Steven I. Aronin

Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing.

Despite advances in antibiotic therapy, bacterial meningitis continues to cause significant morbidity and mortality [1]. Rapid diagnosis and therapy are the cornerstones of management, but patient presentation and clinical outcomes vary. Whether clinical outcomes are influenced more by disease severity or delay in initiation of antibiotic therapy remains a problematic and litigious issue [2-4]. Accurate prognostic stratification at presentation facilitates interpretation of individual treatment results and of benefits of therapeutic interventions in clinical trials. Unfortunately, methodologic limitations of existing studies prevented the development of a clinically useful prognostic model for persons with bacterial meningitis [1, 5-26]. To create a prognostic model and risk stratification system, we conducted a retrospective, observational cohort study of persons with community-acquired, microbiologically proven bacterial meningitis. Methods Patients were identified through review of medical records and microbiology laboratories at four Connecticut hospitals. To develop and test the prognostic model, we divided patients in the total cohort into derivation and validation cohorts. The derivation cohort (n = 176) was assembled from persons at least 16 years of age in whom community-acquired bacterial meningitis was diagnosed at the two hospitals serving New Haven, Connecticut (Yale-New Haven Hospital and Hospital of Saint Raphael), from January 1970 through December 1995. The validation cohort (n = 93) was assembled similarly during the same period for patients given a diagnosis at the two hospitals serving a separate geographic location in Waterbury, Connecticut (Waterbury Hospital Health Center and St. Marys Hospital). Patients with community-acquired meningitis (initial lumbar puncture done within 24 hours of presentation in the emergency department) and a microbiologically identified bacterial cause were included. Bacterial meningitis was diagnosed on the basis of a compatible clinical picture and a positive cerebrospinal fluid culture [n = 226] or a negative cerebrospinal fluid culture with one or more of the following: 1) a positive result on a cerebrospinal fluid bacterial antigen or Quellung test [n = 10], 2) a positive blood culture in the presence of cerebrospinal fluid pleocytosis (defined as a leukocyte count 10 cells/mL of cerebrospinal fluid) [n = 39], or 3) identification of gram-negative diplococci after Gram staining of cerebrospinal fluid (n = 7). Patients with meningitis caused by Mycobacterium species, Treponema pallidum, or Borrelia burgdorferi and patients with intracranial devices were excluded. For patients who had multiple episodes of meningitis during the study period, only the first episode was analyzed. From medical records, we extracted information on sociodemographic data, comorbid conditions, immunocompetence, exposures, presenting symptoms, physical signs, laboratory and cranial imaging results, and clinical outcome. Precise times were recorded for arrival in the emergency department, administration of the first dose of effective antibiotics (defined as antibiotic therapy to which the identified bacteria were susceptible in vitro), and performance of lumbar puncture. Baseline characteristics were assessed at a specified zero time, defined as the time at which the first dose of effective antibiotics was administered. Comorbidity was assessed by using the Charlson comorbidity scale [27]. For the derivation cohort, bivariate analyses were done with the presence or absence of an adverse clinical outcome (defined as neurologic deficit at discharge or death during hospitalization) as the target end point. All patient episodes were followed from admission date to discharge or death. Baseline characteristics associated with adverse clinical outcome in the bivariate analyses were analyzed in a multivariable context by using multiple logistic regression modeling. Using these independently prognostic baseline variables, we developed a prognostic model that stratified patients into three levels of risk (low, intermediate, and high) for adverse clinical outcome. The prediction accuracy of the prognostic model was assessed in both the derivation and validation cohorts. The effect of antibiotic timing was evaluated for the total cohort and was analyzed for episodes in which the patient remained in the same prognostic stage as well as those in which the patients prognostic stage advanced from the time of arrival in the emergency department to the time of initiation of antibiotic therapy. Differences in proportions were tested by using the chi-square test or the Fisher exact test. For contrasts of dimensional variables, the Student t-test and the Wilcoxon rank-sum test were used. We used multiple logistic regression given the binary target outcome. To avoid overfitting, we entered no more than one variable per 10 outcome events in our logistic regression models [28-30]. The goodness of fit of the final model was examined by using the Hosmer-Lemeshow test. Prediction accuracy was calculated by using the concordance index (c-index) [31]. Results Cohort Assembly A total of 269 persons with community-acquired, microbiologically proven bacterial meningitis were identified at the four hospitals [176 patients in the derivation cohort and 93 patients in the validation cohort]. After initial screening of 1024 medical records, 755 episodes were excluded for the following reasons: 1) lumbar puncture was never done [n = 155], 2) lumbar puncture was done more than 24 hours after presentation [n = 185], 3) an incorrect International Classification of Diseases, Ninth Revision, diagnosis code was applied [n = 10], 4) the case definition was not fulfilled [n = 317], 5) the medical record was incomplete [n = 80], or 6) the patients meningitis episode was not the first episode in the study period (n = 8). Baseline Features and Microbial Causes Baseline patient characteristics, laboratory results, and microbial causes are shown in Table 1. The derivation and validation cohorts were similar with respect to age, sex, ethnicity, and baseline laboratory features. Baseline clinical features were also similar, but significantly more patients in the derivation cohort than in the validation cohort were immunocompromised (P = 0.03) and had focal neurologic examinations (P = 0.03). For the total cohort, fever and abnormal mental status were the most common presenting clinical features. Streptococcus pneumoniae caused nearly 50% of all cases, and Neisseria meningitidis, other streptococci, Staphylococcus aureus, and Listeria monocytogenes caused most of the remaining cases. The derivation cohort had a greater proportion of patients whose meningitis was caused by Staphylococcus aureus than did the validation cohort (P = 0.02). Table 1. Patient Characteristics, Laboratory Results, and Clinical Outcome Clinical Outcome The clinical outcome for all patients is shown in Table 1. The hospital mortality rate for the total cohort was 27%, and the median number of hospital days before death was 6 (range, 0 to 65). Of the 269 patients, 56 (28% of survivors; 21% of the total cohort) had a neurologic deficit and 25 (13% of survivors; 9% of the total cohort) had a neurologic deficit that persisted at discharge. The most common persisting neurologic deficit in the total cohort was hearing loss. Clinical outcome for the total cohort did not differ significantly when analyzed by time period (P > 0.2 when adverse outcome were compared between 5-year intervals). However, episodes of Streptococcus pneumoniae meningitis in the total cohort were associated with a greater proportion of adverse clinical outcomes than were episodes that were not caused by Streptococcus pneumoniae (P = 0.005). Bivariate analyses relating baseline characteristics to adverse clinical outcome in the derivation cohort are shown in Table 2 and Table 3. Hypotension (defined as systolic blood pressure 90 mm Hg or a 40 mm Hg decrease in systolic blood pressure), altered mental status (defined as lethargy, disorientation, or coma), seizures, and age all showed a bivariate association with adverse clinical outcome. To determine independent relations with adverse clinical outcome, these variables were entered into a logistic regression model with three other variables that had a biologically plausible relation to clinical outcome (immunocompetence, comorbidity, and leukocyte count in cerebrospinal fluid). In this model, only hypotension (adjusted odds ratio, 2.75 [95% CI, 1.22 to 6.18]; P < 0.001), altered mental status (adjusted odds ratio, 6.56 [CI, 1.71 to 25.2]; P = 0.006), and seizures (adjusted odds ratio, 4.42 [CI, 1.56 to 12.48]; P = 0.005) remained independently associated with adverse clinical outcome after adjustment for age, comorbidity, immunocompetence, and leukocyte count in cerebrospinal fluid. Table 2. Bivariate Association of Baseline Dichotomous Variables and Adverse Clinical Outcome for the Derivation Cohort (n = 176) Table 3. Bivariate Association of Baseline Dimensional Variables and Adverse Clinical Outcome for the Derivation Cohort (n = 176)* Development and Validation of the Prognostic Model Using the three independently predictive baseline variables from the logistic regression model (hypotension, altered mental status, and seizures), we created prognostic stages by stratifying patients who had 0, 1, and at least 2 of the variables into low-, intermediate-, and high-risk subgroups, respectively (Table 4). For the derivation cohort, the observed proportions of patients with adverse clinical outcome were 5% in stage I (low risk), 37% in stage II (intermediate risk), and 63% in stage III (high risk) (P = 0.001). For the validation cohort, the observed proportions of patients with adverse clinical outcome were 14% in stage I, 28% in stage II, and 43% in stage III (P = 0.06). The predicted probabilities of the model for each stage closely match the observ

Review of pneumococcal endocarditis in adults in the penicillin era.

Streptococcus pneumoniae is an infrequent cause of infectious endocarditis in adults. In the past 2 years, however, we have encountered several cases at our institution, and additional cases have been reported in the literature. This infection typically follows pneumonia in the setting of chronic alcoholism and may additionally be complicated by meningitis. Less commonly, pneumococcal endocarditis occurs in other hosts or follows primary infection at other extrapulmonary sites. In such cases, the diagnosis may be initially missed, with a resultant delay in institution of appropriate therapy. Moreover, there are controversies regarding the optimal therapy for infections of this nature in the era of penicillin resistance. Since a comprehensive review of this topic has not been published since 1990, we reviewed cases of pneumococcal endocarditis in the penicillin era, with particular attention to disease recognition, the role of echocardiography, and the dilemmas surrounding medical and surgical therapeutic interventions.

Community-Acquired Bacterial Meningitis in Adults: Categorization of Causes and Timing of Death

The relationship between cause and timing of death in 294 adults who had been hospitalized with community-acquired bacterial meningitis was investigated. For 74 patients with community-acquired bacterial meningitis who died during hospitalization, the underlying and immediate causes of death were identified according to the criteria of the World Health Organization and National Center for Health Statistics. Patients were classified into 3 groups: category I, in which meningitis was the underlying and immediate cause of death (59% of patients; median duration of survival, 5 days); category II, in which meningitis was the underlying but not immediate cause of death (18%; median duration of survival, 10 days); and category III, in which meningitis was neither the underlying nor immediate cause of death (23%; median duration of survival, 32 days). In a substantial proportion of adults hospitalized with community-acquired bacterial meningitis, meningitis was neither the immediate nor the underlying cause of death. A 14-day survival end point discriminated between deaths attributable to meningitis and those with another cause.

Adherence to Standard of Care in the Diagnosis and Treatment of Suspected Bacterial Meningitis

Acute bacterial meningitis (ABM) is a rare but deadly neurological emergency. Accordingly, Infectious Diseases Society of America (IDSA) guidelines summarize current evidence into a straightforward algorithm for its management. The goal of this study is to evaluate the overall compliance with these guidelines in patients with suspected ABM. A retrospective cross-sectional study was conducted of adult patients who underwent lumbar puncture for suspected ABM to ascertain local adherence patterns to IDSA guidelines for bacterial meningitis. Primary outcomes included appropriate utilization of neuroimaging, blood cultures, antibiotics, corticosteroids, and lumbar puncture. In all, 160 patients were included in the study. Overall IDSA compliance was only 0.6%. Neuroimaging and blood cultures were appropriately utilized in 54.3% and 47.5% of patients, respectively. Steroids and antibiotics were appropriately administered in only 7.5% and 5.6% of patients, respectively. Adherence to IDSA guidelines is poor. Antibiotic choice is often incorrect, corticosteroids are rarely administered, and there is an overutilization of neuroimaging.

New perspectives on pneumococcal meningitis.

Streptococcus pneumoniae remains the leading cause of bacterial meningitis. While a new vaccine against this organism is now available, its impact on disease is not yet known. Strategies to guide the evaluation of patients and the treatment of antibiotic-resistant strains can help to improve outcomes in this dangerous disease.

An Overview of Infections Associated With Soft Tissue Facial Fillers: Identification, Prevention, and Treatment

PURPOSE The purpose of this study was to provide an overview of infections associated with facial soft tissue fillers. MATERIALS AND METHODS A literature review was performed which evaluated infections associated with facial soft tissue fillers. RESULTS Infection rates with soft tissue fillers are low and are estimated at 0.04 to 0.2%. Most of these infections arise when skin contaminants infiltrate the injection site at the time of injection. These infections can occur early, up to several days after treatment, or delayed, occurring weeks to years after treatment. Reactions vary based on the filler absorbability and duration. Early recognition and treatment are important factors in managing our cosmetic surgery patients. CONCLUSION Although facial fillers are safe and predictable, infections can still occur. Oral and maxillofacial surgeons need to be able to prevent, recognize, and properly manage infections related to these popular injections.

A depiction of imported malaria in Connecticut

In 2010, there were roughly 219 million cases of malaria reported worldwide resulting in an estimated 660,600 deaths [1]. In contrast, the total number of cases according to the Centers for Disease Control and Prevention (CDC) in the United States (USA) was only 1691 [2]. Of those, 1688 were cases of imported malaria [2]. This is the highest number of cases reported in U.S. since 1980 [2]. Here, we describe a case of imported malaria and conduct a retrospective case series at four Connecticut (CT) hospitals in order to describe the demographics of imported malaria and to identify potential barriers to timely diagnosis and treatment.