Septic Thrombophlebitis


Article Author:
Abdul Waheed
Lisa Foris
Demis Lipe


Article Editor:
Kevin King


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
7/7/2019 8:31:49 AM

Introduction

Suppurative (septic) thrombophlebitis (ST) describes thrombosis in a vein that occurs in the setting of inflammation and infection. This condition is characterized by the presence of a thrombus (with or without pus) that is associated with inflammation and pus formation (suppuration) both in the venous wall and surrounding the vessel. Although this process can occur in both superficial and deep vessels throughout the body, it is seen most commonly in venous structures (e.g. peripheral veins, pelvic veins, superior vena cava, internal jugular vein, portal veins or dural sinuses).[1][2][3]

Etiology

Although it can occur spontaneously, the majority of cases of peripheral ST result from breaks in the skin. Most often, peripheral, inferior vena cava or superior vena cava ST occurs as a consequence of an indwelling catheter (e.g. intravenous catheter (IVC) or peripherally inserted central venous catheter (PICC)), but it can also result from less invasive procedures such as venipuncture done for phlebotomy, or intravenous injection.  Additionally, phlebitis can occur without an underlying infection; simply as a result of catheter-related mechanical or chemical irritation (though infection should always be considered).[4][5][6]

Deep, non-catheter associated (e.g. pelvic, ovarian, pylephlebitis) ST may result from diverticulitis, endometritis, pelvic inflammatory disease, intra-abdominal infections, abdominal surgery, childbirth or septic abortion.

Lemierre syndrome (thrombophlebitis of the internal jugular vein) is most often caused by pharyngitis but may occur secondary to a dental infection as well.  

Dural vein ST may result from an ear, nose or throat infection (e.g. oropharyngeal infection, mastoiditis, otitis media, meningitis).  

All forms of ST can occur as a result of a hypercoagulable state.

Epidemiology

Individuals at the extremes of age (e.g. neonates and the elderly) appear to be the most vulnerable to ST - likely attributable to undeveloped host defenses in neonates, and a decline in immunologic function as well as additional comorbid disease in the elderly. [7][8][9]

The current incidence of catheter-associated (peripheral) ST is estimated at 0.5 cases of bloodstream infections per 1000 days of a peripherally inserted intravenous device. For non-tunneled, non-medicated, central venous catheters, the incidence is estimated at 2.7 per 1000 intravenous device days. Approximately 4.2% of burn patients experience peripheral ST.

Deep (non-catheter associated) ST is seen much less common; the exact incidence therefore not yet described. In the case of pelvic ST (seen most frequently in women of child-bearing age), it has been found to occur in 1 out of every 3000 deliveries, with the incidence being 10-fold greater with cesarean sections than with vaginal deliveries.  

Lemierre syndrome is also rare (an estimated 0.8 cases per 1 million per year in Europe) and often missed.  It occurs most commonly in healthy, young adults around the age of 20. 

Dural sinus ST is the rarest form of ST.

Pathophysiology

Though not all cases of catheter-associated sepsis result in ST, most cases of ST occur as a result of IVC or PICC line infection.

The incidence of ST in peripheral veins is highest in patients that have risk factors such as burns, steroid use or injection drug use. Burn patients are especially at risk due to impaired local host defenses as a result of lost skin integrity, a large number of organisms on the skin, hyperalimentation (e.g. total parenteral nutrition) and use of broad-spectrum antibiotics.

Lemierre's syndrome, which refers to thrombophlebitis of the internal jugular vein, occurs most commonly as a result of bacterial pharyngitis (e.g. pharyngitis that progresses to the formation of a peritonsillar abscess, which then ruptures and spreads to surrounding tissues and venous structures).

Infection in any part of the middle third of the face (e.g. nose, periorbital regions, tonsils, soft palate) poses the greatest risk of dural venous/sinus ST as these structures drain directly into the cavernous sinus (e.g. through ophthalmic veins, facial veins, and the pterygoid plexus). Additionally, meningitis and sinusitis have also been reported to be associated with dural sinus ST (e.g. through the direct spread of infection).

Pylephlebitis, which is ST of the portal vein, is a (rare) complication encountered with diverticulitis, but may also be caused by an intra-abdominal infection (e.g. structures draining into the portal vein).

Pelvic and ovarian vein ST occurs most commonly in the setting childbirth (within the first three weeks post-partum) due to local spread of a uterine infection (e.g. endometriosis) if present. The hypercoagulable state that occurs in the setting of pregnancy contributes to thrombus formation, and damage to iliofemoral vessels during childbirth further promotes this process.

The most common cause of ST is Staphylococcus aureus. Other commonly encountered microorganisms include streptococci and Enterobacteriaceae.  Burn patients may present with a polymicrobial infection.

History and Physical

Patients with ST typically present acutely with a fever along with erythema, tenderness and purulent drainage at the site of the involved vessel. Some patients may have associated respiratory distress (e.g. septic emboli to the lungs are common - may result in infiltrates, lung abscesses, pneumonia or empyema), and in the case of jugular vein ST, may also complain of localized throat or neck pain. Additionally, ulceration, a pseudomembrane or erythema may be visualized in the oropharynx of a patient with jugular vein ST. There may also be tenderness, swelling, or induration over the jugular vein, along with the sternocleidomastoid muscle, or over the angle of the jaw. 

Septic emboli may additionally travel to joints or bones resulting in septic arthritis or osteomyelitis - in which case the patient may complain of joint pains or body aches (e.g. in addition to fever, malaise, and night sweats).

Evaluation

There should be high clinical suspicion for ST in patients with bacteremia that persists for over 72 hours, despite the appropriate antibiotic therapy (especially if there is an IVC or PICC in place).  [10][11]

The best available test remains a contrast-enhanced computed tomography (CT) scan - this will allow for evaluation of any filling defects within a vessel that may potentially contain a clot and may additionally demonstrate any surrounding inflammation. Diagnosis is then made based on this radiographic evidence of thrombosis, taken together with results from blood cultures or cultures of purulent material obtained from a suspected site (e.g. tip culture in the case of catheter-associated thrombophlebitis, or Gram stain and culture of purulent material from a soft-tissue site). Tip cultures from both peripheral and central sites should be sent for comparison if available. It is important to note that a catheter should not be removed if there is a suspicion that the thrombus may be attached.

If CT scanning is unavailable, magnetic resonance imaging (MRI) may also be used for diagnosis of most cases of ST. In fact, MRI combined with MR venography is the most sensitive, non-invasive test for evaluating the dural sinuses.

Ultrasound may be useful in some cases of ST (e.g. if there is an abscess present very close to the involved vessel), and can also be diagnostic if a thrombus is revealed in the setting of a positive blood culture. In the cases of pelvic or dural vein thrombophlebitis, however, ultrasound will not provide an adequate study (due to poor penetration). 

Additional laboratory studies may include a complete blood count (to show leukocytosis), blood chemistries (may reveal acidosis or electrolyte imbalances), hepatic enzymes and liver function tests (if there is a suspicion of pylephlebitis), and International normalized ratio/prothrombin time (to assess whether anticoagulation is warranted).

Treatment / Management

The treatment of ST depends on the source of infection, the organisms involved, the structures being affected, and the individual patient's physiology. The main goals of treatment include removal of the source of infection (e.g. IVC or PICC), intravenous antibiotic administration (starting with empiric therapy and then adjusting according to culture and susceptibility results), and evaluation of surgical intervention (e.g. in the case of ongoing sepsis regardless of antimicrobial therapy) and/or anticoagulation.[12][13]

Consultations

  • Vascular surgeon because in some cases excision of the vein may be required to remove the source of infection.
  • Interventional radiology
  • Infectious disease

Enhancing Healthcare Team Outcomes

ST is not an uncommon diagnosis in hospitals. Because the condition can occur in any vein, the condition is best managed by a multidisciplinary team that includes a surgeon, an interventional radiologist and an infectious disease specialist. Nurses are often the first professionals to note the condition because the condition is often linked to peripheral vein cannulation. Once the condition is diagnosed, immediate treatment is necessary to prevent metastatic foci of infection in the systemic circulation. Mortality rates of 3-30% have been reported depending on the location of the vein and extent of infection. Infections associated with candida have the highest mortality. When the dural sinuses are involved, the mortality can exceed 70%. Today, with better imaging and improved diagnosis, the mortality rates have dropped, but any delay in treatment is associated with high morbidity and mortality. Once discharged, patients often need follow up to ensure that they have not developed endocarditis or a recurrent infection. To lessen the mortality, peripheral vein cannulation should be preferred over central vein cannulation.[14][8] (Level V)

 

 

 

 

 


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Septic Thrombophlebitis - Questions

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A 25-year old gravida 3 para 2, with a history of pelvic inflammatory disease, had prolonged labor of over 36 hours, which ultimately resulted in an emergent cesarean section due to fever of 103.5 degrees Fahrenheit and fetal distress. After the cesarean section, the patient was maintained on broad-spectrum antibiotics for presumed chorioamnionitis. Seventy-two hours after delivery, the patient continued to spike a fever and remained tachycardic, despite antibiotics and intravenous fluids. Her exam was non-focal with a non-tender abdomen. Her laboratory studies were significant for leukocytosis of 12000/microliter. Which of the following is most suggestive of septic pelvic thrombophlebitis?



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An 18-year-old woman with acute myeloid leukemia and no other past medical history presents to the emergency department with headache, fever, right periorbital swelling, decreased vision and eye pain. He exam shows an ill-appearing woman, with vitals showing a temperature of 102.6 degrees Fahrenheit, respiratory rate of 20 breaths per minute, blood pressure of 98/56 mmHg, heart rate of 126 beats per minute and oxygen saturation of 99% on room air. She has an erythematous and swollen right periorbital region and is unable to open her right eye. Upon review of her most recent lab results (from yesterday), you notice she has a white blood cell count of 500/microiter, hemoglobin of 6 grams/deciliter and platelets of 21000/microliter. A review of her chart shows she was discharged from the hospital one week ago after being admitted for neutropenic fever. What is the next step in the evaluation and management of this patient?



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A 32- year old male IV drug user presents to the emergency department with fever, chest pain, shortness of breath along with right arm redness. He has no significant past medical history. His presenting vital signs show a temperature of 101.3 degrees Fahrenheit and a heart rate of 132 beats per minute, oxygen saturation on room air of 95%; while the remaining vitals are within normal limits. His exam shows right arm cellulitis, increased work of breathing, and bibasilar rales. His initial workup revealed a leukocytosis of 23,000/microliters, and a chest radiograph with bilateral lower lobe infiltrates. He is started on broad-spectrum antibiotics upon admission, and despite this, his condition worsens, and he is transferred to the intensive care unit (ICU) for respiratory failure. Once in the ICU, he has a computed tomography scan of the chest that shows multiple septic pulmonary emboli. Which of the following is the next best step in the management of this patient?



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A 59-year-old woman with stage III breast cancer was started on chemotherapy following catheter placement in the left subclavian vein. Two months into treatment she presents with acute fever, chills, and numerous painful, swollen, erythematous lesions in both legs and arms. Following removal of her catheter, she is started on intravenous broad-spectrum antibiotics and blood cultures are sent for analysis. Doppler studies of all limbs did not show any obstruction to blood flow. Despite antibiotic treatment, fever persisted and more painful lesions developed on her limbs, in addition to some evolving into abscesses. All cultures including blood and purulent material from abscesses were negative showing no growth. Chest x-ray revealed multiple, round, irregular, non-cavitating opacities distributed bilaterally throughout the lungs. A transthoracic echo performed a few days later demonstrated a hyperdense structure in the superior vena cava extending 45x10x15 mm. What is the next step in treating this patient?



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A 16-year old male presents to the clinic with complaints of worsening pain in his throat, fever, neck swelling, difficulty in swallowing and pain in his jaw muscles. He was evaluated by his provider one week ago for sore throat and fever. He was treated for presumed streptococcal pharyngitis. On examination, an ill-appearing teenager is seen, febrile to 101.8 F, who is able to handle secretions and has no respiratory compromise but has a muffled voice. With effort, the provider is able to visualize his posterior oropharynx and notices a swollen right tonsil causing uvular deviation to the left with the fullness of the posterior soft palate. What is the next step in the management of this patient?



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Septic Thrombophlebitis - References

References

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Nemakayala DR,P Rai M,Kavuturu S,Rayamajhi S, Atypical Presentation of Lemierre's Syndrome Causing Septic Shock and Acute Respiratory Distress Syndrome. Case reports in infectious diseases. 2018     [PubMed]
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De Smet K,Claus PE,Alliet G,Simpelaere A,Desmet G, Lemierre's syndrome: a case study with a short review of literature. Acta clinica Belgica. 2018 May 21     [PubMed]
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Chirinos JA,Garcia J,Alcaide ML,Toledo G,Baracco GJ,Lichtstein DM, Septic thrombophlebitis: diagnosis and management. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2006;     [PubMed]
Miceli M,Atoui R,Walker R,Mahfouz T,Mirza N,Diaz J,Tricot G,Barlogie B,Anaissie E, Diagnosis of deep septic thrombophlebitis in cancer patients by fluorine-18 fluorodeoxyglucose positron emission tomography scanning: a preliminary report. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004 May 15;     [PubMed]
Miceli M,Atoui R,Thertulien R,Barlogie B,Anaissie E,Walker R,Jones-Jackson L, Deep septic thrombophlebitis: an unrecognized cause of relapsing bacteremia in patients with cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004 Apr 15;     [PubMed]
Giquello JA,Dupoiron D,Lemarié C,Lorimier G,Granry JC, Septic uveitis revealing internal jugular vein thrombophlebitis. The Lancet. Infectious diseases. 2011 Apr;     [PubMed]

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