Antimicrobial stewardship program at a university hospital: an analysis of drug-related problems

Abstract

To evaluate the pharmacotherapeutic interventions in antimicrobials, based on drug-related problems (DRP) implemented by the antimicrobial stewardship program (ASP). This is a posthoc analysis carried out between January 2018 and December 2019 in a University public trauma hospital. The DRP methodology was used to assess correct pharmacotherapy of antibiotics and acceptance by clinicians. Acceptability was defined as accepted within 24 hours, accepted after 24 hours, not accepted, or not accepted with justification. A total of 4,951 prescriptions were audited, of which an average of 16% of interventions resulted in 35.1% in unnecessary medication, 22.6% in administration route. For acceptability, all demonstrated significance according to P values <0.0001. In safety, 49.0% of interventions were performed, 42.0% were needed, and 9.0% were effective. DRP analysis is an important resource to be used within the ASP, bringing significant results both in terms of patient safety and cost minimization.

Keywords:
Antimicrobial stewardship; Pharmacovigilance; Drug-related problems.

INTRODUCTION

The World Health Organization (WHO) highlights the importance of pharmacovigilance in public health, based on the drug-related problems (DRP) analysis. An important tool to be used in the clinical pharmacist’s routine, despite having its therapeutic value, it contributes to the rational prescription of drugs, taking into account risks and benefits (Chaturvedi, Mathur, Anand, 2012; Munir, Khan, Khan, 2024). In this sense, it drives better decision-making of the prescribing physician. The inappropriate prescription of antimicrobials was considered a major concern in infectious diseases. Guidelines for preventing antimicrobial resistance were first published in the 1990s by the Society of Health Epidemiology of America in conjunction with the Society of Infectious Diseases of America (Shlaes et al., 1997).

The Centers for Disease Control and Prevention (CDC) also stressed the importance of antimicrobial stewardship program (ASP) in 2013, which in addition to reducing antimicrobial resistance rates, is an important tool to reduce hospital costs along with environmental sustainability (Fridkin et al., 2014; Karanika et al., 2016). The guidelines recommendations include restricting the inappropriate use of antimicrobials with pre-authorization and/or prospective audit, institutional practice guidelines, and continuing education, which is often used together (Barlam et al., 2016).

Evidence of how to tailor the ASP to the reality of each hospital is an issue that deserves discussion, since human resources, technology, and financial incentives are conflicting factors between the institutions (Goffet al., 2017). The usefulness of the work of the ASP’s multidisciplinary team, including clinical pharmacists, microbiologists, and infectious disease specialists, demonstrates significant results (Dik et al., 2015; Nhan et al., 2019). Antimicrobial resistance rate, the incidence of Clostridioides difficile infection, days of antimicrobial therapy, adverse events, and prescription modifications are data that can be evaluated after ASP implementation to demonstrate the impact of antimicrobial use not only in the hospital as a whole but also in each patient (Wei et al., 2024).

Drug-related problems (DRPs) in the context of antibiotics can lead to adverse events, directly affecting patient safety. Additionally, errors related to medication use may increase hospitalization time, require additional treatments, and significantly raise healthcare costs. For these reasons, addressing antimicrobialrelated DRPs can result in substantial savings for the healthcare system. Another issue associated with DRPs is the compromise in therapeutic efficacy, whether due to incorrect dosages, drug interactions, or inadequate adherence (Parsels et al., 2022).

The identification and resolution of these problems help prevent harm and improve clinical outcomes. In the most recent context, reducing DRPs fosters more efficient and effective care, leading to better clinical outcomes and higher patient satisfaction. This aligns with the global trend of enhancing safety and quality, providing a foundation for hospital certification (Prasad et al., 2024).

The aim of this study was to describe the approach to use the DRP as an important tool to be used in the ASP as a method to report results and actions.

METHODS

This was a prospective study with post-hoc analysis of an antimicrobial rational use program in a Brazilian university hospital, reference for trauma, surgery, and neurosurgery, with 207 beds (29 are intensive care units (ICU), and 178 ward beds). All ICU beds are reference for the same specialties The period for analysis was between January 2018 and December 2019, according to the standardized daily routine of the Center for Epidemiology and Hospital Infection Control (Zequinao et al., 2020).

All patients admitted to wards or ICUs and who had a prescription for antimicrobials for more than one day were included in the analysis, with follow-up occurring until the drug interruption. Data were collected through electronic medical records by the ASP team (Tuon et al., 2024a), consisting of an infectious disease specialist,a clinical pharmacist, and a microbiologist who audit the prescriptions of antimicrobials and microbiological cultures, every day, including weekends, following the infectious disease protocols, which were produced according to the epidemiology of infections acquired in the community or hospital included in the study (Zequinao et al., 2020). Patients under 18 year and unavailable data on medical records were excluded.

Data were collected by the clinical pharmacist from ASP team, including epidemiological data, and other data focused on antibiotic prescription, feeding, as well as potential side effects, including renal function, phlebitis, liver function tests, and hematological parameters. Therefore, the DRP methodology was used to assess dose, frequency, route of administration and oral switch, unnecessary antimicrobial, contraindicated antimicrobial, insufficient pharmacotherapy, infusion rate/time, therapeutic ineffectiveness, inadequate pharmacotherapy, drug or food interaction, antimicrobial incompatibility in the same route of administration, laboratory tests and dilution (Table I) (Ricieri et al., 2021).

TABLE I
Codes for types of incidents related to the therapeutic chain according to the international classification for patient safety

			Identification of Drug-Related Problems
Code	General category	Sub-	DRP description (antimicrobial)	Suggested Intervention
	of DRP	Code
		1.1	Underdose	Elevate the dose
		1.2	Overdose	Lower the dose
1	Dose	1.3	Patient with altered CrCl	Adjust the dose according to ClCr
		1.4	Patient with altered Vancomycin serum level	Adjust the dose according to the
		1.5	Patient with altered Gentamicin serum level	records
2	Frequency	2.1 2.2	Increased Reduced	Lower Frequency Increase Frequency
		3.1 3.2 3.3 3.4	Indication of intravenous antimicrobial Indication of PO ATM	Substitute ATM VO for IV Substitute ATM IV for PO Correct Submission Substitute the route of administration
3	Route of Administration		Wrong Submission Need to change the route according to the clinical condition
		4.1	Patient without infection	Suspend ATM
4	Unnecessary Medicine	4.2	Antimicrobial with prolonged treatment time	Cease the treatment
		4.3	Patient with antimicrobial combination	Suspend ATM
		5.1	Antibiotic R bacteria according to antibiogram	Substitute ATM
	Contraindicated drug	5.2	ATM does not permit adjustment for IR or hepatic	Suspend antimicrobial
		5.3	Patient with previously known ATM allergy	Suspend antimicrobial
		5.4	Patient had an adverse ATM reaction	Substitute ATM
	Insufficient Pharmacothe-	6.1	Need for association for treatment of BGP	Start ATM
6		6.2	Need for association for treatment of BGN	Start ATM
		6.3	Need for fungal treatment association	Start ATM
7	Rate/Time of Infusion	7.1	Extended infusion time	Correct (decrease) infusion time
		7.2	Decreased infusion time	Correct (increase) infusion time
8	Therapeutic ineffectiveness	8.1	Bacteria are not responsive to antimicrobials Antimicrobial without tissue penetration into the	Substitute ATM
		9.1	infectious site	Increase the dose or replace
		9.2	Antimicrobial without indication of a probable	Replace ATM
9	Non-adequate pharmaco-therapy	9.3	infectious site Restricted spectrum antimicrobial	Schedule antibiotic therapy or associate
		9.4	Broad spectrum antimicrobial without specific	De-escalate or suspend
		9.5	restrictions Divergent empirical therapy of laboratory results	Substitute ATM
	Drug or food interaction	10.1	Decreased antimicrobial effectiveness	Alter the ATM’s term
		10.2	Pharmacokinetic change of antimicrobial	Substitute ATM
11	Incompatibility on Y	11.1	Decreased antimicrobial effect	Change the schedule or administra-tion access
	Laboratory exams	12.1 12.2	Monitoring of kidney and liver functions Follow-up of the infectious condition	Request exam
12		12.3	Serum Vancomycin level monitoring	Cancel the order
		12.4	Serum Gentamicin level monitoring
13	Dilution	13.1	Increased dilution	Decreased dilution
13		13.2	Decreased dilution	Increased dilution

For each type of problem related to the antimicrobial, a specific intervention was suggested, and later, the analysis of acceptability by the medical team was defined as accepted within 24 hours, accepted after 24 hours, not accepted, or not accepted with justification.

Antimicrobials are initially prescribed by each medical team; however, it is necessary authorization by the ASP team to prescribe carbapenems, polymyxin, linezolid, ganciclovir, amphotericin, and echinocandins (the first dose is automatically authorized to avoid delay in patients with potential sepsis). The project is approved by the Ethics and Research Committee of PUC/PR, CAAE: 28859719.3.0000.0020. Informed consent was waived considering absence of intervention, and only data collection.

Data were presented in percentages for frequencies. Kolmogorov-Smirnov test was used to evaluate the normality (n > 50). The correlation between the acceptability of interventions after the implementation of the Stewardship program with time was performed using the Pearson’s Product-Moment Correlation (R), evaluating the R2 and considering there to be a correlation of increase or decrease if p <0.05. The pharmacotherapeutic interventions were also adjusted by antibiotic prescription.

RESULTS

During the period analyzed, 4,951 prescriptions were audited (a mean of 206.7/month), of which 16% on average contained pharmacotherapeutic interventions (Figure 1). From 4,951 audit prescription, 35.7% (n=1,768) occurred in the ICU, and other in the wards. The mean age of patients was 54.5+/-17.9 years. 2,634 patients were male (53.2%). The in-hospital mortality was 6.8%, with a higher mortality in the ICU (35.4%) and lower in the ward (3.1%). The main cause of admission were trauma (42.3%), followed by elective surgeries (33.0%), 24.7% were included as clinical conditions and readmission at the emergency room.

FIGURE 1
A total of 4,951 pharmacotherapeutic interventions were performed over two years.

Of the interventions performed, 1,737 (35.1%) resulted in unnecessary medication, 1,121 (22.6%) in administration route, 697 (14.1%) in prescribed dose, 548 (11.1%) in laboratory tests, 336 (6.8%) in nonpharmacological therapy adequate, 222 (4.5%) in frequency and, finally, 290 (5.8%) covered the rest of the interventions (contraindicated drug, insufficient pharmacotherapy, infusion rate/time, therapeutic ineffectiveness, drug and/or food interaction, Y incompatibility and dilution).

As the DRP is based on the concepts of necessity, effectiveness and safety, interventions were also classified in this way. In necessity (unnecessary medication, insufficient pharmacotherapy, therapeutic ineffectiveness, antimicrobial with narrow spectrum, antimicrobial with broad spectrum without specific conditions, and empirical therapy different from the laboratory result) 2,072 (42%) interventions were performed, in effectiveness (underdose, decreased frequency, indication of IV antimicrobial, antimicrobial resistant bacteria according to the antibiogram, antimicrobial without tissue penetration in the infectious site, empirical therapy divergent from the laboratory result, decreased antimicrobial effectiveness, incompatibility in Y, antimicrobial without indication for the likely site of infection and pharmacokinetic change of the antimicrobial) 446 (9%) and in safety (overdose, serum vancomycin, serum gentamicin, clearance of creatinine, increased frequency, need to change the route according to clinical condition, indication of oral switch antimicrobial, incorrect presentation, patient had an adverse reaction, antimicrobial does not allow adjustment for renal and liver failure , restricted to pregnant and lactating women, infusion rate/time, monitoring of renal and/or liver function, dilution, monitoring of the infectious condition, laboratory tests: monitoring of vancomycin and gentamicin levels) 2,433 (49%).

Of the total interventions, 61.3% were performed in the ICU and 38.7% in wards. The acceptability rate in the ICUs was 82.7%, while in the wards it was 58.4%. Regarding the analysis of the adherence to interventions by the medical team during the researched period, it was possible to observe a rise in acceptability within 24 hours, about acceptability in more than 24 hours, to not accepted and not accepted with justification (Figure 2). However, all the interventions proposed throughout the implementation of the ASP, showed significance according to the results of the P value, shown in Table II.

TABLE II
The R² and P values of the acceptability of interventions during implementation of the antimicrobial stewardship program

	Accepted within 24 hours	Accepted in > 24 hours	Not accepted	Not accepted with justification
R2	0.6801	0.6709	0.5403	0.6101
P value	<0.0001	<0.0001	<0.0001	<0.0001

FIGURE 2
Linear regression of the acceptability of interventions after the implementation of the Stewardship program (left). In the right side the data were adjusted for antibiotic prescription in the study period.

DISCUSSION

In the period in which the ASP was establishedin the hospital, in 2018, the data show a low number of interventions, because only the acceptability of one type of intervention was classified, the change from intravenous to oral. In 2019, it was possible to classify more interventions, in addition to acceptability (accepted within 24 hours, accepted after 24 hours, not accepted, and not accepted with justification). This comprehensive audit of 4,951 prescriptions reveals critical insights into pharmacotherapeutic interventions within the healthcare setting. With an average of 16% of prescriptions containing interventions, the data highlight the significant role of medication management in both ICU and ward environments. Notably, 35.7% of interventions occurred in the ICU, where in-hospital mortality was markedly higher.

The number of interventions was not directly proportional over the period, as continuous education work is carried out in the study hospital on prescription. This makes the prescriber more autonomous and start to carry out the prescription according to the use rationale of antimicrobials (Hamilton et al., 2015). The implementation of a good ASP is not a simple task to be performed in a broader sense, especially in an underdeveloped country like Brazil, considering that the reality of each hospital is quite different, which may involve a lack of resources, of a team for program management and even encouragement by leaders (MacDougall, Polk, 2005; da Rocha et al., 2021).

The main intervention in this study was the unnecessary use of antimicrobials, which can generate risks if not performed. Among them is the emergence of multi-resistant bacteria, mainly related to the prolonged use of broad-spectrum antibiotics, those used as prophylaxis for longer than necessary and those redundantly prescribed (Roger et al., 2019). Furthermore, it is an intervention that results in cost reduction, as it discontinues the use of antimicrobials early, in addition to reducing the length of hospital stay for patients (Loesch et al., 2021). A recent review examined the costs associated with prolonged hospitalization in patients who improperly utilize antibiotic therapy, resulting in higher expenses and increased mortality rates (Tuon et al., 2024b). Improving diagnostic strategies could be an alternative to reducing the antibiotic spectrum, particularly through the use of molecular diagnostics (Tuon et al., 2024b). Accurate interpretation of minimum inhibitory concentrations in antibiograms also facilitates dose adjustment based on pharmacokinetics and pharmacodynamics (Telles et al., 2021). Alternative infusion techniques,such as continuous infusion for beta-lactams and reduced intervals for aminoglycosides, are also measures that can mitigate adverse events (Tuon et al., 2018; Yamada et al., 2020; Telles et al., 2023).

Switching from intravenous to oral administration route was the second most performed when classified as an intervention that directly impacts patient safety by reducing the risk of infections related to the use of venous access, such as phlebitis, bacteremia, and endocarditis (Cyriac, James, 2014; Gasparetto et al., 2019). An example would be the switch from intravenous vancomycin tosulfamethoxazole/trimethoprimas an oral tablet or suspension, in infections caused by methicillin-sensitive or resistant Staphylococcus aureus (Paul et al., 2015). Previous study evaluated the switch from intravenous to enteral therapy in ICU patients, demonstrating safety, cost reduction, and decreased workload in Brazil (Gasparetto et al., 2019). In our study, the majority of interventions focused on necessity (42%) and safety (49%), indicating a pressing need to address unnecessary medications and optimize therapeutic effectiveness. The higher acceptability rate of interventions in the ICU (82.7%) compared to the wards (58.4%) suggests a greater willingness among ICU staff to adapt to recommendations, reflecting the critical nature of care in these settings.

Regarding dose and frequency adjustment interventions, the use of aminoglycosides and glycopeptides, if used incoherently, can increase the risk of nephrotoxicity and ototoxicity (Abdelmessih et al., 2022). For nephrotoxicity to be minimized, the adjustment and monitoring of doses of these drugs is an important intervention, especially in patients who have some type of acute renal failure, which in this hospital, due to active DRP, the acute kidney injury rate with aminoglycosides is similar to the use of carbapenems (Tuon et al., 2016). Frequency adjustment is relatedto the administration of aminoglycosides once a day, which aims to achieve the desired therapeutic effect more quickly, which reduces the time of antimicrobial therapy and, consequently, the risk of nephrotoxicity (Gilbert, Robbins, Livornese, 2011; Pitta et al., 2020).

On the other hand, serum monitoring of vancomycin enables the reduction of nephrotoxicity when administered in continuous infusion compared to intermittent infusion, as it reaches the steady state more quickly, in addition to facilitating dose adjustment when necessary (Tuon et al., 2018; Yamada et al., 2020; Tuon et al., 2021). Regarding the rapid infusion time of this antimicrobial, it can cause adverse reactions such as phlebitis, pain, and hypersensitivity reactions (Bruniera et al., 2015).

Some limitations are present in this study, one of them would be the lack of individual data, an important tool to assess the DRP according to the number of visits relating to each patient’s information. However, as there is a large volume of interventions, the time for collecting these data would be restricted and a greater number of professionals would be needed to perform this task.

The observed increase in adherence to proposed interventions over time underscores the importance of continuous monitoring and evaluation in the ASP. These findings not only emphasize the potential for reducing medication errors and enhancing patient safety but also demonstrate the effectiveness of structured pharmacotherapeutic interventions in improving clinical outcomes. The study advocates for ongoing education and collaboration among healthcare professionals to further enhance the efficacy of medication management practices.

ACKNOWLEDGMENTS

Felipe Tuon is a CNPQ Reseacher.

• FINANCIAL SUPPORT
  No financial support was provided relevant to this article.

REFERENCES

• Abdelmessih E, Patel N, Vekaria J, Crovetto B, SanFilippo S, Adams C, Brunetti L. Vancomycin area under the curve versus trough only guided dosing and the risk of acute kidney injury: Systematic review and meta-analysis. Pharmacother. 2022;42(9):741-753.
• Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-77.
• Bruniera FR, Ferreira FM, Saviolli LR, Bacci MR, Feder D, da Luz Gonçalves Pedreira M, et al. The use of vancomycin with its therapeutic and adverse effects: a review. Eur Rev Med Pharmacol Sci. 2015;19(4):694-700.
• Chaturvedi VP, Mathur AG, Anand AC. Rational drug use - As common as common sense? Med J Armed Forces India. 2012;68(3):206-8.
• Cyriac JM, James E. Switch over from intravenous to oral therapy: A concise overview. J Pharmacol Pharmacother. 2014;5(2):83-7.
• da Rocha LGDO, Ribeiro VST, de Andrade AP, Gonçalves GA, Kraft L, Cieslinski J, et al. Evaluation of Staphylococcus aureus and Candida albicans biofilms adherence to PEEK and titanium-alloy prosthetic spine devices. Eur J Orthop Surg Traumatol. 2022;32(5):981-989.
• Dik JW, Hendrix R, Friedrich AW, Luttjeboer J, Panday PN, Wilting KR, et al. Cost-minimization model of a multidisciplinary antibiotic stewardship team based on a successful implementation on a urology ward of an academic hospital. PLoS One. 2015;10(5):e0126106.
• Fridkin S, Baggs J, Fagan R, Magill S, Pollack LA, Malpiedi P, et al. Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep. 2014;63(9):194-200.
• Gasparetto J, Tuon FF, Dos Santos Oliveira D, Zequinao T, Pipolo GR, Ribeiro GV, et al. Intravenous-to-oral antibiotic switch therapy: a cross-sectional study in critical care units. BMC Infect Dis. 2019;19(1):650.
• Gilbert B, Robbins P, Livornese LL Jr. Use of antibacterial agents in renal failure. Infect Dis Clin North Am. 2011;95(4):677-702, vii.
• Goff DA, Kullar R, Bauer KA, File TM Jr. Eight Habits of Highly Effective antimicrobial stewardship programs to meet the joint commission standards for hospitals. Clin Infect Dis. 2017;64(8):1134-1139.
• Hamilton KW, Gerber JS, Moehring R, Anderson DJ, Calderwood MS, Han JH, et al. Point-of-prescription interventions to improve antimicrobial stewardship. Clin Infect Dis. 2015;60(8):1252-8.
• Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E. Systematic review and meta-analysis of clinical and economic outcomes from the implementation of hospital-based antimicrobial stewardship programs. Antimicrob Agents Chemother. 2016;60(8):4840-52.
• Loesch GH, Cruz JAW, Gasparetto J, Oliveira DDS, Telles JP, Tuon FF. Cost minimization analysis of outpatient parenteral/oral antibiotic therapy at a trauma hospital: Public health system. Infect Control Hosp Epidemiol. 2021;42(12):1445-1450.
• MacDougall C, Polk RE. Antimicrobial stewardship programs in health care systems. Clin Microbiol Rev. 2005;18(4):638-56.
• Munir MZ, Khan AH, Khan TM. Healthcare professionals’ understanding and perception of drugrelated issues linked to off-label pharmacological medications used forCOVID-19.ExpertRev Anti Infect Ther. 2024;22(6):487-493. doi: 10.1080/14787210.2024.2310004. Epub 2024 Jan 31. PMID: 38263904.
  » https://doi.org/10.1080/14787210.2024.2310004.
• Nhan D, Lentz EJM, Steinberg M, Bell CM, Morris AM. Structure of antimicrobial stewardship programs in leading us hospitals: Findings of a nationwide survey. Open Forum Infect Dis. 2019;6(4):ofz104.
• Parsels KA, Kufel WD, Burgess J, Seabury RW, Mahapatra R, Miller CD, Steele JM. Hospital discharge: An opportune time for antimicrobial stewardship. Ann Pharmacother. 2022;56(8):869-877.
• Paul M, Bishara J, Yahav D, Goldberg E, Neuberger A, Ghanem-Zoubi N, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ. 2015;350:h2219.
• Pitta RD, Gasparetto J, De Moraes TP, Telles JP, Tuon FF. Antimicrobial therapy with aminoglycoside or meropenem in the intensive care unit for hospital associated infections and risk factors for acute kidney injury. Eur J Clin Microbiol Infect Dis. 2020;39(4):723-728.
• Prasad N, Lau ECY, Wojt I, Penm J, Dai Z, Tan ECK. Prevalence of and risk factors for drug-related readmissions in older adults: A systematic review and meta-analysis. Drugs Aging. 2024;41(1):1-11.
• Ricieri M, Barreto H, Pasquini-Netto H, Okumura L, Sofka D, Fachi M, Motta F. PRAT tool: a harmonization of antimicrobial stewardship program interventions. J Basic Appl Pharm Sci. 2021;42:e735.
• Roger PM, Montera E, Lesselingue D, Troadec N, Charlot P, Simand A, et al. Risk factors for unnecessary antibiotic therapy: A major role for clinical management. Clin Infect Dis. 2019;69(3):466-472.
• Shlaes DM, Gerding DN, John JF Jr, Craig WA, Bornstein DL, Duncan RA, et al. Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals. Clin Infect Dis. 1997;25(3):584-99.
• Telles JP, Leme RCP, Campos ML, Ito C, Bail L, Nogueira KDS, Tuon FF. Ceftriaxone and methicillinsusceptible staphylococcus aureus: a perspective from pharmacokinetics/pharmacodynamics studies. Expert Opin Drug Metab Toxicol. 2021;17(9):1039-1048.
• Telles JP, Morales R Jr, Yamada CH, Marins TA, D’Amaro Juodinis V, Sztajnbok J, et al. Optimization of antimicrobial stewardship programs using therapeutic drug monitoring and pharmacokineticspharmacodynamics protocols: A cost-benefit review. Ther Drug Monit. 2023;45(2):200-208.
• Tuon FF, Aragao BZ, Santos TA, Gasparetto J, Cordova K, Abujamra M. Acute kidney injury in patients using amikacin in an era of carbapenem-resistant bacteria. Infect Dis (Lond). 2016;48(11-12):869-71.
• Tuon FF, Romero R, Gasparetto J, Cieslinski J. Vancomycin trough level and loading dose. Infect Drug Resist. 2018;11:2393-2396.
• Tuon FF, Yamada CH, Cieslinski J, Dos Santos Oliveira D, Ribeiro VST, Gasparetto J, Telles JP. Cerebrospinal fluid penetration of vancomycin during continuous infusion therapy in patients with nosocomial ventriculitis. Ther Drug Monit. 2021;43(6):807-811.
• Tuon FF, Zequinao T, da Silva MS, Silva KO. eHealth and mHealth in antimicrobial stewardship to reduce mortality in empirical antimicrobial therapy and a systematic review with a meta-analysis of adequate therapy. Infect Dis Rep. 2024a;16(4):707-723.
• Tuon FF, Zequinao T, da Silva MS, Silva KO. eHealth and mHealth in antimicrobial stewardship programs. Digit Biomark. 2024b;8(1):194-206.
• Wei C, Hu M, Chen G, Yan Z, Yin W, Wu Z. Costeffectiveness analysis of pharmaceutical care in adult critically ill patients: based on a prospective cohort study. Front Pharmacol. 2024;15:1446834.
• Yamada CH, Telles JP, Oliveira DDS, Cieslinski J, Ribeiro VST, Gasparetto J, Tuon FF. Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units. Braz J Infect Dis. 2020;24(4):356-359.
• Zequinao T, Gasparetto J, Oliveira DDS, Silva GT, Telles JP, Tuon FF. A broad-spectrum beta-lactamsparing stewardship program in a middle-income country public hospital: antibiotic use and expenditure outcomes and antimicrobial susceptibility profiles. Braz J Infect Dis. 2020;24(3):221-230.

Edited by

• Associate Editor:
  Silvana Nair Leite

Publication Dates

• Publication in this collection
  12 Jan 2026
• Date of issue
  2025

History

• Received
  12 July 2024
• Accepted
  09 Dec 2024