Debbie Qua, M. Tan
Mar 1, 2009
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Infectious Diseases in Clinical Practice
Abstract
Nafcillin is a semisynthetic penicillin extensively used for treatment of infections caused by penicillinase-producing staphylococci. It has been known to cause adverse reactions such as hypersensitivity reactions, rash, and phlebitis. However, there are only a few reports that describe nafcillin as a possible cause of hypokalemia (JAMA. 1979; 242:544, J Pediatr. 1980; 97:841Y842). It is thought to be largely due to nafcillin acting as an impermeant, nonreabsorbable anion, increasing potassium excretion. This report describes a patient treated with nafcillin for methicillin-susceptible Staphylococcus aureus psoas abscess who developed hypokalemia with apparent renal potassium wasting. (Infect Dis Clin Pract 2009;17: 130Y131) REPORT OF THE CASE A 58-year-old female with no known prior illness presented with a 1-week history of low back pain radiating to both knees. Computerized tomography scan of the abdomen revealed right psoas abscess; subsequent drainage of the abscess grew methicillinsensitive Staphylococcus aureus. She was given nafcillin 2 g intravenously every 4 hours and rifampin 300 mg orally every 12 hours. The baseline potassium level before treatment was 3.6 to 3.8 mEq/L. No follow-up panel was obtained during admission, and the patient was sent home on the above medications. On outpatient follow-up 2 days after discharge, the patient reported generalizedweakness; potassium levelwas found to be 1.8mEq/L, with a bicarbonate level of 32 mEq/L. Patient denied vomiting, diarrhea, or change in diet. Creatinine was 0.6 to 0.8 mg/dL. She was subsequently readmitted, and rifampin was discontinued. Renin, cortisol, and thyrotropin levels were normal. Shewas given a total of 300 mEq potassium supplement over the next 2 days; however, potassium level remained low at 2.2 to 2.7 mEq/L. On day 3, potassium supplements were given with maintenance intravenous fluids, and serum potassium level was noted to return to baseline at 3.5 mEq/L. Nafcillin was switched to ertapenem 1 g daily. After the switch, potassium level remained within normal limits (3.9 mEq/L) even without potassium supplementation. Bicarbonate level was also noted to return to normal at this time. Potassium levels through 2 weeks’ follow-up remained normal at 3.9 to 4.6 mEq/L (creatinine 0.6Y0.8 mg/dL). DISCUSSION Nafcillin is a semisynthetic penicillin extensively used as the drug of choice in the treatment of infections caused by penicillinase-producing staphylococci. These include conditions such as endocarditis, catheter-related infections, and complicated soft tissue infections. In a study done from 1990 to 1994, a total of 2488 courses of anti-infective therapy in patients of a home infusion company were documented. Nafcillin and oxacillin accounted for 105 courses, with an adverse drug reaction rate of 31.4%; 99 patients received 1 of these 2 drugs, and 24 had adverse drug reactions, with rash and phlebitis noted to be the most common. Other known side effects include local swelling and inflammation, superinfection, fever, nausea, diarrhea, pseudomembranous colitis, agranulocytosis, bone marrow suppression, neutropenia, skin sloughing, anaphylactoid/hypersensitivity reactions, and acute interstitial nephritis. Our patient was noted to be hypokalemic a few days after she was given nafcillin at 135 mg/kg/d, with resolution of hypokalemia after discontinuation of the drug. There are limited data on nafcillin causing hypokalemia. However, there has been a case report of nafcillin-associated hypokalemia in an adult receiving 200 mg/kg/d of the antibiotic. Decreasing the dose to 100 mg/kg/d was associated with correction of the potassium wasting. This is thought to be due to the drug acting as a nonreabsorbable anion. The negative electrical gradient created by sodium reabsorption in the lumen of the cortical collecting tubule is partially attenuated by chloride reabsorption. In the case of high-dose nafcillin therapy, sodium is presented to the distal nephron with relatively large quantities of a nonreabsorbable anion (nafcillin). Sodium will be reabsorbed in exchange for potassium, leading to a potentially marked increase in potassium excretion. Similarly, in a rat study by Lipner et al, carbenicillin was found to act as an impermeant anion, prompting diuresis and resultant increase in urinary potassium level and ammonium excretion. As with nafcillin, the effect of such anions is thought to increase the distal luminal transtubular electronegativity, increasing the electrical force for passive movement of potassium and hydrogen ions across the epithelium into the lumen. In light of this, our patient was noted to have renal potassium wasting with a urine potassium level of 42 mEq. A healthy subject can, in the presence of potassium depletion, lower urinary potassium excretion level less than 25 to 30 mEq/d. Similar renal potassium wasting was observed in a pediatric case report done in 1980 after the patient received 300 mg/kg/d of nafcillin. Two days after decreasing the dose to 150 mg/kg/d, the hypokalemic alkalosis resolved. In a study done among pediatric patients with malignant neoplasms and treated with the antibiotic combination of carbenicillin, gentamicin, and methicillin or nafcillin, 23 of 35 courses were associated with hypokalemia. Hypokalemia was usually discovered within 4 days after initiation of antibiotics. In most cases, normal potassium levels could not be attained before discontinuing antibiotics despite large amounts of potassium given intravenously. It was likewise noted that serum bicarbonate levels were increased in most patients when hypokalemia developed. As in the studies mentioned earlier, this is thought to be secondary to the impermeant anion effect of the antibiotic on the renal tubule. These are all consistent with the findings in our patient. Other possible causes of hypokalemia would also have to be investigated. Aside from nonreabsorbable anions, increased urinary losses of potassium may also be caused by other medications (ie, diuretics, amphotericin, and ibuprofen), to which our patient was not exposed. Similarly, mineralocorticoid excess CASE REPORT 130 Infectious Diseases in Clinical Practice & Volume 17, Number 2, March 2009 From the Department of Internal Medicine, Summa Health System, Akron, OH. Reprints: Debbie Anne C. Qua, MD, Department of Internal Medicine, Summa Health System, 55 Arch Street, Suite 1A, Akron, OH 44304. E-mail: debs.qua@gmail.com. Copyright * 2009 by Lippincott Williams & Wilkins ISSN: 1056-9103 9 Copyright @ 200 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. and metabolic acidosis (renal tubular acidosis) can cause hypokalemia. These factors are not seen in our patient given that renin and cortisol levels were normal and that her bicarbonate level was a little increased during her hypokalemic episodes. Salt-wasting nephropathies (Bartter, Gitelman, and tubulointerstitial diseases such as interstitial nephritis from Sjogren or systemic lupus erythematosus) likewise warrant consideration in hypokalemia. However, our patient was normokalemic at baseline and with noted return to normal potassium levels after withdrawal of nafcillin. Other known causes of hypokalemia include decreased potassium intake, increased entry into cells (with use of insulin, albuterol, or heroin exposure), increased losses through gastrointestinal loss or sweat, and history of hypokalemic periodic paralysis. None of these were present in our patient. A study by Cheng and Kahn linked potassium wasting to rifampin-associated interstitial nephritis. However, our patient did not exhibit fever or eosinophilia; her urine did not reveal white cells, red cells, or eosinophils; and her creatinine remained stable. Although interstitial nephritis cannot be totally ruled out without biopsy, it is less likely in this case. In summary, nafcillin is the likely cause of hypokalemia in our patient given that the patient was normokalemic at baseline, had no other significant contributing factors leading to hypokalemia, and had resolution of her hypokalemia after discontinuation of nafcillin. Despite large amounts of potassium replacement, the patient remained hypokalemic during the first 2 days; the patient was still receiving potassium supplements on day 3 even when the potassium level became normal. Arguably, the normal potassium level might merely have reflected the large amount of potassium the patient was receiving intravenously despite renal potassium wasting caused by nafcillin. However, the potassium normalized after the antibiotic switch. This transient hypokalemia likely points to an acute and reversible cause, and the most viable explanation is nafcillin-associated hypokalemia. REFERENCES 1. Drug Lib. Nafcillin (nafcillin sodium)Vsummary. Available at: http:// www.druglib.com/druginfo/nafcillin. Accessed February 24, 2008. 2. Ramsdale DR, Turner-Stokes L. Prophylaxis and treatment of infective endocarditis in adults: a concise guide. Clin Med. 2004;4: 545Y550. 3. Dahlgren AF. Adverse drug reactions in home care patients receiving nafcillin or oxacillin. 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