Septic Thrombophlebitis Medication

The fibrinolytics reteplase and alteplase are used 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.

Anticoagulation with some form of heparin, although essential in patients with septic phlebitis, does not by itself insure a successful patient outcome. The disease may progress despite full and effective heparin anticoagulation.

Antibiotics are chosen based on blood culture results or on Gram stain and culture of material taken from the suppurative vessel or from a metastatic septic focus. Broad-spectrum antibiotics to cover S aureus, streptococci, and Enterobacteriaceae should be administered if suppuration or infection is noted. Polymicrobial infections are particularly common in burn patients.

Anaerobic infection coverage requires particular attention in patients with Lemierre syndrome (often caused by F necrophorum), whereas intra-abdominal septic thrombosis requires coverage of gram-negative organisms and anaerobes.

Because many infections are caused by S aureus, coverage of MRSA should be seriously considered, depending on local resistance patterns.

Class Summary

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 does 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)

Reteplase is a second-generation recombinant tissue-type plasminogen activator. As a fibrinolytic agent, it seems to work faster than its forerunner, alteplase, and also may be more effective in patients with larger clot burden. In addition, reteplase has been reported to be more effective than other agents in the lysis of older clots. In patients being treated for peripheral vascular disease, reteplase has been reported to cause fewer bleeding complications than alteplase.

Contrast venography is used to guide the duration and intensity of therapy. For local lysis of arterial thrombosis (with or without associated infection), the suggested dose is lower (0.5U/h infusion).

Alteplase (Activase)

Alteplase was the first recombinant tissue plasminogen activator to be released for clinical use; it is the agent with which EDs are most familiar.

Although alteplase is best known as a fibrinolytic agent used for coronary artery occlusion and pulmonary embolism, it is also widely used for catheter-directed lysis of deep venous thrombosis, for dissolution of catheter-related thrombus, and for reopening of occluded central lines and thrombosed dialysis grafts. Contrast venography is used to guide the duration and intensity of therapy.

Class Summary

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 clots.

When low-molecular-weight heparin (LMWH) is used, checking the activated partial thromboplastin time (aPTT) has no utility, because the aPTT does not correlate with the therapeutic effect or the 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 intravenously 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

The initial bolus used for patients with inflammatory and septic thrombosis is lower than that needed for spontaneous deep venous thrombosis and pulmonary embolism. This is because most patients with inflammatory or septic thrombophlebitis do not have underlying hypercoagulability. Patients with deep venous thrombosis or pulmonary embolism require more aggressive therapy because deep venous thrombosis is a manifestation of an active hypercoagulable state.

Do not check the aPTT until 6 hours after the initial bolus of unfractionated heparin, as an extremely high or low value during this time should not provoke any action.

Enoxaparin (Lovenox)

Enoxaparin was the first LMWH released in United States. It is the only LMWH now approved by the FDA for both the treatment and the prophylaxis of deep venous thrombosis. Enoxaparin is widely used in pregnancy, although clinical trials are not yet available to demonstrate that it is as safe as unfractionated heparin. There is no utility in checking the aPTT; enoxaparin has a wide therapeutic window and the aPTT does not correlate with the anticoagulant effect.

Class Summary

The choice of antibiotic depends on the results of blood cultures or Gram stain and the 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 (which is often due to F necrophorum). Candidal phlebitis is treated with amphotericin B.

Penicillin G (Pfizerpen)

Penicillin G interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Aqueous penicillin G is the first choice for treatment of susceptible infections because of its rapid onset of action.

Penicillin G is useful in infections of the head and neck due to Streptococcus, Clostridium, Actinomycosis, Listeria, Erysipelothrix, and Pasteurella species, as well as in fusospirochetal infections.

Clindamycin (Cleocin)

Clindamycin is a lincosamide used for the treatment of serious skin and soft-tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). Clindamycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.

Piperacillin and tazobactam sodium (Zosyn)

This is an antipseudomonal penicillin plus a beta-lactamase inhibitor. It inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.

Vancomycin

Vancomycin is used in prophylaxis. It is a potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Vancomycin is useful in the treatment of septicemia and skin-structure infections. It is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes.

To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose, drawn 0.5 hour prior to the next dosing. Use creatinine clearance to adjust the dose in patients diagnosed with renal impairment.

Vancomycin is used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents (except Clostridium difficile enterocolitis).

Chloramphenicol

Chloramphenicol binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria.

Amphotericin B liposomal (AmBisome)

Amphotericin B, which is produced by a strain of Streptomyces nodosus, can be fungistatic or fungicidal (effective against candidal phlebitis). It binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.