Inadequate Empirical Antimicrobial Therapy Research Articles

Determinants of Inadequate Empiric Antimicrobial Therapy in ICU Sepsis Patients in Al-Madinah Al-Munawwarah, Saudi Arabia: A Comparison of Artificial Neural Network and Regression Analysis.

In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and to identify the determinants of inadequate EAMT. The aim of this study was to evaluate the adequacy of empiric antimicrobial therapy in patients admitted to the ICU with sepsis or septic shock, and the determinants of inadequate EAMT. The data of patients admitted to the ICU units due to sepsis or septic shock in two tertiary healthcare facilities in Al-Madinah Al-Munawwarah were retrospectively reviewed. The current study used logistic regression analysis and artificial neural network (ANN) analysis to identify determinants of inadequate empiric antimicrobial therapy, and evaluated the performance of these two approaches in predicting the inadequacy of EAMT. The findings of this study showed that fifty-three per cent of patients received inadequate EAMT. Determinants for inadequate EAMT were APACHE II score, multidrug-resistance organism (MDRO) infections, surgical history (lower limb amputation), and comorbidity (coronary artery disease). ANN performed as well as or better than logistic regression in predicating inadequate EAMT, as the receiver operating characteristic area under the curve (ROC-AUC) of the ANN model was higher when compared with the logistic regression model (LRM): 0.895 vs. 0.854. In addition, the ANN model performed better than LRM in predicting inadequate EAMT in terms of classification accuracy. In addition, ANN analysis revealed that the most important determinants of EAMT adequacy were the APACHE II score and MDRO. In conclusion, more than half of the patients received inadequate EAMT. Determinants of inadequate EAMT were APACHE II score, MDRO infections, comorbidity, and surgical history. This provides valuable inputs to improve the prescription of empiric antimicrobials in Saudi Arabia going forward. In addition, our study demonstrated the potential utility of applying artificial neural network analysis in the prediction of outcomes in healthcare research.

Risk factors and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary-care hospital in China: an eight-year retrospective study

BackgroundThe prevalence of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) is increasing worldwide. CRKP-BSI is associated with high rates of morbidity and mortality due to limited antibiotic choices. Here, we aim to identify the prevalence and risk factors for infection and mortality of CRKP BSI.MethodsThis was a retrospective study of the past data from January 1st, 2012 to December 31st, 2019 of adult patients with KP-BSI in Xiangya Hospital, China.ResultsAmong the 706 incidences included in this study, 27.4% of them (212/753) being CR-KP strains. The occurrence of CRKP-BSI was increased from 20.69 to 37.40% from 2012 to 2019. Hematologic malignancies and ICU acquired infection were identified to be substantial risk factors of carbapenem resistance. The overall 28-day mortality rates of CRKP-BSI patients was significantly higher than that of CSKP-BSI (P < 0.001). Logistic regression analysis identified severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset as the independent predictors of 28-day mortality of CRKP-BSI patients. However, high dose carbapenem combination therapy was identified as anticipated factors of low 28-day mortality.ConclusionThe occurrence of CRKP-BSI was significantly increased during the study period. Hematologic malignancies and ICU acquired infection were associated with the development of CRKP BSI. Severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset caused significant increase of mortality rates in CRKP-BSI patients. High dose carbapenem combination therapy was associated with better outcome.

Outcomes of Beta-Lactam Allergic and Non-Beta-Lactam Allergic Patients with Intra-Abdominal Infection: A Case-Control Study.

In the case of intra-abdominal infections (IAI) in beta-lactam (BL) allergic patients, empiric antimicrobial therapy without BL is recommended; however, data regarding the outcome with alternative regimens are scarce. This study aimed to compare the outcomes of BL allergic (BLA) patients with IAI to those who were non-BLA (NBLA). We conducted a case-control study in a French teaching hospital, between 1 January 2016 and 31 August 2021. BLA patients with IAI treated with fluoroquinolone or aztreonam and metronidazole were matched with controls treated with BL, on age, sex, disease severity, IAI localization, and healthcare-associated infection (HAI) status. We compared rates of therapeutic failures, adverse events, and HAI, and then assessed factors associated with therapeutic failure using a logistic regression model. The therapeutic failure rate was 14% (p &gt; 0.99) in both groups of 43 patients, and there was no significant difference in the adverse events rate (p &gt; 0.99) and HAI rate (p = 0.154). Factors independently associated with therapeutic failure were higher BMI (OR 1.16; 95%CI [1.00-1.36]; p = 0.041), longer hospital length of stay (OR 1,20; 95%CI [1.08-1.41]; p = 0.006), and inadequate empiric antimicrobial therapy (OR 11.71; 95%CI [1.43-132.46]; p = 0.025). The outcomes of BLA patients with IAI treated without BL were the same as those for NBLA patients treated with BL.

Clinical impact of multidrug-resistant bacteria in older hospitalized patients with community-acquired urinary tract infection

IntroductionPrevious studies have described some risk factors for multidrug-resistant (MDR) bacteria in urinary tract infection (UTI). However, the clinical impact of MDR bacteria on older hospitalized patients with community-acquired UTI has not been broadly analyzed. We conducted a study in older adults with community-acquired UTI in order to identify risk factors for MDR bacteria and to know their clinical impact.MethodsCohort prospective observational study of patients of 65 years or older, consecutively admitted to a university hospital, diagnosed with community-acquired UTI. We compared epidemiological and clinical variables and outcomes, from UTI due to MDR and non-MDR bacteria. Independent risk factors for MDR bacteria were analyzed using logistic regression.Results348 patients were included, 41.4% of them with UTI due to MDR bacteria. Median age was 81 years. Hospital mortality was 8.6%, with no difference between the MDR and non-MDR bacteria groups. Median length of stay was 5 [4–8] days, with a longer stay in the MDR group (6 [4–8] vs. 5 [4–7] days, p = 0.029). Inadequate empirical antimicrobial therapy (IEAT) was 23.3%, with statistically significant differences between groups (33.3% vs. 16.2%, p < 0.001). Healthcare-associated UTI variables, in particular previous antimicrobial therapy and residence in a nursing home, were found to be independent risk factors for MDR bacteria.ConclusionsThe clinical impact of MDR bacteria was moderate. MDR bacteria cases had higher IEAT and longer hospital stay, although mortality was not higher. Previous antimicrobial therapy and residence in a nursing home were independent risk factors for MDR bacteria.

Prehospital delay is an important risk factor for mortality in community-acquired bloodstream infection (CA-BSI): a matched case–control study

ObjectivesThe aim of this study was to identify prehospital and early hospital risk factors associated with 30-day mortality in patients with blood culture-confirmed community-acquired bloodstream infection (CA-BSI) in Sweden.MethodsA retrospective...

Risk Factors Associated With 30-Day Mortality Among Neonates With A. baumannii Sepsis.

Acinetobacter baumannii sepsis constitutes an extreme threat with a poor prognosis and is a difficult infection to control, especially in Asia. Moreover, a knowledge gap in the risk of mortality in neonatal A. baumannii sepsis still exists. This study aimed to identify the risk factors of mortality in neonates with A. baumannii sepsis in Thailand from 1996 to 2019. A multivariable logistic regression model was analyzed for nonsurvivors and survivors of neonatal A. baumannii sepsis. In a 24-year period, 91 neonates with A. baumannii sepsis were reviewed. The median (interquartile range) gestational age and birth weight were 33 (28.5, 37.5) weeks and 1740 (987.5, 2730.0) g, respectively. The 30-day case fatality rate was 36.3% (33/91). In univariable analysis, nonsurvivors of neonatal A. baumannii sepsis was associated with smaller neonates, lower Apgar scores, septic shock, mechanical ventilation, umbilical catheterization, neutropenia, severe thrombocytopenia, carbapenem-resistant A. baumannii sepsis, inadequate empiric antimicrobial therapy, and acute kidney injury. In multivariable analysis, nonsurvivors of neonatal A. baumannii sepsis were associated with septic shock (adjusted odds ratio [OR] = 41.38; 95% confidence intervals [CI]: 3.42-501.13; P = 0.003), severe thrombocytopenia (adjusted OR = 33.70; 95% CI: 3.44-330.55; P = 0.002), and inadequate empiric antimicrobial therapy (adjusted OR = 10.05; 95% CI: 1.40-71.98; P = 0.02). In high multidrug-resistant areas, empiric treatment with broader spectrum antimicrobials should be considered in neonates with sepsis shock or severe thrombocytopenia.

The factors affecting inadequate empirical antimicrobial therapy and clinical course in upper urinary tract infections of the elderly patients

The factors affecting inadequate empirical antimicrobial therapy and clinical course in upper urinary tract infections of the elderly patients

Predictive factors for Enterococcus faecalis in complicated community-acquired urinary tract infections in older patients.

Risk factors for complicated community acquired Enterococcus faecalis urinary tract infection (UTI) in older patients are not well known. We identified the predictive factors for E. faecalis on a cohort of 659 older patients admitted to hospital with complicated UTI. We also examined the adequacy of empirical antimicrobial therapy and outcomes in E. faecalis UTI. Multivariable logistic regression was used to identify predictors of E. faecalis UTI. A total of 87 (13.2%) patients had E. faecalis UTI; of these 63.2% were men, their mean age was 82.3 years and they had a great number of comorbidities. Severe sepsis or septic shock was present in 50.5%, and bacteremia was present in 26%. Indwelling urinary catheter and previous urinary instrumentation were risk factors for E. faecalis UTI by multivariate analysis (OR 2.05; 95% CI 1.15-3.65 and OR 2.16; 95% CI 1.08-4.34, respectively). Inadequate empirical antimicrobial therapy was higher in E. faecalis UTI than in UTI caused by Gram-negative microorganisms (66.6% vs 19%, P < 0.001). No significant differences in length of hospital stay or mortality were noted between E. faecalis and Gram-negative UTI. In older patients admitted to hospital with complicated community-acquired UTI, E. faecalis should be considered for empirical treatment if the patient has a urinary catheter or previous urinary tract instrumentation in order to avoid inadequate empirical antibiotic therapy. Geriatr Gerontol Int 2019; ••: ••-••.

Community-onset Pseudomonas aeruginosa urinary sepsis in elderly people: Predictive factors, adequacy of empirical therapy and outcomes.

Purpose To know the predictive factors for Pseudomonas aeruginosa (PA) urinary sepsis in hospitalised elderly patients coming from community, the adequacy of empirical antibiotic therapy and its outcomes. Methods Retrospective case-control study conducted between 2007 and 2017. Patients aged 65years or older with PA urinary sepsis were included as cases. Three age-matched controls, with urinary sepsis caused by other microorganisms, were selected for each case. Predictors for PA urinary sepsis were determined by logistic regression analysis. Adequacy of empirical antibiotic therapy and outcomes were compared between both groups. Results A total of 332 patients, from which 83 were cases, were included. Predictive factors for PA urinary sepsis were as follows: male sex (OR 3.16, 95% CI 1.61-6.10; P<.001), urinary catheter (OR 3.25, 95% CI 1.73-6.11; P<.001) and healthcare-associated infection (OR 5.52, 95% CI 1.76 -17.29; P=.003). Inadequate empirical antimicrobial therapy (IEAT) and length of hospital stay were higher in PA group (42% vs 24%, P=.002; 7.45±4.36days vs 6.43±3.82days, P=.045, respectively), but mortality was not different (7.2% vs 8.8%, P=.648). Conclusions Pseudomonas aeruginosa urinary sepsis in elderly people was associated with male sex, urinary catheter and healthcare-associated infection. These infections had a higher rate of IEAT and a longer hospital stay than urinary sepsis caused by other microorganisms.

Prevention of healthcare-associated infections (HAIs) in a surgical urology ward: observational study—analysis of the problem and strategies for implementation

Our purpose is to present the results of our working group, with a view to reduce the incidence and improve the management of healthcare-associated infections (HAIs) in a urology ward. The study consists on an observational database designed with the view to analyse the incidence and characteristics of HAIs in Urology. Based on the results obtained, a critical evaluation was carried out and specific measures put in place to reduce HAIs. Finally, the impact and results of the implemented measures were periodically evaluated. The incidence of HAIs in urology decreased from 6.6 to 7.3% in 2012-2014 to 5.4-5.8% in 2016-2018. In patients with immunosuppression the incidence of HAIs decreased from 12.8 to 18% in 2012-2013 to 8.1-10.2% in 2017-2018, in those with a previous urinary infection fell from 13.6 to 4.8%, in those with a urinary catheter prior to admission from 12.6 to 10.8%, and in patients with a nephrostomy tube from 16 to 10.9%. The effect of the protocol also demonstrated a reduction in the percentage of patients with suspicion of HAIs for whom no culture was taken, from 6% in 2012 to zero in 2017 and 2018. Moreover, the implementation of protocols for empirical treatment has reduced the incidence of patients experiencing inadequate empirical antimicrobial therapy from 20 to 8.1%. It is essential to monitor the incidence of HAIs, and preventive measures play a useful role in reducing the rate of infection and in optimising their management.

Inadequate empiric antimicrobial therapy and mortality in geriatric patients with bloodstream infection: A target for antimicrobial stewardship.

Bloodstream infections are responsible for a large proportion of deaths among geriatric patients. Japan is a rapidly aging society; however, little is known about the epidemiology of bloodstream infections in geriatric patients in Japanese institutions. We conducted a retrospective cohort study of patients aged ≥65 years old with a bloodstream infection in a Japanese tertiary care hospital in 2013. We defined inadequate empiric antimicrobial therapy as either antimicrobial treatment that was ineffective against subsequently isolated organisms or treatment initiated after notification of a positive culture. Predictors of inadequate antimicrobial therapy and 30-day mortality among geriatric patients with bloodstream infections were evaluated. We identified 275 patients with a bloodstream infection, of which 42.2% of cases (116/275) were healthcare-associated, hospital-onset. The most common source of bloodstream infection was hepatobiliary (28.0%). Inadequate empiric antimicrobial therapy occurred in 29.8% of the patients. Factors associated with inadequate empiric therapy included a history of surgery prior to bloodstream infection during index hospitalization (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.18-9.12). In 275 patients, 38 (13.8%) died within 30 days after the first positive blood culture. Predictors of 30-day mortality was Pitt bacteremia score >6 (aOR 9.80; 95% CI 4.72-20.36). Inadequate empiric antimicrobial therapy occurred in approximately one-third of episodes of bloodstream infection in geriatric patients. Severity at the time of bloodstream infection was likely to have contributed to mortality. The initiation of adequate empiric antimicrobial therapy may have important implications for antimicrobial stewardship even in the elderly population.

The epidemiology, antibiograms and predictors of mortality among critically-ill patients with central line-associated bloodstream infections.

For high risk of central line-associated bloodstream infections (CLABSIs) in patients of intensive care units (ICUs) and scarcely epidemiology and therapeutic recommendations in Asia, we aimed to evaluate the annual change in epidemiology, antibiogram, and risk factors for 14-day mortality. A retrospective study of ICUs patients with CLABSIs at a medical center in Taiwan (2010-2016), where central line care bundle implemented since 2014, by reviewing clinical data, pathogens, and the antibiogram. Gram-negative bacteria (59.3%) were main microorganisms of CLABSIs, and 9.0% of all GNB were MDROs. Acinetobacter spp., Enterobacter spp., and Stenotrophomonas maltophilia were the most frequently isolated. In multivariate analysis, malignancy, inadequate empirical antimicrobial therapy, inadequate definite antimicrobial therapy, and infection by fungi or multidrug-resistant organisms (MDROs) were associated with 14-day mortality (all p<0.05). The CLABSI incidence rate decreased from 5.54 to 2.18 per 1000 catheter-day (from 2014 to 2015) with improved compliance to care bundle. Carbapenem and aminoglycoside were suitable empirical drugs in the hospital setting when GNB is predominant for CLABSI. Significant decreasing susceptibility of ampicillin/sulbactam in Enterobacter spp. (36.7%-0.0%), and ampicillin/sulbactam (12.5%-0.0%), ceftazidime (100.0%-52.9%), and tigecycline (87.5%-35.3%) in Serratia marcescens. We identified Gram-negative bacteria as leading pathogens of CLABSIs in a Taiwan medical center, and good compliance to care bundle is associated with reduced CLABSI incidence rate. Malignancy, infection by MDROs or fungi, inadequate empirical or definite antimicrobial therapy are significant factors for 14-day mortality.

A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients

ObjectivesTo describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance. MethodsCirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model. ResultsWe enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure–SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29–18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93–5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28–1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73–4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48–4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12–0.73; p 0.008). ConclusionsMDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.

Multidrug-resistant Gram-negative bacteria-resistant infections: epidemiology, clinical issues and therapeutic options

In the last decade, we have witnessed a dramatic increase in the number of multidrug resistant Gram-negative (MDRGN) bacterial pathogens, both in Italy and worldwide, with Enterobacteriacae (mostly Klebsiella pneumoniae), Pseudomonas aeruginosa and Acinetobacter baumannii being the major threats in clinical practice. Inadequate empirical antimicrobial therapy of severe infections caused by MDR Enterobacteriacae has been associated with an increased morbidity and mortality. However, a careful selection of patients who may receive empirical treatment covering MDR Enterobacteriacae is important to avoid the overuse of broad-spectrum antibiotics. The aim of this review is to describe the mechanism of resistance, epidemiology, risk factors, clinical issues, and therapeutic options for MDRGN pathogens.

Prescription of antibiotics in community-acquired pneumonia in children: are we following the recommendations?

ObjectiveTo assess the adequacy of antibiotic prescription in children hospitalized for pneumonia in a reference pediatric hospital in Brazil.MethodsThis was a cross-sectional study involving children aged between 1 month and 5 years who were hospitalized between October 2010 and September 2013. The classification of community-acquired pneumonia (CAP) was based on the clinical and radiological criteria of the World Health Organization (WHO). The analysis of antibiotic adequacy was performed according to the main guidelines on CAP treatment, which include the WHO guidelines, Brazilian Society of Pediatrics guidelines, and international guidelines (Pediatrics Infectious Diseases Society, the Infectious Disease Society of America, British Thoracic Society, and Consenso de la Sociedad latinoamericana de Infectología). A multivariate analysis was performed including variables that have statistical significance of P≤0.25 in the bivariate analysis.ResultsThe majority of the 452 hospitalized children were classified as having severe or very severe CAP (85.18%), and inadequate empiric antimicrobial therapy was started in 26.10% (118/452) of them. Ampicillin was the most used empiric antibiotic therapy (62.17%) for pneumonia, followed by a combination of ampicillin and associated with gentamicin. The initially proposed regimen was modified in 29.6% of the patients, and the most frequent change was the replacement of ampicillin by oxacillin combined with chloramphenicol. The median hospitalization time was 8.5 days, and the lethality rate was 1.55%. There was no statistical difference in adequacy in relation to the severity of pneumonia or degree of malnutrition. In the bivariate analysis, inadequacy of antibiotic therapy regimen was higher in patients undergoing oxygen therapy (P<0.05), which was given to 219 patients (48.45%). Pleural effusion was observed in 118 patients (26.11%) and was associated with higher prescription inadequacy, and it was the only factor that remained in the multivariate analysis (odds ratio =8.89; 95% confidence interval 5.20–15.01).ConclusionAdherence to the main guidelines for antimicrobial therapy according to the childhood CAP was unsatisfactory. Compliance with the guidelines is essential for both the management of pneumonia cases and the decrease in bacterial resistance and it is one of the cornerstone of WHO police of controlling antibiotic resistance.

Nosocomial Gram-negative bacteremia in intensive care: epidemiology, antimicrobial susceptibilities, and outcomes

To describe the epidemiology, antimicrobial susceptibilities, treatment, and outcomes of intensive care unit (ICU)-acquired Gram-negative bacteremia. Patients with ICU-acquired Gram-negative bacteremia from 2004 to 2012 were reviewed retrospectively. Independent predictors of mortality were examined using multivariable Cox regression. Seventy-eight cases of ICU-acquired Gram-negative bacteremia occurred in 74 patients. The infection rate was 0.97/1000 patient-days. Mean patient age was 55 years, 62% were male. The most common admission diagnoses were respiratory failure (34%) and sepsis/septic shock (45%). Mortality was 35% at 30 days. The most common source of bacteremia was pneumonia (33%). Of 83 Gram-negative isolates, Escherichia coli (20%) and Pseudomonas aeruginosa (18%) were most common. For aerobic isolates, susceptibilities to ciprofloxacin (61%) and piperacillin/tazobactam (68%) were low. For pseudomonal isolates, susceptibilities to ciprofloxacin (53%), piperacillin/tazobactam (67%), and imipenem (53%) were equally disappointing. Adequate empiric antimicrobial therapy was prescribed in 85% of bacteremia cases. On multivariable analysis, adequate empiric therapy (adjusted hazard ratio (aHR) 0.38, 95% confidence interval (CI) 0.16-0.89), immune suppression (aHR 3.4, 95% CI 1.4-8.3), and coronary artery disease (aHR 4.5, 95% CI 1.7-11.9) were independently associated with 30-day mortality. ICU-acquired Gram-negative bacteremia is associated with high mortality. Resistance to ciprofloxacin, piperacillin/tazobactam, and carbapenems was common. Coronary artery disease, immune suppression, and inadequate empiric antimicrobial therapy were independently associated with increased mortality.

Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study.

Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals. The cohort included 661 adults with bloodstream infections (BSIs; n = 447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤8 mg/L. KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.

Sequential time to positivity of blood cultures can be a predictor of prognosis of patients with persistent Staphylococcus aureus bacteraemia

A short time to positivity (TTP) correlates with poor clinical outcome in patients with Staphylococcus aureus bacteraemia, but the association between sequential TTPs and the outcome of these patients is unclear. Sequential TTPs from patients with S. aureus bacteraemia persisting for >48 h were analysed with respect to clinical parameters and patient outcome at a tertiary hospital. During the 5-year study period, 87 patients (9.2%; mean age of 64 years) had persistent S. aureus bacteraemia, with an average Pittsburgh bacteraemia score of 2.7. Forty-eight patients (55%) had methicillin-resistant S. aureus infection, and 28 (32%) had nosocomial infection. The most common underlying disease was end-stage renal disease (43%). The most common type of infection was catheter-related infection (31%), followed by infective endocarditis (18%). The in-hospital mortality rate was 40%. Higher Pittsburgh scores (p 0.005; OR 1.37; 95% CI 1.1–1.7) and a second TTP/first TTP ratio of <1.5 (p 0.004; OR 0.2; 95% CI 0.07–0.6) were independent risk factors for mortality. Among patients receiving adequate empirical therapy, a second positive blood culture growing within 12 h was more frequent in patients who finally died. Factors associated with a second TTP/first TTP ratio of <1.5 included older age (p 0.02; OR 0.96; 95% CI 0.92–0.99) and inadequate empirical antimicrobial therapy (p 0.01; OR 3.53; 95% CI 1.42–8.78). Among patients with persistent S. aureus bacteraemia, a second TTP/first TTP ratio of <1.5 is a predictor of poor outcome. Physicians should search for interventions guaranteeing that all patients with S. aureus bacteraemia receive adequate empirical therapy.

De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock

We set out to assess the safety and the impact on in-hospital and 90-day mortality of antibiotic de-escalation in patients admitted to the ICU with severe sepsis or septic shock. We carried out a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock. De-escalation was defined as discontinuation of an antimicrobial agent or change of antibiotic to one with a narrower spectrum once culture results were available. To control for confounding variables, we performed a conventional regression analysis and a propensity score (PS) adjusted-multivariable analysis. A total of 712 patients with severe sepsis or septic shock at ICU admission were treated empirically with broad-spectrum antibiotics. Of these, 628 were evaluated (84 died before cultures were available). De-escalation was applied in 219 patients (34.9%). By multivariate analysis, factors independently associated with in-hospital mortality were septic shock, SOFA score the day of culture results, and inadequate empirical antimicrobial therapy, whereas de-escalation therapy was a protective factor [Odds-Ratio (OR) 0.58; 95% confidence interval (CI) 0.36-0.93). Analysis of the 403 patients with adequate empirical therapy revealed that the factor associated with mortality was SOFA score on the day of culture results, whereas de-escalation therapy was a protective factor (OR 0.54; 95% CI 0.33-0.89). The PS-adjusted logistic regression models confirmed that de-escalation therapy was a protective factor in both analyses. De-escalation therapy was also a protective factor for 90-day mortality. De-escalation therapy for severe sepsis and septic shock is a safe strategy associated with a lower mortality. Efforts to increase the frequency of this strategy are fully justified.

Epidemiología y pronóstico tardío de la sepsis en ancianos

ObjectivesA study was made of the epidemiological data of sepsis requiring admission to the ICU in patients over 65 years of age, with an evaluation of independent predictors of survival at 2 years. DesignA prospective cohort study was made. PatientsPatients meeting criteria for sepsis upon admission to the ICU. SettingA 40-bed ICU in a tertiary hospital. ResultsThe study group included 237 elderly patients (≥65 years of age) and 281 controls (<65 years of age) (n=518). At least one chronic comorbid condition was present in 70% of the elderly patients as compared to only 56.1% of patients under age 65 (P<.01). There were several epidemiological differences between the groups: the prevalence of chronic diseases (diabetes, chronic obstructive pulmonary disease, and chronic heart failure), presentation as septic shock (52.3% vs 42%; P<.05), and the abdomen as the source of sepsis (52% vs 36%; P<.01) were all more frequent in elderly patients. Nine percent of the global patients discharged from hospital died in the 2-year follow-up period, but this rate reached 20% among the elderly. Independent predictors of 2-year mortality in the elderly were: chronic heart failure (adjusted hazard ratio [aHR] 2.24, 95% confidence interval [CI 95%] 1.28-3.94; P<.01), acute renal failure (aHR 3.64, 95%CI 2.10-6.23; P<.01), acute respiratory failure (aHR 3.67, 95%CI 2.31-5.86; P<.01), and inappropriate empirical antimicrobial therapy (aHR 2.19, 95%CI 1.32-3.62; P<.01). ConclusionsSepsis showed different demographic characteristics and clinical presentations in the elderly. In the aging cohort, after adjusting for potential confounders, inadequate empirical antimicrobial therapy was associated to a 2-fold decrease in survival at two years.