REVIEWS

Clinical, Microbiologic and Therapeutic Aspects of

Purulent Pericarditis

ROBERT H. RUBIN, M.D.

ROBERT C. MOELLERING. Jr., M.D.

Boston, Massachusetts

From the Department of Medicine, Harvard Medical School; and the Medical Service (Infec- tious Disease Unit) of the Massachusetts Gener- al Hospital, Boston, Massachusetts. Requests for reprints should be addressed to Dr. Robert H. Rubin. Infectious Disease Unit, Massachu- setts General Hospital, Fruit Street, Boston, Massachusetts 02114. Manuscript accepted September 26, 1974.

Twenty-six patients wlth purulent perlcarditls were seen at the Massachusetts General Hospital between 1960 and 1974. The dl- agnosls was made in 16 of them during life, but only 6 survived, with an over-all mortality rate of 77 per cent. In eight patients, purulent pericarditls developed In the early postoperative period after thoraclc surgery. In seven, purulent pericardltls was the re- sult of contiguous spread of lnfectlon from a pleural, medlastinal or pulmonary focus In nonsurgical patients. In five patients, it was the result of direct spread to the pericardium from an intra- cardiac Infection. In the remaining six patients, puruient pericar- dltls developed as the result of a systemic bacteremia. Immuno- suppresslve therapy, extensive thermal burns, lymphoprolifera- tive disease and other systemic processes affecting host resis- tance were present in at least half the patlents. Staphylococcus aureus was the etiologic agent in the largest number of patients (6 of 26 In this report). However, in contrast to previous studies, In a significant number of the patients (five), purulent pericarditis was the result of fungal infection (In three patients subjected to thoracic surgery and In two immunosuppressed patients).

This report confirms that purulent perlcardltls is an acute dis- ease with a fulminant course. The diagnosis is easily missed since classic signs of pericarditis (Including chest pain, friction rub and diagnostic electrocardiographic abnormalities) may be absent. The echocardiogram shows considerable promise in al- lowing earlier diagnosis of the pericardial effusion which accom- panies purulent pericardltls. Optimal therapy consists of pro- longed antlblotlc therapy and aggressive drainage of the pericar- dium. In this series, there were 6 survivors among the 11 patients (55 per cent) who received appropriate therapy.

Although purulent pericarditis has been recognized since Galen’s day [ 11, the nature of the disease has changed-changed even from that described in Boyle, Pearce and Guze’s classic review in 1961 [2]. These investigators documented the overwhelming im- portance of pleuropulmonary disease and uncontrolled gram-posi- tive coccal infection-that due to Staphylococcus aureus, Strepto- coccus pneumoniae and Streptococcus pyogenes-in the patho- genesis of suppurative infection of the pericardium in the preanti- biotic and early antibiotic eras. Even in their series, however, sev- eral trends were noted: a marked decrease in the incidence of con- comitant pleuropulmonary infection; a fall-off in the occurrence of

69 July 1975 The American Journal of Medlclne Vdume 59

PURULENT PERICARDITIS-RUBIN. MOECLERING

pneumococcal disease; an increase in the incidence

of hospital-acquired, antibiotic-resistant infection; and

an increase in the number of cases in elderly patients

and in patients with complicating systemic illnesses.

In the years since then, these trends have continued,

and today puruient pericarditis is more commonly a

disease of the debilitated patient with impaired host

defenses: of the patient who has undergone exten-

sive thoracic and/or cardiac surgery: of the patient

with preexisting, nonpyogenic inflammatory disease

of the pericardium; and of the patient with uncon-

trolled myocardial and/or endocardial infection. In ad-

dition, more traditional forms of the disease still

occur. Two aspects of purulent pericarditis that have

not changed since Galen’s day are the insidiously

subtle presentation it may have, and the large per

cent of cases that go undiagnosed until postmortem

examination.

Our purpose is to review the experience with this

disease at the Massachusetts General Hospital during

the period 1960 to 1974, emphasizing the following

points: the clinical and epidemiologic settings within

which purulent pericarditis now occurs, the microbio-

logic culprits of the disease today, the pathogenetic

mechanisms by which the disease is produced, and

modern methods of diagnosis and therapy. It is hoped

that such information will provide a basis for a more

effective attack on this ancient problem.

MATERIALS AND METHODS

The records of all patients with purulent infection of the

pericardium seen at the Massachusetts General Hospital

from July 1, 1960, to June 30, 1974, were reviewed, and

form the basis for this study. Four of the patients have

been the subjects of separate reports [3-61. All patients

included in this study fulfilled at least two of the three fol-

lowing criteria: (1) The demonstration of gross or micro-

scopic evidence of an acute pericarditis with a predomi-

nance of polymorphonuclear leukocytes in the inflammato-

ry infiltrate in material obtained at autopsy or surgery; or

the demonstration of purulent fluid (more than 30,000

white blood cells/mm3 with more than 90 per cent poly- morphonuclear leukocytes) at pericardiocentesis. (2) The demonstration of bacteria or fungi on gram stain of peri- cardial fluid. (3) The isolation of a bacterium (other than

Mycobacterium tuberculosis) or fungus from cultures of

pericardial tissue or fluid, or from cultures of immediately

contiguous structures and/or blood.

Excluded from the series were patients who had a vari-

ety of infections and evidence of pericardial effusions by

either echocardiogram, roentgenogram, radioisotope scan or electrocardiogram, but who recovered without precise definition of the pericardial process.

Specimens for culture were inoculated on Brucella agar plates containing 5 per cent horse blood, McConkey agar

and thioglycollate broth, and were incubated at 37°C in air

enriched with 5 per cent carbon dioxide. During the last 5

years covered by this report, primary anaerobic cultures

were usually performed as well. In selected patients, Sa-

boraud’s medium was used for fungal isolation.

The patients with purulent pericarditis have been

grouped according to the portal of infection and whether

the disease occurred as a result of a surgically-induced in-

fection or was acquired de novo as part of a “medical” ill-

ness. Group I: Patients with contiguous spread from a postoperative infection. Group II: Nonsurgical patients with contiguous spread from a pleural, mediastinal or pulmo-

nary focus. Group III: Nonsurgical patients with contiguous spread from intracardiac infections. Group IV: Nonsurgical patients with noncontiguous spread during systemic bac-

teremia

RESULTS

Twenty-six patients with purulent pericarditis were

identified during the 14 years of this study. Twenty of

these patients died, for an over-all mortality of 77 per cent. The diagnosis of purulent pericarditis was made

during life in 18 of the 26 (69 per cent) and at autop-

sy in the remainder. No particular age group had- a

preponderance of cases (Figure 1). Fifteen of the 26

patients were male.

Predisposing Conditions. Table I delineates the

clinical settings in which purulent pericarditis oc-

curred. In eight patients (group I), the disease devel-

oped in the early postoperative period (1 to 3 weeks

after thoracic surgery). In two, transthoracic esopha-

geal surgery was associated with esophageal perfo-

ration and contiguous spread of infection from the

mediastinum to the pericardium: in the remaining six,

open heart surgery was complicated by extensive

sternal wound infection, sternal osteomyelitis, medi-

astinitis and, again, contiguous spread to the pericar-

dium. In seven patients (group II), the disease devel-

oped in association with primary pleural, mediastinal

and/or pulmonary infection. Four of these patients

had left-sided pneumonia and empyema (two of

these had bilateral pneumonias and empyemas); two

had pneumonia in the lower lobe of the left lung with-

out accompanying pleural space involvement. The

pulmonary infection was believed to be the primary

event in these six patients, with contiguous spread

occurring to the adjacent pleural and/or pericardial spaces. In the remaining patient, a patient with 50

per cent third degree total body burns and persistent

Salmonella bacteremia, purulent pericarditis was

secondary to contiguous spread from a mediastinal

abscess that had developed. In five patients (group Ill), it was a complication of intracardiac infection; as

a result of contiguous spread from infected heart

valves (two aortic and one mitral) in three and as a

result of contiguous spread from a myocardial ab-

scess in two. Six patients (group IV) had purulent

pericarditis as a result of a systemic bacteremia.

July 1975 The American Journal of Medicine Volume 59 69

PURULENT PERICARDITIS-RUBIN. MOELLERING

7

6 c

I SURVIVED rl

o-9 IO-19 20-29 30-39 40-49 50-59 60-69 70+

AGE, years

Two of the six patients with pleuropulmonary infec-

tion (group II) and four of the six with bacteremia

(group IV) survived. None of the patients in groups I (postsurgical) and Ill (intracardiac infection) survived:

the development of purulent pericarditis represented

the final coupe-de-grace in a desperately ill group of

patients.

Associated systemic diseases that may have im-

paired host resistance were present in 12 patients

(hepatic failure in 2, uremia in 1, diabetes mellitus in

3, leukopenia in 1, extensive third degree burns in 2,

acute lymphoblastic leukemia in 1 and large dose

corticosteroid and azathioprine therapy in 2). Two

patients with preexisting nonsuppurative pericarditis

had a secondary infection from a transient bacter-

emia originating from an extrathoracic site. One of

TABLE I Classification of the 26 Patients with Purulent Pericarditis According to Route of Infection, Clinical Setting and Outcome

No. of Patients

Group Description Survived Died

I Patients with contiguous

spread from a postopera-

tive infection 0 8 II Nonsurgical patients with

contiguous spread from a

pleural, mediastinal or pul- monary f0cUS 2 5

III Nonsurgical patients with

contiguous spread from in-

tracardiac infections 0 5 IV Nonsurgical patients with

noncontiguous spread to the pericardium during sys-

temic bacteremia 4 2

these patients

Figure 7. Age and mortality in 26 pa- tients with purulent pericarditis.

had bacteremia due to Klebsiella

pneumoniae from a site of acute pyelonephritis, with

the development of a Klebsiella pericarditis superim-

posed on preexisting uremic pericarditis. The other

patient had idiopathic (presumably viral) pericarditis

for 3 weeks [4] with partial recovery before the de-

velopment of an acute decompensation due to Bac-

teroides species superinfection of the pericardial

space.

Microbiology. A wide variety of organisms caused

purulent pericarditis in these patients (Table II). The

most common were Staph. aureus (eight patients);

fungi (five patients: due to Candida species infection

in three, to Aspergillus species in one, and to both

Aspergillus and Candida species in one); Strep. pneu-

moniae (two patients) and H. influenzae (two pa-

tients). Purulent pericarditis due to staphylococci oc-

curred after cardiac surgery in three patients (group

I), after intracardiac infection in three patients (group

Ill) (resulting from acute bacterial endocarditis of the

aortic valve in two and from a myocardial abscess in

one patient with staphylococcal bacteremia), was

secondary to pneumonia in one (group II) and due to

bacteremia in one. Purulent pericarditis due to fungi

occurred postoperatively in three patients (after car-

diac surgery in two and after esophageal surgery in

one), and after pulmonary infection in two immuno-

suppressed patients (one had leukemia and one was receiving large doses of corticosteroid). Both patients

with purulent pericarditis due to pneumococci had pneumonia and empyema. Meningitis with septicemia

preceded the onset of pericarditis in both cases due

to H. influenzae.

Relatively unusual organisms causing single cases of purulent pericarditis included the following: Salmo-

nella typhimurium in the previously described burn patient with mediastinal infection and persistent bac-

70 July 1975 The American Journal of Medicine Volume 59

PURULENT PERICARDITIS-RUBIN MOELLERING

TABLE II Microbiology of 26 Cases of Purulent

Pericarditis -.

Patients

Organism __ _ _ _~~_....

Staphylococcus aureus

Fungal infection*

Streptococcus pneumoniae

Hemophilus influenzae

Neisseria meningitidis

Klebsiella pneumoniae

Pseudomonas aeruginosa

Bacteroides species

Salmonella typhimurium

Nocardia asteroides

Streptococcus mitis

Mixed bacterial infectiont

No. %

8 30.8 5 19.2 2 7.7 2 7.7 1 3.8 1 3.8 1 3.8 1 3.8 1 3.8 1 3.8 1 3.8 2 7.7

* Candida species infection in three, Aspergillus species in

one and mixed Aspergillus and Candida infection in one.

t Escherichia coli, Klebsiella pneumoniae, and nonhemolytic

streptococci in one and Klebsiella pneumoniae, Enterobacter

species, Escherichia coli and Citrobacter species in the other.

teremia; Nocardia asteroides in a renal transplant pa-

tient receiving large doses of corticosteroids and

azathioprine in whom disseminated nocardial infec-

tion developed, including a myocardial abscess that

spread into the pericardial space; Streptococcus

mitis that spread from an infected aortic valve to the aortic root and then to the pericardium: Pseudomo-

nas aeruginosa in a patient with Pseudomonas pneu-

monia and contiguous spread to the pericardium; and

Bacteroides species infection in a patient with proba-

ble antecedent viral pericarditis and no source identi-

fied for the preceding Bacteroides bacteremia.

Clinical Manifestations. Purulent pericarditis is

clearly an acute illness of few days’ duration (the

mean length of symptoms before hospitalization was

3 days, with a range of 1 to 6 days*) characterized

by high spiking fevers, frank rigors and complaints

referrable to the cardiorespiratory systems (Table Ill).

Noteworthy in these patients was the absence of

chest pain: only 7 of the 26 patients had chest dis-

comfort, and of these, 5 had other intrathoracic sites

of infection (1 mediastinal, 4 pleuropulmonary) that

could have been the cause of the pain. The presen-

tation of the disease varied, depending on the portal

by which the pericardium became infected.

In group I patients (postsurgical) the picture was

reasonably uniform. Between 1 and 3 weeks after

initial survival of extensive surgery, the patients showed signs of systemic infection with hectic tem-

* In four patients (two with pneumococcal. one with staphylo- coccal and one with mixed bacterial pericarditis) precise data concerning the duration of symptoms prior to hospitalization were not available.

perature curves, rigors and cardiorespiratory com-

promise. Frequently, there was evidence of signifi-

cant wound infection and/or pneumonia. There was

little difficulty in making a diagnosis of infection, or

even infection in the chest, in these patients; the diffi-

culty lay in making the diagnosis of pericardial in-

volvement. Typically, the patients subjected to cardi-

ac surgery had had a stormy immediate postopera-

tive course, with bleeding points that required second

and even third explorations of the wound, placement

of drainage tubes within the pericardium or mediasti-

num, and prolonged hypotension with resuscitative

efforts. Since the pericardium is not closed after car-

diac surgery, it is understandable that tamponade

was not noted in these patients. However, tampo-

nade was present and was the immediate cause of

death in one of the patients who had had esophageal

surgery. Of the eight patients in group I, the diagnosis

of purulent pericarditis was made before autopsy in

only two.

In group II patients (pleuropulmonary disease) the

presenting symptoms were those of an acute, severe

bacterial pneumonia with respiratory embarrass-

ment, cough and purulent sputum production, spiking

fevers and pleuritic chest pain. Approximately 2 to 4

days after the development of this symptom com-

plex, evidence of circulatory compromise developed,

with five of these seven patients manifesting some

evidence of impaired venous return to the heart or

frank tamponade. The two patients in whom circula-

TABLE III Clinical Manifestations in 26 Patients with

Purulent Pericarditis -_ ________.. ._ ~~- -----.-

Per cent of

Manifestations Patients -._____._____ ._._. ~~~ .~. _.

Symptoms

Fever 96

Chills 62

Night sweats 62

Dyspnea 54

Cough 42

Chest pain* 27

Signs

Tachycardia (pulse rate greater than lOO/

min) 100

Friction rubs? 46

Hypotension and/or pulse pressure less

than 25 mm Hg 42

Pulsus paradoxus more than 10 mm Hg 38

Elevated central venous pressure (more

than 10 cm H20) 31

Hepatomegaly 15 .___~.._____. ~ _ --.- --

*Seven patients had chest pain; it was pleuritic in four, precordial and nonpleuritic in two and both pleuritic and pre-

cordial in one. t Twelve patients had a friction rub; it was pericardial in origin

in nine, pleural in two, both pericardial and pleural in one.

July 1975 The American Journal of Medicine Volume 59 71

PURULENT PERICARDITIS-RUBIN. MOELLERING

tory compromise did not develop had only minimal,

microscopic changes at autopsy, and the pericarditis

was not an important part of the clinical course.

In group Ill patients (intracardiac infection) the

major manifestations were those of the underlying in-

fections, acute bacterial endocarditis in three pa-

tients and myocardial abscess secondary to a bac-

teremia in two. However, the sudden circulatory de-

compensation that led to death in all five of these pa-

tients included spread of infection into the pericar-

dium with resulting hemodynamic embarrassment. All patients were receiving appropriate antimicrobial

therapy for their infections, and in none would sur-

gery have been likely to alter the outcome: in all in-

stances, spread of infection within the myocardium,

as well as within the pericardium, would have made

these patients inoperable.

In group IV patients (systemic bacteremia) fever,

chills and tachycardia of sudden onset with subse-

quent development of hemodynamic embarrassment

was the typical presentation. The duration of illness

from onset to either death or recognition and therapy

was less than 5 days in all cases. Five of these six

patients had evidence of impaired venous return; four

of them manifested significant pulsus paradoxus. The

one patient without circulatory manifestations, and

the only one in this group who died before a diagno-

sis was made, was a 17 year old boy with acute

meningococcemia of less than 16 hours’ duration

who only had microscopic evidence of disease (plus

positive cultures) at postmortem. Despite the pre-

dominance of cardiac findings in these patients, fric-

tion rubs were present in only one of the group IV pa-

tients, being found predominantly in group I and group

II patients.

Laboratory Findings. The presence of significant

acute inflammation was reflected in the white blood

cell counts of virtually all the patients, white blood

cell counts of more than 12,000/mm3 (with 20 of the

26 patients having white blood cell counts of more

than 17,000/mm3) and marked shifts to the left in the

polymorphonuclear leukocyte population being pres-

ent in all but 3 patients. The three exceptions includ-

ed one patient with leukemia, one renal transplant

patient who was receiving large doses of corticoste-

roids and azathioprine, and one patient with underly- ing neutropenia of unknown etiology-all adequate

reasons for lack of a leukocytosis. Moderate anemia

(hematocrit values between 30 and 35 per cent) was

present in 15 of the patients (58 per cent), but other blood tests were less helpful, with only minimal ab-

normalities of liver function and cardiac muscle en-

zymes being noted.

Chest roentgenograms were performed in 25 of

the 26 patients. Twenty-four of these showed abnor- malities (increased heart size in 19 (76 per cent),

pneumonia in 12 (48 per cent), pleural effusion in 8

(32 per cent) and mediastinal widening in 3 (12 per

cent)). In the majority of instances, the roentgeno-

gram suggested the pathologic process (such as

pneumonia, empyema or mediastinitis) accompa-

nying the purulent pericarditis without giving clear-cut evidence of pericardial disease. In 11 instances, the

finding of progressive enlargement of the cardiac sil-

houette with a “waterbottle-like” configuration in the

absence of pulmonary vascular congestion was high-

ly suggestive of significant pericardial fluid accumula-

tion. Three echocardiograms were carried out, and

all three were positive, including two in patients in

whom neither the chest roentgenogram nor electro-

cardiogram was particularly helpful. A right heart

catheterization was carried out in one patient, reveal-

ing the elevated central venous pressure, poor cardi-

ac pulsations, typical pressure tracing and increased

thickness between right atrial endocardium and peri-

cardial border that are characteristically found in pa-

tients with cardiac tamponade.

Electrocardiograms were obtained in 23 patients.

The tracings were normal or showed no changes

from a previous electrocardiogram in eight patients,

and were abnormal in 15. Nonspecific S-T and T

wave changes were noted in seven patients and

were the most common findings. More classic abnor-

malities associated with pericarditis, including diffuse

S-T wave elevation (five patients) and diffuse T wave

inversion (three patients, one of whom also demon-

strated low QRS voltage and electrical alternans),

were seen in the other eight patients. Arrhythmias

that could be ascribed to the pericarditis and not to

digitalis, electrolyte disturbances, hypoxia, acid-base

disturbances, myocardial abscesses and the like

were distinctly unusual.

Detailed analyses were carried out on pericardial

fluid obtained from five patients. The white blood cell

counts of the fluid ranged from 6,100 to 241 ,OOO/

mm3, being greater than 50,000/mm3 in four of the

five. Differential counts revealed more than 90 per

cent polymorphonuclear leukocytes in all instances.

Sugar levels were less than 35 mg/ 100 ml in all but

one patient, and the protein level ranged from 3.3 to

6.2 g/100 ml (mean 4.7 g/100 ml). In one patient, a

patient with pleuropulmonary disease, fluid was rela- tively clear, the white blood cell count was only

6,1 00/mm3 (94 per cent polymorphonuclear leuko- cytes), the sugar level was 79 mg/ 100 ml and the

protein level was 4.2 g/100 ml, but gram-positive

cocci were seen on gram stain and Staph. aureus

grew on culture. All the other patients had low sugar levels and higher white blood cell counts. Pericardial

fluid lactic dehydrogenase values were determined in

two patients and were 4,800 and 6,700 units/ml, re-

spectively (normal values are 60 to 120 units/ml).

72 July 1975 The American Journal of Medicine Volume 59

PURULENT PERICARDITIS-RUBIN, MOELLERING

Therapy and Complications. Eleven patients re- which is at first clear, then contains organisms, has ceived treatment consisting of more than 2 days of fibrin deposition and only later becomes grossly puru- appropriate antibiotics and at least one pericardio- lent [2,7]. In this series, four of the five patients who centesis. Six of these survived, for a mortality rate of underwent detailed pericardial fluid examination had 44 per cent in those in whom adequate therapy was the “late picture” of gross purulence, high white instituted. Two of the survivors were treated only with blood cell count and low sugar content. However, in pericardiocentesis plus antibiotics. The four others one patient with purulent pericarditis accompanying required thoracotomy and at least partial pericardiec- Staph. aureus bronchopneumonia. there was a rela- tomy in addition to this. In two of these, the indication tively low white blood cell count in the pericardial fluid for surgery was repeated reaccumulation of fluid; in and a normal sugar content. When comparing this two, acute pericardial constriction developed 1 and 3 last patient with the other four, it is apparent that this weeks, respectively, after therapy had been institut- patient had had an acute staphylococcal infection for ed. In one of these, a large epicardial abscess was less than 36 hours, whereas the others had been found and drained at the time of surgery. Antimicro- sick for more than 4 days. It is believed that these bial therapy was continued for 4 to 6 weeks in all sur- findings correspond to a very early stage in the vivors pathogenetic series of events.

Of the remaining 15 patients, the correct diagnosis was made during life in 7 and at autopsy in 8. The seven diagnosed but inadequately treated patients in- cluded two from group I (postsurgical) and five from group Ill (intracardiac infection). All of these, in addi- tion to six of the eight in whom the diagnosis was made at autopsy, had received at least 10 days of appropriate antibiotic therapy without pericardial

drainage before they died.

COMMENTS

The microbiologic, clinical and therapeutic features of purulent pericarditis have changed dramatically

over the past decade. Previously, it was a disease of children and young adults [2] ; today, it is found equally in all age groups. Previously pleuropulmonary disease was the cause of approximately 50 per cent of the cases [2]; today, less than 25 per cent occur in this setting. Once Staph. aureus and Strep. pneu- moniae accounted for at least half of all cases [2] ; today, fungi, gram-negative bacilli and associated un- usual pathogens are the cause of many cases. Once primary infection in healthy patients was the rule;

today, major thoracic and cardiac surgery, immuno- suppressive therapy, extensive thermal burns, lym- phoproliferative diseases and other systemic pro- cesses are the substrata within which this disease occurs. The major area in which there has been no change, however, is in the unacceptably high mortali- ty rate. In view of this a reexamination of the patho- genesis, clinical presentations, etiologies, and the di- agnostic and therapeutic approaches available ap- pears to be in order. Pathogenesis. The pathogenesis of purulent peri- carditis has been best worked out in those cases ac- companying intrathoracic disease and occurring by contiguous spread of infection. The first lesion ob- served is a local area of acute inflammation of the parietal pericardium adjacent to the site of contigu- ous infection. Next there is an accumulation of fluid,

Direct extension from the pleural space or lung accounts for the majority of cases of pericarditis ac- companying thoracic infections, but the observation that right-sided pneumonia or empyema may accom- pany purulent pericarditis has suggested that other mechanisms may be at work [2,7-131. Although systemic bacteremia may well be the final common

denominator, Hahn et al. [ 1 l] and others [ 121 have suggested that microscopic septic emboli from a pul- monary focus of suppuration may go directly to the pericardium, myocardium or mediastinum via the bronchial arteries, without involving the rest of the

systemic circulation. Clinical Setting and Presentation. Purulent pericar- ditis is a disease that almost always occurs as a complication of another illness [ 2,14,15], be it surgi- cal wound infection, intrathoracic infection or bacter- emia. In all instances that we have observed, it is an

acute progressive, septic process of less than 6 days’ duration that requires prompt and aggressive attention. Early recognition and effective therapy of pericardial disease is impossible unless the physician is alert to the disease settings in which spread of the

infection to the pericardium may take place. Pericardial disease occurring in the postoperative

patient (group I) in this series did not ever present as an isolated phenomenon, but rather as part of gross intrathoracic infection in patients with sternal wound infection or mediastinal abscess. Aggressive surgical drainage plus prolonged antibiotic therapy may be successful even in this group of desperately ill pa- tients [ 161. In patients who have undergone esopha- geal surgery, recognition that pericardial involver ent can occur via esophageal perforation and mediasti- nai contamination should prompt the attending physi- cian to look closely for the clinical and laboratory correlates of pericardial disease, particularly in the presence of circulatory compromise and a febrile postoperative course.

Purulent pericarditis secondary to intracardiac in-

July 1975 The American Journal of Medicine Volume 59 73

PURULENT PERICARDITIS-RUBIN, MOELLERING

fection (group III) is likewise difficult to treat. Ideal therapy is eradication of cardiac infection before spread to the pericardium rather than after. Evidence of pericarditis has been noted in 13.2 per cent of pa- tients with bacterial endocarditis examined at nec- ropsy [ 171. Myocardial abscesses have been found at autopsy in about 20 per cent of patients with en- docarditis, and in a small percentage of patients with bacteremia [ 18,191. The risk of development of both myocardial abscesses and purulent pericarditis ap- pears to be especially high in patients with endocar- ditis due to Staph. aureus. In one recent report [20] of autopsies, in 39 patients who died with Staph. au- reus endocarditis, 36 per cent had myocardial ab- scesses and 10 per cent had purulent pericarditis. In bacterial endocarditis, myocardial abscesses may develop as localized lesions secondary to the sys- temic bacteremia or from direct extension from the infected ualvular vegetation [ 19,2 1,221. They are dif- ficult to detect clinically. Their presence should be suspected under the following circumstances: con- tinuing evidence of infection in patients with bacterial endocarditis receiving effective antibiotic chemother- apy [ 18,191, particular electrocardiographic abnor- malities [ 18,231 and circulatory compromise not ex- plainable by valvular dysfunction alone. Infection spreading from aortic valve vegetations into the ad- joining high septal tissue may be associated with the following electrocardiographic findings: a prolonged P-R interval, atrioventricular dissociation, left bundle branch block and multifocal ventricular ectopic beats [23]. In mitral valve infection, accelerated junctional rhythms and Wenckebach type block may occur be- cause of the close relation of the mitral valve and junctional tissue. Unfortunately, isolated, scattered myocardial abscesses are often silent until after irre- versible spread to adjoining tissues has occurred. Several workers [24,25] have stressed the impor- tance of erosion of the aortic valve annulus due to in- fection in the pathogenesis of pericarditis in patients with endocarditis, pointing out that this is relatively common in patients with Staph. aureus infection but quite rare in those with Strep. viridans infection.

Group II (pleuropulmonary) and group IV (bactere- mic) patients are worthy of the most attention since they are the most likely to survive. In this series, 6 of the 12 patients in these two groups survived (mortali- ty 50 per cent). It is in these patients that circulatory measurements and close observation for evidence of cardiac tamponade can be most helpful. Ten of these 12 patients manifested such abnormalities. On the other hand, chest pain and pericardial friction rubs were seen only infrequently in this group. The lack of chest pain is not surprising since the visceral and inner surface of the parietal pericardium are in- sensitive to pain [26]. Accordingly, ancillary diag-

nostic clues must be sought. These include the fol- lowing: (1) Echocardiography may be the most help- ful noninvasive technic available. It provides a very sensitive indicator of a pericardial fluid collection and distinguishes clearly pericardial fluid from enlarge- ment of the cardiac silhouette due to tumor or cham- ber dilatation [ 27-321. (2) Electrocardiographic ab- normalities, especially in patients without known cor- onary artery disease, can be useful. However, a di- agnostic pattern [33] is relatively uncommon and was present in only 8 of 23 patients in this series. (3) Enlargement or change in configuration of the cardi- ac silhouette in the absence of pulmonary vascular engorgement on chest roentgenogram may provide evidence of pericardial effusion, although this is rela- tively nonspecific. (4) Cardiac catheterization is the traditional definitive but highly invasive technic that can be used in making the diagnosis prior to surgical intervention.

In this series, associated systemic diseases that interfered with host defense against infection were present in at least 50 per cent of the patients. Of particular interest were two patients with extensive third degree burns who died with purulent pericarditis: one of contiguous spread from a mediastinal site in the setting of a persistent gram-negative bacteremia, and one from bacteremic spread to the myocardium and pericardium. A recent review from the U.S. Army Institute of Surgical Research has documented the importance of suppurative infections of the heart in burn victims, reporting 64 cases over a 17 year peri- od [34]. Among these were four cases of purulent pericarditis, three secondary to contiguous spread from a myocardial abscess and one from mediastini- tis.

Two of the patients in this series had preceding nonsuppurative pericardial disease. This possibility was first suggested by Solomon et al. [35], who cul- tured streptococci at postmortem examination from the pericardium of four patients with uremic pericar- ditis. Others [36-381, reviewing the data in patients with uremic and viral pericarditis, were unable to confirm this association. However, two of our pa- tients, in whom bacterial pericarditis appeared to have complicated preexisting nonsuppurative peri- carditis, reopen this question. At the least, the diag- nosis of bacterial superinfection should be consid- ered and pursued aggressively in any patients with preceding nonsuppurative pericardial disease who suddenly show signs of unexplained infection, espe- cially when there is evidence of circulatory impair- ment [4].

A variety of unusual conditions have been reported to lead to purulent pericarditis, although they were not seen in this series; bacteremic seeding of a site of myocardial infarction with subsequent spread to

74 July 1975 The American Journal oi Medicine Volume 59

PURULENT PERICARDITIS--RUBIN MOEILLERING

the adjacent pericardium [39-411, contiguous

spread through the diaphragm due to a congenital

abnormality or catastrophic rupture through the dia-

phragm (perforated ulcer [42], infected choledochal

cyst [ 431, a pericardioperitoneal communication in a

patient with peritonitis [ 441, subphrenic abscess

[45], etc.), contiguous spread from a retropharyn-

geal abscess to the mediastinum and pericardium

[8] and, finally, penetrating wounds [42,46]. Fortu-

nately, these are rare occurrences.

The pediatric population merits special attention

when considering purulent pericarditis, because sup-

purative disease ranks second only to rheumatic

fever among the causes of pericarditis in this age

group [ 15,471. In this subset of patients, bacteremia

and pleuropulmonary infection are the major etiologic

considerations, with Staph. aureus, Strep. pneumo-

niae, H. influenzae and N. meningitidis being the most

common organisms [ 15,47-501. The major diag-

nostic problem is to distinguish pericardial fluid col-

lections from acute dilatation of the heart secondary

to myocarditis and heart failure [3,48,49]. Friction

rubs are present in only 15 per cent of pediatric pa-

tients with purulent pericarditis [ 151, electrocardio-

graphic abnormalities seen with pericarditis are diffi-

cult to distinguish from those due to myocarditis

[3,15,32,47], and, especially in infants with respira-

tory distress, measurements of pulsus paradoxus are

often inaccurate [3]. The echocardiogram can be

most useful here, and is perhaps the greatest single

advance in the early diagnosis of purulent pericarditis

in this age group [ 321.

Microbiology. Staph. aureus remains the most fre-

quent cause of purulent pericarditis. In this series, in-

fections in 8 of 26 patients were due to Staph. au-

reus. Three of these represented hospital-acquired

infection, one a nosocomial pneumonia and two re-

lated to contaminated intravenous lines and bacter-

emia. Since 1935, at least 15 per cent of cases of

staphylococcal pericarditis have been hospital-ac-

quired [ 21. Boyle’s report [2] and our experience

would suggest that hospital-acquired disease is even

more important today. Complications, particularly

acute constriction [2,47,48,51-531, associated my-

cotic aneurysms of the proximal aorta [54] and sys-

temic bacteremia with metastatic infection, are quite

prevalent in staphylococcal pericardial disease. Be-

cause of the dangers of acute cardiac tamponade or

constriction, circulatory status of patients with staph-

ylococcal pericarditis should be closely monitored to

assess the possible need for thoracotomy and peri-

cardiectomy [2,47,48,51-531.

Kauffman et al. [lo] recently described five pa- tients with pneumococcal pericarditis, reminding us

that this disease has not become extinct. These in- vestigators made the following important clinical ob-

servations: (1) Pericardial friction rubs, pulsus para-

doxus and an enlarged cardiac silhouette may be ab-

sent in this form of the disease despite circulatory

embarrassment. (2) A preceding pneumonia was

present in 93.1 per cent of 113 patients described in

the medical literature, and in 66.6 per cent both

pneumonia and empyema were present. (3) In most

circumstances, pericardial involvement occurs as a

late event in patients, such as alcoholics, in whom

there is a long delay between onset of pneumonia

and initiation of penicillin therapy. Among the cases

recorded since 1945, this delay in obtaining therapy

averaged 21 days [ 10,55-581. Both of our patients

with pneumococcal pericarditis had pneumonia and

empyema; both had been ill and presumably had

pneumonia for some days prior to their admission to

the hospital (one was an alcoholic who had been on

a binge and one was an elderly resident in a nursing

home); both lacked friction rubs, although other evi-

dence of pericardial disease was present.

In 1950, Zimmerman [59] predicted an increase in

the incidence of infection due to fungi because of the

wide use of antimicrobial and cytotoxic agents. At

the time of Boyle’s review article [ 21 (all cases re-

ported up through 1957), no case of Candida or As-

pergillus infection had been described. Since then a

variety of single case reports of Aspergillus pericardi-

tis have appeared [60], but the finding in this series

of five cases of fungal pericarditis is the first major

confirmation of Zimmerman’s prediction as far as

pericardial infection is concerned. In this series all

the patients with fungal pericarditis had received

broad-spectrum antimicrobial therapy. Three had

underlying diseases or were receiving drugs that ren-

dered them immunosuppressed, and two had recent-

ly undergone major surgical procedures. A closely

related case was that due to Nocardia asteroides in a

renal transplant patient who was receiving cortico-

steroids, azathioprine and broad-spectrum antibiot-

ics. Other cases due to Nocardia have been reported

[ 6 1,621 and, like the true fungal cases, carry a mor-

tality rate approaching 100 per cent.

H. influenzae infection was documented in two pa-

tients: one a 26 year old healthy adult with a probable

H. influenzae infection of the upper respiratory tract complicated by bacteremia that infected the pericar-

dium: and one a 14 month old child with bacteremia

and meningitis. H. influenzae pericarditis has not

been uncommon in the pediatric population, particu-

larly in the age group under 5 [3,15,47-491. Usually

these patients had a history of acute respiratory dis-

ease (laryngitis or pneumonia); meningitis was fre-

quently present; and in only one did pericarditis occur

without evidence of infection elsewhere [63-66 1. All

but three of the previously described patients with H. influenzae pericarditis have been less than 12 years

July 1975 The American Journal of Medicine Volume 59 75

PURULENT PERICARDITIS-RUBIN. MOELLERING

of age [66,67]. Crossley et al. [66] surveyed this subject in detail and pointed out that there may be an increasing incidence of H. influenzae type b disease in adults, not only of the pericardium, but also of the lungs, epiglottis, joints and meninges. This perhaps reflects a decrease in the prevalence of bactericidal antibody against type b H. influenzae in the adult pop- ulation [ 68-7 1 ] .

There have been a large number of reports [72- 88] of pericarditis associated with meningococcal disease, and there has been some confusion as to when in the course of meningococcal infection the pericardium becomes infected and whether or not immunologic mechanisms may play a role [87,88]. Our single case of meningococcal disease demon- strates that the pericardium may become infected very early in the bacteremic process. Others [83- 86] have pointed out that meningococcal pericarditis may occur without evidence of meningococcal dis- ease elsewhere, presumably due to a transient bac- teremia that had no other clinical effects. In addition, in several recent reports [87,88], it has been sug- gested that late pericarditis may commonly occur in the convalescent stage of meningococcal disease. This seems to represent a hypersensitivity phenome- non, does not require antimicrobial therapy, and usu- ally responds to salicylate and/or corticosteroid ther-

apy. A wide variety of miscellaneous causes of purulent

pericarditis were noted in this series and others have been reported in the literature: Clostridium species [89], Salmonella species [41,90-921, a variety of other gram-negative enteric bacilli [2], P. tularensis [2], H. pertussis [93], N. gonorrhoeae [2,94], mixed cases of granulomatous (either tuberculous or acti- nomycotic) and pyogenic infection [2], Vibrio fetus [95], Listeria monocytogenes [96] and others [2]. One of the more interesting single cases in this se- ries was that due to Strep. mitis. In this patient, Strep. mitis infection of the aortic valve spread to the aortic root and then to the pericardium. Strep. mitis is a “viridans” Streptococcus, usually causing a sub- acute form of disease [97]. In our patient, however, an acute bacterial endocarditis was caused, analo- gous to that usually associated with Staph. aureus in- fection. This is an example of the point emphasized by Weinstein et al. [ 181 in their recent review of bac-

terial endocarditis-the differentiation of acute and subacute disease is a clinical one based not on the organism, but rather on the pace of the infection and the virulence of the etiologic agent.

Since such a large variety of organisms can po- tentially cause purulent pericarditis, and since ob- taining material for culture requires invasive technics, it is essential that appropriate culture media and methods be employed from the beginning. Pericardial fluid should routinely be cultured for aerobic and an- aerobic bacterial pathogens, as well as for acid-fast bacilli and fungi. Treatment. As with any localized form of infection, the therapy of purulent pericarditis requires adequate drainage and appropriate antimicrobial therapy. Some workers have advocated the use of repeated pericardiocenteses for drainage [98], and this was successful in two of our six patients who survived, in association with 4 to 6 weeks of antimicrobial thera- py. However, recurrences of effusions are the rule and multiple pericardial aspirations may be hazard- ous [99], so we, and others [ 10,48,56] have quickly resorted to open drainage if one or two pericardio- centeses are not successful in controlling fluid accu- mulation. Acute pericardial constriction also de- mands prompt surgical intervention. Whether peri- cardiectomy or just a pericardial window will be nec- essary is dependent upon what is found at operation: adherent, thickened pericardium with or without thick pus requires pericardiectomy; whereas thinner fluid, with acutely rather than chronically inflammed peri- cardium, may be treated with a pericardial window. Both the transthoracic and the subxiphoid approach have been utilized for pericardial windows [ lOO,lOl]. The latter has the advantage that it does not require violation of the pleural space.

Antimicrobial therapy is the basis of the medical management. A variety of reports of intrapericardial instillation of antibiotics in such patients have ap- peared [2,6,102,103], but a recent study by Tan et al. [ 1041 showing excellent penetration of antimicro- bial agents into pericardial fluid suggest that this is not necessary. In our limited experience, prompt drainage and adequate drug therapy prevented the occurrence of chronic constrictive pericarditis, a complication noted in the past in some patients with purulent pericarditis.

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