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Pneumococcal Pneumonia.

Pneumococcal pneumonia accounts for about one-sixth to two-thirds of all cases of community-acquired pneumonia. Its high frequency of occurrence worldwide and the high number of deaths associated with it--especially with bacteremic (invasive) disease--mark its importance. Invasive disease is associated with case-fatality rates of 15% to 25% among elderly adults. Penicillin-resistant Streptococcus pneumoniae (PRSP) first appeared in the 1970s, and its increased incidence in the late 1980s signaled its emerging importance. In individual patients in whom PRSP infection is suspected, the clinician must follow guidelines for empiric antibiotic therapy for community-acquired pneumonia until microbiological test results are known. When a diagnosis of pneumococcal pneumonia is established, the clinician should change to a regimen that targets the pneumococcus. Adults at highest risk for death from pneumococcal pneumonia include immunocompetent persons with underlying chronic diseases, immunocompromised persons, elderly persons, and unvaccinated residents of nursing homes and other chronic care facilities. Safe and effective, polyvalent polysaccharide pneumococcal vaccine should be used in persons 2 years of age and older who are at increased risk for serious pneumococcal pneumonia and in all persons 65 years of age and older.

Journal Article↗

Microbiological and inflammatory factors associated with the development of pneumococcal pneumonia.

Pneumococcal pneumonia still is associated with a high mortality rate, despite appropriate antimicrobial therapy. Many gaps remain in the understanding of the pathogenesis of this deadly infection. The microbial and inflammatory events that characterize survival or death after intranasal inoculation of mice with an LD(50) inoculum of Streptococcus pneumoniae were investigated. Survival was associated with rapid bacterial clearance and low inflammation (surfactant and red blood cells in alveoli), but no neutrophil recruitment or lung tissue injury was noted. By contrast, death was preceded by strong bacterial growth that peaked 48 h after the infection and was associated with gradual increases in pulmonary levels of interleukin-6, macrophage inflammatory protein (MIP)-1alpha, MIP-2, monocyte chemoattractant protein-1, KC, and neutrophil recruitment. The injection of tumor necrosis factor-alpha or the addition of lipopolysaccharide or heat-killed S. pneumoniae to the inoculum enhanced early host response and survival. These observations may help develop appropriate markers of evolution of pneumonia, as well as new therapeutic strategies.

Animals↗

Pathogenesis of pneumococcal pneumonia.

Pneumococcal pneumonia poses a serious threat to children in developing countries and remains an important disease in the industrialized world. Capsular polysaccharide is the only bacterial factor proven to contribute to pathogenesis. However, the mechanisms responsible for the hypoxemia, toxemia, crisis, and death associated with this common infection are poorly understood. Toxins secreted by the bacteria, byproducts of bacterial breakdown (e.g., pneumolysin or teichoic acid), or constituents of the intense inflammatory response in the lung might play a role in these phenomena. Malnourished children presumably carry less metabolic reserve with which they can resist the exceptional stresses of pneumococcal disease, and underlying parasitic infestation or other chronic infections, through release of potent mediators such as tumor necrosis factor or platelet-activating factor, might prime the mechanisms of host defense for a more fulminant and systemic response to infection. Vaccines that can protect infants are badly needed, and a better understanding must be gained of the mechanisms by which this pathogen continues to cause such devastating disease in the world's children and elderly.

Child↗

Diagnosis of pneumococcal pneumonia.

Pneumococcal pneumonia presents peculiar problems to the diagnostician. It is at once the most common form of community-acquired bacterial pneumonia and simultaneously the most difficult to document microbiologically. Bacteremia, empyema, meningitis, or septic arthritis due to S pneumoniae unmistakably verifies this bacterium as the cause of a coexistent pneumonia; this coexistence fortunately occurs infrequently. The diagnostic dilemma arises in the less sick patient. While recognizing the common presence of pneumococci in the oropharynx of healthy individuals, we give undue credence to S pneumoniae cultured from sputum obtained by expectoration. At the same time, pneumococci are frequently not found in cultures of sputum obtained from patients with confirmed bacteremic disease. More invasive techniques (transtracheal aspiration, protected bronchoscopic catheter, lung needle aspiration) are too complex, dangerous, or both for routine use. Attempts to detect pneumococcal antigen in blood, sputum, or urine by modern immunologic techniques give promise of avoiding the problems of either contamination or lack of bacteriologic growth. However, they have not yet been evaluated in sufficiently large groups with pneumonia of independently determined bacterial etiology to calculate test sensitivity and specificity. At the present time then, the careful clinician will use all the epidemiologic and clinical evidence at hand, including a careful Gram's stain and culturing of sputum, blood, and other sources, to arrive at the most likely etiology. The probabilities must be weighed in light of the imprecision of current laboratory confirmation and modified by clinical course. Choice of antimicrobial therapy still favor penicillin for patients with community pneumonia severe enough to warrant hospitalization, despite ominous trends in multiple resistance of S pneumoniae.

Anti-Bacterial Agents↗

Pathogenesis of pneumococcal pneumonia.

Pneumococcal pneumonia is the most severe of the common community-acquired pulmonary infections. The recent release of the complete DNA sequence reveals the entire capability of the bacteria and the current challenge is to map gene products to the mechanics of disease. This process will reveal antibiotic targets and protein vaccine candidates crossing serotype boundaries. Choline is a major constituent of surfactant and it is also a required nutrient for the pneumococcus. It appears that choline incorporated into the cell wall can bind the bacteria to the receptor for platelet activating factor, the gateway to invasion. The choline also serves as an antenna to which multifunctional proteins dock, thereby decorating the bacterial surface. This set of 12 choline binding proteins is subject to phase variation of expression resulting in display of different combinations of proteins that adapt the bacteria to survival on the mucosa versus the blood stream. These changes affect protective antigens, adhesions, and lytic proteins tying together the major elements of pneumococcal physiology: natural DNA transformation, adherence and invasion of host cells, and autolysis. Taking these components and building an understanding of disease is challenging. Clearly, the toxin pneumolysin is a major mediator of cell damage in the lung. Inflammation is also incited by cell wall components. The signal transduction pathways that explain pneumococcal inflammation are more complex than those for gram-negative endotoxin.

Animals↗

Pneumonia and pneumococcal infections, with special reference to pneumococcal pneumonia. The 1979 J. Burns Amberson lecture.

An etiologic classification of acute pneumonia was presented and the relative importance of some of the causative agents was briefly reviewed. The early developments of the therapy of pneumococcal pneumonia with type-specific antisera, sulfonamide drugs, and antimicrobial drugs were reviewed, mostly from the experiences of the author at Boston City Hospital. Changes in the occurrence and relative importance of the pneumococcus as a cause of infections associated with bacteremia, empyema, and meningitis were demonstrated, based on cases observed at Boston City Hospital during 12 selected years between 1935 and 1972. These findings, among others, indicate that the pneumococcus is still one of the most important causes of serious bacterial infections and of mortality from such infections, particularly in the elderly. Some possible indications for polyvalent pneumococcal capsular polysaccharide vaccine were discussed, and the need for further extensive clinical and field trials to demonstrate its range of effectiveness was stressed.

Age Factors↗

[Serious infections in alcoholics. 1. Bacteremia, lobar pneumococcal pneumonia and pneumococcal meningitis in alcoholics 1974-1987].

During the period 1974-1987, the frequency of infections in alcoholics discharged from hospitals in Funen showed an increase of 5.53 +/- 3.38 (p = 0.0039) per 10,000 alcoholics discharged per year. The frequency of discharged alcoholics increased by 3.72 +/- 0.60 per 10,000 discharged patients per year. Infections were diagnosed in 0.48 per cent of the discharged alcoholics and in 0.18 per cent of the discharged non-alcoholics (p less than 0.00001). Pneumococcal infections were relatively more frequent in alcoholics (p less than 0.05).

Alcoholism↗

IL-1beta and IL-6 in community-acquired pneumonia: bacteremic pneumococcal pneumonia versus Mycoplasma pneumoniae pneumonia.

Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels in 20 patients with bacteremic Streptococcus pneumoniae community-acquired pneumonia (CAP) were compared with these cytokine levels in 20 patients with Mycoplasma pneumoniae CAP. All 40 patients survived hospitalization and underwent a follow-up examination one month later. Serum IL-1beta and IL-6 levels were determined by the enzyme immunoassay (EIA) method using commercial kits. In the acute phase of CAP, IL-6 levels were significantly higher in the S. pneumoniae group (p = 0.014), while IL-1beta levels were higher in the M. pneumoniae group (p = 0.046). In the convalescence phase, the two cytokines were detected in a considerable number of patients in both groups. In this phase, only the level of IL-1beta was significantly higher in the M. pneumoniae group than in the S. pneumoniae group (p = 0.03). We conclude that the levels of IL-1beta and IL-6 are different between patients with S. pneumoniae-CAP and M. pneumoniae-CAP during the acute phase. In the convalescence phase, cytokine levels remain high in some of the CAP patients, but a significant difference between the groups exists only for IL-1beta. Further studies are required.

Adult↗

Intrathoracic lymphadenopathy in hospitalized patients with pneumococcal pneumonia.

PURPOSES: Pneumococcal pneumonia is the most common etiology for community-acquired pneumonia. The prevalence of lymphadenopathy seen on CT scans in these patients is uncertain. The purpose of this series was to assess the prevalence of intrathoracic lymphadenopathy in hospitalized patients with pneumococcal pneumonia. MATERIALS AND METHODS: We retrospectively identified 35 hospitalized patients with pneumococcal pneumonia who had been evaluated with CT scanning between January 1998 and April 2002. There were 18 men and 17 women with a mean age of 56 years. The study inclusion criteria were as follows: blood culture positive for Streptococcus pneumoniae, clinical diagnosis of pneumonia, and chest CT scan. The study exclusion criteria were known causes of lymphadenopathy. Charts were reviewed for HIV status, smoking history, and comorbidities. CT scans were reviewed for the presence and degree of lymphadenopathy, and the characteristics of pneumonia. The number of enlarged lymph nodes was graded as few (one to two), moderate (three to five), or many (six or more). Pneumonias were described by location, the number of involved lobes, the presence of cavitation, and the presence of pleural effusion. Patients with different comorbidities and different imaging characteristics of pneumonia were compared. RESULTS: Among the 35 patients with pneumococcal pneumonia, intrathoracic lymphadenopathy was present on CT scans in 54% of patients (19 of 35 patients). The lymphadenopathy was ipsilateral to the pneumonia in 100% of patients (19 of 19 patients). One patient also had contralateral lymphadenopathy. The lymphadenopathy was graded as few in 37% of patients (7 of 19 patients), moderate in 37% of patients (7 of 19 patients), and many in 26% of patients (5 of 19 patients). The pneumonia was right-sided in 26% of patients (9 of 35 patients), left-sided in 17% of patients (6 of 35 patients), and bilateral in 57% of patients (20 of 35 patients). Comorbidities included the following: HIV infection (n = 15); smoking (n = 21); emphysema (n = 5); hepatitis C (n = 5); and diabetes (n = 3). The characteristics of pneumonia included the following: multilobar (n = 25); pleural effusion (n = 25); and cavitation (n = 5). The prevalence of lymphadenopathy according to comorbidities and characteristics of pneumonia ranged from 40 to 100%. None of the differences in prevalence of lymphadenopathy among the subgroups was statistically significant. CONCLUSION: Lymphadenopathy is a common CT scan feature of pneumococcal pneumonia in hospitalized patients, in a variety of settings. Therefore, when a patient with pneumococcal pneumonia has lymphadenopathy seen on a CT scan, other etiologies for the lymphadenopathy need not be suspected.

Adult↗

[Analysis of period of positive urinary antigen detection kit for Streptococcus pneumoniae in patients with pneumococcal pneumonia].

The objectives of this study were to investigate the usefulness of the urinary antigen detection kit for Streptococcus pneumoniae and to analyze the duration of urinary antigen presence in pneumococcal pneumonia. We evaluated this kit in 51 patients whose symptoms and laboratory data suggested pneumococcal pneumonia and who were admitted to Toho University Hospital (Tokyo, Japan) between July 2000 and June 2001. S. pneumoniae urinary antigen was detected in 21 of 51 patients. These 21 patients were further investigated with their clinical characteristics and the duration of a positive urinary antigen reaction. S. pneumoniae was isolated by sputum or blood culture in 10 cases (47.6%), whereas 11 cases (52.4%) showed positive results only with urinary antigen but not in cultures. When the urinary antigen kits were tested, 19 cases (90.5%) were treated with antibiotics. Eleven of the 21 patients were continuously tested with this kit. The mean duration for which these patients were urinary antigen-positive was 7.3 weeks. Patients whose pneumonia was severe or who had positive culture results tended to be positive for urinary antigen for a prolonged period. This kit has high sensitivity and specificity, is suitable for rapid diagnosis and is effective after antibiotic therapy. However, because the positive test kit results are prolonged after recovery from pneumonia in some cases, this kit is not suitable for the evaluation of therapeutic effect.

Adult↗

Bacteremic pneumococcal pneumonia in the elderly.

Pneumococcal pneumonia is an increasingly important disorder of the elderly. We reviewed, retrospectively, the clinical and laboratory manifestations of 29 elderly patients with bacteremic pneumococcal pneumonia during a five year period and surveyed the capsular serotypes of all blood isolates. Pneumococcal pneumonia frequently presented with subtle manifestations in these elderly patients: 50% lacked historical features suggestive of pneumonia at the time of diagnosis. A common presentation was fever, altered mental status and dehydration. Recognizing this will allow earlier diagnosis and initiation of therapy. Sixty percent of patients had potential pulmonary pathogens other than pneumococcus in cultures of sputum at the time of pneumococcal bacteremia. Reversible abnormalities of liver function were frequent. Sixty-nine percent of pneumonias were caused by serotypes included in the commercially available vaccine. Continued surveillance of pneumococcal serotypes is important to determine if the widespread use of the vaccine will result in an increased incidence of infection by serotypes which are not in the vaccine. The high mortality associated with pneumococcal pneumonia (31% in this series), particularly in the elderly, emphasizes the need for an effective vaccine.

Aged↗

Clinical profile of serologically diagnosed pneumococcal pneumonia.

OBJECTIVE: To describe the characteristics of serologically diagnosed pneumococcal pneumonia and compare them with those of respiratory syncytial virus (RSV) pneumonia and bacteremic pneumococcal pneumonia. METHODS: IgG antibodies to pneumococcal pneumolysin and C-polysaccharide as well as immune complexes containing IgG antibodies to pneumolysin and C-polysaccharide were measured from acute and convalescent sera of 254 children with community-acquired pneumonia. Evidence of pneumococcal infection was found in 93 children. Clinical and laboratory data were retrospectively collected from the records of 38 children with sole (all tests for 16 other microbes negative) pneumococcal pneumonia and compared with 26 sole RSV-induced pneumonia from the present series and with the data of our 85 bacteremic pneumococcal pneumonia cases reported earlier. RESULTS: Serologically diagnosed sole pneumococcal pneumonia clinically overlapped with RSV pneumonia, but RSV pneumonia was more often associated with tachypnea (45% vs. 17%, P < 0.05) and low white blood cell counts (means, 12.0 x 109/l vs. 20.8 x 109/l; P < 0.001) as well as low serum C-reactive protein levels (means, 28 mg/l vs. 137 mg/l; P < 0.001). Alveolar infiltrates were found in 15% of chest radiographs of children with RSV pneumonia compared with 76% of those in children with sole pneumococcal pneumonia (P < 0.001). Patients with bacteremic pneumonia more often appeared ill (79% vs. 50%, P < 0.001) and more often had typical pneumococcal pneumonia with high fever, leukocytosis and lobar infiltrates in their chest radiographs (70% vs. 34%, P < 0.05) than those with serologically diagnosed pneumococcal pneumonia. CONCLUSIONS: Serologically detected pneumococcal pneumonia differs significantly from RSV pneumonia in laboratory and chest radiography findings, but the clinical signs and symptoms overlap considerably. Bacteremic pneumococcal pneumonia is a more severe illness than the serologically diagnosed one.

Adolescent↗

Cellulitis in complicated pneumococcal pneumonia.

Serious complications of pneumococcal pneumonia have become uncommon. This has been attributed to decline in pneumococcal infection (van Roy et al. 1971; Foy et al. 1975), but in this country it is more likely to be due to effective antibiotic therapy. We report a case of pneumococcal pneumonia with severe complications (including a very unusual one) which probably arose through antibiotic failure.

Aged↗

Plasma volume expansion in canine pneumococcal pneumonia: its effects on respiratory gas exchange and pneumonia size.

Patients with pneumococcal pneumonia are often given fluids intravenously for hydration and maintenance of circulating blood volume. We studied the effects of plasma volume expansion on respiratory gas exchange and pneumonia size in a canine model of lobar pneumonia. Seven ventilated anesthetized dogs (Group T) with left lower lobe pneumococcal pneumonia were infused with dextran 75 in 0.9% saline solution to increase the pulmonary capillary wedge pressure to 10 mmHg for 3 h. These were compared with 7 control dogs (Group C) with left lower lobe pneumonia. Measurements of cardiac output, intrapulmonary shunt (QS/QT), and lobar distribution of perfusion were taken at baseline (B), immediately after volume infusion (V), and 3 h later (F); similar intervals were used in control animals. In Group T, QS/QT increased significantly from 24% at B to 34% at F. Part of this increase in QS/QT occurred immediately after volume infusion (29% at V) and was associated with the concomitant increase in cardiac output (4.7 L/min at B to 10.6 L/min at F). In Group C, there were no changes in cardiac output or QS/QT. At autopsy, mean wet weight for both lower lobes in Group T were greater than in Group C. Accordingly, small elevations in pulmonary capillary wedge pressure associated with fluid administration caused large increases in lobar wet weights. At least in part, these increases represented transudation of plasma and crystalloid into alveolar spaces and suggested large increases in extravascular lung liquid flux from inflamed vessels in infected lung.

Animals↗

Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia.

BACKGROUND: Although monotherapy for pneumococcal pneumonia is standard, a survival benefit of combination beta-lactam and macrolide therapy has been suggested. HYPOTHESIS: Initial empirical therapy with a combination of effective antibiotic agents would have a better outcome than a single effective antibiotic agent in patients with bacteremic pneumococcal pneumonia. METHODS: A review of adult bacteremic pneumococcal pneumonia within the Methodist Healthcare System, Memphis, Tenn, between January 1, 1996, and July 31, 2000. Empirical therapy was defined as all antibiotic agents received in the first 24 hours after presentation. On the basis of culture results, empirical therapy was classified as single effective therapy (SET), dual effective therapy (DET), or more than DET (MET). Acute Physiology and Chronic Health Evaluation II (APACHE II)-based predicted mortality, and Pneumonia Severity Index scores were calculated. RESULTS: Of the 225 patients identified, 99 were classified as receiving SET, 102 as receiving DET, and 24 as receiving MET. Compared with the other groups, patients who received MET had statistically significantly more severe pneumonia as measured by the Pneumonia Severity Index score (P =.04) and predicted mortality (P =.03). Mortality within the SET group was significantly higher than within the DET group (P =.02, odds ratio, 3.0 [95% confidence intervals, 1.2-7.6]), even when the DET and MET groups (P =.04) were combined. In a logistic regression model including antibiotic therapy and clinical risk factors for mortality, SET remained an independent predictor of mortality with a predicted mortality-adjusted odds ratio for death of 6.4 (95% confidence intervals, 1.9-21.7). All deaths occurred in patients with a Pneumonia Severity Index score higher than 90, and the predicted mortality-adjusted odds ratio for death with SET in this subgroup was 5.5 (95% confidence intervals, 1.7-17.5). CONCLUSIONS: We found that SET is associated with a significantly greater risk of death than DET. Therefore, monotherapy may be suboptimal for patients with severe bacteremic pneumococcal pneumonia who have Pneumonia Severity Index scores higher than 90.

APACHE↗

IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection.

Secondary pneumococcal pneumonia is a serious complication during and shortly after influenza infection. We established a mouse model to study postinfluenza pneumococcal pneumonia and evaluated the role of IL-10 in host defense against Streptococcus pneumoniae after recovery from influenza infection. C57BL/6 mice were intranasally inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS (control) on day 0. By day 14 mice had regained their normal body weight and had cleared influenza virus from the lungs, as determined by real-time quantitative PCR. On day 14 after viral infection, mice received 10(4) CFU of S. pneumoniae (serotype 3) intranasally. Mice recovered from influenza infection were highly susceptible to subsequent pneumococcal pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after pneumococcal infection. Furthermore, 1000-fold higher bacterial counts at 48 h after infection with S. pneumoniae and, particularly, 50-fold higher pulmonary levels of IL-10 were observed in influenza-recovered mice than in control mice. Treatment with an anti-IL-10 mAb 1 h before bacterial inoculation resulted in reduced bacterial outgrowth and markedly reduced lethality during secondary bacterial pneumonia compared with those in IgG1 control mice. In conclusion, mild self-limiting influenza A infection renders normal immunocompetent mice highly susceptible to pneumococcal pneumonia. This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs.

Animals↗