OVERVIEW: What every practitioner needs to know
Are you sure your patient has mediastinitis? What should you expect to find?
Acute mediastinitis is an uncommon but potentially devastating infection involving the structures of the mediastinum. This infection can arise from perforation of the esophagus or spread from an oropharyngeal source, but most commonly occurs as a complication after median sternotomy. It may present subtlely with mild symptoms of chest pain and fever or occur precipitously with florid sepsis. The pathogens involved vary depending on the source of infection; oral flora predominates with esophageal and oropharyngeal sources, and gram positive cocci such as Staphylococci and Streptococci, are found most commonly in post-surgical cases.
Treatment involves a combination of systemic antimicrobials coupled with surgical debridement and drainage. Chronic mediastinitis, also known as sclerosing or fibrosing mediastinitis, is a rare disorder thought to be primarily due to Histoplasma capsulatum. The symptoms and signs of mediastinitis vary depending on where the infection originated from.
Esophageal or oropharyngeal source
Patients with mediastinitis due to oropharyngeal infections present with the symptoms of their original infection including localized pain, swelling and fever. Progressive chest pain, difficulty breathing and odynophagia are typical of progressive extension into the mediastinum. Esophageal perforation may be obvious or subtle. Examination often reveals signs of the inciting infection with fever, tachycardia and crepitus or edema of the neck, suggesting mediastinal extension.
Symptoms usually manifest within 2 weeks of surgery and may be subtle, with fever and greater than normal chest pain being most common. Fever with sepsis may be the only findings. Evidence of wound infection may be present with pain, cellulitis, drainage, erythema, or wound breakdown, but it is not diagnostic and a high level of suspicion should be maintained.
The majority of patients are asymptomatic with the diagnosis usually suggested by incidental imaging. Symptoms, when they do occur, are due to invasion or obstruction of mediastinal structures. Patients may complain of chest pain, dyspnea or hemoptysis. Exam findings may include venous engorgement or the findings of superior vena cava syndrome. Fever and systemic symptoms are usually absent.
How did the patient develop mediastinitis? What was the primary source from which the infection spread?
Acute mediastinitis is an infection that develops due to either spread from another source or direct inoculation into the mediastinum.
Previously, most cases of mediastinitis due to esophageal perforation were secondary to perforation associated with vomiting, but currently most episodes result from medical procedures, particularly esophagogastroduodenoscopy. Perforation allows oral and gastric secretions to enter the mediastinum and cause infection.
In the pre-antibiotic era, untreated odontogenic and pharyngeal infections often progressed to involve the neck and subsequently passed into the mediastinum via fascial planes. This leads to what is termed “descending necrotizing mediastinitis” which, while less common with current antimicrobials, still occasionally occurs.
The rise of cardiothoracic surgery has led to post-surgical mediastinitis becoming the most common form of this disease. Most infections are thought to arise from contamination of the wound at the time of surgery or in the immediate post-operative period. Skin flora organisms are most commonly involved. Excellent epidemiological studies have also linked nasal colonization with Staphylococcus aureus with post-surgical mediastinitis and surgical wound infection.
Chronic mediastinitis is a poorly understood, uncommon disease which likely represents a common end point of a number of heterogeneous inciting infections. The infection most commonly associated with chronic mediastinitis is histoplasmosis, which may be responsible for more than 70% of cases, but other infections including tuberculosis, coccidioidomycosis, aspergillosis, actinomycosis, and others have been reported rarely.
Which individuals are of greater risk of developing mediastinitis?
Esophageal perforation – Up to 75% of perforations are due to iatrogenic injury. Risk factors for perforation during esophagogastroduodenoscopy (EGD) include operator inexperience, underlying esophageal disease (malignancy, stricture, diverticulum, etc.), increasing age, systemic disease (scleroderma, diabetes, cirrhosis), and complexity of procedure performed. The procedures which most increase risk include procedures to stop bleeding (sclerotherapy and cautery), placement of stents, thermal treatment of malignancy, and dilation, with dilation of strictures due to achalasia and caustic injury at very high risk for perforation (4-17%).
Oropharyngeal infection – The specific predisposing conditions which cause mediastinitis are pharyngeal and odontogenic infections which can progress to mediastinitis. Risk factors for these infections are described elsewhere. No specific studies have addressed the risks for progression to mediastinitis, but diabetes and other immunosuppressive states are disproportionately represented in case series and should be considered risk factors. Also, neglect of the original infection places individuals at increased risk.
Post-cardiac surgery – Risk factors for post-surgical mediastinitis have been evaluated in numerous studies and can be divided into pre-operative, intra-operative and post-operative risk factors. Pre-operative factors associated with increased risk include increasing age, diabetes, obesity, previous cardiac surgery, chronic lung disease, peripheral vascular disease, renal failure, cardiogenic shock, smoking, removal of hair pre-operatively with a razor as opposed to electric clippers, and prolonged pre-surgical hospitalization. Intra-operative factors include emergent surgery, prolonged surgical time or time on heart-lung bypass, use of bilateral internal mammary arteries, complexity of procedure, use of an aortic balloon pump, and lack of appropriate antibiotic prophylaxis. Post-operative risk factors include the need for re-exploration, poor post-operative glucose control, prolonged ICU stay or mechanical ventilation, and post-operative myocardial infarction. A discussion of risk factor modification to decrease infection risk is included in the section on prevention.
There are no known risk factors or predisposing conditions for developing chronic mediastinitis.
Beware: there are other diseases that can mimic mediastinitis:
Mediastinitis in post-cardiac surgery patients can be protean in its presentation. Other diseases that may appear with similar symptoms, such as chest pain and fever, include post-operative pneumonia, acute myocardial infarction, or pulmonary embolism. Also other systemic infections in the post-operative period are associated with fever (line infections, urinary tract infection, etc.) and may not have signs of symptoms which are clearly attributable to these sites.
Mediastinitis should be considered in any oropharyngeal infection or esophageal perforation and ruled-out based on imaging.
Chronic mediastinitis shares common symptoms with idiopathic retroperitoneal fibrosis.
What laboratory studies should you order and what should you expect to find?
Results consistent with the diagnosis
No laboratory finding is specifically diagnostic of acute mediastinitis, but certain findings may suggest the diagnosis.
Leukocytosis with a left shift is a common finding in mediastinitis, as are elevations in biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). PCT may be particularly helpful in differentiating infection and rejection in transplant patients in whom the picture is often complex. PCT levels are often elevated after major surgery but the dynamics of PCT are most helpful. For example, post-operative PCT levels which trend down toward normal suggest infection is unlikely while increasing PCT levels often indicate uncontrolled bacterial infection.
Blood cultures should be obtained, but are of variable yield in mediastinitis. Patients with infections due to S. aureus or gram-negative pathogens are often bacteremic, but those with less virulent infections, such as coagulase-negative staphylococci, are infrequently bacteremic.
Wound cultures may be helpful in determining the pathogen, but sampling of mediastinal material is preferred over wound swabs as wound colonization may mislead treatment decisions. Wound cultures should be interpreted cautiously.
Routine cultures of epicardial pacer wires should not be obtained as they have a high false positive rate and do not accurately predict infection.
Routine cultures of sternal wounds before closure have not been shown to predict mediastinitis and should not be obtained.
Most patients with chronic mediastinitis have minimal laboratory abnormalities unless an inciting condition is present such as a malignancy. Markers of inflammation such as CRP, sedimentation rate, or platelets may be elevated or be normal.
The use of histoplasma serology or antigens and tests for tuberculosis are useful to evaluate for active disease as an alternative diagnosis, but are not particularly useful in making the diagnosis.
Results that confirm the diagnosis
No specific laboratory finding is confirmative of acute mediastinitis. The diagnosis of mediastinitis is best made through a correlation of clinical, laboratory and imaging findings.
Chronic mediastinitis is diagnosed via biopsy of the affected tissue. Such biopsies are necessary to rule out other conditions such as infection or malignancy (particularly Hodgkin’s disease). Pathologic findings can vary from granulomatous lesions with significant inflammation to an acellular fibrosing mass without inflammation. These lesions may contain caseating granulomas and densely hyalinized collagenous tissue infiltrating other mediastinal structures. Stains for fungi may reveal possible histoplasma organisms, but cultures are usually negative.
What imaging studies will be helpful in making or excluding the diagnosis of mediastinitis?
Computed tomography (CT) scan of chest: CT is the most useful imaging technique for making the diagnosis of mediastinitis. Typical findings of mediastinitis include soft tissue swelling, pericardial and/or pleural effusions, and fluid collections which may or may not contain air. There may be some difficulty in differentiating usual post-operative collections of fluid or air from findings due to infections in the first 2 weeks after surgery. The findings of Dressler’s syndrome may also be difficult to differentiate from mediastinitis. ($$$)
Indium 111-labeled leukocyte scanning: This may be useful for the diagnosis of mediastinitis when CT is equivocal or unable to be performed. ($$)
Chest radiograph: May show mediastinal widening or pneumomediastinum but usually of little value. ($)
Magnetic resonance imaging (MRI) has not been the topic of much study and is usually not helpful in post-operative infections due to metallic bodies being present. ($$$$)
Chest radiograph: Often reveals mediastinal widening and calcifications but non-specific. May have hilar mass or evidence of superior vena cava syndrome. ($)
CT scan of chest: Typically shows an infiltrative mediastinal mass which obliterates normal planes and encases structures. Narrowing of the esophagus, bronchi, pulmonary arteries, or superior vena cava is not uncommon. Two distinct patterns have been described: a localized mass with calcification which is often due to histoplasmosis, and termed granulomatous mediastinitis and a diffuse, non-calcified pattern which is seen with fibrosing mediastinitis. ($$$)
MRI/MRA: With its multiplanar capabilities MRI techniques are useful in defining the extent of disease and determining vascular structure integrity. ($$$$)
Ventilation/Perfusion Scan: Not useful in diagnosis, but helpful in determining vascular perfusion deficits due to stenosis. ($$)
*($ = 60-125, $$ 125-500, $$$ 500-1,000, $$$$ > 1,000)
What consult service or services would be helpful for making the diagnosis and assisting with treatment?
In cases of acute mediastinitis, involvement of a cardiothoracic surgeon is essential as surgery is the primary therapy. In cases of head and neck infections, or esophageal perforations, a head and neck surgeon or general surgeon/gastroenterologist should be consulted. Antimicrobial decisions should involve an infectious disease specialist.
Chronic mediastinitis may require interventional radiology or vascular surgery to assist with treatment of vascular stenoses.
If you decide the patient has mediastinitis, what therapies should you initiate immediately?
Immediate surgical debridement of affected tissues is the most effective therapy and should be performed in an expeditious fashion.
The initiation of broad spectrum antibiotics targeted to possible pathogens is also essential.
Antibiotic choices for esophageal perforations and oropharyngeal infections should include coverage of oral pathogens including Staphylococci, Streptococci, anaerobes, and enteric gram-negative rods.
Coverage for post-surgical mediastinitis should cover nosocomial pathogens such as staphylococci (including methicillin-resistant species), enterococci, and gram-negative rods, keeping in mind that resistance in all these pathogens is more common in the hospital.
1. Anti-infective agents
If I am not sure what pathogen is causing the infection what anti-infective should I order?
Reasonable empiric regimens are listed below:
Esophageal perforations and head and neck infections
A beta-lactam/bata-lactamase inhibitor such as piperacillin/tazobactam OR
A carbapenem such as ertapenem, imipenem, doripenem, or meropenem OR
A cephalosporin such as cefepime plus metronidazole for anaerobic coverage
Methicillin-resistant Staphylococcus aureus (MRSA) is an unusual cause of these infections, but in patients with known colonization it is reasonable to include coverage for this with either vancomycin or daptomycin
Ceftaroline could be considered as it covers MRSA, streptococci and enteric gram-negative, but should be coupled with metronidazole for anaerobes. Also it is not active against pathogens producing extended-spectrum beta-lactamases.
Post-cardiac surgery mediastinitis
Agent active against MRSA, enterococci, and streptococci such as vancomycin or daptomycin PLUS
Agent active against gram-negative pathogens including pseudomonas and other resistant bacteria:
A beta-lactam/beta-lactamase inhibitor such as piperacillin/tazobactam OR
A carbapenem such as imipenem, doripenem, or meropenem OR
A cephalosporin (preferably cefepime) plus metronidazole for anaerobic coverage
Definitive therapy is based upon the isolated bacterial pathogens. Suggested definitive therapy for individual pathogens is listed in
|Staphylococcus aureusMethicillin-resistant Staphylococci(MRSA, MRSE)||Oxacillin/NafcillinVancomycinDaptomycin||2g Q4H15mg/kg Q12H6mg/kg daily||Cefazolin 2g Q8HLinezolid 600mg Q12HCeftaroline 600mg Q12H|
|EnterococciAmpicillin-resistantVancomycin-resistant (VRE)||AmpicillinVancomycinLinezolid||2g Q4H +/- gentamicin 3mg/kg q8h15mg/kg Q12H600mg Q12H||Daptomycin 6mg/kg dailyQuinupristin/dalfopristin 7.5mg Q8H (E. faecium only)|
|Enteric Gram Negative Rods(E. coli, Klebsiella, Enterobacter, etc) ESBL-producing isolates||CeftriaxoneCefepimeErtapenem||2g daily1g Q6H or 2g Q12H1g daily||Aztreonam 2g Q8HCiprofloxacin/Levofloxacin/MoxifloxacinImipenem 500mg Q6HMeropenem 1g Q8HDoripenem 500mg Q8H|
|Pseudomonas aeruginosa||CefepimePiperacillin/tazobactamMeropenem||1g Q6H or 2g Q8H4.5g Q6H or 3.375g Q8H over 4 hours1g Q8H or 500mg Q6H||Imipenem 500mg Q6HDoripenem 500mg Q8HAztreonam 2g Q8HCiprofloxacin/Levofloxacin|
|Candida speciesFluconazole-sensitive speciesFluconazole-resistant species||FluconazoleMicafungin/Caspofungin/AnidulafunginLiposomal Amphotericin B||12mg/kg load, then 6mg/kg daily3-5mg/kg daily||Micafungin 100mg dailyCaspofungin 70mg load, then 50mg dailyAnidulafungin 200mg load, then 100mg dailyVoriconazole 6mg/kg X 2 doses, then 4mg/kg Q12HAmphotericin B deoxycholate 0.5-1mg/kg daily|
|AnaerobesFusobacterium, Anaerobic StreptococciBacteroides sp.||PenicillinClindamycinMetronidazole||2-4 million units Q4H600-900mg Q8H500mg Q8H||Ampicillin/sulbactam 3g Q6HPiperacillin/tazobactam 3.375g Q6HErtapenem 1g daily|
2. Other key therapeutic modalities
Esophageal perforation – Traditionally patients with esophageal perforations are managed surgically. Patients with large, uncontained perforations, clear mediastinal contamination, mediastinal abscesses, or sepsis syndromes should undergo urgent surgical management. The ideal management is drainage with primary repair, although esophageal diversion or esophagectomy may be necessary depending on local pathology. Occasionally patients may be managed without surgery. Clinically stable patients with minimal symptoms with well contained abscesses draining into the esophagus are candidates for non-surgical management. Also, those with iatrogenic perforations which are promptly recognized before contamination occurs can usually be managed without surgery. Non-surgical management consists of treatment with broad-spectrum antibiotics, nasogastric suction, nothing per mouth, and parenteral nutrition.
Oropharyngeal infection – Prompt and complete surgical drainage is key to resolution of this infection. Achievement of adequate surgical drainage and debridement of all necrotic tissue is the goal of surgical therapy, although the ideal method to achieve this is unclear. Trans-cervical drainage may be adequate in infections confined to the superior mediastinum, but the trans-thoracic approach should be strongly considered in any patient with more extensive involvement. The use of video-assisted thorascopic surgery (VATS) has been described and may be better tolerated than traditional thoracotomy or sub-xiphoid approaches.
Post-cardiac surgery – Surgical debridement is the cornerstone of management and 2 major approaches exist: open and closed techniques. The preferred approach is unknown with success using both approaches published in the literature. The decision about which modality to use depends on patient factors, the extent of infection and boney debridement necessary, and local surgical expertise.
Open techniques involve debridement of any infected tissue and bone with the wound left open and packed, typically with gauze dressings. This wound may be allowed to heal by secondary intention or may be filled at a later date using a tissue flap. Complete sternal removal is generally not necessary and increases thoracic instability. Disadvantages of the open technique include possible hemorrhage due to exposed vessels, delayed healing of surgical wound, and possible respiratory insufficiency due to lack of thoracic support. Open techniques are often coupled with vacuum-assisted closure (VAC) devices as either a primary closure technique or as a bridge to flap. No randomized trials have compared the use of VAC devices with conventional treatment but published studies have associated VAC use with decreased number of dressing changes needed, decreased need for flap, shorter hospital stay, and lower cost. VAC use is common among cardiac surgeons, particularly as a bridge to a flap.
Closed techniques involve debridement and immediate closure of the sternum accomplished by simple wound closure, sternal rewiring or plating, or immediate placement of a soft tissue flap. Drains may be left in place and some authors advocate irrigation with various antiseptic solutions. Soft-tissue flaps as either a primary or delayed sternal closure are usually harvested from the pectoralis muscle, although abdominal muscle and omental flaps have been utilized.
Medical therapy directed at the inciting lesions in the mediastinum has generally been unsuccessful. Despite the presumed fungal etiology no clear evidence supports the use of antifungals. Case reports of success with steroid therapy have been published but again, routine use has not shown benefit. Success in treating idiopathic retroperitoneal fibrosis has led some to utilize the selective estrogen receptor modulator tamoxifen with occasional success.
Surgical interventions are generally directed at resolving the complications, such as vascular obstruction. Resection of the mediastinal lesion is not recommended as it may worsen symptoms due to disruption of vascular flow. Stenting of narrowed vascular and respiratory structures has been well described. Stenting of the superior vena cava, pulmonary arteries and pulmonary veins has been shown to decrease vascular pressures and improve symptoms. Stenting should be considered in patients with symptoms due to vascular obstruction and elevated pulmonary pressures. Stenting of bronchi is not advocated because of the risk of recurrent stenosis.
What complications could arise as a consequence of mediastinitis?
Local complications due to mediastinitis are due to spread to adjacent structures which include the pericardium (effusion or tamponade), pleural space (empyema), costochondral cartilage, peritoneum (peritonitis), and sternal bone (osteomyelitis or sternal dehiscence). Oropharyngeal infections often result in airway compromise and the need for tracheostomy. Severely ill patients may suffer from the complications of sepsis such as renal failure. Complications due to surgical treatment of mediastinitis may include unstable sternum, sternal malunion, need for prolonged mechanical ventilation, prolonged hospitalization, and nosocomial infections such as pneumonia. The impact of mediastinitis on long-term graft patency in cardiac surgery is unknown.
Cost: An important complication of mediastinitis in post-cardiac surgery patients is the additional length of stay and cost associated with treatment of the infection. Estimates have varied with a doubling of the length of stay generally being anticipated and costs commensurate with that stay (usually 2- to 3-fold higher). Another important point is the US Center for Medicaid and Medicare Services views these infections as completely preventable and will no longer reimburse hospitals for additional costs associated with caring for these infections.
Complications due to chronic mediastinitis develop due to obstruction of mediastinal structures such as the pulmonary arteries, veins, superior vena cava, esophagus, or bronchi. Obstruction of the pulmonary vasculature can lead to pulmonary hypertension, cor pulmonale, hemoptysis, right heart failure, syncope, a “pseudo-mitral valve stenosis” syndrome, and pulmonary infarction. Bronchial or tracheal stenosis can result in shortness of breath or wheezing and recurrent bouts of pneumonia. Superior vena cava syndrome can occur as well and chronic mediastinitis is the second most common cause of this syndrome.
What should you tell the family about the patient's prognosis?
Death due to esophageal perforation occurs in 15-20% of episodes with cause and location of injury, underlying esophageal pathology, time to diagnosis, and method of treatment being important determinants of mortality. Early treatment (<24 hours after injury) has been associated with significantly improved outcomes while delays in therapy increase the fatality rate.
Mortality due to descending oropharyngeal infections has decreased over the last 30 years with recent series showing mortality rates of 10-20%. Decreased mortality has been associated with rapid diagnosis and both prompt and aggressive surgical management.
Mortality in post-surgical mediastinitis has improved over time and many series now report early mortality rates of less than 5%. The most important predictor of mortality is the length of time to diagnosis and institution of definitive surgical and antimicrobial therapy. Other negative prognostic indicators identified have included increasing age, renal failure, increased white blood cell count, culture positivity, bacteremia, shock, post-operative stroke, early onset mediastinitis, need for prolonged mechanical ventilation, need for intra-aortic balloon pump support, and cytomegalovirus shedding.
The impact of mediastinitis on overall survival after recovery has varied with older, shorter follow-up studies finding no impact on survival after accounting for early mortality. More recent long-term analyses have come to conflicting conclusions with one large European study noting a 59% increase in risk of death at 10 years, while a US study found no increased risk of death after recovery from mediastinitis. It is likely that patients who have survived an episode of mediastinitis are at some increased risk of death compared to those who did not experience such an infection, although reasons for this are unknown at this time.
Prognosis is difficult to determine with some patients having progressive obstruction of mediastinal structures resulting in death and others having complete resolution of disease without therapy. Patients with bilateral involvement of the pulmonary arteries or veins are more likely to die.
How do you contract mediastinitis and how frequent is this disease?
Acute mediastinitis occurs generally via one of 3 routes: esophageal perforation, spread of oropharyngeal infections, or post-cardiac surgery.
Mediastinitis occurs after esophageal perforation when oral and/or gastric contents are allowed to enter the mediastinum. In the era before cardiac surgery esophageal perforation was the most common cause of mediastinitis with most cases due to spontaneous rupture after vomiting, known as Boerhaave’s syndrome. This continues to account for 15-20% of all esophageal perforations but the most common cause is now iatrogenic injury. The risk of perforation with diagnostic EGD is 0.03% but increases depending on the intervention performed and patient risk factors and may be as high as 17%. Risk factors for perforation are described earlier. Other less common causes of perforation include foreign body ingestion and trauma.
Mediastinitis occurs with complicated oropharyngeal infections when these infections expand beyond their site of origin and enter into the fascial planes of the neck allowing them to track into the mediastinum. In the pre-antibiotic era these infections accounted for up to 30% of cases of mediastinitis, but currently rarely occur. Middle aged males predominate in case series with the source of infection varying. Odontogenic and pharyngeal are the most common sources by far and cause about an equal number of these infections. How frequently mediastinitis follows a complicated oropharyngeal infection is not well documented, but it is likely less than 5% of the time. Some authors have suggested that infections which are present in or spread to the danger space are more likely to progress to mediastinitis.
Incidence: The exact incidence of these infections varies with mediastinitis rates of 0.5-4.5% after cardiac surgery. More recent surveys have revealed generally lower rates (1-2%) with a large survey of greater than 300,000 cardiac surgeries, noting an incidence of 0.9%. The National Healthcare Safety Network (NHSH), which is the national reporting system for health care infections reported post-CABG mediastinitis, showed rates for 2006-2008 were 0.58 infections per 100 surgeries. Based on NHSH risk criteria (ASA class, wound type and surgery duration) rates varied from 0.35 infections per 100 surgeries in the lowest risk to 1.89 infections per 100 surgeries in the highest risk group. Other patient groups such as those undergoing heart or lung transplant are at increased risk (2.5-7.5%), while children are at lower risk (0.5% or less). Risk factors for infection are described earlier.
Mode of spread: The pathogenesis of infection is thought to involve inoculation of the wound with bacteria either at the time of, or soon after surgery, although hematogenous seeding may rarely occur. These bacteria are then allowed to multiply in the relatively avascular surgical site. Evidence of increased infection rates in patients who have increased opportunity for bacterial contamination, such as those with prolonged surgical time, highly complex procedures or who require re-operation, support this theory. There is evidence that the source of the infecting organisms may vary. Generally the primary source of the infection is the patient’s own endogenous flora, particularly their skin flora, including coagulase-negative staphylococci and S. aureus.
Nasal colonization with S. aureus is a well described risk factor for infection. Epidemiologic studies have found isolates which pre-operatively colonized the nares subsequently caused mediastinal infection. Not all S. aureus infections are associated with endogenous colonization; other studies have noted nosocomial strains of MRSA to be a major cause of mediastinitis. These strains were presumably acquired sometime in the post-operative period from either the environment or healthcare workers. Outbreaks of mediastinitis have been associated with contamination of the environment as well as surgeons’ hands or nares.
Fibrosing mediastinitis is a very rare disease and the exact prevalence is unknown. No specific risk factors have been identified for this disease although the frequency of association with histoplasmosis suggests Midwestern US residence may be a risk factor. Also, a predominance of African Americans in certain case series and histopathologic findings similar to keloid formation suggests this syndrome may be more common in African Americans.
What pathogens are responsible for this disease?
The pathogens most commonly isolated depend upon the source of infection.
Mediastinitis secondary to esophageal perforation or oropharyngeal infection
Infections are typically polymicrobial with oral flora predominating. Infections involving both oral anaerobes and gram-negative bacilli are common with the most common organisms listed below:
Gram-positive cocci – Peptostreptococcus
Gram-positive bacilli – Actinomyces, Lactobacillus, Eubacterium
Gram-negative cocci – Veillonella
Gram-negative bacilli – Bacteroides, Prevotella, Porphyromonas, Fusobacterium
Gram-positive cocci – Streptococci (including beta-hemolytic and S. viridans group), Staphylococci Fungi – Candida albicans (unusual)
Gram-positive bacilli – Corynebacterium
Gram-negative cocci – Moraxella
Gram-negative bacilli – Enterobacteriaceae, Eikenella corrodens, Pseudomonas
Mediastinitis secondary to cardiac surgery
The most common pathogens are gram-positive cocci, particularly Staphylococci. The relative frequency of S. aureus versus coagulase-negative staphylococci varies with some reports attributing up to 60% of mediastinitis to S. aureus. Improved culture techniques are improving detection of fastidious pathogens such as Propionibacterium acnes. Listed below are the common pathogens and the range of their frequencies:
Staphylococcus aureus (7-67%)
Coagulase-negative Staphylococci (6-46%)
Escherichia coli (0-13%)
C. albicans (0-14%)
Unusual Causes of Mediastinitis
Unusual causes of mediastinitis exist including Bacillus anthracis which may cause a rapidly fatal hemorrhagic mediastinitis. Other unusual causes of mediastinitis include brucella, actinomyces, and paragonimiasis.
The exact cause of this syndrome has been debated although most cases are now to be attributed to Histoplasma capsulatum infection. Other infectious and non-infectious agents have been associated with this condition, including Mycobacterium tuberculosis, nocardia, blastomycosis, coccidioidomycosis, aspergillus, sarcoidosis, lymphoma, mesothelioma, Behcet’s disease, sclerosing cholangitis, and idiopathic retroperitoneal fibrosis.
How do these pathogens cause mediastinitis?
Mediastinitis secondary to esophageal perforation or oropharyngeal Infection
Esophageal injury at any point can result in mediastinitis. Injuries allow the release of esophageal contents either directly into the mediastinum or into the fascial planes of the neck. The negative intra-thoracic pressure of respiration then draws any spillage into the chest. This exposure results in an initial necrotizing chemical mediastinitis which is usually followed by a polymicrobial bacterial infection.
Odontogenic and pharyngeal infections are unusual causes of mediastinitis. Mediastinitis occurs when infections of the head and neck area spread into potential fascial spaces and planes which communicate with the mediastinum. These spaces and planes include the pretracheal space, viscerovascular space (includes carotid sheath), lateral pharyngeal space, retropharyngeal space, prevertebral space, and the danger space. These spaces may communicate with different aspects of the mediastinum.
For example, spread of infection into the pretracheal space leads to infection of the superior mediastinum primarily, while infections which spread into the danger space which runs all the way to the diaphragm often have much deeper mediastinal involvement. In the classic example of Ludwig’s angina, infection of the molars spreads to the sublingual and submandibular spaces. Infection in these spaces can then spread to the lateral pharyngeal space and track via the retropharyngeal space or carotid sheath into the mediastinum. Infection of the lateral pharyngeal space and subsequent spread into the chest can result from extension of infection of the tonsils, pharyngitis and epiglottis.
Rare cases of contiguous spread to the mediastinum can occur. Infections reported to have caused this include pneumonia, pleural space infections, pancreatitis, subphrenic abscess, osteomyelitis of the boney structures of the thorax, and very rarely hematogenous seeding. Spread from local infections generally occurs as these infections escape their localized area and allow purulent material to extend into the mediastinum. As mentioned above, inhalational anthrax caused by Bacillus anthracis is a mediastinal disease. The bacterial spores after ingestion by the alveolar macrophages are transported to the mediastinal lymph nodes where they escape and rapidly multiply leading to bacteremia, sepsis and frequently death. Further information about this infection is available elsewhere.
Mediastinitis secondary to cardiac surgery
Infection of the surgical wound can occur through contamination at or after the surgery. The primary pathogenesis of post-surgical mediastinitis is likely due to innoculation of endogenous organisms into the wound at the time of surgery. These bacteria then flourish in the relatively avascular surgical wound causing infection. Risk factors that increase contamination, such as prolonged surgical length, need for re-operation, and complexity of surgery, are highly supportive of this mechanism. Pre-operative colonization with Staphylococcus aureus has been associated with the development of mediastinitis as well. This organism is particularly adept at causing infection via a variety of virulence genes associated with attachment, avoidance of the immune system, and production of toxins. More information on S. aureus is available elsewhere.
Varying radiographic patterns suggest that there may be more than one possible pathophysiologic mechanism. Whatever the mechanism, this syndrome is likely the end manifestation of an abnormal host response to a variety of infectious or inflammatory agents. A number of possible pathophysiologic mechanisms have been suggested. The first is rupture of infected or inflamed mediastinal lymph nodes sets off an intense and fibrotic inflammatory response. The second is a delayed hypersensitivity response to Histoplasma antigens present in the mediastinum. The third is the disease represents a syndrome similar to idiopathic retroperitoneal fibrosis with chronic inflammation, fibroblast proliferation, and abnormal extra-cellular matrix deposition.
What other clinical manifestations may help me to diagnose and manage mediastinitis?
The diagnosis of mediastinitis may be difficult as signs and symptoms may be subtle. Certain findings may be present which suggest the diagnosis.
Occurs most frequently after EGD, but can occur after any procedure involving the esophagus, including transesophageal echocardiogram, nasogastric (NG) tube placement, or even rapid sequence intubation. Patients with post-procedure symptoms of pain, fever, or the exam finding of subcutaneous air should be investigated for possible perforation and mediastinitis. Perforation in the cervical area is typically associated with neck pain exacerbated by movement, while thoracic perforations locate pain in the substernal area. Subcutaneous air and crepitation of the tissue is more frequently found with cervical perforations. Patients with post-vomiting esophageal rupture often relate to an episode of severe vomiting or retching (which may be self-induced) followed by excruciating chest pain.
Oropharyngeal infections leading to mediastinitis are generally quite obvious and their presence should prompt evaluation for mediastinal involvement. It may be difficult to determine mediastinal involvement based on history and exam findings. Some patients may demon Hamman’s sign which is a crunching or rasping sound heard over the precordium synchronous with the cardiac rhythm. Early signs of oropharyngeal infections depend on the source.
Odontogenic infections such as Ludwig’s angina present with mouth pain with woody swelling of the lower jaw and severely tender swelling of the lower oropharyngeal area. Trismus is usually absent with Ludwig’s angina.
Peritonsillar abscess (quinsy) begins with a severely sore throat which is usually unilateral with odynophagia. The patient’s voice may be muffled, and trismus may be present if the infection has spread to the fascial planes of the neck. Exam may reveal uvular deviation to the non-affected side with swelling and fullness of the tonsillar area.
Pharyngeal space infections occur when oropharyngeal infections spread into this space. Classic symptoms include trismus, swelling below the angle of the mandible, and medial bulging of the pharyngeal wall. Patients with spread to this area may complain of dyspnea due to swelling and airway obstruction. Involvement of the various structures can lead to Horner’s syndrome or hoarseness (neurologic involvement), carotid artery erosions or mycotic aneurysms, or suppurative jugular thrombophlebitis (Lemierre’s syndrome) which is classically associated with pharyngeal infections due to Fusobacterium and results in septic pulmonary emboli.
Infections of the posterior spaces such as the prevertebral, danger and retropharyngeal spaces are less obvious due to their location. Prevertebral infections often present with posterior neck pain and neurologic symptoms as these infections generally arise from spinal infections. Danger or retropharyngeal space infection is associated with sore throat and difficulty swallowing or breathing, and may cause trismus.
Patients often must undergo multiple debridements, and adequate drainage of all infected tissue and fascial planes is key to resolution. Patients who do not show evidence of improvement (declining WBC and fever, improving clinical stability) after initial drainage are likely to have undrained sites of infection and should be re-evaluated either by imaging or repeat surgical exploration.
The history and exam findings suggesting mediastinitis in the post-cardiac surgery period vary. Typically, patients present with symptoms within 14 days of surgery, but with relatively avirulent organisms this time may be significantly extended. Systemic symptoms such as fevers and chills are typically the first manifestations of infection, although they are very non-specific. Often, patients initially have minimal or no local signs or symptoms of infection, although most eventually develop some local findings. In other cases local signs and symptoms may be very prominent with severe pain, obvious sternal wound dehiscence, wound cellulitis, or bubbles from the sternal wound.
How can mediastinitis be prevented?
Prevention of mediastinitis depends on the cause. Mediastinitis due to oropharyngeal infection can be prevented by the rapid diagnosis and treatment of the inciting infection to prevent further spread. Esophageal injury can be avoided through careful selection of appropriate patients for procedures and good technique. Prevention of post-surgical mediastinitis is an area of much research. A variety of practices has been shown to be effective in decreasing post-cardiac surgery surgical site infections and should be considered standard care in patients undergoing cardiac surgery. These include treating any current infections before surgery if possible; removal of hair if necessary using clippers, not a razor; appropriate skin antisepsis; maintaining post-operative normothermia; keeping initial surgical dressings intact for 24-48 hours; minimization of blood transfusions; and pre-operative smoking cessation if possible.
The importance of certain practices as measures of quality of surgical care has been increasingly emphasized and national reporting of certain measures is ongoing. These measures include those centered around antibiotic prophylaxis including timing, choice of agent, and timely discontinuation; surgical hair removal; and post-operative glucose control. Antimicrobial prophylaxis, glucose control, and Staphylococcus decolonization are addressed below.
The principles of surgical antimicrobial prophylaxis include giving the appropriate agent at the ideal dose and duration based on weight and renal function for the appropriate duration.
Prophylaxis is most effective when given immediately before the procedure and every effort should be made to give the agent 30-60 minutes before the procedure. Exceptions to this rule are vancomycin or fluoroquinolones which require prolonged infusion times and should be given within 2 hours of the procedure.
In patients with prolonged procedures intra-operative redosing should be performed for agents with short half lives (generally at 3 hours for cefazolin and cefuroxime).
Antibiotic doses should be adjusted based on weight with patients of greater mass receiving higher doses (i.e. cefazolin <80kg = 1g, 80-160kg = 2g, >160kg = 3g).
The frequency of post-operative dosing should be adjusted for renal function to prevent toxicity.
The duration of surgical prophylaxis for most procedures is either a single pre-operative dose or less than 24 hours. Cardiac surgery is an exception to this rule, with increasing amounts of data supporting continuing prophylactic antibiotics for 24-48 hours after the surgery. Regimens should not be continued longer than 48 hours as this has not shown benefit and has been associated with increased isolation of resistant pathogens.
The preferred agent for prophylaxis is much debated. Published guidelines have recommended either cefazolin or cefuroxime as prophylaxis in patients undergoing cardiac surgery. Vancomycin is recommended only in those patients with significant beta-lactam allergy or proven/suspected MRSA colonization. Some studies have suggested that vancomycin may be inferior to cephalosporin based prophylaxis, but a recent meta-analysis which stratified their analysis by duration found no difference in infection rate. Another unanswered question is whether an additional agent should be added to vancomycin for better coverage of gram-negative organisms. Published recommendations have conflicted on this point, with recent guidelines leaving it to clinician’s discretion. Which agent is most appropriate in this role is unknown, but aminoglycosides have traditionally been the agent of choice. These drugs are associated with renal toxicity and some centers have transitioned to fluoroquinolones instead.
Implantable gentamicin-collagen sponges, while initially showing promise in Europe, did not reduce sternal wound infections in a large US trial and are not recommended.
Peri-operative glucose control
Diabetics have increased rates of surgical site infection after cardiac surgery with numerous studies demonstrating an association between high glucose levels and mediastinitis. Control of glucose levels in the immediate post-operative period has been associated with a significant decrease in deep sternal wound infections. This is usually achieved using intensive IV insulin protocols in the first few days after surgery.
Pre-operative Staphylococcus aureus decolonization
Colonization with S. aureus has been clearly associated with post-operative wound infection. Numerous studies have evaluated various methods of decolonization and have usually showed a reduction in wound infections. Decolonization is generally performed using 2% mupirocin ointment applied intra-nasally twice daily. The timing and duration of use has varied, but it is generally recommended to start pre-operatively if possible and to treat for 3-5 days immediately before the surgery. Roughly 30% of the population is colonized with S. aureus so only those patients who had been identified as colonized should receive treatment.
Various methods exist for identifying S. aureus carriers including PCR and culture and center preferences depend on turn-around time, cost and local needs and expertise. Both methicillin-sensitive and methicillin-resistant S. aureus can cause infection and decolonization strategies should be designed to detect both. S. aureus colonization can occur at other sites including the skin and decolonization of these sites may be achieved using chlorhexidine baths or scrubs in the pre-operative period, although the impact of this practice has not been quantified.
WHAT'S THE EVIDENCE for specific management and treatment recommendations?
Albers, EL, Pugh, ME, Hill, KD, Wang, L, Loyd, JE, Doyle, TP. “Percutaneous Vascular Stent Implantation as Treatment for Central Vascular Obstruction Due to Fibrosing Mediastinitis”. Circulation. vol. 123. 2011. pp. 1391-1399. (Description of a large series (N=58) of patients with fibrosing mediastinitis who underwent vascular stenting at a single institution. Reports outcomes of stenting and clinical outcomes over median time of 115 months. Identified bilateral disease as risk factor for poor outcome after stenting)
Baillot, R, Cloutier, D, Montalin, L, Cote’, L, Lellouche, F, Houde, C, Gandreau, G, Voisine, P. “Impact of deep sternal wound infection management with vacuum-assisted closure therapy followed by sternal osteosynthesis: a 15-year review of 23 499 sternotomies”. European Journal of Cardio-thoracic Surgery. vol. 37. 2010. pp. 880-887. (Cohort analysis of >23,000 open heart surgery cases. Risk factors for mediastinitis identified, microbiology trends described, and long-term mortality provided out to 10 years. Analysis of impact of wound VAC therapy found decreased mortality although was compared to historical controls.)
Bhatia, NL, Collins, JM, Nguyen, CC, Jaroszewski, DE, Vikram, HR, Charles, JC. “Esophageal Perforation as a Complication of Esophagogastroduodenoscopy”. Journal of Hospital Medicine. vol. 3. 2008. pp. 256-262. (Excellent review of esophageal perforation. Synthesize diverse information on causes, risk factors, presentation, diagnosis, and management)
Bode, LGM, Kluytmans, JAJW, Wertheim, HFL, Bogaers, D, Vandenbroucke-Grauls, CMJE, Roosendaal, R, Troelstra, A, Box, ATA, Voss, A, van der Tweel, I, vanBelkum, A, Verbrugh, HA, Vos, MC. “Preventing Surgical-Site Infections in Nasal Carriers of “. N Engl J Med. vol. 362. 2010. pp. 9-17. (Double-blind, randomized-controlled, multicenter study where patients primarily admitted to surgical services were screened for S. aureus and then if positive, randomized to decolonization with mupirocin intra-nasally and chlorhexidine washes or placebo. The rate of S. aureus infections decreased by over half and the decolonization regimen was particularly effective at preventing deep surgical site infections [RR 0.21; 95% CI, 0.07 to 0.62].)
Brinster, CJ, Singhal, S, Lee, L, Marshall, MB, Kaiser, LR, Kucharczuk, JC. “Evolving Options in the Management of Esophageal Perforation”. Ann Thorac Surg. vol. 77. 2004. pp. 1475-1483. (Narrative review and summary of published literature on esophageal perforation describing 559 cases.)
Carr, JM, Selke, FW, Fey, M, Doyle, MJ, Krempin, JA, de la Torre, R, Liddicoat, JR. “Implementing tight glucose control after coronary artery bypass surgery”. Ann Thorac Surg.. vol. 80. 2005. pp. 902-909. (Description of the implementation of tight glucose control in post-CABG patients over 2 years. Rate of mediastinitis decreased to zero during this intervention.)
Edwards, FH, Engelman, RM, Houck, P, Shahian, DM, Bridges, CR. “The Society of Thoracic Surgeons Practice Guidelines Series: Antibiotic Prophylaxis in Cardiac Surgery, Part I: Duration”. Ann Thorac Surg. vol. 81. 1006. pp. 397-404.
Engelman, R, Shahian, D, Shemin, R, Guy, TS, Bratzler, D, Edwards, F, Jacobs, M, Fernando, H, Bridges, C. “The Society of Thoracic Surgeons Practice Guideline Series: Antibiotic Prophylaxis in Cardiac Surgery, Part II: Antibiotic Choice”. Ann Thorac Surg. vol. 83. 2007. pp. 1569-1576. (These 2 articles from the Society of Thoracic Surgeons provide an excellent literature review and graded recommendations regarding antimicrobial prophylaxis in cardiac surgery)
Fowler, VG, O’Brien, SM, Muhlbaier, LH, Corey, GR, Ferguson, TB, Peterson, ED. “Clinical Predictors of Major Infections After Cardiac Surgery”. Circulation. vol. 112. 2005. pp. I-358-I-365. (Using a very large national database of >300,000 CABG procedures the authors developed a risk stratification model for using both pre-operative characteristics and also both pre- and intra-operative data. The model numerically scores patients based on presence of risk factors and is moderately accurate. They also described mortality and length of stay in patients with infection.)
Furnary, AP, Zerr, KJ, Grunkemeier, GL, Starr, A. “Continuous Intravenous Insulin Infusion Reduces the Incidence of Deep Sternal Wound Infection in Diabetic Patients After Cardiac Surgical Procedures”. Ann Thorac Surg.. vol. 67. 1999. pp. 352-60. (Study describing the implementation of IV insulin protocol in diabetic undergoing cardiac surgery. Glucose control was associated with significant reductions in mediastinitis and saved money)
Hillis, LD, Smith, PK, Anderson, JL. “2011 ACCF/AHA guideline for coronary artery bypass graft surgery”. JACC. vol. 58. 2011. pp. e123-210. (American Heart Association guidelines regarding CABG procedures. They include a discussion brief literature review on prevention of mediastinitis with graded recommendations)
Hollenbeak, CS, Murphy, DM, Koenig, S, Woodward, RS, Dunagan, WC, Fraser, VJ. “The Clinical and Economic Impact of Deep Chest Surgical Site Infections Following Coronary Artery Bypass Graft Surgery”. Chest. vol. 118. 2000. pp. 397-402. (Case control series describing risk factors for mediastinitis. Economic analysis also described the burden created by these infections.)
Lador, A, Nasir, H, Mansur, N, Sharoni, E, Biderma, P, Leibovici, L, Paul, M. “Antibiotic prophylaxis in cardiac surgery: systematic review and meta-analysis”. J Antimicrob Chemother. 2011. pp. dkr470v1-dkr470.
Misthos, P, Katsaragakis, S, Kakaris, S, Theodorou, D, Skottis, I. “Descending Necrotizing Anterior Mediastinitis: Analysis of Survival and Surgical Treatment Modalities”. J Oral Maxillofac Surg. vol. 65. 2007. pp. 635-639.
Ridder, GJ, Maier, W, Kinzer, S, Teszler, CB, Boedeker, CC, Pfeiffer, J. “Descending Necrotizing Mediastinitis: Contemporary Trends in Etiology, Diagnosis, Management, and Outcome”. Ann Surg. vol. 251. 2010. pp. 528-534. (Case series of 45 patients with descending necrotizing mediastinitis over 12 years at a single center. Also includes summary of 278 cases from 26 published studies with associated analysis of cases.)
Risnes, I, Abdelnoor, M, Almdahl, SM, Svennevig, JL. “Mediastinitis After Coronary Artery Bypass Grafting Risk Favors and Long-Term Survival”. Ann Thorac Surg. vol. 89. 2010. pp. 1502-1510. (Case-control study evaluating the role of S. aureus nasal colonization in post-sternotomy mediastinitis. Authors demonstrate that MSSA nasal colonization is the source of majority of MSSA infections, but MRSA infection arose from a nosocomial source.)
Rossi, SE, McAdams, HP, Rosado-de-Christenson, ML, Franks, TJ, Galvin, JR. “From the Archives of the AFIP: Fibrosing Mediastinitis”. Radio-Graphics. vol. 212. 2001. pp. 737-757. (Extensive review of published case series summarizing pathology, clinical presentation, prognosis, treatment and extensive review of radiographic features. Synthesis of pathology findings and possible pathophysiologic causes also included.)
San Juan, R, Chaves, F, Lopez Gude, MJ, Diaz-Pedroche, C, Otero, J, Cortina Romero, JM, Rufilanchas, JJ, Aguado, JM. “Staphylococcus aureus poststernotomy mediastinitis: Description of two distinct acquisition pathways with different potential preventative approaches”. J Thorac Cardiovasc Surg.. vol. 134. 2007. pp. 670-676. (Meta-analysis of 59 trials evaluating antibiotic prophylaxis in cardiac surgery. Evaluated questions of need for addition of gram-negative coverage, prophylaxis duration, use of glycopeptides, and couple of other questions. Findings supported vancomycin as reasonable choice, duration of 24-48 hours, and supported use of gram-negative coverage. Gram-negative coverage did not decrease surgical site infection but did decrease post-operative pneumonia.)
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has mediastinitis? What should you expect to find?
- How did the patient develop mediastinitis? What was the primary source from which the infection spread?
- Which individuals are of greater risk of developing mediastinitis?
- Beware: there are other diseases that can mimic mediastinitis:
- What laboratory studies should you order and what should you expect to find?
- What imaging studies will be helpful in making or excluding the diagnosis of mediastinitis?
- What consult service or services would be helpful for making the diagnosis and assisting with treatment?
- If I am not sure what pathogen is causing the infection what anti-infective should I order?
- What complications could arise as a consequence of mediastinitis?
- What should you tell the family about the patient's prognosis?
- How do you contract mediastinitis and how frequent is this disease?
- What pathogens are responsible for this disease?
- How do these pathogens cause mediastinitis?
- What other clinical manifestations may help me to diagnose and manage mediastinitis?
- How can mediastinitis be prevented?
- WHAT'S THE EVIDENCE for specific management and treatment recommendations?