Michael J. Fine

Enterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistance during Therapy

OBJECTIVES To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia. DESIGN Prospective, observational study of consecutive patients with Enterobacter bacteremia. SETTING Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers. PATIENTS A total of 129 adult patients were studied. MEASUREMENTS The two main end points were emergence of resistance during antibiotic therapy and death. MAIN RESULTS Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy. CONCLUSIONS More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.

Cholesterol Crystal Embolization: A Review of 221 Cases in the English Literature:

Cholesterol crystal embolization (CCE) frequently presents with nonspecific manifestations that mimic other systemic diseases. The authors reviewed 221 cases of histologically proven CCE in the English literature to define the clinical, laboratory, and pathologic characteristics of this disorder. CCE affected predominantly elderly males (mean age sixty-six) with a frequent history of hypertension (61%), atherosclerotic cardiovascular disease (44%), renal failure (34%), and aortic aneurysms (25%) at presentation. At least one possible predisposing factor was present in 31 % and included operative and radiological vascular procedures and the use of anticoagulants. Cutaneous findings (34%) and renal failure (50%) were two of the most common clinical findings throughout the course of CCE. The nonspecific signs and symptoms included: fever (7%), weight loss (7%), myalgias (4%), and headache (3%). Premortem diagnoses were established in 31 % of patients most commonly by biopsy of the muscle, skin, and kidney. Mortality was high (81 %) and was most commonly due to multifactorial, cardiac, and renal etiologies. The authors conclude that CCE should be strongly considered in elderly patients with atherosclerotic vascular disease who have the onset of renal insufficiency and cutaneous manifestations. CCE may be confirmed by a skin or muscle biopsy.

Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial

BACKGROUND Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care. METHODS We undertook an open-label, randomised non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. We randomly assigned patients with acute, symptomatic pulmonary embolism and a low risk of death (pulmonary embolism severity index risk classes I or II) with a computer-generated randomisation sequence (blocks of 2-4) in a 1:1 ratio to initial outpatient (ie, discharged from hospital ≤24 h after randomisation) or inpatient treatment with subcutaneous enoxaparin (≥5 days) followed by oral anticoagulation (≥90 days). The primary outcome was symptomatic, recurrent venous thromboembolism within 90 days; safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. We used a non-inferiority margin of 4% for a difference between inpatient and outpatient groups. We included all enrolled patients in the primary analysis, excluding those lost to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00425542. FINDINGS Between February, 2007, and June, 2010, we enrolled 344 eligible patients. In the primary analysis, one (0·6%) of 171 outpatients developed recurrent venous thromboembolism within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2·7%; p=0·011). Only one (0·6%) patient in each treatment group died within 90 days (95% UCL 2·1%; p=0·005), and two (1·2%) of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL 3·6%; p=0·031). By 90 days, three (1·8%) outpatients but no inpatients had developed major bleeding (95% UCL 4·5%; p=0·086). Mean length of stay was 0·5 days (SD 1·0) for outpatients and 3·9 days (SD 3·1) for inpatients. INTERPRETATION In selected low-risk patients with pulmonary embolism, outpatient care can safely and effectively be used in place of inpatient care. FUNDING Swiss National Science Foundation, Programme Hospitalier de Recherche Clinique, and the US National Heart, Lung, and Blood Institute. Sanofi-Aventis provided free drug supply in the participating European centres.

SMART-COP: A Tool for Predicting the Need for Intensive Respiratory or Vasopressor Support in Community-Acquired Pneumonia

BACKGROUND Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

Advancing Health Disparities Research Within the Health Care System: A Conceptual Framework

We provide a framework for health services-related researchers, practitioners, and policy makers to guide future health disparities research in areas ranging from detecting differences in health and health care to understanding the determinants that underlie disparities to ultimately designing interventions that reduce and eliminate these disparities. To do this, we identified potential selection biases and definitions of vulnerable groups when detecting disparities. The key factors to understanding disparities were multilevel determinants of health disparities, including individual beliefs and preferences, effective patient-provider communication; and the organizational culture of the health care system. We encourage interventions that yield generalizable data on their effectiveness and that promote further engagement of communities, providers, and policymakers to ultimately enhance the application and the impact of health disparities research.

Impact of Penicillin Susceptibility on Medical Outcomes for Adult Patients with Bacteremic Pneumococcal Pneumonia

The impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia was evaluated in a retrospective cohort study conducted during population-based surveillance for invasive pneumococcal disease in the greater Atlanta region during 1994. Of the 192 study patients, 44 (23%) were infected with pneumococcal strains that demonstrated some degree of penicillin nonsusceptibility. Compared with patients infected with penicillin-susceptible pneumococcal strains, patients whose isolates were nonsusceptible had a significantly greater risk of in-hospital death due to pneumonia (relative risk [RR], 2.1; 95% confidence interval [CI], 1-4.3) and suppurative complications of infection (RR, 4.5; 95% CI, 1-19.3), although only risk of suppurative complications remained statistically significant after adjustment for baseline differences in severity of illness. Among adults with bacteremic pneumococcal pneumonia, infection with penicillin-nonsusceptible pneumococci is associated with an increased risk of adverse outcome.

Testing Strategies in the Initial Management of Patients with Community-Acquired Pneumonia

The clinician is faced with diagnostic and prognostic challenges in the initial management of patients with suspected community-acquired pneumonia. Each challenge corresponds to a specific management decision. The diagnostic question Does this patient have community-acquired pneumonia? corresponds to the decision on whether to treat with antimicrobial drugs. While other acute cough illnesses, such as acute exacerbations of chronic bronchitis and sinusitis, are antibiotic responsive, community-acquired pneumonia is the only acute respiratory tract infection in which delayed antibiotic therapy has been associated with increased risk for death (1). This emphasizes the importance of prompt, accurate diagnosis. The prognostic question Does this patient with community-acquired pneumonia have a high severity of illness? corresponds to decisions regarding the intensity of management. These decisions, including the need for parenteral therapy and supportive care, ultimately relate to the decision on whether to hospitalize the patient. Accordingly, we review the test characteristics of the history, physical examination, and laboratory findings in diagnosing community-acquired pneumonia and predicting short-term risk for death from the infection. We review the literature and summarize the test characteristics of individual diagnostic and prognostic factors, as well as groups of factors in diagnostic or prognostic rules. Finally, we consider the implications of these test characteristics from the perspective of decision thresholds that reflect the balance of the costs and harms of false-positive and false-negative information against the benefits of true-positive and true-negative information. This review does not consider the accuracy of clinical and laboratory findings in determining the cause of community-acquired pneumonia. Recent guidelines for the treatment of patients with community-acquired pneumonia summarize the limited value of testing to determine cause in many clinical settings and emphasize the importance of empirical guidelines to aid antibiotic selection, primarily on the basis of illness severity (2, 3). Methods This paper is expanded from two previous systematic reviews of the diagnosis (4) and prognosis (5) of community-acquired pneumonia (5). We updated our publication database by including updated search strategies from MEDLINE from January 1996 through December 2000 (search strategies available upon request) and reviewing the references from all retrieved new articles. Articles on the Diagnosis of Community-Acquired Pneumonia We emphasized studies with consecutive series of patients suspected of having pneumonia who had a chest radiograph regardless of the results of diagnostic testing and had it interpreted without knowledge of the other clinical findings (6). We excluded articles that did not report findings for patients with and without pneumonia. We excluded studies of children and inpatients and studies that did not obtain chest radiographs in all patients suspected of having community-acquired pneumonia. We abstracted the total number of persons studied and the number of true-positive, true-negative, false-positive, and false-negative results for each diagnostic test, using the results of chest radiography as the gold standard. Because of the heterogeneity in study designs, we did not pool data. Instead, we calculated positive and negative likelihoods for each finding in each study. We report the range of likelihood ratios only for findings that were statistically significantly (P < 0.05) associated with the presence or absence of pneumonia in two or more studies. Positive likelihood ratios equal the probability of a positive test result in patients with disease divided by the probability of a positive result in patients without disease. Negative likelihood ratios equal the probability of a negative test result in patients with disease divided by the probability of a negative result in patients without disease. Likelihood ratios represent the degree to which positive results raise the pretest probability of disease and negative results lower the pretest probability of disease. Likelihood ratios greater than 5 or less than 0.2 generate moderate to large shifts in disease probability; likelihood ratios of 2 to 5 and 0.5 to 0.2 generate small changes in probability; and likelihood ratios of 1 to 2 and 0.5 to 1 generate rarely important changes in probability (7). Articles on the Prognosis of Community-Acquired Pneumonia We included studies only if radiographic confirmation of pneumonia was an inclusion criterion. We excluded studies of nosocomial pneumonia, nursing homeacquired pneumonia, noninfectious pneumonia, pediatric pneumonia, and pneumonia in patients with HIV infection. The cause, treatment, and prognosis of these different types of pneumonia are substantially different from those in community-acquired pneumonia in adults. We also excluded articles with small case series (<25 participants), review articles without original data, and trials of antibiotic efficacy. Finally, we excluded articles that did not report the data in a form that permitted calculation of summary odds ratios (ORs) for the risk factors. We collected the number of deaths of patients with and without each factor, limiting ourselves to factors reported in at least two independent publications. We used summary ORs and their associated 95% CIs to quantify the risk for death associated with each prognostic factor, combining ORs by the MantelHaenszel method (8, 9). Diagnosis of Pneumonia Community-acquired pneumonia is defined as an acute infection of the lung parenchyma accompanied by symptoms of acute illness. Patients who acquire the infection in hospitals or long-term care facilities are typically excluded from the definition (2). The gold standard for diagnosing community-acquired pneumonia should be the identification of a microbiological pathogen isolated directly from the lung tissue. However, such a test (for example, lung puncture or biopsy) is rarely undertaken for the routine diagnosis of community-acquired pneumonia. An alternative gold standard could be based on a combination of clinical symptoms; radiographic, laboratory, and microbiological findings; and clinical response to antimicrobial therapy. However, in both clinical and research settings, isolated findings on chest radiography are often interpreted as the gold standard for the initial diagnosis of pneumonia even though chest radiography is neither 100% sensitive nor 100% specific for this condition. In terms of sensitivity, pneumonia can be present in the absence of an infiltrate on chest radiography at the time of diagnosis. However, the occurrence of this phenomenon has only limited support in the published literature. In an independent, blinded comparison of chest radiography with high-resolution computed tomography, chest radiography missed 8 of 26 (31%) cases of possible pneumonia that were identified on high-resolution computed tomography as any opacification or consolidation compatible with acute-phase lung involvement (10). While many of these missed cases had clinical and laboratory evidence of acute infection, it is not correct to assume that the sensitivity of chest radiography is as low as 69%, because these additional cases were not validated as true cases of community-acquired pneumonia based on microbiological evidence or response to antibiotic therapy. Dehydration may play an important role in the occurrence of pneumonia without findings on chest radiography (11), and a recent study suggests that patients with signs of dehydration on admission are more likely to have worsening chest radiographs over several days compared with patients without these signs (12). Thus, chest radiography is an imperfect gold standard test. The effect of these test characteristics on the decision to perform chest radiography depends on the pretest probabilities of the infection and the relative costs of over- and underdiagnosis of this infection. In the next section, we consider the effect of history and physical examination findings on the pretest probability of community-acquired pneumonia. Prevalence of Pneumonia in Patients The probability of pneumonia before the ordering of additional diagnostic testing depends on the clinical setting and the results of the medical history and physical examination. We examine the influence of each factor independently and then in combination. Clinical Setting The prevalence of pneumonia in patient populations presenting with acute respiratory illnesses varies substantially across study samples. In one study that examined consecutive patients with acute respiratory symptoms presenting to emergency departments and outpatient medical clinics, the prevalence of radiographically confirmed pneumonia was 7% (13). In a study examining patients with acute cough presenting to a military emergency department, the prevalence was only 2.6% (14). Recently, a prospective study of previously well adults (that is, no history of chronic lung or heart disease) with acute cough illness presenting to general practitioners in the United Kingdom found that 6% of patients met criteria for radiographic pneumonia (15). In contrast, in a recent study of patients presenting to a Veterans Affairs hospital with acute cough and change in sputum, 24 of 52 patients (46%) had chest radiographs consistent with pneumonia (16). However, this study included a nonconsecutive sample of predominately older male patients with underlying pulmonary and cardiac diseases. In our review of data from the National Ambulatory Medical Care Survey for 1980 to 1994, pneumonia was diagnosed in 4.7% of patients with acute cough who visited a primary care provider (17). Medical History Symptoms at presentation distinguish poorly between community-acquired pneumonia and other causes of respiratory illnesses. The likelihood ratio for these findings is typically close to 1.0 (

Sensitivity and specificity of patient self-report of influenza and pneumococcal polysaccharide vaccinations among elderly outpatients in diverse patient care strata

National surveys of adult vaccination indicate moderate self-reported immunization rates in the US, with limited validity data. We compared self-report with medical record abstraction for 820 persons aged > or =66 years from inner-city health centers, Veterans Affairs (VA) outpatient clinics, rural and suburban practices. For influenza vaccine, sensitivity was 98% (95% CI: 96-99%); specificity was 38% (95% CI: 33-43%). For pneumococcal polysaccharide vaccine, sensitivity was 85% (95% CI: 82-89%) and specificity was 46% (95% CI: 42-50%). The VA had the highest sensitivity and lowest specificity for both vaccines while the converse was true in inner-city centers. High negative predictive values indicate that clinicians can confidently vaccinate based on negative patient self-report.

Progression to Traditional Cigarette Smoking After Electronic Cigarette Use Among US Adolescents and Young Adults

IMPORTANCE Electronic cigarettes (e-cigarettes) may help smokers reduce the use of traditional combustible cigarettes. However, adolescents and young adults who have never smoked traditional cigarettes are now using e-cigarettes, and these individuals may be at risk for subsequent progression to traditional cigarette smoking. OBJECTIVE To determine whether baseline use of e-cigarettes among nonsmoking and nonsusceptible adolescents and young adults is associated with subsequent progression along an established trajectory to traditional cigarette smoking. DESIGN, SETTING, AND PARTICIPANTS In this longitudinal cohort study, a national US sample of 694 participants aged 16 to 26 years who were never cigarette smokers and were attitudinally nonsusceptible to smoking cigarettes completed baseline surveys from October 1, 2012, to May 1, 2014, regarding smoking in 2012-2013. They were reassessed 1 year later. Analysis was conducted from July 1, 2014, to March 1, 2015. Multinomial logistic regression was used to assess the independent association between baseline e-cigarette use and cigarette smoking, controlling for sex, age, race/ethnicity, maternal educational level, sensation-seeking tendency, parental cigarette smoking, and cigarette smoking among friends. Sensitivity analyses were performed, with varying approaches to missing data and recanting. EXPOSURES Use of e-cigarettes at baseline. MAIN OUTCOMES AND MEASURES Progression to cigarette smoking, defined using 3 specific states along a trajectory: nonsusceptible nonsmokers, susceptible nonsmokers, and smokers. Individuals who could not rule out smoking in the future were defined as susceptible. RESULTS Among the 694 respondents, 374 (53.9%) were female and 531 (76.5%) were non-Hispanic white. At baseline, 16 participants (2.3%) used e-cigarettes. Over the 1-year follow-up, 11 of 16 e-cigarette users and 128 of 678 of those who had not used e-cigarettes (18.9%) progressed toward cigarette smoking. In the primary fully adjusted models, baseline e-cigarette use was independently associated with progression to smoking (adjusted odds ratio [AOR], 8.3; 95% CI, 1.2-58.6) and to susceptibility among nonsmokers (AOR, 8.5; 95% CI, 1.3-57.2). Sensitivity analyses showed consistent results in the level of significance and slightly larger magnitude of AORs. CONCLUSIONS AND RELEVANCE In this national sample of US adolescents and young adults, use of e-cigarettes at baseline was associated with progression to traditional cigarette smoking. These findings support regulations to limit sales and decrease the appeal of e-cigarettes to adolescents and young adults.

What affects influenza vaccination rates among older patients? An analysis from inner-city, suburban, rural, and veterans affairs practices

BACKGROUND Despite strong evidence of the effectiveness of influenza vaccination, immunization rates have reached a plateau that is below the 2010 national goals. Our objective was to identify facilitators of, and barriers to, vaccination in diverse groups of older patients. METHODS A survey was conducted in 2000 by computer-assisted telephone interviewing of patients from inner-city health centers, Veterans Affairs (VA) outpatient clinics, rural practices, and suburban practices. The inclusion criteria were age > or =66 years and an office visit after September 30, 1998. RESULTS Overall, 1007 (73%) interviews were completed among 1383 patients. Influenza vaccination rates were 91% at VA clinics, 79% at rural practices, 79% at suburban practices, and 67% at inner-city health centers. There was substantial variability in vaccination rates among practices, except at the VA. Nearly all persons who were vaccinated reported that their physicians recommended influenza vaccinations, compared with 63% of unvaccinated patients (P <0.001). Thirty-eight percent of unvaccinated patients were concerned that they would get influenza from the vaccine, compared with only 6% of vaccinated persons (P <0.001). Sixty-three percent of those vaccinated, in contrast with 22% of unvaccinated persons, thought that an unvaccinated person would probably contract influenza (P <0.001). CONCLUSION Older patients need intentional messages from physicians that recommend vaccination. Furthermore, more patient education is needed to counter myths about adverse reactions.