Assessment of Pattern of Conversion from Intravenous to Oral Antimicrobial Agents at a Tertiary Care Hospital- A Cross-Sectional Study

Introduction

Antimicrobial resistance (AMR) is among the top ten global health threats and poses a serious risk to both the economy and public health.¹ AMR happens when microorganisms evolve over time and cease to respond to antibiotics, making infections more difficult to cure, raising the risk of disease transmission, severe sickness, and death.²

Globally, India is one of the biggest consumers of antibiotics with 10.7 units/person annually, driven by multiple factors such as high burden of infections and excessive use of antibiotics,rising incomes and increasing access.^3,4 

Antimicrobial stewardship (ASP) has been defined as “the optimal selection, dosage, and duration of antimicrobial treatment that results in the best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance”.⁵

ASPs recommend early conversion from intravenous (IV) to oral antimicrobial agents (AMA) therapy, which consist of short course of IV AMAs for 48-72 hours, followed by oral therapy for remainder of the course. This has been shown to have many advantages like early discharge, reduced incidence of cannula-related infections and thrombophlebitis, and reduced cost of treatment.⁶

The conversion of IV to oral therapy can be achieved by three methods: Sequential therapy involves converting the same intravenous AMA to oral form; Switch therapy involves converting to an oral AMA with the same potency; and Step-down therapy involves converting to an oral AMA with a lower potency.⁶

As a step towards rationalizing AMA prescriptions in the hospital, this study was conducted to analyse the practice of conversion of IV to oral AMAs using predefined criteria.

Materials and Methods

Research design

This descriptive cross-sectional study was conducted in March 2024 among in-patients admitted to surgical and medical departments of Victoria Hospital, attached to Bangalore Medical College and Research Institute, Bangalore.

The study was conducted after obtaining approval from the Institutional Ethics Committee of Bangalore Medical College and Research Institute (No. BMCRI/EC/07/24). Informed consent was obtained from each patient before the study.

Sample

Based on a previous study by Shrayteh ZM et al., 26.1% of patients were converted from IV to oral AMAs as soon as the criteria were fulfilled.⁷ By assuming absolute precision of 10%, confidence level of 95% and with estimated missing data of 20%, the overall sample size was determined to be 90.⁷ The participants were selected using computer generated simple random sampling numbers.

Inclusion criteria

Patients of either gender, aged over 18 years and receiving IV AMAs for a minimum of 48 hours, were included in the study. Patients who were ineligible for oral therapy, receiving prophylactic IV AMAs, or admitted in intensive care units were excluded. 

Tools used

The demographic characteristics and comorbidities of patients along with the diagnosis or indication for AMA therapy and investigations were noted from the case record forms at the point of discharge, in a specific proforma. The name and class of AMAs administered with the dose, route, and frequency of administration were noted. Additional information was noted on the conversion from IV to oral AMA therapy, the type of conversion, and details of oral AMAs used. Eligibility for conversion was based on the Antimicrobial Stewardship Program (AMSP) guidelines of the Indian Council of Medical Research (ICMR).⁸ Patients were considered eligible if they could tolerate oral therapy, had no vomiting or diarrhoeadiarrhea, and demonstrated clinical improvement -defined as a temperature below 38°C and a declining trend in white blood cell count -after receiving 48 hours of IV AMAs.

Statistical analysis

The data obtained were analyzed using Microsoft Excel. Descriptive and inferential statistics were applied. Results were expressed as frequencies, percentages, and mean ± standard deviation.

A Chi-square goodness-of-fit test was performed to assess whether the distribution of conversion types differed significantly from a uniform distribution. An unpaired t-test was used to compare the mean IV duration between patients who were converted to oral therapy and those who were not. A one-way ANOVA was conducted to compare the mean IV duration across different conversion types.

A P-value of <0.05 was considered statistically significant.

Results

Patient characteristics

A total of ninety patients were included in the study having a mean age of 44.1+8.77 years. Of these, 53 (58.9%) were male and 37 (41.10%) were female. Among the enrolled patients, 38 patients had at least one underlying comorbidity. The most frequent comorbidities encountered were diabetes mellitus (27; 71.05%), and hypertension (21; 55.26%) (Table 1). 

The most common indications for AMA therapy were abdominal conditions (36.7%), followed by infections affecting the skin and soft tissue (24.4%).). (Table 2).

Details regarding drug therapy

The mean duration of intravenous antimicrobial therapy was longer in patients who were converted to oral therapy (6.5±3.20 days) compared to those who were not converted (5.8±2.47 days); this difference was not statistically significant (P=0.29; Unpaired t-test).

The average number of IV and oral drugs prescribed per patient were five and two, respectively.

Cephalosporins were the most frequently prescribed AMAs, both intravenously (57.80%) and orally (48.30%) (Figure 1). Thirty-four patients were on more than one IV AMA. Six patients were on concurrent oral AMA therapy which included macrolides, albendazole, nitrofurantoin, and oseltamivir. Fifty-seven patients were on other concurrent oral medications with an average of three medications per patient. These mostly included drugs taken for the comorbidities like oral hypoglycemics, anti-hypertensives, aspirin, statins. All the 90 patients were on other concurrent IV medications with an average of 3.5 medications per patient. These mostly included drugs like pantoprazole, antiemetics, and analgesics like paracetamol, tramadol. 

Conversion from IV to PO therapy

Among the study participants, 67% were converted from intravenous to oral AMA, while 33% remained on IV therapy. 

Among the 60 patients converted from IV to oral therapy, switch therapy (45; 40.5%) was significantly more common than sequential (11; 9.9%) and step-down therapies (4; 3.6%) (P <0.001; Chi-square goodness-of-fit test) (Table 3).

The most frequently observed conversion was the switch therapy, with conversion from IV Ceftriaxone to oral Cefixime being the most common (25.60%), followed by IV Piperacillin-Tazobactam to oral Amoxicillin-Clavulanate (20%).

Seventy-eight patients were eligible for early conversion within 48-72 hours as per the criteria, out of which only 37 patients (47.44%) were converted to oral AMA on time. The mean duration of IV treatment among eligible patients was 6.4+3.10 days (Table 4).

A one-way ANOVA was done to compare the mean IV duration across the three conversion types – switch, sequential and step-down therapies. There was no statistically significant difference in IV duration between the groups (F=0.356, P=0.70) (Table 5).

Discussion

WHO has declared AMR as one of the top ten global public health threats faced by humanity. Antibiotic resistance is expected to be the next big pandemic. Antimicrobial resistance is projected to cause 10 million deaths annually worldwide by 2050, with an associated loss of 100 trillion US dollars in global GDP.⁹ 

AMR poses a significant public health problem in terms of mortality and economic loss in India. ICMR has initiated nationwide AMSP to promote rational antibiotic use and thereby reduce AMR and improve patient safety. Setting up of AMSP is now considered a pre requisite for hospital accreditation. Comprehensive guidelines for setting up AMSP have been published by ICMR. Audit of antimicrobial use, providing feedback and timely interventions to streamline antibiotic prescriptions is the core component of AMSP. The prescribed intravenous AMAs should be audited after 48-72 hours of prescription by the AMSP committee. A decision must be made to either continue, discontinue, or modify the antibiotic therapy.³

A Cochrane meta-analysis on the effectiveness of intervention on the antibiotic prescription pattern reported that the duration of antibiotic use was reduced by 1.95 days and the duration of hospitalization by 1.12 days. Implementation of AMSP has been demonstrated to lower the overall dose of antibiotics used as well as the duration of therapy with antibiotics.¹⁰

The majority of in-patients are administered IV antibiotics, even when they are eligible for oral therapy. For non-life-threatening or non-serious infections, transitioning from IV antibiotics to oral equivalents after 2–3 days of treatment is a viable approach. This strategy has been demonstrated to improve clinical outcomes, including shorter hospital stays, enhanced patient convenience, and reduced healthcare costs.

The present study was conducted to assess the trends in pattern of conversion of IV to oral AMAs. The conversion rate was 67%, with the average duration of IV AMA administration being six days.

Many studies conducted in India depicted similar results. Tejaswini et al., reported that 43.68% of antibiotics were converted from IV to oral formulations, while 56.32% of antibiotic courses were not converted, in a tertiary care hospital in Andhra Pradesh, India. Out of all IV to oral conversions, sequential therapy was more commonly used than switch and step-down therapies. The mean duration for IV to oral conversion in sequential therapy was calculated to be 3.95 days.¹¹

Another study from Kerala, India, conducted to assess the practice of IV to oral conversion of AMAs, reported that out of 274 cases, 187 (68.25%) AMAs were converted from IV to oral therapy, while 87 (31.75%) remained unconverted. Step-down conversion was the most commonly noted (42.24%), followed by switch (32.09%) and sequential (25.67%) therapies. The study also mentioned that the early switch reduced the duration of hospital stay.¹²

The predominance of switch therapy over sequential and step-down in the current study suggests a strong clinical preference toward switch therapy. This may be due to the higher availability, familiarity, or perceived efficacy of oral agents like Cefixime and Amoxicillin-Clavulanate which are commonly used in switch conversions.

Among the 78 patients eligible for early conversion within 48-72 hours, only 37 (47.44%) underwent the transition as per the established criteria. The mean duration of IV therapy among eligible patients was prolonged at 6.4 ± 3.10 days, indicating potential overuse of IV therapy in scenarios where oral therapy might have been clinically appropriate. A study by Sharmila et al. in Australia reported that 57% of the patients who met the switch criteria were converted to oral AMA within 24 hours. The median delay in switching was found to be 1.75 days.¹³ The findings in the current study may stem from various factors, including clinical inertia, hesitation due to perceived concerns about oral therapy efficacy, or lack of awareness and adherence to established protocols.

A study to compare the effectiveness of early switch from IV to oral antibiotics in severe pneumonia in children reported that injectable Penicillin and oral Amoxicillin were equivalent for the management of severe pneumonia, and early switch significantly reduced duration of stay in hospital. The study also noted that the patients on IV therapy reported oedema/extravasation, inflammation, and abscess at the site of cannula.¹⁴

Penicillins, Cephalosporins and Fluroquinolones were the most preferred antimicrobial agents for switching from IV to oral route. The oral antibiotics should achieve similar serum bactericidal activity as its IV counterpart for the switch therapy to be effective.¹⁵ There has always been a concern that orally administered AMAs may not yield serum concentrations as high as the IV form. Fluroquinolones, followed by Cephalosporins and Amoxicillin, have been reported to possess good bioavailability and are therefore considered suitable agents for switch therapy.¹⁶

Though ICMR guidelines have been released, a strict implementation of all the core elements of antibiotic stewardship programme is essential to rationalize the use of AMAs. Early switching from IV to oral AMAs offers several advantages, like reducing the complications associated with injections and overall treatment costs.

Limitations

The study enrolled patients with various infections caused by different microorganisms, which may complicate direct comparisons.

Conclusion

The overall rate of IV to oral antibiotic conversion was 67%, with switch therapy being the most common type. Among these, the conversion from IV Ceftriaxone to oral Cefixime was the most common. However, out of 78 patients eligible for early conversion, only 37 transitioned to oral antibiotics. This study highlights the urgent need to develop institutional guidelines for IV to oral AMA conversions aligned with antibiotic stewardship principles. Such guidelines can help minimize prolonged and unnecessary use of parenteral therapy, optimize conversion practices, and positively impact patient health outcomes and healthcare costs.

Conflict of Interest

The authors declare no conflict of interest.