Penicillin Dried Blood Spot Assay for Use in Patients Receiving Intramuscular Benzathine Penicillin G and Other Penicillin Preparations To Prevent Rheumatic Fever

Abstract

Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and Ͼ1 month at Ϫ20°C. Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD.

High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease

“…Penicillin concentrations were assayed using a validated liquid chromatography-mass spectroscopy (LC-MS) assay. [ 25 ] Quality control samples for accuracy and inter- and intra-day variation for across concentrations between 2.5–1000 ng/mL confirmed the assay performance. The assay limits of quantification (LOQ) and detection (LOD) were 1 and 0.5 ng/mL, respectively.…”

Validation of a Dried Blood Spot Ceftriaxone Assay in Papua New Guinean Children with Severe Bacterial Infections

“…However, there is no guidance on the optimal populations, sample size, and reportable outcome requirements for clinical validation studies, sometimes termed bridging studies. Our approach is that, in addition to demonstration of in vitro feasibility and suitability of a microsampling assay, population-specific PK bridging studies should ideally be performed in healthy volunteers (7,8) and accessible patients with the infection of interest (15). This would confirm that, in addition to adequate correlations between plasma and DBS concentrations, important PK parameters also accord in clinical settings of interest.…”

Antibiotic Prescribing Patterns for Patients with Pharyngitis in Malaysian Public Primary Care Clinics

“…Other studies have shown that oral penicillin V for 10 days or a single dose of parenteral penicillin G was the first line of antibiotics to treat GAS pharyngitis and it was reduced the duration of the symptom ( 23 , 24 ). In addition, another study has reported that penicillin antibiotic treatment within 9 days was sufficient to prevent rheumatic fever ( 25 ). In contrast, other studies have proved that treatment of GAS pharyngitis by amoxicillin, erythromycin, oral cephalosporins and clindamycin for 7 days was sufficient to reduce the symptoms ( 26 , 27 ).…”