When Ventricular Cerebrospinal Fluid Assessment Misleads: Basal Meningitis and the Importance of Lumbar Puncture Sampling.

The diagnosis of central nervous system (CNS) infection relies upon analysis of cerebrospinal fluid (CSF). We present 4 cases of CNS infections associated with basal meningitis and hydrocephalus with normal ventricular CSF but grossly abnormal lumbar CSF. We discuss CSF ventricular-lumbar composition gradients and putative pathophysiological mechanisms and highlight clinical clues for clinicians.

Detection of (1,3)-ß-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis.

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-ß-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis.

Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid.

Background: Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis. Methods: Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics. Results: A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases. Conclusions: Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis.

Adverse effects of isoniazid preventative therapy for latent tuberculosis infection: a prospective cohort study.

INTRODUCTION: Isoniazid preventative therapy (IPT) is a widely used intervention for treatment of latent tuberculosis infection (LTBI), particularly in patients at high risk for reactivation. While treatment-limiting adverse effects have been well studied, few prospective studies have considered the range of adverse effects that patients may experience with IPT. METHODS: All patients commencing treatment for LTBI were prospectively enrolled in an ongoing database of LTBI treatment outcomes particularly related to adverse effects, treatment adherence, and treatment completion. RESULTS: Data on the first 100 patients who were prescribed IPT are presented. Fifty-six patients reported at least one adverse effect at some stage during treatment, with six experiencing at least one World Health Organization (WHO) Grade 3-4 adverse effect. Increased age was significantly associated with risk of adverse effects (odds ratio [OR] =1.05 per year; confidence interval [CI] of 1.02-1.08=95%). Eighty-five patients had documented completion of therapy locally, with ten patients ceasing IPT due to adverse effects. DISCUSSION: This report highlights a variety of somatic adverse effects that occurred in a real-world cohort of patients receiving IPT. While adverse effects were frequently identified in this study, the considerable majority were low grade and transient. Despite frequent adverse effects of LTBI in our treatment cohort, the study demonstrated high levels of treatment adherence and completion.

Multiple site surveillance cultures as a predictor of methicillin-resistant Staphylococcus aureus infections.

OBJECTIVE: To determine the relationship between methicillin-resistant Staphylococcus aureus (MRSA) colonization density, colonization site, and probability of infection in a frequently screened cohort of intensive care unit (ICU) patients. METHODS: Patients had swab samples tested for MRSA at admission to the ICU, discharge from the ICU, and twice weekly during their ICU stay, and they were followed up for development of MRSA infection. Swab test results were analyzed to determine the proportion of patients colonized and the proportion colonized at each screening site. Hazard of MRSA infection (rate of infection per day at risk) was calculated using a Cox proportional hazards analysis, and risk factors for MRSA infection, including presence of MRSA, degree of colonization, and pattern of colonization were determined. RESULTS: Among the 4,194 patient episodes, 238 (5.7%) had screening results that were positive for MRSA, and there were 34 cases of MRSA infection. The hazard ratio (HR) for developing an infection increased as more sites were colonized (HR, 3.4 for being colonized at more than 1 site compared with colonization at 1 site [95% confidence interval, 1.2-9.9]). Colonization site was predictive of developing infection (HR for nose or throat colonization compared with no colonization, 168 [95% confidence interval, 69-407]). CONCLUSION: This study demonstrated that the hazard of developing an infection was higher when more sites were colonized and that certain sites were more predictive of infection than others. These results may be useful for predicting infection in ICU patients and may influence treatment.

The limitations of polymerase chain reaction in the setting of possible recurrent tuberculosis: 2 instructional cases.

The interpretation of a positive result for Mycobacterium tuberculosis by nucleic acid amplification such as polymerase chain reaction (PCR) can be challenging. We present 2 cases that illustrate the limitations of tuberculosis PCR on respiratory secretions in previously treated patients, even years after the previous disease episode.

Reduced valve replacement surgery and complication rate in Staphylococcus aureus endocarditis patients receiving acetyl-salicylic acid.

OBJECTIVES: To assess the influence of acetyl-salicylic acid (ASA) on clinical outcomes in Staphylococcus aureus infective endocarditis (SA-IE). METHODS: The International Collaboration on Endocarditis - Prospective Cohort Study database was used in this observational study. Multivariable analysis of the SA-IE cohort compared outcomes in patients with and without ASA use, adjusting for other predictive variables, including: age, diabetes, hemodialysis, cancer, pacemaker, intracardiac defibrillator and methicillin resistance. RESULTS: Data were analysed from 670 patients, 132 of whom were taking ASA at the time of SA-IE diagnosis. On multivariable analysis, ASA usage was associated with a significantly decreased overall rate of acute valve replacement surgery (OR 0.58 [95% CI 0.35-0.97]; p<0.04), particularly where valvular regurgitation, congestive heart failure or periannular abscess was the indication for such surgery (OR 0.46 [0.25-0.86]; p<0.02). There was no reduction in the overall rates of clinically apparent embolism with prior ASA usage, and no increase in hemorrhagic strokes in ASA-treated patients. CONCLUSIONS: In this multinational prospective observational cohort, recent ASA usage was associated with a reduced occurrence of acute valve replacement surgery in SA-IE patients. Future investigations should focus on ASA's prophylactic and therapeutic use in high-risk and newly diagnosed patients with SA bacteremia and SA-IE, respectively.

Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone?--A time series analysis.

BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.

Tumour necrosis factor alpha inhibitors: screening for tuberculosis infection in inflammatory bowel disease.

Tumour necrosis factor (TNF) alpha inhibitors such as infliximab are becoming more widely used for the treatment of selected patients with Crohn's disease, rheumatoid arthritis, and other inflammatory disorders. TNFalpha inhibitors increase the risk of serious infections, including tuberculosis. Screening for and treatment of latent tuberculosis infection before infliximab therapy reduces the risk of developing active tuberculosis. New blood tests that measure interferon gamma production are an alternative to traditional tuberculin skin testing and offer some significant advantages over skin testing for screening of latent tuberculosis infection.

Identifying severe community-acquired pneumonia in the emergency department: a simple clinical prediction tool.

OBJECTIVE: To identify independent predictors of severe pneumonia in a local population, and create a simple severity score that would be useful in the ED. METHODS: Data on the clinical features of patients presenting to hospital with community-acquired pneumonia were collected. Multivariate logistic regression was used to identify independent predictors of death, requirement for ventilatory or inotropic support, and these combined. These predictors were used to modify an existing severity score, and its performance was tested in a second cohort of patients. RESULTS: A total of 392 patients in the derivation, and 330 in the validation cohorts. Independent predictors of 'death and/or requirement for ventilatory or inotropic support' were: systolic blood pressure (BP) <90 mmHg (OR 3.49 [95% CI 1.12-10.38]); acute confusion (OR 5.48 [95% CI 2.74-10.99]); oxygen saturations < or =90% (OR 3.49 [95% CI 1.77-6.89]); and respiratory rate > or =30/min (OR 2.65 [95% CI 1.35-5.21]). Age >65 years was not an independent predictor in this patient group (OR 0.52 [95% CI 0.23-1.16]). This information was used to propose that severe pneumonia could be predicted by two or more of: acute confusion; oxygen saturations < or =90%; respiratory rate > or =30/min; and either systolic BP <90 mmHg; or diastolic BP < or =60 mmHg. In a separate cohort, the performance of this score was similar to other tools. CONCLUSION: This provides a practical tool that can be used to 'flag' impending patient demise. Its advantages are that it is simple, uses predictive variables, does not require invasive testing, and removes bias regarding patient age. Like other tools, its accuracy is not perfect, and it should only be used to augment clinical judgement.

Reduction of broad-spectrum antibiotic use with computerized decision support in an intensive care unit.

OBJECTIVE: To implement and evaluate the effect of a computerized decision support tool on antibiotic use in an intensive care unit (ICU). DESIGN: Prospective before-and-after cohort study. SETTING: Twenty-four bed tertiary hospital adult medical/surgical ICU. PARTICIPANTS: All consecutive patients from May 2001 to November 2001 (N = 524) and March 2002 to September 2002 (N = 536). INTERVENTION: A real-time microbiology browser and computerized decision support system for isolate directed antibiotic prescription. MAIN OUTCOME MEASURES: Number of courses of antibiotic prescribed, antibiotic utilization (defined daily doses (DDDs)/100 ICU bed-days), antibiotic susceptibility mismatches, and system uptake. RESULTS: There was a significant reduction in the proportion of patients prescribed carbapenems [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.39-0.97, P = 0.04], third-generation cephalosporins (OR = 0.58, 95% CI = 0.42-0.79, P = 0.001), and vancomycin (OR = 0.67, 95% CI = 0.45-1.00, P = 0.05) after adjustment for risk factors including Apache II score, suspected infection, positive microbiology, intubation, and length of stay. The decision support tool was associated with a 10.5% reduction in both total antibiotic utilization (166-149 DDDs/100 ICU bed days) and the highest volume broad-spectrum antibiotics. There were fewer susceptibility mismatches for initial antibiotic therapy (OR = 0.63, 95% CI = 0.39-0.98, P = 0.02) and increased de-escalation to narrower spectrum antibiotics. Uptake of the program was high with 6028 access episodes during the 6-month evaluation period. CONCLUSIONS: This tool streamlined collation and clinical use of microbiology results and integrated into the daily ICU workflow. Its introduction was accompanied by a reduction in both total and broad-spectrum antibiotic use and an increase in the number of switches to narrower spectrum antibiotics.

Clostridium septicum bacteremia without gas gangrene as a late consequence of a contaminated wound.

BACKGROUND: Clostridium septicum is an unusual human pathogen associated with colorectal malignancy and gas gangrene. METHODS: A case compilation and literature review are presented. RESULTS: We report the case of an individual with a comminuted tibial fracture complicated by a superficial surgical site infection with C. septicum nine weeks after the original injury and internal fixation, which was complicated by a secondary bacteremia. CONCLUSIONS: This is a unique case in the literature, but it is suggested that the use of cephalosporins as prophylaxis for contaminated wounds may be inferior to penicillins to prevent clostridial infections.

The molecular epidemiology of HIV type 1 among Vietnamese Australian injecting drug users in Melbourne, Australia.

The proportion of human immunodeficiency virus type 1 (HIV-1) among Vietnamese injecting drug users (IDUs) in Melbourne, Australia exceeds that of the background population. To investigate the molecular epidemiology of HIV-1 among this group, the C2-V4 region of the HIV-1 envelope was directly sequenced from 11 Vietnamese Australians and 19 non-Vietnamese Australian controls. A significant difference in the distribution of the HIV-1 subtypes was demonstrated, with greater than 50% of Vietnamese Australian IDU shown to be infected with CRF01_AE-the predominant subtype in Southeast Asia, rather than subtype B, which dominates the Australian epidemic and which was found in 89.5% of the non-Vietnamese controls. The genetic diversity of the CRF01_AE epidemic in Vietnamese Australian IDUs was substantially lower that that of the background subtype B, consistent with a more recent introduction of a limited number of viral strains from Vietnam. These results support public health policy targeting Australian IDUs of Vietnamese ethnicity as a distinct vulnerable population.

HIV, ethnicity and travel: HIV infection in Vietnamese Australians associated with injecting drug use.

BACKGROUND: The movement of people with their constructed identities including ethnicity has always been one of the determinants of the human immunodeficiency virus (HIV) pandemic. An example of the contributions of travel and ethnicity to experiences of HIV can be seen in the Vietnamese community in Australia. OBJECTIVES: This paper seeks to describe the contributions of ethnicity and travel to the Australian HIV epidemic with particular reference to the evolving epidemic within the Vietnamese Australian community. STUDY DESIGN: We reviewed the available data on the HIV epidemic in Australia with reference to overseas acquisition, ethnicity, the epidemic in the Vietnamese community and the determinants of the current patterns of transmission within this community. RESULTS: Available data suggests that 20-25% of HIV infections notified in Australia are acquired overseas. This proportion is higher in some specific categories such as heterosexually acquired infections. Notification rates are no higher in Vietnamese Australians than in the general Australian population apart from infections associated with injecting drug use (IDU) notified in the state of Victoria. The reasons for this increased rate of notification include increased vulnerability to blood borne virus infection in Australia and the additional, unique risk of frequent travel to Vietnam, a country where IDU carries a high risk of HIV infection. CONCLUSIONS: Australia has succeeded in stabilising the HIV epidemic partly through successful interventions to limit the spread of infection among IDUs. There is now early evidence that HIV transmission may be increasing amongst Vietnamese Australian IDUs. Timely responses that help Vietnamese Australian IDUs reduce their accumulation of risk are likely to be important in determining the level of harm associated with IDU throughout Australia.