Amoxicilline crystalluria: an emerging complication with an old and well-known antibiotic

1 1,2 1 1,2 1 3 1 1,2

D. Puyraimond-Zemmour , V. Zeller , T. Sené , V. Meyssonnier , S. Godot , M. Biour , O. Lidove , S. Marmor2, JM. Ziza
1Service de Médecine Interne et Rhumatologie, 2Centre de Référence des Infections Ostéo-Articulaires complexes, GH Diaconesses Croix Saint Simon, Paris, France.
3
Centre Régional de Pharmacovigilance, Hôpital St Antoine, AP-HP, Paris, France

Introduction
Amoxicilline can crystallize in the urinary tract as amoxicillin Characteristics of 10 patients with amoxicillin crystalluria
trihydrate and lead to macroscopic hematuria and acute renal median [range] Treatment
insufficiency (ARI) through tubular obstruction. This event is Amoxicillin withdrawal, IV hydratation and urine
favored by amoxicillin urinary oversaturation (high dosage, alcalinisation.
short half-life, predominant urinary excretion of the drug), Age 70 [47-86]
One patient needed dialysis.
insufficient hydratation and a low urinary pH. However, Two patients with renal pelvis dilatation had a ureteral
Number of women 7
amoxicillin crystalluria is a rare event, whose incidence stent inserted.
remains unknown. During the past year, we observed an Weight, kgs 70 [57-90]
important increase of this complication. Outcome
Creatinine clairance, ml/min 96 [55-138] Complete recovery of previous renal function in all
Objectives (one patient with clairance < 60) patients within a median of 13 [1-24] days.
To report the present and past incidence of amoxicillin
crystalluria. Daily amoxicillin dosage, g/24h 12 [9-15]
Discussion/Conclusion
To describe clinical and biological manifestations of The sharp rise of this complication over the past year,
Number of infusion per 24 hours 3,5 [3-6]
amoxicilline crystalluria, treatment and outcome of the although our prescription modalities have not changed,
patients Amoxicillin dosage per infusion, 3 [2-4] leads us to think that it is related to an increase of
To alert practionners on this increasing complication gramme urinary amoxicillin concentrations, eg, by another drug
or infusion solution, or to the manufacture of the drug.
Patients et methods Number of amoxicillin generics 3 generics Further studies are warranted to answer that question.
Retrospective cohort study taking place in a French 8 cases with the same generic
Reference Center for bone and joint infection. 1. Hentzien M, Lambert D, Limelette A et al. Macroscopic
Other associated nephrotoxic - NSAI in 1 patient amoxicillin crystalluria. Lancet 2015 ; 385 :2296.
Inclusion criteria drugs - gentamicin for 2-4 days (4 cases), 2. Fogazzi G, Cantu M, Saglimbeni L, Daudon M. Amoxycillin,
!ARI developing during high-dose (8-16g/24h) IV amoxicillin administered the day before ARI (1 a rare but possible cause of cristalluria. Nephrol Dial Transplant
therapy case) 2003 ; 18 :212-214.
3. Fritz G, Barner C, Schindler R, Boemke W, Falke K.
!Presence of signs of crystalluria : gross hematuria oliguria,
Time between onset of amoxicillin 14 [1-27] Amoxicillin-induced acute renal failure. Nephrol Dial Transplant
lumbar or abdominal pain, intense burning during urination, 2003 ; 18 :1660-1662.
renal pelvis dilatation therapy and first clinical signs ,
4. Daudon M. Cristallurie. Néphrologie et Thérapeutique 2015;
days
174-190.
Results
Time between onset of amoxicillin 16 [4-31]
Over 10 years (September 2004 to August 2014) we
therapy and ARI , days
managed a cohort of 2348 patients with bone and joint
infections (BJI). Among 228 who received high-dose IV Maximal creatininemia, µmol/l 397 [153-728]
amoxicillin, fewer than one per year developed amoxicillin
Measures to prevent crystalluria
crystalluria with ARI. Clinical signs of crystalluria Gross hematuria (n=10), burning
during urination (n=4), oliguria (n=7), 1. Maximum of 2 grams of amoxicillin per
From 1rst September 2014 to 31rst October 2015, 285 patients abdominal or lumbar pain (n=2) infusion
were treated for BJI in our unit, 56 received IV amoxicillin at a 2. Prolonged IV administration of 2-6 hours
dose of ≥8g/24h for at least 48 hours. Ten patients (18%) Renal pelvis dilatation 2 patients with insertion of an
3. Hydrate with physiological saline infusion
developed acute renal failure with signs of cristalluria. ureteral stent
4. Urine alcalinisation (IV or oral)
5. Watch for signs of cristalluria and stop
During the last study year, no changes in the administration modalities amoxicillin immediately, if present
(dilution, duration of infusion, daily dosage, number of daily infusion, unit => Search for amoxicillin crystals in fresh urine
dose per infusion) of IV amoxicilline took place. on a plain tube