# Role of immune system in prophylaxis antibiotic's surgical site infection control

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $392,500

## Abstract

Role of immune system in prophylaxis antibiotic’s surgical site infection control
Despite many advances in infection control practices – including improved operating room ventilation, barriers,
sterilization methods, improved surgical techniques, surgical site infection (SSI) remains a significant cause of
morbidity, prolonged hospitalization, and death with an estimated annual cost of $3.5 to $10 billion in
healthcare expenditures in the US alone. Administration of prophylaxis antibiotics in the perioperative period
(~1h prior to surgery) is the standard of care for most surgical procedures. However, even short-term antibiotic
use is associated with the emergence of antibiotic resistance, as well as, increased risk for Clostridium difficile
infection, and immunological and neurological diseases, many of which have been attributed to dysbiosis in the
gut flora due to antibiotics. Novel approaches (preferably antibiotic-free) are urgently needed to address SSI.
Surgical site infection is considerably worse in immunocompromised patients where prophylaxis antibiotics are
considerably much less effective, even in the case where the infective pathogen is sensitive to the
administered antibiotics. Whether or not immune system plays a direct role in boosting prophylaxis antibiotics
effectiveness or prophylaxis antibiotics functioning in heightening immune system has not been studied.
Rather, reduced antibiotic effectiveness in immunocompromised patients has been blamed on factors, such as
therapy-induced neutropenia, or disregulated innate immune responses, and/or impaired neutrophil functions.
Driven by our preliminary data, we hypothesize that bacterial killing by prophylaxis antibiotics at the site of
infection results in immune system activation which in turn directly boosts the effectiveness of antibiotics by
mobilizing immune leukocytes to the site of infection. In aim 1 of this proposal, we will assess the molecular
mechanism(s) that couple innate immune system with prophylaxis antibiotics. In aim 2, we will test our
hypothesis that immunomodulators -- that can mobilize and activate immune system at the site of infection --
will be effective in controlling surgical site infections even in the absence of prophylaxis antibiotics. We will use
an implant and a wound animal models for surgical site infection to evaluate the effectiveness of
immunomodulator-based therapies (single vs. in combination with antibiotics) as compared to prophylaxis
antibiotics alone in controlling local and systemic infections. We will also assess the possible deleterious side-
effects of immunomodulator-based approaches on animal health and normal physiological processes.
These comprehensive studies will tackle surgical site infection which is an important public health concern.
They will address critical knowledge gaps in our understanding of the direct role that immune system plays in
boosting infection control by prophylaxis antibiotics. And they will lay the groundwork...

## Key facts

- **NIH application ID:** 10269052
- **Project number:** 5R01AI150668-02
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** SASHA H SHAFIKHANI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2020-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10269052

## Citation

> US National Institutes of Health, RePORTER application 10269052, Role of immune system in prophylaxis antibiotic's surgical site infection control (5R01AI150668-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10269052. Licensed CC0.

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