Christian N. Meyer

Antibiotic treatment delay and outcome in acute bacterial meningitis

OBJECTIVES To identify to what degree in-hospital delay of antibiotic therapy correlated to outcome in community acquired bacterial meningitis. METHODS All cases of culture-positive cerebrospinal fluids in east Denmark from 2002 to 2004 were included. Medical records were collected retrospectively with 98.4% case completeness. Glasgow Outcome Scale was used. Multiple regression outcome analyses included the hypothesised factors: delay of therapy, age, bacterial aetiology, adjuvant steroid therapy, coma at admission and the presence of risk factors. RESULTS One hundred and eighty seven cases were included. Adult mortality was 33% and the proportion of unfavourable outcome in adults was 52%, which differed significantly from that of children (<18 years) with a mortality of 3% (OR=15.8, 95% confidence interval: 3.7-67.6) and an unfavourable outcome of 14% (OR=12.7, CI: 4.3-37.2). Delay of antibiotic therapy correlated independently to unfavourable outcome (OR=1.09/h, CI: 1.01-1.19) among the 125 adult cases. In the group of adults receiving adequate antibiotic therapy within 12h (n=109), the independent correlation between antibiotic delay and unfavourable outcome was even more prominent (OR=1.30/h, CI: 1.08-1.57). The median delay to the first dose of adequate antibiotics was 1h and 39min (1h and 14min in children vs. 2h in adults, p<0.01), and treatment delay exceeded 2h in 21-37% of the cases with clinically evident meningitis. CONCLUSION The delay in antibiotic therapy correlated independently to unfavourable outcome. The odds for unfavourable outcome may increase by up to 30% per hour of treatment delay.

Bacteremia in HIV-positive and AIDS patients : incidence, species distribution, risk-factors, outcome, and influence of long-term prophylactic antibiotic treatment

From a cohort of 837 adult, mainly homosexual HIV-infected patients, 76 bacteremic/fungemic episodes were identified in 63 patients over a 5-year period. Compared with an age-matched reference population with an incidence of 10.3 bacteremias/10,000 person-years, the incidence was 170 among pre-AIDS (p < 0.001) and 3,200 among AIDS patients (p < 0.001). Staphylococcal infections comprised 35% of all episodes, while the HIV-related pathogens Streptococcus pneumoniae, Salmonella spp. and C. neoformans together accounted for 34%. The overall mortality associated with clinical bacteremia was 12%, but nil for Salmonella spp. and S. pneumoniae. Predisposing factors for the infection were: low CD4 count (< 100 x 10(6)/l) in 71%, permanent intravenous line, 44%; neutropenia, 11% and active intravenous drug abuse, 7%. Hence, in this population, intensified hygienic precautions for intravenous lines should be the primary target for intervention. Long-term cotrimoxazole prophylaxis may prevent bacteremia with S. pneumoniae and Salmonella spp.

Bacteriological aetiology and antimicrobial treatment of pleural empyema.

Abstract Background: Our aims were to describe the aetiologies of culture-positive pleural infections and to evaluate the choice of empiric antimicrobial treatment regimens according to antimicrobial sensitivity, and to evaluate the possible influence of this on outcome. Methods: All cases over a 9-y period were identified from 3 hospitals using the laboratory databases of the clinical microbiology departments, and were verified by evaluating the medical records. Results: We identified 291 isolates in pleural fluid cultures from 158 patients. These included viridans streptococci (25%), Staphylococcus aureus (18%), anaerobic bacteria (17%), Enterobacteriaceae (12%), Staphylococcus epidermidis (10%), and Streptococcus pneumoniae (7%), with differences between nosocomial and community-acquired infections. The mortality (overall 27%) was highest among the patients with Enterobacteriaceae (50%) and S. aureus (36%) infections, and in patients with mixed infections (34%). The actual empiric treatment or the recommended penicillin plus metronidazole had low antimicrobial coverage (49%) compared to the proposed cefuroxime plus metronidazole (78%). Thoracentesis was often delayed (median 2 days). The adequacy of empiric antimicrobial therapy was independently correlated with mortality (odds ratio 0.43, 95% confidence interval 0.30–0.62). Conclusions: The early diagnosis of pleural infection could be optimized. In this North-European patient population, we suggest that the recommended empiric antimicrobial treatment be changed to cefuroxime plus metronidazole for community-acquired and nosocomial infections.

Adjunctive steroid treatment: Local guidelines and patient outcome in adult bacterial meningitis

Our objective was to evaluate local guidelines regarding early steroid treatment in adult community acquired bacterial meningitis, and assess the actual treatment given and its correlation to clinical outcome. Patient outcome was obtained retrospectively from the medical records of 210 adults admitted to 47 hospitals in Denmark during 2002–2004 (population 5.4 million) and was combined with results from a questionnaire regarding treatment guidelines in these hospitals. In 36 of 47 departments responding to the questionnaire, 21 recommended early steroid treatment, but none did so initially during 2002. Early steroid treatment was given to 15% of patients and was given more often when recommended locally (41% vs 11%, OR =5.7 (2.4–13.5)). Unfavourable outcome was demonstrated rarely in patients treated with early steroids compared to the non-steroid group (17% vs 42%, p<0.05). In the 32 cases with petechial skin lesions, these were caused by pneumococci (15), meningococci (15), Staphylococcus aureus (1) and enterococci (1), and thus the presence of such lesions should not make the clinician abstain from early steroid treatment of bacterial meningitis. In conclusion, concordance with the new consensus of early steroid treatment was poor on a national basis, and better (41%) when adequate local guidelines were available. Early steroid treatment was associated with favourable outcome, and improved implementation of adequate guidelines may contribute to better patient outcome in bacterial meningitis.

Outcome and clinical characteristics in pleural empyema: A retrospective study

Abstract Background: Pleural empyema is a serious condition with a considerable mortality rate and morbidity. This study evaluated the correlations between several potential prognostic factors (age, predisposing diseases, early drainage, insufficient initial antimicrobial therapy, thoracic surgical treatment, intrapleural fibrinolysis, and nosocomial status) and outcome. Methods: Danish patients with positive pleural cultures attending 3 hospitals over a 9-y period, were identified in the laboratory databases. Clinical details and outcome were evaluated retrospectively by audit of the medical records. Results: We included 158 patients in this study. The overall mortality was 27% and the median length of stay was 29 days. Mortality correlated independently with several factors: nosocomial infection (odds ratio (OR) 2.62, 95% confidence interval (CI) 1.71–4.16), predisposing conditions (OR 2.17, 95% CI 1.50–3.14), and also with the possibly interventional factors of sufficient initial antimicrobial therapy (OR 0.45, 95% CI 0.31–0.65), thoracic surgery treatment (OR 0.27, 95% CI 0.14–0.52) and local fibrinolytic therapy (OR 0.13, 95% CI 0.06–0.28). Delay in chest tube drainage more than 2 days was not independently correlated with mortality. The initial biochemical diagnostics of non-purulent pleural effusions (63%) did not follow the current international guidelines. Conclusion: Factors correlating independently with survival included the possible interventional parameters of fibrinolytic therapy, insufficient initial antimicrobial therapy, and having thoracic surgery treatment.

Use of tiotropium Respimat versus HandiHaler and mortality in patients with COPD

To the Editor: Verhamme et al. [1] recently compared the possible mortality effect of two delivery systems of tiotropium in their Dutch observational cohort study of 11 287 chronic obstructive pulmonary disease (COPD) first-time users of tiotropium in primary care. They concluded that “until further data become available, physicians should be aware that patients with arrhythmia or a history of cardiovascular disease might be particularly at risk” when using tiotropium Respimat [1]. Although arrhythmia, renal disease and certain cardiac diseases are relative contraindications of tiotropium and, clinically, it may be important to consider whether an increased mortality risk in such patients with these relatively contraindicative comorbidities overrides the additional well-being of the bronchodilatation effect of tiotropium therapy. The evidence on this question is sparse or not available; thus independent randomised trials may be needed. Several publications have considered the pro-arrhythmogenic character and possible detrimental dose-dependent effects of anticholinergics in COPD patients with co-incident cardiac disease or renal disease (assigned to decreased drug excretion). A recent publication found that a large proportion of real life COPD patients (38%) may have such comorbidity and, therefore, be ineligible for inclusion in the previously performed randomised controlled trials [2]. In the Dutch study [1], no statistical significant difference in mortality rate was found in patients …

Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL‐2 in HIV‐positive patients

Neutralizing cytokine antibodies are found in healthy and diseased individuals, including patients treated with recombinant cytokines. Identification of CCR‐5 as co‐receptor for HIV has focused interest on CC chemokines and their potential therapeutic use. Chemokine‐binding components in plasma of HIV‐infected patients were therefore assessed by radioimmunoassay and radioreceptor assay. IgG from 4/505 HIV patients and 9/2000 healthy controls (p>0.05) bound rMIP‐1α and rMIP‐1β, but not rRANTES. No other plasma factors bound the chemokines. The antibodies inhibited receptor binding of both chemokines. There was no association between presence of antibodies and disease stage or HIV progression rate. Three of 11 patients treated with rIL‐2 developed IgG antibodies suppressing cellular binding and growth promotion of rIL‐2. Hence, circulating factors, including antibodies MIP‐1α/MIP‐1β, are uncommon in healthy individuals and HIV patients, and are apparently without prognostic significance. In contrast to earlier reports, IL‐2 antibodies were found only in HIV patients treated with rIL‐2.

Clinical signs of bacterial meningitis at admission

To identify clinical signs of high sensitivity in adult community acquired bacterial meningitis on the time of admission to a hospital.

Admission diagnosis and timing of lumbar puncture in bacterial meningitis

To evaluate the possible influence of admission diagnosis and clinical signs on delay in time to lumbar puncture in adult community acquired bacterial meningitis.

Outcome and non-chemotherapeutic treatment in pleural empyema

The aim with this study was to describe correlations between hypothesised factors (surgery, local thrombolytic, nosocomiel infection, late pleural drainage) and unfavourable outcome in pleural empyema.