Background -The prevalence of microorganisms causing community-acquired pneumonia in patients who required admission to hospital was investigated and the percentage of cases whose aetiology remained unknown due to the study design and logistical problems estimated. Methods -Between January 1991 and April 1993 all patients with community-acquired pneumonia admitted to six hospitals were included in the study. Aetiological diagnosis, categorised as definite, probable and possible, was based on the results of routine microbiological and serological tests.Results -Three hundred and thirty four patients with a median age of 65 (range 17-92) years were enrolled in the study. The diagnosis of community-acquired pneumonia was definite in 108 cases, and probable or possible in 73 and 27 cases, respectively, including dual infections. Streptococcus pneumoniae was the predominant pathogen (27%) followed by viruses and Haemophilus influenzae (both about 8%) and Mycoplasma pneumoniae (6%). Chlamydia spp (3%) and Legionella pneumophila (2%) were less frequently detected. No diagnosis was made in 45% of the cases. With adjustment for antimicrobial therapy before admission and for other logistical considerations, it is estimated that the aetiology could have been ascertained in 65% of the cases. Conclusions -Streptococcus pneumoniae is the most frequently detected cause of community-acquired pneumonia. The inability to detect a micro-organism results mainly from the use of routine diagnostic tests and, to a lesser extent, from logistical problems or the use of antibiotics before admission. (Thorax 1995;50:543-547)

Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

The objective of this study was to assess the predictive value of signs, symptoms, and rapidly available laboratory parameters for pneumococci in community-acquired pneumonia (CAP). A prospective study on patients with CAP who were admitted to hospital was conducted. Clinical and laboratory data were collected according to a protocol. Two hundred sixty-eight patients aged 18 years or older, not living in a nursing home or not admitted to hospital within one week of this admission, with a new infiltrate on the chest radiograph consistent with pneumonia were included. According to microbiological and serological tests, patients were allocated to one of two aetiological groups, Streptococcus pneumoniae or "other pathogens". Seventy-three variables were examined for a correlation with one of the aetiological categories by means of univariate and multivariate analysis. The resulting discriminant function was considered a clinical test for which posttest probabilities for pneumococcal pneumonia were calculated. Streptococcus pneumoniae was demonstrated in 79 patients and other pathogens in 83; no pathogens were detectable in 106 patients. The variables "cardiovascular disease", "acute onset", "pleuritic pain", "gram-positive bacteria in the sputum Gram stain", and "leucocyte count" correctly predicted the cause of CAP in 80% of all cases in both groups. Depending on the prevalence of Streptococcus pneumoniae, posttest probabilities for pneumococcal pneumonia were up to 90%. It is concluded that data on history, together with the result of the Gram stain of sputum and the leucocyte count, can help to distinguish Streptococcus pneumoniae from other pathogens causing CAP.

After an oral dose of 500 mg of azithromycin in patients with community-acquired pneumonia, their serum concentrations ranged between 0.06 and 0.25 mg/liter during the first 12 hours; the calculated percentages of unbound drug varied between 45 and 86%. This study shows that in these patients, the total levels of azithromycin in serum are lower than those expected and that the percentage of bound drug is clinically irrelevant.The pharmacokinetics of azithromycin, one of the new macrolides, are characterized by high tissue concentrations and relatively low serum concentrations. In healthy volunteers, an oral dose of 500 mg of azithromycin leads to maximum serum concentrations of 0.4 to 0.45 mg/liter within 2 to 3 h (10). Azithromycin mainly binds to ␣ 1 -acid glycoprotein (AAG) (10). Concentrations of AAG may increase two-to fourfold during an infection (5), which could result in a decrease of the unbound, i.e., active, fraction of the drug (12). However, although the influence of an infection on the pharmacokinetics of azithromycin has not yet been examined in detail, dosage schedules are based on pharmacokinetics in healthy subjects.The aim of the present study was to establish whether the concentration of azithromycin in patients with community-acquired pneumonia (CAP) corresponds to that found for healthy volunteers. The concentration of AAG was used to calculate the estimated percentage of unbound drug.The Review Committee of the Leiden University Hospital had no objections to this study. Patients with CAP participated in the present study after giving informed consent. Some of the exclusion criteria were the need for intravenous treatment or the presence of disorders which affect the absorption of orally administered drugs. On the 1st day, the patients received 500 mg of azithromycin orally twice, which was followed by 500 mg once daily for the next 4 days. Eight patients, including four females, ranging in age from 32 to 75 years old were enrolled. Streptococcus pneumoniae was detected in four patients (all sensitive to the study drug), and Legionella pneumophila and Mycoplasma pneumoniae were detected each in one patient. In two patients, no pathogen could be found. Only in one patient (subject 5), who had a mycoplasmal pneumonia, did treatment fail.Blood samples were collected immediately before and 3 and 12 h after the first and second doses of azithromycin. Total (bound plus unbound) serum concentrations were determined by an agar well diffusion bioassay (3). The amount of AAG was determined by kinetic nephelometry (Beckman Array Protein System; Beckman Instruments, Inc., Galway, Ireland) in blood samples collected prior to the first dose of azithromycin.Although physical-chemical properties of AAG can change during disease states, values of K d (dissociation constant) and CB max (maximum binding capacity) are found in a relatively small range (6). Therefore, we used the results of a proteinbinding study of azithromycin in healthy volunteers performed by Foulds et al. (2) where CB and CU are the serum ...

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