Randomised controlled trial of preoperative antibiotic prophylaxis in the prevention of surgical site infections in tertiary care hospital of central India

Dr. Simran Dhole; Dr Chandrashekhar Mahakalkar

doi:10.12688/f1000research.143982.1

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Study Protocol

Randomised controlled trial of preoperative antibiotic prophylaxis in the prevention of surgical site infections in tertiary care hospital of central India

[version 1; peer review: 2 approved with reservations]

Dr. Simran Dhole ¹, Dr Chandrashekhar Mahakalkar¹

PUBLISHED 26 Apr 2024

Author details Author details

¹ Department of Surgery, Jawaharlal Nehru Institute of Medical College, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe),, Wardha, Maharashtra, 442001, India

Dr. Simran Dhole
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Dr Chandrashekhar Mahakalkar
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Datta Meghe Institute of Higher Education and Research collection.

Abstract

Background

Surgical site infections (SSI) remain a significant concern in the realm of surgical interventions, posing a threat to both patient well-being and healthcare systems. This study protocol outlines a rigorous investigation aimed at assessing the effectiveness of pre-operative antibiotic prophylaxis in the prevention of SSIs in clean and clean-contaminated surgical cases within the tertiary care setting of central India. The primary aim is to determine the best suitable antibiotic regimen, optimal timing for administration, and the associated economic burden of SSIs.

Method

The study utilizes a Randomized Controlled Trial (RCT) design with four intervention groups, each receiving distinct antibiotic prophylaxis protocols. Comprehensive post-operative monitoring, adhering to the Centers for Disease Control and Prevention (CDC) guidelines, will be employed to identify SSI occurrences. Key data collection points include clinical evaluations, temperature monitoring, wound inspection, pain assessments, and culture and sensitivity testing.

Expected outcome

The study also emphasizes post-operative follow-up assessments, incorporating outpatient visits at 15-, 30-, and 90-days post-surgery. These evaluations will be instrumental in assessing the time duration for effective prophylactic antibiotic administration and determining the economic burden associated with SSI. The findings of this research endeavor hold the potential to enhance patient outcomes, minimize SSI incidences, and reduce the economic impact of SSIs on healthcare systems. By optimizing pre-operative antibiotic prophylaxis practices, this study aims to advance evidence-based guidelines for SSI prevention in clean and clean-contaminated surgical cases.

CTRI

REF/2023/07/070549

Keywords

Surgical Site Infections, Pre-operative Antibiotic Prophylaxis, Randomized Controlled Trial, Post-operative Monitoring, Tertiary Care Hospital, Economic Burden

Corresponding author: Dr. Simran Dhole

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2024 Dhole DS and Mahakalkar DC. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Dhole DS and Mahakalkar DC. Randomised controlled trial of preoperative antibiotic prophylaxis in the prevention of surgical site infections in tertiary care hospital of central India [version 1; peer review: 2 approved with reservations]. F1000Research 2024, 13:400 (https://doi.org/10.12688/f1000research.143982.1) First published: 26 Apr 2024, 13:400 (https://doi.org/10.12688/f1000research.143982.1) Latest published: 26 Apr 2024, 13:400 (https://doi.org/10.12688/f1000research.143982.1)

Introduction

Surgical site infections (SSIs) continue to be a significant concern within the realm of surgical procedures, posing a substantial threat to patient well-being and a substantial economic burden on healthcare systems. SSIs are among the most prevalent healthcare-associated infections worldwide, accounting for a considerable proportion of postoperative complications and prolonged hospital stays.¹ Consequently, SSIs contribute to increased healthcare costs, decreased patient quality of life, and an elevated mortality risk.²

Preventive measures, such as pre-operative antibiotic prophylaxis, have been a cornerstone in the battle against SSIs. While prophylactic antibiotics are considered standard practice in many surgical settings, questions linger regarding the most effective antibiotic regimens and the optimal timing of administration.³ This study seeks to address these issues by conducting a randomized controlled trial (RCT) to assess the efficacy of pre-operative antibiotic prophylaxis in preventing SSIs, specifically in clean and clean-contaminated surgical cases.

The World Health Organization (WHO) recognizes the importance of evidence-based strategies for SSI prevention, emphasizing the need for tailored approaches to specific surgical contexts.⁴ In alignment with this global perspective, our study is set in a tertiary care hospital in central India. By focusing on this setting, we aim to provide insights and recommendations relevant to the local healthcare landscape and can be extrapolated to comparable healthcare environments.

This RCT design randomly allocates patients to different antibiotic prophylaxis groups, offering a platform to rigorously assess the efficacy of distinct antibiotic regimens and their associated impact on SSI incidence. Additionally, this study emphasizes meticulous post-operative monitoring per the Centers for Disease Control and Prevention (CDC) guidelines.⁵ This approach is essential for early detection and management of SSIs, ultimately contributing to the generation of robust data.

The economic repercussions of SSIs are profound, encompassing not only direct medical costs but also indirect expenses, such as extended hospital stays and potential legal consequences.⁶ Understanding the economic burden of SSIs is integral to the broader objective of enhancing patient outcomes and healthcare system efficiency.

The outcomes of this investigation hold the promise of advancing evidence-based guidelines for SSI prevention in clean and clean-contaminated surgical cases. By optimizing pre-operative antibiotic prophylaxis practices, we aim to mitigate the occurrence of SSIs and curtail their associated economic costs, ultimately enhancing patient care and healthcare sustainability.

Aim

The study aims to investigate the efficacy of pre-operative antibiotic prophylaxis in preventing surgical site infections (SSI) in clean and clean-contaminated surgical cases in a tertiary care hospital in central India.

Objectives

1. Determination of SSI incidence: The primary objective is to determine the incidence of surgical site infections in patients undergoing elective surgery in the clean and clean-contaminated categories.
2. Identification of best preoperative antibiotic prophylaxis: To assess the best preoperative antibiotic prophylaxis in preventing surgical site infections.
3. Time interval for antibiotic prophylaxis: To determine the optimal time interval for administering preoperative antibiotic prophylaxis.
4. Economic burden estimation: To estimate the economic burden of patients who develop surgical site infections.

Methods

Study setting

The study will be conducted in the Department of Surgery at Jawaharlal Nehru Medical College (JNMC) and Acharya Vinoba Bhave Rural Hospital (AVBRH) in Wardha, Maharashtra, India. These facilities serve as the study locations set up for the 2023-2024 period.

Inclusion criteria

• Patients undergoing elective surgery in the clean and clean-contaminated categories.
• Age between 5 and 60 years.
• Presence of specific comorbidities.
• Both genders are included in the study.

Exclusion criteria

• Patients undergoing contaminated surgical cases.
• Patients with uncontrolled diabetes.
• Obese patients.

Interventions

Patients will be divided into four groups based on the timing and type of preoperative antibiotic prophylaxis they receive:

1. Group A: Patients receive a preoperative single dose of ceftriaxone (Ceftrisol Plus) CAS [104376-79-6] 4gm, administered 31-60 minutes before surgery.
2. Group B: Patients receive a preoperative single dose of Augmentin 1.2gm (amoxicillin-clavulanate) CAS No: 74469-00-4, administered 31-60 minutes before surgery.
3. Group C: Patients receive a preoperative single dose of ceftriaxone, administered 0-30 minutes before surgery.
4. Group D: Patients receive a preoperative single dose of Augmentin, administered 0-30 minutes before surgery.

Outcomes

1. Primary outcome: Determination of the best suitable antibiotic for preventing surgical site infections in clean and clean-contaminated cases.
2. Secondary outcomes:
- • Effective time duration for the administration of prophylactic antibiotics.
- • Estimation of the economic burden associated with surgical site infections.

Participant timeline

1. Pre-intervention evaluation: This involves collecting clinical history, conducting clinical examinations, and routine tests (complete blood count, kidney function tests, liver function tests, random blood sugar, electrocardiogram).
2. Surgery and antibiotic administration: Participants receive the allocated preoperative antibiotic prophylaxis.
3. Post-operative monitoring: Post-operative monitoring, as per the guidelines provided by the Centers for Disease Control and Prevention (CDC).⁷
Timing and duration of post-operative monitoring: The CDC recommends the vigilant monitoring of patients for at least 30 days following their surgical procedure, with a more extended duration, up to 90 days, for cases involving implant placement. This extended monitoring period ensures the detection of delayed infections that may occur post-surgery.
Clinical evaluation: Post-surgery, patients will undergo routine clinical evaluations. This includes a comprehensive assessment for any signs or symptoms of SSI. Clinical indicators include redness, swelling, tenderness, delayed wound healing, warmth around the surgical site, and purulent discharge. Any such manifestations should be recorded and evaluated promptly.
Temperature monitoring: Body temperature monitoring is a vital part of post-operative assessment. Measurement of the patient’s temperature should be conducted at regular intervals. A fever, a body temperature exceeding 38.0 degrees Celsius, can be an early indicator of infection and should be closely monitored.
Wound inspection and assessment: Routine wound inspection is necessary. During these assessments, examining the surgical incision site for any abnormal changes is crucial. This includes looking for signs of infection, such as purulent discharge or localized redness. Any deviations from the expected healing process should be noted.
Assessment of pain: Pain assessment is integral to post-operative monitoring. Significant localized pain at the surgical site can strongly indicate infection. Monitoring pain levels and changes in pain perception is essential to early detection.
Swelling and tenderness: Continual monitoring for localized swelling and tenderness around the surgical incision site is paramount. These are common indicators of SSI, and any observed symptoms should be documented and addressed promptly.
Culture and sensitivity testing: In cases where infection is suspected, the collection of swabs or samples from the surgical site is necessary. These samples should be forwarded for culture and sensitivity testing to identify the microorganisms responsible for the infection and their antibiotic sensitivity profiles. These results are crucial for effective treatment planning.
Wound dressing changes: If dressings are in place, they should be regularly inspected for signs of soakage or infection. Soiled or infected dressings should be changed, and the wound should be re-evaluated to assess the progression of healing and any signs of SSI.
Suture removal and follow-up appointments: Sutures or staples should be removed according to the established timeline, typically around the 7th day post-surgery. Additionally, it is essential to schedule follow-up appointments for patients at specific intervals, such as 15, 30, and 90 days after their surgical procedures. During these follow-up visits, a thorough assessment should be conducted to evaluate temperature, pain, tenderness, and any indications of localized infection.
Detailed documentation: Comprehensive records should be maintained for all post-operative monitoring activities. This includes detailed documentation of temperature measurements, wound assessments, culture reports, and any interventions or treatments administered in response to suspected infections. Accurate record-keeping is crucial for analyzing and evaluating the study’s primary and secondary outcomes.
Unblinding procedure: In situations where unblinding is necessary due to patient safety or treatment requirements, a well-defined and documented procedure should be in place to ensure the study’s integrity is maintained throughout the process.
4. Follow-up visits: Participants are followed up at specific intervals postoperatively: 15 days, 30 days, and a final visit at 90 days.
5. Active surveillance: Active surveillance is conducted throughout the postoperative period to monitor patient outcomes.

Recruitment: Patients who meet the inclusion criteria and do not fall under the exclusion criteria are eligible for recruitment. Informed consent will be obtained from all patients before enrollment. Recruitment occurs at the study locations (JNMC and AVBRH) as part of the patient evaluation process for elective surgery in the clean and clean-contaminated categories. The study will ensure that patients are informed about the study’s objectives, procedures, and potential risks and benefits before obtaining their consent for participation.

Sample size

The sample size for the study has been calculated to be 200 patients based on the formula:

n \geq ({Z_{(1 - α / 2)}}^{2} * p * (1 - p)) / d^{2}

Where:

• α (alpha) = 0.05 (significance level, typically set at 0.05 for a 95% confidence level)
• p (proportion) = 0.033 (the estimated proportion of surgical site infection in patients postoperatively as per the reference article)
• d (estimated error) = 0.05 (5% margin of error)

By plugging in these values, get:

n \geq ({1.96}^{2} * 0.033 * (1 - 0.033)) / {0.05}^{2} \approx 200

Allocation

1. Randomization: The allocation of patients to different intervention groups will be performed through computer-generated randomization. This process ensures that each patient has an equal chance of being assigned to any of the four study groups (Group A, B, C, or D). Randomization will be conducted by an independent statistician not directly involved in patient recruitment or care to reduce bias. The randomization sequence will be concealed until the point of assignment.
2. Concealment of allocation: The randomization sequence will be kept in sealed, opaque envelopes, and the allocation will occur just before the administration of preoperative antibiotics. This process ensures that the clinical team and patients know their group assignment once the intervention is administered.
3. Assignment of interventions: Based on the assigned group, patients will receive preoperative antibiotic prophylaxis per the study protocol. The assignment will be performed by a nurse or healthcare professional not part of the primary clinical team.

Blinding

1. Double-blind procedure: Both patients and the clinical team responsible for patient care will be blinded to the group assignment. The antibiotics used in the study will be prepared and labeled by a pharmacy team who are not directly involved in the patient’s care. This ensures that the identity of the antibiotics remains concealed from the clinical team and patients.
2. Data collection: The personnel responsible for data collection and outcome assessment will be kept separate from the clinical team providing patient care. They will need access to information about the patients’ group assignments. This separation helps maintain blinding during data collection and outcome assessment.
3. Unblinding procedure: An unblinding procedure will be in place in emergencies where knowledge of the group assignment is essential for patient safety. The unblinding process will be overseen by an unblinded third party to ensure the integrity of the study remains intact.

Data collection methods

1. Pre-operative evaluation: Detailed pre-operative evaluations will be conducted for each patient before surgery. This includes clinical history, proforma, physical examination, and routine laboratory tests, such as complete blood count, kidney function tests, liver function tests, and random blood sugar levels. Electrocardiograms will also be performed to assess cardiac health.
2. Allocation and intervention data: Data related to the allocation of patients to specific intervention groups (Groups A, B, C, or D) and the timing of antibiotic administration will be recorded. This includes the type of antibiotic administered, the timing of administration about the surgery (in minutes), and any deviations from the protocol.
3. Surgical procedures: Details of the surgical procedures, including the type of surgery, duration, and any complications encountered during the surgery, will be documented.
4. Post-operative management: Patients will be monitored during their post-operative period following surgery. This includes assessing signs and symptoms of surgical site infections and any other complications that may arise. The presence of fever, pain, tenderness, redness, swelling, delayed healing, or any other relevant indicators will be recorded.
5. Microbiological data: Swabs will be collected from the surgical site for culture and sensitivity testing in cases where infection is suspected. The results of these tests, including the types of organisms and their antibiotic sensitivity profiles, will be documented.
6. Follow-up visits: Patients will undergo follow-up visits on days 15, 30, and 90 postoperatively. Data related to fever, purulent discharge, pain, tenderness, local swelling, culture results, and any changes in total leukocyte count (TLC) will be collected during these visits. These data points will help assess patient recovery and the occurrence of SSIs.

Data management

1. Data entry and storage: All collected data will be entered into a secure electronic database with restricted access. The data will be organized and stored in a way that ensures patient confidentiality and data integrity.
2. Quality control: Regular checks and quality control measures will be implemented to ensure the accuracy and completeness of the data.
3. Data security: Measures will be taken to safeguard the data against unauthorized access or loss. Backup procedures and encryption will be used to protect the data.
4. Data monitoring committee: An independent data monitoring committee may oversee the data collection process and ensure data quality and integrity.

Statistical methods

In the statistical analysis, Firstly, descriptive statistics, encompassing measures like means, medians, standard deviations, and frequencies, will provide an overview of patient characteristics and baseline data. Secondly, inferential statistics will be the focus of the primary analysis, involving a comparison of surgical site infection incidence across the four intervention groups (Groups A, B, C, and D). Statistical tests like chi-squared and t-tests will be employed to evaluate outcome differences. Thirdly, survival analysis techniques, including Kaplan-Meier curves and Cox proportional hazards models, will be used to assess the time until the occurrence of surgical site infections (SSI). Additionally, economic analysis will be conducted, estimating the economic burden through cost-effectiveness analysis, involving the assessment of SSI-associated costs and healthcare utilization, with the computation of cost-effectiveness ratios. Multivariable regression analysis will be employed to account for potential confounding variables, utilizing logistic regression for binary outcomes and linear regression for continuous outcomes. The entire statistical analysis will be conducted using the R studio Version 4.3.1 software package, and results will be considered statistically significant if the p-value is below a predetermined alpha level of 0.05.

Ethical considerations and consent

The Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol (Reference number: DMIHER (DU)/IEC/2022/57. Date:18-07-2022). Before commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives.

Dissemination

After the completion of the study, we will publish it in an indexed journal or conference.

Study status

The study has yet to start. After the publication of the protocol, we will start recruitment in the study.

Discussion

The primary objective of this study is to determine the most effective antibiotic prophylaxis regimen for preventing SSIs in clean and clean-contaminated surgical cases. Evidence from previous studies has highlighted the importance of selecting appropriate antibiotics with optimal coverage for the specific pathogens associated with the surgical procedure.⁸ Our RCT design, which randomly assigns patients to different antibiotic groups, provides a robust platform for assessing the comparative efficacy of antibiotic regimens.

The study is particularly relevant given the varying resistance patterns of pathogens in different regions and healthcare settings.⁹ By conducting this research in a tertiary care hospital in central India, we aim to provide insights tailored to the local epidemiological context. These findings will be invaluable for clinicians and healthcare systems in similar settings, enhancing their capacity to make informed decisions about pre-operative antibiotic prophylaxis.

Another critical aspect of the study is evaluating the optimal timing for antibiotic administration. Recent research has indicated that the timing of antibiotic prophylaxis relative to the incision significantly prevents SSIs.¹⁰ Our study includes groups receiving antibiotics 30 minutes or 60 minutes before surgery, allowing for a comparison of their efficacy. The outcomes will provide valuable guidance to surgeons regarding the ideal timing of antibiotic administration to maximize SSI prevention.

The economic burden of SSIs extends beyond direct medical costs and includes indirect expenses, such as prolonged hospital stays, legal consequences, and the impact on healthcare system efficiency.¹¹ This study’s focus on estimating the economic burden of SSIs offers a comprehensive perspective on the true costs associated with these infections. Understanding the financial implications of SSIs is pivotal for healthcare providers and policymakers aiming to allocate resources efficiently and reduce the overall economic impact of SSIs.

Ethical considerations and consent

The Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol (Reference number: DMIHER (DU)/IEC/2022/57. Date:18-07-2022). Before commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives.

Author contribution

1. Dr. Simran Dhole: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing
2. Dr. Chandrashekhar Mahakalkar: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Data availability

No data are associated with this article.

Extended data

Zenodo: Proforma for the data collections ‘Randomised controlled trial of preoperative antibiotic prophylaxis in the prevention of surgical site infections in tertiary care hospital of central India’, https://doi.org/10.5281/zenodo.10983223.

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Reporting guidelines

Zenodo SPIRIT checklist for ‘Randomised controlled trial of preoperative antibiotic prophylaxis in the prevention of surgical site infections in tertiary care hospital of central India’, https://doi.org/10.5281/zenodo.10983159.

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

References

1. Allegranzi B, Pittet D: Role of hand hygiene in healthcare-associated infection prevention. J. Hosp. Infect. 2009; 73: 305–315. Publisher Full Text
2. Costabella F, Patel KB, Adepoju AV, et al.: Healthcare Cost and Outcomes Associated With Surgical Site Infection and Patient Outcomes in Low- and Middle-Income Countries. Cureus. 15: e42493. PubMed Abstract | Publisher Full Text | Free Full Text
3. Crader MF, Varacallo M: Preoperative Antibiotic Prophylaxis. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
4. Surgical site infection: Accessed: October 17, 2023. Reference Source
5. Healthcare Equipment|Disinfection & Sterilization Guidelines|Guidelines Library|Infection Control|CDC.2019. Accessed: February 20, 2024. Reference Source
6. Anderson DJ, Podgorny K, Berríos-Torres SI, et al.: Strategies to Prevent Surgical Site Infections in Acute Care Hospitals: 2014 Update. Infect. Control Hosp. Epidemiol. 2014; 35: 605–627. PubMed Abstract | Publisher Full Text | Free Full Text
7. Surgical Site Infection|Guidelines|Infection Control|CDC: 2019. Accessed: October 17, 2023. Reference Source
8. Bratzler DW, Houck PM: Surgical Infection Prevention Guideline Writers Workgroup: Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Am. J. Surg. 2005; 189: 395–404. PubMed Abstract | Publisher Full Text
9. Allegranzi B, Pittet D: Healthcare-associated infection in developing countries: simple solutions to meet complex challenges. Infect. Control Hosp. Epidemiol. 2007; 28: 1323–1327. PubMed Abstract | Publisher Full Text
10. Weber WP, Marti WR, Zwahlen M, et al.: The timing of surgical antimicrobial prophylaxis. Ann. Surg. 2008; 247: 918–926. Publisher Full Text
11. de Lissovoy G , Fraeman K, Hutchins V, et al.: Surgical site infection: incidence and impact on hospital utilization and treatment costs. Am. J. Infect. Control. 2009; 37: 387–397. Publisher Full Text

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Version 1

VERSION 1 PUBLISHED 26 Apr 2024

Author details Author details

¹ Department of Surgery, Jawaharlal Nehru Institute of Medical College, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe),, Wardha, Maharashtra, 442001, India

Dr. Simran Dhole
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Dr Chandrashekhar Mahakalkar
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (1)

version 1

Published: 26 Apr 2024, 13:400

https://doi.org/10.12688/f1000research.143982.1

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© 2024 Dhole DS and Mahakalkar DC. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Dhole DS and Mahakalkar DC. Randomised controlled trial of preoperative antibiotic prophylaxis in the prevention of surgical site infections in tertiary care hospital of central India [version 1; peer review: 2 approved with reservations]. F1000Research 2024, 13:400 (https://doi.org/10.12688/f1000research.143982.1)

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PUBLISHED 26 Apr 2024

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Reviewer Report 02 Aug 2024

John Alverdy, Department of Surgery, University of Chicago, Chicago, USA

Approved with Reservations

https://doi.org/10.5256/f1000research.157715.r305239

The statement “Additionally, this study emphasizes meticulous post-operative monitoring per the Centers for Disease Control and Prevention (CDC) guidelines.5 This approach is essential for early detection and management of SSIs, ultimately contributing to the generation of robust data” is in ... Continue reading

The statement “Additionally, this study emphasizes meticulous post-operative monitoring per the Centers for Disease Control and Prevention (CDC) guidelines.5 This approach is essential for early detection and management of SSIs, ultimately contributing to the generation of robust data” is in need of revision. It is not clear to this reviewer how the study will be able to assess those patients that actually suffer from an SSI. The CDC criteria state that if a clinician observes a postoperative wound and deems it to be “infected” then it is logged as an SSI. Most SSIs today are superficial wound infections, most are not opened and most are treated non-operatively with antibiotics only. Using this CDC guideline approved method, the CDC criteria cannot distinguish between those superficial SSIs (which represent the majority >75%) that are actually SSI versus those that are are simply postoperative inflammation. The assertion that the PI will “swab all wounds” in which an SSI is suspected cannot account for this, swabbing a closed wound will only yield skin flora which cannot be deterministically linked to the SSI itself. The only way to do this would be to open all wounds, inspect them and determine which is actually infected—which itself is complicated. So investigators call this a “pragmatic trial” meaning, this is all we can do to get the answer, which belies the methods needed. However, in India, where multi-drug resistant strains are emerging as highly threatening to surgical patients and based on emerging knowledge in the field that today many (but not all) infections arise from pathogens endogenous to the patient not exogenously, (see Long DR, et.al.2024 (Ref 1) while a single IV dose of an antibiotic is probably safe, broadening coverage in complete ignorance to its long term effects needs to be carefully considered (although this is a universal trend in surgery—meaning if some is good, more is better). A better (and of course more expensive way) to do this is to swab wounds just prior to closure and also swab the mouth, rectum, skin and urine, bank samples for later analysis, and when an SSI develops retrieve the sample from the SSI and use NGS (next generation sequencing) to determine the resistance genes present and where the pathogen actually came from. This requires strain-level genetic analysis and of course retrieval of the pathogen actually in the SSI site. No one will do this, cuz its too costly and labor intensive. But is has been done (see- ref 1) and is the only way to drive SSI rates from where they are now down toward zero. Empirically adding more and showing a P value of a difference does not reconcile “within-group” differences. For example, if group A (standard antibiotics) has a SSI rate of 20% and broader antibiotic coverage (group B) results in a lower SSI rate of 10% and the P value is <0.05, why did 80% of group A patients NOT develop an SSI and why did 10% of group B patients still develop an SSI? Without this information, independent of the noisy swab data intended to be obtained in this study, not much will be learned except that if some is good then more is better (perhaps then the answer to driving the 10% further down is to add a second antibiotic, then if it ends up at 3-5% then add a third antibiotic and so on).

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

No
Are sufficient details of the methods provided to allow replication by others?

No
Are the datasets clearly presented in a useable and accessible format?

Not applicable

References

1. Long DR, Bryson-Cahn C, Waalkes A, Holmes EA, et al.: Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery.Sci Transl Med. 2024; 16 (742): eadk8222 PubMed Abstract | Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: molecular pathogenesis of postoperative infection

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Reviewer Report 27 May 2024

Stefan Acosta, Lund University, Malmö, Sweden

Approved with Reservations

https://doi.org/10.5256/f1000research.157715.r280716

Overall evaluation: This study protocol is well written. The study intends to avoid common biases such as performance or assessor bias. There will be computer-generated randomization. Also state (in Methods) whether this study will receive industry company funding or if ... Continue reading

Overall evaluation: This study protocol is well written. The study intends to avoid common biases such as performance or assessor bias. There will be computer-generated randomization. Also state (in Methods) whether this study will receive industry company funding or if the investigators have any connection with industry providing the antibiotics. 90-day follow up is optimal and is a major strength of this study. I think the authors should add cases – approximately 20% to the sample size estimation for loss to follow-up, especially for the 90-day follow up mark.
These methodological strengths are merited to be outlined in the discussion, especially the double-blind design, since outcome assessor bias often is a problem in these kinds of studies where the investigators in charge also evaluate the wounds.

This kind of study requires funding to be run comfortably. How will this be achieved? Research nurse? Some information on funding should be stated in the manuscript (In Methods).

Introduction:
Some words on the antimicrobial profiles of the two given antibiotics would be appropriate, and why you choose these antibiotics.
Some words on the expected type of surgery. Expected percentage of laparotomy?

Specific com:

1. CTRI should be spelled out. I believe this is a formal registration of the study protocol in a clinical register
2. Secondary outcomes. “Effective time duration” – you mean “effective time period of preoperative administration of prophylactic antibiotics”
3. Sample size calculation – state the reference article (stating that the SSI rate is 3.3%) here as well.

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Vascular surgery, surgical site infections,

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Stefan Acosta, Lund University, Malmö, Sweden
John Alverdy, University of Chicago, Chicago, USA

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02 Aug 2024 | for Version 1

John Alverdy, Department of Surgery, University of Chicago, Chicago, USA

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Approved With Reservations

The statement “Additionally, this study emphasizes meticulous post-operative monitoring per the Centers for Disease Control and Prevention (CDC) guidelines.5 This approach is essential for early detection and management of SSIs, ultimately contributing to the generation of robust data” is in need of revision. It is not clear to this reviewer how the study will be able to assess those patients that actually suffer from an SSI. The CDC criteria state that if a clinician observes a postoperative wound and deems it to be “infected” then it is logged as an SSI. Most SSIs today are superficial wound infections, most are not opened and most are treated non-operatively with antibiotics only. Using this CDC guideline approved method, the CDC criteria cannot distinguish between those superficial SSIs (which represent the majority >75%) that are actually SSI versus those that are are simply postoperative inflammation. The assertion that the PI will “swab all wounds” in which an SSI is suspected cannot account for this, swabbing a closed wound will only yield skin flora which cannot be deterministically linked to the SSI itself. The only way to do this would be to open all wounds, inspect them and determine which is actually infected—which itself is complicated. So investigators call this a “pragmatic trial” meaning, this is all we can do to get the answer, which belies the methods needed. However, in India, where multi-drug resistant strains are emerging as highly threatening to surgical patients and based on emerging knowledge in the field that today many (but not all) infections arise from pathogens endogenous to the patient not exogenously, (see Long DR, et.al.2024 (Ref 1) while a single IV dose of an antibiotic is probably safe, broadening coverage in complete ignorance to its long term effects needs to be carefully considered (although this is a universal trend in surgery—meaning if some is good, more is better). A better (and of course more expensive way) to do this is to swab wounds just prior to closure and also swab the mouth, rectum, skin and urine, bank samples for later analysis, and when an SSI develops retrieve the sample from the SSI and use NGS (next generation sequencing) to determine the resistance genes present and where the pathogen actually came from. This requires strain-level genetic analysis and of course retrieval of the pathogen actually in the SSI site. No one will do this, cuz its too costly and labor intensive. But is has been done (see- ref 1) and is the only way to drive SSI rates from where they are now down toward zero. Empirically adding more and showing a P value of a difference does not reconcile “within-group” differences. For example, if group A (standard antibiotics) has a SSI rate of 20% and broader antibiotic coverage (group B) results in a lower SSI rate of 10% and the P value is <0.05, why did 80% of group A patients NOT develop an SSI and why did 10% of group B patients still develop an SSI? Without this information, independent of the noisy swab data intended to be obtained in this study, not much will be learned except that if some is good then more is better (perhaps then the answer to driving the 10% further down is to add a second antibiotic, then if it ends up at 3-5% then add a third antibiotic and so on).

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

No
Are sufficient details of the methods provided to allow replication by others?

No
Are the datasets clearly presented in a useable and accessible format?

Not applicable

References

1. Long DR, Bryson-Cahn C, Waalkes A, Holmes EA, et al.: Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery.Sci Transl Med. 2024; 16 (742): eadk8222 PubMed Abstract | Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

molecular pathogenesis of postoperative infection

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Reviewer Report

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27 May 2024 | for Version 1

Stefan Acosta, Lund University, Malmö, Sweden

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Approved With Reservations

Overall evaluation: This study protocol is well written. The study intends to avoid common biases such as performance or assessor bias. There will be computer-generated randomization. Also state (in Methods) whether this study will receive industry company funding or if the investigators have any connection with industry providing the antibiotics. 90-day follow up is optimal and is a major strength of this study. I think the authors should add cases – approximately 20% to the sample size estimation for loss to follow-up, especially for the 90-day follow up mark.
These methodological strengths are merited to be outlined in the discussion, especially the double-blind design, since outcome assessor bias often is a problem in these kinds of studies where the investigators in charge also evaluate the wounds.

This kind of study requires funding to be run comfortably. How will this be achieved? Research nurse? Some information on funding should be stated in the manuscript (In Methods).

Introduction:
Some words on the antimicrobial profiles of the two given antibiotics would be appropriate, and why you choose these antibiotics.
Some words on the expected type of surgery. Expected percentage of laparotomy?

Specific com:

1. CTRI should be spelled out. I believe this is a formal registration of the study protocol in a clinical register
2. Secondary outcomes. “Effective time duration” – you mean “effective time period of preoperative administration of prophylactic antibiotics”
3. Sample size calculation – state the reference article (stating that the SSI rate is 3.3%) here as well.

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Vascular surgery, surgical site infections,

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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[1] 1. Allegranzi B, Pittet D: Role of hand hygiene in healthcare-associated infection prevention. J. Hosp. Infect. 2009; 73: 305–315. Publisher Full Text

[2] 2. Costabella F, Patel KB, Adepoju AV, et al.: Healthcare Cost and Outcomes Associated With Surgical Site Infection and Patient Outcomes in Low- and Middle-Income Countries. Cureus. 15: e42493. PubMed Abstract | Publisher Full Text | Free Full Text

[3] 3. Crader MF, Varacallo M: Preoperative Antibiotic Prophylaxis. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.

[4] 4. Surgical site infection: Accessed: October 17, 2023. Reference Source

[5] 5. Healthcare Equipment|Disinfection & Sterilization Guidelines|Guidelines Library|Infection Control|CDC.2019. Accessed: February 20, 2024. Reference Source

[6] 6. Anderson DJ, Podgorny K, Berríos-Torres SI, et al.: Strategies to Prevent Surgical Site Infections in Acute Care Hospitals: 2014 Update. Infect. Control Hosp. Epidemiol. 2014; 35: 605–627. PubMed Abstract | Publisher Full Text | Free Full Text

[7] 7. Surgical Site Infection|Guidelines|Infection Control|CDC: 2019. Accessed: October 17, 2023. Reference Source

[8] 8. Bratzler DW, Houck PM: Surgical Infection Prevention Guideline Writers Workgroup: Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Am. J. Surg. 2005; 189: 395–404. PubMed Abstract | Publisher Full Text

[9] 9. Allegranzi B, Pittet D: Healthcare-associated infection in developing countries: simple solutions to meet complex challenges. Infect. Control Hosp. Epidemiol. 2007; 28: 1323–1327. PubMed Abstract | Publisher Full Text

[10] 10. Weber WP, Marti WR, Zwahlen M, et al.: The timing of surgical antimicrobial prophylaxis. Ann. Surg. 2008; 247: 918–926. Publisher Full Text

[11] 11. de Lissovoy G , Fraeman K, Hutchins V, et al.: Surgical site infection: incidence and impact on hospital utilization and treatment costs. Am. J. Infect. Control. 2009; 37: 387–397. Publisher Full Text

Randomised controlled trial of preoperative antibiotic prophylaxis in the prevention of surgical site infections in tertiary care hospital of central India

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