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Comparison of bacteraemic community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae in an intensive care unit.

In a study of 41 consecutive patients with bacteraemia-associated community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae an attempt was made to determine whether distinguishing criteria of disease due to these organisms could be identified according to demographic features and the results of initial clinical and laboratory investigations. Such information would aid in the early initiation of appropriate antimicrobial therapy. The most significant difference between the two groups of patients was the lower platelet count in the K. pneumoniae group (p less than 0.005). In addition leucopenia (p less than 0.05), higher serum albumin (p less than 0.05), and the male sex (p less than 0.05) featured with an increased frequency in patients with pulmonary infection due to K. pneumoniae. Initial antimicrobial therapy in critically ill patients with community-acquired lobar pneumonia and thrombocytopenia, particularly when associated with leucopenia and in male patients, should include agents effective against K. pneumoniae.

Adult

Chlamydia pneumoniae strain TWAR, Mycoplasma pneumoniae, and viral infections in acute respiratory disease in a university student health clinic population.

Clinical and serologic data were collected on 667 University of Washington students who presented to the David Hall Student Health Center between 1983 and 1987 with acute respiratory disease. Sera were tested for evidence of acute or past infections with Chlamydia pneumoniae strain TWAR, Chlamydia trachomatis, Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenovirus, and respiratory syncytial virus. Pharyngeal swab specimens were cultured for C. pneumoniae and C. trachomatis, but not for the other agents. Evidence of acute infection with C. pneumoniae was found in 20 patients and evidence of an acute infection with M. pneumoniae in 29 patients. C. pneumoniae was associated with 9% and M. pneumoniae with 11% of 149 pneumonias diagnosed clinically, and with 20% and 22%, respectively, of the 59 pneumonias confirmed on chest radiograph. There was no evidence of seasonality in C. pneumoniae or M. pneumoniae infections. Compared with patients with M. pneumoniae, patients with C. pneumoniae were less likely to have a temperature greater than 37.8 degrees C (10% vs. 34%), but were more likely to present with a sore throat (80% vs. 52%) or hoarseness (30% vs. 3%). The mean number of days from onset of symptoms until enrollment was longer in patients with C. pneumoniae infections than in those with M. pneumoniae (12.8 vs. 7.9 days), or those with a viral infection (12.8 vs. 7.3 days), suggesting a more gradual onset of disease caused by C. pneumoniae.

Adolescent

[Analysis of immunoprotection against fatal experimental Klebsiella pneumoniae pneumonia].

Comparatively little is known about the immunoprotective mechanisms against K. pneumoniae pneumonia. Whether the antibody against K. pneumoniae protects against K. pneumoniae pneumonia is not fully known. This study was designed to investigate some of the murine host factors responsible for immunization with K. pneumoniae DT-S to infection by aerosol inhalation with K. pneumoniae DT-S: in particular, the role of the antibody and the immunoprotective antibody which was the antibody against which component of K. pneumoniae was investigated. Mice preimmunized by aerosol inhalation with live or formalin-killed DT-S and mice preimmunized intravenously with live DT-S did not protect against infection by aerosol inhalation with DT-S. Mice preimmunized intravenously with formalin-killed DT-S were shown to protect significantly against fatal experimental K. pneumoniae pneumonia (p less than 0.01). This immunoprotection against fatal experimental pneumonia was related to titers of anti-ultrasonicates of DT-S antibody detected by an Enzyme-linked immunosorbent assay (ELISA). That this immunoprotection is dependent on the antibody against which component of DT-S was investigated by ELISA. An ELISA was performed to detected antibody against purified capsular polysaccharide (CPS), lipopolysaccharide (LPS) and outer membrane proteins (OMP). Mice preimmunized intravenously with formalin-killed DT-S were detected to have antibodies against LPS, but not to CPS and OMP. Then the immunoprotection against fatal experimental pneumonia was related to titers of anti-LPS antibody. These findings indicate that anti-LPS antibody may play a major role in the protection against fatal experimental K. pneumoniae pneumonia.

Animals

Relation of physicians' predicted probabilities of pneumonia to their utilities for ordering chest x-rays to detect pneumonia.

To investigate the relation between physicians' predicted probabilities of pneumonia and their utilities for ordering chest x-rays to detect pneumonia, the authors studied 52 physicians who ordered chest x-rays of 886 patients presenting to an emergency department with fever or respiratory complaints. Physicians estimated the probability of pneumonia prior to obtaining the results of the chest x-ray. Utilities were assessed by asking physicians to consider a hypothetical patient presenting with acute respiratory symptoms, with unknown chest x-ray status, and to rank on a scale from +50 ("best thing I could do") to -50 ("worst thing I could do") their rating scale utilities for not diagnosing pneumonia and not ordering a chest x-ray when the patient had pneumonia (i.e., missing a pneumonia), and for diagnosing pneumonia and ordering a chest x-ray when the patient did not have pneumonia (i.e., ordering an unnecessary x-ray). The utility for ordering an unnecessary x-ray was negatively correlated with average predicted probability (r = -0.1495, p = 0.29), whereas the utility for missing a pneumonia was positively correlated with average predicted probability (r = 0.2254, p = 0.11), although the correlations were not statistically significant. Relative chagrin, defined as the difference in these utilities, was significantly inversely correlated with average predicted probability (r = -0.2992, p less than 0.035), even after adjusting for the prevalence of pneumonia seen by each physician (partial r = -0.42, p less than 0.0027). It is concluded that physicians who experienced greater regret over missing a pneumonia than over ordering an unnecessary x-ray estimated lower probabilities of pneumonia for patients for whom they ordered x-rays.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis

Detection of IgM antibodies to Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci from Japanese infants and children with pneumonia.

Chlamydia trachomatis (C. trachomatis) is now well established as a pathogen of neonatal inclusion conjunctivitis and infantile pneumonia. C. pneumoniae (TWAR) and C. psittaci also cause pneumonia and other respiratory infections. Serum samples from 223 Japanese infants and children with pneumonia were tested for IgM antibodies to C. trachomatis, C. pneumoniae and C. psittaci. IgM antibodies to C. trachomatis were measured by an enzyme immunoassay (EIA) and by a microimmunofluorescence (MIF) test. IgM antibodies to C. pneumoniae and C. psittaci were determined by MIF. Of 223 patients, 48 (21.5%) were positive for IgM antibodies to C. trachomatis, 11 (4.9%) were positive for C. pneumoniae and 5 (2.2%) were positive for C. psittaci. From nasopharyngeal swabs collected from 87 infants with pneumonia (0 to 1 year of age), we attempted to isolate C. trachomatis with tissue culture. C. trachomatis was isolated from 23 (26.4%) of 87 infants with pneumonia, and IgM antibodies to C. trachomatis were detected in 17 (19.5%) of them. Our data suggest a role for chlamydial infection in childhood pneumonia beyond infancy with both C. trachomatis and C. pneumoniae being contributing pathogens.

Adolescent

Parenteral followed by oral ofloxacin for nosocomial pneumonia and community-acquired pneumonia requiring hospitalization.

We report a multicentric, open trial of intravenous followed by oral ofloxacin, 400 mg every 12 h, as therapy for 100 cases of nosocomial pneumonia and community-acquired pneumonia requiring hospitalization. The typical subject was 57 yr old, and underlying diseases, such as chronic obstructive pulmonary diseases (COPD), diabetes mellitus, and congestive heart failure, were common. For 10 subjects previous therapy had failed. There were 118 pathogens isolated in blood or sputum; S. pneumoniae was the most common (42), followed by H. influenzae (13), Klebsiella spp. (11), and S. aureus (10). Ofloxacin was administered for an average of 5.7 days intravenously followed by 6.9 days orally. Response to therapy was judged to be cure in 71 subjects, improvement in 24, and failure in 5. Among the more seriously ill subjects, ofloxacin therapy was successful for four of five immunocompromised subjects, for 12 of 12 subjects with nosocomial pneumonia, three of whom were on the ventilator, and for nine of 10 subjects with community-acquired pneumonia and bacteremia, including seven of eight cases due to S. pneumoniae. Univariate risk factor analysis revealed underlying COPD and/or tachypnea upon admission to be associated with failure of ofloxacin therapy, with bacteremia suggestive of failure. Conversely, ofloxacin was equally effective in cases in whom previous therapy failed and in cases of nosocomial pneumonia, multilobar pneumonia, and/or pneumonia due to S. pneumoniae. Results for P. aeruginosa were inconclusive. Intravenous followed by oral ofloxacin was highly effective in many difficult cases of pneumonia.

Administration, Oral

Risk of pneumonia in patients previously treated in hospital for pneumonia.

Although elderly patients who are admitted to hospital for any disease have a higher risk of pneumonia subsequently, whether those treated in hospital for pneumonia are at even greater risk is unknown. Therefore we retrospectively assessed morbidity and mortality due to pneumonia after discharge in 573 consecutive patients admitted to hospital for pneumonia, gastrointestinal infection, renal infection, or erysipelas. Average follow-up was 34 months. The incidence rate for pneumonia was 5.45 times higher in the group of patients discharged after pneumonia than in the other groups combined (95% confidence interval 2.89-10.26; p less than 0.001), and this group also had more deaths due to pneumonia (p = 0.06). For patients 50 years or older Streptococcus pneumoniae is the main cause of pneumonia. Pneumococcal vaccination after hospital treatment for an episode of pneumonia might be a cost-effective means of preventing disease in this group.

Adult

[Role of capsular polysaccharide and lipopolysaccharide of Klebsiella pneumoniae in experimental mice pneumonia model].

In this study, role of capsular polysaccharide (CPS) and lipopolysaccharide (LPS) of Klebsiella pneumoniae was investigated in experimental mice pneumonia model. Inoculation with K. pneumoniae mucoid strain DT-S into mice lung induced expansive, voluminous lethal pneumonia characterized with thickening of the alveolar septa caused by infiltration of inflammatory cell and packing of bacteria within alveolar spaces. On the other hand, mice lung inoculated with K. pneumoniae DT-X, which was non-mucoid mutant isolated from DT-S during natural passage, showed infiltration of inflammatory cell into alveolar spaces but there was no death of mice during the course of this pneumonia. Inoculation of CPS 100 micrograms of DT-S strain into mice lung induced lesser extent of accumulation of inflammatory cell than that of LPS 4 micrograms of this strain. Stimulation of alveolar and peritoneal macrophage with CPS, even at a concentration of 100 micrograms/ml, induced weaker Interleukin-1 (IL-1) activity than stimulation with LPS 4 micrograms/ml. These results suggest that since CPS of K. pneumoniae DT-S encapsulate bacteria including LPS, CPS may inhibit chemotaxis of inflammatory cell and IL-1 production of macrophage to be induced by LPS during course of pneumonia. It is speculated that existence of CPS have important role in modulating host response to bacterial LPS, and this effect of CPS may be related with difference of pathological findings of lung and lethality between K. pneumoniae DT-S and DT-X.

Animals

Analysis of K. pneumoniae by monoclonal antibody: immunohistochemical detection of K. pneumoniae surface antigen injected into mice and rats.

The monoclonal antibody Kp62 recognized surface antigenic determinants of some strains of Klebsiella pneumoniae. The antigen recognized by Kp62 was demonstrated on the bacterial surface using immunoelectron microscopy. Kp62 reacted with K. pneumoniae No. 1 or K. pneumoniae B 5055 and lipopolysaccharide (LPS) from the same bacteria. However, Kp62 was not inhibited by the LPS from Escherichia coli (E. coli) O111:B4 and E. coli O55:B5. Thus, Kp62 might be a useful monoclonal antibody to detect K. pneumoniae and LPS from K. pneumoniae. The possibility to visualize the localization of K. pneumoniae LPS injected into animals using immunohistochemical methods with this monoclonal antibody was examined. It was possible to detect the injected LPS in the spleen of mouse and rat with the monoclonal antibody to K. pneumoniae. In order to detect the early events taking place in the spleen after intravenous injection of LPS, time course of LPS distribution in mice and rats was studied. After 30 min, 2, 4, 8 and 24 h LPS localized in the marginal zone (MZ) in mice and rats, although the degree of LPS positive cells varied. The cells responsible for trapping the injected LPS appeared to be marginal zone macrophages. The early trapping of LPS by marginal zone macrophages was thought to be important for the following immune responses to the injected LPS. Interestingly the antigenic determinant on the injected LPS appeared to last long on or within the cells in the spleen from the injected animals. Such a remaining antigen might be important for the continuous stimulation of B cells by the LPS. With respect to the distribution of red pulp (RP) and white pulp (WP), we found the varied distribution of LPS between mouse and rat, and SPF and conventionally fed (Conv) animals. For example, LPS-positive cells in RP of rat were scarce, while significant degree of LPS-positive cells were observed in mice. And in WP, LPS-positive cells were observed in Conv DA rats, but not in mice or SPF-fed Wistar rats. These results may suggest that the mode of antigen processing may be different in the spleen of rat and mouse or even among the different strain of rats and previous sensitization to the LPS (or the similar antigenic determinants) may lead to the different distribution of LPS in the spleen. The monoclonal antibody specifically raised against K. pneumoniae was shown to be very useful to follow the fate of LPS derived from K. pneumoniae using immunohistochemical method.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Culture-confirmed pneumonia due to Chlamydia pneumoniae.

Diagnosis of infection caused by Chlamydia pneumoniae, a newly recognized respiratory pathogen, has proved difficult. Between July 1987 and April 1988, culture and serologic tests for C. pneumoniae were done on specimens from 49 patients with pneumonia seen at an Atlanta hospital emergency room. Cultures from 3 patients (6%) grew C. pneumoniae. Genus-specific Chlamydia complement fixation titers and microimmunofluorescence titers for C. pneumoniae were suggestive of acute infection in all 3 culture-positive patients. Three other patients had evidence of acute disease by published criteria for antibody titers. Most studies of C. pneumonia have not had culture-proven cases; the 6% rate of positive cultures in this study support the role of C. pneumoniae as a cause of pneumonia. More widespread availability of simplified culture systems for C. pneumoniae is needed. Caution should be used when interpreting serologic tests in the absence of culture confirmation.

Adolescent

Prevalence of Mycoplasma pneumoniae in children with pneumonia in Zaria, Nigeria.

The prevalence of Mycoplasma pneumoniae in children suffering from pneumonia was investigated, using complement fixation and growth inhibition tests. From the sera of 104 children with pneumonia, 32 (31%) showed a CF titre greater or equal to 1:64, while all the 52 control children of the same age and sex had a CF titre less than 1:16. Children 6-10 years of age had the highest positive titre (41%) while the age groups 3-5 years and 0-2 years had positive titres of 30 and 28%, respectively. Both sexes were equally affected (33% male, 29% female). Mycoplasma pneumoniae was isolated in two children whose CF antibody titres were 1:16. It is concluded that M. pneumoniae plays an important role as an aetiological agent of pneumonia in children in Zaria, Nigeria, and could be included in the routine diagnostic protocol of pneumonia, especially during the dry harmattan months when cases of lobar pneumonia are prevalent.

Bronchopneumonia

Mycoplasma pneumoniae and the aetiology of lobar pneumonia in northern Nigeria.

Over a six-month period we studied 74 adult Nigerians who presented consecutively to Ahmadu Bello University Teaching Hospital, Zaria, with lobar or segmental pneumonia. Pneumococcal infection was diagnosed in 50% by the detection of pneumococcal polysaccharide antigen in serum or purulent sputum: 24% had pneumococcal antigenaemia. Twelve patients had evidence of Mycoplasma pneumoniae infection and half of these also had pneumococcal infection. The suggestion that M pneumoniae respiratory infection may predispose to serious bacterial pneumonia is discussed. The initial clinical and radiological features were similar in the pneumococcal and M pneumoniae groups. Raised cold agglutinin titres were not a reliable indication of M pneumoniae infection, perhaps due to altered autoantibody production in Nigerians. Pneumonia was commoner in the dry season, probably related to depressed nasopharyngeal defences caused by drying. Less common causes of lobar pneumonia that were found are also discussed and no cases of legionnaires' disease were identified.

Adult

Comparative activity of fluorinated quinolones in acute and subacute Streptococcus pneumoniae pneumonia models: efficacy of temafloxacin.

We have compared the efficacy of temafloxacin against Streptococcus pneumoniae in experimental murine pneumonia models with that of ofloxacin and ciprofloxacin. Erythromycin and amoxycillin were used as reference agents. Two different strains of mice were used: Swiss mice develop acute pneumonia and die within three to four days, while C57B1/6 mice develop subacute pneumonia and die within eight to ten days. In both cases all animals quickly become bacteraemic. Mice were infected with approximately 10(5) cfu of a virulent S. pneumoniae strain, serotype 3 (P4241), by the intra-tracheal per oral route. In Swiss mice, subcutaneous treatments were initiated early (18 h post-infection) and given every 12 h for 72 h. A 79% cumulative survival rate was obtained in temafloxacin-treated mice (50 mg/kg); a figure not significantly different from those for erythromycin and amoxycillin but far higher than those for ofloxacin and ciprofloxacin (7% survivors). Pulmonary clearance of bacteria was consistent with the survival rates. Complete clearance of bacteria in the lungs and blood was achieved using temafloxacin (50 mg/kg), whereas mice remained bacteraemic even with increased dosages of ofloxacin and ciprofloxacin. In the subacute pneumonia C57B1/6-mice model, the superior efficacy of temafloxacin (compared to ofloxacin and ciprofloxacin) was also seen even when treatment was initiated at late stages of the disease (up to 96 h post-infection). The pharmacokinetics of temafloxacin account for its better efficacy against S. pneumoniae pneumonia relative to the other quinolones.

Acute Disease

[The value of criteria for pneumonia in the diagnosis of a ventilated pneumonia].

Reliable diagnosis of pneumonia in ventilated patients is frequently difficult, since there is no single specific criterion. In the present study, the following diagnostic criteria for pneumonia were checked in 25 ventilated patients: 1. temperature over 38.5 degrees C, 2. leukocytosis over 12,000/mm3, infiltration in the x-ray, 4. positive auscultatory findings, 5. purulent tracheal secretion (TS), 6. positive bacteriological findings (TS). Diagnosis of bacterial pneumonia was assumed if in the bronchoalveolar lavage (BAL) the concentration of a plausible causative organism was greater than or equal to 10(4)/ml and the "Bacterial Index" (BI) was greater than or equal to 6 (16). 15 patients fulfilled more than four criteria for pneumonia. In all patients the concentration of bacteria in the BAL was greater than or equal to 10(4)/ml (median 10(6)/ml, BI: 10). 10 patients fulfilled less than or equal to 4 criteria of pneumonia. In three of the patients, BAL was sterile, in four cases organisms less than 10(4) were isolated; none of these patients received antibiotics and diagnosis of pneumonia was not confirmed in the further course of illness. In three patients, bacteria greater than or equal to 10(4)/ml were isolated (BI 9, 10, 13); they improved under adequate antibiotic therapy. We conclude from these results that "as a rule" more than four of the criteria of pneumonia specified above should be present for diagnosis of pneumonia in ventilated patients in a surgical intensive-care ward. If there is any doubt, BAL should be performed to confirm the diagnosis.

Adult

[A case of pneumonia due to Mycoplasma pneumoniae accompanying high adenosine deaminase activity in pleural effusion].

We experienced a 5-year-old male case of Mycoplasma pneumoniae pneumonia accompanying Adenosine Deaminase (ADA) activity in pleural effusion. Chest roentgenograms revealed the infiltration in the left upper lung field and the left pleural effusion. In serum, the M. pneumoniae CF titer increased to 1:512. The pleural effusion was yellowish in color, with a specific gravity of 1.030, protein 3.7 g/dl, glucose 101 g/dl, and ADA 50 IU/l. Pleural effusion accompanying M. pneumoniae pneumonia is rare, and the high ADA activity in this case has been reported only in one other case. This is a report of a high activity of ADA in the pleural fluid by M. pneumoniae pneumonia.

Adenosine Deaminase