Amoxicillin crystalluria is associated with acute kidney injury in patients treated for acute infective endocarditis

Incidence, associated factors, and effect on renal function of amoxicillin crystalluria in patients receiving high doses of intravenous amoxicillin (The CRISTAMOX Study): A cohort study

“…The acidity of urine pH has long been known to favor AC in patients treated with amoxicillin, because it increases the proportion of amoxicillin excreted in the urine in the unmetabolized trihydrate form 19 , which is less soluble than the sodium form 11 . This data is corroborated by a recent study that found the acidification of urine pH (OR = 0.78 by one increasing pH point, 95% CI [0.62-0.97]) 28 and the increase in amoxicillin blood concentration (OR = 1.03, 95% CI [1.01-1.05]) as risk factors for AC. ACE inhibitors, by vasodilation of the efferent arteriole, induce a decrease in glomerular filtration rate and therefore a decrease in urine output, a factor known to promote AC.…”

“…One other study, with similar methodology but of smaller size, involving 32 patients treated with HDIVA for suspected IE, estimated the incidence of AC at 43.8%. 28 Another French single-center prospective study involving 32 patients found the incidence of AC during treatment with HDIVA to be 21.9%, the diagnosis being retained in the event of evidence of AC but also in the event of obstructive AKI without other obvious identified cause. 29 …”

“…The impact of the occurrence of AC on the occurrence of AKI, widely assumed since the mid-1980s 13 , is supported by our study as well as another study using similar methodology which found a predictive impact of the same order (cause-specific hazard = 7.44, p = 0.005). 28 …”

“…It is easily performed in clinical practice in centers where it is available and would allow practitioners to optimize amoxicillin doses rapidly in terms of PK / PD according to the minimum inhibitory concentrations of the identified pathogens. 28 However, this analysis is not available in all centers and may be subject to a long rendering time, while AC testing can be performed in all laboratories using a simple microscope with the results being immediate.…”

High Incidence of Acute Kidney Injury in Patients Treated with High-Dose Amoxicillin and Cloxacillin Combination Therapy

“…Despite a low level of evidence, the European Society of Cardiology (ESC) Guidelines recommended in 2015 a combination of ampicillin (12 g/day), (flu)cloxacillin or oxacillin (12 g/day), and gentamicin (3 mg/kg/day) as the initial empirical therapy for community-acquired native valve or late prosthetic valve IE in acute severely ill patients prior to pathogen identification [ 2 ]. Acute kidney injury (AKI) has been previously reported in patients treated with high-dose amoxicillin [ 3 , 4 ] or cloxacillin [ 5 , 6 ], but data on the tolerability of this combination are scarce. Therefore, the aim of this study was to analyze the characteristics of patients treated with a combination of high-dose intravenous amoxicillin and cloxacillin and to assess the renal tolerance of this combination.…”