Significance of the physician's and the patient's sex in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Numerous studies have revealed that the sex of the patient or of the attending physician have impact on patient care, treatment, morbidity and mortality. Community-acquired pneumonia (CAP) is a common cause of hospitalization, antibiotic treatment and intensive care unit (ICU) admission. The purpose of this study was to examine if the patient's or the attending physicians' sex may influence the management of hospitalized patients with CAP. METHODS: Our study included 826 consecutive inpatients with CAP (404 females, and 422 male patients, 429 patients initially treated by a female physician and 397 patients initially treated by a male physician). We examined if the patient's, or the initial attending physician's sex, affected treatment and outcome in patients with CAP. RESULTS: Patients mean age was 69 years, 30-day mortality 9%. By use of the pneumonia severity index, male patients were found to be more severely ill at admission (p = .0008). Fewer female physicians' patients were admitted from the emergency department (ED) to the ICU when compared to male physicians' patients, 5% versus 10% (p = .006), and female physicians' patients received their first intravenous (IV) antibiotic dose later than male physicians' patients in the ED (p = .003). CONCLUSION: Our study indicates that the sex of the attending physician may affect the chosen level of care and antibiotic treatment, and that admitted male patients with CAP were more seriously ill than admitted female patients with CAP.

Decreased invasive fungal disease but no impact on overall survival by posaconazole compared to fluconazole prophylaxis: a retrospective cohort study in patients receiving induction therapy for acute myeloid leukaemia/myelodysplastic syndromes.

OBJECTIVE: Posaconazole prophylaxis during induction chemotherapy for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) has been shown to significantly decrease the incidence of invasive fungal disease (IFD) and increase overall survival in a trial setting, but only small real-life studies have been published. METHODS: This was a retrospective cohort study including consecutive patients with AML/MDS treated with intensive induction chemotherapy; 176 patients received fluconazole prophylaxis 2008-2011 and 107 patients received posaconazole prophylaxis 2011-2013. Only proven and probable IFD according to the revised EORTC/MSG criteria were included in the analysis. RESULTS: The two cohorts were well matched without significant differences in patient characteristics. At day 100, patients receiving posaconazole had a significantly lower incidence of total IFD (0.9% vs. 10.8%, P < 0.01), invasive aspergillosis (0% vs. 5.7%, P = 0.02) and invasive candidiasis (0% vs. 4.0%, P < 0.05). There was no significant difference in overall survival, neither at day 100 (87% in the posaconazole group vs. 85% in the fluconazole group) nor at end of follow-up (78% vs. 77%). CONCLUSIONS: Posaconazole prophylaxis decreased the incidence of IFD but did not improve short-term overall survival. Improved treatment efficacy of manifest IFD is likely to explain the lack of survival benefit.

Bacterial Landscape of Bloodstream Infections in Neutropenic Patients via High Throughput Sequencing.

BACKGROUND: Bloodstream infection (BSI) is a common and potentially life-threatening complication in patients with hematological malignancies and therapy-induced neutropenia. Administration of broad spectrum antibiotics has substantially decreased the mortality rate in febrile neutropenia, but bacterial infection is documented in only one-third or fewer of the cases. BSI is typically diagnosed by blood culture; however, this method can detect only culturable pathogens. METHODS: In the present study, a total of 130 blood samples from hematological patients receiving dose-intensive antitumoural treatment were subjected to 16S rRNA PCR and 62 of them were cultured. PCR positive samples were processed to high throughput sequencing by amplifying the V1-V3 regions of the 16S rRNA gene to obtain a full spectrum of bacteria present in BSI. RESULTS: Five phyla and 30 genera were identified with sequencing compared to 2 phyla and 4 genera with culture. The largest proportion of bacteria detected by sequencing belonged to Proteobacteria (55.2%), Firmicutes (33.4%) and Actinobacteria (8.6%), while Fusobacteria (0.4%) and Bacteroidetes (0.1%) were also detected. Ninety-eight percent of the bacteria identified by sequencing were opportunistic human pathogens and 65% belonged to the normal human microbiota. CONCLUSIONS: The present study indicates that BSIs in neutropenic hosts contain a much broader diversity of bacteria, likely with host origin, than previously realized. The elevated ratio of Proteobacteria in BSI corroborates the results found in other systemic inflammatory diseases, such as inflammatory bowel disease or mucosal infections. This knowledge may become of value for tailoring antimicrobial drug administration.

Improvement of CRB-65 as a prognostic tool in adult patients with community-acquired pneumonia.

BACKGROUND: Patients with community-acquired pneumonia (CAP) often require hospitalisation. CRB-65 is a simple and useful scoring system to predict mortality. However, prognostic factors such as underlying disease and blood oxygenation are not included despite their potential to increase the performance of CRB-65. METHODS: The study included 1172 consecutive patients (830 inpatients, 342 outpatients) with CAP. Mortality, sensitivity, specificity, positive predictive value and negative predictive value, and the area under the receiver operating characteristic (ROC) curve with 95% CI were calculated. Prognostic accuracy was evaluated after adding coexisting illnesses according to the Pneumonia Severity Index (malignancy, heart failure, hepatic, renal and cerebrovascular disease) and pulse oximetry (SpO2). RESULTS: Mean age was 65 years, 30-day mortality 7% (inpatients 9%, outpatients 1%). Addition of one point for the presence of ≥1 coexisting condition and one point for SpO2 <90% increased the area under the ROC curve of CRB-65 from 0.82 (95% CI 0.77 to 0.85) to 0.87 (95% CI 0.84 to 0.90; p<0.0001). CONCLUSIONS: Modification of CRB-65 by including hypoxaemia and presence of specified underlying diseases increased the scoring system's prognostic accuracy while retaining its independence of laboratory tests. DS CRB-65 may have the potential to further facilitate site of care decision for patients with CAP.

Klebsiella variicola is a frequent cause of bloodstream infection in the stockholm area, and associated with higher mortality compared to K. pneumoniae.

Clinical isolates of Klebsiella pneumoniae are divided into three phylogroups and differ in their virulence factor contents. The aim of this study was to determine an association between phylogroup, virulence factors and mortality following bloodstream infection (BSI) caused by Klebsiella pneumoniae. Isolates from all adult patients with BSI caused by K. pneumoniae admitted to Karolinska University Hospital, Solna between 2007 and 2009 (n = 139) were included in the study. Phylogenetic analysis was performed based on multilocus sequence typing (MLST) data. Testing for mucoid phenotype, multiplex PCR determining serotypes K1, K2, K5, K20, K54 and K57, and testing for virulence factors connected to more severe disease in previous studies, was also performed. Data was retrieved from medical records including age, sex, comorbidity, central and urinary catheters, time to adequate treatment, hospital-acquired infection, and mortality, to identify risk factors. The primary end-point was 30- day mortality. The three K. pneumoniae phylogroups were represented: KpI (n = 96), KpII (corresponding to K. quasipneumoniae, n = 9) and KpIII (corresponding to K. variicola, n = 34). Phylogroups were not significantly different in baseline characteristics. Overall, the 30-day mortality was 24/139 (17.3%). Isolates belonging to KpIII were associated with the highest 30-day mortality (10/34 cases, 29.4%), whereas KpI isolates were associated with mortality in 13/96 cases (13.5%). This difference was significant both in univariate statistical analysis (P = 0.037) and in multivariate analysis adjusting for age and comorbidity (OR 3.03 (95% CI: 1.10-8.36). Only three of the isolates causing mortality within 30 days belonged to any of the virulent serotypes (K54, n = 1), had a mucoid phenotype (n = 1) and/or contained virulence genes (wcaG n = 1 and wcaG/allS n = 1). In conclusion, the results indicate higher mortality among patients infected with isolates belonging to K. variicola. The increased mortality could not be related to any known virulence factors, including virulent capsular types or mucoid phenotype.

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.

Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.

Procalcitonin levels in community-acquired pneumonia - correlation with aetiology and severity.

We studied procalcitonin (PCT) levels at hospital admittance and their association with aetiology and severity in patients with community-acquired pneumonia (CAP). Median PCT concentrations were higher in bacteraemic patients than in those without bacteraemia (6.11 µg/L vs 0.34 µg/L, p = 0.0002), in patients with non-bacteraemic pneumococcal aetiology than in those infected with other classic bacteria (1.18 vs 0.18, p = 0.038), and in patients with pneumococcal as compared with viral aetiology (2.43 vs 0.24, p = 0.017). When aetiology, bacteraemia and severity according to the pneumonia severity index (PSI) were included in logistic regression analyses with PCT > 0.5 as a dependent variable, the odds ratio (OR) for non-bacteraemic pneumococcal aetiology was 5.7 (p = 0.008) and 3.0 ( p = 0.1) for PSI 4-5. A separate analysis for bacteraemia and PSI 4-5 showed an OR of 17.5 (p = 0.008) and 2.7 (p = 0.092), respectively. In CAP patients, high PCT seems to be a good marker for invasive disease and pneumococcal aetiology. As a predictor of severity it appears to be less important.

Clinical experience of granulocyte transfusion in the management of neutropenic patients with haematological malignancies and severe infection.

BACKGROUND: Prolonged chemotherapy-induced neutropenia is a major risk factor for the development of severe bacterial and fungal infections. Infectious manifestations may progress despite adequate anti-infectious treatment and lead to a very high short-term mortality. Granulocyte transfusion (GT) therapy is often considered. However, its efficacy is not well documented. METHODS: We retrospectively analyzed the clinical characteristics and outcome of a cohort of patients with haematological malignancies receiving GT during neutropenia and severe infection. RESULTS: A total of 30 patients with a median age of 46 y (range 3-82 y) who had received 1 or more GT were included. Acute leukaemia (80%) and non-Hodgkin lymphoma (17%) predominated as the underlying malignancy. All patients had severe and prolonged (median 16 days) neutropenia. The major indications for GT were persistent fever and clinical deterioration despite broad anti-infectious therapy, in combination with progressive pneumonia (n = 16), neutropenic enterocolitis (n = 6), and soft tissue infections (n = 3). GTs were given for a median of 3 transfusions (range 1-14). The median time to fever defervescence after GT was 14 days (range 6-33 days). For 11 patients, the resolution of fever and all signs of infection could directly be related to GT, and 3 of these patients became long-term survivors. Mortality at 30 days post-GT was 40% and at 6 months post-GT was 72%. GT was well tolerated. CONCLUSIONS: A substantial proportion of severely ill neutropenic patients appeared to benefit from GT. The results further underline the need for well- designed, randomized, prospective trials to determine the efficacy of this intervention in patients with life-threatening infectious complications.

Bacteremia in Swedish hematological patients with febrile neutropenia: bacterial spectrum and antimicrobial resistance patterns.

BACKGROUND: The etiology of bacteremia in hematological patients with febrile neutropenia differs geographically and changes over time. Since efficient empirical antibiotic treatment depends on relevant knowledge of the bacterial panorama, the aim of this study was to describe the prevalence of bacteremia, the bacterial spectrum, and the resistance patterns of the isolates in this group today. METHODS: In a cross-sectional study, routine blood cultures from febrile episodes occurring in adult patients with hematological disorders and neutropenia presenting to Karolinska University Hospital, Stockholm, Sweden during a 24-month period, were analyzed. RESULTS: A total of 142 febrile neutropenic episodes occurring in 124 hematological patients were included in the study. Bacteremia was documented in 27% of the episodes, and of these, 58% were due to Gram-positive pathogens. The most common isolates were viridans streptococci, coagulase-negative staphylococci, and Escherichia coli. Low levels of antibiotic resistance were detected. The underlying diagnosis of non-Hodgkin's lymphoma (NHL) was independently negatively associated with documented bacteremia (p < 0.01). CONCLUSIONS: The prevalence of bacteremia and the bacterial spectrum were consistent with recent Scandinavian reports. Substantially lower levels of antimicrobial resistance were registered compared to those found in other European centers. Patients with NHL were less likely to have documented bacteremia in this study.

Prevalence of antibiotic-resistant bacteria in residents of nursing homes in a Swedish municipality: healthcare staff knowledge of and adherence to principles of basic infection prevention.

BACKGROUND: The aims of this study were to investigate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in residents living in Swedish nursing homes, and if carriage of resistant bacteria was related to antibiotic treatment, other risk factors, and/or staff's adherence to guidelines for infection control. METHODS: Five hundred and sixty residents from 9 nursing homes on a total of 67 wards participated in the study and had microbiological cultures taken. Faecal samples were obtained from 495 residents (88.3%). ESBL-positive residents were followed for 2 y with repeated sampling. Two hundred and ninety-six [corrected] staff members were interviewed and observed regarding familiarity with and adherence to infection control guidelines. RESULTS: No resident was positive for MRSA or VRE. Fifteen of the residents were found to be ESBL-positive. Residents living on wards where ESBL-positive residents were identified had been treated more frequently with antibiotics (42%), compared to those on wards where no residents with ESBL were found (28%; p = 0.02). ESBL-positive Escherichia coli isolates from residents living in adjacent rooms were found to be closely genetically related when analysed by pulsed-field gel electrophoresis, indicating transmission between residents. Staff adherence to infection control guidelines sometimes revealed shortcomings, but no significant differences regarding compliance to the guidelines could be found. CONCLUSION: Carriage of resistant bacteria was uncommon and only ESBL-producing Enterobacteriaceae were identified in Swedish nursing homes. Usage of antibiotics was higher on wards where ESBL-positive residents were detected and there was an indication of transmission of ESBL between residents.

Hematological: Low all-cause mortality and low occurrence of antimicrobial resistance in hematological patients with bacteremia receiving no antibacterial prophylaxis: a single-center study.

BACKGROUND: Bacteremia is a major cause of morbidity and mortality in patients with hematological malignancies. OBJECTIVES: The aim of this study was to define temporal trends in species distribution, antimicrobial susceptibility, and all-cause mortality in bacteremic hospitalized patients receiving no antibacterial prophylaxis during chemotherapy-induced neutropenia. METHODS: A total of 677 clinical episodes of bacteremia were identified in 463 patients during 2002-2008, and the results were compared with those published from the same institution during 1980-86 and 1988-2001. No major changes in patient selection were introduced during this period. RESULTS: Between 2002 and 2008, the dominating pathogens were Escherichia coli (18%), coagulase-negative staphylococci (15%), viridans streptococci (14%), Klebsiella spp. (10%), and Enterococcus faecium (8%). The 7-d crude mortality rate was 5.2%. Polymicrobial bacteremia was seen in 25.7% of the patients who died within 7 d and in 13.1% of the survivors (P = 0.04). Acquired resistance was rarely observed, but a statistically significant increase in ciprofloxacin resistance in E. coli was observed. Comparing 2002-2008 with historical data from the same institution, the proportion of Gram-positive isolates remained stable at 53-55% from 1988. CONCLUSIONS: The avoidance of fluoroquinolone prophylaxis may have contributed to a stable proportion of Gram-positive bacteremia. The crude mortality was low in an international perspective. Acquired resistance was uncommon, but ciprofloxacin resistance in E. coli increased significantly. We believe that an indiscriminate use of antibacterial prophylaxis could be avoided in neutropenic patients without a negative impact on mortality.

Efficacy of pivmecillinam for treatment of lower urinary tract infection caused by extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

To evaluate the clinical and bacteriological efficacy of pivmecillinam against lower urinary tract infection (UTI) caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, patients treated for lower UTI with pivmecillinam (n=8) were studied. Patients treated with nitrofurantoin (n=3) and trimethoprim (n=3) or a combination of these agents with pivmecillinam (n=3) were included as a control group. Antimicrobial susceptibility was determined with EUCAST methodology. Bacteriologic cure was defined as <10(3) CFU/ml at follow-up (30 days), and clinical cure as resolved UTI symptoms after completed treatment. All patients receiving pivmecillinam had good clinical response (8/8), but bacteriological cure rates were low (2/8). However, none of the patients with persisting bacteriuria had a relapse of UTI symptoms within 6 months. All isolates were susceptible to the given antimicrobial. Most isolates belonged to the CTX-M-1 group (n=11, 65%) or CTX-M-9-group (n=4, 24%). Four E. coli isolates belonged to the international clone O25b-ST131 (25%). In conclusion, pivmecillinam had good clinical activity against lower UTI caused by ESBL-producing Enterobacteriaceae, but bacteriological cure rates were low. The persistent bacteriuria appears to be of little clinical importance, but larger clinical studies are needed to determine the usefulness of pivmecillinam in infections caused by ESBL-producing bacteria.

Clinical impact of combined viral and bacterial infection in patients with community-acquired pneumonia.

BACKGROUND: New methods for identifying respiratory pathogens have led to several reports of a high yield of mixed infections in patients with community-acquired pneumonia (CAP). The clinical impact of these findings has, however, not been fully evaluated. We aimed to compare patients with a pure bacterial etiology with those with findings of both bacteria and virus regarding severity of illness and length of hospital stay. METHODS: Adults with CAP admitted to Karolinska University Hospital were studied prospectively (N = 184). Microbiological methods included cultures from blood, sputum and nasopharyngeal secretions; sputum samples analyzed with quantitative real-time polymerase chain reaction for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed with polymerase chain reaction and serology for Mycoplasma pneumoniae, Chlamydophila pneumoniae and viruses common in the respiratory tract; and urine antigen assays for detecting pneumococcal and Legionella pneumophila antigens. The pneumonia severity index (PSI) was used to assess the severity of illness. RESULTS: The likelihood of getting a score corresponding to PSI classes IV or V was higher in patients with findings of both bacteria and virus than in those with a bacterial pathogen alone (odds ratio 4.98, 95% confidence interval 2.09-11.89; p < 0.001). The median length of hospital stay was 7 days among patients with mixed infections and 4 days among those with a bacterial etiology alone (p = 0.018). CONCLUSIONS: Patients infected with a virus and a bacterial pathogen more often develop severe CAP and have a longer hospitalization than those with a bacterial etiology alone.

Improvement of CRB-65 as a prognostic scoring system in adult patients with bacteraemic pneumococcal pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of hospitalization among infectious diseases, and is mainly caused by Streptococcus pneumoniae. Modifications were tested to improve the accuracy of CRB-65 as a simple but useful bedside scoring system, and to compare it with 3 established severity scoring systems (PSI, CURB-65 and CRB-65) to predict 30-day mortality in bacteraemic pneumococcal CAP. METHODS: A retrospective analysis was performed on data from 375 adult patients with bacteraemic pneumococcal pneumonia. Mortality, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic (ROC) curve were calculated for stratifications of the PSI, CURB-65 and CRB-65. The prognostic accuracy after addition of underlying disease and/or a peripheral oxygen saturation (SaO2) < 90% was evaluated (DS CRB-65). RESULTS: The mean age of the patients was 61.5 y, and the 30-day mortality was 9%. Coexisting conditions defined according to the pneumonia severity index (PSI) rule (malignancy, liver, cerebrovascular, and renal disease and congestive heart failure, p = 0.006) and SaO2 < 90% (p < 0.0001) were independently associated with mortality. By adding these variables, the area under the ROC curve of CRB-65 increased from 0.77 (95% confidence interval (CI) 0.66-0.84) to 0.83 (95% CI 0.73-0.89) (p = 0.01), similar to that of PSI (0.84) and CURB-65 (0.81). CONCLUSIONS: Modification of CRB-65 with the addition of 1 point for the presence of any underlying disease according to the PSI rule, and with 1 point if SaO2 was < 90%, increased its prognostic accuracy in bacteraemic pneumococcal pneumonia with retained independence of laboratory data. The modified CRB-65 may have potential use in the assessment of prognosis in patients with CAP.

Forecasting drug utilization and expenditure in a metropolitan health region.

BACKGROUND: New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011. METHODS: Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee. RESULTS: The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs. CONCLUSIONS: The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new medicines and various ongoing healthcare reforms and activities to improve the quality and efficiency of prescribing. Nevertheless, we believe our model will be valuable as an early warning system to start developing guidance for new drugs including systems to monitor their effectiveness, safety and cost-effectiveness in clinical practice.

Imported methicillin-resistant Staphylococcus aureus, Sweden.

Countries such as Sweden that have a low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) offer the opportunity to discern and study transmission of imported cases of MRSA. We analyzed 444 imported cases of MRSA acquisition reported in Sweden during 2000-2003. Risk for MRSA in returning travelers ranged from 0.1 (95% confidence interval [CI] 0.01-0.4) per 1 million travelers to Nordic countries to 59.4 (95% CI 44.5-79.3) per 1 million travelers to North Africa and the Middle East. Most imported cases (246, 55%) were healthcare acquired, but regions with the highest risk for MRSA in travelers showed a correlation with community acquisition (r = 0.81, p = 0.001). Characteristic differences in MRSA strains acquired were dependent on the region from which they originated and whether they were community or healthcare acquired. Knowledge of differences in transmission of MRSA may improve control measures against imported cases.

Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods.

BACKGROUND: The microbial etiology of community-acquired pneumonia (CAP) is still not well characterized. During the past few years, polymerase chain reaction (PCR)-based methods have been developed for many pathogens causing respiratory tract infections. The aim of this study was to determine the etiology of CAP among adults-especially the occurrence of mixed infections among patients with CAP-by implementing a new diagnostic PCR platform combined with conventional methods. METHODS: Adults admitted to Karolinska University Hospital were studied prospectively during a 12-month period. Microbiological testing methods included culture from blood, sputum, and nasopharyngeal secretion samples; sputum samples analyzed by real-time quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed by use of PCR; serological testing for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and viruses common in the respiratory tract; and urine antigen assays for detection of pneumococcal and Legionella pneumophila antigens. RESULTS: A microbial etiology could be identified for 67% of the patients (n = 124). For patients with complete sampling, a microbiological agent was identified for 89% of the cases. The most frequently detected pathogens were S. pneumoniae (70 patients [38%]) and respiratory virus (53 patients [29%]). Two or more pathogens were present in 43 (35%) of 124 cases with a determined etiology. CONCLUSIONS: By supplementing traditional diagnostic methods with new PCR-based methods, a high microbial yield was achieved. This was especially evident for patients with complete sampling. Mixed infections were frequent (most commonly S. pneumoniae together with a respiratory virus).