Tande, Aaron J.

Abstract Background Cutibacterium acnes can cause spinal implant infections. However, little is known about the optimal medical management and outcomes of C. acnes spinal implant infections (CSII). Our study aims to describe the management of patients with CSII and evaluate the clinical outcomes. Methods We performed a retrospective cohort study of patients aged 18 years or older who underwent spinal fusion surgery with instrumentation between January 1, 2011, and December 31, 2020, and whose intraoperative cultures were positive for C. acnes. The primary outcome was treatment failure based on subsequent recurrence, infection with another organism, or unplanned surgery secondary to infection. Results There were 55 patients with a median follow-up (interquartile range) of 2 (1.2–2.0) years. Overall, there were 6 treatment failures over 85.8 total person-years, for an annual rate of 7.0% (95% CI, 2.6%–15.2%). Systemic antibiotic treatment was given to 74.5% (n = 41) of patients for a median duration of 352 days. In the subgroup treated with systemic antibiotics, there were 4 treatment failures (annual rate, 6.3%; 95% CI, 1.7%–16.2%), all of which occurred while on antibiotic therapy. Two failures occurred in the subgroup without antibiotic treatment (annual rate, 8.8%; 95% CI, 1.1%–31.8%). Conclusions Our study found that the estimated annual treatment failure rate was slightly higher among patients who did not receive antibiotics. Of the 6 failures observed, 4 had recurrence of C. acnes either on initial or subsequent treatment failures. More studies are warranted to determine the optimal duration of therapy for CSII.

AbstractIn a COVID‐19 sero‐surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of antispike (anti‐S1) IgG antibody levels, (ii) to evaluate whether the levels were associated with protection from SARS‐CoV‐2 infection, and (iii) to assess whether the association was different in the pre‐Omicron compared with the Omicron period. The QuantiVac Euroimmun ELISA test was used to quantify anti‐S1 IgG levels. The entire study period (16 months), the 11‐month pre‐Omicron period and the cross‐sectional analysis before the Omicron surge included 3219, 2310, and 895 reactive serum samples from 949, 919, and 895 individuals, respectively. Mixed‐effect linear, mixed‐effect time‐to‐event, and logistic regression models were used to achieve the objectives. Age and time since infection or vaccination were the only factors associated with a decline of anti‐S1 IgG levels. Higher antibody levels were significantly associated with protection from SARS‐CoV‐2 infection (0.89, 95% confidence interval [CI] 0.82–0.97), and the association was higher during the time period when Omicron was predominantly circulating compared with the ones when Alpha and Delta variants were predominant (adjusted hazard ratio for interaction 0.66, 95% CI 0.53–0.84). In a prediction model, it was estimated that >8000 BAU/mL anti‐S1 IgG was required to reduce the risk of infection with Omicron variants by approximately 20%–30% for 90 days. Though, such high levels were only found in 1.9% of the samples before the Omicron surge, and they were not durable for 3 months. Anti‐S1 IgG antibody levels are statistically associated with protection from SARS‐CoV‐2 infection. However, the prediction impact of the antibody level findings on infection protection is limited.

Abstract Over the last several decades, periprosthetic joint infection has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of periprosthetic joint infection, focusing on frequent clinical challenges and collaborative interdisciplinary care.

AbstractBackgroundIn the management of Gram‐negative bloodstream infection (GN‐BSI), short antimicrobial courses have been increasingly demonstrated to be non‐inferior to prolonged therapy, with lower risk of Clostridioides difficile infection (CDI) and emergence of multi‐drug resistant (MDR) organisms. However, immunocompromised hosts were excluded from these studies. We investigated outcomes of short (≤10 days), intermediate (11–14 days), and prolonged (≥15 days) antimicrobial durations for GN‐BSI in neutropenic patients.MethodsA retrospective cohort study was conducted on neutropenic patients with monomicrobial GN‐BSI between 2018 and 2022. The primary outcome was a composite of all‐cause mortality and microbiologic relapse within 90 days after therapy completion. The secondary outcome was a composite of 90‐day CDI and development of MDR‐GN bacteria. Cox regression analysis with propensity score (PS) adjustment was used to compare outcomes between the three groups.ResultsA total of 206 patients were classified into short (n = 67), intermediate (n = 81), or prolonged (n = 58) duration. Neutropenia was predominantly secondary to hematopoietic stem cell transplantation (48%) or hematologic malignancy (35%). The primary sources of infection included intra‐abdominal (51%), vascular catheter (27%), and urinary (8%). Most patients received definitive therapy with cefepime or carbapenem. No significant difference in the primary composite endpoint was observed for intermediate versus short (PS‐adjusted hazard ratio [aHR] 0.89; 95% confidence interval [95% CI] 0.39–2.03) or prolonged versus short therapy (PS‐aHR 1.20; 95% CI 0.52–2.74). There was no significant difference in the secondary composite endpoint of CDI or MDR‐GN emergence.ConclusionOur data suggest that short antimicrobial courses had comparable 90‐day outcomes as intermediate and prolonged regimens for GN‐BSI among immunocompromised patients with neutropenia. image

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.

The recommended empiric ceftriaxone dosing regimen for acute bacterial meningitis in adults is 2 g every 12 h. After penicillin-susceptible Streptococcus pneumoniae is isolated as a causative microorganism, the ceftriaxone dose may be continued or reduced to a single dose of 2 g every 24 h, per institutional preference. There is no clear guidance that indicates the superiority of one regimen over the other. The objective of this study was to evaluate the susceptibility of S. pneumoniae in the cerebral spinal fluid (CSF) of patients with meningitis and the relationship between ceftriaxone dose and clinical outcomes. We identified 52 patients with S. pneumoniae meningitis with positive CSF cultures who were treated at the University Hospital, Bern, Switzerland, over a 19-year period. We collected clinical and microbiological data for evaluation. Broth microdilution and Etest methods were performed to test penicillin and ceftriaxone susceptibility. All isolates were susceptible to ceftriaxone. Ceftriaxone was empirically used in 50 patients, with a starting dosing regimen of 2 g every 24 h in 15 patients and 2 g every 12 h in 35 patients. In 32 patients started on a twice-daily regimen (91%), doses were reduced to once daily after a median of 1.5 (95% CI 1–2) days. The overall in-hospital mortality was 15.4% (n = 8), and 45.7% of patients reported at least one sequela of meningitis at the last follow-up (median 375, 95% CI 189–1585 days). We found no statistical difference in outcome between the 2 g every 24 h and the 2 g every 12 h ceftriaxone dosing regimens. A ceftriaxone total daily dose of 2 g may be associated with similar outcomes to a 4 g total daily dose, provided that the causative organism is highly susceptible to ceftriaxone. The persistence of neurological and infection sequelae at the last follow-up underscores the need for optimal treatment of these complex infections.

Abstract Days of therapy (DOT) currently serve as the standard antimicrobial utilization metric. However, by assigning the same weight to each agent rather than accounting for differences in spectrum of activity, DOT ignore key differences between agents that are fundamental to infectious diseases and critical to antimicrobial stewardship. Spectrum scoring assigns numeric values to individual antibiotic agents to quantify their spectrum of activity, allowing for the normalization of antibiotic utilization data. When used in conjunction with traditional metrics, spectrum scores may offer further clarity to antibiotic utilization; however, issues related to development, application, and standardization of spectrum scores remain. Despite these challenges, the potential applications of spectrum scores are vast. Here, we summarize existing data and explore the future of spectrum scoring, including application to both data analysis and routine patient care, use in inpatient and outpatient settings, integration within the electronic medical record, and opportunities for future research.

Objectives In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of anti-spike IgG antibody levels, (ii) to evaluate whether the antibody levels were associated with protection from SARS-CoV-2 infection and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. Methods The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis prior to the Omicron surge included 3219, 2310 and 895 reactive serum samples from 949, 919 and 895 study participants, respectively. Mixed-effect linear, mixed-effect time-to-event and logistic regression models were used to achieve the objectives. Results Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Antibody levels were significantly associated with protection from SARS-CoV-2 infection, and the association was higher for the Omicron than for the Alpha and Delta variants. In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by 20% to 30% for 90 days. Conclusions Anti-S1 IgG antibody levels are associated with protection from infection. The levels in the pre-Omicron periods were less significant than during the Omicron surge, which in turn required very high levels for protection in a statistical model.

Abstract Background There are anatomical, pharmacokinetic, and joint biomechanical differences between males and females. Whether these differences result in differing presentation, treatment tolerability and outcomes in periprosthetic joint infection (PJI) has not been widely evaluated. Methods We undertook a retrospective case matched study of patients with staphylococcal PJI managed with two-stage exchange arthroplasty. In order to control for differences other than sex which may influence outcome or presentation, males and females were case-matched for age, causative organism (Coagulase-negative staphylococci vs Staphylococcus aureus) and joint involved. The two matched groups were analyzed for differences in duration of symptoms, inflammatory markers, duration of hospital stay, antimicrobial side effects, post-operative complications and recurrence rate. Recurrence of infection was defined as per Musculoskeletal Infection Society criteria for PJI and included both relapse with original microorganism or with an additional organism. Results 78 pairs of males and females with staphylococcal PJI were successfully matched. There were no significant baseline differences by sex, except for greater use of chronic immunosuppression among females (16.7% vs. 4.1%; p=0.012). Clinical characteristics and outcomes of the patients are summarized in table 1. We did not detect a statistically significant between the outcomes of the two groups. Overall, 16 recurrent infections occurred during a median follow-up time of 2.9 (IQR: 1.5 - 5.3) years. The 3-year cumulative incidence of treatment failure depicted in figure 1 was 16.1% for females, compared with 8.8% for males (p=0.434). Conclusion Success rates for PJI treated with two-stage exchange arthroplasty are high consistent with previously reported literature. A larger cohort of patients may be required to detect differences in relapse rates. This study included only staphylococcal PJI and was thus unable to evaluate the differences in microbiology of PJI between males and females, which could also impact outcomes. This retrospective case-matched study did not detect any significant differences in outcomes between males and females with staphylococcal PJI who underwent two stage exchange arthroplasty. Disclosures Gina A. Suh, M.D., Adaptive Phage Therapeutics (APT): Grant/Research Support|Adaptive Phage Therapeutics (APT): Dr. Suh received grants and has an equity and royalty-bearing know-how agreement with Adaptive Phage Therapeutics but is unrelated to project Aaron J. Tande, M.D., Uptodate: Dr Tande has received an honorarium from Uptodate for medical writing unrelated to this project.

Abstract Background Image-guided biopsies in patients with suspected native vertebral osteomyelitis (NVO) are recommended to establish the microbiological diagnosis and guide antibiotic therapy. Despite recent advances, the microbiological yield of this procedure remains between 48% and 52%. A better understanding of factors associated with this low yield may lead to improved microbiological diagnosis. Methods We retrospectively identified patients with suspected NVO undergoing image-guided biopsies from January 2011 to June 2021 at our institution. Two hundred nine patients undergoing 248 percutaneous biopsies were included. Demographic data, biopsy and microbiologic techniques, clinical characteristics, and antibiotic use were collected. Multivariable logistic regression analysis was conducted to determine factors associated with microbiological yield. Results A total of 110 of 209 (52.6%) initial image-guided biopsies revealed positive microbiological results. This number increased to 121 of 209 (57.9%) when repeat image-guided biopsies were included. In multivariable analysis, aspiration of fluid was associated with a 3-fold increased odds of yielding a positive result (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.39–7.04; P = .006), whereas prior antibiotic use was associated with a 3-fold decreased yield (OR, 0.32; 95% CI, .16–.65; P = .002). A univariate subgroup analysis revealed a significant association between the length of the antibiotic-free period and microbiological yield, with the lowest rates of pathogen detection at 0–3 days and higher rates as duration increased (P = .017). Conclusions Prior antibiotic use in patients with suspected NVO was associated with a decrease in the microbiological yield of image-guided biopsies. An antibiotic-free period of at least 4 days is suggested to maximize yield. Successful fluid aspiration during the procedure also increases microbiological yield.