Although it is rare, intraoperative infection of ACL arthroscopic is a potentially devastating post-operative complication. There has been a marked increase in anterior cruciate ligament reconstruction (ACLR) patients worldwide. Septic arthritis (SA) after ACLR is unfamiliar. The reported occurrence rate fluctuates between 0.14% and 1.8% [1]. The commonly reported predisposing factors implicated in developing SA after an ACLR are (age, body mass index, diabetes, smoking, previous or simultaneous surgeries, prolonged operation time, long tourniquet inflation time, drain application, and graft choice). It may require multiple reoperations in the form of irrigation and debridement, prolonged use of antibiotics, removal of the graft, and sometimes graft revision surgery. It also harms functional outcomes, increases the risk of early osteoarthritis, and causes graft failure [1, 3].

Preoperative intravenous antibiotics given before skin incision in arthroscopic ACLR may not be sufficient enough to reach minimum inhibitory concentration (MIC) levels due to poor vascularity of hamstring tendons, in addition harvested autograft is prone to infection from skin flora, and an adequate concentration of antibiotics to inhibit bacterial growth can be achieved with the local application of antibiotics over the graft during processing [1, 5]. The most common pathogen after ACLR is staphylococci, accounting for 90% of cases of septic arthritis [6]. The anterior cruciate ligament (ACL) is the major stabilizing ligament of the knee, it originates at the medial wall of the lateral femoral condyle and inserts into the middle of the intercondylar eminence area of tibia. Three avascular areas can be detected within the ligament, in the attachment zones of the ligament to the femur and the tibia and avascular zone is located in the center of harvested ACL autograft; the absence of blood vessels in this area may be the result of compressive stress caused by the anterior end of the notch and may encourage bacteria to grow and lead to septic arthritis, also The highly vascularized joint synovium lacks a limiting basement membrane, so it is prone to infection via hematogenous seeding from systemic infection [7, 8] . Infecting organisms multiply in the synovial fluid and synovial lining, some bacteria (e.g., S. aureus) produce virulence factors (adhesins), which allow bacteria to penetrate, remain within and infect joint tissue [9].

Several studies supported using presoaking harvested grafts in vancomycin solution to reduce the incidence of septic arthritis following ACLR [10]. Vancomycin is commonly used because of its properties like heat stability, bactericidal action against organisms like Staphylococcus aureus, but it is costly, reserved to be used for resistance to bacterial infection (MRSA) and concerns like antibiotic resistance, side effects like nephrotoxicity, ototoxicity, red man syndrome and high cost associated with the use of vancomycin [11]. Ceftriaxone is a third-generation antibiotic from the cephalosporin family of antibiotics. It is within the \(\beta\)-lactam family of antibiotics, selectively and irreversibly inhibits bacterial cell wall synthesis by binding to transpeptidases and leads to damage and destruction of the cell wall; also it has a broad spectrum of activity in vitro against Gram-positive and Gram-negative aerobic and some anaerobic bacteria [12]. The objective of the present study was to compare the infection rate between presoaking of harvested hamstring with or without augmentation soft tissue with ceftriaxone and presoaking autograft just with 0.9% sodium chloride (N/S) during ACLR to decrease the infection rate post-operative.

A prospective comparative case-control study was conducted to investigate the impact of local ceftriaxone irrigation on patients undergoing primary Anterior Cruciate Ligament Reconstruction (ACLR). The study spanned from April 2022 to July 2023, and forty patients were recruited from Basrah Teaching Hospital.

Patient Selection

Patients meeting the inclusion criteria, including symptomatic ACL injury, age \(\leq\) 65 years, and proven damage to ACL within 2 years post-injury, were enrolled in the study. Exclusion criteria comprised individuals requiring ACL revision, open procedures, simultaneous osteotomy, bilateral ACL injury, multi-ligamentous injury, ACL injury for more than 2 years, intravenous drug abuse, alcoholism, steroid use, diabetes mellitus, prior history of infection, active local infection near the knee joint, and patients sensitive to ceftriaxone.

Data Collection

Detailed patient histories were obtained, covering identity information, time of injury, main complaints, duration, type of trauma, history of present illness, system review, past medical and surgical history, drug history, family history, and social history. Patients underwent general and local examinations, including special tests for ACL injury (anterior drawer, Lachman, and pivot shift tests).

Clinical Assessment

The Lysholm Score [13] was used for pre and postoperative assessment. Radiological examinations were conducted preoperatively to confirm ACL and associated knee joint injuries. Biochemical laboratory tests, including complete blood count, C-reactive protein, erythrocyte sedimentation rate, renal function tests, liver function tests, random blood sugar, and general urine examination, were performed pre and postoperatively. Pain severity was assessed using the Visual Analog Scale (VAS).

Surgical Procedure

The ACL reconstruction surgical equipment was sterilized preoperatively, and the hamstring tendon, consisting of gracilis and semitendinosus tendons, was used as a soft tissue autograft. The surgeon followed a universal arthroscopic protocol for harvesting the ACL autograft. The ceftriaxone solution (1gm ceftriaxone in 500 mL N/S) was used for irrigation of the harvested graft, and the control group received plain N/S (100 mL). The graft was irrigated with the ceftriaxone solution every 5-10 minutes during the procedure.

Postoperative Follow-up

Patients were routinely followed with laboratory tests (CBC, CRP, ESR, LFT, and RFT) at 2, 4, and 6 weeks postoperatively, along with necessary radiological examinations. Any patient displaying increased postoperative symptoms was subjected to biochemical laboratory testing and joint fluid aspiration to confirm or rule out postoperative infection.

Data Analysis

Data analysis was performed using the Statistical Package for Social Sciences (SPSS) version 25. Descriptive statistics, including mean, standard deviation, frequencies, and percentages, were presented through tables and bar charts. Continuous variables were assessed for statistical normal distribution, and statistical tests, including Student t-test, F-test, and Chi-square, were employed to compare means and frequency distributions, considering a significance level of \(p \leq 0.05\).

Figure 1: Illustrations show Ceftriaxone (1gm. Vial, Sodium Chloride 0.9%).(2.5 B) Micro drip Containing 100ml N/S Ceftriaxone Diluted Formula

Forty patients admitted to the hospital were divided into two groups. Group A (study) were twenty patients with mean age of 28.35\(\pm\)10.42. Group B (control) were twenty patients with mean age of 25.75 \(\pm\) 5.61. All of them are fit for ACL arthroscopic reconstruction; patients’ groups are separated randomly. According to Table 1, there is no significant difference (P >0.05) in the distribution of demographic characteristics between study group and control groups.

According to Table 2, there is no significant difference (P >0.05) in the distribution of associated procedure, type of graft between study group and control groups.

Table 3 shows the clinical characteristics of study group and control groups. According to this table, there is no significant difference (P >0.05) in the distribution of demographic characteristics between study group and control groups except in (Tourniquet Time). This table also shows that the majority of study group are: those with tourniquet time (79-99) minutes (55%) and those with no infection (100%).

Regarding control group, the majority of participants are: those with tourniquet time (67-78) minutes and those with no infection (90%) and with postoperative infection (10%).

Table 4 shows joint fluid aspiration results of two cases from control group with positive parameter of postoperative infection which revealed two infected cases postoperative from control group.

The Table 5 reveals that there is no significant difference (P >0.05) between study group and control group regarding all the markers.

According to Table 6, there is significant decrease (P <0.05) in ESR in the study group compared to control group. The same Table 6 reveals that there is no significant difference (P >0.05) between study group and control group regarding the other markers.

According to Table 7, there is significant decrease (P <0.05) in TLC and PMNs in the study group compared to control group. The same Table 7 reveals that there is no significant difference (P >0.05) between study group and control group regarding the other markers.

Table 8 reveals that there is no significant difference (P >0.05) between study group and control group regarding all the markers.

Table 9 reveals that there is no significant difference (P >0.05) between study group and control group regarding all liver and kidney markers 6weeks postoperative.

According to Table 10, there is a high significant difference (P <0.01) in TLC levels in the study group among the four periods of measurements (preoperative, 2 weeks postoperative, 4 weeks postoperative, 6 weeks postoperative) indicating that TLC levels have decreased after 6 weeks postoperatively.

According to Table 11, there is a high significant difference (P <0.01) in CRP levels in the study group among the four periods of measurements (preoperative, 2 weeks postoperative, 4 weeks postoperative, 6 weeks postoperative) indicating that CRP levels have decreased after 6 weeks postoperatively.

Figure 2: Differences of CRP Levels in the Study Group among four Periods of Measurements

According to Table 12, there is a high significant difference (P<0.01) in ESR levels in the study group among the four periods of measurements (preoperative, 2 weeks postoperative, 4 weeks postoperative, 6 weeks postoperative).

The incidence of septic arthritis as an acute complication after knee arthroscopy is very low [15]. Risk factors can be divided into two categories: surgery-related and patient-related. Using a prophylactic antibiotic given routinely prior to surgery as well as local irrigation or topical application reduces surgical site infection. Studies have used different types of antibiotics, both local and systemic [16]. Prior to October 2018, the surgeons employed vancomycin as a presoaking agent for hamstring grafts, But they later switched to gentamicin because new research shows that using gentamicin irrigation solution to prevent infections during anterior cruciate ligament reconstruction (ACLR) procedures is a good idea [16]. The current study used ceftriaxone to cover a large number of microorganisms, leaving more potent, expensive, and nephrotoxic antibiotics such as vancomycin and gentamycin reserved for resistant MRSA microorganisms. In addition to single antibiotics used to prevent unwanted drug-drug interactions and side effects.

In the current study, there was no statistically significant difference (p > 0.05) between demographic characteristics, clinical history, and associated procedures (like partial medial meniscectomy) and the type of graft. This means that these factors do not increase the rate of infection after ACLR. Similarly, Baron et al. [17] reported a single instance of graft infection following vancomycin presoaking. However, the type of graft and demographic information (type of surgery, concomitant procedures, open or arthroscopic surgery) for this case were not reported.

In Previous research has established smoking and diabetes as risk variables associated with the occurrence of profound intra-articular infection following ACL reconstruction [18]. In a cohort of 13,358 people, Cancienne et al.’s [19] study found that tobacco use was a distinct risk factor for infection following anterior cruciate ligament reconstruction (ACLR). Based on what Preito et al. (2022) found in their study on finding graft contamination spots, the most likely times for graft contamination to happen are when the graft is being prepared and when it is being taken out of the body [20].When considering the selection of antibiotics for the presoaking of grafts, it is important to choose a medication that can reliably target the specific microorganism responsible for producing infection. Furthermore, it is imperative that the proposed solution exhibit low adverse effects, offer a more cost-effective alternative, and present a reduced likelihood of antimicrobial resistance.

There is no significant difference (P > 0.05) in the distribution of clinical characteristics between the study and the control group, except for tourniquet time , which may increase the rate of infection due to decreased plasma levels of soft tissue antibiotics administered intravenously at the time of anesthesia induction or before an hour of arthroscopic ACLR patients in the control group with no postoperative infection (90%) and those with postoperative infection (10%), no patient in the study group with their frequency developed postoperative infection. In spite of the fact that patients in the study group had a tourniquet time of (79-99) minutes and in the control group, most of them had a tourniquet time of (67-78) minutes, this did not affect or increase the infection rate in the study group.

Two patients in the control group developed signs and symptoms of postoperative infection during ten to fourteen days after surgery (increased pain threshold, fever 38\(^{\circ}\)C, mild joint swelling, decreased range of motion), as well as elevated WBC, TLC, CRP, and ESR. Joint fluid aspiration results for these patients were positive, although there was no specific growth of microorganisms on culture or sensitivity. Patients received 14 days of intravenous antibiotics followed by oral 3rd generation cephalosporin for 6 weeks according to their body weight. Patients were improved during the study’s follow-up period.

When comparing the intraoperative presoaking of hamstring grafts in groups A and B, no patients in the study group developed signs or symptoms of postoperative intra-articular infection. Furthermore, the study group had significantly lower levels of erythrocyte sedimentation rate, total leukocyte count, and Polymorphonuclear leukocytes postoperatively. This finding could be attributed to the effect of the ceftriaxone antibiotic or to the normal inflammatory response that occurs after surgery. The discrepancies in inflammatory markers between the study and control groups signifying there was a significant decrease (P <0.05) in CRP in the study group preoperatively, which may indicate that all patients in this group don’t have local and/or general foci of infection in addition to Inflammatory markers (ESR, TLC, and PMNs) was significantly decreased 4-6 weeks postoperatively in the study group.

Increasing CRP and ESR in the postoperative period can be of clinical value. In a retrospective analysis of 122 (83 non-infected and 39 infected) patients’ serology after ACL reconstruction, [21]. Wang et al. found that CRP and ESR were useful in determining the presence of a normal or septic joint. After treatment of the postoperative infection, the CRP level peaked earlier than the ESR level and returned to normal more rapidly. In this study, CRP was more beneficial than ESR for assessing the infection’s response to treatment [22, 23].

The liver function test (LFT) and renal function test (RFT) showed that there is no significant difference (P > 0.05) between the study group and the control group for any of the markers, both before and after surgery. This shows that ceftriaxone didn’t affect liver and kidneys function. This makes it safer to use antibiotics locally and systemically when presoaking ACL-harvested autograft. Repeated measures of ANOVA (analysis of variance) confirmed the significant decrease in TLC (P value =0.00), ESR (P value = 0.007), and CRP (P value = 0.009) levels after six weeks postoperatively in the patients of the study group, which indicated that systemic and local antibiotics decrease the rate of infection in addition to a clean arthroscopic procedure.

ceftriaxone drug does not exhibit the least efficacy compared to other antibiotics in reducing the infection rate following ACL reconstruction. Ceftriaxone shows a significant decrease in inflammatory markers between the study and control groups. It also demonstrate no significant disturbance of (Liver function test, Renal function) pre and postoperative of anterior cruciate ligament reconstruction.

This research paper received no external funding.

The authors declare no conflicts of interest.

All authors contributed equally to this paper. They have all read and approved the final version.

Informed consent was obtained from all participates in the study as needed.

References

1. Bansal, D., Khatri, K., Dahuja, A., Lakhani, A., Malhotra, N., & Malhotra, N. K. (2022). Comparison between vancomycin and gentamicin for intraoperative presoaking of hamstring graft in primary anterior cruciate ligament reconstruction. Cureus, 14(2), e22550.
2. Torres-Claramunt, R., Pelfort, X., Erquicia, J., Gil-Gonzalez, S., Gelber, P. E., Puig, L., & Monllau, J. C. (2013). Knee joint infection after ACL reconstruction: prevalence, management and functional outcomes. Knee Surgery, Sports Traumatology, Arthroscopy, 21, 2844-2849.
3. Demirag, B., Omer, U. N. A. L., & Ozakin, C. (2011). Graft retaining debridement in patients with septic arthritis after anterior cruciate ligament reconstruction. Acta Orthopaedica et Traumatologica Turcica, 45(5), 342-347.
4. Antoci Jr, V., Adams, C. S., Hickok, N. J., Shapiro, I. M., & Parvizi, J. (2007). Antibiotics for local delivery systems cause skeletal cell toxicity in vitro. Clinical Orthopaedics and Related Research, 462, 200-206.
5. Yazdi, H., Gomrokchi, A. Y., Nazarian, A., Lechtig, A., Hanna, P., & Ghorbanhoseini, M. (2019). The effect of gentamycin in the irrigating solution to prevent joint infection after anterior cruciate ligament (ACL) reconstruction. Archives of Bone and Joint Surgery, 7(1), 67-74.
6. Armstrong, R. W., Bolding, F., & Joseph, R. (1992). Septic arthritis following arthroscopy: clinical syndromes and analysis of risk factors. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 8(2), 213-223.
7. Tong, S. Y., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler Jr, V. G. (2015). Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clinical Microbiology Reviews, 28(3), 603-661.
8. Sircana, G., Passiatore, M., Capasso, L., Saccomanno, M. F., & Maccauro, G. (2019). Infections in arthroscopy. European Review for Medical & Pharmacological Sciences, 23, 279-287.
9. Shirtliff, M. E., & Mader, J. T. (2002). Acute septic arthritis. Clinical Microbiology Reviews, 15(4), 527-544.
10. Carrozzo, A., Saithna, A., Ferreira, A., Guy, S., Chadli, L., Monaco, E., ... & Sonnery-Cottet, B. (2022). Presoaking ACL grafts in Vancomycin decreases the frequency of postoperative septic arthritis: a cohort study of 29,659 patients, systematic review, and Meta-analysis from the SANTI Study Group. Orthopaedic Journal of Sports Medicine, 10(2), 23259671211073928.
11. Rubinstein, E., & Keynan, Y. (2014). Vancomycin revisited-60 years later. Frontiers in Public Health, 2, 217.
12. Fischer, J., Ganellin, C. R., & Rotella, D. P. (Eds.). (2012). Analogue-Based Drug Discovery ii I. John Wiley & Sons.
13. Briggs, K. K., Lysholm, J., Tegner, Y., Rodkey, W. G., Kocher, M. S., & Steadman, J. R. (2009). The reliability, validity, and responsiveness of the Lysholm score and Tegner activity scale for anterior cruciate ligament injuries of the knee: 25 years later. The American Journal of Sports Medicine, 37(5), 890-897.
14. Wiesli, M. G., Livio, F., Achermann, Y., Gautier, E., & Wahl, P. (2022). Wound fluid ceftriaxone concentrations after local application with calcium sulphate as carrier material in the treatment of orthopaedic device-associated hip infections. Bone & Joint Research, 11(11), 835-842.
15. Clement, R. C., Haddix, K. P., Creighton, R. A., Spang, J. T., Tennant, J. N., & Kamath, G. V. (2016). Risk factors for infection after knee arthroscopy: analysis of 595,083 cases from 3 United States databases. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 32(12), 2556-2561.
16. Yazdi, H., Moradi, A., & Herbort, M. (2014). The effect of gentamicin in irrigating solutions on articular infection prophylaxis during arthroscopic ACL reconstruction. Archives of Orthopaedic and Trauma Surgery, 134, 257-261.
17. Baron, J. E., Shamrock, A. G., Cates, W. T., Cates, R. A., An, Q., Wolf, B. R., ... & Westermann, R. W. (2019). Graft preparation with intraoperative vancomycin decreases infection after ACL reconstruction: a review of 1,640 cases. The Journal of Bone & Joint Surgery, 101(24), 2187-2193.
18. Brophy, R. H., Wright, R. W., Huston, L. J., Nwosu, S. K., Spindler, K. P., & MOON Knee Group. (2015). Factors associated with infection following anterior cruciate ligament reconstruction. The Journal of Bone and Joint Surgery, 97(6), 450-454.
19. Cancienne, J. M., Gwathmey, F. W., Miller, M. D., & Werner, B. C. (2016). Tobacco use is associated with increased complications after anterior cruciate ligament reconstruction. The American Journal of Sports Medicine, 44(1), 99-104.
20. Perez-Prieto, D., Portillo, M. E., Torres-Claramunt, R., Pelfort, X., Hinarejos, P., & Monllau, J. C. (2018). Contamination occurs during ACL graft harvesting and manipulation, but it can be easily eradicated. Knee Surgery, Sports Traumatology, Arthroscopy, 26, 558-562.
21. Wang, C., Ao, Y., Fan, X., Wang, J., Cui, G., Hu, Y., & Yu, J. (2014). C-reactive protein and erythrocyte sedimentation rate changes after arthroscopic anterior cruciate ligament reconstruction: guideline to diagnose and monitor postoperative infection. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 30(9), 1110-1115.
22. Abbas Al-Huesini, L. M., Al-Mudhaffer, R. H., Hassan, S. M., & Hadi, N. R. (2019). DMF ameliorating cerebral ischemia/reperfusion injury in meal rats. Systematic Reviews in Pharmacy, 10(1), 206-213.
23. Hassan, S. M., Obeid, H. A., Hasan, I. S., & Abbas, A. N. (2023). Etanercept ameliorated cerebral damage during global cerebral ischemia-reperfusion injury in male rats. Azerbaijan Pharmaceutical and Pharmacotherapy Journal, 22(1), 53-58.