Antiplatelet therapy for Staphylococcus aureus bacteremia: Will it stick?

Staphylococcus aureus bacteremia (SAB) remains a clinically challenging infection despite extensive investigation. Repurposing medications approved for other indications is appealing as clinical safety profiles have already been established. Ticagrelor, a reversible adenosine diphosphate receptor antagonist that prevents platelet aggregation, is indicated for patients suffering from acute coronary syndrome (ACS). However, some clinical data suggest that patients treated with ticagrelor are less likely to have poor outcomes due to S. aureus infection. There are several potential mechanisms by which ticagrelor may affect S. aureus virulence. These include direct antibacterial activity, up-regulation of the innate immune system through boosting platelet-mediated S. aureus killing, and prevention of S. aureus adhesion to host tissues. In this Pearl, we review the clinical data surrounding ticagrelor and infection as well as explore the evidence surrounding these proposed mechanisms of action. While more evidence is needed before antiplatelet medications formally become part of the arsenal against S. aureus infection, these potential mechanisms represent exciting pathways to target in the host/pathogen interface.

Can gas and infection coexist in the intervertebral disc? A retrospective analysis of percutaneously biopsied suspected discitis-osteomyelitis cases.

OBJECTIVES: To retrospectively evaluate the correlation between intradiscal gas and infection in patients percutaneously biopsied for suspected discitis-osteomyelitis. MATERIALS AND METHODS: We retrospectively reviewed all CT-guided discitis-osteomyelitis biopsies performed between 2002 and 2022. Two independent trained musculoskeletal radiologists evaluated for presence of gas on CT and/or MRI within 1 week of the biopsy. Disagreements were resolved by a third musculoskeletal radiologist. CT was considered the gold standard for the detection of intradiscal gas. Pathology, microbiology, and imaging and clinical follow-up were used as the gold standard for presence of infection. Interrater agreement on CT and MRI, sensitivity, and positive predictive value were calculated, using the presence of gas as an indicator (test positive) for "no infection." RESULTS: There were 284 biopsies in 275 subjects (mean age 58 ± 1.0 (range 4-99) years; 101 (37%) females and 174 (63%) males). Of the biopsies, 12 (4%) were cervical, 80 (28%) were thoracic, 192 (68%) were lumbar, and 200 (70%) were considered true discitis-osteomyelitis based on pathology, imaging, and clinical follow-up. Interrater agreement was excellent for CT (kappa = 0.83) and poor for MRI (kappa = - 0.021). The presence of gas had a 94% specificity and 76% negative predictive value for the absence of infection. CONCLUSION: CT is the preferred method for detecting intradiscal gas. The presence of gas means that discitis-osteomyelitis is unlikely. If intradiscal gas is present in the setting of discitis-osteomyelitis, the gas bubbles tend to be smaller and fewer in number.

Periprosthetic Joint Infection: Current Clinical Challenges.

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.

Executive Summary: Periprosthetic Joint Infection-Current Clinical Challenges.

Over the last several decades, periprosthetic joint infection (PJI) 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 PJI, focusing on frequent clinical challenges and collaborative interdisciplinary care. The more detailed review including diagnosis, surgical considerations, and a detailed antimicrobial discussion is presented in the online version.

Rates and Outcomes of Periprosthetic Joint Infection in Persons Who Inject Drugs.

BACKGROUND: The risk of periprosthetic joint infection (PJI) is higher in persons who inject drugs (PWID) after total joint arthroplasty (TJA), though reported rates vary widely. This study was designed to assess outcomes of TJA in PWID and to describe factors associated with improved PJI outcomes among PWID. METHODS: A retrospective matched cohort study was performed using a 1:4 match among those with and those without a history of injection drug use (IDU) undergoing TJA. Demographic, surgical, and outcome variables were compared in multivariate logistic regressions to determine PJI predictors. Kaplan-Meier analyses were constructed to characterize the difference in survival of patients who did not have PJI or undergo joint explantation between PWID and the matching cohort. RESULTS: PWID had a 9-fold increased risk of PJI compared to the matched cohort (odds ratio 9.605, 95% CI 2.781-33.175, P < .001). Ten of 17 PWID whose last use was within 6 months (active use) of primary TJA had a PJI, while 7 of 41 PWID who did not have active use developed a PJI. Of PWID with PJI, treatment failure was seen in 15 of 17, while in patients who did not have an IDU history, 5 of 8 with PJI had treatment failure. CONCLUSION: IDU is a significant risk factor for PJI following TJA. Future work investigating the effect of a multidisciplinary support team to assist in cessation of IDU and to provide social support may improve outcomes and reduce morbidity in this vulnerable population.

Antibiotic Prophylaxis for Total Joint Arthroplasty.

Total joint arthroplasty is an important therapeutic option for patients suffering from osteoarthritis and other degenerative joint diseases. However, joint replacements are susceptible to periprosthetic joint infection especially by staphylococci and other gram-positive organisms. Antibiotic prophylaxis, or systemic administration of antibiotics prior to primary arthroplasty, has been shown to reduce rates of surgical site infection and periprosthetic joint infection. The motivation and goals behind antibiotic prophylaxis, current guidelines, the choice of antibiotic agents, and important factors in antimicrobial administration, including its dose, timing, and duration, are reviewed.

Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Best Practices: CT-Guided Percutaneous Sampling of Vertebral Discitis-Osteomyelitis and Technical Factors Maximizing Biopsy Yield.

Vertebral discitis-osteomyelitis is an infection of the intervertebral disk and vertebral bodies that may extend to adjacent paraspinal and epidural soft tissues. Its incidence is increasing, likely because of improved treatments and increased life expectancy for patients with predisposing chronic disease and increased rates of IV drug use and intravascular intervention. Because blood cultures are frequently negative in patients with vertebral discitis-osteomyelitis, biopsy is often indicated to identify a causative microorganism for targeted antimicrobial therapy. The reported yield of CT-guided percutaneous sampling is 31-91%, which is lower than the reported yield of open biopsy of 76-91%. However, the less invasive approach may be favored given its relative safety and low cost. If paravertebral fluid collections are present, CT-guided aspiration should be performed. If aspiration is unsuccessful or no paravertebral fluid collections are present, CT-guided percutaneous biopsy should be performed, considering technical factors (e.g., anatomic approach, needle selection, and needle angulation) that may improve microbiologic yield. Although antimicrobial therapy should be withheld for 1-2 weeks before biopsy if clinically feasible, biopsy may still be performed without stopping antimicrobial therapy if needed. Because of the importance of targeted antimicrobial therapy, repeat biopsy should be considered after 72 hours if initial biopsy does not identify a pathogen.

MRI and clinical features of acute fungal discitis/osteomyelitis.

OBJECTIVES: To compare imaging and clinical features of fungal and Staphylococcus aureus discitis-osteomyelitis (DO) for patients presenting for CT-guided biopsies. METHODS: Our study was IRB-approved and HIPAA-compliant. A group of 11 fungal DO (FG) with MRI within 7 days of the biopsy and a control group (CG) of 19 Staphylococcus aureus DO were evaluated. Imaging findings (focal vs diffuse paravertebral soft tissue abnormality, partial vs complete involvement of the disc/endplate), biopsy location, pathology, duration of back pain, immune status, history of intravenous drug, history of prior infection, current antibiotic treatment, and history of invasive intervention. Differences were assessed using the Fisher exact test and Kruskal-Wallis test. Naïve Bayes predictive modeling was performed. RESULTS: The most common fungal organisms were Candida species (9/11, 82%). The FG was more likely to have focal soft tissue abnormality (p = 0.040) and partial disc/endplate involvement (p = 0.053). The clinical predictors for fungal DO, in order of importance, back pain for 10 or more weeks, current antibiotic use for 1 week or more, and current intravenous drug use. History of invasive instrumentation within 1 year was more predictive of Staphylococcus aureus DO. CONCLUSION: MRI features (focal partial soft tissue abnormality and partial involvement of the disc/endplate) in combination with clinical features may help to predict fungal species as a causative organism for DO. KEY POINTS: • MRI features of discitis-osteomyelitis (focal partial soft tissue abnormality and partial involvement of the disc/endplate) in combination with clinical features may help to predict fungal species as a causative organism for DO.

CT-guided discitis-osteomyelitis biopsies: needle gauge and microbiology results.

PURPOSE: To compare the microbiology results and needle gauge for CT-guided biopsies of suspected discitis-osteomyelitis. METHODS: All CT-guided biopsies performed for suspected discitis-osteomyelitis at our institution between 2002 and 2019 were reviewed. Biopsy location, needle type and gauge, microbiology, pathology, and clinical and imaging follow-up were obtained through chart review. Yield, sensitivity, specificity, and accuracy were calculated. A pairwise analysis of different needle gauges was also performed with calculations of odds ratios. Naïve Bayes predictive modeling was performed. RESULTS: 241 (age: 59 ± 18 years; 88 [35%] F, 162 [65%] M) biopsies were performed. There were 3 (1%) 11 gauge (G), and 13 (5%) 12-G biopsies; 23 (10%) 13-G biopsies; 75 (31%) 14-G biopsies; and 90 (37%) 16-G, 33 (14%) 18-G, and 4 (2%) 20 G biopsies. True disease status (presence of infection) was determined via either pathology findings (205, 86%) or clinical and imaging follow-up (36, 14%). The most common true positive pathogen was Staphylococcus aureus (31, 33%). Overall biopsy yield, sensitivity, specificity, and accuracy were 39%, 56%, 89%, and 66%, respectively. Pooled biopsy yield, sensitivity, specificity, and accuracy was 56%, 69%, 71%, and 69% for 11-13-G needles and 36%, 53%, 91%, and 65% for 14-20-G needles, respectively, with an odds ratio between the two groups of 2.29 (P = 0.021). Pooled biopsy yield, sensitivity, specificity, and accuracy was 48%, 63%, 85%, and 68% for 11-14-G needles and 32%, 49%, 91%, and 64% for 16-20-G needles, respectively, with an odds ratio between the two groups of 2.02 (P = 0.0086). CONCLUSION: The use of a larger inner bore diameter/lower gauge biopsy needle may increase the likelihood of culturing the causative microorganism for CT-guided biopsies of discitis-osteomyelitis.

CT-guided discitis-osteomyelitis biopsies with negative microbiology: how many days should we wait before repeating the biopsy?

PURPOSE: To determine the number of days to positive CT-guided biopsy sample culture in patients with discitis-osteomyelitis. METHODS: Our study was IRB approved and HIPAA compliant. All CT-guided biopsies performed for acute discitis-osteomyelitis with positive microbiology between 2002 and 2018 were reviewed. Microbiological organism and days to positive biopsy were documented. Mean, median, skew, and standard deviation were calculated. The proportion of positive cultures that become positive after each day has elapsed was also calculated. RESULTS: There were 96 true positive cultures, with 64 (67%) male and 32 (33%) female, ages 57 ± 18 (range 19-87) years. Overall, including all culture results, the mean number of days to positive culture was 2.9 ± 3.5 days. The median number of days was 2, with a positive skew of 2.9. At days 1, 2, 3, 4, and 5, 48%, 68%, 78%, 85%, and 89%, respectively, of biopsy samples had a positive microbiology culture. CONCLUSION: Approximately three-quarters of discitis-osteomyelitis pathogens will be identified by biopsy sample culture by 3 days after CT-guided biopsy. This finding should be considered if planning for a repeat biopsy in the setting of a negative microbiology culture.

Early Infectious Diseases Specialty Intervention Is Associated With Shorter Hospital Stays and Lower Readmission Rates: A Retrospective Cohort Study.

Background: Intervention by infectious diseases (ID) physicians improves outcomes for inpatients in Medicare, but patients with other insurance types could fare differently. We assessed whether ID involvement leads to better outcomes among privately insured patients under age 65 years hospitalized with common infections. Methods: We performed a retrospective analysis of administrative claims data from community hospital and postdischarge ambulatory care. Patients were privately insured individuals less than 65 years old with an acute-care stay in 2014 for selected infections, classed as having early (by day 3) or late (after day 3) ID intervention, or none. Key outcomes were mortality, cost, length of the index stay, readmission rate, mortality, and total cost of care over the first 30 days after discharge. Results: Patients managed with early ID involvement had shorter length of stay, lower spending, and lower mortality in the index stay than those patients managed without ID involvement. Relative to late, early ID involvement was associated with shorter length of stay and lower cost. Individuals with early ID intervention during hospitalization had fewer readmissions and lower healthcare payments after discharge. Relative to late, those with early ID intervention experienced lower readmission, lower spending, and lower mortality. Conclusions: Among privately insured patients less than 65 years old, treated in a hospital, early intervention with an ID physician was associated with lower mortality rate and shorter length of stay. Patients who received early ID intervention during their hospital stay were less likely to be readmitted after discharge and had lower total healthcare spending.

Percutaneous CT-guided sacroiliac joint sampling for infection: aspiration, biopsy, and technique.

OBJECTIVE: To evaluate methods of CT-guided sacroiliac joint sampling in patients with suspected infection. MATERIALS AND METHODS: All CT-guided sacroiliac joint sampling procedures for suspected infection were reviewed for sampling type (aspiration, lavage aspiration, biopsy), microbiology results, and clinical and imaging follow-up. The primary gold standard was anatomic pathology. If pathology was not available, then positive blood culture with the same organism as SIJ sampling, imaging and clinical follow-up, or clinical follow-up only were used. Anterior and posterior joint distention was evaluated by MRI within 7 days of the procedure. RESULTS: A total of 34 patients (age 39 ± 20 (range, 6-75) years; 21 F, 13 M) were included. Aspiration samples only were obtained in 13/34 (38%) cases, biopsy samples only in 9/34 (26%) cases, and both samples in 12/34 (35%) cases. There was an overall 54% sensitivity and 86% specificity. For the aspiration samples, sensitivity and specificity were 60 and 81%, respectively, compared to 45 and 90% for the biopsy samples. In cases with both samples, biopsy did not add additional microbial information. Seventeen (17/34, 50%) patients had an MRI. The anterior joint was more distended than the posterior joint in 15/17 (88%) of patients, and this difference was significant (P = 0.0003). All of these 17 patients had an attempted aspiration by a posterior approach; 6/17 (35%) resulted in a successful aspiration. CONCLUSIONS: Aspiration of the sacroiliac joint has a higher sensitivity than biopsy and should always be attempted first. MRI may be helpful for procedure planning.

Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics.

BACKGROUND: Although drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. OBJECTIVE: We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). METHODS: We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least 1 differential blood count. We used multivariate Cox proportional hazards models with time-varying antibiotic treatment indicators to assess the effect of demographic data and antibiotic exposures on eosinophilia and subsequent HSRs, including documented rash, renal injury, and liver injury. Possible drug rash with eosinophilia and systemic symptoms (DRESS) syndrome cases were identified and manually validated. RESULTS: Of 824 patients (60% male; median age, 60 years; median therapy duration, 41 days), 210 (25%) had eosinophilia, with median peak absolute eosinophil counts of 726/mL (interquartile range, 594-990/mL). Use of vancomycin, penicillin, rifampin, and linezolid was associated with a higher hazard of having eosinophilia. There was a subsequent HSR in 64 (30%) of 210 patients with eosinophilia, including rash (n = 32), renal injury (n = 31), and liver injury (n = 13). Patients with eosinophilia were significantly more likely to have rash (hazard ratio [HR], 4.16; 95% CI, 2.54-6.83; P < .0001) and renal injury (HR, 2.13; 95% CI, 1.36-3.33; P = .0009) but not liver injury (HR, 1.75; 95% CI, 0.92-3.33; P = .09). Possible DRESS syndrome occurred in 7 (0.8%) of 824 patients; 4 (57%) were receiving vancomycin. CONCLUSIONS: Drug-induced eosinophilia is common with parenteral antibiotics. Although most patients with eosinophilia do not have an HSR, eosinophilia increases the hazard rate of having rash and renal injury. DRESS syndrome was more common than previously described.

Is Biopsying the Paravertebral Soft Tissue as Effective as Biopsying the Disk or Vertebral Endplate? 10-Year Retrospective Review of CT-Guided Biopsy of Diskitis-Osteomyelitis.

OBJECTIVE: The purpose of this study was to determine whether there is a difference in biopsying bone (endplate), disk, or paravertebral soft tissue to culture the pathogenic organism causing diskitis-osteomyelitis. MATERIALS AND METHODS: A retrospective review was conducted of 111 spinal biopsies performed between 2002 and 2011. Pathologic examination was used as the reference standard for detecting diskitis-osteomyelitis. Microbiologic yield, sensitivity, and specificity were calculated. The yields for different groups were compared by use of Fisher exact test. The analysis was repeated with biopsy samples from patients not being treated with antibiotics at the time of biopsy. RESULTS: A total of 122 biopsy specimens were obtained from 111 spinal biopsy procedures on 102 patients. Overall, 27 (22%) biopsies were performed on the endplate-disk, 61 (50%) on the disk only, and 34 (28%) on paravertebral soft tissue only. The microbiologic yield was 36% for all biopsies, 19% for endplate-disk biopsies, 39% for disk-only biopsies, and 44% for soft-tissue biopsies. The sensitivity and specificity of the microbiologic results for all specimens were 57% and 89%; endplate-disk, 38% and 86%; disk only, 57% and 89%; and paravertebral soft tissue, 68% and 92%. There was no statistically significant difference between the yields of the endplate-disk, disk-only, and paravertebral soft-tissue biopsies. CONCLUSION: Paravertebral soft-tissue changes, when present, may be considered a viable target for biopsy in cases of diskitis-osteomyelitis, even in the absence of a paravertebral abscess.

Comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting.

BACKGROUND: Nafcillin and cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents. METHODS: In this retrospective cohort analysis of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated. RESULTS: Three hundred sixty-six and 119 patients were treated with nafcillin or cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16-37) and 29 (IQR, 24-39) days, respectively, for those treated with nafcillin and cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs cefazolin groups was 2.81 (95% confidence interval [CI], 1.26-3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4-27.3) and 4.8 (95% CI, 1.1-10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to cefazolin; all 9 completed treatment with no further observed DEEs. CONCLUSIONS: Nafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.

Tolerability of cefazolin after immune-mediated hypersensitivity reactions to nafcillin in the outpatient setting.

The objective of the present study was to assess the safety and tolerability of cefazolin therapy among patients with methicillin-sensitive Gram-positive bacterial infections who develop non-IgE-mediated hypersensitivity reactions (HSRs) to nafcillin. In this retrospective cohort analysis of the Outpatient Parenteral Antimicrobial Therapy program at the Massachusetts General Hospital from 2007 through 2013, we identified patients switched from nafcillin to cefazolin after an immune-mediated HSR. We reviewed patient demographics, details about the original HSR, and outcomes after the switch to cefazolin therapy. HSRs were classified by reaction type and likely mechanism. There were 467 patients treated with nafcillin, of which 60 (12.8%) were switched to cefazolin during their prescribed course. Of the 60 patients who transitioned to cefazolin, 17 (28.3%) were switched because of non-IgE-mediated HSRs. HSRs included maculopapular rash (n = 10), immune-mediated nephritis (n = 3), isolated eosinophilia (n = 2), immune-mediated hepatitis (n = 1), and a serum sickness-like reaction (n = 1). All but one patient (94.1%) who switched to cefazolin tolerated the drug with resolution of the HSR and completed their therapy with cefazolin. No patient experienced worsening of their rash or progressive organ dysfunction. With appropriate monitoring, therapy with cefazolin after non-IgE-mediated HSRs to nafcillin appears to be safe.