4. Abramson JS, Givner LB. Bacterial resistance due to antimicrobial drugaddiction among physicians. Arch Fam Med 1999;8:79-80.

5. Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media: manage-ment and surveillance in an era of pneumococcal resistance—a reportfrom the Drug-resistant Streptococcus pneumoniae Therapeutic WorkingGroup. Pediatr Infect Dis J 1999;18:1-9.

Rifampin-Related Acute Renal Failure, Thrombocytopenia, andLeukocytoclastic Vasculitis

TO THE EDITOR: Rifampin is a first-line drug in the treatment of My-cobacterium kansasii. Acute renal failure and thrombocytopenia due torifampin have been reported sporadically,1,2 and a case presenting with askin lesion suggestive of vasculitis has been described.3 This is the firstcase in which rifampin administration was followed by these 3 adversereactions concurrently in the same patient, with histological confirmationof a vasculitic lesion.

Case Report. A 76-year-old man with a past history of stable anginapectoris treated with aspirin was transferred to our hospital with a one-week history of fever, dry cough, dyspnea, oliguria, and bilateral edemain lower extremities. Two months earlier the patient had been diagnosedwith M. kansasii pulmonary disease and was treated with a combinedpreparation of isoniazid 50 mg, rifampin 120 mg, and pyrazinamide 300mg (Rifater). He was taking 5 tablets daily (total daily dose: isoniazid250 mg, rifampin 600 mg, pyrazinamide 1500 mg). At that time, labora-tory parameters included hemoglobin 15.3 g/dL, white blood cell(WBC) count 7540/µL, platelets 232 × 103/µL, serum creatinine 1.1mg/dL, and urea 56 mg/dL.

On the patient’s admission, laboratory data showed acute renal failure(serum creatinine 9.6 mg/dL, urea 168 mg/dL) and thrombocytopenia(platelets 85 × 103/µL). Other results were WBC count 13,300/µL, he-

moglobin 13.9 g/dL, and proteinuria, with urine protein 1.5 g/L. Liverenzymes (aspartate aminotransferase and alanine aminotransferase) andcoagulation parameters were within reference ranges. Renal ultrasoundand Doppler studies did not show any obstructive or vascular cause toexplain the acute renal failure. An extensive diagnostic workup yieldedno positive results; therefore, an adverse drug reaction was suspected.Rifater was withdrawn and broad-spectrum antimicrobials (linezolid,piperacillin/tazobactam, ethambutol, levofloxacin) were introduced.

Two weeks after Rifater was discontinued, clinical and analytic pa-rameters normalized. With the goal of treating M. kansasii with at least 2first-line drugs, a controlled trial of rifampin at increasing doses (80 mgthe first day, 150 mg the second day, 200 mg the third day) was attempt-ed a week later. The day following reintroduction, a palpable purpura ap-peared, serum creatinine increased (1.9 mg/dL), and the platelet countdropped (Figure 1). Rifampin was withdrawn on the fourth day; 4 dayslater, the serum creatinine level returned to within normal limits and skinpurpura disappeared. Skin purpura biopsy demonstrated leukocytoclasticvasculitis. Two weeks later, the patient was discharged with normal renalfunction and platelet count.

Discussion. The few previously reported cases of acute renal failuredue to rifampin have most frequently been associated with intermittentor interrupted treatment.1,2 The deterioration in renal function typicallyappears acutely after reintroduction of rifampin. However, a few caseshave described this adverse reaction as developing with continuous ad-ministration of the drug.1,2 Rifampin was not reintroduced in any of thesecases; therefore, causal relationship is difficult to establish.

Rifampin-induced renal failure is mediated by mechanisms of hyper-sensitivity type II or, less frequently, type III. It is hypothesized that anti-rifampin antibodies bind to the I antigen present on the cellular surfaceof adult erythrocytes, platelets, and renal tubular epithelium. This bind-ing then induces cellular destruction.4,5 Other mechanisms have been de-scribed as causes of thrombocytopenia, such as the development of anti-bodies to the glycoprotein Ib-IX complex on the platelet surface.

The Annals of Pharmacotherapy n 2008 May, Volume 42 n 727www.theannals.com

Figure 1. Time course showing changes in serum creatinine and platelets during rifampin therapy.

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This is, to the best of our knowledge, the first reported case of histo-logically confirmed rifampin-induced leukocytoclastic vasculitis. Iredaleet al.3 reported on a patient with a skin lesion suggestive of vasculitis, butthere was no histological confirmation.

Use of the Naranjo probability scale indicated a probable relationshipbetween rifampin and acute renal failure, thrombocytopenia, and leuko-cytoclastic vasculitis.6 This case has been reported to the Spanish HealthAuthorities (number 07-121).

Miriam Estébanez Muñoz MDClinical SpecialistInternal Medicine ServiceUniversity Hospital of La PazPaseo de la Castellana, 261 28046 Madrid, Spainfax 34-913148011a.borobia@gmail.com

Pilar Ruiz MDClinical SpecialistInternal Medicine ServiceUniversity Hospital of La Paz

Alberto M Borobia MD Clinical SpecialistClinical Pharmacology Service, Pharmacology DepartmentUniversity Hospital of La PazSchool of MedicineAutonomous University of MadridMadrid

Bárbara Pagán MDClinical SpecialistInternal Medicine ServiceUniversity Hospital of La Paz

Jose R Pano-Pardo MD PhDClinical SpecialistInternal Medicine ServiceUniversity Hospital of La Paz

Jorge Gómez Cerezo MD PhDClinical Specialist, ProfessorInternal Medicine ServiceUniversity Hospital of La Paz

We gratefully thank E Ramirez Garcia MD PhD and AJ Carcas Sansuan MD PhD,clinical pharmacologists of University Hospital of La Paz, for their comments andsuggestions on the manuscript.

Published Online, 15 Apr 2008, www.theannals.comDOI 10.1345/aph.1K634

REFERENCES

1. Covic A, Goldsmith DJ, Segall L, et al. Rifampicin-induced acute renalfailure: a series of 60 patients. Nephrol Dial Transplant 1998;13:924-9.

2. Muthukumar T, Jayakumar M, Fernando EM, Muthusethupathi MA.Acute renal failure due to rifampicin: a study of 25 patients. Am J Kid-ney Dis 2002;40:690-6.

3. Iredale JP, Sankaran R, Wathen CG. Cutaneous vasculitis associated withrifampin therapy. Chest 1989;96:215-6.

4. Burgess JK, Lopez JA, Gaudry LE, Chong BH. Rifampicin-dependentantibodies bind a similar or identical epitope to glycoprotein IX–specificquinine-dependent antibodies. Blood 2000;95:1988-92.

5. Fenniche S, Maalej S, Fekih L, Hassene H, Belhabib D, Megdiche ML.[Manifestations of rifampicin-induced hypersensitivity] French. PresseMed 2003;32:1167-9.

6. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating theprobability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.

Pharmacist-Administered Admission Histories: Focus onImmunizations in Medication Reconciliation

TO THE EDITOR: Several national programs provide guidelines andgoals for both medication reconciliation and immunizations.1-4 The JointCommission on Accreditation of Healthcare Organizations has recog-nized medication reconciliation as a national patient safety goal since2004.1 Specifically, Goal 8 is to “accurately and completely reconcilemedications across the continuum of care.” The Institute for HealthcareImprovement also supports medication reconciliation, defining it as “cre-ating the most accurate list possible of all medications a patient is tak-ing—including drug name, dosage, frequency, and route—and compar-ing that list against the physician’s admission, transfer, and/or dischargeorders with the goal of providing correct medications to the patient at alltransition points within the hospital.”2 Immunizations can also become apart of the medication reconciliation process. The Healthy People 2010objectives strive for a pneumococcal and influenza vaccination rate of90% for patients 65 years of age and older.4 These programs illustrate aneed to develop medication reconciliation programs that improve immu-nization rates.

Pharmacists can help in achieving these national goals, since they ob-tain medication histories that are often more complete than those ob-tained by physicians or nurses.5,6 The purpose of this study was todemonstrate how pharmacists can (1) perform admission histories to im-prove patient care during hospitalization and (2) improve immunizationrates during medication reconciliation.

Methods. The study was conducted at a community teaching hospital,approved by the institutional review board, and piloted over a 7-day pe-riod on the short-stay unit. Patients 18 years of age and older were eligi-ble. Those with mental status changes were excluded. Upon a patient’sadmission, a nurse or medical resident obtained the admission history.Within 24 hours, a pharmacist reinterviewed the patient for approximate-ly 10 minutes. The pharmacist inquired about admission medications, al-lergies and reactions, adherence, outpatient pharmacies, social history,medication management, medication assistance needs, and vaccinationhistory.

Results. Eleven males (average age 61 y) and 24 females (averageage 59 y) were interviewed. Prior to admission, each patient took an av-erage of 5 medications. The most common interventions are listed inTable 1. Vaccinations were recommended for 13 of 35 patients. The in-fluenza and pneumococcal vaccination was recommended in 7 (20%)and 6 patients (17%), respectively.

Pharmacists contribute a vital role by developing medication reconcil-iation programs. The number of interventions was limited since manypatients were ineligible. The primary difficulty was that patients did notknow the names or have a list of their medications, resulting in increasedtime spent by the pharmacists in retrieving this information. Languagebarriers and translating services also increased wait time for the pharma-cist; however, opportunities for patient education were ample. Anotherbarrier was inadequate pharmacist staffing. Immunization history barri-ers included patient recall. Possible solutions include incorporating vac-

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Table 1. Admission Medication Reconciliation Interventionsa

NumberType of Intervention (%)

Restarting home medication 44 (58)Recommending a vaccine 13 (17)Documenting corrections of allergy or reaction, 11 (15)including correcting names of drugs

Counseling on adherence 4 (5)Documenting corrections of social history 3 (4)Providing medication assistance or associated referrals 1 (1)

aN = 76 pts.

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