2.2. Participants
Inclusion Criteria: The study targets neonates who were administered gentamicin therapy. Participants were aged from 1 day to 1 month. To be considered for inclusion, neonates needed to have complete medical records that detail demographic data, precise information on gentamicin dosing, thorough therapeutic drug monitoring (TDM) data, and documented clinical outcomes. This approach is designed to ensure a comprehensive evaluation of gentamicin’s impact within this age group, considering the necessary therapeutic and outcome-related information.
Exclusion Criteria: Neonates were excluded from the study if they exhibited any renal impairment, as gentamicin’s pharmacokinetics are significantly altered in such conditions, and we did not wish to have any confounding factor that would shift the study away from its main objective. Additionally, cases where gentamicin sampling errors occurred, or where therapy was discontinued before the administration of a second dose, were omitted to maintain data integrity. Incomplete medical records also warranted exclusion, ensuring that the study’s findings were based on complete and accurate data sets, as per the Ministry of Health guidelines. Consideration was also given to exclude neonates on medications that could interact with gentamicin, or with pre-existing conditions such as liver dysfunction or other congenital anomalies influencing gentamicin’s efficacy. These conditions might influence the drug’s absorption, metabolism, or excretion, leading to atypical therapeutic responses or adverse effects, which could skew the study’s results.
2.3. Study Procedure
At the Maternity and Children’s Hospital in Makkah, MCH, Saudi Arabia, a data collection form was designed and used for all gentamicin prescribing and monitoring activity on neonatal patients. The study duration for sample collection and consideration was from July 2020 to July 2022. The following information was collected: file number, age, gender, vital signs, indication, bacterial culture (type of infection), initial dose, trough and peak levels, renal function tests as serum creatinine, blood urea nitrogen (BUN), liver functions as AST, ALT, duration of hospitalization, and adverse drug reaction (ADR). Creatinine clearance was obtained using the Schwartz formula CrCl = K×ht (cm) *88.4/SCr (micromole/L), where height (ht) is patient height and K = 0.33. Creatinine clearance was taken from the (CareWare) system.
The level of compliance with TDM guidelines for gentamicin in neonates was determined by measuring the initial dose, trough and peak levels, hospitalization, and adverse drug response (ADR). According to Saudi MOH regulation, the starting dose for neonates and infants < 2 months of age is based on the gestational age and postnatal age which is categorized as follows: the initial dose for neonates < 30 weeks is 5 (mg/kg) q48h from 0–14 days; the dose for neonates <30 weeks is 5 (mg/kg) q36h after 14 days; the initial dose for neonates between 30–34 weeks is 5 (mg/kg) q36h from 0–10 days; the dose for neonates between 30–34 weeks is 5 (mg/kg) q36h after 10 days; the initial dose for neonates ≥ 35 weeks is 4 (mg/kg) q24h between 0–7 days; and the dose for neonates ≥ 35 weeks is 5 (mg/kg) q24h for more than 7 days.
A trough level should be acquired immediately prior to the administration of the third dose, according to Saudi MOH policy, and after 30 min of the completion of the third dosage infusion, the physician or pharmacist should attain a peak level. The gentamicin target trough and peak were categorized based on the type of illness. In the case of a serious illness, the target trough is less than 2 mg/L, and the target peak is between 6 and 8 mg/L. In the case of a serious illness, the target trough is less than 2 mg/L, and the target peak is between 8 and 10 mg/L. In the case of a urinary tract infection, the target trough is less than 2 mg/L, and the target peak is between 4 and 6 mg/m. In the case of synergy against Gram-positive bacteria, the target trough is less than 2 mg/L, and the target peak is between 3 and 5 mg/mL.
The next critical step was to guarantee that healthcare professionals followed TDM guidelines based on the trough and peak results. For example, if the trough is 2 mg/L and the peak is 3 to 10 mg/L, this indicates that the trough and peak are within the target. Thus, the response here, according to the MOH protocol, is to continue the same regimen and examine again in 3–4 days. When the trough is >2 mg/L and the peak is any result, the trough is considered high. Thus, according to the MOH procedure, defer the next dose and retest the level in 24 h. If indeed the result is less than 2 mg/L, continue the regimen with a less frequent interval (e.g., Q8 to Q12) and then reassess the trough and peak around the third dose.
When the trough is less than 2 mg/L and the peak is greater than 10 mg/L, the peak is considered high. Thus, according to the MOH’s TDM policy, the action here is to reduce the dose by 25% and keep the same interval, and then reassess the trough and peak around the third dose. Serum creatinine must be monitored every other day while being on aminoglycoside therapy, and the CBC should be examined twice weekly.
Due to the prevalence of COVID-19, health precautionary protocols and procedures were implemented inside the Maternity and Children’s Hospital in Makkah, Saudi Arabia (including wearing a face mask, social distancing, and washing hands with soap, hand disinfectant, and anti-bacterial alcohol gel, as well as spraying all tools and materials that were used in the research with isopropyl alcohol 70 percent spray). When addressing patients, the principal investigator and other data collectors were following all medical cautious guidelines and procedures, ensuring that they and the participants were safe throughout the data collecting phase, which lasted no more than 20–30 min.