Risk factors and outcomes for ineffective empiric treatment of sepsis caused by gram-negative pathogens: Stratification by onset of infection

ABSTRACT Sepsis and septic shock remain serious consequences of infections, with reported mortality rates in excess of 40 percent. Timely antibiotic therapy in cases of sepsis and septic shock is recognized as an important determinant of outcome. However, the administration of ineffective empirical treatment (IET) (an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results) is associated with excess mortality compared to effective empirical treatment (EET). We examined all hospitalized patients at Barnes-Jewish Hospital with a sterile site (blood or pleural, abdominal, cerebrospinal, synovial, and pericardial fluid) culture positive for Gram-negative (GN) bacteria combined with a primary or secondary ICD-9-CM code for severe sepsis (995.92) or septic shock (785.52) between January 2010 and October 2015. Variables significantly associated with early-onset (&lt;48 h of hospitalization) IET of GN sterile site sepsis and septic shock included age, recent hospitalization, and prior intravenous antibiotics. Late-onset IET was associated with increasing numbers of hospitalization days before infection onset and prior intravenous antibiotic administration. For patients with early-onset infection, we found no difference in rates of survival between patients receiving IET and EET. However, patients in the late-onset infection group receiving IET had a statistically lower rate of survival than those receiving EET. These data suggest that risk factors and outcomes for IET can vary based on the time of onset of infection. Our results also highlight the importance of prior intravenous antibiotic exposure as a risk factor for IET in infections by GN bacteria regardless of the time of onset of infection. </jats:p

Importance of site of infection and antibiotic selection in the treatment of carbapenem-resistant Pseudomonas aeruginosa sepsis

ABSTRACT In a retrospective analysis of 215 patients with carbapenem-resistant Pseudomonas aeruginosa sepsis, we observed a significantly higher risk of mortality associated with respiratory tract infection (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.04 to 1.39; P = 0.010) and lower risk with urinary tract infection (RR, 0.80; 95% CI, 0.71 to 0.90; P = 0.004). Aminoglycoside monotherapy was associated with increased mortality, even after adjusting for confounders (adjusted RR, 1.72; 95% CI, 1.03 to 2.85; P = 0.037), consistent across multiple sites of infection. </jats:p

Outcomes associated with bacteremia in the setting of methicillin-resistant Staphylococcus aureus pneumonia: A retrospective cohort study

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) remains an important pathogen in pneumonia. Bacteremia may secondarily complicate MRSA pneumonia. The epidemiology and outcomes associated with bacteremia in the setting of MRSA pneumonia are unknown. We sought to describe the prevalence of bacteremia in MRSA pneumonia and its impact on hospital mortality and length of stay (LOS). METHODS: We conducted a single-center retrospective cohort study (2008–2013) including adult patients hospitalized with pneumonia caused by MRSA. We defined pneumonia based on clinical criteria and all cases were culture confirmed. MRSA bacteremia was identified based on positive blood cultures. Pneumonia was categorized as either community-onset (CO, occurring at presentation or within 2 days of admission) or hospital-onset (HO, occurring > 2 days after admission). We compared bacteremic and non-bacteremic groups with respect to their demographic and clinical characteristics and outcomes. A logistic regression and a generalized linear model (GLM) were constructed to examine the impact of bacteremia on hospital mortality and post-pneumonia onset LOS, respectively. RESULTS: Among the 765 patients with MRSA pneumonia (33.1 % CO), 93 (12.2 %) had concurrent bacteremia (37.6 % CO). Patients with bacteremia were similar to non-bacteremic subjects based on demographic and clinical characteristics with the exception of frequency of a hospitalization within prior 180 days (48.4 % bacteremic and 37.7 % non-bacteremic, p = 0.047), prevalence of chronic liver disease (17.2 % vs. 9.5 %, p = 0.030), and the mean APACHE II score at the onset of pneumonia (17.5 ± 6.0 vs. 16.1 ± 6.0, p = 0.045). Both unadjusted mortality (33.7 % vs. 23.8 %, p = 0.067) and median post-pneumonia LOS (18.2 vs. 12.2 days, p < 0.001) were greater in the bacteremic than the non-bacteremic group. In a logistic regression, bacteremia showed a trend toward an association with increased mortality (odds ratio 1.56, 95 % confidence interval 0.93 to 2.61). Concomitant bacteremia was independently associated with a 10.3-day increase in the post-pneumonia hospital LOS (95 % confidence interval 6.7 to 13.9 days). CONCLUSIONS: Concurrent bacteremia occurred with moderate frequency in the setting of hospitalization with MRSA pneumonia. Although bacteremia did not appear to independently impact mortality, this was likely due to our study’s limited sample size. However, bacteremia complicating MRSA pneumonia added between 1 and 2 weeks to the hospital LOS

Clinical implications for patients treated inappropriately for community-acquired pneumonia in the emergency department

BACKGROUND: Community-acquired pneumonia (CAP) is one of the most common infections presenting to the emergency department (ED). Increasingly, antibiotic resistant bacteria have been identified as causative pathogens in patients treated for CAP, especially in patients with healthcare exposure risk factors. METHODS: We retrospectively identified adult subjects treated for CAP in the ED requiring hospital admission (January 2003-December 2011). Inappropriate antibiotic treatment, defined as an antibiotic regimen that lacked in vitro activity against the isolated pathogen, served as the primary end point. Information regarding demographics, severity of illness, comorbidities, and antibiotic treatment was recorded. Logistic regression was used to determine factors independently associated with inappropriate treatment. RESULTS: The initial cohort included 259 patients, 72 (27.8%) receiving inappropriate antibiotic treatment. There was no difference in hospital mortality between patients receiving inappropriate and appropriate treatment (8.3% vs. 7.0%; p = 0.702). Hospital length of stay (10.3 ± 12.0 days vs. 7.0 ± 8.9 days; p = 0.017) and 30-day readmission (23.6% vs. 12.3%; p = 0.024) were greater among patients receiving inappropriate treatment. Three variables were independently associated with inappropriate treatment: admission from long-term care (AOR, 9.05; 95% CI, 3.93-20.84), antibiotic exposure in the previous 30 days (AOR, 1.85; 95% CI, 1.35-2.52), and chronic obstructive pulmonary disease (AOR, 2.05; 95% CI, 1.52-2.78). CONCLUSION: Inappropriate antibiotic treatment of presumed CAP in the ED negatively impacts patient outcome and readmission rate. Knowledge of risk factors associated with inappropriate antibiotic treatment of presumed CAP could advance the management of patients with pneumonia presenting to the ED and potentially improve patient outcomes

Fluid balance and cardiac function in septic shock as predictors of hospital mortality

INTRODUCTION: Septic shock is a major cause of morbidity and mortality throughout the world. Unfortunately, the optimal fluid management of septic shock is unknown and currently is empirical. METHODS: A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325) hospitalized with septic shock who had echocardiographic examinations performed within 24 hours of shock onset were enrolled. RESULTS: A total of 163 (50.2%) patients with septic shock died during hospitalization. Non-survivors had a significantly larger positive net fluid balance within the 24 hour window of septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid balance at 24 hours and eight days post-shock onset respectively were found to predict hospital mortality, and the greatest quartile of positive net fluid balance at eight days post-shock onset was an independent predictor of hospital mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004). Survivors were significantly more likely to have mild left ventricular dysfunction as evaluated by bedside echocardiography and non-survivors had slightly elevated left ventricular ejection fraction, which was also found to be an independent predictor of outcome. CONCLUSIONS: Our data confirms the importance of fluid balance and cardiac function as outcome predictors in patients with septic shock. A clinical trial to determine the optimal administration of intravenous fluids to patients with septic shock is needed