Standards of aminoglycoside therapeutic drug monitoring in a South African private hospital: perspectives and implications

Abstract

Summary Background Therapeutic drug monitoring (TDM) is essential to ensure that aminoglycoside peak concentrations are high enough for effective antimicrobial treatment and trough levels are low enough to minimise toxicity. Inappropriate utilisation of TDM may lead to suboptimal therapy, toxicity and waste of resources. This study aimed to investigate the standard of aminoglycoside TDM performed in adult hospitalised patients. Design An observational, descriptive, cross-sectional study. Setting A 221-bed private hospital. Participants All patients, older than 18 years, on intravenous aminoglycosides for more than 48 hours were included. Interventions None, was observational. A computerised database and patient files were used to obtain the information required for this study. Descriptive statistical analysis was used. Main outcomes measures Aminoglycoside blood levels and estimated glomerular filtration rate (eGFR) in the patients. Results One hundred and three (103) patients were included: 65 on gentamicin and 38 on amikacin. Blood levels were performed in only 19 gentamicin (29.23%) and 22 amikacin (57.89%) patients. Trough levels were taken more than 2 hours before the next dose in 12 gentamicin (63.16%) and 12 amikacin (54.54%) patients. The majority of patients (96.92% on gentamicin and 84.21% on amikacin) received once daily doses. TDM was performed in all patients with an estimated glomerular filtration rate (eGFR) lower than 60 mL/min/1.73m 2 and in 23.31% of gentamicin patients and 56.76% of amikacin patients with an eGFR higher than 60 mg/min/1.73m 2 . Conclusions Incorrect sampling times and unnecessary levels taken in patients with normal renal function indicate a need for aminoglycoside treatment guidelines in the private hospital. Funding None

High-throughput identification and determination of aminoglycoside antibiotics in human plasma using UPLC–Q-ToF-MS

“…Under optimal conditions the LOD and LLOQ values of aminoglycosides were 0.5–2.0 µg/mL and 1.0–4.0 µg/mL, respectively. The therapeutic and intoxicating serum levels of these aminoglycosides have been reported as 4–33 µg/mL 1,22–24 and 4–50 µg/mL 25 , respectively. Autopsy levels are reported as 2.2 µg/mL in the serum, 794 µg/g in the kidney, 48 µg/mg in the lung, and 30 µg/g in the liver for amikacin; and 207 µg/mL in the serum for streptomycin.…”

“…The observed concentrations were within the normal therapeutic levels. 1,22–24 The maximum concentrations of streptomycin in the three plasma samples was reached at 0.5–2.0 h. The highest concentration after 1.0 h for Volunteer A (female, body weight 50 kg) was 98.4 µg/mL, that after 0.5 h for Volunteer B (male, body weight 60 kg) was 72.5 µg/mL. and that after 2 h for Volunteer C (male, body weight 73 kg) was 24.8 µg/mL.…”

Utility, promise, and limitations of liquid chromatography‐mass spectrometry‐based therapeutic drug monitoring in precision medicine

“…In contrast, for patients with impaired renal function, burns, or sepsis, two samples (peak and trough) are needed for an improved adjustment of the dose and/or the dosing frequency. 115 , 117 Therefore, it is crucial to develop multiplexed methods to accuratly measure antibiotics levels in plasma for the precise individualization of antimicrobial therapies. Barco et al have introduced a clinicaly validated LC–MS/MS multiplexed method for rapid quantitation of 14 antibiotics (amikacin, amoxicillin, ceftazidime, ciprofloxacin, colistin, daptomycin, gentamicin, linezolid, meropenem, piperacillin, teicoplanin, tigecycline, tobramycin, and vancomycin) and a beta‐lactamase inhibitor (tazobactam).…”

“…For example, aminoglycosides antibiotics that are concentration dependent are normaly monitored by the C max /MIC ratio which should be maintained between 8 and 10 when analyzing a blood sample that was taken 30 min after the end of the intravenous infusion, in order to determine the C max . In contrast, for patients with impaired renal function, burns, or sepsis, two samples (peak and trough) are needed for an improved adjustment of the dose and/or the dosing frequency 115,117 …”

Review on Population Pharmacokinetics of Amikacin in Paediatrics

“…[4][5][6] Several studies and practice guidelines recommend a target serum Amikacin peak concentration to be 20 to 35 mg/L, trough concentrations >5-10 mg/L. 7,14,25 The recommended dosing in neonates and infants is 15mg/kg IV, Once daily (OD) and 7.5mg/kg, twice daily (BD). Comparatively, the OD regimen has reduced toxicity and increased efficacy than the BD regimen.…”