Amoxicillin Crystalluria, an Emerging Complication with an Old and Well-Known Antibiotic

Zeller, Valérie; Puyraimond-Zemmour, Déborah; Sené, Thomas; Lidove, Olivier; Meyssonnier, Vanina; Ziza, Jean-Marc

doi:10.1128/aac.00359-16

Cited by 21 publications

(22 citation statements)

References 4 publications

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“…Finally, the increase in AICN incidence is currently reported only in France (Zeller et al [5] and this study), while AICN cases previously have been reported in Belgium, Sweden, Germany, Italy, the Netherlands, and the United States (2,3,8,9,11,15,(24)(25)(26)(27)(28)(29). AICN increase might be obvious in France because i.v.…”

Section: Discussionmentioning

confidence: 48%

“…Indeed, all cases were serious, more than one-third of patients developed KDIGO stage 2 to 3 AKI, two-thirds of cases involved patients who received ultrashort treatment with AMX/AMX-CLA as prophylaxis for scheduled surgery, and one-quarter of patients required ICU admission for life-threatening complications or emergent renal replacement therapy. AICN was formerly reported in case reports, and the largest series published by Zeller et al included only 10 medical patients briefly described in a letter; thus, to date, our study reports the largest description of this adverse drug reaction (5).…”

Section: Discussionmentioning

confidence: 79%

“…high doses of AMX for osteoarticular infections. In their center, AICN incidence increased from less than one patient per year from 2004 to 2014 to 10 patients per year during 2014 to 2015, without evident explanation or change in medical practices (5).…”

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confidence: 99%

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Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers

Vodovar

Thomas

Lepeule

et al. 2018

Antimicrob Agents Chemother

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An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection ( = 15) or as surgical prophylaxis ( = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 79%

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Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers

Vodovar

Thomas

Lepeule

et al. 2018

Antimicrob Agents Chemother

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“…In addition, targeting f TϾMIC of 100% in all burn patients would require larger doses and concentrations of amoxicillin that could increase its toxicity without a thorough monitoring by TDM. Indeed, adverse reactionsm such as crystalluria, have been reported with the use of high doses of amoxicillin (37,38). Unlike renal function, interindividual changes in BW did not appear to have a clinically relevant influence on amoxicillin PD in adult burn patients.…”

Section: Discussionmentioning

confidence: 93%

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center

Fournier

Goutelle

Que

et al. 2018

Antimicrob Agents Chemother

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The objective of this study was to investigate the population pharmacokinetics (PK) of amoxicillin in ICU burn patients and the optimal dosage regimens. This was a prospective study involving 21 consecutive burn patients receiving amoxicillin. PK data were analyzed using nonlinear mixed-effects modeling. Monte-Carlo simulations assessed the influence of various amoxicillin dosage regimens with identified covariates on the probability to achieve a target (PTA) value of time during which free amoxicillin concentrations in plasma exceeded the MIC (T>MIC). A two-compartment model best described the data. Creatinine clearance (CL) and body weight (BW) influenced amoxicillin CL and central volume of distribution (), respectively. The median CL (Cockcroft-Gault formula) was high (128 ml/min), with 25% of patients having CLs of >150 ml/min. The CL, , and half-life () values at steady state for a patient with a CL of 110 ml/min and BW of 70 kg were 13.6 liters/h, 9.7 liters, and 0.8 h, respectively. Simulations showed that a target T>MIC of ≥50% was achieved (PTA > 90%) with standard amoxicillin dosage regimens (1 to 2 g every 6 to 8 h [q6-8h]) when the MIC was low (<1 mg/liter). However, increased dosages of up to 2 g/4 h were necessary in patients with augmented CLs or higher MICs. Prolonging amoxicillin infusion from 30 min to 2 h had a favorable effect on target attainment. In conclusion, this population analysis shows an increased amoxicillin CL and substantial CL PK variability in burn patients compared to literature data with nonburn patients. Situations of augmented CL and/or high bacterial MIC target values may require dosage increases and longer infusion durations. (This study has been registered at ClinicalTrials.gov under identifier NCT01965340.).

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“…Amoxicillin (AMX) is one of the most widely prescribed antibiotics used for antimicrobial prophylaxis or the treatment of established infections. Its main side effects are well known, however, in last years, AMX-induced crystal nephropathy (AICN), a complication thought to be rare, has been reported with a high incidence in France [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

High Incidence of Amoxicillin-Induced Crystal Nephropathy in Patients Receiving High Dose of Intravenous Amoxicillin

Garnier

Dellamaggiore

Brilland

et al. 2020

JCM

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Background: Amoxicillin (AMX)-induced crystal nephropathy (AICN) is considered as a rare complication of high dose intravenous (IV) AMX administration. However, recently, its incidence seems to be increasing based on French pharmacovigilance centers. Occurrence of AICN has been observed mainly with IV administration of AMX and mostly under doses over 8 g/day. Given that pharmacovigilance data are based on declaration, the real incidence of AICN may be underestimated. Thus, the primary objective of the present study was to determine the incidence of AICN in the current practice. Materials and Methods: We conducted a retrospective study between 1 January 2015 and 31 December 2017 in Angers University Hospital. Inclusion criteria were age over 18 years-old and IV AMX administration of at least 8 g/day for more than 24 h. Patients admitted directly into the intensive care units were excluded. Medical records of patients that developed Kidney Disease:Improving Global Outcome (KDIGO) stage 2–3 acute kidney injury (AKI) were reviewed by a nephrologist and a specialist in pharmacovigilance. AICN was retained if temporality analysis was conclusive, after exclusion of other causes of AKI, in absence of other nephrotoxic drug administration. Results: A total of 1303 patients received IV AMX for at least 24 h. Among them, 358 (27.5%) were exposed to AMX doses of at least 8 g/day and were included. Patients were predominantly males (68.2%) with a mean age of 69.1 years-old. AMX was administered for a medical reason in 78.5% of cases. Patients received a median dose of AMX of 12 g/day (152.0 mg/kg/day). Seventy-three patients (20.4%) developed AKI, 42 (56.8%) of which were KDIGO stage 2 or 3. Among the latter, AICN diagnosis was retained in 16 (38.1%) patients, representing an incidence of 4.47% of total patients exposed to high IV AMX doses. Only female gender was associated with an increased risk of AICN. AMX dose was not significantly associated with AICN development. Conclusion: This study suggests a high incidence of AICN in patients receiving high IV AMX doses, representing one third of AKI causes in our study. Female gender appeared as the sole risk factor for AICN in this study.

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Amoxicillin Crystalluria, an Emerging Complication with an Old and Well-Known Antibiotic

Cited by 21 publications

References 4 publications

Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers

Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center

High Incidence of Amoxicillin-Induced Crystal Nephropathy in Patients Receiving High Dose of Intravenous Amoxicillin

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