JAC Advance Access originally published online on April 3, 2008
Journal of Antimicrobial Chemotherapy 2008 61(6):1396-1398; doi:10.1093/jac/dkn117
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Research letters |
Severe hypokalaemia caused by flucloxacillin
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
* Corresponding author. Tel: +31-10-4635335; Fax: +31-10-4633008; E-mail: ejhoorn{at}gmail.com
Keywords: aldosterone , collecting duct , kaliuresis , solute diuresis , spironolactone , spondylodiscitis
Hypokalaemia has been reported during treatment with penicillin G and broad-spectrum penicillins.1 We report, to our knowledge for the first time, a case of severe hypokalaemia during treatment with yet another penicillin, namely sodium flucloxacillin (floxacillin). Our aim was to illustrate that hypokalaemia is a class-effect of penicillins, to reiterate the importance of penicillin-induced hypokalaemia and to further investigate its mechanism and potential treatment.
A 67-year-old woman (height 165 cm and weight 45 kg) was treated with flucloxacillin (2 g six times daily) for spondylodiscitis during two admissions. Spondylodiscitis had developed after an elective colectomy for diverticulosis, which was complicated by an abscess in the rectouterine pouch and Staphylococcus aureus bacteraemia.
During both admissions, hypokalaemia developed after flucloxacillin was started (after 3 and 2 days, respectively) and resolved after it was stopped. Hypokalaemia was caused by renal potassium loss (Table 1). Other causes of renal potassium loss were absent, including diuretics, hypomagnesaemia, ketonuria, bicarbonaturia, renal tubular acidosis (no acid–base disorder) and, finally, hyperaldosteronism (low-normal renin and aldosterone levels, Table 1). Moreover, dietary potassium intake was normal and no causes of a shift of potassium into the cell (e.g. alkalosis or insulin) or its loss from the gastrointestinal tract (e.g. diarrhoea or laxatives) were present.
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Penicillin-induced hypokalaemia is thought to develop because a penicillin derivative acts as a non-reabsorbable anion, resulting in more sodium reabsorption in exchange for potassium.2 This effect is believed to be mediated by volume depletion,3 because this will increase aldosterone and decrease distal chloride delivery, thereby maintaining a lumen-negative gradient.4 In fact, a low urinary chloride concentration is considered a diagnostic feature of hypokalaemia due to a non-reabsorbable anion.5
Surprisingly, the findings in our case contradicted the above. First, serum renin and aldosterone levels were low-normal and urinary chloride levels were high, both arguing against volume depletion (Table 1). However, aldosterone levels may have been higher early on and should also be interpreted in the context of hypokalaemia, which reduces aldosterone secretion. Secondly, treatment with intravenous fluids (2 L of 0.9% NaCl) and a 15 day trial of spironolactone (25 mg once daily) failed to prevent hypokalaemia, nor did it reduce kaliuresis. Triamterene (50 mg once daily), which was tried for 2 days, was also unable to decrease the renal potassium loss.
This calls into question the mechanism of penicillin-induced hypokalaemia. Given the large amounts of sodium administered with penicillin and intravenous fluids (6 x 2 + 2 x 9 = 30 g or 517 mmol), an alternative explanation could be the occurrence of a solute diuresis. A solute diuresis causes a high flow rate in the cortical collecting duct and subsequent potassium excretion,6 probably via the so-called BK channels.7 A number of additional observations support the presence of a solute diuresis: the majority of osmoles being sodium and potassium, the magnitude of their fractional excretions and the presence of polyuria (Table 1).8 We emphasize that a solute diuresis does not exclude a role for a non-reabsorbable anion. In fact, both mechanisms may act synergistically, because both can increase distal sodium delivery and therefore promote kaliuresis.
In summary, our case illustrates the class-effect of penicillins to cause hypokalaemia and its development in the absence of volume depletion, hyperaldosteronism and low distal chloride delivery. It also illustrates that low body mass index patients receiving high-dose penicillin therapy are at risk for developing severe hypokalaemia. The ineffectiveness of probenecid (reported in Mittal et al.9), volume repletion and potassium-sparing diuretics (reported here) suggest an obligatory renal potassium loss that may exceed roughly 100 mmol/L. Thus, the mainstay of treatment remains aggressive potassium supplementation, for which special measures (potassium infusion pump, central venous catheter, intra-arterial line for monitoring) may be required.
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This study was funded internally by the Erasmus Medical Center.
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TopFundingTransparency declarationsReferences |
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None to declare.
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1 Brunner FP, Frick PG. Hypokalaemia, metabolic alkalosis, and hypernatraemia due to ‘massive’ sodium penicillin therapy. BMJ (1968) 4:550–2.
2 Lipner HI, Ruzany F, Dasgupta M, et al. The behavior of carbenicillin as a nonreabsorbable anion. J Lab Clin Med (1975) 86:183–94.[Web of Science][Medline]
3 Nanji AA, Lindsay J. Ticarcillin associated hypokalemia. Clin Biochem (1982) 15:118–9.[CrossRef][Web of Science][Medline]
4 Carlisle EJ, Donnelly SM, Ethier JH, et al. Modulation of the secretion of potassium by accompanying anions in humans. Kidney Int (1991) 39:1206–12.[Web of Science][Medline]
5 Sterns RH, Palmer BF. Fluid electrolyte acid–base disturbances. NephSAP (2007) 6:199–280.
6 Halperin ML, Kamel KS. Potassium. Lancet (1998) 352:135–40.[Web of Science][Medline]
7 Grimm PR, Sansom SC. BK channels in the kidney. Curr Opin Nephrol Hypertens (2007) 16:430–6.[CrossRef][Web of Science][Medline]
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Oster JR, Singer I, Thatte L, et al. The polyuria of solute diuresis. Arch Intern Med (1997) 157:721–9.
9 Mittal VK, Pierce AK, Priestley JC. Use of probenecid in ticarcillin-induced hypokalemia. Clin Ther (1980) 3:125–8.[Web of Science][Medline]
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