d-[5-11C]-Glutamine Positron Emission Tomography Imaging for Diagnosis and Therapeutic Monitoring of Orthopedic Implant Infections.

Orthopedic implant infections (OIIs) present diagnostic and therapeutic challenges, owing to the lack of methods to distinguish between active infection and sterile inflammation. To address this unmet need, d-amino-acid-based radiotracers with unique metabolic profiles in microorganisms have emerged as a novel class of infection-specific imaging agents. Given the pivotal role of d-glutamine in bacterial biofilm formation and virulence, herein, we explored the potential of positron emission tomography (PET) imaging with d-[5-11C]-Glutamine (d-[5-11C]-Gln) for early detection and treatment monitoring of OIIs. In vitro studies confirmed an active uptake of d-[5-11C]-Gln by Staphylococcus aureus (S. aureus) biofilm commonly associated with OIIs. In vivo evaluations included PET imaging comparisons with d-[5-11C]-Gln vs l-[5-11C]-Gln or 2-deoxy-2-[18F]-fluoroglucose ([18F]-FDG) in a rat OII model with tibial implantation of sterile or S. aureus-colonized stainless-steel screws before and after treatment. These studies demonstrated that the uptake of d-[5-11C]-Gln was significantly higher in the infected screws than that in sterile screws (∼3.4-fold, p = 0.008), which displayed significantly higher infection-to-background muscle uptake ratios (∼2-fold, p = 0.011) with d-[5-11C]-Gln as compared to l-[5-11C]-Gln. Following a 3 week vancomycin treatment, imaging with d-[5-11C]-Gln showed a significant reduction in uptake at the infected sites (∼3-fold, p = 0.0008). Further regression analyses revealed a superior correlation of residual infection-associated radiotracer uptake with the postimaging ex vivo bacterial counts for d-[5-11C]-Gln (k = 0.473, R2 = 0.796) vs [18F]-FDG (k = 0.212, R2 = 0.434), suggesting that d-[5-11C]-Gln PET had higher sensitivity for detecting residual bacterial burden than [18F]-FDG PET. Our results demonstrate the translational potential of d-[5-11C]-Gln PET imaging for noninvasive detection and treatment monitoring of OIIs.

Outpatient Parenteral Antimicrobial Therapy in a Safety Net Hospital: Opportunities for Improvement.

Background: Outpatient parenteral antimicrobial therapy (OPAT) is a safe and cost-effective transitional care approach administered via different delivery models. No standards exist for appropriate OPAT program staffing. We examined outcomes of patients receiving OPAT via different care models to identify strategies to improve safety while reducing health care overuse. Methods: Retrospective demographic, clinical, and outcome data of patients discharged with OPAT were reviewed in 2 periods (April-June 2021 and January-March 2022; ie, when staffing changed) and stratified by care model: self-administered OPAT, health care OPAT, and skilled nursing facility OPAT. Results: Of 342 patients, 186 (54%) received OPAT in 2021 and 156 (46%) in 2022. Hospital length of stay rose from 12.4 days to 14.3 in 2022. In a Cox proportional hazards regression model, visits to the emergency department (ED) within 30 days of OPAT initiation (hazard ratio, 1.76; 95% CI, 1.13-2.73; P = .01) and readmissions (hazard ratio, 2.34; 95% CI, 1.22-4.49; P = .01) increased in 2022 vs 2021, corresponding to decreases in OPAT team staffing. Higher readmissions in the 2022 cohort were for reasons unrelated to OPAT (P = .01) while readmissions related to OPAT did not increase (P = .08). Conclusions: In a well-established OPAT program, greater health care utilization-length of stay, ED visits, and readmissions-were seen during periods of higher staff turnover and attrition. Rather than blunt metrics such as ED visits and readmissions, which are influenced by multiple factors besides OPAT, our findings suggest the need to develop OPAT-specific outcome measures as a quality assessment tool and to establish optimal OPAT program staffing ratios.

Limited Clinical Utility of Routine Mycobacterial Cultures for the Management of Diabetic Foot Infections.

Mycobacterial infections of the foot and ankle are uncommon. In a cohort of 2340 patients with diabetic foot infection (DFI) in a region with increased prevalence of mycobacterial disease, we identified no clinically significant positive cultures over a 3-year period. Routine mycobacterial culture of DFIs is of limited clinical utility.

Pathophysiology and Molecular Imaging of Diabetic Foot Infections.

Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host's immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections.

A Wandering Missionary's Burden: Persistent Fever and Progressive Somnolence in a Returning Traveler.

Human African trypanosomiasis incidence has declined, but diagnosis remains difficult, especially in nonendemic areas. Our patient presented with fever, progressive lethargy, and weight loss for 5 months and had previously traveled to Ghana and Cameroon but had not been to areas with recently reported African trypanosomiasis. Extensive workup was negative, except for lymphocytic pleocytosis in cerebrospinal fluid; ultimately, a bone marrow aspiration revealed necrotizing granulomatous inflammation with 2 trypanosomes discovered on the aspirate smear, consistent with Trypanosoma brucei. The patient was treated with combination nifurtimox and eflornithine with full recovery.

Imaging of Actively Proliferating Bacterial Infections by Targeting the Bacterial Metabolic Footprint with d-[5-11C]-Glutamine.

Since most d-amino acids (DAAs) are utilized by bacterial cells but not by mammalian eukaryotic hosts, recently DAA-based molecular imaging strategies have been extensively explored for noninvasively differentiating bacterial infections from the host's inflammatory responses. Given glutamine's pivotal role in bacterial survival, cell growth, biofilm formation, and even virulence, here we report a new positron emission tomography (PET) imaging approach using d-5-[11C]glutamine (d-[5-11C]-Gln) for potential clinical assessment of bacterial infection through a comparative study with its l-isomer counterpart, l-[5-11C]-Gln. In both control and infected mice, l-[5-11C]-Gln had substantially higher uptake levels than d-[5-11C]-Gln in most organs except the kidneys, showing the expected higher use of l-[5-11C]-Gln by mammalian tissues and more efficient renal excretion of d-[5-11C]-Gln. Importantly, our work demonstrates that PET imaging with d-[5-11C]-Gln is capable of detecting infections induced by both Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) in a dual-infection murine myositis model with significantly higher infection-to-background contrast than with l-[5-11C]-Gln (in E. coli, 1.64; in MRSA, 2.62, p = 0.0004). This can be attributed to the fact that d-[5-11C]-Gln is utilized by bacteria while being more efficiently cleared from the host tissues. We confirmed the bacterial infection imaging specificity of d-[5-11C]-Gln by comparing its uptake in active bacterial infections versus sterile inflammation and with 2-deoxy-2-[18F]fluoroglucose ([18F]FDG). These results together demonstrate the translational potential of PET imaging with d-[5-11C]-Gln for the noninvasive detection of bacterial infectious diseases in humans.

Healthcare-associated Legionnaires' disease: Limitations of surveillance definitions and importance of epidemiologic investigation.

Healthcare-associated Legionnaires' disease (HCA LD) causes significant morbidity and mortality, with varying guidance on prevention. We describe the evaluation of a case of possible HCA LD and note the pitfalls of relying solely on an epidemiologic definition for association of a case with a facility. Our detailed investigation led to the identification of a new Legionella pneumophila serogroup 1 sequence type, confirmed a healthcare association and helped build the framework for our ongoing preventive efforts. Our experience highlights the role of routine environmental cultures in the assessment of risk for a given facility. As clinicians increasingly rely on urinary antigen testing for the detection of L. pneumophila, our investigation emphasises the importance of clinical cultures in an epidemiologic investigation.

Serratia fonticola, pathogen or bystander? A case series and review of the literature.

Serratia fonticola is an unusual human pathogen, previously described primarily as causing skin and soft tissue infections following trauma. There is little information in the literature about its treatment or susceptibilities. We describe the case of a 67-year-old male with paraplegia who developed urosepsis due to S. fonticola. Blood and urine cultures obtained prior to the initiation of antimicrobials both grew S. fonticola. The patient completed a 15-day course of antimicrobials and had an uneventful recovery. We reviewed 17 other patients with clinical cultures positive for S. fonticola. Of these, 11 isolates were from the genitourinary system, most often as part of a polymicrobial culture. The majority of the other organisms recovered were recognized pathogens from the Enterobacteriaceae family. The cases suggest that when recovered in conjunction with other organisms, S. fonticola does not lead to enhanced virulence or worse clinical outcomes and may be a bystander. When detected alone, which is a rare occurrence, S. fonticola may function as a human pathogen.