Trimethoprim-sulfamethoxazole-induced hyponatremia in an elderly lady with Achromobacter xylosoxidans pneumonia

Abstract

Rationale: Hyponatremia occurs frequently in the hospital setting and may be attributable to a host of etiologies. Drugs are frequently implicated. Trimethoprim-sulfamethoxazole (TMP/SMX) represents a well-recognized pharmacologic precipitant of drug-induced hyponatremia, with several reports extant in the retrievable literature. Nephrologists thus debate the mechanisms giving rise to TMP/SMX-induced hyponatremia and the precise mechanism by which treatment with TMP/SMX generates reductions of serum sodium concentration remain controversial. The agent has a well-known effect of antagonizing the effects of aldosterone upon the distal nephron. Renal salt wasting and the syndrome of inappropriate antidiuretic hormone secretion represent implicated mechanistic intermediaries in TMP/SMX-induced hyponatremia. Patient concerns: The patient endorsed no explicit concerns. Diagnoses: We describe the case of an 83-year-old female clinically diagnosed with pneumonia found to have an initial serum sodium in the range of 130 to 134 mEq/L consistent with mild hyponatremia upon admission. Sputum cultures grew Achromobacter xylosoxidans susceptible to TMP/SMX. The patient's serum sodium concentration precipitously decline following institution of treatment with TMP/SMX to 112 to 114 mEq/L during the course of 5 days. Interventions: Severe hyponatremia proved recalcitrant to initial therapy with supplemental salt tabs and standard doses of the vasopressin receptor antagonist tolvaptan. Outcomes: Escalating doses of tolvaptan increased the patient's sodium to 120 to 124 mEq/L. The patient was transferred to another hospital for further management. During her stay, the patient did not exhibit frank or obvious clinical features consistent with hyponatremia nor readily appreciable evidence of volume depletion. Lessons: TMP/SMX represents a frequent, though underreported cause of hyponatremia in the hospital setting several authors believe natriuresis may represent the most common mechanism underlying TMP/SMX-induced hyponatremia. Evidence implicating natriuresis to be mechanistic in TMP/SMX-induced hyponatremia include clinically appreciable hypovolemia and resolution of hyponatremia with oral or intravenous salt repletion. Salt repletion failed to monotherapeutically enhance our patient's hyponatremiadisfavoring renal salt wasting as originately mechanistic. Contemporaneous refractoriness of serum sodium to fluid restriction nor standard doses of tolvaptan confounded our initial attempts to mechanistically attribute the patient's hyponatremia to a specific cause. Clinical euvolemia and rapid response of hyponatremia to exceptionally high doses of tolvaptan strongly favors syndrome of inappropriate antidiuretic hormone to represent the chief mechanism by which TMP/SMX exacerbates hyponatremia.

Severe hyponatremia due to trimethoprim-sulfamethoxazole-induced SIADH

“… 2 – 6 Some, maybe a couple, of the reported cases cited SIADH as the cause of hyponatremia; these patients received much lower doses of oral TMP-SMX. 6 – 8 Based on the previously published studies, we speculate that higher IV and oral doses of TMP-SMX may cause natriuresis more frequently than lower oral doses and vice versa. Our patient received a lower dose of TMP-SMX (160/800), 1 tablet twice daily for 3 days.…”

“…5 SIADH is more likely to occur with lower doses of oral TMP-SMX (once or twice daily dosing) than with the higher doses typically used for treating pneumocystis jiroveci pneumonia (PJP). 6 , 7 Dilutional hyponatremia may also occur with high doses of IV TMP-SMX. In cases of moderate to severe PJP pneumonia, the recommended dose of TMP is 15–20 mg/kg/day for 21 days.…”

Analysis of the Clinical Characteristics of Hyponatremia Induced by Trimethoprim/Sulfamethoxazole

“…We identified and screened 1,276 studies using the search strategy described in the Methods section. After careful review by 2 independent authors, only 21 studies were included according to the inclusion and exclusion criteria (Table 1 ) [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. The basic information of 24 patients (10 male and 14 female) is summarized in Table 2 .…”

“…The effectiveness and safety of vasopressin receptor antagonists in treating symptomatic or acute hyponatremia are not yet well established. However, a few studies have proven that a massive dose of tolvaptan (30 mg) can effectively treat hyponatremia caused by TMP/SMX in patients who are refractory to salt tablets and fluid restriction [ 10 ]. Our study found that the serum sodium concentration returned to the normal range approximately 4 days after stopping TMP/SMX.…”

Achromobacter xylosoxidans as emerging pathogen in healthcare settings: A mini review

“…Ocular-, pulmonary-, and cardio-related comorbidities were found in multiple cases [6,[15][16][17]29]. Interestingly, hyponatraemia was among the associated comorbidity [30]. The origin of the samples used for diagnosis varied across the studies, such as sputum [30], ear and/or lung swabs [15,22], lung tissue [15,29], and wounds [24].…”