Dragan Ljutić

Possible interaction between azithromycin and cyclosporin: a case report.

Dragan Ljutić, MD, Clinical Hospital Split, Department of Internal Medicine, Spinćeva 1, 58000 Split (Croatia) Dear Sir, Azithromycin, an azalide antimicrobial agent derived from the macrolide antibiotic erythromycin, has a similar mechanism of activity, but different antimicrobial profile, pharmacokinetics and metabolism [1]. While erythromycin is known to interfere with cyclosporin metabolism by inhibiting cytochrome P450 and decreasing clearance of that drug [2], azithromycin has not been shown to affect cytochrome P450 in rats [3]. Indeed, azithromycin interactions with other drugs have not been reported so far. We report here the case of a transplant recipient in whom azithromycin probably interacted with cyclosporin, i.e. increased cyclosporin blood levels. A 44-year-old female renal transplant patient was admitted because of high fever, cough and dispnea. Her chest X-rays revealed bilateral pulmonary infiltrations; atypic pneumonia was supposed, and treatment with azithromycin (500 mg 1st day + 250 mg daily for another 4 days) was started. She was transplanted 5 years before this event. Her immunosuppressive therapy was not changed and included: cyclosporin (2 mg/kg/day), azathioprine (25 mg) and prednisone (20 mg). Actually, she had a failing graft with stable renal function (serum creatinine was around 400 μmol/l). After 10 days of hospitalization, she was discharged in good clinical condition. During and after azithromycin treatment, her cyclosporin blood concentrations were closely followed up, looking for possible azithromycin/cyclo-sporin interaction. Table 1. Cyclosporin levels (ng/ml) using monoclonal RIA 2 months before admission Days after azithromycin exposure 6th 3rd 10th 20th 30th 149 66 45 50 28 27 References

Should Glucose Be Administered Before, With, or After Insulin, in the Management of Hyperkalemia?

To assess the hypokalemic effect of intravenous glucose (25 g i.v. in 5 min) followed by regular insulin (10 U) bolus, as well as the incidence of hypoglycemia, a well-known side effect of this intervention, nine uremic patients on maintenance hemodialysis were studied. Measurements were done of plasma potassium, glucose, insulin, and C-peptide before, and 15, 30, 45, and 60 min after glucose and insulin. The intervention induced a significant fall in plasma potassium level, a significant rise and then fall in plasma glucose, and a significant increase in the insulin and C-peptide levels. These data suggest that hypertonic glucose infusion should precede, not follow, the insulin bolus in the management of hyperkalemia. Such an approach is clinically effective and well tolerated, with no hypoglycemic side effects.

Acute Renal Failure as a Complication of Acute Pancreatitis

To assess the prevalence of acute renal failure (ARF) in patients with acute pancreatitis, as well as the factors predictive of a lethal outcome, we retrospectively studied the data of all patients admitted to our hospital over a 5-year period. Between 1989 and 1993, 554 patients presented with acute pancreatitis, of which 24 (4.4%) subsequently developed ARF. Death occurred in 14/24 (58%) of patients with ARF, and was associated with an increased incidence of multiorgan failure. There was no statistically significant difference in the age, admission blood pressure, or admission pulse rate of the patients who survived and those who died. In contrast, death was associated with a higher Ranson score, and the increased prevalence of multiorgan failure. The length of hospitalization of the nonsurviving group was significantly shorter. Acute renal failure is not a common finding in patients with acute pancreatitis. However, when it occurs, it is associated with a poor prognosis, and is predicted by a higher Ranson score and the presence of multiorgan failure.

Tubulointerstitial nephritis with uveitis syndrome following varicella zoster reactivation.

A 49-year-old Woman was referred to the Renal Unit because of azotemia and fatigue. Two months earlier she had herpes zoster. Twenty days after skin eruption, iridocyclitis of the left and right eye were diagnosed. In the present case, typical clinical and laboratory findings of TINU syndrome followed herpes zoster. The quoestion is whether preceding viral reactivation could be a trigger, the cause, or a consequence of the immunological disorder underlyng TINU.

Ramipril Decreases Chlorthalidone‐Induced Loss of Magnesium and Potassium in Hypertensive Patients

A double‐blind clinical trial was conducted to compare the efficacy of and electrolyte changes caused by ramipril‐chlorthalidone combination treatment (5 mg + 25 mg) and chlorthalidone monotherapy (25 mg daily) in patients with hypertension. After a 4‐week placebo period, 32 patients (mean age, 51 ± 9 years) with essential hypertension (average blood pressure of 181.4/104.5 ± 13.0/6.9 mmHg) were randomly assigned to receive combination therapy (group A, n = 17) or monotherapy (group B, n = 15). After 12 weeks of active treatment, systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively, for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for patients taking monotherapy. The difference was significant for between‐group comparisons. There were no changes in serum sodium concentration, but a significant similar increase in 24‐hour urinary sodium excretion was seen in both groups. Serum calcium levels increased slightly and 24‐hour urinary calcium excretion decreased significantly in both groups, probably due to chlorthalidone administration. Serum potassium levels increased slightly in group A (from 4.16 ± 0.39 mmol/L to 4.30 ± 0.42 mmol/L) and decreased slightly in group B (from 4.18 ± 0.32 mmol/L to 3.99 ± 0.49 mmol/L). Urinary potassium excretion did not change significantly in group A, but increased by ∼15% in group B. There was a decrease in 24‐hour urinary magnesium excretion (from 4.01 ± 1.24 mmol/24 hours to 3.50 ± 0.93 mmol/24 hours) in group A and an increase (from 3.49 ± 0.98 mmol/24 hours to 4.35 ± 1.12 mmol/24 hours) in group B. At the end of the trial these changes were significant in between‐group comparisons. Consistent with the previously shown amelioration by ramipril of thiazide‐induced metabolic side‐effects, ramipril appears to improve magnesium balance during cotreatment with chlorthalidone.

Acute Renal Failure Associated with Rhabdomyolysis in Acute Q Fever

The clinical presentation of Q fever is polymorphic and non-specific, and it may be presented as an acute or chronic disease. Renal complications of acute Q fever such as acute glomerulonephritis are not uncommon. Acute renal failure induced by rhabdomyolysis in acute Q fever has until now never been reported in the literature. We presented a case of acute Q fever associated by extreme rhabdomyolysis and consecutive acute renal failure. A male patient was treated with doxycycline and continuous venovenous hemodiafiltration. After two weeks of treatment, the patient completely recovered kidney function, and there were no clinical abnormalities. Acute Q fever must be considered as a possible cause of rhabdomyolysis and acute renal failure. The continuous venovenous hemodiafiltration may be effective, and it seems to be the treatment of choice in severe rhabdomyolysis and consecutive acute renal failure.