Dose-ranging study of a single injection of pneumococcal conjugate vaccine (1 ×, 2 ×, or 4 ×) in healthy subjects aged 70 years or older.

Healthy adults aged ≥ 70 years (N=443) with no history of pneumococcal vaccination received 7- or 9-valent pneumococcal conjugate vaccine (PCV7 or PCV9) at 1 × (PCV7 only), 2 × (PCV7+PCV9), or 4 × (2 × PCV7+2 × PCV9) dosage in a randomised, open-label study evaluating pneumococcal protein conjugate vaccine (PnC). Controls received 23-valent pneumococcal polysaccharide vaccine (PPV). Both geometric mean concentration enzyme-linked immunosorbent assay and opsonophagocytic activity antibody titres assessed 1 month after vaccination were significantly increased over baseline titres for all PCV7 serotypes, with a trend toward a dose-dependent immune response. Local reactions for the 4 × dose, but not the 2 × dose, were statistically significantly higher than for the 1 × dose. No treatment-related serious adverse events occurred.

Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia: linezolid or vancomycin? - Comparison of pharmacology and clinical efficacy.

The incidence of nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus strains (MRSA) is on the rise worldwide. For years, vancomycin has been used as the drug of choice in the treatment of MRSA infections and was recommended as such by clinical guidelines. There is growing evidence that vancomycin, despite low resistance rates is a suboptimal therapeutic option in critically ill patients, particularly in patients with pneumonia. Disadvantages of vancomycin are i) slow bactericide action, ii) poor penetration into pulmonary tissue, iii) the globally slowly increasing vancomycin MICs ("creep") that result in increased clinical failure despite being susceptible according to defined break points and iv) nephrotoxicity. In contrast to other novel antibiotics with MRSA activity, Linezolid is currently approved for the treatment of nosocomial pneumonia in the USA and Europe. Several studies have compared vancomycin with linezolid for nosocomial pneumonia with conflicting results. This review compares both substances regarding pharmacodynamics, resistance, safety and clinical efficacy and discusses preliminary data of the ZEPHyR study. This study compared linezolid versus vancomycin in patients with proven MRSA pneumonia and was the largest trial ever conducted in this population.

Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection.

Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL(-1). Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73-0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%.

[Modern artificial respiration concepts in the treatment of acute respiratory distress syndrome]. / Moderne Beatmungskonzepte in der Therapie des akuten Atemnotsyndroms (ARDS).

In current intensive care medicine mechanical ventilation is of particular importance. In recent years new ventilation concepts have been established. Most notably, the idea of protective ventilation of patients suffering from ARDS had lasting effects in the ventilation management on these patients. In contrast to other ventilation concepts, a significant survival benefit was shown. Alternative treatment options are high-frequency-oscillatory ventilation, extracorporeal assist devices or a combination of both in order to apply an extrem small tidal volume. These alternative treatment options have never been evaluated in randomised controlled trials, so a definite statement for practical application cannot be made.

Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory.

BACKGROUND: High functional antibody responses, establishment of immunologic memory, and unambiguous efficacy in infants suggest that an initial dose of conjugated pneumococcal polysaccharide (PnC) vaccine may be of value in a comprehensive adult immunization strategy. METHODS: We compared the immunogenicity and safety of 7-valent PnC vaccine (7vPnC) with that of 23-valent pneumococcal polysaccharide vaccine (PPV) in adults >/=70 years of age who had not been previously vaccinated with a pneumococcal vaccine. One year later, 7vPnC recipients received a booster dose of either 7vPnC (the 7vPnC/7vPnC group) or PPV (the 7vPnC/PPV group), and PPV recipients received a booster dose of 7vPnC (the PPV/7vPnC group). Immune responses were compared for each of the 7 serotypes common to both vaccines. RESULTS: Antipolysaccharide enzyme-linked immunosorbent assay antibody concentrations and opsonophagocytic assay titers to the initial dose of 7vPnC were significantly greater than those to the initial dose of PPV for 6 and 5 of 7 serotypes, respectively (P < .01 and P < .05, respectively). 7vPnC/7vPnC induced antibody responses that were similar to those after the first 7vPnC inoculation, and 7vPnC/PPV induced antibody responses that were similar to or greater than antibody responses after administration of PPV alone; PPV/7vPnC induced significantly lower antibacterial responses, compared with those induced by 7vPnC alone, for all serotypes (P < .05). CONCLUSION: In adults, an initial dose of 7vPnC is likely to elicit higher and potentially more effective levels of antipneumococcal antibodies than is PPV. In contrast with PPV, for which the induction of hyporesponsiveness was observed when used as a priming dose, 7vPnC elicits an immunological state that permits subsequent administration of 7vPnC or PPV to maintain functional antipolysaccharide antibody levels.

[Chikungunya: fever and joint pains after vacation in a tropical area]. / Chikungunya-Fieber und Gelenkschmerzen nach Tropenaufenthalt.

HISTORY: A 27-year-old man was admitted to our hospital, two days after returning from a vacation in Mauritius, with fever, chills, headache and myalgia, as well as arthritis of the legs. He had a temperature of 38.6 C and painful swellings of both talocalcanean joints. INVESTIGATIONS: Laboratory studies revealed leukopenia, lymphopenia and thrombopenia, as well as a slight elevation of transaminases and serum bilirubin. Diagnostic tests for malaria were negative, as were tests for antibodies against Epstein-Barr virus, cytomegalovirus, leptospirosis, dengue, chikungunya and hepatitis viruses, legionella, streptococcus and HIV. But PCR with chikungunya virus RNA was positive, establishing the diagnosis of acute chikungunya. DIAGNOSIS, TREATMENT AND COURSE: All symptoms disappeared on administration of analgesics and antipyretics. But after two days a maculopapular rash on the trunk and limbs was noted: it responded well to the application of clemastine. The patient was discharged from hospital three days after admission. CONCLUSION: Chikungunya virus belongs to the family of alphaviruses and is common in Southeast Asia and Africa. It can be transmitted to humans by bites of the Aedes mosquitoes. Symptoms are similar to those of dengue and consist of fever, headache, arthralgia, myalgia and conjunctivitis. After two or three days these symptoms subside and a maculopapular rash appears. The fever may return. Arthralgia can persist over weeks and even months. While the diagnosis is normally established by antibody tests, these may be negative in early stages of the disease. when the diagnosis can be made by PCR. Treatment is symptomatic with analgesics and antipyretics.

Predicting outcome and survival in patients with Wegener's granulomatosis treated on the intensive care unit.

OBJECTIVE: This study was designed to search for risk factors predicting mortality of patients with Wegener's granulomatosis (WG) treated on the intensive care unit (ICU). METHODS: Seventeen patients admitted to the ICU of an University Hospital for an acute illness related to WG were analysed retrospectively over 4 years. A variety of clinical and laboratory variables were recorded. Contingency table analyses, univariate logistic regression, and discriminate analysis were performed to determine which factors influenced a negative outcome. RESULTS: Reasons for ICU admission were respiratory failure (n = 10), severe haemoptysis (n = 13), sepsis (n = 9), acute renal failure (n = 6), and gastrointestinal bleeding (n = 1). Patients were treated for a median of 6 days (range 4-121 days). During the stay in the ICU, five patients died within 24-121 days (overall mortality 29.4%). Causes of death were cerebral haemorrhage (n = 2), pulmonary embolism (n = 1), and sepsis (n = 2). Significantly associated with death were: Acute Physiology and Chronic Health Evaluation II (APACHE II) score>24 [p = 0.004, odds ratio (OR) 0.568, 95% confidence interval (CI) 0.327-0.989], period of time in the ICU>10 days (p = 0.001, OR 0.795, 95% CI 0.589-1.072), and treatment with cyclophosphamide during the stay in the ICU (p = 0.013, OR 0.799, 95% CI 0.651-0.980). No association was found for higher age, C-reactive protein (CRP), pulmonary involvement, serum creatinine, and requirement of haemodialysis. CONCLUSIONS: The prognosis for WG patients in the ICU is serious, but the majority can survive. To achieve a more favourable outcome, patients should stay in the ICU for as short a time as possible. The occurrence of renal failure did not influence the outcome in our patients.

Impact of corticosteroids on the immune response to a MF59-adjuvanted influenza vaccine in elderly COPD-patients.

The influence of steroids on the antibody response to a MF59-adjuvanted influenza vaccine in elderly COPD patients has not been studied previously. In the influenza season 2001/02 (October-February) elderly COPD patients were recruited at 14 doctor's offices and our 250-bed hospital. Patients were stratified into three groups according to current treatment regimen: (a) > 10 mg of prednisolone/day (SS); (b) inhaled steroids (IS); (c) no steroid treatment (control group, CG). All patients were vaccinated with the MF59-adjuvanted influenza vaccine. Antibodies against the influenza strains A/H1N1, A/H3N2, and B were measured at baseline, 4 and 24 weeks after vaccination by hemagglutination inhibition (HI) assay. One-hundred and sixty-two patients completed the study (CG n = 42; IS n = 87; SS n = 33). Mean age was 71.3 years (range 60-89). Twenty-one percent of all patients reported local reactions; no serious adverse events were observed. Four weeks after vaccination, mean geometric HI titres (GMT) for A/H1N1, A/H3N and B increased significantly in all groups (p < or = 0.05). After 24 weeks, GMTs to A/H1N1 and A/H3N2 returned to baseline, while GMTs to type B remained significantly higher than baseline in all groups. Significant differences between the groups as regards GMTs, seroconversion (56-89%) or seroprotection rates (64-93%) were not observed. Systemic steroids did not influence the antibody response towards the MF59-adjuvanted influenza vaccine. We found that the strains included in the vaccine showed varying long-term immunogenicity.

Ciprofloxacin treatment failure in a patient with resistant Streptococcus pneumoniae infection following prior ciprofloxacin therapy.

Reported here is the case of a patient with underlying chronic obstructive pulmonary disease (COPD) in whom ciprofloxacin treatment of a lower respiratory tract infection failed subsequent to ciprofloxacin treatment of an exacerbation of COPD several weeks earlier. During the second course of ciprofloxacin therapy, the patient's condition continued to deteriorate, and she was admitted to the intensive care unit. Bilateral pneumonia was diagnosed. Streptococcus pneumoniae, serotype 11A, resistant to ciprofloxacin was isolated from the sputum. Sequencing revealed a S79F mutation in parC and there was evidence of an efflux pump. The patient improved rapidly after administration of azithromycin and ampicillin/sulbactam. This report of treatment failure due to ciprofloxacin-resistant Streptococcus pneumoniae shows that fluoroquinolones should be avoided when treating patients who have recently received this class of antibiotics.

Pulmonary infiltrates in Costello Syndrome.

This paper reports on a patient with diffuse pulmonary infiltrates directly related to Costello Syndrome. This congenital disorder is characterised by multiple congenital abnormalities, such as psychomotor retardation, short stature, redundant skin, papillomata, curly hair, relative macroencephaly, distinctive face and various defects of internal organs. This study is the first to document the histopathological findings in the lungs. Most conspicuous was the depositing of abnormal collagen and elastic fibres and the development of endogenous lipid pneumonia.

Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.

A major feature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is the accumulation of activated neutrophils in the bronchial tree. This phenomenon can be explained by an increased migration and/or by a prolonged survival due to an inhibition of spontaneous apoptosis. The aim of this study was to assess the apoptotic behaviour of peripheral blood neutrophils in COPD patients during an acute exacerbation. Thirty-six hospitalised COPD patients with an acute exacerbation and 10 healthy volunteers were included. Blood samples were obtained at admission, after 3-5 days and at discharge. Spontaneous apoptosis of isolated neutrophils was measured based on Annexin V-PE binding and nuclear morphology after culturing for 18 h. At admission, significantly lower rates of spontaneous apoptosis were noted in COPD patients compared with healthy volunteers (mean +/- SD 31 +/- 13% versus 44 +/- 18%). The mean percentages of apoptotic neutrophils were 31 +/- 13% at admission, 39 +/- 15% after 3-5 days and 47 +/- 18% at discharge. There was a statistically significant difference between the rates of spontaneous apoptosis on the first day and at discharge. Neither forced expiratory volume in one second < 35% predicted, smoking habit, corticosteroid therapy nor evidence of bacterial infection showed any influence on the spontaneous apoptosis in this study. In conclusion, during acute exacerbations of chronic obstructive pulmonary disease, neutrophil granulocytes show a reduced spontaneous apoptosis that increases progressively after treatment and clinical remission. This raises the question of the importance of neutrophil apoptosis in the development and resolution of exacerbations of chronic obstructive pulmonary disease.

[Diagnosis of multiple myeloma by demonstrating plasma cells in bronchoalveolar lavage]. / Diagnose eines Multiplen Myeloms durch den Nachweis von Plasmazellen in der bronchoalveolären Lavage.

HISTORY AND CLINICAL FINDINGS: A 61-year-old man was transferred from a peripheral hospital with the diagnosis of interstitial lung disease and an unclear mediastinal tumour. At the time of admission the patient had congestive heart disease NYHA class IV. INVESTIGATIONS: The echocardiogram showed a small left ventricle with concentric hypertrophy and a left ventricular ejection fraction of 35 %. The myocardium was relatively echo-rich with solid structures inside. Chest X-ray showed a massive rightsided pleural effusion. The abdominal ultrasound demonstrated ascites and hepatomegaly. The bronchoalveolar lavage showed an increased part of CD3 negative and CD16/CD56 positive cells, which were identified as plasma cells by light and electron microscopy. Aspiration and investigation of the bone marrow verified the diagnosis of a IgG multiple myeloma, highly differentiated characterised by monoclonal expression of light-lambda chains. Additionally Bence-Jones-proteins were found in the urine and osteolysis in the x-ray of the skull and the humerus. DIAGNOSIS: Multiple myeloma, IgG-lambda, stage IIA. THERAPY AND CLINICAL COURSE: Chemotherapy with prednisolone and melphalan was initiated. His general condition increased after administration of the first cycle of chemotherapy. CONCLUSION: Cardiopulmonary involvement is seldom seen in multiple myeloma but should be excluded when clinical symptoms are present.

Effect of calcium carbonate on bioavailability of orally administered gemifloxacin.

We investigated the effect of calcium carbonate on the oral bioavailability of gemifloxacin. Gemifloxacin was administered alone, 2 h before, simultaneously, or 2 h after calcium carbonate in 16 volunteers. Data for 320 mg of gemifloxacin alone were as follows: maximum concentration of drug in serum (C(max)),13 microg/ml; half-life, 7.33 h; and area under the concentration-time curve from 0 h to infinity (AUC( infinity )), 6.79 microg. h/ml. Only simultaneous coadministration of calcium carbonate reduced C(max) (-17%) and AUC( infinity ) (-21%) significantly.

ABT-773: pharmacokinetics and interactions with ranitidine and sucralfate.

We assessed the pharmacokinetics and interaction of ABT-773 in 12 volunteers receiving ABT-773 alone or concomitantly with ranitidine or sucralfate. Data for 150 mg of ABT-773 were as follows: the maximum concentration of the drug in plasma (C(max)) was 318 ng/ml, its half-life was 5.66 h, and its area under the plasma concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 1,662 ng. h/ml. Coadministration of ranitidine, reduced the C(max) (-25.7%) and AUC(0- infinity ) (-15.8%) significantly. Sucralfate had no impact on the bioavailability of ABT-773.

Cerebriform nodular amelanotic metastases of malignant melanoma: a challenge in differential diagnosis of a rare variant.

High variability of the clinical appearance of malignant melanoma (MM) and its metastases render the differential diagnosis of solid amelanotic tumours difficult. We report a 71-year-old woman with several unusual cutaneous tumours of cerebriform morphology, suggesting skin metastases from occult internal cancer. Histopathological findings and thorough investigations, however, revealed a late-stage metastatic MM. We discuss the differential diagnosis of skin metastases of various origin and underline the difficulties for early detection of MM.