Pneumococcal pneumonia is an acute bacterial infection of the lungs caused by pneumococcus and characterized clinically by an abrupt onset, with rigor, fever, chest pain, cough, and bloody sputum.
History Of Pneumonia
Although pneumonia was known to Hippocrates, its usual cause was not learned until late in the nineteenth century. Pneumococcus was first isolated from normal saliva in 1881 by Pasteur and by Sternberg. Several years later its causative role in pneumonia was demonstrated independently by Frankel and Weichselbaum. Identification of different serologic types of pneumococci, which began with the studies of Neufeld in Germany and Dochez in this country, led eventually to serum therapy and to the highly significant observations of Avery, Enders, Heidelberger, and Goebel concerning the chemical nature of the capsular antigen and its relation to pathogenicity. In 1928 Griffith demonstrated that pneumococci of one type may be transformed into pneumococcal cells of another type.
This remarkable transforming reaction was shown by Avery and his collaborators to depend upon the highly polymerized deoxyribonucleic acid of the bacterial cell, thus initiating the modern revolution in molecular biology. Present concepts of the pathogenesis of pneumococcal pneumonia derive from the systematic histologic investigations of Robertson and Loeschcke. The seriousness of the disease in man was drastically modified by the advent of sulfonamide therapy in the late 1930’s, and later treatment was further improved by the introduction of penicillin and other antimicrobial drugs.
Bacteriology and Immunology
Bacterial pneumonias occurring in otherwise healthy persons are usually caused by Diplococcus pneumoniae. The somatic portion of the lancet-shaped pneumococcal cell is gram-positive. In its virulent form pneumococcus has an outer capsule consisting of a loosely packed gel containing a high molecular polysaccharide polymer that is specific for each serologic type. In addition to the type- specific capsular antigen, there is a species- specific carbohydrate in the cell wall, known as the “C” substance. A non-tvpe-specific protein antigen can also be demonstrated in the somatic portion of the cell, and Austrian and MacLeod have identified a type-specifk protein analogous to the M substance of beta-hemolytic streptococci.
The capsule of pneumocOccus- acts as an armor against phagocytic cells and thus contributes significantly to the pathogenicity of the organism. Pneumococcal variants having no capsules (rough or R strains) are essentially a virulent. Antibody to the type-specific carbohydrate promotes phagocytosis by combining with the highly polymerized polysaccharide of the capsular gel. Antibodies to the other antigens have never been shown to affect significantly the invasive properties of the organism. The pneumococcal cell also produces hyaluronidase, a pneumolysin that causes hemolysis in blood agar, and autolytic enzymes that, when activated, render the organism gram-negative and eventually cause its dissolution.
Pneumococci can be grown on a variety of bacteriologic media. Blood agar and beef infusion broth containing 0.5 per cent dextrose and 5 to 10 per cent blood or serum are the media most commonly used. The pH of the medium should be approximately 7.5. In a suitable broth the organism grows rapidly, and on blood agar virulent (smooth, S) strains form circular, glistening, dome-shaped colonies that are alpha-hemolytic. Because of the great quantity of capsular polysaccharide formed by type III pneumococcus, its colonies are more mucoid and usually about twice as large (2 mm. in diameter) as those of other types. Unlike the alpha-hemolytic Streptococcus, pneumococcus is soluble in bile, sodium deoxycholate and other surface-active agents, is highly sensitive to optochin, and is mouse-virulent. Most strains are virulent for mice, rats, rabbits, dogs, and monkeys as well as for man.
The extraordinary virulence of pneumococci for mice may be made use of in isolating the organisms from sputum. The technique usually used consists in injecting intraperitoneally 0.5 ml. of sputum previously emulsified by having been drawn repeatedly into a tuberculin syringe. When virulent pneumococci are present, the mouse usually dies within 48 hours, and a pure culture of the organism can be isolated from the heart’s blood. Since other bacteria in the sputum do not ordinarily produce fatal infections in mice, the animal serves as a convenient and highly sensitive differential “culture medium” for the isolation of pneumococci.
More than 82 different serologic types of pneumococci have been identified by agglutination tests with specific antiserums or by the quellung test. The latter is based upon the characteristic capsular “swelling” (quellung) caused by homologous type-specific antibody. Tests used for the identification of type-specific antibody in serums and other body fluids include, in addition to the agglutination and quellung methods, mouse protection tests, precipitin reactions, and opsonic cytophagic and bactericidal tests.
Anticapsular antibody usually appears in the blood of patients with pneumococcal pneumonia between the fifth and tenth days of the disease. In some untreated patients its appearance coincides with recovery; in others no such relation is demonstrable. In severe pneumococcal infections, specific polysaccharide, which has diffused away from the multiplying bacteria, can often be identified in the urine by precipitin test and sometimes can even be detected in the blood. Patients frequently continue to excrete the capsular carbohydrate in the urine for days and even weeks after recovery.
Pneumococcal pneumonia may occur at any season, but is most common during the winter and early spring, when viral respiratory infections are most prevalent The types of pneumococci that most commonly cause pneumonia in adults are types I, III, IV, V, VII, VIII, XII, XIV, and XIX. Together, these nine types account for more than three quarters of all cases. The most common types encountered in childhood pneumonias are I. VI; XIV, and XIX.
Pneumococci, particularly of the higher types, are frequently present in the respiratory tracts of normal subjects. Ordinarily the prevalence of carriers of highly pathogenic types is relatively low, except for type III, which is a common inhabitant of the normal pharynx. Nevertheless, there is evidence that normal carriers play a more important role in the dissemination of infective types than do patients ill with pneumonia. Occasionally, in relatively closed communities, high carrier rates of pathogenic types are encountered. In such circumstances the occurrence of widespread viral disease of the respiratory tract may result in an epidemic of pneumococcal pneumonia. Except for these rare epidemics, most of which occur in hospitals or custodial institutions, the disease is sporadic. Pneumococcal pneumonia occurs frequently in patients with multiple myeloma or hypogammaglobulinemia.
Pathogenesis and Pathology.
The lung IS the only major viscus of the body exposed to air. As the atmosphere, particularly in congested places, contains many pathogenic bacteria, it is remarkable that pneumonia is not more common. The failure of normal subjects to acquire acute bacterial pneumonia as an air-borne infection is due to the efficient defense-barriers of the lower respiratory tract. These include (1) the epiglottal reflex, which prevents gross aspiration of infected secretions from the pharynx; (2) the sticky mucus that lines the bronchial tree and to which airborne organisms adhere; (3) the cilia of the respiratory epithelium, which keep the infected mucus moving constantly upward toward the pharynx (at a rate of 1 to 3 cm. per hour); (4) the cough reflex, which serves to propel the mucus out of the lower tract; (5) the lymphatics that drain the terminal bronchi and bronchioles; and (6) the mononuclear phagocytes (dust cells) that are -ever present in the normal alveoli. In addition, the alveoli themselves are relatively dry and thus offer a poor medium for growth to the few bacteria that succeed in reaching them. Only when the defense barriers of the normal respiratory tract are disturbed does acute bacterial pneumonia result.
The thesis that bacterial pneumonia usually results from aspiration of infected secretions from the upper respiratory tract is strongly supported by both experimental and clinical observations. Rats infected with pneumococci in the nasopharynx regularly exhibit pulmonary lesions only when subjected to experimental procedures involving chilling of the body, anesthesia, administration of morphine, or alcoholic intoxication, all of which are common predisposing factors in human pneumonia and have been shown in laboratory animals to slow the epiglottal reflex and thus to facilitate aspiration.
Experimental pneumonia can best be produced by intrabronchial inoculation of organisms suspended in mixtures of gastric mucin or starch having viscosities similar to that of mucus. Viral infection of the upper respiratory tract in man usually precedes the onset of acute bacterial pneumonia by several days. Not only is the volume of secretion from the nasopharynx greater than normal during viral infections such as the common cold, but also the number of pathogenic micro-organisms in the secretions is significantly increased.
Thus, the stage is set for aspiration of infected mucus. That such aspiration often occurs at the onset of human pneumonia is suggested by the usual sites of initial involvement of the lung. The earliest lesions of bacterial pneumonia usually appear in those parts of the lungs into which aspirated fluid is most likely to drain. Whereas most airborne bacteria are caught on the sticky surfaces of the bronchial tree and never reach the alveoli, organisms contained in thin nasopharyngeal secretions are readily carried into the alveoli by the liquid mucus. The latter, like Lipiodol/cannot all be ejected by ciliary action, and much of it penetrates to the farthest reaches of the bronchial tree, where it establishes the initial focus of infection.
Other factors known to predispose patients to acute bacterial pneumonia include exposure to noxious gases and anesthetics, cardiac failure, influenza viral infection of the lungs, trauma to the thorax, and pulmonary stasis resulting from prolonged bed rest. A feature common to all these conditions is the accumulation of -fluid in the alveoli. Harford (1950) has shown that the dry lungs of normal mice are able to rid themselves of large numbers of inspired bacteria, whereas lungs containing fluid are readily infected. This observation suggests that pulmonary edema, by providing a suitable culture medium for the bacteria, may facilitate the establishment of active infection within the alveoli.
Occasionally the primary source of an acute pneumonic lesion is chronic pulmonary disease, such as bronchiectasis or lung abscess. Pneumococcal pneumonia may also occur as a complication of bronchogenic carcinoma.
Once the infection has gained a foothold within the alveoli, the lesion evolves in a characteristic manner. The first response of the lung to bacterial invasion is an outpouring of edema fluid into the alveoli. This serous fluid not only serves as a suitable culture medium for the organisms but also “floats” them into new alveoli through the pores of Kohn and terminal bronchioles (see accompanying figure, a). Centrifugal spread of the alveolar fluid is enhanced by motion of the pulmonary parenchyma caused by respiration and cough. After the outpouring of edema fluid, polymorphonuclear leukocytes and some erythrocytes accumulate in the infected alveoli, first in small numbers (figure, b), but later in such quantities as to ii\\ each alveolus and thus render the area completely consolidated (figure, c). Once the infected alveoli become crowded with leukocytes, phagocytosis of bacteria takes place, and the invading organisms are destroyed.
Macrophages appear in the exudate, and resolution begins only after most of the organisms have been ingested. The macrophages that accomplish the final cleaning of cellular debris from the resolving lesion appear to be derived both from monocytes of the blood and from the septal cells of the alveolar walls, which become characteristically thickened during the process of resolution (figure. d>.
Three stages in the inflammatory reaction account for the distinguishing histologic features of the spreading pneumonic lesion. In the outermost portion there appears an “edema zone” in which the alveoli are filled with acellular serous fluid containing many bacteria. Inside the edema zone a second zone may be ideiitified in which there are signs of early consolidation with leukocytes in most of the alveoli. Here phagocytosis is often noted. Still more centrally a third transition to a “zone of advanced consolidation” is noted where the alveoli are packed with cells and where beginning resolution may be evident. In the central zone of advanced consolidation, fibrin is often noted in the alveolar exudate, the large fibrinogen molecules having passed through the injured walls of the alveolar capillaries along with erythrocytes.
From the foregoing description it is clear that all stages of inflammation can be found in a spreading lesion. In the most recently invaded areas at the periphery, edema and hemorrhage predominate, causing “red hepatization,” whereas in the older, more central parts of the lesion, dense consolidation with leukocytes accounts for the characteristic color of “gray hepatization.” Only if the infection has stopped spreading hours before necropsy will the entire lesion be in the stage of “gray hepatization.” Thus, the spread of pneumococcal pneumonia may be likened to that of a grass fire, in which the flames, having spread centrifugally, are concentrated at the periphery, leaving behind a charred and burned-out center.
Not all pneumococcal pneumonia causes lobar consolidation. Less malignant lesions may be patchy in distribution and concentrated particularly about the bronchi. Because a clear-cut distinction between pneumococcal bronchopneumonia and lobar pneumonia cannot always be made even by the pathologist, and because management of the two conditions is essentially the same, it is rarely important for the clinician to differentiate them. The etiology rather than the anatomy of the lesion determines therapy.
If the pneumonic process has involved all the parenchyma of a single lobe, its spread may be stopped by the pleural boundaries of the lobe, and spontaneous recovery may then ensue. Often, however, the infection spreads to other lobes of the lungs. Interlobar spread has been shown in experimental pneumonia to result from the flow of infected edema fluid (figure, e) from bronchi of the involved lung into the bronchial tree of a new lobe. Spread to a given lobe may be brought about by suspending the infected.
Bacteremia frequently occurs during the course of pneumococcal pneumonia, particularly when the infection is fulminating. The fact that organisms appear in the thoracic duct in experimental pneumonia before they appear in the systemic circulation suggests that most of them reach the blood stream via the lymphatics. (It is well known that particles introduced experimentally into the alveoli are cleared primarily by lymphatic drainage.)
To cause bacteremia the lymph-borne organisms must first traverse the cellular defenses of the regional (hilar) lymph nodes to reach the thoracic duct and enter the blood. Once there they must accumulate in sufficient numbers to overpower the combined cellular defenses of the reticuloendothelial system and circulating phagocytes of the blood stream. In other words, their rate of entrance into the circulation must exceed their rate of destruction. Hence, a positive blood culture in pneumococcal pneumonia indicates that the infection is out of control and that the patient’s condition is therefore serious.
Invasion of Pleura and Pericardium.
The exact mechanism whereby pneumococci invade the pleura or pericardium is not known. As the lymphatics at the periphery of the lung drain outward toward the pleura, it is possible that pleural invasion results from lymphangitic spread. On the other hand, it is also possible that organisms are carried through the visceral pleura along with edema fluid that accumulates in infected subpleural alveoli. When infection of a pleural or pericardial cavity occurs, there results an outpouring of serous fluid followed by the deposit of fibrin. Later, leukocytes accumulate in the infected cavity, and, if infection persists, a purulent focus results.
The pus in such cavities is at first thin but later becomes thick and stringy as a result not only of fibrin formation but also of the precipitation of deoxyribonucleic acid derived from the nuclei of disintegrating leukocytes. Finally, the thick fibrinous pus becomes walled off, forming loculated foci of chronic suppuration.
Similar purulent foci may occur in the meninges, peritoneum, or joints, as a result of hematogenous spread. Acute vegetations on the endocardium of the heart valves are sometimes encountered, and acute splenic tumor indicative of systemic infection is a common finding in fatal cases observed at necropsy. Degeneration of renal tubules is also occasionally noted, and, as identical changes can be produced in the kidneys of laboratory animals by repeated injections of killed pneumococci, the lesions are assumed to be of pneumococcal origin.
Mechanism of Recovery
Surface Phagocytosis. Owing to the antiphagocytic properties of their capsules, fully encapsulated, virulent pneumococci are resistant to phagocytosis when suspended in a fluid medium devoid of opsonins^ In the presence of relatively immovable cellular surfaces, however, as in the alveolar, leukocytes are able to trap the encapsulated organisms and ingest them without the aid of opsonizing antibody (see figure). The efficiency of “surface phagocytosis,” which operates also in the interstices of fibrin clots, is greatly enhanced when the leukocytes have accumulated in sufficient numbers to utilize each others’ surfaces in the trapping process.
Leukocytes in vivo are also assisted, right from the start of infection, by heat-labile opsonins that are present in normal mammalian plasma. These opsonins, which gain access to acute inflammatory exudates, are immunologically polyspecific, i.e., they act on all sorts of bacteria, in contrast to the monospecific anti- capsular antibody that is eventually generated in the infected host (see below). Their opsonizing action on pneumococci has recently been shown to involve multiple components of the complement, system, including C3. Its cleavage product, C3b, appears to act as a ligand between the organism on which it is deposited and the surface of the phagocyte.
Most patients with pneumococcal pneumonia, who survive long enough, eventually generate an excess of mono- specific anticapsular antibody. As already stated, the process usually takes five to ten days. These newly formed immunoglobulins, when present in sufficient quantity, not only agglutinate the pneumococci in the edema zone of the lesion and thereby inhibit their spread, but also act as potent accessory opsonins and further increase the efficiency of phagocytosis. Their opsonizing action involves at least two sets of ligands between the organism and the phagocyte. The first is provided by the Fc fragment of the antibody molecule itself; the second results from fixation of complement by the antigen-antibody reaction in the capsule and the generation of the C3b ligands already mentioned. The potentiating effect of the combined ligands can be readily demonstrated in vitro.
Stages of Immunity.
It is thus evident that, in the early phases of pneumococcal pneumonia, pneumococci in the lesions are destroyed by surface phagocytosis and by phagocytosis resulting from the poly specific action of heat-labile opsonins. Only after the patient has been ill for a number of days do monospecific anti capsular immunoglobulins, also acting synergistically with heat-labile opsonins, play a significant role in recovery. The efficiency of the early cellular defense accounts for the prompt destruction of bacteria that occurs even in spreading pneumonic lesions. It likewise helps to explain why patients treated with antimicrobial drugs that are merely bacteriostatic often recover many hours before anticapsular antibodies can be detected in their blood.
The exact role of the “macrophage reaction” in the recovery process is not entirely clear. Because the appearance of macrophages in the alveolar exudate coincides in general with the disappearance of organisms from the lesion, it has long been assumed that these large mononuclear phagocytes take an active part in destroying the bacteria, and in the final analysis tip the scales in favor of the cellular defenses of the host. Studies relating to experimental lymphadenitis cast some doubt upon this assumption. The “macrophage reaction” in a regional lymph node draining an area of active infection can be artificially initiated at any stage of the nodal inflammation by merely cutting the afferent lymph vessels bringing bacteria to the node.
Thus it appears that macrophages accumulate in the exudate only when the active stimulus of direct bacterial invasion has been eliminated. If this interpretation is correct, the polymorphonuclear leukocytes may be looked upon as the “shock troops” that play the major role in controlling the infection, whereas the macrophages serve primarily to remove the particulate debris from the resolving exudate and thus promote clearing of the lesion.
One of the most remarkable features of pneumococcal pneumonia is the completeness with which it resolves. Even when several lobes are completely consolidated at the height of the illness, recovery usually results in restoration of the entire pulmonary parenchyma to its normal state within a few weeks. Not all the processes that take part in this dramatic resolution have been identified, but they appear to include (1) the action of cytolytic enzymes upon disintegrating leukocytes; (2) increased acidity of the exudate; (3) transport of cells from the lesion via lymphatics; and (4) phagocytosis and digestion of cellular debris by macrophages.
The rarity with which tissue necrosis occurs in pneumococcal pneumonia, despite the violence of the inflammatory response, appears to account for the completeness of the healing. Occasionally recovery proceeds more slowly than usual and leads to “delayed resolution.” The factors responsible for delaying the removal of exudate from the lesion in such cases are not known. In rare instances, as the result of irreversible damage to the pulmonary parenchyma, resolution fails to take place altogether, and the lesion becomes the site of intense fibroblastic activity that leads to the permanent scarring of “organized pneumonia.” Although resolution is usually complete in pneumococcal pneumonia, infection with type III pneumococcus may occasionally lead to pulmonary suppuration.
This particular type of pneumococcus, in its most virulent form, has a large capsular “slime layer” that interferes with phagocytosis and accounts, at least in part, for its extraordinary pathogenicity. Type III pneumococci may accumulate in huge numbers in infected alveoli and on occasion cause necrosis, not only of leukocytes, but also of the alveolar walls. If the necrosis-is sufficiently widespread, chronic lung abscesses result.
Suppurative Extrapulmonary Foci.
Suppurative pneumococcal lesions, which usually occur in such extrapulmonary sites as the pleura, pericardium, meninges, joints, mastoids, or accessory sinuses, resolve much less readily, even with intensive chemotherapy, than does uncomplicated pneumococcal pneumonia. In such areas of suppuration, phagocytosis is relatively inefficient because most of the leukocytes in the exudate are not viable. In addition, antimicrobial drugs administered systemically probably do not penetrate subacute or chronic suppurating lesions as readily as they do areas of acute pneumonia. But even when a drug Jike penicillin reaches the organisms in a purulent focus, it usually does not destroy them; for pneumococci do not multiply rapidly in pus of long standing, and “resting” bacteria are not susceptible to the bactericidal action of penicillin. In fact, most purulent pneumococcal lesions respond satisfactorily only when chemotherapy is combined with some form of drainage that removes the bulk of the necrotic exudate.
Clinical Manifestations. Symptoms of Pneumococcal Pneumonia.
Victims of pneumococcal pneumonia are often seriously ill when first seen. The degree of prostration may be such that an adequate history can be obtained only from ’the family or some other close associate of the patient. The story of a mild nasopharyngitis preceding by several days the onset of major symptoms is frequently elicited by careful questioning. The first distressing symptom is usually a shaking chill lasting for several, minutes to a half hour. More than 80 per cent of patients with pneumococcal pneumonia experience one or more chills during the earliest stages of the disease. The initial rigor is often so violent as to cause the bed to shake and the patient’s teeth to chatter. It is followed in about one case in three by vomiting. The exact cause of the initial chill is not known, but it usually coincides with bacterial invasion of the lung and marks the onset of fever. Several chills may occur at the start of pneumococcal pneumonia, but repeated attacks of rigor late in the disease suggest an extrapulmonary complication such as endocarditis or empyema.
In approximately 70 per cent of cases severe chest pain occurs at the onset and may even precede the rigor. The pain, which is “stabbing” in character and is exaggerated by cough and respiration, is caused by inflammation of the pleura resulting from the characteristically peripheral location of the initial lesion. There may be local tenderness in the chest wall at the site of the pleurisy. When the diaphragmatic surfaces of the pleura are affected, the pain is referred either to the corresponding side of the lower chest wall and upper abdomen or to the shoulder, depending upon whether the peripheral (intercostal innervation) or central < phrenic innervation) part of the diaphragm is involved. The patient may gain some relief from the knifelike pain by lying on the affected sice thereby partially splinting that half of the thorax.
A cough may be absent at the onset, but usually is a prominent symptom during the course of the disease. Stimulation of the cough reflex results from irritation of the lower respiratory tract and from accumulation -cf mucus and exudate within the bronchial tree. Approximately 75 per cent of patients raise diffusely bloody or ‘”rusty” sputum in contrast to “blood-streaked” sputum. The thorough mixing of the blood and mucus appears to be due to the fact that bleeding occurs directly into the alveolar exudate and thus constitutes an integral part of the inflammatory response to the infection. When the sputum is particularly sticky or jelly-like, type III pneumococcus or Klebsiella should be suspected as the cause of the pneumonia, because both these organisms produce, during growth, an, inordinate amount of capsular polysaccharide that causes the exudate to be highly viscous.
Fever and Toxemia. Constant features of the disease are fever and toxemia, with the temperature usually ranging between 103 and 106° F. During the febrile period complaints of malaise, anorexia, weakness, myalgia, and general prostration are extremely common.
Since pneumococcal pneumonia may occasionally progress with great rapidity and the general condition of the patient may deteriorate alarmingly-within a few hours, it is essential that the initial physical examination be as thorough as possible.The temperature, pulse rate, and respiratory rate are usually elevated by the time the patient seeks the aid of a physician. The temperature should be taken by rectum, because oral measurement with the subject breathing rapidly through the mouth is likely to be inaccurate. The pulse pressure is characteristically widened, as in any high fever, and the pulse at the wrist may be collapsing in quality. Subnormal blood pressure indicates shock and a poor prognosis.
Patients with well established pneumococcal pneumonia appear acutely ill. There is moderate to severe respiratory distress. The nostrils dilate with each inspiration. Paroxysms of hacking cough, often productive of bloody or rusty sputum, occur during the examination. The chest pain, which is usually unilateral, may be so severe as to interfere with the patient’s breathing and coughing; in these circumstances grunting expiration results. The location of the pain indicates immediately the approximate site of at least part of the lesion. The patient occasionally appears apprehensive and may even be delirious.
The skin is usually hot and moist with beads of perspiration visible on the face and forehead. Cold extremities may indicate impending shock. Herpetic blisters are frequently noted about the mouth. The lips, mucous- membranes, and nail beds are often cyanotic as a result of blood passing through poorly aerated lung. The cyanosis may be exaggerated by lowered respiratory exchange associated with rapid shallow breathing, often resulting from pleural pain. Icterus of the sclerae should be carefully looked for because of the prognostic significance of overt jaundice in pneumonia (see below). Only rarely are petechiae found in the skin of patients suffering from complicating pneumococcal endocarditis.
The ears should always be examined with an otoscope to exclude the presence of active otitis.Tenderness over a mastoid process or over an accessory nasal sinus should also be noted. The presence of exudate in the pharynx or over the tonsils suggests the possibility of streptococcal pneumonia. Definite nuchal rigidity is usually indicative of pneumococcal meningitis, a serious complication of pneumonia. The neck veins must be carefully examined to detect the presence of increased venous pressure caused by complicating congestive heart failure. Deviation of the trachea constitutes an important sign of either atelectasis (toward the involved side) or pleural effusion (away from the involved side).
Examination of the Chest.
The thorax must be examined with the utmost care. Diminished respiratory excursion or a slight inspiratory lag of one side of the chest often reveals the site of the principal lesion. A localized area of tenderness in the chest wall, noted during percussion, may be one of the earliest signs of pleural invasion. The presence of large pleural effusion sometimes causes a noticeable fullness of intercostal spaces. Careful percussion and auscultation do not always reveal signs of consolidation. In early cases, particularly, there may be no conclusive physical signs. Lesion’s at a distance from the chest wall are difficult to outline „by percussion. Breath sounds may be only slightly depressed if normal lung tissue separates the lesion from the large bronchi. When consolidation is extensive, the typical findings of dullness to percussion, bronchial or tubular breath sounds, and fine crackling rales are easily elicited, except in the presence of complicating bronchial obstruction or extensive pleural effusion. A coarse “leathery” friction rub is frequently audible in the region of consolidation.
Examination of the heart may be difficult because of loud respiratory sounds. Its position and size should be carefully determined by palpation and percussion. A later shift in the position of the left cardiac border may indicate any one of the following complications: cardiac enlargement from heart failure, invasion of the pericardial cavity, atelectasis, or pleural effusion. An apical systolic murmur is frequently heard during high fever and is often of no significance, although it may be due to bacterial vegetation. Diastolic murmurs, on the other hand, arising from either the mitral or aortic valve are usually indicative of underlying organic heart disease or complicating pneumococcal endocarditis. A pericardial friction rub often constitutes the first sign of spread of the pneumococcal infection to the pericardial cavity. Ventricular premature contractions are not uncommon in the presence of any moderate or severe infection.
Distention of the abdomen is frequently encountered in advanced bacterial pneumonia. When tympany is noted in the left axilla and left upper quadrant, acute gastrectasia should be suspected. Occasionally, the examiner will note rigidity and even tenderness in one or both upper quadrants of the abdomen, suggesting a subdiaphragmatic lesion. This sign is usually due to referred pain resulting from involvement of the parietal pleura over the outer part of the diaphragm. The right upper quadrant should be carefully examined for signs of enlargement or tenderness of the liver resulting from congestive heart failure.
In addition to edema from heart failure, the most important physical signs to be detected in the extremities are those of phlebothrombosis. As pulmonary infarction may closely resemble acute bacterial pneumonia, it is of the utmost importance to look for evidence of venous thrombosis of the legs.
The neurologic examination is rarely abnormal in pneumococcal pneumonia except in the presence of meningitis or brain abscess. Digital examination of the rectum may be postponed if the patient is acutely ill, but in women a sufficiently complete pelvic examination should be performed to rule our the possibility of an infected abortion, which often leads to metastatic bacterial pneumonia.
laboratory Findings. The most important laboratory findings of pneumococcal pneumonia may be grouped under die following headings:
Findings Indicating ‘re Presence of an Acute Infection. As in most acute bacterial infections, the total leukocyte count in pneumococcal pneumonia is elevated, and there is a “shift to the left” in the differentia’, count: the erythrocyte sedimentation rate is a iso increased. The number of leukocytes in the peripheral blood during the active infection usually ranges from 15,000 to 40,000 per cubic millimeter: counts above 40,000 are occasionally encountered- Leukopenia (with a “shift to the left” is observed in fulminating pneumococcal infections, particularly in the presence of bacteremia.
Findings Indicating Pulmonary Consolidation.
Although the presence and location of the pulmonary lesion can usually be determined by physical examination, confirmatory roentgenographic evidence is often helpful. Both posteroanterior and lateral views of the chest should be taken. The lateral film may be of great value in (1) detecting retrocardiac consolidation in the left lower lobe, (2) indicating whether a lesion visible in the posteroanterior view is located anteriorly or posteriorly and thus in what lobe it is situated, and (3) identifying interlobar accumulations of fluid. If the patient is too ill to be subjected to such a complete examination, a portable chest film should be taken at the bedside. Proper management of pneumococcal pneumonia in the home does not necessarily require roentgenographic examination.
Findings Indicating Etiology.
Whenever the diagnosis of pneumococcal pneumonia is suspected, the patient’s blood should be cultured. Anaerobic (candle jar) as well as aerobic cultures are recommended, as many strains of pneumococci grow best at an elevated C02 tension. A positive blood culture provides important information regarding both etiology and prognosis. The physician should also make a real effort to obtain a suitable specimen of sputum. Whenever possible, the patient should be made to expectorate mucus raised directly from the bronchial tree; secretions from the nasopharynx taken to the laboratory immediately to be cultured and smeared for Gram stain. Alpha hemolytic, gram-positive cocci isolated on a culture should be reported as pneumococci only if shown to be bile soluble or sensitive to optochin. Because of the scarcity of type-specific antisera and the effectiveness of modern antimicrobial therapy, typing of pneumococci is now rarely performed.
Neglect of this relatively simple procedure, however, deprives the attending physician o important information regarding prognosis (.see Prognosis). When no sputum specimen can be obtained, particularly from a child, a throat swab may be cultured. Although it is not a hazardous procedure, lung puncture is now rarely used to determine the etiology of acute bacterial pneumonia.
Other laboratory examinations that may be of value in the management of the patient include blood electrolyte and urea determinations.
During the course of the disease the patient should be examined carefully once a day. More frequent physical examinations may unduly exhaust an acutely ill subject. The common complications of pneumococcal pneumonia should be specifically looked for during each examination, particularly when fever persists.
The fever of untreated pneumococcal pneumonia may either terminate abruptly by “crisis” five to ten days after onset or may gradually subside by lysis. When effective antibacterial therapy is used, a dramatic crisis may occur within 24 hours, or the fever may persist for several days (see Antibacterial Therapy).
Sometimes a slight secondary rise in temperature occurs after the crisis. Not only does defervescence often begin promptly after effective therapy, but the patient may experience a striking relief of symptoms and exhibit a noticeable improvement in appearance. Physical signs in the chest may also change, coarse sticky tales of resolution replacing the fine crepitant rales and tubular breath sounds of consolidation. Complete clearing of the pulmonary lesion may occur within a few days, but usually the auscultatory signs of resolution persist for a week or more after defervescence. If resolution is not complete within 21 days, it is arbitrarily classified as delayed.
The promptness of defervescence and the speed of resolution are in general inversely proportional to the age and extent of the lesion at the time treatment is begun.Crisis marking the start of recovery must be differentiated from the “pseudocrisis” occasionally noted at the onset of shock or at the time of interlobar spread of the infection. Although the temperature may fall precipitously during a pseudocrisis, the pulse rate remains elevated, and the patient’s general condition fails to improve.
Relapse may occur in pneumococcal pneumonia when chemotherapy is discontinued too soon.
The symptoms and signs of pneumococcal pneumonia are usually so characteristic as to make the diagnosis relatively simple. Atypical cases occasionally occur in which a definitive diagnosis cannot be made and in which antimicrobial treatment on suspicion is justified. Sometimes the disease is mistaken for less serious forms of respiratory tract infection, such as acute tracheobronchitis or “grippe.” This error can often be avoided if proper significance is attached to the history of chills, bloody sputum, and chest pain, if the lungs are carefully examined at frequent intervals for signs of pulmonary consolidation, and if posteroanterior and lateral roentgenograms are made of the chest.
Pneumonia resulting from organisms other than pneumococcus may at times be difficult to differentiate from pneumococcal pneumonia. Only by bacteriologic study of the sputum can pneumonia caused by Klebsiella pneumoniae (Friedlander’s Bacillusbacillus), Staphylococcus aureus, or group A beta- hemolytic Streptococcus be identified. Tuberculous, pneumonia rarely causes the acute prostration characteristic of coccal infection. Mycoplasmal pneumonia and other nonbacterial infections of the lungs, such as psittacosis and Q fever, do not often cause shaking chills, diffusely bloody sputum, severe pleural pain, or a marked leukocytosis, although they may at times by confused with acute bacterial pneumonia.
Tularemia pneumonia and pneumonia caused by H. influenzae in young children must also be considered. When the diagnosis is in doubt, repeated examinations of the sputum should be made, using both the Gram and Ziehl- Neelsen stains. Sputum specimens should not only be cultured but should be injected into mice. Specific diagnosis of pneumonia is of great practical importance, because of therapy. Whereas tuberculosis, tularemia, Klebsiella and H. influenzae pneumonia often respond to streptomycin, and the course of mycoplasmal pneumonia is favorably influenced by tetracyclines, most other forms of acute pneumonia (except that caused by penicillin- resistant staphylococci) are best treated with penicillin.
Non Pulmonary Bacterial Infections.
Bacterial infections other than pneumonia must be considered in the differential diagnosis. Pleurisy involving the outer part of the diaphragm and resulting from right lower lobe pneumonia often causes referred pain to the right side of the abdomen, thus simulating acute appendicitis. Subdiaphragmatic abscess arising from perforation of the appendix conversely may simulate pneumonia. Acute pyelonephritis with chills, fever, flank pain, and leukocytosis must not be confused with pneumonia; the diagnosis is usually established by examination of the urine and by the absence of signs of frank consolidation in the lungs. Differentiation of acute pyelonephritis from pneumococcal pneumonia is of primary importance, as most urinary tract infections are caused by organisms not susceptible to penicillin.
Among the essentially noninfectious processes that must be differentiated from pneumococcal pneumonia are congestive heart failure, pulmonary infarction, and atelectasis. That congestive heart failure predisposes to acute bacterial pneumonia has already been emphasized. The two conditions frequently coexist, but occasionally congestive heart failure is mistaken for pneumococcal pneumonia. This error is most frequently made in patients with dyspnea, cough, blood-streaked sputum, and signs in the chest that simulate those of consolidation, but in reality are due to hxtxg under a pleural effusion. In such cases the absence of high fever and leukocytosis and the presence of distended neck veins and peripheral edema usually suggest the correct diagnosis.’
Patients suffering from pneumococcal pneumonia should be kept at limited to the immediate family. Pleural pain, if mild, may be treated with codeine sulfate (30 to 60 mg.) orally, and, if severe, with subcutaneous morphine sulfate (10 to 15 mg.), an equivalent analgesic such as methadone hydrochloride (5 to 10 mg., subcutaneously), or intercostal nerve
block. A tight chest-binder is sometimes helpful in providing “something to cough against.” Restlessness and insomnia, which are most commonly associated with delirium, are best controlled by chloral hydrate (1 to 1.5 grams by mouth) or by paraldehyde (4 to 12 ml. by mouth or 10 to 20 ml. in 20 to 30 ml. of olive oil by rectum). Dyspnea and cyanosis should be treated with oxygen, administered by tent (40 to 60 per cent oxygen) or by nasal catheter (35 to 50 per cent oxygen, when gas is delivered at 4 to 7 liters per minute). Oxygen masks are usually unsuitable because of the patient’s cough and expectoration.
Fluid and Electrolytes.
During the acute state of pneumococcal pneumonia considerable fluid is lost from the body, chiefly through the skin as the result of high fever. Dehydration may develop rapidly and, if severe, may become a contributing factor in the development of shock. Most patients require between 3 and 4 liters of fluid and 6 to 10 grams of sodium chloride a day when the fever is high. In the presence of congestive heart failure the use of supplementary sodium chloride is, of course, contraindicated. In the absence of renal disease, glycosuria or congestive heart failure, the patient’s state of hydration may be estimated by the specific gravity of the urine. When hydration is adequate, the specific gravity should remain below 1.020.
Many patients with pneumococcal pneumonia are too ill to tolerate a full diet and should receive only liquids during the height of the fever. Fruit juices, ginger ale, and soups are well tolerated. After the crisis a regular diet may be prescribed.
The patient should be kept in bed until the temperature is approximately normal and should be observed closely until the pneumonic lesion has resolved. As already emphasized, all patients should be subjected to a follow-up roentgenographic examination three to four weeks after recovery.
Treatment of Complications.
Shock, Patients with peripheral vascular collapse (shock) resulting from severe pneumococcal pneumonia usually respond poorly to the accepted forms of antishock therapy. The prognosis is almost invariably grave when this complication develops. Oxygen therapy should be begun immediately, even if cyanosis is absent. Norepinephrine is one of the best drugs available for combating the hypotension of shock. It should be given continuously by intravenous drip in sufficient amounts to maintain the systolic pressure at levels between 100 and 110. Enough norepinephrine (one vial contains 4 mg.) must be added to each liter of salt solution so that the hypotension can be controlled by the administration of not more than 2000 to 3000 ml. of fluid in 24 hours present. The treatment of congestive heart failure in patients with pneumococcal pneumonia is essentially the same as that of heart failure under other conditions (see Treatment of Congestive Heart Failure).
Abdominal distention is best managed by the use of gastric suction, daily enemas, the insertion of a rectal tube, the administration of ‘oxygen, and repeated hypodermic injections of Prostigmin methylsulfate (0.5 mg.). The Prostigmin injections should be repeated every hour until a definite effect is obtained; subsequent doses should be spaced at intervals of two to four hours and maintained as long as is necessary.
Delirium may sometimes be difficult to control, particularly in patients with a history of chronic alcoholism. The use of 30 to 90 ml. of whiskey per day may quiet alcoholic patients during the acute phase of the disease. The safest hypnotic to use is paraldehyde. A restraining net over the bed is often required to prevent the patient from climbing out of bed and injuring himself.
Empyema and Pericarditis.
For the reasons already discussed under Mechanisms of Recovery: Suppurative Extrapulmonary Foci, the treatment of established empyema and persistent pericarditis is primarily surgical. During World War I, Graham demonstrated (1918) that open thoracotomy must always be delayed until the pus aspirated from the chest is relatively thick and the area of infection is sufficiently well walled off to prevent marked shift of the mediastinum. Since the advent of penicillin, cases of both empyema and pericarditis have been successfully treated by repeated aspiration and injection of aqueous penicillin (50,000 to 200,000 units daily) through either a thoracentesis needle or a thoracotomy tube (closed drainage). When these measures are not effective, open surgical drainage with continued systemic antimicrobial therapy should be instituted.
The treatment of the remaining two major complications of pneumococcal pneumonia, namely, meningitis and endocarditis, are discussed elsewhere (see Meningitis and Bacterial Endocarditis).
The case fatality rate in untreated pneumococcal pneumonia ranges from 20 to 40 per cent. The widespread use of sulfonamide drugs in the late 1930’s resulted in a lowering of the fatality rate among treated patients to approximately 10 per cent. Penicillin therapy has lowered the rate still further. At present approximately 95 per cent of patients with pneumococcal pneumonia recover when properly treated with penicillin.
The prognosis in pneumococcal pneumonia is influenced adversely by each of the following: (1) old age (arid also infancy), (2) late treatment, 3 infection with certain types of pneumococci particularly types IT and III), (4) involvement of more than one lobe of the lung, (5) leukopenia, (6) occurrence of bacteremia, (7) jaundice, (8) the presence of complications (notably shock and meningitis), (9) pregnancy (particularly in the third trimester), (10) the presence of other disease such as heart disease or cirrhosis of the liver, and (11) alcoholic intoxication and delirium tremens. Through a consideration of these factors a rough estimate may be made of the severity of the infection in each case, and therapy may be modified accordingly.
Even with the most intensive penicillin treatment a significant number of patients will die of pneumococcal pneumonia. A recent study, for example, has revealed that in patients destined, at the onset of illness, to die within five days (because of complicating disease, old age, etc.) penicillin therapy has little, if any effect. Similarly, the case fatality rate in type III pneumococcal pneumonia with bacteremia still exceeds 50 per cent regardless of treatment.
Because pneumococcal pneumonia is not highly contagious and usually responds promptly to early therapy, prophylaxis constitutes less of a problem than in many other infectious diseases. It is estimated that only one in every 500 persons of all ages in the United States may be expected to contract the disease in any one year. In certain closed communities, however, and in areas where the pneumococcal carrier rate is particularly high, epidemics occasionally occur. Under such conditions, immunization with pneumococcal polysaccharide may be indicated. During World War II, the effectiveness of polyvalent pneumococcal vaccine in preventing pneumonia and in lowering the pneumococcal carrier rate was clearly demonstrated in a controlled experiment on Army personnel. Although immunization may prove, to be of value in military medicine, its application to the general population is not indicated because the incidence of the disease in ordinary circumstances is too low to justify vaccination. For persons at especially high risk, however, because of age or chronic systemic disease, particularly of the heart or lungs, its use would seem justified.
Although pneumococcal pneumonia can undoubtedly be prevented (or at least aborted) in many patients by the intensive treatment of every upper respiratory tract infection with antimicrobial drugs, their indiscriminate use for this purpose should be avoided. The possible inconvenience to the patient of hypersensitivity reactions and the theoretical danger of favoring drug-resistant strains of bacteria outweigh the advantages to be gained in preventing such a relatively uncommon and readily treatable disease as pneumococcal pneumonia. Such chemoprophylaxis during outbreaks of epidemic influenza, on the other hand, might conceivably be indicated (see Influenza).
The cross-infection rate in pneumococcal pneumonia is low and patients receiving chemotherapy are probably not highly infectious. The danger of cross-infection in a general hospital, particularly among patients with congestive heart failure, pulmonary edema, or other severe debilitating diseases, may be greater than in the general population, and care should be taken to protect them from exposure.