Adrienne Showler

Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study

BACKGROUND We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB). METHODS A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups. A competing risk model with propensity score adjustment was used to compare in-hospital mortality and time to discharge. RESULTS Of 847 SAB patients, 506 (60%) patients received an ID consultation and 341 (40%) patients did not. Echocardiography was done for 371 (73%) IDC and 191 (56%) NIDC patients (P < .0001) in hospital. Blood cultures were repeated within 2-4 days of bacteremia in 207 (41%) IDC and 107 (31%) NIDC patients (P = .0058). The infectious foci removal rate was not statistically different between the 2 groups. For empiric therapy, 474 (94%) IDC and 297 (87%) NIDC patients received appropriate antibiotics (P = .0013). For patients who finished the planned course of antibiotics, 285 of 422 (68%) IDC and 141 of 262 (54%) NIDC patients received the appropriate duration of antibiotic therapy (P = .0004). In hospital, 204 (24%) patients died: 104 of 506 (21%) IDC and 100 of 341 (29%) NIDC patients. Matched by propensity score, ID consultation had a subdistribution hazard ratio of 0.72 (95% confidence interval [CI], .52-.99; P = .0451) for in-hospital mortality and 1.28 (95% CI, 1.06-1.56; P = .0109) for being discharged alive. CONCLUSIONS ID consultation is associated with better adherence to quality measures, reduced in-hospital mortality, and earlier discharge in patients with SAB.

Comparative effectiveness of cefazolin versus cloxacillin as definitive antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort study

OBJECTIVES We compared the effectiveness of cefazolin versus cloxacillin in the treatment of MSSA bacteraemia in terms of mortality and relapse. METHODS A retrospective cohort study examined consecutive patients with Staphylococcus aureus bacteraemia from six academic and community hospitals between 2007 and 2010. Patients with MSSA bacteraemia who received cefazolin or cloxacillin as the predominant definitive antibiotic therapy were included in the study. Ninety-day mortality was compared between the two groups matched by propensity scores. RESULTS Of 354 patients included in the study, 105 (30%) received cefazolin and 249 (70%) received cloxacillin as the definitive antibiotic therapy. In 90 days, 96 (27%) patients died: 21/105 (20%) in the cefazolin group and 75/249 (30%) in the cloxacillin group. Within 90 days, 10 patients (3%) had a relapse of S. aureus infection: 6/105 (6%) in the cefazolin group and 4/249 (2%) in the cloxacillin group. All relapses in the cefazolin group were related to a deep-seated infection. Based on the estimated propensity score, 90 patients in the cefazolin group were matched with 90 patients in the cloxacillin group. In the propensity score-matched groups, cefazolin had an HR of 0.58 (95% CI 0.31-1.08, P = 0.0846) for 90 day mortality. CONCLUSIONS There was no significant clinical difference between cefazolin and cloxacillin in the treatment of MSSA bacteraemia with respect to mortality. Cefazolin was associated with non-significantly more relapses compared with cloxacillin, especially in deep-seated S. aureus infections.

Diagnostic Accuracy of Transthoracic Echocardiography for Infective Endocarditis Findings Using Transesophageal Echocardiography as the Reference Standard: A Meta-Analysis

Background: Echocardiography is important for the diagnosis of infective endocarditis (IE), for which transesophageal echocardiography (TEE) is superior to transthoracic echocardiography (TTE). Methods: A systematic review and meta‐analysis of observational studies was performed with the objective of evaluating diagnostic properties of TTE, with transesophageal findings of IE as the reference standard in patients with suspected IE. Results: The literature search yielded 377 unique articles, of which 16 met the inclusion criteria. The 16 studies included 2,807 patients, of whom 793 (28%) had vegetations on TEE. For detecting vegetations, harmonic TTE had sensitivity of 61% (95% CI, 45%–75%) and specificity of 94% (95% CI, 85%–98%) with a negative likelihood ratio (NLR) of 0.42 (95% CI, 0.26–0.61). NLR for harmonic TTE can be improved by including only patients without prosthetic valves (NLR = 0.36; 95% CI, 0.22–0.55) or by having strict criteria for conclusively negative results on TTE (NLR = 0.17; 95% CI, 0.10–0.28). In the setting of patients without prosthetic valves, harmonic TTE had likelihood ratios of 0.14 (95% CI, 0.09–0.23) for a conclusively negative result, 0.66 (95% CI, 0.53–0.81) for an indeterminate result, and 14.60 (95% CI, 3.37–70.40) for a positive result. Conclusions: Modern harmonic TTE still has the potential to miss many vegetations detected on TEE. When limited to patients without prosthetic valves, a conclusively negative TTE under optimal view greatly decreases likelihood of IE. All other transthoracic results are not useful for ruling out IE, and subsequent TEE is almost always required. HighlightsModern harmonic TTE still has the potential to miss many vegetations detected on TEE.Completely normal results on TTE in patients without prosthetic valves can aid in ruling out endocarditis.Any results on TTE other than completely normal require subsequent TEE to rule out endocarditis.

Cutaneous Leishmaniasis in Travellers: a Focus on Epidemiology and Treatment in 2015

Imported cutaneous leishmaniasis (CL) is a growing problem with increasing global travel to endemic areas. Returned travellers seeking care encounter significant barriers to treatment, including diagnostic delays and difficult access to anti-leishmanial drugs. Treatment recommendations in non-endemic settings are a moving target, reflecting recent developments in Leishmania diagnostics and therapeutics. Accumulating experience with molecular-based species identification has enabled species-directed therapy. Clinicians are reevaluating more toxic traditional regimens in light of newly approved therapeutic agents and emerging data on local cutaneous treatments. Referral centers are implementing treatment decision algorithms designed to maximize efficacy while minimizing adverse events. Although management strategies continue to evolve, treatment of CL in non-endemic settings remains controversial. Persistent reliance on expert opinion reflects lack of research focused on travellers and limited randomized controlled trial evidence. We herein review the current epidemiology of cutaneous leishmaniasis in travellers and species-specific evidence for available therapies.

Parasitic diseases in travelers: a focus on therapy

Parasitic infections are an important cause of illness among returned travelers, and can lead to considerable morbidity and, in some cases, mortality. The complexity of parasitic life cycles and geographic specificities can present diagnostic challenges, particularly in non-endemic settings to which most travelers return for care. Clinical manifestations reflect the diverse taxonomy and pathogenesis of parasites, and appropriate diagnosis and management therefore necessitate a high index of suspicion of parasitic illnesses. Much of our knowledge surrounding management of parasitic infections in travelers is extrapolated from evidence derived in endemic populations, or is based on expert opinion and case series. We herein provide an overview of parasitic diseases of short-term travelers, and summarize current therapeutic strategies for each illness.

Clinical prediction rules in Staphylococcus aureus bacteremia demonstrate the usefulness of reporting likelihood ratios in infectious diseases

Infectious diseases specialists often use diagnostic tests to assess the probability of a disease based on knowledge of the diagnostic properties. It has become standard for published studies on diagnostic tests to report sensitivity, specificity and predictive values. Likelihood ratios are often omitted. We compared published clinical prediction rules in Staphylococcus aureus bacteremia to illustrate the importance of likelihood ratios. We performed a narrative review comparing published clinical prediction rules used for excluding endocarditis in S. aureus bacteremia. Of nine published clinical prediction rules, only three studies reported likelihood ratios. Many studies concluded that the clinical prediction rule could safely exclude endocarditis based on high sensitivity and high negative predictive value. Of the studies with similar high sensitivity and high negative predictive value, calculated negative likelihood ratios were able to differentiate and identify the best clinical prediction rule for excluding endocarditis. Compared to sensitivity, specificity and predictive values, likelihood ratios can be more directly used to interpret diagnostic test results to assist in ruling in or ruling out a disease. Therefore, a new standard should be set to include likelihood ratios in reporting of diagnostic tests in infectious diseases research.

Usefulness of previous methicillin-resistant Staphylococcus aureus screening results in guiding empirical therapy for S aureus bacteremia.

Staphylococcus aureus bacteremia (SAB), which may be caused by methicillin-resistant S aureus (MRSA), is a leading cause of bloodstream infections. SAB and MRSA can cause an increase in mortality, result in longer hospital stays and increase medical costs. However, it is possible that MRSA colonization may predict infection. Using a retrospective cohort investigation, this study evaluated the clinical utility of past MRSA screening swabs for predicting methicillin resistance and its use in guiding empirical antibiotic therapy for SAB.

Parasitic Liver Disease in Travelers

Liver disease is an important source of morbidity among ill returning travelers. Jaundice is one of the most common and obvious symptoms of liver disease, the differential diagnosis of which is extensive, especially in travelers. Jaundice in travelers can arise from both infectious and noninfectious causes. We herein summarize the most common parasitic etiologies that may lead to jaundice in the returned traveler, visitors of friends and relatives, or new immigrants, and describe the etiology, epidemiology, and pathogenesis of clinical features of each.

Clinicians should use likelihood ratios when comparing tests.

We are thankful for the thoughtful comments provided by Cohen and colleagues in their letter to the editor, and appreciate the opportunity to respond below. First, Cohen and colleagues make an excellent point that sensitivity and specificity as well as likelihood ratios change with different settings, and offer a good example. When we wrote BUnlike predictive values, likelihood ratios do not vary with prevalence^, we were simplifying the concept before introducing the concept of variability across disease spectrums. Later in the same paragraph, we wrote BThus, a study’s likelihood ratio can be applied to a patient population with a prevalence that is different from that in the study under the assumption that the study sample is representative of the population in terms of disease spectrum. When applying the likelihood ratio to another population, it should be noted that sensitivity, specificity and likelihood ratios are not fixed test properties and may vary across settings^. This was the same point raised by Cohen et al. regarding variability of sensitivity, specificity, and likelihood ratios reflecting differences in patient and disease spectrum across studies or subgroups. We would like to point out that sensitivity and specificity are no better than likelihood ratio in terms of variability across study settings. Second, Cohen et al. disagreed with our point on likelihood ratios being of more direct use than sensitivity and specificity to interpret diagnostic results. We agree that sensitivity and specificity are very important considerations in understanding the behavior of diagnostic tests. However, after the diagnostic test is done, it does not have a direct clinical meaning when interpreting a test result. When interpreting a diagnostic test result, the disease status of the patient is not known and only the diagnostic test result is known. Using the example from Cohen et al., a sensitivity of 90%means 90% of patients with disease will have a positive test result. This has no direct interpretation for a patient with a positive result, because it is not known if the patient has disease or not. In contrast, we agree with their assertion that, Blikelihood ratio says something about the test result^. Likelihood ratios can be used to interpret a diagnostic test result. For a patient with a positive result, the positive likelihood ratio is able to convert from a pre-test probability to a post-test probability of disease. Third, Cohen et al. rightfully state that the conversion from pre-test to post-test probability of disease using likelihood ratios requires assumptions such as likelihood ratios being the same for every patient. However, the same argument holds true for the application of any of the diagnostic test properties, including sensitivity, specificity, and predictive values, to a patient. Without these assumptions, any diagnostic property cannot be applied to an individual patient. In the clinical setting, the application of likelihood ratios to an individual patient is well accepted and widely used [1]. As an example, the JAMA Rational Clinical Examination Series summarizes likelihood ratios for clinicians to use when examining a patient [2]. * A. M. Morris andrew.morris@sinaihealthsystem.ca

925A Normal Transthoracic Echocardiogram can be Used to Rule Out Infective Endocarditis in Patients with Staphylococcus aureus Bacteremia

Infective Endocarditis in Patients with Staphylococcus aureus Bacteremia Adrienne Showler, MD; Lisa Burry, PharmD; Anthony Bai, BSc; Daniel Ricciuto, MD; Marilyn Steinberg, RN; Tania Fernandes, PharmD; Anna Chiu, PharmD; Sumit Raybardhan, BSc, Phm, MPH; Eshan Ferndando, MD; Chaim Bell, MD, PhD; Andrew Morris, MD, SM; University of Toronto, Toronto, ON, Canada; Mount Sinai Hospital, Toronto, ON, Canada; University of Ottawa, Ottawa, ON, Canada; Lakeridge Hospital, Oshawa, ON, Canada; Mount Sinai Hospital, 600 University Ave, Toronto, ON, Canada; Trillium Health Center, Toronto, ON, Canada; North York General Hospital, Toronto, ON, Canada