Vancomycin Therapeutic Drug Monitoring

Vancomycin: Therapeutic drug monitoring

A. Johnson

Internship, Clinical Pharmacist, Kauvery Hospital, Trichy

Background

Vancomycin is a potent glycopeptide antibiotic that has been in use since the mid-20^th century, originally derived from Streptococcus orientalis. It works as a bactericidal agent, primarily by inhibiting the synthesis of bacterial cell walls. This makes it particularly effective against various gram-positive bacteria, including streptococci, enterococci, and staphylococcus aureus, with notable effectiveness against methicillin-resistant staphylococcus aureus (MRSA) infections¹.

Despite its effectiveness, Vancomycin administration comes with several challenges. It has a narrow therapeutic index, meaning that the difference between a therapeutic dose and a toxic dose is minimal. Elevated drug levels can lead to significant adverse reactions, including nephrotoxicity (kidney toxicity), ototoxicity (ear toxicity), neutropenia (low white blood cell count) and infusion-related side effects like nausea, vomiting and chills. In some cases, it can also cause serious skin reactions, such as exfoliative dermatitis and Stevens-Johnson syndrome,

On the other hand, insufficient dosing may fail to control infections effectively, particularly against multi-drug resistant bacteria, and can contribute to the development of vancomycin resistance. Consequently, therapeutic drug monitoring (TDM) is crucial for managing vancomycin therapy, ensuring that drug levels remain within a safe and effective range².

TDM of Vancomycin

Vancomycin therapeutic drug monitoring (TDM) is a crucial in managing serious infections, particularly those caused by Methicillin-Resistant Staphylococcus Aureus (MRSA) in critically ill patients.TDM is recommended for individuals at high risk of renal toxicity, those with unstable renal function, and patient requiring prolonged therapy of 3–5 days. Antibiotic Under the Area Curve(AUC) guided monitoring approach, targeting an area under the curve to minimum inhibitory concentration (AUC/MIC) ratio of 400–600mg h/L, preferred over trough-only monitoring through a trough level of 15–20 mg/L may be used if AUC monitoring is not feasible. For patient with a high minimum inhibitory concentration (MIC) above 2 mg/L, therapy adjustments are advised to avoid toxicity. In critical cases, an initial dose of 15–20 mg/kg (up to a maximum of 3000 mg) is recommended to quickly reach therapeutic levels, and continuous infusion may improve drug efficacy while reducing toxicity. Monitoring frequency depends on clinical stability: daily for unstable patients and weekly for stable ones.

In pediatric patients, a dose of 60–80 mg/kg/day divided into multiple doses is standard, while neonates may require 10–20 mg/kg every 8–48 h based on weight and renal function. Dose adjustments are necessary for patients with renal insufficiency, obesity or those on nephrotoxic drugs. Toxicity prevention is crucial, with AUC level maintained below 800 mg h/L, and doses above 80 mg/kg/day are generally avoided to minimize the risks. This monitoring strategy helps optimize vancomycin dosing, enhancing efficacy and safety for each patients³.

Dilution and renal dose adjustment⁴

Dilute reconstituted solutions with at least 100 ml of diluents.
Max concentration = 5mg/ml
For fluid-restricted patients, a concentration of up to 10mg/ml may be used.

Standard Dilution = Amount of the drug + Infuse volume + Infusion rate

Eg: Concentration less than or equal to 5 mg/ml

Dose	Volume	Infusion hours
0–500 mg	100 ml	60 min
501–1250 mg	250 ml	90 min
>1251 mg	500 ml	120 min

Administration

Max rate = 10 mg per min.

Drops factors = Total volume * drops factor (drip set) / Hours* 60

Renal Dose Adjustment⁵

CrCL (ml/minute)	Suggested loading dose(when applicable) mg/kg	Suggested initial maintenance dose mg/kg	Suggested dosing interval (hr)
>90 to <130	25–30	15–20	8–12
50 to 90	20–25	15–20	12
15 to 50	20–25	10–15	24
<15	20–25	10–15	48–72

Case presentation

Case 1

He presented with fever for one week, accompanied by chills and rigors, along with a cough and nasal congestion and fast breathing for 5 Days. He had a history of fall from bicycle on day 1 of illness Sustained injury to left knee, now complaints of pain & mid swelling of left knee.

He was initially treated in nearby hospital for severe pneumonia/scrub typhus with antibiotics and high flow oxygen support. Later Scrub typhus IgM was negative, and blood culture was sterile. They referred here for further management.

On presenting in the ER, the patient was febrile, in respiratory distress, wheezing, and with mild swelling of the left knee.

Initial blood investigations revealed anemia, leukocytosis and elevated CRP (90.0 mg/dl)

Chest X-ray showed bilateral heterogeneous opacity and bilateral pleural effusion (Right more than left) and minimal Pericardial effusion.

Mycoplasma IgM antibody test was negative.

Pleural fluid culture showed growth of staph aureus (MSSA).

He was diagnosed to have bilateral pneumonia, right empyema, left pyopneumothorax, and left knee septic arthritis.

He was treated with Inj. Ceftriazone 1250 mg BD for 12 days, Inj. Vancomycin 500 mg TDS for 7 days, Inj. Meropenem 600 mg TDS for 5 days, Inj. Pantocid 40 mg od for 10 days, Inj. Flucloxacillin 250 mg for 8 days and Inj. Neurobion forte for 8 days.

Intervention

After few days of therapy, the patient had signs of AKI- decrease in urine output and elevated Creatinine and urea level. So, he was considered to have vancomycin-induced acute kidney injury then vancomycin was discontinued.

Close monitoring of renal function was initiated, focusing on urine output and Creatinine levels. Supportive management was given. Renal function gradually improved after discontinuation of vancomycon

Case 2

He presented with a history of fever lasting 10 days, followed by loose stools, vomiting, cough, and decreased appetite over the last 3 days. On admission, he was dull-looking and febrile, with notable crepitations in the left infrascapular area.

Initial blood investigations showed leucopenia and significantly elevated CRP levels at 63.9 mg/L. He was suspected of lower respiratory tract infection/enteric fever. The blood and urine cultures were sent, and the results were sterile. He continued to have recurrent fever spikes. Mycoplasma antibody positive was noted.

“Chest X-ray revealed a homogeneous opacity in the left lower zone. To further evaluate, an ultrasound lung screening was done, which showed consolidation in the left lower lobe along with a synpneumonic effusion.”

He was diagnosed as left lower lobe pneumonia with consolidation and effusion.”

He was treated with Inj. Ceftriaxone 700 mg BD for 10 days, Inj. Vancomycin 700 mg TDS for 7 days, Inj. Clindamycin 300 mg TDS for 7 days, Inj. Pantocid 30 mg OD for 12 days, Neb. Levolin TDS for 6 Days.

An intervention

A patient was given Vancomycin 700 mg in 100 ml NS over 1 h, At the end of the infusion, the patient had developed rashes and itching all over the body. Therefore, the infusion was stopped and Inj. Avil was given. We intervened in the adverse drug reaction that occurred due to the rapid infusion of vancomycin.

In this case, the infusion rate was calculated at 11.6 mg per min, as the dose of vancomycin 700 mg was administered over 60 min.

Generally, vancomycin should be infused at a rate of less than 10 mg per min.

The drop factor formula is,

Total volume = Drop factor/Total hour of infusion.

In this case, the drop factor was calculated as 33 drops per min. This corresponds to an infusion rate of 11.6 mg per min.

We recommended extending the infusion time to 120 min.

The resumed dose of vancomycin was given over 120 min. The revised drop factor was 16 drops per min. This corresponds to an infusion rate of 5.83 mg per min.

Conclusion

The management of vancomycin therapy is crucial due to its narrow therapeutic index. Low therapeutic levels can lead to treatment failure, while elevated levels increase the risk of nephrotoxicity and other adverse effects.

To optimize treatment outcomes and minimize the risk of toxicity, we must ensure accurate dosing, and infusion rate adjustment, and closely monitor renal function and serum drug concentration levels.

Reference

Shenoy B, Joshi DN, Doddikoppad P. Vancomycin Therapeutic Drug Monitoring. Pediatric Infectious Disease. 2023 Apr 15; 5(1):17-9.
Rybak M, Lomaestro B, Rotschafer JC, Moellering Jr R, Craig W, Billeter M, Dalovisio JR, Levine DP. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy. 2009 Jan 1; 66(1):82-98.
Welty TE, Copa AK. Impact of vancomycin therapeutic drug monitoring on patient care.
Rodvold KA, Blum RA, Fischer JH, Zokufa HZ, Rotschafer JC, Crossley KB, Riff LJ. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrobial agents and chemotherapy. 1988 Jun; 32(6):848-52.
Reardon J, Lau TT, Ensom MH. Vancomycin loading doses: a systematic review. Annals of pharmacotherapy. 2015 May; 49(5):557-65.

Vancomycin – Therapeutic Drug Monitoring

Vancomycin: Therapeutic drug monitoring

A. Johnson

Nightingale Journals