You are in: eMedicine Specialties > Emergency Medicine > INFECTIOUS DISEASES Thrombophlebitis, SepticArticle Last Updated: Sep 8, 2006AUTHOR AND EDITOR INFORMATIONAuthor: Christian Theodosis, MD, MPH, Resident Physician, Section of Emergency Medicine, Yale School of Medicine Coauthor(s): Craig Feied, MD, FACEP, FAAEM, FACPh, Professor of Emergency Medicine, Georgetown University; Director, National Institute for Medical Informatics; Director, Federal Project ER One; Director, National Center for Emergency Medicine Informatics; Jonathan A Handler, MD, Director of Informatics, Assistant Professor, Department of Emergency Medicine, Northwestern Memorial Hospital Editors: Richard S Krause, MD, Clinical Assistant Professor, Residency Program Director, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eddy Lang, MDCM, CCFP (EM), CSPQ, Assistant Professor, Department of Family Medicine, McGill University; Consulting Staff, Department of Emergency Medicine, The Sir Mortimer B Davis-Jewish General Hospital; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Charles V Pollack, Jr, MD, MA, FACEP, Professor, Department of Emergency Medicine, University of Pennsylvania College of Medicine; Chairman, Department of Emergency Medicine, Pennsylvania Hospital Author and Editor Disclosure Synonyms and related keywords: septic phlebitis, septic thrombophlebitis, septic emboli, septic shock, catheter-related septic phlebitis, suppurative superficial thrombophlebitis, septic pelvic thrombophlebitis, septic ovarian vein thrombophlebitis, septic pelvic phlebitis INTRODUCTIONBackgroundThe clinical course and severity of septic thrombophlebitis are quite variable. Many cases present as benign localized lesions that require minimal intervention after which complete recovery is expected. Some cases present as severe systemic infections culminating in profound shock, refractory even to aggressive management, including operative intervention and appropriate treatment in the intensive care unit. The approach to septic phlebitis depends on which veins are involved, the underlying etiology of the phlebitis, which organisms are involved, and the patient's underlying physiology. Peripheral septic thrombophlebitis is a common problem that can develop spontaneously but more often is associated with breaks in the skin. Peripheral septic phlebitis is most commonly caused by intravenous catheters, venipuncture for phlebotomy, or intravenous injection. Septic phlebitis may produce septic emboli, which can seed distant sites. Extensive showering of septic emboli may initiate a systemic inflammatory response, culminating in septic shock, which has a poor prognosis even when managed ideally. Catheter-related septic phlebitis is one of the most common causes of fever after the third postoperative day. Catheter-associated phlebitis may develop at any site but is most frequent after cannulation of lower limb veins and veins at the groin. Catheter-related phlebitis also can result from chemical or mechanical irritation without infection, but infection must be strongly suspected in any patient with catheter-related phlebitis. Sterile superficial phlebitis should be evaluated and managed as discussed in Thrombophlebitis, Superficial. Septic phlebitis of a superficial vein without frank purulence is known as simple phlebitis. Simple phlebitis can be benign, but when progressive, it may cause serious complications including death. Suppurative superficial thrombophlebitis, in which actual purulent material can be expressed from a vein, portends a much poorer prognosis. Such cases are often associated with frank sepsis and therefore confer a substantial risk of mortality even when treated aggressively. Patients with this condition are likely to appear toxic (eg, high fevers, rigors, sweats, chills, altered sensorium, poor urine output). Septic phlebitis of the deep veins is a life-threatening emergency that may fail to respond to even the most aggressive therapy. Septic pelvic thrombophlebitis and septic ovarian vein thrombophlebitis are seen principally as complications of puerperal infection and septic abortion. Occasionally, septic pelvic phlebitis may be secondary to pelvic inflammatory disease or progressive infection of the urinary tract. In diverticulitis, infection may spread to cause septic phlebitis of the portal venous system (pylephlebitis). Lemierre syndrome is an anaerobic suppurative thrombophlebitis of the internal jugular vein, most commonly as a complication of pharyngeal, dental, or mastoidal infection. Lemierre syndrome is much more common than generally appreciated, and it may be complicated by septic emboli. Septic emboli can lodge in the lungs (septic pulmonary emboli). Less commonly, septic emboli may traverse a patent foramen ovale resulting in distant metastatic infections. Secondary infections may include septic arthritis, paravertebral abscess, cutaneous abscess, periorbital cellulitis, meningitis, and osteomyelitis. Thrombophlebitis of the intracranial venous sinuses is a particularly serious problem. Infection of the medial third of the face is associated with cavernous sinus thrombophlebitis. Mastoiditis is associated with septic phlebitis involving the lateral sinuses. Cases of intracranial septic thrombophlebitis are fatal in more than a third of cases. PathophysiologySeptic phlebitis can develop spontaneously or as a result of a break in the skin through which offending organisms are introduced. Septic phlebitis most commonly occurs in association with protracted use of intravenous cannulas for administration of fluids or medications. Prolonged catheterization, use of semipermeable transparent dressings, and a jugular insertion site are independent risk factors for developing septic phlebitis. Septic phlebitis often complicates other illnesses that depress the immune response, including malnutrition, diabetes, liver disease, and malignancy, and in patients taking immunosuppressant agents. Catheter-associated septic thrombophlebitis often progresses to involve the deep veins; nearly one fourth of long-term central venous catheters result in septic phlebitis in deep veins. Deep or superficial septic phlebitis also can occur by direct invasion from adjacent nonvascular infections. Endometritis or urinary tract infections, for example, may spread to cause septic pelvic thrombophlebitis or septic ovarian vein thrombophlebitis. Pylephlebitis (septic thrombophlebitis of the portal vein) usually occurs as a complication of diverticulitis or another infection in the region drained by the portal venous system. Systemic effects can be due to bacteremia per se or may be related to bacterial endotoxin production. Streptococcal toxic shock syndrome has been reported in association with pediatric peripheral septic thrombophlebitis. Regardless of the original etiology or site of infection, septic thrombophlebitis may produce secondary endocarditis, arteritis, or pneumonia due to septic thromboemboli. Embolic pneumonias have a high incidence of abscess formation and cavitation (empyema). Peripheral septic metastases are seen in patients who develop left-sided endocarditis and in those with right-sided endocarditis who also have a patent foramen ovale. The etiologic agent of septic or suppurative phlebitis usually can be cultured both from blood and from metastatic sites of infection. Septic phlebitis can be caused by gram-positive or gram-negative organisms or by candidal or mycobacterial species. Staphylococcus epidermidis, group A streptococci, and Klebsiella and Enterobacter species are common causes of phlebitis. The most severe cases are seen in patients with phlebitis due to Candida species, Pseudomonas aeruginosa, or Staphylococcus aureus. The offending organism often can be predicted by the site of infection. Peripheral bacterial phlebitis virtually always is caused by aerobic organisms, while septic pelvic thrombophlebitis and septic internal jugular phlebitis (Lemierre syndrome) usually are caused by anaerobic pathogens. The organism most frequently associated with Lemierre syndrome is Fusobacterium necrophorum, an endotoxin-producing gram-negative obligate anaerobe found in the upper respiratory, gastrointestinal, and genitourinary tracts. Other organisms that may cause Lemierre syndrome include Bacteroides melaninogenicus, Eikenella corrodens, and non-group A streptococci. The bacteremia of pylephlebitis is often polymicrobial, reflecting the underlying diverticular source, but the most common blood isolate is Bacteroides fragilis. Septic cavernous sinus thrombophlebitis most often is caused by S aureus. FrequencyUnited StatesThe annual incidence is unknown, but septic phlebitis due to intravenous catheters is one of the most common causes of fever after the third postoperative day, occurring in at least 12% of patients who have undergone surgery. Patients in the intensive care unit (ICU) are at particularly high risk: 24% of ICU patients with central venous catheters and 9% of those with peripheral catheters develop fever and bacteremia and have positive results on culture of the venous catheter tip. InternationalIncidence in developing countries is thus far unstudied and therefore unknown. In resource-poor settings, a definitive diagnosis is often impossible. Patients in whom the diagnosis is strongly suspected should certainly receive empiric antibiotic therapy. The decision to anticoagulate must be carefully weighed against local capacity to manage potential complications. Mortality/MorbidityMajor complications occur in one third of all episodes of peripheral septic phlebitis caused by percutaneously inserted catheters.
Age
CLINICALHistory
Physical
CausesAny event producing cutaneous discontinuity (break in skin) predisposes the human organism to soft-tissue infections that may result in septic phlebitis.
DIFFERENTIALSAbortion, Septic Appendicitis, Acute Bites, Animal Bites, Human Bites, Insects Candidiasis Catscratch Disease Cavernous Sinus Thrombosis Cellulitis Cholangitis Cholecystitis and Biliary Colic Deep Venous Thrombosis and Thrombophlebitis Endocarditis Erysipelas Mastoiditis Necrotizing Fasciitis Otitis Externa Ovarian Torsion Pelvic Inflammatory Disease Peritonsillar Abscess Pharyngitis Pregnancy, Postpartum Infections Prostatitis Shock, Septic Sinusitis Thrombophlebitis, Septic Thrombophlebitis, Superficial Toxic Shock Syndrome Urinary Tract Infection, Female
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| Drug Name | Reteplase (Retavase) |
|---|---|
| Description | Second-generation recombinant tissue-type plasminogen activator. As fibrinolytic agent, seems to work faster than its forerunner, alteplase, and also may be more effective in patients with larger clot burden. Also has been reported to be more effective than other agents in lysis of older clot. In patients being treated for peripheral vascular disease, has been reported to cause fewer bleeding complications than alteplase. Contrast venography used to guide duration and intensity of therapy. For local lysis of arterial thrombosis (with or without associated infection), suggested dose is lower (0.5 U/h infusion). |
| Adult Dose | For venous thrombus: 1 U/h local/regional IV infusion for 18-36 h For infected catheter thrombus or fibrin sleeve: 1 U/h IV for 3 h For thrombosed dialysis grafts: 5-10 U/h IV bolus by pulse-spray delivery |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; uncontrolled hypertension; recent intracranial surgery; arteriovenous malformation or aneurysm; bleeding diathesis |
| Interactions | May increase effects of warfarin, heparin, and aspirin |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmias; when used as infusion for local or regional fibrinolysis, some monitor fibrinogen levels at 6 h intervals; if systemic fibrinogen levels drop below 100 U, infusion rate reduced by half |
| Drug Name | Alteplase (Activase) |
|---|---|
| Description | First recombinant tissue plasminogen activator to be released for clinical use, and agent with which EDs are most familiar. Although best known as fibrinolytic agent used for coronary artery occlusion and for PE, also widely used for catheter-directed lysis of DVT, for dissolution of catheter-related thrombus, and for re-opening of occluded central lines and thrombosed dialysis grafts. Contrast venography used to guide duration and intensity of therapy. |
| Adult Dose | For catheter-directed treatment of DVT: 5 mg IV bolus and 1 mg/h IV infusion for 12-24 h For infected catheter thrombus or fibrin sleeve: 1 mg/h for 3 h For occluded dialysis grafts: 10 mg IV bolus delivered into graft site, repeated q2h for 4 doses prn |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; active internal bleeding; cerebrovascular accident or stroke within last 2 mo; intracranial or intraspinal surgery or trauma; intracranial hemorrhage on pretreatment evaluation; suspicion of subarachnoid hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; bleeding diathesis; severe uncontrolled hypertension |
| Interactions | Drugs that alter platelet function (eg, aspirin, dipyridamole, abciximab) may increase risk of bleeding prior to, during, or after therapy; may give heparin with and after alteplase infusions to reduce risk of rethrombosis—either heparin or alteplase may cause bleeding complications |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor for bleeding, especially at arterial puncture sites, with coadministration of vitamin K antagonists; control and monitor BP frequently during and following administration (when managing acute ischemic stroke); do not use >0.9 mg/kg to manage acute ischemic stroke; doses >0.9 mg/kg may cause ICH |
Anticoagulation with some form of heparin is essential in patients with septic phlebitis, but anticoagulation alone does not guarantee a successful outcome. Progression of the disease may occur despite full and effective heparin anticoagulation.
Heparin works by activating antithrombin III to slow or prevent the progression of venous thrombosis. Heparin does not dissolve existing clot.
When low-molecular-weight heparin (LMWH) is used, checking the aPTT has no utility, because aPTT does not correlate with therapeutic effect or with bleeding risk in patients receiving LMWH.
When unfractionated heparin is used, an aPTT of at least 1.5 times the control value is necessary for a therapeutic effect. To achieve this, unfractionated heparin must be given IV in adequate doses. Low-dose subcutaneous unfractionated heparin should not be used, as it is neither an effective therapy for septic phlebitis nor an effective prophylaxis against progression of the disease.
Warfarin should not be used in the acute treatment of septic phlebitis, because the early risk of increased thrombogenesis outweighs any convenience of oral therapy.
| Drug Name | Heparin |
|---|---|
| Description | Initial bolus used for patients with inflammatory and septic thrombosis is lower than that needed for spontaneous DVT and PE, because most patients with inflammatory or septic thrombophlebitis do not have underlying hypercoagulability. Patients with DVT or PE require more aggressive therapy because DVT is manifestation of active hypercoagulable state. Do not check aPTT until 6 h after initial bolus of unfractionated heparin, as extremely high or low value during this time should not provoke any action. |
| Adult Dose | 60 U/kg (max 4000 U) IV bolus, followed by a 12 U/kg/h (max 1000 U/h) maintenance infusion After bolus, check aPTT every 6 h until stable, and adjust dosing as follows: If aPTT is low ( <1.5 times control value), rebolus with 4000 U and increase drip by 10% If aPTT is high (>2.5 times control value), decrease drip 10% If aPTT is extremely high (>100 sec), hold heparin drip for 1 h and decrease drip 10% |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia |
| Interactions | Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Thromboembolism may occur if dosing inadequate; may cause hemorrhagic complications and can trigger immune thrombotic thrombocytopenia 1-2 wk after beginning treatment; platelet-consuming disseminated thrombosis refractory to traditional treatment can be fatal if not recognized quickly and managed appropriately; if significant bleeding develops, 15 mg of protamine (infused over 3 min) usually reverses anticoagulant effect; in neonates, preservative-free heparin recommended to avoid possible toxicity (ie, gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock |
| Drug Name | Enoxaparin (Lovenox) |
|---|---|
| Description | First LMWH released in US. Only LMWH now approved by FDA for both treatment and prophylaxis of DVT. Widely used in pregnancy, although clinical trials not yet available to demonstrate that it is as safe as unfractionated heparin. No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). |
| Adult Dose | Thrombosis: 1 mg/kg SC q12h Prophylaxis: 30 mg SC q12h |
| Pediatric Dose | Not established; suggested dose 1.6 mg/kg SC bid if aged <2 months and 1 mg/kg/dose SC bid if > 2 months |
| Contraindications | Documented hypersensitivity; major bleeding; thrombocytopenia |
| Interactions | Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | If thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminases may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated LMWH; 1 mg of protamine sulfate reverses effect of approximately 1 mg of enoxaparin if significant bleeding complications develop |
Choice of antibiotic depends upon results of blood cultures or Gram stain and culture of material taken from the suppurative vessel or from a metastatic septic focus.
For superficial phlebitis, aerobic coverage is sufficient.
Anaerobic coverage is required for patients with abscess formation, those with pelvic or ovarian vein phlebitis, and those with Lemierre syndrome of internal jugular phlebitis (often due to F necrophorum).
Candidal phlebitis is treated with amphotericin B.
| Drug Name | Penicillin G (Pfizerpen) |
|---|---|
| Description | Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Aqueous penicillin G is first choice for treatment of susceptible infections because of its rapid onset of action. Useful in infections of the head and neck due to Streptococcus, Clostridium, Actinomycosis, Listeria, Erysipelothrix, and Pasteurella species as well as fusospirochetal infections. |
| Adult Dose | 3-4 million U IV q4h |
| Pediatric Dose | 30,000-40,000 U/kg IV q4h |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid can increase effects; tetracyclines can decrease effects; ethacrynic acid, aspirin, indomethacin, and furosemide may compete for renal tubular secretion, resulting in increase in penicillin serum concentrations |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution in impaired renal function |
| Drug Name | Clindamycin (Cleocin) |
|---|---|
| Description | Lincosamide for treatment of serious skin and soft-tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. |
| Adult Dose | 150-300 mg IV q6h |
| Pediatric Dose | 2-4 mg/kg IV q6h Severe infections: 5 mg/kg IV q6h |
| Contraindications | Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis |
| Interactions | Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis |
| Drug Name | Metronidazole (Flagyl) |
|---|---|
| Description | Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis). |
| Adult Dose | Initial dose: 15 mg/kg IV over 1 h Subsequent doses: 7.5 mg/kg over 1 h q6-8h; not to exceed 4 g in 24 h |
| Pediatric Dose | 5-10 mg/kg IV q 8 h; not to exceed 500 mg/dose |
| Contraindications | Documented hypersensitivity |
| Interactions | Cimetidine may increase toxicity; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy |
| Drug Name | Chloramphenicol (Chloromycetin) |
|---|---|
| Description | Binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. |
| Adult Dose | 12-25 mg/kg IV q6h; not to exceed 4 g/d |
| Pediatric Dose | 12-20 mg/kg IV q6h |
| Contraindications | Documented hypersensitivity |
| Interactions | Barbiturates may decrease serum levels while barbiturate levels may increase, causing toxicity; sulfonylureas may cause manifestations of hypoglycemia; rifampin may reduce serum levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity and increasing or decreasing chloramphenicol levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Use only for indicated infections, or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur—evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome) |
| Drug Name | Amphotericin B (AmBisome) |
|---|---|
| Description | Produced by strain of Streptomyces nodosus. Can be fungistatic or fungicidal (effective against candidal phlebitis). Binds to sterols, such as ergosterol, in fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death. |
| Adult Dose | 3 mg/kg IV qd administered over 2 h |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antineoplastic agents may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; cyclosporine increases risk of renal toxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) if interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion) |
Thrombophlebitis, Septic excerpt
Article Last Updated: Sep 8, 2006