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

Treedepth vs circumference

The circumference of a graph $G$ is the length of a longest cycle in $G$, or$+\infty$ if $G$ has no cycle. Birmel\'e (2003) showed that the treewidth of agraph $G$ is at most its circumference minus one. We strengthen this result for$2$-connected graphs as follows: If $G$ is $2$-connected, then its treedepth isat most its circumference. The bound is best possible and improves on anearlier quadratic upper bound due to Marshall and Wood (2015).<br

Relationship between past myocardial infarction, periodontal disease and Porphyromonas gingivalis serum antibodies: A case-control study

Background: The relationship between chronic periodontitis (CP) and increased risk for cardiovas­cular disease (CVD) is known but quantitative assessments and mechanisms are not fully understood. The aim of this study was to assess the relationship between past myocardial infarction (MI) and the severity of CP, and the level of serum antibody titer against Porphyromonas gingivalis gingipains. Methods: The study sample consisted of 97 patients after MI and 113 high risk controls with no history of coronary heart disease (CHD) matched with age, sex and place of residence (urban vs. rural). Data on the history of CHD and presence of risk factors were collected. Periodontal status was assessed using the Community Periodontal Index (CPI), clinical attachment loss (CAL), bleeding on probing (BOP) and pocket depth. Results: After adjustment for potential confounders patients with BOP = 20–50% and BOP &gt; 50% had more than four times higher odds of past MI (OR = 4.56; 95% CI 2.03–10.27). Patients with CPI code = 4 had a three times higher odds of past MI (OR = 3.18, 95% CI 1.01–10.06). CAL ≥ 6 was related to higher odds of past MI (OR = 1.28, 95% CI 1.11–1.49). Patients with moderate antibody titer levels had an almost 3 times higher odds of past MI (OR = 2.82, 95% CI 1.02–7.84). Conclusions: There was an association between CP and past MI, which was independent of classical CVD risk factors and confirmed by an association between past MI and immunological reaction against P. gingivalis gingipains

Timing of antibiotic therapy in the ICU

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics

Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: An opportunity for stewardship

INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization

Epidemiology, co-infections, and outcomes of viral pneumonia in adults an observational cohort study

Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk