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LWW-EMN_AUG-09-0701-Jang's Pearls-PNK:. 18/07/09 7:46 PM Page 1 Exclusively for EM-News.com: August 2009
By Timothy Jang, MD, &
Daniel K. Hoh, MD
Case:
A 65-year-old woman with anticardi-
olipin syndrome and a previous DVT presents with fever and She is on lifelong warfarin, and denies any other symptoms.
Her vital signs are normal with the exception of a fever of Questions:
1. How does warfarin work?
2. Assume the patient had three days of cough, crackles on careful with antibiotics in these patients.
pulmonary exam, and a chest x-ray demonstrating a right- Our first scenario highlights community-acquired pneu- sided infiltrate. Which antibiotics should be used? monia therapy. Quinolones are often used for single-agent 3. Assume the patient had two days of fever, urinary fre- coverage, but they are significant p450 inhibitors. In partic- quency, urgency, and dysuria. Urinalysis reveals leuko- ular, levofloxacin is associated with a high rate of suprather- cytes and nitrites. Which antibiotics should be used? apeutic INR. Macrolides, especially erythromycin, also 4. Assume the patient had a 2ϫ2 cm follicular abscess on her inhibit p450. Pneumococcal resistance rates now favor azithromycin, which appears to have less effect on INR.
5. Are there any other important antibiotic considerations Aminopenicillins and cephalosporins have only mild effects on anticoagulation so amoxicillin/clavulanate or a second- or third-generation cephalosporin could be a reasonable Discussion:
choice, according to some guidelines.
Warfarin decreases the hepatic synthesis of vitamin K-depen- Our second scenario focuses on therapy for urinary tract dent clotting factors (II, VII, IX, and X) and proteins C and S.
infections and pyelonephritis. As previously stated, quinolones It is metabolized by the hepatic p450 system, has a relatively such as levofloxacin and ciprofloxacin are notorious p450 long half-life, and requires several days for equilibration.
inhibitors, and should be avoided. Some physicians still use There are many guidelines for maintaining safe and effective trimethoprim/sulfamethoxazole for UTI, but it should be avoid- anticoagulation with warfarin for atrial fibrillation, DVT, pul- ed because it strongly inhibits p450 and is commonly implicat- monary embolism, and other diseases.
ed in cases of supratherapeutic INR. For this patient, I suggest Systemic anticoagulation confers significant morbidity, a cephalosporin or nitrofurantoin, the latter of which has not from ecchymosis and epistaxis to intracranial bleeds and been shown to disturb warfarin therapy. I would probably give retroperitoneal hematomas. Every 0.5 increase in the INR a dose of IV ceftriaxone in the ED, and discharge her with doubles the risk of intracranial hemorrhage. It is important to remember the potential drug interactions between war- Our final scenario focuses on MRSA skin and soft tissue farin and other therapies we provide. This is especially true infections. If the abscess is small and there is only minimal cel- for the elderly and those with prior stroke or multiple lulitis, several options exist. The abscess can be treated with incision and drainage, close follow-up, good hygiene, and no Drugs that inhibit the p450 system will increase the antico- antibiotics. This is appropriate for most abscesses, but be agulation effect of warfarin and vice versa. Patients taking mindful of increased bleeding from anticoagulation. A second antibiotics while on warfarin are six times more likely to devel- approach is to treat only with antibiotics, close follow-up, and op an INR above 7.0 and associated morbidity. We must be good hygiene. Many abscesses under 2 cm will resolve with LWW-EMN_AUG-09-0701-Jang's Pearls-PNK:. 18/07/09 7:46 PM Page 2 Exclusively for EM-News.com: August 2009
this approach, but may expose the patient to alterations in anti- ■ Extended pencillins, such as nafcillin and oxacillin, are
coagulation. A final option is to incise and drain the abscess, known to significantly increase the INR, and should be and then discharge with antibiotics for the mild cellulitis. This patient will be exposed to both bleeding risk and potential INR ■ Metronidazole is a strong inhibitor of p450, and should be
avoided in patients on warfarin as much as possible. If you If antibiotics are necessary for cellulitis, then TMP/SMX are worried about changes in gut flora when using the should be avoided, as stated above. Our preference is to use ciprofloxacin/metronidazole combination, consider an alter- clindamycin (IV in the ED and oral as an outpatient) native like clindamycin/ceftriaxone. If you are worried because there has only been one case report of clin- about C. difficile, use oral alternatives to metronidazole.
damycin-related change in anticoagulation. In areas with ■ Vancomycin does not have a significant effect on INR.
higher rates of clindamycin resistance, I would give a dose It can be used for admitted patients with MRSA, resis- of IV vancomycin (minimal effect on the INR), and dis- tant pneumococcus, and health care facility-related charge with doxycycline. While tetracycline has a notable effect on warfarin meta bolism, there is less evidence impli- Dr. Jang is an assistant professor of medicine at the David Some other important antibiotic considerations: Geffen School of Medicine at UCLA and the director of the ■ Gentamicin has not been shown to significantly alter the
emergency ultrasound at Harbor-UCLA Medical Center, in INR in patients on warfarin. It can be used for pyelonephri- Sylmar. Dr. Hoh is an emergency physician at Cedars-Sinai tis, complicated UTI, and sepsis in these patients.

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