How To Rationally Use Antibiotics in Dialysis Patients

Hemodialysis patients are at higher risk of arrhythmias and sudden cardiac death (SCD), accounting for about 35% of all-cause deaths. Electrolyte disturbance, especially disturbance of potassium ion metabolism is a key risk factor leading to cardiovascular events.

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For dialysis patients, there are two reasons for the disturbance of potassium ion metabolism:

① Potassium ions in the patient's blood will be removed immediately during dialysis, resulting in significant differences in potassium ion levels before and after dialysis, which may lead to cardiovascular events.

②Drugs such as azithromycin and fluoroquinolone antibiotics can cause prolongation of the QT interval. Studies have suggested that QT prolongation is closely related to SCD, so many scholars believe that hemodialysis patients should avoid using the above antibiotics.

This year, the May issue of Kidney Medicine published a study from the United States. The study shows that hemodialysis patients can use azithromycin and fluoroquinolone antibiotics, but the dialysis prescription needs to be adjusted, and the patient's serum potassium and ECG should be monitored regularly. It is best to avoid the difference between blood and dialysate potassium concentration ≥ 3mEq/L.

Methods

This is a retrospective cohort study to evaluate the effect of dialyzed serum potassium, azithromycin, or levofloxacin/moxifloxacin on SCD in hemodialysis patients. The data comes from the United States Renal Data System (USRDS), and the interception time is from 2007 to 2017.

Enrolled patients were adult dialysis patients receiving azithromycin, levofloxacin/moxifloxacin, and amoxicillin. Previous studies have shown that amoxicillin does not increase the risk of QT prolongation in hemodialysis patients, so the control group in this study was amoxicillin.

According to previous studies, the risk of QT prolongation in hemodialysis patients is low when the difference between blood and dialysate potassium concentrations is less than 3 mEq/L. Therefore, the differences in serum potassium and dialysate potassium concentrations in patients in the intervention group were categorized by a 2-point method.

The study was divided into 3 major phases, namely a 180-day baseline period, a 30-day washout period, and a 14-day follow-up period. The primary endpoint of the study was SCD, ie whether patients developed SCD within 14 days after a single dose of antibiotics. Secondary endpoints of the study were the occurrence of SCD or arrhythmia requiring hospitalization, and cardiovascular death.

It is worth noting that the subgroup analysis of this study was divided into three groups according to the difference in potassium concentration in blood and dialysate, which were <2 mEq/L, 2-3 mEq/L, and ≥3 mEq/L.

Results

A total of 89,379 patients were enrolled, and patients received 113,516 azithromycin treatments and 103,493 amoxicillin treatments. Overall, patients treated with azithromycin had a higher risk of developing SCD compared with control patients (treated with amoxicillin) (HR = 1.68; 95% CI, 1.31-2.16). Moreover, the risk of SCD was significantly associated with the difference in blood and dialysate potassium concentrations in hemodialysis patients.

Compared with the difference between blood and dialysate potassium concentration ≥3mEq/L, hemodialysis patients with a difference of blood and dialysate potassium concentration<3mEq/L had a lower risk of SCD (HR=2.22[95% CI,1.46~3.40] vs HR = 1.43 [95% CI, 1.04~1.96]; P = 0.07).

For secondary endpoints, differences in blood and dialysate potassium concentrations in hemodialysis patients had a significant impact on the risk of SCD or arrhythmias requiring hospitalization and cardiovascular death.

Further subgroup analysis found that the risk of SCD in patients in the azithromycin group was related to the difference in blood and dialysate potassium concentrations, and the smaller the concentration difference, the lower the risk, but there was no similar trend for levofloxacin/moxifloxacin.

Discussion

The study found that the use of azithromycin and fluoroquinolone antibiotics in hemodialysis patients was associated with an increased risk of SCD. In addition, differences in blood and dialysate potassium concentrations can affect the risk of SCD.

Currently, the instructions for azithromycin and fluoroquinolone antibiotics do not list hemodialysis patients as high-risk groups. However, compared with the normal population, QT prolongation, and SCD are more likely to occur in hemodialysis patients. Therefore, some scholars believe that hemodialysis patients should avoid using the above antibiotics.

Blood potassium levels are critical for heart conduction. Patients with chronic kidney disease (CKD) are prone to electrolyte disturbances, including hyperkalemia and hypokalemia, and are closely related to hemodialysis. The reduction rate of blood potassium is related to the potassium ion concentration of the dialysate. If the potassium ion concentration of the dialysate is low (such as <2mEq/L), the removal rate of blood potassium in dialysis patients will be accelerated, which may increase the risk of hypokalemia. Increased risk of QT prolongation and SCD.

In clinical practice, the potassium ion concentration of the dialysate is usually not individually configured. This is due to the low availability of blood potassium testing, and some dialysis centers lack related equipment for blood potassium testing.

Therefore, the researchers suggest that for patients who need to use azithromycin and fluoroquinolone antibiotics, the potassium ion concentration of the dialysate should be individually configured according to the results of serum potassium and electrocardiogram monitoring, to reduce the risk of QT prolongation and SCD.

In general, this study suggests that azithromycin and fluoroquinolone antibiotics can be used in hemodialysis patients, but attention should be paid to monitoring serum potassium and electrocardiogram during use to avoid a difference of ≥3 mEq/L between blood and dialysate potassium concentrations.

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References:

1. Patrick H Pun, Magdalene M. Assimon, Lily Wang, et al. QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis. Kidney Medicine. Vol 5 丨Iss 5 丨May 2023. Feb 15, 2023.