Deep, respiratory tract and ear infections caused by Pseudallescheria (Scedosporium) and Microascus (Scopulariopsis) in Finland. A 10-year retrospective multi-center study.

Deep, respiratory tract and ear infections due to Microascaceae (Pseudallescheria, Scedosporium, Microascus or Scopulariopsis) were studied nationwide in Finland during 1993-2002. The data were based on 52,000 fungal cultures that represented about 50% of all such specimens in Finland and included all Finnish cases of profound immunosuppression. There were 39 cases that were re-evaluated as clinically significant, i.e., three pneumonias, two deep pedal infections and five wound infections, 11 sinusitis and 18 ear infections. The pedal infections and most pneumonias occurred in immunocompromised patients. Most cases, except the ear infections, were due to Pseudallescheria boydii. Two patients had lethal P. boydii pneumonia and a deep P. boydii infection of the foot contributed to a third lethal case. Two of the patients with lethal outcomes had received an allogeneic haematopoietic stem cell transplantation (AHSCT). Two patients with haematological malignancies were cured of deep site infections by a prolonged course of itraconazole. Wound, sinus and ear infections were cured or improved by local surgery or topical therapy. There were 0.8-1.7 cases of any type of infection per million inhabitants per year (MY) and 3.4 cases/1000 AHSCT. Mortality associated with Microascaceae in any type of patient was 0.06-0.12 MY.

Severe sepsis in autologous stem cell transplant recipients: microbiological aetiology, risk factors and outcome.

Infectious complications are the main reason for early treatment-related mortality after autologous stem cell transplantation (ASCT). We evaluated retrospectively microbiological aetiology, risk factors and clinical consequences of severe sepsis in this patient cohort. From 1996 to 2006 a total of 319 patients underwent ASCT at our institution. Antibacterial prophylaxis was not used. Neutropenic fever occurred in 83% (n=265) and was complicated by severe sepsis in 5% (n=17) of patients. Severe sepsis tended to be more common in patients with non-Hodgkin's lymphoma (NHL) than in other patients (9% vs 3%, p=0.009). Bacteraemia was observed more commonly in patients with severe sepsis (76% vs 22%, p<0.001); Pseudomonas sp. was found in 30% (n=5) of these patients. Kinetics of C-reactive protein (CRP) more commonly coincided with, rather than predicted, the development of severe sepsis. All other observed risk factors for severe sepsis (length of neutropenia, fever and blood culture findings) were late indicators. Severe sepsis was fatal in 9 patients (53%), and all had NHL (p=0.003 compared to other patients). Severe sepsis is an important cause of early mortality after ASCT, especially in NHL patients. Ways to prevent development of severe sepsis or predict its development might reduce early mortality among ASCT recipients.

A retrospective nationwide case study on the use of a new antifungal agent: patients treated with caspofungin during 2001-2004 in Finland.

The aim of this study was to evaluate the efficacy and safety of caspofungin in patients treated in Finland during the period 2001-2004. The medical records of 78 adult patients treated with caspofungin in five major hospitals were reviewed retrospectively. Fifty-nine (76%) patients had proven invasive fungal infection, of whom 22 (28%) had aspergillosis and 37 (47%) had candidiasis. Nineteen (24%) patients were treated empirically; only 13 (17%) patients received caspofungin as primary therapy. A favourable response was achieved in 52 (67%) patients. The response rate was 78% in patients with candidiasis, and 50% in patients with aspergillosis. At the end of the study period, 40 (51%) patients remained alive; of the 38 deaths, nine (24%) were caused by fungal infection. The response rates were lower, although not significantly, for patients with high (>20) vs. low (< or =20) Acute Physiology and Chronic Health Evaluation (APACHE II) scores (response rate 50% vs. 68%, p 0.48, respectively), and were also lower in patients with long-term (>20 days) vs. shorter duration (< or =20 days) neutropenia (55% vs. 73%, p 0.32, respectively), and in those with an underlying haematological malignancy vs. patients with other diseases (59% vs. 73%, p 0.2, respectively). In five (6%) patients, caspofungin therapy was discontinued prematurely because of adverse drug reactions (ADRs) (elevated liver enzyme values in three patients, neuropathic pain in one, and skin rash in one). Serious ADRs occurred in two (3%) patients (severe hepatic insufficiency with consequent death, and eosinophilia with elevated alkaline phosphatase levels), and laboratory abnormalities, mostly mild and reversible, in 24 (31%) patients. In this unselected patient population, caspofungin was safe, well-tolerated, and had an efficacy comparable to that in previous reports from prospective trials.

Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia when added to the standard treatment: a prospective and randomized clinical trial of 381 patients.

OBJECTIVES: To study whether levofloxacin, added to standard treatment, could reduce the high mortality and complication rates in Staphylococcus aureus bacteraemia. DESIGN: A prospective randomized multicentre trial from January 2000 to August 2002. SETTING: Thirteen tertiary care or university hospitals in Finland. SUBJECTS: Three hundred and eighty-one adult patients with S. aureus bacteraemia. Patients with meningitis, and those with fluoroquinolone- or methicillin-resistant S. aureus were excluded. INTERVENTIONS: Standard treatment (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n = 191). Supplementary rifampicin was recommended if deep infection was suspected. MAIN OUTCOME MEASURES: Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points. RESULTS: Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69-5.54). CONCLUSIONS: Levofloxacin combined with standard treatment in S. aureus bacteraemia did not decrease mortality or the incidence of deep infections, nor did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia appeared to be more common than previously reported.

Prognosis after community-acquired pneumonia in the elderly: a population-based 12-year follow-up study.

BACKGROUND: Only a few studies have investigated the long-term effects of community-acquired pneumonia (CAP). These studies have focused on cases treated in the hospital, and, to our knowledge, no long-term survival studies that include all cases of CAP are available. METHODS: A prospective observational study on the survival rates in a population-based cohort of elderly inhabitants aged 60 years or older at baseline in 1 township in eastern Finland in 1983. A total of 4167 (99% of the total elderly population), 122 of whom survived CAP during a prospective pneumonia surveillance period from 1983 to 1985, were followed up for mortality from 1983 to 1994 for a median of 9.2 years. The relative risk (RR) of death in patients who survived CAP was compared with that in elderly inhabitants without CAP by Cox multivariate regression analysis. Data on causes of death were obtained from a central register based on death certificates. RESULTS: The long-term survival rate was significantly lower in persons who had survived CAP or pneumococcal CAP (PCAP) than in the rest of the study population. The RR of pneumonia-related mortality was 2.1 (95% confidence interval [CI], 1.3-3.4; P = .004) in all patients with CAP and 2.8 (95% CI, 1.5-5.3; P = .001) in patients with PCAP. The respective numbers for total mortality were 1.5 (95% CI, 1.2-1.9; P = .001) in all patients with CAP and 1.6 (95% CI, 1.1-2.2; P= .01) in those with PCAP. Also the risk of cardiovascular mortality was increased in persons with CAP (RR, 1.4; 95% CI, 1.0-1.9; P = .02) and in those with PCAP (RR, 1.6; 95% CI, 1.0-2.4; P= .04). CONCLUSIONS: The present results indicate that elderly patients treated for CAP are at high risk of subsequent mortality for several years. Based on the high incidence and negative long-term effects of pneumonia, it can be concluded that there is a clear need for prevention, eg, by influenza and pneumococcal immunization.

Clinical efficacy of pneumococcal vaccine in the elderly: a randomized, single-blind population-based trial.

PURPOSE: To study the efficacy of pneumococcal capsular polysaccharide vaccine among the elderly by use of a population-based intervention in one township, Varkaus, Eastern Finland. PATIENTS AND METHODS: A randomized, controlled trial in which elderly inhabitants (aged 60 years or older) of the catchment area were randomized to receive either pneumococcal and influenza vaccines (PI group = vaccinated) or influenza vaccine alone (I group = controls) and offered participation. The response rate was 67.4%. The PI group consisted of 1,364 persons and the I group of 1,473 persons. The vaccinations were performed in the municipal health center in the fall of 1982, and all elderly inhabitants were followed for 3 years for the development of radiologically confirmed pneumonia. Pneumococcal etiology was identified by serological methods. RESULTS: The incidence of pneumonia was 18.8 per 1,000 person-years in the PI group (73 pneumonia episodes) and 16.6 per 1,000 person-years in the I group (69 episodes). Pneumococcal etiology was found in 27 episodes in the PI group (incidence 7.0 per 1,000 person-years) and in 36 episodes in the I group (incidence 8.6 per 1,000 person-years). In controls (I group) the incidence of pneumococcal pneumonia was significantly higher among persons with increased risk for contracting pneumonia (19 per 1,000 person-years) than among controls with low risk status (4 per 1,000 person-years). No significant protection from pneumococcal pneumonia was found in the study group as a whole (vaccine efficacy 15%, 95% CI -43% to 50%). However, in persons with medical risk factors for contracting pneumonia, there was a statistically significant protective efficacy of 59% (95% CI, 6% to 82%). CONCLUSION: Pneumococcal vaccination significantly reduced the incidence of pneumococcal pneumonia in elderly persons at increased risk for contracting pneumonia. This increased/high-risk category comprised 34% of the population aged 60 years or older. Because targeted vaccination of this large group may be difficult to organize in an efficient manner, vaccinating all elderly persons may be the best strategy to prevent this rather common and often fatal disease.

Effect of immunosuppressive therapy on the clinical presentation of legionellosis.

To determine whether the clinical course of legionellosis in patients treated with immunosuppressive agents differs from that seen in other patient groups, data on 52 Finnish patients with legionellosis confirmed by culture or by the direct immunofluorescent antibody test was reviewed. Of these patients 44% were immunosuppressed, 23% had other underlying diseases and 33% had no predisposing conditions. Among those without predisposing conditions, only Legionella pneumophila serogroup 1 was observed, whereas among the immunosuppressed patients, serogroup 6 dominated. Legionellosis was nosocomial in 73% of the immunosuppressed patients and in 33% of the patients with other underlying diseases but was travel-associated in 76% of those without predisposing factors. The case fatality rate (37%) was high but was not associated with preceding immunosuppression. These results indicate that although the serogroups and the sources of legionellosis differ in immunosuppressed patients compared with other groups, the clinical presentation is not more severe.

Risk factors for pneumonia in the elderly.

PURPOSE: To investigate the prevalence of certain chronic conditions among the elderly and to estimate the relative risk for pneumonia associated with each condition. PATIENTS AND METHODS: Medical records of all inhabitants aged 60 years or more (4,175 persons) in one township (population 24,716) in Finland were reviewed, seeking 15 chronic conditions. Which patients had pneumonia in the same population was prospectively ascertained over a period of 3 years (185 patients). RESULTS: Hypertension was the most frequent chronic condition (36.4%) in the study population. Other common conditions were heart disease (23.7%, with chronic compensated heart failure in 96.3% of these), other cardiovascular disease (13.1%), and diabetes (13.1%). The prevalence of any other condition was less than 5%. The following conditions were significantly more common among pneumonia patients than among control subjects: heart disease (38.4% versus 23.0%), lung disease (13.0% versus 3.8%), bronchial asthma (11.9% versus 3.1%), immunosuppressive therapy (2.7% versus 0.8%), alcoholism (2.2% versus 0.3%), and institutionalization (8.6% versus 3.9%). By multivariate logistic regression analysis, independent risk factors for pneumonia were alcoholism (relative risk [RR] = 9.0, confidence interval [CI] = 5.1 to 16.2), bronchial asthma (RR = 4.2, CI = 3.3 to 5.4), immunosuppressive therapy (RR = 3.1, CI = 1.9 to 5.1), lung disease (RR = 3.0, CI = 2.3 to 3.9), heart disease (RR = 1.9, CI = 1.7 to 2.3), institutionalization (RR = 1.8, CI = 1.4 to 2.4), and age (70 years or more versus 60 to 69 years; RR = 1.5, CI = 1.3 to 1.7). One third of the study population and 57% of the pneumonia patients had one or more of these risk factors. Diabetes, chronic pyelonephritis, and malignancies of sites other than the lungs were not associated with increased risk for pneumonia. CONCLUSION: We found which elderly persons have an increased risk for pneumonia. Although the highest relative risk was associated with alcoholism, that condition was rare in this elderly population. Chronic obstructive lung diseases were more common and were also associated with a high relative risk. Heart disease had the highest public health impact because it was very common among the elderly and increased the risk of contracting pneumonia almost twofold; it also increased the risk of pneumonia-related death. These population-based data confirm and extend previous findings derived from selected patient groups and are useful for designing cost-effective pneumonia prevention programs.

Effect of rifampicin treatment on the kinetics of mexiletine.

To study the effects of enzyme induction on its pharmacokinetics, a single oral dose of the new antiarrhythmic agent mexiletine hydrochloride 400 mg was administered to 8 healthy volunteers before and after treatment with rifampicin 300 mg b.i.d. for ten days. The absorption and distribution of mexiletine were not changed after rifampicin, but its elimination half-life fell from 8.5 +/- 0.8 h (mean +/- SE) to 5.0 +/- 0.4 h (p less than 0.01), and its nonrenal clearance increased from 435 +/- 68 ml/min to 711 +/- 101 ml/min (p less than 0.01). The mean renal clearance of mexiletine did not change, but it showed an exponential correlation with urinary pH. The amount of unchanged mexiletine excreted in urine over two days decreased from 32 +/- 7 to 18 +/- 3 mg (p less than 0.01). The half-life of antipyrine fell from 11.8 +/- 0.4 to 5.5 +/- 0.3 h and its clearance increased from 40 +/- 3 ml to 74 +/- 3 ml/min (p less than 0.01). There was a significant (p less than 0.05) positive linear correlation between both the half-lives and the clearances of antipyrine and mexiletine. The clearances were positively correlated with serum gamma-glutamyl transpeptidase. The results suggest that the dosage of mexiletine should be adjusted when enzyme inducing drugs are started or stopped during therapy with it.