Infective Endocarditis on a Native Valve
The pathogenesis of infective endocarditis (IE) usually involves transient bloodstream invasion by microorganisms, followed by adherence of the organism to the endocardial surface and multiplication of the microorganism within a layer of platelets and fibrin that is relatively inaccessible to host phagocytic defenses. The likelihood that a patient with or without underlying valvular heart disease may develop IE depends on the species and concentration of microorganisms in the blood, the duration of the bloodstream invasion, the presence or absence of antimicrobial agents in serum at the time of bacteremia/fungemia, and the characteristics of the endocardium. Clearly, some microorganisms are much more likely to adhere to endocardium than others. Staphylococcus aureus, enterococci, and other streptococci are most adherent. Enteric gram-negative bacilli and anaerobic microorganisms are less so. Since S. aureus is adherent and invasive, is found commonly on the skin, and causes skin infection that can result in transient bacteremia, this organism is associated with acute bacterial endocarditis, even in patients without significant underlying valvular heart disease. Viridans-type streptococci, which are normal flora of the upper airway, may gain access to the bloodstream from trauma to the teeth or gingiva (as in dental work) and cause IE nearly always in a patient with a significant predisposing valvular abnormality. Many distinctions between acute and subacute endocarditis are blurred. Enteric gram-negative organisms, because they are much less adherent to endocardium, cause fewer cases of endocarditis relative to the frequency of bacteremia caused by these organisms. However, gram-negative organisms that have a greater propensity to adhere to surfaces, such as Pseudomonas aeruginosa, and that can gain access to the circulation via contaminated intravenous injections (as in drug abusers) or infection at other body sites produce a significant proportion of cases. The most common nosocomial pathogenesis of IE in critically ill patients is from central venous catheters, with peripheral IVs and urologic instrumentation also identified as sources.1–4
Clinical and Laboratory Features
Table 49-2 lists the most common signs and symptoms encountered in patients with native-valve IE. Table 49-3 lists the most commonly encountered laboratory abnormalities. Because most reports stress community-acquired disease, patients developing IE while hospitalized in an ICU may not manifest identical findings. Fernandez-Guerrero and colleagues1 reported fever in 100% of patients with hospital-acquired IE. A murmur was present in only 20% of patients with vascular catheter–associated IE but was present in 75% of patients with IE following a urologic procedure. Still, fever and a heart murmur are the most common findings in IE; both are found in at least 80% of patients with community-acquired left-sided IE. The incidence is less in patients with right-sided disease only.5
Table 49–2. Frequency of Symptoms and Signs at Presentation of Infective Endocarditis ||Download (.pdf)
Table 49–2. Frequency of Symptoms and Signs at Presentation of Infective Endocarditis
|Symptoms||Frequency, %||Signs||Frequency, %|
Table 49–3. Frequency of Various Laboratory Abnormalities in Infective Endocarditis ||Download (.pdf)
Table 49–3. Frequency of Various Laboratory Abnormalities in Infective Endocarditis
|Laboratory Finding||Frequency, %|
|Increased erythrocyte sedimentation rate||95|
A number of peripheral manifestations may be present in patients with IE. A number of skin lesions occur, petechiae being most common. These are 1- to 2-mm red, nonblanching macules that become darker and fade within 2 to 3 days. These are seen in less than 50% of patients but, when present, are seen most often on the conjunctiva, soft palate, and distal portions of the extremities.6 Vascular hemorrhages in the optic fundus are referred to as Roth spots. Splinter hemorrhages are vascular hemorrhages occurring under the nails, and often they are difficult to distinguish from traumatic lesions. Splinter hemorrhages due to trauma are more common and are more typically an isolated finding. Osler nodes are erythematous, tender subcutaneous papules that occur on the finger pads (Fig. 49-1). They are 2 to 5 mm in diameter and may be multiple. Janeway lesions are painless, erythematous macules, larger than Osler nodes, that occur on the palms and soles (Fig. 49-2). It is unclear whether Osler nodes and Janeway lesions are due to septic emboli directly or to immunologic phenomena.
Subacute bacterial endocarditis: nontender, purpuric macules with irregular borders scattered on the toes (Janeway lesions).
Osler's nodes: randomly distributed tender nodules on the palm of the hand in a patient with Staphylococcus aureus endocarditis.
Systemic emboli occur in approximately 40% of patients with left-sided valvular infection. In the central nervous system (CNS), embolic occlusion of peripheral arteries results in the stroke syndrome. Emboli to the spleen and kidney often cause abdominal pain. Emboli to mesenteric arteries may cause ischemic bowel disease or frank infarction of bowel. Emboli to muscles are common but usually clinically unapparent. Embolic disease can occur after the institution of antibiotics; patients at increased risk for this complication include those with embolic disease prior to the institution of antibiotics, those with larger vegetations, those with mitral valve involvement, and those infected with staphylococci.7 Drug abusers with right-sided IE frequently have evidence of septic pulmonary emboli on chest x-ray.5
Patients with IE also may present with heart failure due to valve malfunction, embolic myocardial infarction, myocarditis, or systemic toxicity owing to sepsis syndrome. Renal insufficiency is also a prominent sequela of untreated IE, whether occurring on a native or prosthetic valve.
Disorders of the CNS are prominent in patients with IE. Between 10% and 50% of patients with IE will develop some neurologic abnormality. Mental status changes such as confusion, delirium, and psychosis are most common. Focal neurologic symptoms and signs may be caused by an embolic stroke, a bleeding mycotic aneurysm, meningitis, or cerebral artery vasculitis. Overall, approximately 30% of patients with IE will have evidence of a focal neurologic event during their illness.
Anemia is common in patients with IE. Leukocytosis occurs in about 40% of patients. Changes in the renal sediment, particularly proteinuria and microscopic hematuria, usually are present in patients with IE. In long-standing disease, rheumatoid factor is present in about one-half of patients.
Blood cultures are the most important laboratory tests in the diagnosis of IE. The vast majority of blood cultures obtained when a patient is not receiving antimicrobial therapy will be positive. In approximately 5% to 10% of patients with presumed IE, no etiologic organism is isolated initially. The causes of culture-negative endocarditis are prior antibiotics and endocarditis due to fastidious organisms, including anaerobes, nutritionally deficient streptococci, Coxiella burnetii, Legionella pneumophila, Chlamydia psittaci, C. pneumoniae, members of the HACEK group, and various fungi. HACEK is an acronym for a group of small, fastidious, gram-negative bacilli that includes Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae.8 Longer incubation of cultures, special culture techniques to aid in isolation of fastidious microorganisms, and use of serologic studies for Coxiella, Bartonella, and Chlamydia may aid in diagnosis. Other potentially useful laboratory techniques currently under study for intravascular infections and endocarditis include the urinary histoplasmosis antigen, polymerase chain reaction (PCR) using universal bacterial (16S) and fungal (18S, 28S, and 5.8S) RNA primers,9 and serology for lipid S, a component of the gram-positive cell wall.10
Echocardiography is useful in identifying vegetations or local complications of IE. Transthoracic echocardiography has around 60% sensitivity in detecting vegetations in IE. Transesophageal echocardiography (TEE) has emerged as a major tool in the diagnosis and management of native-valve endocarditis (NVE). The sensitivity of TEE in the diagnosis of NVE is 90% to 99%, with a specificity of 90%. Therefore, when NVE is likely clinically but blood cultures are sterile, a TEE may be obtained to assist in diagnosis.11–13 A TEE also should be obtained in patients with an equivocal transthoracic echocardiogram (TTE) or those with a complicated course. One study has suggested that if the pretest probability of IE is between 4% and 60%, it is cost-effective to proceed to TEE without TTE.15 Durack and colleagues12 have proposed criteria for diagnosis of infective endocarditis, and they have been proved useful by other investigators.13 Finally, intracardiac echocardiography is an emerging diagnostic tool that has been used to identify pacemaker lead vegetations even in patients whose TEE is unremarkable.16
Patients encountered in the ICU with fever, cardiac murmurs, or other findings suggesting the possibility of IE always should be evaluated for the possibility of valve infection; this evaluation should include multiple blood cultures and echocardiography. While this evaluation proceeds, two central questions arise: Which clinical situations warrant empirical antimicrobial therapy, and what empirical therapy should be selected? In general, physicians managing patients with possible IE should initiate therapy when one of the following situations is present: (1) the patient is critically ill, (2) antimicrobial therapy appears be necessary for some other infectious disorder, (3) early valve replacement is contemplated because of valve malfunction, and (4) IE is suspected clinically and one or more blood cultures are positive for an etiologic microorganism.
In patients with undiagnosed fever or other findings suggesting IE as a diagnostic consideration but without any of these indications for immediate therapy, withholding antimicrobials is reasonable until blood cultures and the results of other investigations provide support for the diagnosis.
In centers with lower rates of methicillin-resistant S. aureus (MRSA), it is still reasonable to initiate therapy with IV nafcillin at 2 g every 4 hours plus IV ampicillin at 2 g every 4 hours and gentamicin. Gentamicin doses should be at lower levels (1 mg/kg q8h) because synergistic killing with β-lactam agents does not require conventional gentamicin dosage. In the many hospitals and communities where increasing rates of infection with MRSA have been identified, empirical therapy with vancomycin rather than nafcillin should be considered. However, this regimen may not be adequate for IE secondary to vancomycin-resistant enterococci (VRE), which are being reported from many centers. Newer agents, such as linezolid and quinupristin-dalfopristin (faeceium isolates only), may be useful alternatives if VRE are identified and other agents, especially ampicillin, are also unavailable because of resistance profiles.14
In a febrile patient without the usual risk factors for coronary artery disease admitted with acute myocardial infarction, careful consideration of a diagnosis of IE should be undertaken prior to the administration of thrombolytics because catastrophic CNS bleeds from ruptured mycotic aneurysms have been reported.17
In patients with an established diagnosis of IE, management entails a careful choice of antimicrobial therapy based on identification of the etiologic microorganism and ongoing consideration of surgical measures that may be necessary. Table 49-4 lists the most common etiologic microorganisms causing community-acquired NVE and the valves involved. Staphylococci, enterococci, and Candida are the most common microorganisms responsible for nosocomial IE.1 Table 49-5 describes the recommended antimicrobial regimens for treatment of IE. Certain principles are followed when treating patients with IE. Parenteral antibiotics are preferred over oral agents because of more sustained antibacterial activity associated with IV antibiotics and erratic absorption associated with many oral drugs. Bactericidal agents are superior to bacteriostatic drugs. Long-term antimicrobial therapy almost always is required for cure. However, 2 weeks of antibiotics may be adequate in selected patients with uncomplicated viridans streptococcal IE or staphylococcal IE of the tricuspid valve.18,19 Determination of minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of antimicrobial agents necessary to inhibit or kill the microorganism, respectively, are useful in choosing treatment regimens in patients with streptococcal or enterococcal infections. The serum bactericidal test (Schlicter test) is a measurement of antibacterial activity of the patient's serum, at peak and trough antimicrobial concentrations, against the patient's microorganisms. This test remains somewhat controversial. However, some investigators believe that a peak serum inhibitory concentration (SIC) of 1:8 or greater is more likely to be associated with successful treatment of IE.
Table 49–4. Etiology and Valve Involvement in Native-Valve Endocarditis ||Download (.pdf)
Table 49–4. Etiology and Valve Involvement in Native-Valve Endocarditis
|Distribution of valvular lesions:|
Table 49–5. Antimicrobial Therapy for Infective Endocarditis and Other Intravascular Infectionsa ||Download (.pdf)
Table 49–5. Antimicrobial Therapy for Infective Endocarditis and Other Intravascular Infectionsa
|1. Penicillin-sensitive streptococci (MIC ≤ 0.1)||
Penicillin G 10–20 million units IV qd for 4 wks plus aminoglycosidec for first 2 wks (streptomycin 7.5 mg/kg [< or = 500 mg] IM q12h||Cefazolin 2 g IV q8h for 4 wksb plus aminoglycoside for 2 weeks|
|Gentamicin 1.0 mg/kg IM or IV q8h||Ceftriaxone 2 g IV qd for 4 wks|
|2. Relatively "resistant" streptococci (Penicillin MIC 0.2–0.5)||
Penicillin G 20 million units/d for 4 wks plus aminoglycosided for 4 wks||Cefazolin 2 g IV q8h for 4 weeksbplus aminoglycoside for 4 wks|
|3. Resistant streptococci and enterococci (MIC >0.5)||
Penicillin G 20–30 million units IV qd for 6 wks (ampicillin 12 g IV qd is alternative) plus aminoglycosided for 6 wksb||Vancomycin 30 mg/kg qd for 6 wksa|
|4. Staphylococci (methicillin-sensitive)—in absence of prosthetic valve||Nafcillin 2.0 g IV q4h for 4–6 wkse ornafcillin 2 g IV q4h or gentamicin 1 mg/kg q8h for 2 wksh||Cefazolin 2 g IV q8h for 4–6 wksb|
|5. Methicillin-resistant staphylococci—in absence of prosthetic valve||Vancomycin 30 mg/kg IV per day +/− rifampin 300 mg PO q8h for 6 wks||Same|
|6. Staphylococci (methicillin-sensitive)||Nafcillin 2.0 g IV q4h for 6–8 wks plus rifampin 300 mgf PO q8h for 6–8 wks plus aminoglycoside for 2 wks||Cefazolin 2 g IVb q8h for 6–8 wks plus rifampin
f plus aminoglycoside for 2 wks|
|7. Staphylococci (methicillin-resistant)—in presence of prosthetic valve||Vancomycin 30 mg/kg 24h IV for 6–8 wks, rifampin 300 mg q8h for 6–8 wksf plus aminoglycoside for 2 wks||Same|
Penicillin G 20–30 million units IV qd for 6 wks plus aminoglycoside for 6 wks||Vancomycin 30 mg/kg qd IV for 6 wks|
|9. Gram-negative bacilli |
| Enterobacteriaceae||Therapy should be directed by in vitro susceptibilities||Same|
Pseudomonas||Therapy should be directed by in vitro susceptibilities, though usual regimen includes tobramycin (8 mg/kg per day) plus extended-spectrum penicillin||Same, though ceftazidime plus tobramycin (8 mg/kg per day) frequently used|
| HACEK group||Ampicillin 2.0 g IV q4h is commonly used, though therapy should be directed by in vitro susceptibilities (aminoglycoside frequently used in combination)||Third-generation cephalosporins (e.g., ceftriaxone 2g IV qd for 4 wks)|
Coxiella burnetti||Tetracycline 500 mg PO q6h for at least 1 yr plus trimethoprim 480 mg plus sulfamethoxazole 2400 mg qd until there is no evidence clinically of disease or phase I antibody titer is <.1:128||Same|
Amphotericin B plus surgery||Same|
Valve replacement may be life-saving in patients with IE. Indications for urgent valve replacement include severe heart failure, valvular obstruction, fungal endocarditis, ineffective antimicrobial therapy, and the presence of an unstable prosthetic device.20 A point system to aid in evaluation of the need for surgical intervention in IE has been described.21 The various complications that develop during IE are assigned a weighted point value according to their importance as indicators for valve replacement. A total of five or more points indicates the need for urgent surgery. Table 49-6 lists the conditions associated with need for valve replacement and their relative point ratings. Severe heart failure is considered heart failure that does not respond to maximal medical therapy (see Chaps. 22 and 23). Moderate heart failure is failure that is still present after routine but not maximal medical therapy.
Table 49–6. Point System for Assessing the Need for Cardiac Surgery in Infective Endocarditis ||Download (.pdf)
Table 49–6. Point System for Assessing the Need for Cardiac Surgery in Infective Endocarditis
|Complication||Native-Valve IE||Prosthetic-Valve IE|
|Organism other than streptococci||1||2|
|Relapse after medical therapy||2||3|
|Single major embolus||2||2|
|Two or more emboli||4||4|
|Vegetations by echocardiography (2D)||1||1|
|Early closure of mitral valve by echocardiography (2D)||2||NA|
|Ruptured chordae tendineae or papillary muscle||3||NA|
|Rupture of sinus of Valsalva or ventricular septum||4||4|
|Early prosthetic valve endocarditis||NA||2|
The outcome of treatment for IE is heavily influenced by the relative pathogenicity of the infecting organism, the location of the infected valve, and the presence of complications of the infection. S. aureus typically produces a severe and destructive endocarditis that is fatal in more than a third of patients when the infection occurs on the aortic or mitral valve. In patients with tricuspid valve endocarditis, as typically occurs in intravenous drug users, the prognosis is substantially better.5 Recent data indicate that patients with large (>1 cm) vegetations have an increased morbidity and mortality.22 Other factors associated with worse prognosis include mitral valve involvement, severe cardiac failure, shock, major arterial emboli, myocardial abscess formation, and associated major organ system failure. As noted earlier, several of these would constitute indications for surgical intervention.
Prevention of IE in susceptible individuals has been emphasized for many years because of the significant morbidity and mortality associated with the disease. Prophylactic antimicrobial therapy is based on evidence suggesting that bacteremia commonly occurs during certain procedures and that certain cardiac abnormalities place patients at an increased risk for the development of IE following bacteremia. Procedures most frequently associated with bacteremia and for which prophylaxis is recommended include dental extractions, periodontal surgery, lower gastrointestinal procedures, and genitourinary procedures. Bronchoscopy, endoscopy, and barium enemas are also associated with bacteremia but much less commonly, and none of these procedures routinely justifies antimicrobial prophylaxis. Most of the common procedures carried out in ICUs, including endotracheal intubation, urethral catheterization, and insertion of central vascular catheters percutaneously, pose little risk of bacteremia and do not require prophylaxis (except for urethral catheterization in the presence of a urinary tract infection).
Cardiac abnormalities that appear to especially predispose patients to IE following bacteremia include significant aortic and mitral valve deformity/disease, unrepaired ventricular septal defects, patent ductus arteriosus, coarctation of the aorta, prosthetic heart valves, and previously infected native valves. Patients with atrial septal defects, cardiac pacemakers, and atherosclerotic lesions are at much less risk. Mitral valve prolapse with a systolic murmur and/or redundancy of the valve seen on echocardiogram may be an indication for prophylaxis.
The specific antimicrobial agents chosen for prophylaxis depend on the specific procedure to be performed, the cardiac abnormality present, and the presence or absence of penicillin allergy (Table 49-7). In critically ill patients with underlying cardiac abnormalities who are undergoing procedures with a risk of bacteremia, a parenteral regimen usually is appropriate.
Table 49–7. Endocarditis Prophylaxis ||Download (.pdf)
Table 49–7. Endocarditis Prophylaxis
|Procedure||Standard Regimen||Standard Oral Regimen for PCN-Allergic Patients||Alternative Parenteral Regimens|
|Dental or respiratory tract procedure||Amoxicillin 3.0 g PO 1 h before, then 1.5 g 6 h later||Erythromycin 1.0 g PO 2 h before, then 500 mg 6 h later or clindamycin 300 mg PO 1 h before, then 150 mg 6 h later||Ampicillin 2.0 g IV or IM 30 min before, then 1.0 g 6 h later or clindamycin 300 mg IV 30 min before, then 150 mg 6 h later or vancomycin 1.0 g IV over 1 h|
|Gastrointestinal or genitourinary tract procedure||Ampicillin 2.0 g IV or IM plus gentamicin 1.5 mg/kg of body weight IV or IM given 30 min before, repeat 8 h later||Vancomycin 1.0 g IV slowly over 1 h, plus gentamicin 1.5 mg/kg of body weight IV or IM, given 1 h before, repeat 8 h later|
Pathogenesis and Microbial Etiology
Mycotic aneurysms are aneurysmal dilations of arteries caused by infection of the vessel wall with consequent weakening of the vessel's structure. These aneurysms occur most commonly in patients with IE and in that instance usually involve vessels of smaller caliber. The pathogenesis probably involves embolic localization of a valvular vegetation with extension of suppuration from the lumen circumferentially into the vessel wall. Another proposed mechanism is embolization of the vasa vasorum by infected material from the valve. In the absence of underlying IE, mycotic aneurysm may occur following transient bacteremia with seeding of a previously damaged site in a large artery, most commonly an ulcerated atherosclerotic plaque in the abdominal aorta. Mycotic aneurysms also may occur in intravenous drug abusers who both damage and contaminate the wall of a large artery by direct intra-arterial injections of drugs; mycotic aneurysms of the lower extremity, particularly the femoral artery, are most common in this population.
Endocarditis-associated mycotic aneurysms are caused by the same microorganisms causing the IE—streptococci, staphylococci, and occasionally, gram-negative enteric bacilli, the latter being more common among drug abusers. S. aureus and Salmonella spp. are the most frequent causes of mycotic aneurysms of the abdominal aorta and usually are not associated with IE.
Intracranial mycotic aneurysms are encountered most commonly in patients who already carry a diagnosis of IE. These aneurysms usually are asymptomatic unless they rupture. In that circumstance, symptoms and signs are consistent with subarachnoid or intracerebral hemorrhage, with sudden onset of severe headache, decrease in the level of consciousness, and focal neurologic signs. Mycotic aneurysms of visceral arteries have a variable presentation based on the organ involved. In the case of the small bowel, there may be colicky abdominal pain and symptoms of small-bowel obstruction. In the case of hepatic arterial aneurysms, an important differential diagnostic consideration is ascending cholangitis because of fever, right upper quadrant pain, and jaundice. Mycotic aneurysms of the external iliac artery may present with pain in the lower anterior abdomen, quadriceps wasting, diminished deep tendon reflexes, and arterial insufficiency of the ipsilateral lower extremity.23
Patients with mycotic aneurysms of the abdominal aorta present with pain and fever, often of weeks' or months' duration. In as many as one-third of patients with abdominal aortic aneurysms, there is extension into the lumbar or thoracic vertebrae with resulting osteomyelitis. Aortoenteric fistula may occur if an aneurysm erodes into bowel lumen. On physical examination, in addition to fever, there may be a palpable mass in the abdomen.
In patients with IE, clinical suspicion of a mycotic aneurysm usually arises after an episode of new neurologic symptoms in the case of intracranial aneurysms or local findings suggestive of aneurysms, as noted earlier. Clinical suspicion of a leaking intracerebral aneurysm should prompt contrast- and non–contrasted-enhanced computed tomographic (CT) examinations initially; however, an angiogram generally is necessary to exclude or confirm the diagnosis. The diagnosis of mycotic aneurysm of the abdominal aorta is also made on the basis of clinical suspicion, demonstration of bacteremia, and radiologic examination. CT scan of the abdomen may indicate a perivascular collection of fluid or actual blood in an aneurysm or pseudoaneurysm. Arteriography also may be helpful in demonstrating an aortic mycotic aneurysm, and bone films may show erosion of adjacent vertebral bodies.
The management of mycotic aneurysm depends on the organ involved. In the case of intracranial mycotic aneurysms, there is debate regarding the most appropriate therapy. For peripheral intracranial aneurysms, clipping probably is indicated. For deep lesions, for which a surgical approach is felt to be hazardous, antimicrobial therapy alone is advisable because many aneurysms will resolve spontaneously with medical treatment. A history of bleeding, large aneurysm size, and persistence of the aneurysm following antimicrobial therapy are all factors that increase the advisability of surgery for accessible lesions. In the case of abdominal aortic aneurysms, surgical resection of the involved aorta is almost always necessary. Antimicrobial therapy for mycotic aneurysms and other intravascular infections without foreign bodies is outlined in Tables 49-5 and 49-8.
Table 49–8. Recommended Duration of Antimicrobial Therapy for Patients with Various Intravascular Infections ||Download (.pdf)
Table 49–8. Recommended Duration of Antimicrobial Therapy for Patients with Various Intravascular Infections
|Patients Without Intravascular Foreign Bodies|
|Infectious Disorder||Duration of Treatment|
|Cavernous sinus thrombosis||2 weeks following the resolution of all signs of the disease (usually 4 weeks)|
|Mycotic aneurysm||4–6 weeks; 2–4 weeks after resection of the aneurysm|
|Postanginal sepsis||4 weeks or 10 days following resolution of local symptoms and signs|
|Pelvic vein thrombophlebitis||4 weeks (consider anticoagulation)|
|Pylephlebitis||4–6 weeks; if associated with liver abscess, consider additional treatment until abscess is resolved|
Cavernous Sinus Thrombosis
Cavernous sinus thrombosis usually results from direct spread of bacteria from a contiguous focus of infection. Extension of bacteria may occur by several routes, including septic thrombophlebitis of the angular and ophthalmic veins from facial cellulitis, along the lateral sinus and petrosal sinuses from middle ear infections, via the pterygoid venous plexus from a peritonsillar abscess, following a dental infection from osteomyelitis of the maxilla or from a cervical abscess, and along the venous plexus surrounding the internal carotid artery from the middle ear or jugular bulb.
S. aureus is the cause of cavernous sinus thrombosis in about 60% to 70% of patients. Streptococci, anaerobes, and other aerobes account for most of the rest.24 Patients with cavernous sinus thrombosis generally present with the early onset of external ophthalmoplegia with decreased sensation around the eye. The physical examination reveals periorbital edema and chemosis, and as the illness develops, meningismus, altered mental status, and cranial nerve palsies, especially of cranial nerves III, IV, V, and VI, become evident. Examination of the fundus often reveals striking venous congestion. The differential diagnosis of cavernous sinus thrombosis includes orbital cellulitis and rhinocerebral phycomycosis (mucormycosis). The distinction between cavernous sinus thrombosis and orbital cellulitis is sometimes difficult. Bilateral involvement and fifth nerve palsy, a fixed, dilated pupil, and signs of meningitis are all more likely in cavernous sinus thrombosis than in orbital cellulitis.
Although the diagnosis may be evident on clinical grounds alone, several imaging modalities can be useful. Ultrasound examination of the orbit can be useful in defining a periorbital abscess that may require surgical intervention. CT examination with contrast or MRI also can aid in this, will be useful in demonstrating sinusitis or underlying osteomyelitis, and may establish the diagnosis of cavernous sinus thrombosis as well. Carotid angiography and orbital venography also have been used to establish the diagnosis but are not recommended because they are unlikely to influence management. Following CT scan, a lumbar puncture is warranted, but it is usually sterile (80%)24 with a parameningeal inflammatory pattern: pleocytosis and elevated protein without significant hypoglycorrhachia. Blood cultures are mandatory and often are positive (70%)24; if sinus or abscess drainage is performed, fluid should be cultured for both aerobic and anaerobic bacteria. When rhinocerebral mucormycosis is a consideration, usually in a diabetic patient with blackish nasal discharge in addition to the rest of the syndrome, surgical exploration with biopsy and histologic examination for fungi is needed to establish the diagnosis.
Successful management of cavernous sinus thrombosis depends on early, effective antimicrobial therapy. Even with the best medical and surgical therapy, the outcome is often unsatisfactory. For this reason, adjunctive therapies such as corticosteroids and anticoagulation have been tried without success, and they cannot be recommended. The regimens shown in Tables 49-5 and 49-8 can be used when a bacterial etiology has been established. Prior to bacteriologic confirmation, empirical therapy depends on the underlying infection suspected.
In 1936, in an article entitled, “On Certain Septicemias Due to Anaerobic Organisms,” Lemierre25 described a group of patients with pharyngitis complicated by bacteremia due to anaerobic microorganisms. Subsequently, this disorder, usually referred to as postanginal sepsis, has been described frequently.26 The pathogenesis is thought to involve bacterial invasion of the mucosa of the posterior pharynx with extension of suppurative thrombophlebitis (ST) into the internal jugular veins. Bacteremic spread of the infection is common, with lung, liver, and joints the most common sites of metastatic disease. Clinically, patients present with sore throat, chills, fever, and occasionally jaundice. On physical examination, in addition to the toxicity and fever, there may be palpable tender thrombosis of the jugular vein as well as evidence of septic arthritis, pleuropulmonary disease, or jaundice. An enhanced CT scan usually will demonstrate internal jugular vein thrombophlebitis and is useful to localize purulent collections requiring drainage. Chest radiograph may show scattered infiltrates owing to septic pulmonary emboli. Fusobacterium necrophorum has been isolated most commonly from blood, although Bacteroides fragilis and other mouth anaerobes have been reported as well.
Management includes early recognition and treatment of the disorder with effective antimicrobial therapy. Antibiotics should be directed against anaerobic bacteria, with drugs such as metronidazole, chloramphenicol, imipenem-cilastatin, or ticarcillin-clavulanic acid. Prompt surgical intervention to drain any purulent material present locally or distantly is required in addition to antibiotics.
Septic Pelvic Vein Thrombophlebitis
Pelvic vein thrombophlebitis develops most often 1 to 2 weeks after delivery or gynecologic surgical intervention or in the setting of pelvic suppuration, such as following septic abortion or post–Cesarean section endometritis. Symptoms include fever, chills, anorexia, nausea, vomiting, and abdominal pain.27 On physical examination, there may be tenderness in the lower quadrants, and tender venous structures may be palpated in one-third of patients.28 Eighty percent of pelvic vein thromboses complicating pregnancy and delivery occur on the right side, perhaps because of compression of the right ovarian vein at the pelvic brim by the enlarged uterus. In 5% of episodes, thrombosis is apparent only on the left, and in 14%, it is bilateral. Spread distally to femoral veins is unusual.
The most serious complication of suppurative pelvic vein thrombosis is pulmonary embolization. When this occurs, the patient presents with respiratory distress associated with pulmonary opacities that often are pleural-based. Even though the process is associated with thrombosis and bacterial suppuration in the venous lumen, bacteremia is unusual, with an overall prevalence of only 30%. Microorganisms isolated from the blood, or from the veins if surgery is carried out, include those that are normally present in the pelvis, particularly Peptostreptococcus spp., Peptococcus spp., B. fragilis, aerobic gram-negative bacilli such as Escherichia coli, Klebsiella, and Enterobacter, group A and group B β-hemolytic streptococci, and rarely, staphylococci.
The diagnosis can be difficult because the findings are similar to a wider range of other pelvic and lower abdominal inflammatory conditions. Probably the best imaging modality to support the diagnosis is contrast-enhanced CT scan; ultrasound examination also may be useful if the intravascular thrombus can be demonstrated.
Successful treatment frequently requires both antimicrobial therapy and heparinization; indeed, in the appropriate clinical context, fever that is failing to respond to apparently appropriate antimicrobials and that responds to the addition of intravenous heparin can be regarded as support for the diagnosis.29 Complications are mainly those related to suppurative pulmonary emboli.
Pylephlebitis is septic thrombosis of the portal vein and its branches. It is a rarely seen complication of intra-abdominal suppuration and was first described in patients with appendicitis or diverticulitis. The illness evolves in three phases. In the first phase, symptoms and signs of the original intra-abdominal disorder such as acute appendicitis or perforated diverticulum predominate. The second phase involves portal bacteremia, with resulting invasion and thrombosis of portal veins. In the third phase, abscesses form in the liver owing to proximal spread of the suppurative material. Late signs and symptoms include fever, abdominal pain, jaundice, and right upper quadrant tenderness. The liver is enlarged in one-half of patients. Laboratory studies reveal an elevated white blood cell count with increased numbers of immature granulocytes and abnormal liver function tests, particularly elevations of the alkaline phosphatase and aspartate aminotransferase (AST) levels. Bacteremia is not a consistent finding. CT scan is especially useful in demonstrating this disorder, showing clot in the portal veins and occasionally gas in portal vein radicals in the liver. The microorganisms responsible reflect large bowel flora and include aerobic gram-negative bacilli such as E. coli, Klebsiella, and Enterobacter; anaerobic microorganisms such as Peptococcus, Peptostreptococcus, B. fragilis, and Fusobacterium; and gram-positive aerobic species such as staphylococci and enterococci.
Successful therapy requires surgical correction of the primary problem, as well as high-dose antibacterial therapy directed against the offending pathogens. Pyogenic liver abscesses resulting from this disorder usually are best treated with prolonged medical therapy alone, unless they are few and relatively large, in which case percutaneous drainage may be useful. Surgical drainage of multiple small abscesses is very difficult, often requires a transperitoneal approach, and is not recommended. The effectiveness of antibacterial therapy may be judged by physical examination, resolution of fever and leukocytosis, and improvement of abnormalities demonstrated by ultrasound or CT scan.