[An early switch from intravenous to oral antibiotics is equally effective as the standard intravenous therapy in severe community acquired pneumonia]. / Vroege omschakeling van intraveneuze naar orale antibiotica even effectief als standaard intraveneuze therapie bij ernstige, buiten het ziekenhuis opgelopen pneumonie.

OBJECTIVE: To compare an early switch from intravenous to oral antibiotics with the standard intravenous therapy in patients admitted to hospital with severe community acquired pneumonia. DESIGN: Multicentre randomised prospective trial with follow-up at 28 days. METHOD: Patients with severe pneumonia who were admitted to hospital were randomised for 7 days intravenous antibiotic therapy (control group) or for an early switch to oral antibiotic therapy after 3 days of intravenous antibiotic therapy (intervention group). An intention-to-treat analysis was performed. The primary outcome measure was clinical cure. The length of hospital stay was a secondary outcome measure. RESULTS: Out of the 302 patients included in the trial, data was analysed from 265 patients. The mortality rate in the intervention group did not differ significantly from that of the control group (mean difference: 2%; 95% CI: -3-8). After 28 days, 83% of the patients in the intervention group and 85% in the control group were clinically cured (mean difference: 2%; 95% CI: -7-10). The length of hospital stay was 1.9 days shorter in the intervention group (95% CI: 0.6-3.2 days). CONCLUSION: An early switch from intravenous to oral antibiotics in patients admitted to hospital for severe community acquired pneumonia is safe and reduces the length of hospital stay by approximately 2 days.

Predicted effects on antibiotic use following the introduction of British or North American guidelines for community-acquired pneumonia in The Netherlands.

This study evaluated the possible changes in antibiotic use that might follow the implementation of British or North American guidelines for the treatment of community-acquired pneumonia (CAP) in The Netherlands. Patients admitted for mild, moderate and severe CAP were evaluated prospectively. Volume of antibiotic use, based upon guidelines of the British Thoracic Society (BTS), the Infectious Diseases Society of America (IDSA) or the American Thoracic Society (ATS), was estimated and compared to current practice. For 248 patients, current antibiotic use was 3087 defined daily doses. Antibiotic use would increase by 38% if based on ATS guidelines, by 23% if based on IDSA guidelines, and by 21% if based on BTS guidelines. The most significant increase in antibiotic use would occur for cases of moderate CAP, with incremental antibiotic costs of 1 750 000-3 500 000 Euros in The Netherlands.

Increased risk of early virological failure in non-European HIV-1-infected patients in a Dutch cohort on highly active antiretroviral therapy.

OBJECTIVE: To compare early and late responses to highly active antiretroviral therapy (HAART) in European and non-European HIV-1 infected patients in a Dutch cohort. METHODS: We retrospectively analysed the response to HAART of 216 previously treatment-naive HIV-1-infected patients using the University Medical Centre Utrecht HIV database. African (n=51), Asian (n=7), and Central/South American (n=6) patients were classified as non-European, and others as European (n=152). Early failure was defined as a viral load that remained above 400 HIV-1 RNA copies/mL after 6 months of treatment with HAART. Late-phase failure was determined in patients who were successfully treated in the early phase and was defined as two consecutive viral load measurements above 400 copies/mL, a new AIDS-defining event or death. RESULTS: In the early phase, four of 152 (2.6%) European and eight of 64 (12.5%) non-European patients failed HAART. A significant increased risk of virological failure in the early phase of treatment was observed for non-Europeans as compared to Europeans (odds ratio 4.6; 95% confidence interval 1.1-20.2). Low serum drug levels in the absence of resistant virus were often seen at the time of early failure. No difference in late-phase failure was observed between the two groups (adjusted hazard ratio 0.6; 95% confidence interval 0.3-1.2). CONCLUSIONS: Non-European patients had a 4.6 times higher risk of virological failure than their European counterparts in the first 6 months of treatment with HAART. This failure seemed to be associated with low serum drug levels at the time of failure. However, if HAART was successful in the early phase, response rates in the late phase were similar for Europeans and non-Europeans.

[Post-exposure prophylaxis following exposure to HIV: adaptation to the situation may be indicated]. / Postexpositieprofylaxe na blootstelling aan HIV: aanpassing aan de situatie kan geïndiceerd zijn.

A woman aged 36 injured herself on a needle that had been used to take an iliac-crest biopsy from an HIV-positive patient and a man aged 34 and a woman aged 35 had sexual contact with their HIV-positive partners during which the condom tore. They were given post-exposure prophylaxis (PEP) which was formulated using medication and virus resistance data from the HIV-positive individual. At 3 and 6 months the patients were all still HIV-negative. After occupational or non-occupational exposure to HIV, PEP is initiated if there is a reasonable risk of transmission of HIV. In The Netherlands a combination of 3 antiretroviral drugs is advised based on demonstrated antiviral effectiveness in the regular treatment of HIV-infections. Frequently a standard PEP-regimen is prescribed. If the source patient has a history of antiretroviral therapy, the virus might be resistant to standard PEP-regimens. In these cases the choice of drugs in the PEP-regimen can be individualised based on the antiretroviral medication history of the source patient and known resistance patterns of the source virus.

[The increase in pneumonia-related morbidity and mortality among adults in the Netherlands and possible explanations for it]. / Toename van pneumoniegerelateerde ziekte en sterfte onder volwassenen in Nederland en mogelijke verklaringen daarvoor.

As seen in several national registration systems, the morbidity and mortality due to pneumonia-related disease has increased in the Netherlands in the past 10 years. It is unlikely that the observed increase in mortality due to pneumonia is purely the result of the registration system used or misclassification. An increase in the elderly population is the most likely, albeit only partial, explanation. An increase in underlying diseases such as chronic obstructive pulmonary disease and diabetes mellitus is also a possible explanation. Increased antibiotic resistance, inadequate treatment or a shift in the spectrum of micro-organisms causing pneumonia are less likely explanations. Reducing the morbidity and mortality due to pneumonia demands an integrated approach aimed at elderly patients or patients with co-existing disease and executed by specialists in the fields of geriatrics, internal medicine, pulmonary disease and infectious diseases.

Differential CD4 T-cell response in HIV-1-infected patients using protease inhibitor-based or nevirapine-based highly active antiretroviral therapy.

OBJECTIVES: To study the dynamics of CD4 T-lymphocyte counts (CD4 counts) after the initiation of either protease inhibitor (PI)-based or nevirapine (NVP)-based first-line highly active antiretroviral therapy (HAART). DESIGN AND METHODS: A retrospective cohort study of 1029 HIV-infected antiretroviral therapy-naive patients initiating either PI-based or NVP-based HAART was carried out. Patients were censored as soon as they experienced virological failure, or changed their original antiretroviral regimen for any reason. RESULTS: In total, 920 and 109 patients initiated PI- and NVP-based HAART, respectively. The patients in the PI group more often had AIDS (15 vs. 6% in the NVP group), had a lower median baseline CD4 count (234 vs. 250 cells/microL in the NVP group) and had higher median baseline plasma HIV-1 RNA levels (pVL) (5.0 vs. 4.7 log10 HIV-1 RNA copies/mL in the NVP group). After 96 weeks of follow-up, the mean increase from baseline in CD4 count, adjusted for baseline CD4 count, age, gender and baseline pVL, was 310 cells/microL in the PI group and 212 cells/microL in the NVP group (P=0.003). This difference was mainly attributable to the patients in the NVP group initiating HAART with a baseline CD4 count below 200 cells/microL. There were no differences between the PI and NVP groups with respect to the change in the number of CD4 cells as a proportion of the total number of lymphocytes. CONCLUSION: Patients successfully treated with NVP-based HAART have a smaller increase in absolute CD4 cells compared with those treated with PI-based HAART.

Algorithm to determine cost savings of targeting antimicrobial therapy based on results of rapid diagnostic testing.

A rapid diagnosis of pneumococcal pneumonia may allow the earlier use of narrow-spectrum antimicrobial therapy. It is unknown, however, whether rapid diagnostic testing of patients hospitalized with community-acquired pneumonia (CAP) admitted to hospital lowers costs. Therefore, an algorithm to calculate the costs associated with the diagnosis and treatment of CAP was formulated. Subsequently, the algorithm was applied to clinical data for 122 consecutively admitted patients with CAP whose sputum samples were Gram stained and whose urine was tested for Streptococcus pneumoniae antigen. The costs of initial antimicrobial therapy, personnel, and materials were measured. Compared to the most expensive empirical regimen, rapid diagnostic testing would result in cost savings per patient (PP) of 3.51 Euros for Gram staining and 8.11 Euros for urinary pneumococcal antigen testing (1 Euro is equal to 1.13 US dollars, from 2000 to 2002). Compared to the cheapest regimen, Gram staining would increase the cost by 2.25 Euros PP, and urinary antigen testing would increase the cost by 24.26 Euros PP. In our setting, the use of rapid diagnostic testing would not lower costs. Cost savings depend, however, on the differences in the prices of the different antibiotics chosen and the proportion of evaluable and positive samples.

How good is the evidence for the recommended empirical antimicrobial treatment of patients hospitalized because of community-acquired pneumonia? A systematic review.

BACKGROUND: For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP). A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e. Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected. However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP. We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone. METHODS: We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP. RESULTS: Eight relevant studies were selected. In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides. The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens. However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies. As a consequence, the results may have been influenced by confounding by indication. In addition, the outcomes showed several inconsistencies. CONCLUSIONS: A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies. Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data.

[Community acquired pneumonia; no reason to revise current Dutch antibiotic guidelines]. / Buiten het ziekenhuis opgelopen pneumonie; geen reden om huidige antibioticumrichtlijn te herzien.

Community-acquired pneumonia is an important cause of hospital admission and mortality in the adult population. The recommended antibiotic for pneumonia caused by Streptococcus pneumoniae is a beta-lactam antibiotic and, for so-called atypical pathogens, a macrolide. In the US and elsewhere, the current recommendation is to start with a beta-lactam antibiotic and a macrolide or with one of the new quinolones. The available literature consists largely of retrospective studies. Because of possible selection bias in these analyses and inconsistencies in reported outcomes, it is not possible to draw any well-founded conclusions from these studies. Reasons for a possible additional benefit of adding a macrolide to the therapy could include: a higher prevalence of undiagnosed atypical pathogens, the anti-inflammatory effects of macrolides, and resistance of the main pathogens against beta-lactam antibiotics. None of these appear to play a significant role. There is no need to revise Dutch guidelines.