Lumbar fusions are common procedures1–3 for which surgical site infections (SSIs) are a rare, potentially devastating complication.4,5 As such, several efforts are made to minimize the risk of SSIs, including optimizing perioperative antibiotics.6 Although cefazolin is the most commonly used perioperative antibiotic, the addition of aminoglycosides (gentamycin or tobramycin) is considered at some centers.

For lumbar fusions, SSIs occur in approximately 0.4 to 4% of cases.7,8 Factors associated with the development of SSI include patient characteristics (such as diabetes,9 steroid use,9 and morbid obesity)9,10 and surgical variables (such as approach,10 open versus minimally invasive,11 and instrumentation).7 For all patients, prophylactic antibiotics are the standard of care to minimize the risk of SSI.6,12

While a single dose of cefazolin is the most common perioperative antibiotic prophylaxis regimen used,6,13 the addition of an aminoglycoside is considered at some centers.14 These provide gram-negative coverage but are also associated with risks such as renal complications.15,16 Several single-institution retrospective studies have concluded that the addition of an aminoglycoside (either gentamicin or tobramycin) is not associated with a markedly decreased rate of SSI among patients undergoing several orthopaedic procedures including femoral neck fracture fixation and neuromuscular scoliosis fusions.17,18 Furthermore, several meta-analyses have demonstrated increased rates of acute kidney injury (AKI) among orthopaedic patients receiving gentamicin prophylaxis.15,16

A meta-analysis that pooled six prospective, randomized clinical trials examined a cohort of 843 patients undergoing various spinal procedures, not limited to spinal fusions, demonstrated efficacy of prophylactic antibiotic regimens in markedly decreasing the infection rate from 5.9% to 2.2%, but did not identify the benefit of additional gram-negative coverage because it found similar SSI rates among cohorts assigned to a cephalosporin arm or a vancomycin and gentamicin arm.19 However, this study grouped together patients undergoing a variety of spinal procedures and varied the gram-positive coverage between the study groups.

This study sought to examine 90-day postoperative outcomes and 2-year revision rates among a national cohort of patients undergoing single-level posterior lumbar fusions (PLFs) in a large national database using administrative coding for the administration of cefazolin versus cefazolin and either gentamicin or tobramycin. The goal of this study was to compare the SSI rates of the two groups and put this in the context of potential associated adverse outcomes.

Methods Study Cohort

This study used data from the 2010 to 2021 October M157 Ortho PearlDiver database, a large, multi-insurance, national claims database which contains data regarding approximately 157 million orthopaedic patients. Because the output data are aggregated and deidentified, our institutional review board (IRB) determined studies using this database exempt from review.

Adult patients (18 years and older) undergoing single-level PLF were queried identified by the Current Procedural Terminology (CPT) codes 22612, 22630, and 22633. Patients were excluded if they had received a traumatic, neoplastic, or infectious diagnosis in the 90 days before their operation or if they were not active in the M157 database for 90 days after their procedure. To identify patients undergoing isolated single-level PLF, patients undergoing concurrent anterior procedures, multilevel fusions, or any cervical or thoracic procedures on the same day of their single-level PLF were excluded.

Intraoperative antibiotic prophylaxis regimens were determined using CPT J codes, which were used to identify intravenous (IV) cefazolin (CPT-J0690), gentamicin (CPT-J1580), and tobramycin (CPT-J3260, CPT-J7685, CPT-J7682) administration on the day of surgery. Patients were separated into two antibiotic subgroups: (1) cefazolin alone and (2) cefazolin and either gentamicin or tobramycin (the latter groups termed cefazolin and gentamicin/tobramycin). Patients were only included in the study if they fell in one of these two subgroups.

Patient variables were extracted from the data set. These included patient age at the time of procedure, sex, and Elixhauser Comorbidity Index (ECI, a measure of comorbidity burden based on a total of 38 comorbidities).

Postoperative Outcomes

Ninety-day incidence of adverse events and readmissions were identified based on the occurrence of ICD-9 or ICD-10 diagnosis codes of the adverse event using methods previously described.20–22 Severe adverse events were classified based on the occurrence of one of the following: SSI, sepsis, deep vein thrombosis, pulmonary embolism (PE), and cardiac event (either myocardial infarction or cardiac arrest). Minor adverse events were classified based on the occurrence of one of the following: wound dehiscence, pneumonia, urinary tract infection (UTI), AKI, hematoma, and transfusion. Any adverse event was defined if there was the occurrence of a serious or minor adverse event.

Readmission rates were assessed using the “Admission” code in PearlDiver in the 90 days after single-level PLF as previously described.23 Two-year revision rates were determined based on ICD-9 and ICD-10 procedural coding for the posterior approach for lumbar fusion revision surgery.

Statistical Analyses

Differences in patient characteristics among the unmatched and matched populations were assessed with univariable analysis by Student t-tests, chi-square tests, or Fisher exact tests, where appropriate. Differences in 90-day outcomes and 2-year revision rates among the matched populations were assessed with univariable analysis using chi-square tests.

Multivariable logistic regression analyses were then conducted to assess odds of any, severe, and minor 90-day adverse events and readmissions and 2-year revision rates between the two antibiotic subgroups.

Analyses were conducted in Excel version 16.16, PearlDiver Bellwether software, and Prism 8. Significance was defined as P-values < 0.05 for all comparisons. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for case-control studies.

Results Study Cohort

Of 8161 PLF patients, 7562 (92.7%) received cefazolin alone and cefazolin and gentamicin/tobramycin was given to 599 (7.3%; Figure 1, Table 1). For the cefazolin-only group, the average ± standard deviation age was 60.03 ± 12.75 years, 54.0% were female, and the average ± standard deviation ECI was 4.86 ± 3.37. For the cefazolin and gentamicin/tobramycin group, the average ± standard deviation age was 60.58 ± 12.82 years, 55.3% were female, and the average ± standard deviation ECI was 4.95 ± 3.27. Antibiotic subgroups did not vary in age, sex, or ECI.

Figure 1:

Pie chart showing relative utilization of cefazolin ± gentamicin/tobramycin among adult patients who underwent single-level posterior lumbar fusion between 2010 and 2021 October.

Table 1 - Patient Characteristics of Adult Patients Who Underwent Single-Level Posterior Lumbar Fusion Between 2010 and 2021 October Who Received Cefazolin ± Gentamicin/Tobramycin Cefazolin Only Cefazolin + Gentamicin/Tobramycin P Total 7562 (92.7%) 599 (7.3%) Age (mean ± SD) 60.03 ± 12.75 60.58 ± 12.82 P = 0.3052 Sex P = 0.5700  Female 4081 (54.0%) 331 (55.3%)  Male 3481 (46.0%) 268 (44.7%) ECI 4.86 ± 3.37 4.95 ± 3.27 P = 0.5283

ECI = Elixhauser Comorbidity Index, SD = standard deviation

Postoperative Adverse Events and Revision Rates

Univariable analysis of 90-day postoperative outcomes and 2-year revision rates for the subgroups is presented in Supplemental Table 1 (https://links.lww.com/JG9/A341). On univariable analysis, the antibiotic subgroups did not differ in 90-day individual or aggregated adverse outcomes (P > 0.05 for all). The antibiotic subgroups also did not differ in 2-year revision rates (P > 0.05).

On multivariable analysis, the antibiotic subgroups did not differ in the 90-day outcomes assessed, specifically SSI, sepsis, deep vein thrombosis, PE, cardiac event, wound dehiscence, pneumonia, UTI, AKI, hematoma, or transfusion (P > 0.05 for all). Furthermore, the antibiotic subgroups did not differ in aggregated 90-day adverse events, severe adverse events, minor adverse events, or readmission rates (P > 0.05 for all). The antibiotic subgroups did not differ in 2-year revision rates as well (P > 0.05; Supplemental Table 2, https://links.lww.com/JG9/A342).

Discussion

Postoperative spine SSI is associated with notable morbidity and mortality after spine surgery. Determining an optimal antibiotic prophylaxis regimen for the prevention of development of postoperative SSI is of utmost importance. This study sought to examine postoperative outcomes and revision rates among patients undergoing stand-alone single-level PLF between 2010 and 2021 October, who received either cefazolin alone or cefazolin + gentamicin/tobramycin.

Among the 8161 patients who underwent single-level PLF, most of the patients (92.7%, n = 7,562) received intravenous cefazolin alone while the minority of patients (7.3%, n = 599) received cefazolin + gentamicin/tobramycin. This predominance of use of cefazolin alone mirrors antibiotic regimens described in several practice guidelines.24,25 That being said, there were a small minority of patients who received an additional intravenous aminoglycoside, which may reflect hospital policies mandating use of aminoglycosides as antibiotic prophylaxis.

On univariable and multivariable analyses, the two antibiotic subgroups were not associated with markedly differing rates of infectious or wound-related 90-day adverse events, specifically wound dehiscence, SSI, sepsis, pneumonia, UTI, or 2-year revision rates. Thus, our findings are consistent with previous findings among single-institution, retrospective studies17,18 and provide data among a nationally representative sample of patients that the addition of aminoglycosides to the antibiotic prophylaxis regimen may not confer a reduced risk of infection in the immediate postoperative period or of revision surgery in the long term.

Although in this study the rate of AKI was not markedly different between the cephalosporin + aminoglycoside cohort and the cephalosporin-alone cohort, several previous studies have described an increased risk of developing AKI among those patients receiving aminoglycoside antibiotics.15,16 In addition, given nationwide efforts to increase antibiotic stewardship to minimize unnecessary antibiotic use, which may lead to the development of multidrug-resistant organisms, ensuring that antibiotic use is evidence based is of the utmost importance.

Our study had several limitations, including those inherent to retrospective studies. These include limitations such as any coding errors that may have occurred and possible omittance of confounding variables not captured in claims. In addition, while it is possible that patients without coding for intravenous antibiotics who in reality received one of the two antibiotic regimens included in this study were excluded, it is likely that those included in the study did in fact receive the antibiotics noted in their records. Given this, we believe this study provides insight into a meaningful question which has not been well characterized in the literature thus far.

Overall, this study examined a cohort of patients undergoing isolated single-level PLF between 2010 and 2021 October, who received either cefazolin alone or cefazolin + gentamicin/tobramycin. The addition of an aminoglycoside to cefazolin antibiotic prophylaxis was not found to have differences in rates of 90-day adverse outcomes (including SSI) and 2-year revision surgery. Additional studies should seek to examine the relative risk/benefit profile of addition of an aminoglycoside to antibiotic prophylaxis, especially regarding the potential development of multidrug-resistant organisms.

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