.69 (.29-1.65); and PS-based matched pairs, 0.98 (.76-1.26). LDE was not associated with mortality. De-escalation was not associated with clinical failure or length of hospital stay. CONCLUSIONS: De-escalation in patients with monomicrobial bacteremia due to Enterobacteriaceae was not associated with a detrimental impact on clinical outcome.

Impact of the MIC of piperacillin/tazobactam on the outcome for patients with bacteraemia due to Enterobacteriaceae: the Bacteraemia-MIC project.

OBJECTIVE: Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial. PATIENTS AND METHODS: A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6). CONCLUSIONS: We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.

Evaluation of new antimicrobials for the hospital formulary. Policies restricting antibiotic use in hospitals.

In Spain, the inclusion of new antibiotics in hospital formularies is performed by the Infection Policy Committee or the Pharmacy and Therapeutic Committee, although now the decision is moving to a regional level. Criteria for the evaluation of new drugs include efficacy, safety and cost. For antimicrobial drugs evaluation it is necessary to consider local sensibility and impact in bacterial resistance to determinate the therapeutic positioning. There is compelling evidence that the use of antibiotics is associated with increasing bacterial resistance, and a great number of antibiotics are used incorrectly. In order to decrease the inappropriate use of antibiotics, several approaches have been proposed. Limiting the use of antimicrobials through formulary restrictions, often aimed at drugs with a specific resistance profile, shows benefits in improving antimicrobial susceptibilities and decreasing colonization by drug-resistant organisms. However, the restriction of one agent may result in the increased utilization of other agents. By using antibiotic cycling, the amount of antibiotics is maintained below the threshold where bacterial resistance develops, thus preserving highly efficient antibiotics. Unfortunately, cumulative evidence to date suggests that antibiotic cycling has limited efficacy in preventing antibiotic resistance. Finally, although there is still little clinical evidence available on antibiotic heterogeneity, the use of most of the existing antimicrobial classes could limit the emergence of resistance. This review summarizes information regarding antibiotic evaluation and available restrictive strategies to limit the use of antibiotics at hospitals with the aim of curtailing increasing antibiotic resistance.

Evaluation of new antimicrobials for the hospital formulary. Policies restricting antibiotic use in hospitals / Evaluación de nuevos antibióticos para el formulario de hospital. Normas restrictivas del uso de antibióticos en los hospitales

In Spain, the inclusion of new antibiotics in hospital formularies is performed by the Infection Policy Committee or the Pharmacy and Therapeutic Committee, although now the decision is moving to a regional level. Criteria for the evaluation of new drugs include efficacy, safety and cost. For antimicrobial drugs evaluation it is necessary to consider local sensibility and impact in bacterial resistance to determinate the therapeutic positioning. There is compelling evidence that the use of antibiotics is associated with increasing bacterial resistance, and a great number of antibiotics are used incorrectly. In order to decrease the inappropriate use of antibiotics, several approaches have been proposed. Limiting the use of antimicrobials through formulary restrictions, often aimed at drugs with a specific resistance profile, shows benefits in improving antimicrobial susceptibilities and decreasing colonization by drug-resistant organisms. However, the restriction of one agent may result in the increased utilization of other agents. By using antibiotic cycling, the amount of antibiotics is maintained below the threshold where bacterial resistance develops, thus preserving highly efficient antibiotics. Unfortunately, cumulative evidence to date suggests that antibiotic cycling has limited efficacy in preventing antibiotic resistance. Finally, although there is still little clinical evidence available on antibiotic heterogeneity, the use of most of the existing antimicrobial classes could limit the emergence of resistance. This review summarizes information regarding antibiotic evaluation and available restrictive strategies to limit the use of antibiotics at hospitals with the aim of curtailing increasing antibiotic resistance

En España, la evaluación de nuevos antibióticos para su inclusión en los formularios de los hospitales se realiza en la Comisión de Infecciones y la Comisión de Farmacia y Terapéutica, aunque hay una tendencia a que la decisión se traslade al ámbito de la comunidad autónoma. Los criterios de evaluación de nuevos medicamentos incluyen los datos de eficacia, seguridad y coste. En el caso de los antimicrobianos es necesario además valorar la sensibilidad local y el impacto en las resistencias bacterianas, para determinar su posicionamiento terapéutico. Hay numerosas evidencias de que el consumo de antibióticos se asocia con un aumento de las resistencias bacterianas y, además, muchos antibióticos se utilizan de forma incorrecta. Para reducir el uso inadecuado de los antibióticos se han propuesto distintos abordajes. En primer lugar limitar el uso de antibióticos mediante formularios restrictivos, a menudo relacionados con antibióticos asociados a un perfil de resistencias determinado. Esta estrategia ha demostrado beneficios en sensibilidad y reducción de la colonización por microorganismos resistentes, aunque la restricción de un fármaco concreto pueda conllevar el aumento del consumo de otros. Mediante el uso cíclico de antibióticos se pretende que el consumo total de antibióticos se mantenga por debajo de un determinado umbral a partir del cual se desarrollarían resistencias, lo que permitiría un uso ecológico de los antibióticos. Desafortunadamente, en la práctica la evidencia acumulada sugiere que el uso cíclico tiene una eficacia limitada para evitar las resistencias. Finalmente, la estrategia que en la actualidad se considera más prometedora está en relación con la diversificación o uso heterogéneo de antibióticos. El uso de diversas clases de antibióticos existentes, sin que se sobrecargue especialmente un grupo, podría limitar el desarrollo de resistencias de los diferentes antibióticos utilizados, aunque todavía hay poca evidencia en la eficacia de esta estrategia. Esta revisión resume la información disponible sobre la evaluación de antibióticos y las estrategias restrictivas existentes para limitar el uso de antibióticos en los hospitales, con el objetivo de reducir el aumento de las resistencias bacterianas

Impact of an evidence-based bundle intervention in the quality-of-care management and outcome of Staphylococcus aureus bacteremia.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. Several aspects of clinical management have been shown to have significant impact on prognosis. The objective of the study was to identify evidence-based quality-of-care indicators (QCIs) for the management of SAB, and to evaluate the impact of a QCI-based bundle on the management and prognosis of SAB. METHODS: A systematic review of the literature to identify QCIs in the management of SAB was performed. Then, the impact of a bundle including selected QCIs was evaluated in a quasi-experimental study in 12 tertiary Spanish hospitals. The main and secondary outcome variables were adherence to QCIs and mortality. Specific structured individualized written recommendations on 6 selected evidence-based QCIs for the management of SAB were provided. RESULTS: A total of 287 and 221 patients were included in the preintervention and intervention periods, respectively. After controlling for potential confounders, the intervention was independently associated with improved adherence to follow-up blood cultures (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.78-4.49), early source control (OR, 4.56; 95% CI, 2.12-9.79), early intravenous cloxacillin for methicillin-susceptible isolates (OR, 1.79; 95% CI, 1.15-2.78), and appropriate duration of therapy (OR, 2.13; 95% CI, 1.24-3.64). The intervention was independently associated with a decrease in 14-day and 30-day mortality (OR, 0.47; 95% CI, .26-.85 and OR, 0.56; 95% CI, .34-.93, respectively). CONCLUSIONS: A bundle orientated to improving adherence to evidence-based QCIs improved the management of patients with SAB and was associated with reduced mortality.

Reappraisal of the outcome of healthcare-associated and community-acquired bacteramia: a prospective cohort study.

BACKGROUND: Healthcare-associated (HCA) bloodstream infections (BSI) have been associated with worse outcomes, in terms of higher frequencies of antibiotic-resistant microorganisms and inappropriate therapy than strict community-acquired (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment protocols may have modified this association. The objective of this study was to analyse the etiology, therapy and outcomes for CA and HCA BSI in our area. METHODS: A prospective multicentre cohort including all CO-BSI episodes in adult patients was performed over a 3-month period in 2006-2007. Outcome variables were mortality and inappropriate empirical therapy. Adjusted analyses were performed by logistic regression. RESULTS: 341 episodes of CO-BSI were included in the study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4% (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for age, Charlson index, source, etiology, presentation with severe sepsis or shock and inappropriate empirical treatment, acquisition type was not associated with an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th-day mortality for Gram negatives BSI showed a statically significant difference (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate empirical treatment in the community were: catheter source, cancer, and previous antimicrobial use; no association with HCA acquisition was found. CONCLUSION: HCA acquisition in our cohort was not a predictor for either inappropriate empirical treatment or increased mortality. These results might reflect recent changes in therapeutic protocols and epidemiological changes in community pathogens. Further studies should focus on recognising CA BSI due to resistant organisms facilitating an early and adequate treatment in patients with CA resistant BSI.

Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis.

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.

High prevalence of hepatitis C virus infection among noninjecting drug users: association with sharing the inhalation implements of crack.

BACKGROUND: Most of the prevalent cases of hepatitis C virus (HCV) infection are attributable to intravenous drug using. However, a substantial number of individuals, particularly noninjecting drug users (NIDU), report no identifiable source of HCV exposure. This may be interpreted as inaccurate reporting of past intravenous exposure or as the presence of an unidentified source of HCV infection. Because of this, we evaluated the prevalence of and factors associated with HCV infection among NIDU. METHODS: One hundred and eighty-two individuals who were attended from 2003 to 2004 in a drug addiction facility because of noninjecting drug use were included. RESULTS: HCV infection was detected in 23 (12.6%) participants. Sharing the inhalation tube of crack cocaine [adjusted odds ratio (AOR) 3.6, 95% confidence interval (CI) 1.3-9.8, P=0.01], presence of tattoos (AOR 3.5, 95% CI 1.3-9.1, P=0.02) and age >or=34 years (AOR 3.9, 95% CI 1.3-11.6, P=0.01) 3.9 were independently associated with HCV infection. CONCLUSION: The prevalence of HCV infection in NIDU is higher than in general population. HCV infection is more likely among older drug users, those with tattoos and crack cocaine users that share the inhalation implements.

Frequency of visceral leishmaniasis relapses in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

There are contradictory data about whether highly active antiretroviral therapy (HAART) prevents visceral leishmaniasis (VL) relapses in human immunodeficiency virus type 1 (HIV-1)-infected patients. The aim of this study was to assess the frequency of VL relapses in individuals receiving HAART. Thirty-one patients who received HAART after developing VL were included in a retrospective cohort study. Ten of them received secondary chemoprophylaxis and the rest did not. Eight (38%) patients without secondary chemoprophylaxis showed a VL relapse. None of the seven subjects with VL relapses and 6 of 11 without recurrence (P = 0.038), in whom all scheduled data were available, showed an increase of more than 100 CD4+ cells/mm(3) during the follow-up. Patients with relapse showed higher levels of HIV RNA viral load at their last visit (P = 0.047). The frequency of VL relapses in patients receiving HAART is high. Relapses of VL are observed only in individuals with uncontrolled HIV replication and/or poor immunologic responses.