Patient Factors

The importance of host physiology in musculoskeletal infections has been emphasized in the literature. Systemic host factors include comorbidities that may compromise the host defense against pathogens. A recent study demonstrated that diabetes mellitus was a significant risk factor for postoperative SA after ACL reconstruction. Patients with diabetes had an infection rate of 8.7% compared with 0.77% in patients without diabetes. A study on persistent infections reported comorbidities in three out of five patients. Sonnery-Cottet et al. reported a significant increase of SA in professional athletes compared with nonprofessional ones (5.7% vs. 0.37%).

Local Factors

Local risk factors for SA after ACL reconstruction include previous or concomitant secondary knee procedures. Potential explanations include the increased operative time, additional or larger incisions with more extensive dissection in cases where complex reconstructive surgery takes place, and implantation of additional foreign material. A large registry study reported that deep surgical site infection developed in 0.8% (9) of 1091 revisions, compared with 0.3% (44) of 15,101 primary ACL reconstructions.

Graft Type

Graft choice has been implicated as a risk factor for SA after ACL reconstruction. Despite concerns that allograft tissue may result in a higher infection risk compared with autograft, this has not been demonstrated in the literature. In contrast, hamstring autograft has been the graft type associated with a higher risk for infection.

Maletis et al. demonstrated a significant association of graft type with infection in a large registry. Deep surgical site infection developed in 0.61% (20) of 3257 patients who received hamstring autograft compared with 0.27% (12) of 4404 patients with allograft and 0.07% (2) of 2965 patients with bone–patellar tendon–bone (BPTB) autograft. The likelihood of a patient with a hamstring autograft having a deep infection was significantly higher than that of a patient with a BPTB autograft (odds ratio 8.2, P = .01). The likelihood of a patient with an allograft having a deep infection was higher—but not significantly—compared with a patient with BPTB autograft (odds ratio 3.6, P = .10).

Brophy et al. reported a SA rate of 0.3% (3 of 931) in patients receiving BPTB autograft, 1.3% (8 of 639) in patients receiving hamstring autograft, and 1% (6 of 628) in patients who received allograft. The risk was significantly increased with use of hamstring autograft compared with BPTB autograft (odds ratio 4.6, P = .026) and with use of allograft compared with BPTB autograft (odds ratio 4.3, P = .047).

The increased infection risk associated with hamstring autografts may be attributed to the additional surgical dissection and the potential for formation of hematoma. Inadequate sterilization of equipment, such as tendon harvesters, may play a role.

Contamination of Instruments

Contaminated inflow cannulas have been identified as a source of infection. Viola et al. reported a sudden increase in their infection rate from 0.1% (period from 1991 to 1996) to 14.2% (period from December 1996 to February 1996). “Sterile” sets of inflow cannulas used for ACL reconstructions were found to be contaminated with coagulase-negative Staphylococcus. Following the discovery of the contaminated instruments, the infection rate dropped to 0.25%.

In another study, contamination with coagulase-negative Staphylococcus was present on supposedly sterile suture clamps on graft preparation boards. Inadequate disinfection of arthroscopic equipment and flash sterilization of meniscus repair cannulas with residual debris in the lumen have been reported as potential causes of SA following arthroscopy. Failure to disassemble a tube-within-a-tube tendon harvester during the sterilization process has also been implicated in postoperative infections after ACL reconstruction.

A study that investigated clusters of infections after ACL reconstruction found shortfalls in the decontamination and sterilization of surgical equipment, as well as wide variation in perioperative care practices among surgeons. Implementation of ACL pathway guidelines significantly reduced the infection rate from 1.96% (24 of 1226 cases from 2002 to 2008) to 0% (0 of 500 cases from 2008 to 2011).

Graft Contamination

Graft contamination has been demonstrated in several studies in the literature that evaluated the graft with intraoperative cultures. Diaz-de-Rada et al. reported that allograft cultures were positive in 13% of cases (24 of 181). Antibiotics were given for 2 weeks and no clinical infections developed after a minimum 1-year follow-up. Centeno et al. found positive cultures in 4.8% of allografts (10 of 210). Highly pathogenic bacteria were identified in three patients and they were treated with antibiotics, whereas the remaining seven patients were observed and no clinical infections developed.

In other studies positive cultures were not treated with antibiotics. Guelich et al. reported positive allografts cultures in 9.7% of patients (24 of 247). No additional antibiotics were given and no clinical infections developed after a mean follow-up of 38 months. Fowler et al. found positive allograft cultures in 2.6% of patients (3 of 115). No additional antibiotics were given and no clinical infections developed after a mean follow-up of 38 months.

Hantes et al. obtained culture specimens before implantation of autografts and reported that cultures were positive in 12% of patients (7 of 60). No additional antibiotics were given and no clinical infections developed after a minimum 1-year follow-up. Similarly, positive cultures of hamstring autografts were present in 10% of patients (9 of 89) in another series. No additional antibiotics were given and no infections developed postoperatively.

From these studies it appears that positive graft cultures are not associated with postoperative infections. On the other hand, some authors have reported significant reduction in infection rates by presoaking the graft in vancomycin solution.

The source of graft contamination remains unclear. Undetected intraoperative contamination of the graft may take place, and in the case of allografts, contamination may also occur during harvesting and storage.

Allografts and Infections in Anterior Cruciate Ligament Surgery

The use of allografts in ACL surgery has generated concerns regarding the transmission of viral disease and bacterial pathogens from the donor to the recipient via contaminated allografts.

Viral disease, including human immunodeficiency virus (HIV) infection, hepatitis B, and hepatitis C, has been transmitted by transplantation of musculoskeletal allografts harvested from infected donors prior to implementation of a screening process. Therefore adherence to screening methods is critical to exclude grafts from infected individuals from being used. The US Food and Drug Administration requires that potential donors undergo a screening process that includes serologic tests for HIV-1, HIV-2, hepatitis B, and hepatitis C viruses. However, a time window exists from infection with one of these viruses to development of a detectable antibody response. Transmission of hepatitis C has been reported, and transmission of hepatitis B could not be ruled out after allograft implantation for ACL reconstruction.

Implantation of contaminated allograft tissue has been reported as a source of unusual infections following ACL reconstruction and other knee procedures. The Centers for Disease Control and Prevention (CDC) in 2001 reported four cases of SA following ACL reconstruction associated with contaminated BPTB allografts and warned that allograft contamination should be suspected when SA develops. This is particularly important in polymicrobial, Gram negative, or anaerobic infections. One patient developed Clostridium sordellii septicemia and died within 1 week from receiving an osteochondral allograft, and another patient developed an invasive streptococcal infection after ACL reconstruction with an allograft. The CDC as of March 2002 had identified 26 cases of bacterial infections associated with musculoskeletal allografts, and 18 (69%) of these infections occurred following allograft implantation for ACL reconstruction.

Investigation of an outbreak of infections following ACL reconstruction in one outpatient surgical center revealed that all infections occurred in patients receiving aseptically processed—but not sterilized—allografts (11 of 250, 4%), compared with no infections in patients receiving autografts or sterilized allografts.

These infections highlight the need for allograft sterilization. Aseptic processing and preservation of the graft without sterilization do not ensure patient safety because endogenous contamination of the allograft may exist at the time of harvesting. Therefore in addition to aseptic harvesting and processing, allograft tissue should undergo a sterilization process to avoid the transmission of infectious agents.

Confirmed cases of pathogen transmission from contaminated allografts after ACL reconstruction are still being reported, including an invasive group A streptococcal infection and two cases of Elizabethkingia meningoseptica infections. Multiple allografts can be harvested from a single infected donor, and contamination of the processing facilities can affect multiple allografts. Therefore it is important to immediately report allograft-associated infections to the appropriate health authorities as well as the tissue provider.

Biofilm Formation

Biofilm formation is a key mechanism for persistence or recurrence of infection. The biofilm is an aggregation of microbial colonies enclosed within an extracellular polysaccharide matrix (glycocalyx) that adheres on the surface of implants or devitalized tissue. The presence of avascular graft and metal fixation devices in ACL reconstruction creates conditions conducive to biofilm development if postoperative SA is not treated early and adequately. The biofilm protects the organism from antibiotics and host defense mechanisms, such as antibody formation and phagocytosis; thus infection may exist in a subclinical state and eventually recur. In chronic musculoskeletal infections, removal of the biofilm by removal of implants and débridement of devitalized tissue is necessary for successful treatment of infection.

Clinical Findings

Mean time for development of SA following ACL surgery has varied in the literature from 8 days to 32 days, and it has been classified as acute (less than 2 weeks postoperatively), subacute (2 weeks–2 months), and late (more than 2 months).

The typical clinical presentation includes knee pain, effusion, erythema, and warmth. Such symptoms in the first 2 postoperative days may be due to the procedure, but persistence beyond the second day, especially if pain is increasing, should raise suspicion of infection. Fever and drainage from the surgical incision may be present.

An alternative presentation is with emergence of symptoms at a later time following a symptom-free interval. The clinical picture may consist of mild pain, effusion, and difficulty performing physical therapy without the systemic signs of infection. As Burks et al. warned, the surgeon should not interpret this relatively benign presentation as the absence of infection. A high index of suspicion is necessary. Patients who do not demonstrate steady postoperative improvement; who present with increased pain, effusion, and stiffness following a symptom-free interval; or develop systemic symptoms (fever, chills, malaise) should be considered to have a septic knee until proven otherwise. Patients should be instructed to contact their physician immediately in case knee symptoms develop postoperatively and should be evaluated without delay.

Laboratory Findings

Peripheral white blood cell (WBC) count may be within normal limits. In contrast, markers of inflammation, such as the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are almost always elevated and are helpful in the diagnosis. Mean CRP levels in patients with ACL postoperative infections have ranged from 2.6 to 17.5 mg/dL ¹⁹ in existing studies. Elevated levels of ESR have been similarly reported, with mean values ranging from 48 to 87 mm/h.

The anticipated increase of inflammatory markers in the immediate postoperative period may confound the diagnostic picture in the first 2 weeks. Margheritini et al. reported a postoperative increase of both CRP and ESR, peaking on the 3rd and 7th days, respectively. The CRP returned to nearly normal levels by the 15th postoperative day, which was faster compared with the ESR. Therefore CRP is a more sensitive indicator of postoperative septic complications. Similarly, Calvisi et al. reported that CRP levels peak on the 3rd postoperative day and normalize by the 15th day. Elevated levels of CRP beyond the 15th postoperative day strongly point toward a septic etiology for the patient’s symptoms, especially if greater than 2.5 mg/dL. Wang et al. compared CRP and ESR levels in patients with and without postoperative infections and concluded that CRP was more useful than ESR for the diagnosis of infection, and the optimal threshold was 4.1 mg/dL on the 5th postoperative day.

Aspiration of the involved knee joint is necessary, and synovial fluid should be sent for Gram stain, WBC count, differential, and culture—both aerobic and anaerobic. In the case of persistent, chronic infections, atypical organisms should be suspected and fungal and mycobacterial cultures should be sent as well. Gram stain has very low sensitivity and, if negative, does not rule out infection.

Mean WBC count has ranged from 49,400/mm ³ to 115,000/mm ³ . The commonly used threshold of 50,000/mm ³ is not sensitive enough. Sechriest et al. reported that 44% (14 of 32) of patients with infections had synovial WBC count less than 50,000/mm ³ , and 13% (4 of 32) had synovial WBC count less than 25,000/mm ³ . Paci et al. reported that aspiration of noninfected knees at a mean time of 5.5 days postoperatively revealed a mean WBC count of 9600/mm ³ with a 98% confidence interval of 2900–16,200/mm ³ . There was no comparison group of patients with infected knees in this study, but the authors used data from studies literature and concluded that a synovial WBC count greater than 16,200/mm ³ had 86% sensitivity and 92% specificity for the diagnosis of infection.

Mean percentage of PMN cells has been 72%–94%. Aspiration of noninfected knees at a mean time of 5.5 days postoperatively demonstrated 66% PMN cells with a 98% confidence interval of 51%–81%.

Imaging Studies

Magnetic resonance imaging (MRI) can help determine the extent of bone involvement and the presence of any extra-articular fluid collections that otherwise could have been missed.

Microbiology

SA following ACL surgery is caused by staphylococcal species in most cases. Staphylococcus aureus or coagulase-negative Staphylococci (including Staphylococcus epidermidis ) have been the most common pathogens in all studies. S. aureus was identified in 83% and 64% of positive cultures, in the studies by Barker et al. and Gille et al., respectively. Coagulase-negative Staphylococci were identified in 92% and 72% of positive cultures, in the studies by Sonnery-Cottet et al. and Sechriest et al., respectively.

It should be noted that joint fluid cultures may still be negative in the presence of infection. Negative cultures were reported in 26% of postoperative infections (9 of 34) by Maletis et al. and in 32% of infections (12 of 37) by Sechriest et al.

Case reports of unusual infections following autograft ACL reconstruction have been reported, including Clostridium perfringens, Mycobacterium tuberculosis, and mucormycosis.