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

Augmented renal clearance is not a risk factor for mortality in Enterobacteriaceae bloodstream infections treated with appropriate empiric antimicrobials

The main objective of the study was to assess whether augmented renal clearance was a risk factor for mortality in a cohort of patients with Enterobacteriaceae sepsis, severe sepsis, or septic shock that all received appropriate antimicrobial therapy within 12 hours. Using a retrospective cohort from Barnes-Jewish Hospital, a 1,250-bed teaching hospital, we collected data on individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock who received appropriate initial antimicrobial therapy between June 2009 and December 2013. Clinical outcomes were compared according to renal clearance, as assessed by Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, sepsis classification, demographics, severity of illness, and comorbidities. We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were nonsurvivors. Augmented renal clearance was uncommon (5.1% of patients by MDRD and 3.0% by CKD-EPI) and was not associated with increased mortality. Our results are limited by the absence of prospective determination of augmented renal clearance. However, in this small cohort, augmented renal clearance as assessed by MDRD and CKD-EPI does not seem to be a risk factor for mortality in patients with Enterobacteriaceae sepsis. Future studies should assess this finding prospectively

Bench-to-bedside review: Understanding the impact of resistance and virulence factors on methicillin-resistant Staphylococcus aureus infections in the intensive care unit

Methicillin-resistant Staphylococcus aureus (MRSA) displays a remarkable array of resistance and virulence factors, which have contributed to its prominent role in infections of the critically ill. We are beginning to understand the function and regulation of some of these factors and efforts are ongoing to better characterize the complex interplay between the microorganism and host response. It is important that clinicians recognize the changing resistance patterns and epidemiology of Staphylococcus spp., as these factors may impact patient outcomes. Community-associated MRSA clones have emerged as an increasingly important subset of Staphyloccocus aureus and MRSA can no longer be considered as solely a nosocomial pathogen. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has long been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for existing and investigational agents demonstrating efficacy in this role

An institutional perspective on the impact of recent antibiotic exposure on length of stay and hospital costs for patients with gram-negative sepsis

<p>Abstract</p> <p>Background</p> <p>Prior antibiotic exposure has been associated with the emergence of antibiotic resistance in subsequent bacterial infections, whose outcomes are typically worse than similar infections with more antibiotic susceptible infections. The influence of prior antibiotic exposure on hospital length of stay (LOS) and costs in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia has not been previously examined.</p> <p>Methods</p> <p>A retrospective cohort study of hospitalized patients (January 2002-December 2007) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. Patients with Gram-negative bacteremia complicated by severe sepsis or septic shock had data abstraction from computerized medical records. We examined a consecutive cohort of 754 subjects (mean age 59.3 ± 16.3 yrs, mean APACHE II 23.7 ± 6.7).</p> <p>Results</p> <p><it>Escherichia coli </it>(30.8%), <it>Klebsiella pneumoniae </it>(23.2%), and <it>Pseudomonas aeruginosa </it>(17.6%) were the most common organisms isolated from blood cultures. 310 patients (41.1%) had exposure to antimicrobial agents in the previous 90 days. Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% v. 21.2%; p < 0.001) and hospital mortality (51.3% v. 34.0%; p < 0.001) compared to patients without recent antibiotic exposure. The unadjusted median LOS (25^thpercentile, 75^thpercentile) following sepsis onset in patients with prior antimicrobial exposure was 13.0 days (5.0 days, 24.0 days) compared to 8.0 days (5.0 days, 14.0 days) in those without prior antimicrobial exposure (p < 0.001). In a Cox model controlling for multiple confounders, prior antibiotic exposure independently correlated with remaining hospitalized (Adjusted hazard ratio: 1.473, 95% CI: 1.297-1.672, p < 0.001). Adjusting for potential confounders indicated that prior antibiotic exposure independently increased median attributable LOS by 5.0 days. Similarly, total hospital costs following sepsis onset was significantly greater among patients with prior antimicrobial exposure (median values: $94,737 v.$21,329; p < 0.001).</p> <p>Conclusions</p> <p>Recent antibiotic exposure is associated with increased LOS and hospital costs in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians and hospital administrators should consider the potential impact of recent antibiotic exposure when formulating empiric treatment decisions for patients with serious infections attributed to Gram-negative bacteria.</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