Impact of the timing of antibiotic prophylaxis on the surgical site infections in patients undergoing elective general surgery

Abstract

INTRODUCTION:

Surgical site infections are one of the major challenges in surgical practice. The antibiotic prophylaxis, though scientific, still lacks clarity on the timing of the administration of the drugs.

METHODS:

An interventional study was planned in the Department of General Surgery at PGIMER, Chandigarh. One hundred twenty-seven patients who met the inclusion and exclusion criteria were enrolled. They were divided into two groups using a table of random numbers into Group A (n = 67) where the drug was administered 0–30 min before incision, and Group B (n = 60) where the drug was injected 30–60 min before incision. Both the surgical team and the investigator for the SSI were blinded.

RESULTS:

The distribution of sex ratio, comorbidities, and the hematological parameters was equal among groups. The mean blood loss, operative times, and the type of surgical procedures were also distributed equally. There was significantly low SSI in Group A (n = 2) versus Group B (n = 8) (P = 0.03). Drains were placed in 41 patients; 9 out of the 10 patients who reported SSI had an intraoperative drain placed. The placement of the drain was significantly associated with SSI (P < 0.001).

CONCLUSIONS:

Administering prophylactic antibiotics within 30 min before the surgical incision is effective. Placement of the Drain must be avoided to prevent SSI.

Introduction

Surgical site infections are one of the major causes of morbidity among surgical patients. Although multiple interventions have been advised and investigated, it still remains a major challenge to address these problems.[1] The Surgical site infection (SSI) is primarily caused by the inoculation of the bacterial flora at the wound site. Presurgical cleansing of the incision site using the antiseptic solution, providing adequate preoperative antibiotic cover, and better sterilization techniques have stood the test of time for preventing these complications.[2]

Antibiotic prophylaxis is traditionally administered before the incision is made. It is usually given at the start of the time of the induction of anesthesia.[3] However, the choice of the antibiotic and the timings primarily depend upon the type of surgery, the flora of the bacteria that has to be addressed, and the time the drug takes to reach the maximal concentration at the surgical site. The commonly used antibiotic in general surgical procedures is cefuroxime in the dose of 1.5/3 g. This is usually repeated if the procedure is prolonged more than 4–6 h.[4]

Although there is no debate as to whether the antibiotics must be given or not[5] but the timing of the prophylaxis may pose a definite threat of surgical infections.[3] Usually, the timings of the antibiotic administration may be divided into two time slots, i.e. after shifting the patient to the operating room or before that. The antibiotic, if administered just before the patient is shifted to the OR provides enough time for the drug to reach maximum concentration; however, it can be counterproductive if there is a delay in the start of surgery or the anaesthetic induction takes time. With an intent to establish the precise timings of the preoperative antibiotic prophylaxis, this study was planned at a tertiary care institute in northern India.

Methods

A prospective study was planned in the department of General Surgery at PGIMER Chandigarh, a tertiary care hospital in north India. It was approved by the institutional ethics committee vide letter no INT/IEC/2021/SPL1802 dated December 27, 2021. One hundred twenty-seven patients who underwent clean or clean-contaminated surgery in the department between July 2021 to December 2022 were included in the study. The inclusion criteria were patients between 18 and 80 years of age who underwent clean or clean-contaminated surgery with informed consent. The patients who were immunocompromised, had positive cultures, or in whom the intraoperative antibiotic irrigation was used were excluded from the study. A detailed history and other demographic details were noted. All the patients underwent general physical examination and local area examination which was entered in the Excel sheet. The subjects were then prescribed biochemical tests such as liver function tests, serum electrolytes, blood sugars, and renal function tests. They also underwent complete blood counts and coagulation profiles along with chest X-ray and electrocardiogram as part of preanesthetic workup. Radiological tests like ultrasound, Computerized tomography, or magnetic resonance imaging were performed only if required during the evaluation of a particular ailment. All the patients were then optimized for the existing comorbidities, and necessary clearances from the associated departments were obtained.

All the patients were then randomized into two groups using a table of random numbers. Group A (n = 67) were the patients who were given a shot of injection cefuroxime 1.5 g after entering the operating room, i.e. between 0 and 30 min of surgery. Group B (n = 60) comprised patients who were injected with the antibiotic in the preoperative room, i.e. these patients were administered the dose 30–60 min before the incision. The anesthesia team was aware of the patient allocation, whereas the surgical team was blinded to the patient allocation. The intraoperative fluid management and anesthetic protocols were similarly followed in both groups.

These patients were then assessed by a blinded principal investigator for the signs of infection, discharge, redness, swelling, and any other complications. The wounds were classified using the Southampton wound grading system.[6] The morbidity of the patients was classified using the Clavien-Dindo classification.[7]

Statistical analysis

Data were entered into a Microsoft Excel sheet. It was analyzed using SPSS version 27, IBM SPSS Statistics, Somers, NY, USA. Continuous variables were represented as mean with standard deviation. Categorical variables were represented as proportions. The Chi-square test was used to analyze the significance of qualitative variables. T-test was used to test the significance of quantitative variables. P <0.05 was considered significant.

Results

Demographic data

There were 67 patients in group A and 60 patients in group B. The average age of the study participants was 44.83 ± 14.9 years. The average age for males was 44.03 ± 15.07 years and for females 45.17 ± 14.91 years. The male-to-female ratio and other demographic parameters and the comorbidities were equally distributed among the two groups [Table 1].

Table 1.

The demographic details

Parameter	Group A (n=67)	Group B (n=60)	P
Males	21	17	0.96
Females	46	43	0.67
Age of participants	45.39±14.98	43.98±15.3	0.69
Hypertension	7	6	1.00
Hypothyroidism	3	2	0.876
Diabetes	8	5	0.54
Coronary disease	1	0	0.72
Asthma	0	2	0.433
Jaundice	1	0	0.23
Hb <10 (g/dL)	2	2	0.99

Hb=Hemoglobin

Operative parameters

The operative parameters such as mean operative time, mean blood loss, and type of surgeries were equally distributed among the groups [Table 2].

Table 2.

The operative parameters

Parameter	Group A (n=67)	Group B (n=60)	P
Mean duration <30 min	35	32	0.34
Mean duration 30–60 min	30	24	0.588
More than 60 min	2	4	0.218
Mean blood loss (mL)	45±23.6	51±32.6	0.11
Drain placement	20	21	0.23
Type of surgery
Clean surgery	32	22	0.08
Clean contaminated	35	38	0.76
Surgical procedures
Laparoscopic cholecystectomy	31	29	0.66
Laparoscopic appendectomy	0	3	0.79
Open cholecystectomy	2	3	0.87
CBD exploration	1	1	0.34
Extended cholecystectomy	1	2	0.12
Breast surgery	18	12	0.67
Hernioplasty	12	9	0.23
Cervical rib excision	1	0	0.45
Soft-tissue tumor excision	1	1	1.00

CBD=Common bile duct

Postoperative parameters

There were reports of wound infections in Group A, whereas there were eight infections in Group B which was significant (P = 0.03). The two infections reported in Group A were subsequent to laparoscopic cholecystectomy and extended cholecystectomy, whereas it was subsequent to laparoscopic cholecystectomy, laparoscopic appendectomy, and extended cholecystectomy in Group B. This may be due to a higher number of clean-contaminated surgeries in this group [Table 3].

Table 3.

The postoperative parameters

Parameter	Group A (n=67)	Group B (n=60)	P
Wound infections	2	8	0.03
Infective organisms
Staphylococcus aureus	1	1	0.22
Klebsiella	0	3	0.07
Enterococcus spp.	1	4	0.110
Morbidity (class)
I	65	52	0.74
II	1	4	0.06
III	1	4	0.1

Effect of drains on wound infections

Out of the total 127 patients, 41 patients had intraoperatively placed drains among whom 9 were infected. Placement of intraoperative drain was associated with significantly high post op wound infections, P < 0.001 [Table 4].

Table 4.

The effect of intraoperative drains on surgical site infections

Intraoperative drain	SSI		P
	Yes	No
Yes	9	32	<0.001
No	1	85

SSI=Surgical site infections

Discussion

Surgical site infections were, and are still, one of the nightmares for a practicing surgeon. Despite the change in the guidelines and improved techniques of sterilization, there are multiple reports of these infections in daily surgical practice. These may be attributed to certain human errors and technical errors during the surgical procedure.[8] The spectrum of SSI can vary from simple erythematous changes to a morbid organ space infection.[9] The patients with surgical site infections may require additional doses of antibiotics, debridement, aspiration, and percutaneous drainage of the collected pus. Various strategies have been reviewed and investigated with regard to the prevention of these infections; however, only a few have stayed the test of time.

Preoperative antibiotics are one of the well-engraved strategies to prevent the SSI. The antibiotic, if given before the incision, reduces the microbial flora at the site and prevents the further colonization of bacteria in the wound. It is so effective that this has been placed as a component in the World Health Organization safety checklist.[10] Although a well-known strategy, the timings of the administration of the drug still remains an area of investigation. There are studies who have favored the administration within 30 min of incision, whereas there are others which present an opposite view.[3,11]

The choice of drug and its pharmacokinetic properties govern the timing of the administration of these drugs. This is also compounded by the fact that the type of surgery also interlaces with the above factors. The drug used in the current study was cefuroxime 1.5 g[11] which is the drug of choice for the procedures done in the study. The administration and the timings of the injection were known to the anesthetist; however, the investigator as well as the surgeons were blinded to the allocation which might have led to improved observer bias and the Hawthorne effect.

There was a significantly higher infection rate in the patients where the drug was administered more than 30 min before the incision. This might be due to the fact that the prolonged surgery >60 min, higher mean blood loss, and higher number of patients with drains were present in this group. The placement of the drain was a single factor which determined the occurrence of infection in the postoperative period.[12] Nine out of the ten patients who developed SSI were from the group with drains. The placement of the drain exposes the peritoneal cavity to the exterior. It also allows a surface for biofilm formation and antibiotic resistance.[13] The drains when placed must be removed at the earliest. There is enough literature available where the placement of drains in various emergency or elective surgeries has led to increased postoperative morbidity. The drains must be used with caution and should only be placed if required.[14]

The study demonstrates the fact that the preoperative antibiotic must be administered just in time for it to achieve maximal concentration at the time of giving incision. The choice of antibiotic is determined by the pharmacokinetic properties of the drug and the type of surgery being done. Small sample size with monocentric recruitment of patients might have hampered the study outcomes. We recruited only clean and clean-contaminated general surgical patients. Recruiting a wide sample from various spectrums of surgical specialties might have given us more generalized and reliable outcomes. This was a single-center trial, with only cefuroxime used as a preanesthetic antibiotic. Multicentric trials with various other recommended drugs might help us to make consensus guidelines for the question under study.

Conclusion

To conclude the preoperative administration of prophylactic antibiotics within 30 minutes of surgery helps to prevent SSI. Moreover, the drains must be used jud.

Data availability statement

The data of the study is available with the corresponding author, LK, who can be produced on demand.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.