Purulent pericarditis

INTRODUCTION — Prior to the widespread use of antibiotics, purulent pericarditis was a frequent complication of pneumococcal pneumonia. In modern times, most cases of purulent pericarditis are associated with nosocomial bloodstream infections (such as in the setting of dialysis), thoracic surgery, or immunosuppression (eg, HIV, chemotherapy).

Galen (AD 129 to 217) was one of the first clinicians to recognize and attempt to treat purulent pericarditis. While removing the "putrefied" sternum of a patient with posttraumatic pericarditis, he directly observed "mortification of the pericardium" in a patient who survived [1].

By the beginning of the 19th century, clinicians were aware that purulent fluid collections in the pericardium could occur in patients with pneumonia and pleurisy, and were attempting treatment with percutaneous drainage and pericardiectomy [2].

Issues related to purulent pericarditis will be reviewed here. Other causes of pericarditis and the management of acute pericarditis are discussed separately. (See "Etiology of pericardial disease" and "Acute pericarditis: Clinical presentation and diagnosis" and "Acute pericarditis: Treatment and prognosis".)

DEFINITION — Purulent pericarditis is defined as a localized infection of the pericardial space characterized by gross pus in the pericardium or microscopic purulence (>20 leukocytes per oil immersion field). This distinction is important since purulent material in the pericardium is not synonymous with infectious pericarditis, and not all infections produce purulent effusions. As an example, pericarditis due to Mycoplasma hominis or viral infection is rarely macroscopically or microscopically purulent. By contrast, a variety of noninfectious conditions produce an inflammatory exudate that may contain >50,000 white cells/microL [3].

EPIDEMIOLOGY — The incidence and etiologies of purulent pericarditis have changed significantly in the antibiotic era. In modern practice, purulent pericarditis is relatively uncommon. In a retrospective review performed in Spain between 1972 and 1991, only 33 cases were observed among an inpatient population of 593,600; the diagnosis was not established until postmortem in 14 of these cases [4].

Predisposing factors — One study compared 55 patients who died from purulent pericarditis during the post antibiotic era with 145 patients who died from the same condition during the period 1889 to 1943 [5]. The following conclusions were reached:

●In the preantibiotic period, the majority of patients had a primary infectious disease such as pneumonia (72/145), endocarditis (11/145), or other (41/145). Other infectious foci resulting in bacteremia and pericardial infection included the central nervous system, bone, pelvic, skin, and otic structures.

●In the modern era, only 22 percent of patients with purulent pericarditis had a recognized underlying primary infectious disease, such as pneumonia (3/55) or meningitis (4/55).

●In the preantibiotic era, only 14 percent of patients had an underlying non-infectious condition or disease. By contrast, in modern practice, 78 percent had one or more predisposing causes including recent thoracic surgery (12/55), chronic renal failure (9/55), or malignancy (8/55).

●In the antibiotic era, many patients with purulent pericarditis also had preexisting pericardial diseases due to conditions or causes, such as uremia, tumor, or collagen vascular disease.

Other predisposing factors include immunosuppression, alcohol abuse, thoracic surgery, and chest trauma [6].

PATHOGENESIS — There are several mechanisms by which patients develop purulent pericarditis:

●Direct spread from an intrathoracic focus of infection, including extension from a myocardial focus or direct contamination from trauma or thoracic surgery

●Hematogenous spread

●Extension from a subdiaphragmatic suppurative focus

In the preantibiotic era, direct pulmonary extension accounted for the probable route of acquisition in almost two-thirds of cases. In two of the larger series of cases of purulent pericarditis in the antibiotic era, direct pulmonary extension accounted for 20 and 25 percent of infections respectively, while hematogenous spread occurred in 29 and 22 percent, perforating injury or surgery in 24 and 29 percent, and myocardial abscess and/or endocarditis in 22 and 14 percent [1,5].

Direct spread of infection from an intrathoracic focus — Virtually any organism can spread from infected lung into the pericardium; Streptococcus pneumoniae is the most common organism. In a review of 113 cases of pneumococcal pericarditis between 1900 and 1973, 93 percent of cases had a preceding pneumonia and 67 percent had pneumonia with empyema [7].

Infection can also spread to the pericardium following esophageal perforation. This complication is usually devastating, with a survival rate of only 17 percent in one review of 60 patients with pyopneumopericardium secondary to esophageal perforation [8].

Hematogenous spread — Virtually any organism can spread to the pericardial sac via the hematogenous route. Numerous case reports document an array of common and uncommon bacteria and fungi that have caused purulent pericarditis. Of these pathogens, Staphylococcus aureus and various streptococci are most common [2].

Pneumonia or empyema may be accompanied by bacteremia; in such cases, patients can develop pericardial infection from hematogenous spread or via microscopic septic emboli into the bronchial arterial circulation, with secondary spread to the pericardium, myocardium, or adjacent mediastinum [1].

Extension from a myocardial focus — Infective endocarditis can be complicated by perivalvular ring abscess, septic coronary artery emboli, or myocardial abscess, all of which can result in direct extension of infection to the pericardium. In addition, occasionally a sterile inflammatory pericardial collection can develop in the setting of endocarditis. Therefore a clinical presentation of pericarditis and/or pericardial fluid in the setting of endocarditis or mural thrombus does not always imply purulent pericarditis, although such findings should be evaluated carefully.

Rarely, myocardial infarction can be complicated by infection, resulting in abscess formation and secondary purulent pericarditis [9]. A myocardial abscess can also occur as metastatic infection in patients with bacteremia due to organisms such as S. aureus or Salmonella. Such patients may, in turn, develop purulent pericarditis from direct extension of the abscess into the pericardium. In rare cases, coronary artery stents can become infected with S. aureus, resulting in coronary artery aneurysms and purulent pericarditis [10].

Perforating injury or surgery — Purulent pericarditis may develop as an early or late complication of perforating injury or thoracic surgery. Most of these patients have associated clinical signs or symptoms of mediastinitis or empyema. In some post-thoracotomy patients it may be difficult to distinguish between pericardial injury syndrome and purulent pericarditis. S. aureus, enteric gram-negative rods, and Candida species are the most likely pathogens, although virtually any bacteria can cause purulent pericarditis in such situations. Purulent pericarditis due to knife wounds is often polymicrobial; bullet or shell fragment wounds may result in clostridial pericarditis [2]. (See "Pericardial complications of myocardial infarction".)

Extension of infection from a subdiaphragmatic suppurative focus — Undrained subphrenic abscesses result in pericardial extension in 2 percent of cases [11]. Rare subdiaphragmatic processes that can result in purulent pericarditis include intrahepatic amoebic abscess, ruptured duodenal or gastric ulcer, infected choledochal cyst, peritonitis, or erosion of intraabdominal tumor into the pericardium [12,13].

MICROBIOLOGY — S. aureus is the most common cause of purulent pericarditis, accounting for 31 percent of cases in one series and 22 percent in another [1,5]. In these reviews, gram-positive organisms caused approximately 40 to 45 percent of all infections; polymicrobial infections were uncommon. S. pneumoniae is the most common cause of purulent pericarditis in the setting of direct spread of infection from an intrathoracic focus. Salmonella bacteremia can also result in purulent pericarditis [14]. Many other bacterial organisms have been reported to cause purulent pericarditis, including rare cases of infection with anaerobic bacteria [15].

Fungal pathogens have become more common causes of purulent pericarditis. In one series of 26 patients, fungi were the etiology of purulent pericarditis in 19 percent of cases; these patients had predisposing factors for candidemia [1]. In two reviews summarizing the clinical features of 10 cases of Candida pericarditis, six patients had one or more well known predisposing factors for candidemia including parenteral hyperalimentation, steroid administration, prolonged antibiotic therapy, malignancy, burns, or alcoholism [16,17]. The remaining four patients had had recent cardiac surgery.

Tuberculosis is the most common cause of subacute or chronic purulent pericarditis in resource-limited countries, particularly where the prevalence of HIV is high [18]. (See "Tuberculous pericarditis".)

CLINICAL MANIFESTATIONS — Purulent pericarditis is typically an acute illness characterized by high fever, tachycardia, cough, and chest pain (regardless of the pathogen involved or the pathogenesis of infection) [6]. In one series, the mean duration of symptoms before hospitalization was three days (range one to six days) [1]. In another series, clinical features of pericarditis developed a mean of 10 days after onset of predisposing infection [4].

Fever is present in virtually all patients [1,4]. Chest pain is less common in purulent pericarditis than in acute pericarditis of other etiologies (25 to 37 percent of patients) [1,4]. Chest pain may be pleuritic or nonpleuritic. In the postoperative setting, most patients with purulent pericarditis have other signs of mediastinitis or sternal wound infection [1]. (See "Postoperative mediastinitis after cardiac surgery" and "Etiology of pericardial disease".)

A pericardial friction rub is present in 35 to 45 percent of patients with purulent pericarditis [1,4]. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Pericardial friction rub'.)

The incidence of cardiac tamponade has varied from 42 to 77 percent in different series; sudden cardiac decompensation can rapidly lead to death [1,4]. There is indirect evidence that the concomitant use of antiplatelet and antithrombotic therapies is not associated with an increased risk of cardiac tamponade; however, these data were obtained in patients with idiopathic or viral acute pericarditis, so the application to patients with purulent pericarditis is uncertain [19]. (See "Cardiac tamponade".)

The majority of patients with purulent pericarditis are acutely ill; occasional patients have a relatively indolent course of infection. One such case was reported in a hemodialysis patient who was treated twice for lengthy periods for S. aureus bacteremia and then presented with dyspnea, fatigue, and chest discomfort [20]. Chest computed tomography (CT) revealed a large anterior mediastinal mass compressing the heart (image 1); the patient underwent pericardiectomy and drainage of pus from the pericardial space. Salmonella may also cause a more indolent course of purulent pericarditis.

Laboratory findings — General laboratory tests are nonspecific in purulent pericarditis. Anemia and leukocytosis are present in most patients, although those receiving chemotherapy may be leukopenic.

In one case series, chest radiographs were abnormal in 25 of 26 patients with purulent pericarditis (image 2) [1]. The findings included:

●Cardiomegaly (19/25)

●Pulmonary infiltrates (12/25)

●Pleural effusions (8/25)

●Mediastinal widening (3/25)

Electrocardiography — The majority of patients with purulent pericarditis have electrocardiographic findings typical of acute pericarditis. However, the electrocardiogram may be normal in 10 to 35 percent of patients [1,4]. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram'.)

Echocardiography — Echocardiography is very useful for detecting fluid in patients with purulent pericarditis, but cannot distinguish between purulent collections and sterile inflammatory effusions. (See "Echocardiographic evaluation of the pericardium" and "Pericardial effusion: Approach to diagnosis", section on 'Cardiac imaging'.)

DIAGNOSIS — The diagnosis of purulent pericarditis can be overlooked and delayed, particularly since it can be a complication of a variety of primary infectious diseases, trauma, surgery, and diseases in adjacent structures [5]. The widespread availability of two-dimensional echocardiography and computerized tomography has improved the antemortem diagnosis. Ultimately, however, the diagnosis of purulent pericarditis is established by obtaining pericardial fluid for culture and microscopy. Since many patients with purulent pericarditis have clinical signs compatible with tamponade, this procedure can be both diagnostic and therapeutic.

The diagnosis of purulent pericarditis can be especially difficult when patients with preexisting conditions associated with pericardial effusions develop fever and leukocytosis. In addition, some pathogens (such as Neisseria meningitidis) cause sterile pericardial inflammatory fluid during the convalescent stage of illness, presumably immune-mediated [21,22]. Distinguishing sterile inflammation from purulent pericarditis is difficult.

Pericardiocentesis — The diagnosis of purulent pericarditis is established by obtaining pericardial fluid for culture and microscopy [6]. Echocardiographically-guided pericardiocentesis using portable echocardiographic equipment is preferable [23]. Alternatively, pericardiocentesis can be performed by a "blind" subxiphoid approach or under fluoroscopic guidance and electrocardiographic needle monitoring. (See "Pericardial effusion: Approach to management", section on 'Technique'.)

Pericardial fluid should be sent for protein, glucose and cell count, along with Gram stain, acid fast stain, fungal stain, and cultures. Typically the protein concentration is high and glucose levels are less than 35 mg/dL (2 mmol/L). Pericardial fluid leukocyte counts generally are markedly elevated, ranging from 6000 to 240,000/microL. It is important to obtain an adequate sample of pericardial fluid for culture; swabs taken at the time of surgery are not adequate for obtaining cultures. A minimum of 0.5 mL of fluid should be sent to the microbiology laboratory but a sample of 1 mL or greater is preferred.

Additional investigations — For circumstances in which purulent pericarditis is accompanied by bacterial pneumonia, urinary S. pneumoniae antigen testing may be a useful diagnostic tool [24].

TREATMENT — Treatment for purulent pericarditis consists of pericardial drainage and antimicrobial therapy [6]. The best method of drainage remains controversial. Since purulent pericarditis is often a rapidly progressive and fatal infection, the expertise and experience of local clinicians and the availability of technology usually determines which of the following techniques is utilized. (See "Pericardial effusion: Approach to management", section on 'Choice of pericardial drainage procedure'.)

Pericardial drainage — A number of options are available for drainage of the infected pericardial fluid.

●Pericardiocentesis – Pericardiocentesis is the simplest and often the fastest way to drain the pericardial space. However, thick fluid may either drain poorly or result in loculations in the pericardial space. Furthermore, pericardial constriction may occur following recovery if pericardiocentesis is the primary drainage method [4].

Fibrin formation appears to be an essential step in the evolution to constrictive pericarditis and persistent purulent pericarditis. Because of potential morbidity associated with pericardiectomy, intrapericardial fibrinolysis during pericardiocentesis may be considered as a less invasive effort to prevent persistent purulent pericarditis and constrictive pericarditis [25,26]. Nevertheless, if pericardiocentesis is not feasible or if fibrinolysis fails, pericardiectomy remains the primary option for complete eradication of infection.

●Subxiphoid pericardiotomy – Subxiphoid pericardiotomy usually allows more complete and permanent drainage than pericardiocentesis because a pericardial "window" is established during the procedure and because manual lysis of adhesions and loculations is easily accomplished with the finger of the operating surgeon. This procedure is usually performed in an operating room, but, when necessary, can be performed at the bedside using local anesthesia [27]. This approach was recommended as the preferable course of management by the 2015 ESC guidelines [6].

Postoperative constrictive pericarditis can occur following this procedure, but is uncommon. A detailed discussion of constrictive pericarditis is presented separately. (See "Constrictive pericarditis: Diagnostic evaluation".)

●Pericardiectomy – Pericardiectomy has a higher morbidity and mortality than subxiphoid pericardiotomy. However, pericardiectomy usually achieves complete drainage, and is frequently required in patients with dense adhesions, loculated and thick purulent effusion, recurrent tamponade, persistent infection, and progression to constriction. A full discussion of pericardiectomy is presented separately. (See "Constrictive pericarditis: Management and prognosis", section on 'Treatment of late (chronic) disease'.)

●Video-assisted thoracic surgery – Video-assisted thoracic surgery (VATS) requires intubation and deflation of the left lung. It is usually performed through a small left chest incision. A pericardial window can usually be performed with this procedure, but complete pericardial stripping is not possible. Although this procedure usually achieves good drainage of the pericardial space, it adds little to a subxiphoid pericardiotomy and carries more risk.

Intrapericardial fibrinolysis has been proposed as a less invasive method than pericardiectomy for prevention of persistent purulent pericarditis and constrictive pericarditis, and early consideration of this approach is warranted to prevent both constrictive and persistent purulent pericarditis; however, pericardiectomy remains the preferred approach for complete eradication of infection.

Experimental data demonstrate that fibrin formation, which occurs during the first week of the disease, is an essential step in the evolution to constrictive pericarditis and persistent purulent pericarditis. In a clinical review including 40 patients who underwent intrapericardial fibrinolysis for management of purulent pericarditis, only two (treated by late fibrinolysis) encountered failure requiring pericardiectomy [25]. No patient encountered clinical or echocardiographic features of constriction during follow-up, and only one serious complication was described.

Antimicrobial therapy — Intravenous antimicrobial therapy should be started as soon as the diagnosis of purulent pericarditis is suspected. Initial empiric antibiotic treatment should include coverage for the likely or suspected pathogens [6]. (See 'Microbiology' above.)

Empiric regimen — The selection of an empiric regimen depends on careful consideration of patient-specific factors that can give clues to an etiologic diagnosis. These factors include:

●Whether the patient is immunosuppressed

●Whether the infection began in a health-care setting or in the community

●The presence of a concurrent infection at another body site

●The presence of intravascular lines or prosthetic devices

●Local patterns of antimicrobial resistance

●Whether the patient has received recent antimicrobial therapy

In general, empiric therapy for infections that occur in immunosuppressed patients or in a health care setting should include coverage for both gram-positive and gram-negative bacterial pathogens. Possible regimens include:

●Vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose); goal is a vancomycin trough serum level of 15 mcg/mL or greater, plus either

●Ceftriaxone (2 g IV once daily), cefotaxime (2 g every eight hours) or gentamicin (3 mg/kg per 24 hours divided equally in two or three doses) OR

●A carbapenem, such as imipenem (500 mg IV every six hours) or meropenem (1 g IV every eight hours) OR

●A beta-lactam plus beta-lactamase inhibitor, such as ticarcillin-clavulanate (3.1 g IV every four hours), piperacillin-tazobactam (4.5 g every six hours) or ampicillin-sulbactam (3 g IV every six hours) OR

●Cefepime (2 g IV every 12 hours)

In addition, empiric therapy with fluconazole (200 to 400 mg intravenously once daily) is recommended for patients who are severely immunosuppressed, for those who have had recent care in an intensive care unit, or for recipients of recent broad-spectrum antimicrobial therapy.

Pathogen-directed therapy — After a microbiologic diagnosis has been established by blood and/or pericardial fluid cultures, therapy should be directed at the specific pathogen isolated. If a methicillin-susceptible S. aureus is recovered from cultures of the blood and/or pericardial fluid, nafcillin or oxacillin (2 g IV every four hours) should be substituted for vancomycin in patients who are not allergic to beta-lactam antibiotics. There is no role for pericardial instillation of antibiotic, since therapeutic levels in the pericardial fluid are achieved by intravenous administration of antibiotics.

Duration of therapy — The duration of therapy must be individualized. Intravenous therapy should be continued until fever and clinical signs of infection have resolved and until the white blood cell count is normal. In general this usually consists of a total of approximately two to four weeks of therapy, depending on the adequacy of drainage and the antimicrobial susceptibility of the infecting bacteria.

Prognosis — Purulent pericarditis is a life-threatening disease. Reported mortality rates are between 20 and 30 percent. Constrictive pericarditis occurs over the course of purulent pericarditis in at least 3.5 percent of cases and is possible in up to 20 to 30 percent [25,28]. Timely recognition and treatment is of paramount importance for better outcomes and to prevent the development of constriction.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pericardial disease".)

SUMMARY AND RECOMMENDATIONS

●Purulent pericarditis is a localized infection of the pericardial space producing fluid that is macroscopically or microscopically purulent. This distinction is important since purulent material in the pericardium is not synonymous with infectious pericarditis, and not all infections produce purulent effusions. (See 'Definition' above.)

●The mechanisms by which patients develop purulent pericarditis include: direct spread from an intrathoracic focus of infection, hematogenous spread, extension from a myocardial focus, direct contamination from trauma or thoracic surgery, and extension from a subdiaphragmatic suppurative focus. (See 'Pathogenesis' above.)

●Staphylococcus aureus is the most common cause of purulent pericarditis. Other important pathogens include Streptococcus pneumoniae, Salmonella, Candida, and tuberculosis. Polymicrobial infections are uncommon. (See 'Microbiology' above.)

●Purulent pericarditis is typically an acute illness characterized by high fever, tachycardia, cough, and chest pain. Chest pain, however, is less common in purulent pericarditis than in acute pericarditis of other etiologies; when present it may be pleuritic or nonpleuritic. In the postoperative setting, most patients with purulent pericarditis have signs of mediastinitis or sternal wound infection. (See 'Clinical manifestations' above.)

●The diagnosis of purulent pericarditis is established by obtaining pericardial fluid for culture and microscopy. Echocardiographically-guided pericardiocentesis is preferable. Pericardial fluid should be sent for protein, glucose and cell count, along with Gram stain, acid fast stain, fungal stain, and cultures. (See 'Diagnosis' above.)

●Treatment for purulent pericarditis consists of pericardial drainage and antimicrobial therapy. Pericardiocentesis is frequently the fastest way to drain the pericardial space, although thick fluid may either drain poorly or result in loculations in the pericardial space. Subxiphoid pericardiotomy usually allows more complete and permanent drainage than pericardiocentesis because a pericardial "window" is established during the procedure and because manual lysis of adhesions and loculations is easily accomplished. (See 'Treatment' above.)

●Intravenous antimicrobial therapy should be started as soon as the diagnosis of purulent pericarditis is suspected. Initial empiric antibiotic treatment should include coverage for the likely or suspected pathogens. The selection of an empiric regimen depends on careful consideration of patient-specific factors that can give clues to an etiologic diagnosis. (See 'Empiric regimen' above.)

●After a microbiologic diagnosis has been established by blood and/or pericardial fluid cultures, therapy should be directed at the specific pathogen isolated. The duration of therapy must be individualized. Intravenous therapy should be continued until fever and clinical signs of infection have resolved and until the white blood cell count is normal. In general this usually requires a total of two to four weeks of therapy. (See 'Pathogen-directed therapy' above and 'Duration of therapy' above.)