eMedicine Specialties > Emergency Medicine > Infectious Diseases
Thrombophlebitis, Septic: Treatment & Medication
Updated: Jul 24, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
- Septic phlebitis does not require any prehospital intervention.
Emergency Department Care
- Uncomplicated superficial septic phlebitis due to a peripheral IV catheter often responds to systemic antibiotics and removal of the cannula.
- Peripheral intravenous catheters should be removed at the first sign of erythema, induration, or edema.
- The temptation to try to preserve a peripheral intravenous catheter must be resisted, because the morbidity and mortality rates associated with septic phlebitis are substantial and increase dramatically over time if the catheter is left in place.
- Once phlebitis has become suppurative, simply removing the cannula is no longer sufficient. Suppurative superficial veins must be removed surgically as soon as possible.
- Immediate excision of the involved purulent vein dramatically reduces the likelihood of spread into the deep system and of septic metastasis.
- In many cases, the best method of removal is to perform percutaneous phlebectomy using Ramelet or Mueller hooks (or other similar phlebectomy hooks) to extract the vein through a series of needle punctures or tiny stab incisions. If necessary, suppurative veins may be removed by cutdown, but the results are less cosmetically pleasing.
- Some authors believe that a fully open approach to phlebectomy is always best because it allows the wounds to be packed open to prevent re-accumulation of pus in the subcutaneous tissues.
- Some authors believe that the presence of bacteremia in a patient with superficial septic phlebitis is an indication for immediate phlebectomy even in the absence of any demonstrable purulent material.
- In contrast to peripheral catheters, infected central venous catheters should not be removed precipitously. Infected central catheters often have an extensive infected free-floating fibrin sheath, and a large mass of septic thrombus may be attached to the catheter. If the catheter is withdrawn precipitously, this septic material may embolize to cause septic pulmonary emboli or septic distant metastases.
- Before an infected central catheter is removed, contrast venography should be performed through the catheter to identify any fibrin sheath or thrombus. If thrombus or a sheath is present, removal should be delayed until antibiotic levels are therapeutic and until the infected thrombus or sheath can be dissolved by local fibrinolysis.
- Fibrinolysis in this setting is very easy and effective because the catheter tip usually is positioned perfectly to permit delivery of lytic agents directly into the fibrin sheath and thrombus. In most cases, complete dissolution of the local thrombus is possible using low doses of lytic agents without producing a systemic lytic state. Block et al describe safe removal of a catheter by thrombolysis using local urokinase infusion for catheter-related C albicans thrombophlebitis.4
- Dissolving a large mass of septic thrombus rather than letting it embolize as a whole is worth the effort. This transcatheter procedure is performed routinely by interventional radiologists, but it may be carried out easily in the ED if assistance from interventional radiology is not immediately available.
Consultations
- Well-localized superficial phlebitis, even if suppurative, does not require any consultation provided the emergency physician is capable of performing the indicated superficial phlebectomy. Patients with widespread suppurative phlebitis or suppurative phlebitis threatening the deep venous system, however, benefit from consultation with a vascular surgeon.
- Infected central lines with an extensive fibrin sheath or with associated thrombus benefit from fibrinolysis and antibiotics prior to removal of the catheter. If the emergency physician cannot carry out this fibrinolysis, an interventional radiologist should be consulted prior to removing the catheter.
- The mortality and morbidity rates of septic phlebitis are so high that antibiotic choice and dosing always should be guided by current recommendations from an expert in infectious diseases.
Medication
To be effective, treatment of progressive septic phlebitis (at any location) must include both antibiotics and heparin.
Whenever possible, the choice of initial antibiotics should be based upon the Gram stain and the results of bacterial culture. When Gram stain is not possible, empiric therapy must take into consideration the location of the septic thrombus, the underlying etiology, and the condition of the host. No matter what the organism, extended high-dose antimicrobial therapy is recommended because of the high risk of endocarditis or of septic emboli.
Heparin is essential because infected thrombus provides a dangerous nidus for infection that is refractory to treatment with antibiotics. Heparin halts the progression of septic thrombophlebitis and eliminates an ongoing source of septic emboli.
Because heparin alone cannot dissolve existing infected clot, septic thrombophlebitis of the deep veins is an indication for local-regional treatment with fibrinolytic agents along with antibiotics and heparin. Fibrinolysis also is indicated when septic phlebitis involves a dialysis graft, when septic phlebitis is resistant to antibiotics and heparin, and when catheter-associated thrombus and fibrin sheaths cause sequestration of infection and make it resistant to treatment. Because removal of an infected indwelling catheter often causes septic emboli, fibrinolytic agents also are used before removing an infected central catheter that has an extensive fibrin sheath and thrombus associated with it.
Fibrinolytics (thrombolytics)
The goal of fibrinolytic therapy is to dissolve an infected fibrin sheath or an infected thrombus that can serve as a nidus for resistant infection and as a source of septic emboli.
Catheter-directed local infusions of fibrinolytic agents are safer than systemic fibrinolytic regimens because they use a low dose of the drug and usually do not produce a systemic lytic state. Several fibrinolytic agents currently are available for local-regional lysis of infected thrombus.
Reteplase is a second-generation recombinant tissue-type plasminogen activator that seems to work more quickly and to have a lower bleeding risk than the first-generation agent (alteplase).
Alteplase is the first-generation recombinant tissue-type plasminogen activator. It is the fibrinolytic agent most familiar to EDs and the one most often used for the treatment of coronary artery thrombosis, pulmonary embolism, and acute stroke.
Urokinase is the fibrinolytic agent most familiar to interventional radiologists and the one that has been used most often for septic phlebitis. At the time of this writing, urokinase is not available from the manufacturer. The future availability of urokinase is not known. In the meantime, the US Food and Drug Administration (FDA) has encouraged the off-label use of reteplase and alteplase for local-regional lysis of venous and arterial thrombus at any location.
Streptokinase is a less-expensive alternative that unfortunately is highly antigenic and produces a high incidence of untoward reactions. This drawback limits the usefulness of streptokinase in the clinical setting.
Reteplase (Retavase)
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
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
Not established
May increase effects of warfarin, heparin, and aspirin
Documented hypersensitivity; uncontrolled hypertension; recent intracranial surgery; arteriovenous malformation or aneurysm; bleeding diathesis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
Alteplase (Activase)
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
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
Administer as in adults
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
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
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
Anticoagulants
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.
Heparin
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
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
Administer as in adults
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity
Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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
Enoxaparin (Lovenox)
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
Thrombosis: 1 mg/kg SC q12h
Prophylaxis: 30 mg SC q12h
Pediatric
Not established; suggested dose 1.6 mg/kg SC bid if aged <2 months and 1 mg/kg/dose SC bid if >2 months
Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding
Documented hypersensitivity; major bleeding; thrombocytopenia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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
Antibiotics
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.
Penicillin G (Pfizerpen)
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
3-4 million U IV q4h
Pediatric
30,000-40,000 U/kg IV q4h
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
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function
Clindamycin (Cleocin)
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
150-300 mg IV q6h
Pediatric
2-4 mg/kg IV q6h
Severe infections: 5 mg/kg IV q6h
Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis
Metronidazole (Flagyl)
Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).
Adult
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
5-10 mg/kg IV q 8 h; not to exceed 500 mg/dose
Cimetidine may increase toxicity; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy
Chloramphenicol (Chloromycetin)
Binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Adult
12-25 mg/kg IV q6h; not to exceed 4 g/d
Pediatric
12-20 mg/kg IV q6h
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
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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)
Amphotericin B (AmBisome)
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
3 mg/kg IV qd administered over 2 h
Pediatric
Administer as in adults
Antineoplastic agents may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; cyclosporine increases risk of renal toxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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)
More on Thrombophlebitis, Septic |
| Overview: Thrombophlebitis, Septic |
| Differential Diagnoses & Workup: Thrombophlebitis, Septic |
 Treatment & Medication: Thrombophlebitis, Septic |
| Follow-up: Thrombophlebitis, Septic |
| References |
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Further Reading
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, Lemierre syndrome
