Intrawound Low-dose Vancomycin (250 mg) Powder has Lower Risk of Wound Dehiscence than Higher Doses in Spine Surgeries

Introduction: Surgical site infection post spinal surgery is a known complication which can be serious and may require aggressive intervention. Intrawound vancomycin powder application is an evolving method to prevent such complication. Although it has very low systemic complications, wound dehiscence with negative culture is reported in the literature. The aim of this study was to find the risk of wound dehiscence with low-dose intrawound vancomycin in comparison to 1 gr and its effectiveness in prevention of surgical site infection. Methodology: A chart review of all patients who underwent posterior thoracic, lumbar or sacral spine surgeries from December 2009 to September 2016 in a single center was done. Patients were categorized into three groups. First, patients who did not receive any intrawound vancomycin; second, patients who received high-dose vancomycin (1 gr); and third, patients who received low-dose vancomycin (250 mg). Additionally, patients’ demographic information, clinical data, and surgical variables were collected. Primary outcome was the presence of wound dehiscence or surgical site infection. Result: In total, 391 patients were included in this study, of which 56 (14.3%) received high-dose intrawound vancomycin, 126 (32.2%) received low dose, and 209 (53.5%) did not receive any. The overall incidence of wound dehiscence was 6.14% (24 out of 391 patients). Wound dehiscence was statistically and significantly higher (p = 0.039) in the high-dose vancomycin group in comparison to the patients who received low dose. The overall incidence of postoperative infection was 2.05% (eight patients). There was no statistically significant difference between the groups. Conclusion: The use of intrawound low-dose vancomycin (250 mg) has less wound dehiscence in comparison with other higher standard doses. Further trials are needed to evaluate the effectiveness of this dose in preventing postoperative infections.

1239. Ceftaroline versus Vancomycin as First-Line Therapy for MRSA Bacteremia

Background Beta-lactams have demonstrated superior outcomes over vancomycin in MSSA bacteremia. Despite this, studies of the anti-MRSA beta-lactam ceftaroline in MRSA bacteremia (MRSAB) are largely limited in size or focus on combination or salvage regimens. This study sought to further examine ceftaroline as first-line therapy for MRSAB. Methods This was a retrospective matched cohort study at the San Diego VA Medical Center between November 2010 and June 2020. Patients had to have received at least 72 hours of ceftaroline or vancomycin for MRSAB and less than 72 hours of prior MRSA therapy. Adjunct MRSA therapy was allowed only if routinely indicated for the infection (e.g. rifampin for prosthesis). Patients in the vancomycin group were matched 1:1 to patients in the ceftaroline group by age (+/- 10 years) and Pitt bacteremia score (+/- 1 point). The primary outcome was duration of bacteremia after initiation of MRSA therapy, including time on prior MRSA therapy. Results Fifteen patients were included in each group, with a median age of 65 years and Pitt bacteremia score of 0. Patients in the ceftaroline group were more likely to have CKD; to have been on a different MRSA agent prior to initiation of the study drug, with a median of 1 day of prior treatment; and to have been on adjunctive rifampin or clindamycin. Though not significant, more patients in the ceftaroline group also had endovascular sources, uncontrolled sources, and longer durations of therapy. The median duration of bacteremia after initiation of MRSA therapy did not significantly differ between ceftaroline and vancomycin (4 vs. 3 days, p = 0.806). In addition, 30-day all-cause mortality, in-hospital mortality, 90-day readmission or treatment failure, inpatient length of stay, total duration of bacteremia, and rate of adverse events did not significantly differ between groups. Conclusion This study suggests ceftaroline may be an appropriate first-line agent for the treatment of MRSA bacteremia with similar outcomes between groups despite the ceftaroline group likely experiencing more difficult-to-treat infections. However, it was not powered to detect differences between groups, and its retrospective nature has the potential to introduce bias. Prospective comparative studies are needed to corroborate these findings. Disclosures All Authors: No reported disclosures

232. Safety and Effectiveness of Intravenous to Oral De-escalation Compared to Continued Vancomycin Therapy in Orthopedic Infections

Background The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial determined oral antibiotics administered during the first six weeks of therapy were non-inferior to parenteral antibiotics. There was no difference in the incidence of serious adverse effects. The objective of this study was to evaluate the safety and effectiveness of de-escalating to oral therapy compared to continuing parenteral vancomycin therapy in patients with orthopedic infections in a real-world setting. Methods We conducted a single-center, retrospective cohort study of patients discharged between April 1, 2018 and April 1, 2020 with an orthopedic infection, a prescription for at least four weeks of parenteral vancomycin, and documented follow-up. The primary outcome was incidence of adverse events defined as provider documentation of the event and changes to therapy. The secondary outcome was incidence of 6-month treatment failure defined as repeat surgical intervention or therapy escalation. Results One hundred fifty-seven patients were included. Twenty-nine (18.5%) patients were de-escalated to oral therapy. Three (10%) patients in the oral therapy group had an adverse event compared to 35 (27%) in the vancomycin group (p=0.058). Of the 35 patients with an adverse event in the vancomycin group, eight were due to parenteral access-related complications. Treatment failure occurred in three (10%) patients in the oral therapy group compared to 27 (21%) patients in the vancomycin group (p=0.29). Three (10%) patients in the oral therapy group had an unplanned readmission compared to 25 (20%) patients in the vancomycin group (p=0.24). Baseline Characteristics, Unplanned Readmission Rates, and Incidence of Adverse Events and 6-Month Treatment Failure Conclusion Patients de-escalated to oral therapy had fewer adverse events and similar incidences of treatment failure compared to patients maintained on parenteral vancomycin. Switching to oral therapy avoids some adverse events related to parenteral access. Our results in an uncontrolled, real-world setting are consistent with the OVIVA trial. Though limited by sample size, our data indicate switching to oral therapy in patients with an orthopedic infection improves safety outcomes without compromising effectiveness compared to continued parenteral vancomycin therapy. Disclosures Russell J. Benefield, PharmD, Paratek Pharmaceuticals (Grant/Research Support)

1315. Ceftaroline Versus Vancomycin for the Treatment of Acute Pulmonary Exacerbations of Cystic Fibrosis in Adults

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent colonizer in cystic fibrosis (CF) patients that causes acute pulmonary exacerbation (APE). Vancomycin is the first line treatment for APE of CF; however, optimal alternatives remain poorly defined. The goal of this study was to determine the safety and efficacy of ceftaroline in CF patients presenting with an APE caused by MRSA. Methods This study was a single-center, retrospective cohort study from January 1, 2011 to January 1, 2020. The study included adult CF patients admitted for APE with %FEV1 > 10% lower than the patient’s baseline. A positive MRSA culture within 90 days before or 21 days after hospital admission and receipt of > 7 days of either vancomycin or ceftaroline was required for inclusion. Patients were excluded for receipt of a lung transplant, > 48 hours of alternative MRSA therapy, renal replacement therapy, or an APE secondary to fungal or mycobacterium infection. The primary outcome was the return to > 90% of baseline lung function measured by discharge %FEV1 in comparison to baseline %FEV1. Results Fifty-six patients were included in the analysis (22 ceftaroline; 34 vancomycin). There were no differences in baseline characteristics (Table 1). Eleven (50%) patients in the ceftaroline group and 19 (56%) in the vancomycin group met the primary outcome (P = 0.79) (Figure 1A). FEV1 measurements at baseline, admission, and discharge were not different between treatments (Figure 1B). Patients treated with ceftaroline had a longer length of stay during hospital admission, 14 days (IQR 13-14) vs.10 days (IQR 7-14), P = 0.01. Other secondary outcomes were similar between the ceftaroline and vancomycin groups, respectfully, including 30-day readmission rate, 6 (27%) vs. 12 (35%), P = 0.57; 30-day mortality, 0 (0%) vs. 2 (6%), P = 0.51; neutropenia 3 (12%) vs. 1 (3%), P = 0.29; Clostridioides difficile infection 0 (0%) vs. 1 (3%), P = >0.99; or acute kidney injury 2 (9%) vs. 5 (15%), P = 0.69. Table 1. Baseline characteristics for ceftaroline and vancomycin treated patients 1Lumacaftor/ivacaftor, tezacaftor/ivacaftor; 2Piperacillin/tazobactam, aminoglycoside, furosemide, contrast dye, lisinopril, NSAIDs, colistin, phenylephrine; 3Methimazole, sulfasalazine, trimethoprim/sulfamethoxazole; 4Albuterol, hypertonic saline, dornase alpha, azithromycin, ibuprofen, inhaled aminoglycoside, inhaled colistin, corticosteroid; 5Azithromycin, aminoglycoside, fluroquinolone, cephalosporin, carbapenem, piperacillin/tazobactam. Data represents n (%) unless noted. CFTR=cystic fibrosis transmembrane conductance regulator. Figure 1. %FEV1 trend from baseline to discharge in patients treated with ceftaroline or vancomycin (A) Percentage (%) of patients who met the primary outcome in each group; (B) Mean %FEV1 change between ceftaroline (square) and vancomycin (circle) with error bars representing standard deviations Conclusion This study found no difference in safety and efficacy outcomes between vancomycin and ceftaroline. Our small cohort supports ceftaroline as an alternative agent for the treatment of MRSA mediated APE of CF. Disclosures All Authors: No reported disclosures

1112. Vancomycin Nephrotoxicity Relative to Alternative Antibiotic Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Vancomycin is one of the most frequently prescribed antibiotics. Existing clinical evidence on vancomycin nephrotoxicity is limited to observational studies which are prone to confounding and bias. The purpose of this systematic review and meta-analysis is to compare acute kidney injury between vancomycin and comparator anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics using randomized controlled trial (RCT) data. Methods PubMed and Embase were searched for RCTs comparing intravenous vancomycin to other anti-MRSA antibiotics in adult patients, published from 1990 to January 2021. Studies were included if they reported comparative data on renal outcomes. The primary outcome was change in renal function, referred to as ‘nephrotoxicity’ in this study. Studies where another known nephrotoxic medication was part of study therapy in any treatment group were excluded. Eighteen studies met the inclusion criteria, and two independent reviewers assessed the risk of bias. Data on nephrotoxicity definition, comparator drug, infection type, vancomycin dosing strategy, duration of treatment, and concurrent gram-negative coverage were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Figure 1. Flow chart of article selection. Results Of 1,426 studies identified, 18 encompassing 8,966 patients were included. Treatment with vancomycin was associated with significantly increased odds of nephrotoxicity (OR, 2.41; 95% CI, 1.71 to 3.40; P< 0.00001) relative to its alternatives. A subgroup analysis grouping studies by reported vancomycin dosing approach revealed a stronger association between vancomycin and nephrotoxicity in studies with fixed-dose vancomycin regimens (OR 5.31; 95% CI 1.93 to 14.56; P=0.001) relative to studies with vancomycin therapeutic drug monitoring (TDM) (OR 2.17; 95% CI 1.51 to 3.13; P< 0.0001). Figure 2. Forest plot indicating the risk of nephrotoxicity associated with vancomycin vs. comparators. Odds ratios (ORs) and 95% confidence intervals (95% CIs) are shown for each study and the pooled analysis using a random effects model and the Mantel-Haenszel method. OR>1 means that the risk of kidney injury in the vancomycin group is greater than that in the comparator group. Figure 3. Forest plot indicating a strong association between vancomycin and nephrotoxicity in studies with fixed-dose vancomycin regimens relative to studies with vancomycin therapeutic drug monitoring (TDM). Odds ratios (ORs) and 95% confidence intervals (95% CIs) are shown for each study and the pooled analysis using a random effects model and the Mantel-Haenszel method. OR>1 means that the risk of kidney injury in the vancomycin group is greater than that in the comparator group. Table 1. Summary of included studies. Conclusion This analysis shows that intravenous vancomycin is associated with greater odds of renal toxicity relative to alternative antibiotics. This effect was not as pronounced in studies where vancomycin TDM was used potentially indicating benefit of TDM although further study is required to confirm this. Disclosures All Authors: No reported disclosures

Linezolid Versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus Aureus Acute Hematogenous Osteomyelitis in Children: Higher Anemia Rate During Therapy.

Background: Clinical use of linezolid for the treatment of methicillin-resistant staphylococcus aureus (MRSA) acute hematogenous osteomyelitis (AHO) is still limited by lacking data about clinical outcomes and adverse effects of long-term usage in children. This study aimed to compare the efficacy and safety of linezolid and vancomycin for the treatment of MRSA AHO in children.Methods: This retrospective study was conducted between January 2011 and December 2018 at the Xijing Hospital, Air Force Military Medical University, China, and compared the clinical efficacy and safety of linezolid and vancomycin in children with MRSA AHO. Demographics, clinical features, laboratory tests, susceptibilities of isolates, treatment outcomes, and adverse events were collected. Variables were analyzed by Fisher’s exact test or Mann-Whitney U-test.Results: 17 patients with MRSA AHO were included in this study (6 children received linezolid and 11 children received vancomycin). Statistically significant differenc was observed in the minimum hemoglobin during the treatment between 2 groups [71.0 (IQR 65.0-91.0) vs 102.0 (IQR 91.0-114.0) g/L, P=0.009], and patients in the linezolid group presented higher anemia rate [5 (83.3%) vs 3 (27.3%), P=0.049] than those in the vancomycin group. Conclusions: Although linezolid and vancomycin have no significant difference in efficacy and safety in the treatment of children with MRSA AHO, the incidence rate of anemia was higher during therapy. Children seemed to be more sensitive to the transient bone marrow suppression effect of linezolid in the prolonged use for MRSA AHO.

Dual Topical Antibiotic Application Prior to Sternotomy Closure Reduces Sternal Wound Infection Rates: A Simple Solution to a Grave Morbidity

Background: A significant cohort of patients who undergo cardiac surgery suffer from diabetes and atherosclerosis. These patients have impaired tissue perfusion, hence a reduction in antibiotic concentration in the subcutaneous tissues at the side of the mammary artery harvesting. Topical application of gentamicin and vancomycin before wound closure broadens the antibiotic spectrum and reduces the incidence of deep sternal wound infection. In this article, we compare the use of single versus dual application of vancomycin and/or gentamicin in sternotomy wounds in a single tertiary center. Methods: An observational cohort analysis with three sequential patient groups (N = 2550) was performed at Ain Shams University Hospital in Cairo. A control group (N = 850), vancomycin only group (N = 850), and vancomycin plus gentamicin group (N = 850) were included in the study, during the three-year period from January 2017 to December 2019. Patients who had minimal access surgery were excluded from this study. The presence of an infected postoperative sternotomy wound was assessed in all patients. Results: The presence of an infected sternotomy wound (El Oakley class 2B) was present in 38 patients (4.5%) in the control group, in 19 patients (2.2%) in the vancomycin group, and in nine patients (1.1%) in the dual antibiotic group, respectively (P < .001). In contrast to the usual, we had a proliferous growth of gram-negative organisms 29 (3.4%) in the control group, 10 (1.2%) in the vancomycin group, and five (0.6%) in the dual antibiotic group, respectively (P < .001). Conclusion: Deep sternal wound infection is a major cause of post-cardiac surgery morbidity and prolonged hospital stay. Adding the simple step of topical application of vancomycin and gentamicin to the sternotomy wound at the end of the procedure appeared to significantly reduce deep wound infection rates.

Use of Tropical Vancomycin in Decreasing the Incidence of Surgical Site Infection in Open Heart Surgery

Aim: To study the effect of vancomycin tropically in decreasing the incidence of sternal wound infection in patients undergoing open cardiac surgery. Study design: Randomized controlled trial Place and duration: Department of Cardiovascular & Thoracic Surgery Sheikh Zayed Hospital Lahore from 1st January 2019 to 31st July 2020. Methods: A total of 180 male and female planned for elective open heart surgery is selected for this research work. All patients age is between 40 and 70 years and these patients are bifurcated in two groups. In Group I there are 90 patients in which vancomycin is used on the sternal edges, while in Group II there are 90 patients in which only normal saline wash is used at the time of sternal approximation. At the end incidence of sternal wound infection is monitored to establish the benefits of tropical vancomycin. Results: One hundred and thirty three (73.89%) were males and 47 (26.11%) were females. Topical vancomycin group has decreased rate of superficial and deep sternal wound infections as compared to the patients in which topical vancomycin is not applied (2.22% vs 6.67%) and (1.11% vs 4.4%). Conclusion: Application of vancomycin tropically at surgical site at the time of closure of sternum in conjunction with prophylactic use of antibiotics reduces wound infection in open heart surgery. Keywords: Open heart surgery, Vancomycin, Sternal wound infection

Low post-arthroplasty infection rate is possible in developing countries: long-term experience of local vancomycin use in Iran

Background Utilizing intrawound vancomycin powder in TKA surgery has yielded rather contrasting results in the current literature. Furthermore, CDC criteria, although effective in general, are not specifically designed for post-TKA infections. Here, we present a 7-year experience of vancomycin use in primary TKA in a high-volume tertiary knee center in Iran. Also, new criteria are proposed to detect suspected superficial post-TKA infections. Methods This is a retrospective analysis of primary total knee arthroplasties performed in a tertiary knee center, from March 2007 to December 2018, by a single senior knee surgeon. All patients with follow-up periods of less than 1 year were excluded from the study. Since March 2011, all patients received vancomycin (powder, 1 g) before water-tight closure of the joint capsule. A comparison was made between this group and historical control subjects (operated from March 2007 to March 2011). Results Altogether, 2024 patients were included in the study. The vancomycin and the control groups included 1710 and 314 cases respectively. Patients were mostly women (male to female ratio, 1 to 4), with a mean age of 65.20 (SD = 10.83) years. In the vancomycin group, the rate of suspected SII (1.87%) and PJI (0.41%) was significantly lower than the control group (P = 0.002). Conclusions Our experience shows that application of local vancomycin during TKA surgery could be a reasonable infection prevention measure, although prospective randomized studies are required to evaluate its efficacy.

Intrawound vancomycin application after spinal surgery: a propensity score–matched cohort analysis

OBJECTIVE Surgical site infection (SSI) following spine surgery is associated with increased morbidity and healthcare costs. In an effort to reduce SSI rates, the application of intrawound vancomycin powder has gained popularity. However, there is limited high-quality evidence to support the safety and efficacy of this practice. The authors sought to determine if intrawound application of vancomycin powder improves 90-day overall SSI rates. METHODS The authors performed a retrospective, vancomycin exposure–matched cohort study at a single tertiary care hospital over 21 months. They included all patients undergoing elective spinal surgery and stratified the patients into two groups: those who received intrawound vancomycin powder application and those who received no application of vancomycin powder. The primary outcome of interest was the 90-day overall SSI rate. Secondary outcomes included rates of superficial SSI, deep SSI, wound disruption, and a post hoc analysis of the microbiology and minimum inhibitory concentrations. Baseline patient demographics, clinical presentation, comorbidities, perioperative factors, and 90-day postoperative outcomes were manually abstracted from patient charts. To mitigate bias, we performed 1:1 matching after calculating propensity scores and identified 1 patient from the no-vancomycin cohort for each patient in the vancomycin cohort. RESULTS A total of 997 patients met our inclusion criteria (473 patients receiving vancomycin and 524 patients not receiving vancomycin). Propensity score matching produced 221 matched pairs. Risk-adjusted analysis demonstrated similar overall SSI rates between the groups (OR 1.9, p = 0.329). On unadjusted analysis, the overall 90-day SSI rate was greater in the vancomycin group (n = 10 [4.5%]) than in the no-vancomycin group (n = 5 [2.3%]) (p < 0.001), as were the superficial SSI rate (7 [3.2%] vs 4 [1.8%], p < 0.001), deep SSI rate (3 [1.4%] vs 1 [0.5%], p < 0.001), and wound disruption rate (5 [2.3%] vs 1 [0.5%], p < 0.001). No cultured isolate demonstrated vancomycin resistance. CONCLUSIONS The authors observed no difference in SSI rates after the intrawound application of vancomycin powder during spine surgery. Vancomycin use did not contribute to antimicrobial resistance; however, it may select out gram-negative bacteria and increase rates of wound disruption.