How We Approach Suppressive Antibiotic Therapy Following Debridement, Antibiotics, and Implant Retention for Prosthetic Joint Infection.

The optimal treatment of prosthetic joint infection (PJI) remains uncertain. Patients undergoing debridement, antibiotics, and implant retention (DAIR) receive extended antimicrobial treatment, and some experts leave patients at perceived highest risk of relapse on suppressive antibiotic therapy (SAT). In this narrative review, we synthesize the literature concerning the role of SAT to prevent treatment failure following DAIR, attempting to answer 3 key questions: (1) What factors identify patients at highest risk for treatment failure after DAIR (ie, patients with the greatest potential to benefit from SAT), (2) Does SAT reduce the rate of treatment failure after DAIR, and (3) What are the rates of treatment failure and adverse events necessitating treatment discontinuation in patients receiving SAT? We conclude by proposing risk-benefit stratification criteria to guide use of SAT after DAIR for PJI, informed by the limited available literature.

Oritavancin as sequential therapy for Gram-positive bloodstream infections.

BACKGROUND: Oritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE). METHODS: We conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received ≥ 1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance. RESULTS: Overall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5-17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient). CONCLUSIONS: The use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Buprenorphine Prescribing and Dosing Limits: Evidence and Policy Goals.

The opioid misuse epidemic is a serious public health crisis. Opioid-involved deaths continue to rise and the potency of illicitly manufactured synthetic opioids has increased, creating challenges for the healthcare system to provide multifaceted specialized care. Elements of the regulation around buprenorphine, 1 of 3 drugs approved to treat opioid use disorder (OUD), constrain treatment options for patients and providers alike. Updates to this regulatory framework, particularly around dosing and access to care, would enable providers to better treat the changing landscape of opioid misuse. Specific actions to this end are to: (1) Increase buprenorphine dosing flexibility based on FDA labeling which drives payor policies; (2) Restrict local government and institutional impositions of arbitrary access and dosing limits for buprenorphine; and (3) Liberalize buprenorphine initiation and maintenance via telemedicine for OUD.

Opioid Use and Chronic Infections: The Value of Addressing the Syndemic in Correctional Settings Via Telemedicine Guidance and Broader Use of Long-Acting Medications.

In the United States, we are experiencing linked epidemics (a syndemic) of substance use disorders (SUDs) and infections associated with drug use, including unsafe injecting and unsafe sex in exchange for drugs or money. Current drug laws, together with risk-taking behavior among persons with SUDs, contribute to disproportionately high prevalences of these conditions in correctional settings. Detection and treatment of diseases with a high impact on public health are best addressed in the settings where such conditions are most prevalent (ie, jails and prisons for SUDs and chronic infections). The effectiveness, safety, cost of care. and public health impact of these conditions can be improved by means of broader screening and expanded access to specialty consultations through telemedicine/telehealth, along with broader use of long-acting medications for the treatment of human immunodeficiency virus and SUDs. Expanding telemedicine/telehealth, first for specialties which do not require advanced technology (eg, infectious diseases, addictions), can eventually lead to further advancements in correctional healthcare.

Access to Specialty Services: Opportunities for Expansion of Telemedicine to Support Correctional Health Care in Colorado.

Introduction: The United States has the largest correctional population in the world and many inmates lack access to timely health care. Studies have shown that telemedicine could improve the situation in a practical and cost-effective fashion. We aimed to evaluate currently established services as well as any potential need for expansion of telemedicine within correctional settings in Colorado. Methods: We designed a prospective survey-based pilot study using mixed methods research techniques. Results: Colorado has 50 county jails, 19 prisons, and 3 private prison facilities. Of these, 46 correctional facilities (45 jails and the state prison) were contacted. Twenty responded (19 jails and the prison) representing 43.5% response rate. Only 10% did not have on-site health care providers available at all, 31.6% were already using telemedicine for some of their needs, 52.9% were "very interested," 5.9% "somewhat interested," 17.6% "not so interested," and 23.5% were "not at all interested" in further information regarding telemedicine services. Discussion: Our study as well as current literature suggest that telemedicine could serve to fill in certain gaps of care within correctional populations, especially for over-represented conditions (i.e., chronic infectious diseases, such as HIV and hepatitis C virus, substance use disorders, or mental health disorders). Conclusions: There is enthusiasm but also certain amount of skepticism among Colorado's jail administrators with respect to the implementation, or even the cost-effectiveness potential of telemedicine. Telemedicine in these settings may require individualized approach and enough creative flexibility to allow for nimble adjustments based on the constraints and needs of individual institutions.

On- and off-label utilization of dalbavancin and oritavancin for Gram-positive infections.

BACKGROUND: Long-acting lipoglycopeptides (laLGPs) are FDA approved only for acute bacterial skin and skin structure infections (ABSSSIs). However, these antibiotics show promise for off-label use, reductions in hospital length of stay (LOS) and healthcare cost savings. OBJECTIVES: To assess the effectiveness, safety, impact on LOS and estimated cost savings from laLGP treatment for Gram-positive infections. METHODS: Retrospective cohort of adult patients who received at least one dose of laLGPs at the University of Colorado Health system. Descriptive statistics were utilized for analysis. RESULTS: Of 59 patients screened, 56 were included: mean age 47 years, 59% male and 30% injection drug users/polysubstance abusers (dalbavancin, 71%; oritavancin, 25%; both, 4%). Most common indications for laLGP: ABSSSIs (36%), osteomyelitis (27%) and endocarditis (9%). Most common isolated pathogens: MSSA and MRSA (25% and 19%, respectively), Enterococcus faecalis (11%) and CoNS (11%). Previous antibiotics were administered for a median of 13 days (IQR = 7.0-24.5 days) and laLGPs for a median of one dose (IQR = 1-2 doses). Ten (18%) patients were lost to follow-up. Clinical failure was found in 7/47 (15%) cases with adequate follow-up. Mild adverse effects occurred in six (11%) patients. Projected reduction in hospital LOS and health-system costs were 514 days (9.18 days/person average) and $963456.72 ($17204.58/person average), respectively. CONCLUSIONS: Prospective trials are needed to validate the use of these antibiotics for Gram-positive infections in practice, with the hope that they will reduce hospital LOS and the need for daily antibiotic infusions to provide alternative options for patients not qualifying for outpatient parenteral antimicrobial therapy.

Sex-based differences in treatment approaches and outcomes among patients with mpox: Limitations of real-world data.

BACKGROUND: Limited data on females with mpox restricts understanding of potential sex-based disparities in treatment and outcomes. This study aims to investigate these differences using administrative claims and clinical data repositories. METHODS: We retrospectively analyzed adults diagnosed with mpox using TriNetX, stratifying cohorts by sex. The primary outcome included urgent care, emergency room, and hospitalization visits, with secondary outcomes including clinical findings, vaccination, and treatment. RESULTS: Among 2011 cases, 90% were male. Males were older, more likely to identify as Hispanic or Latino, and had higher HIV prevalence and sexually transmitted infection rates. Hospitalization rates were low for both groups, with similar healthcare utilization. However, males received fewer opioid analgesics, glucocorticoids, and antiemetics versus females. Vaccination and tecovirimat use were minimal in both groups. CONCLUSION: Addressing sex disparities in mpox treatment and outcomes is crucial, but existing data sources like administrative claims and clinical data repositories pose limitations.

Substance use disorder-associated infections' treatment with dalbavancin enabling outpatient transition (SUDDEN OUT) - an investigator-initiated single-arm unblinded prospective cohort study.

Background: Severe gram-positive infections are frequent in people who inject drugs, and successful completion of treatment presents unique challenges in this population. Objectives: We aimed to evaluate the feasibility of a long-acting antibiotic, dalbavancin, as an alternative to standard-of-care antibiotics for severe infections due to vancomycin-susceptible pathogens requiring ⩾2 weeks of therapy. Design: We designed an investigator-initiated single-arm unblinded prospective cohort study to evaluate the safety and efficacy of an early switch to dalbavancin in two doses administered 1 week apart. Methods: We screened patients admitted with bloodstream infection, osteomyelitis, septic arthritis, infective endocarditis or deep abscesses, and comorbid substance use disorder (SUD) for eligibility. Consenting patients were switched to dalbavancin within 7 days from their index culture. They were monitored in the hospital for efficacy and safety of the treatment until the second dose of dalbavancin 7 days later and then discharged if stable. Study participants were evaluated with a decision support engine for a hypothetical appropriate level of care regarding their SUD after discharge. Their follow-up was planned for 12 months from the index culture, either in-person or via telehealth/telephone. Results: The enrollment was terminated early due to significant loss-to-follow-up. In all, 11 patients were enrolled, 4 completed 12 months of follow-up, 2 completed 8 months of follow-up, and 1 was seen once after discharge. The remaining five patients were lost to follow-up immediately after discharge. All 11 patients continued to improve after switching to dalbavancin between the first and second doses. There were two per-protocol failures of treatment. Dalbavancin was well tolerated, though some adverse events were reported. Conclusion: Dalbavancin may be a safe and effective alternative for an early switch in treating severe gram-positive infections. Trial registration: The trial was registered as NCT04847921 with clinicaltrials.gov.

Bone and Skin/Subcutaneous Tissue Concentrations of Cefiderocol During Treatment of Extensively Drug-Resistant Pseudomonas aeruginosa.

Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the treatment of an extensively drug-resistant Pseudomonas aeruginosa bacteremia, and presumed osteomyelitis in a patient with severe pyoderma gangrenosum and associated immunosuppressive therapy while being medically optimized for skin grafting. We obtained bone and skin/subcutaneous tissue while the patient was on cefiderocol under an institutional review board-approved biologic waste recovery protocol. Cefiderocol concentrations in bone and skin/subcutaneous tissue were 13.9 and 35.9 mcg/g, respectively. The patient recovered from bacteremia and underwent autografting without further complications. Cefiderocol at approved dosing of 2 g IV (3-hour infusion) every 8 hours resulted in bone and skin/subcutaneous tissue concentrations adequate to treat extensively drug-resistant Gram-negative bacteria that remain susceptible to cefiderocol.

Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.

INTRODUCTION: Previous studies have reported a decreased risk of dementia with herpes zoster vaccination. Given this background, this systematic review and meta-analysis aimed to investigate the association between herpes zoster vaccination and the risk of dementia. METHODS: We searched five databases until November 2023 for case-control, cross-sectional, or cohort studies investigating the association of herpes zoster vaccination and dementia. Odds ratios and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were also conducted. RESULTS: We evaluated a total of five studies (one cross-sectional, one case-control, and four cohort studies) that included a total number of 103,615 patients who were vaccinated with herpes zoster vaccine. All the studies were of high quality, ranging from 7 to 9. Due to the high heterogeneity (I2 = 100%, p < .00001) observed in our study, a random effect model was used for the analysis. The pooled odds ratio was 0.84 (95% CI: 0.50, 1.43), p (overall effect) = .53), indicating that herpes zoster vaccination reduces the risk of dementia. CONCLUSION: Herpes zoster vaccination is associated with a reduction of the risk of dementia. More epidemiological studies are needed to confirm the association.

National HIV and HCV Screening Rates for Hospitalized People who Use Drugs Are Suboptimal and Heterogeneous Across 11 US Hospitals.

Background: To end the HIV and hepatitis C virus (HCV) epidemics, people who use drugs (PWUD) need more opportunities for testing. While inpatient hospitalizations are an essential opportunity to test people who use drugs (PWUD) for HIV and HCV, there is limited research on rates of inpatient testing for HIV and HCV among PWUD. Methods: Eleven hospital sites were included in the study. Each site created a cohort of inpatient encounters associated with injection drug use. From these cohorts, we collected data on HCV and HIV testing rates and HIV testing consent policies from 65 276 PWUD hospitalizations. Results: Hospitals had average screening rates of 40% for HIV and 32% for HCV, with widespread heterogeneity in screening rates across facilities. State consent laws and opt-out testing policies were not associated with statistically significant differences in HIV screening rates. On average, hospitals that reflexed HCV viral load testing on HCV antibody testing did not have statistically significant differences in HCV viral load testing rates. We found suboptimal testing rates during inpatient encounters for PWUD. As treatment (HIV) and cure (HCV) are necessary to end these epidemics, we need to prioritize understanding and overcoming barriers to testing.

Perceived Risks and Benefits and Frequency of Cannabis Use Among People with HIV in Different Legal Environments.

We sought to describe the prevalence of and motivation for cannabis use and whether legalization of cannabis impacts the frequency and perceived risks and benefits of use in people living with HIV (PWH). The study was based on two HIV clinics located in Cleveland, Ohio, and Aurora, Colorado. Participants responded to a 45-question survey, and responses were summarized in aggregate and stratified by the frequency of cannabis use and site. Three hundred ninety-seven participants completed the survey. The frequency of use was not different between the sites. Daily cannabis users compared with yearly or never users identified the benefits of cannabis as relief from stress, anxiety, or depression, improved sleep, improved creativity, improved focus or concentration, and increased energy. The benefits of pain management, improved appetite, and helping to decrease or stop other medications were selected at similar rates, regardless of the frequency of use. Daily users were less likely to identify treatment of disease as a benefit and legal problems, addiction to cannabis, impaired memory, increased use of other drugs, personal or relationship problems, decrease in intelligence, new or worsening health problems, and getting high as risks of use compared with yearly or never users. Compared with participants in Ohio, Coloradoans were more likely to identify cannabis benefits as decreasing/stopping other medications and getting high, and less likely to identify legal problems and addiction as risks. Legalization of cannabis did not affect the frequency of cannabis use in PWH. Daily cannabis users are more likely to identify benefits and less likely to identify risks of use compared with yearly or never users. A better understanding of the potential benefits and risks of cannabis use can help guide safer use of cannabis in PWH and allow physicians to provide better counseling on risk reduction.

Augmented Renal Function in Burn Patients: Occurrence and Discordance With Commonly Used Methods to Assess Renal Function.

Augmented renal clearance (ARC) is defined by supraphysiologic renal function and is associated with drug failure due to subtherapeutic drug exposure. Burn patients are cited as being at high risk for ARC, yet rates of ARC have not been well described. This retrospective study described the prevalence and incidence of ARC, and compared 12-hour urine collection values (CrCl-12) vs. common estimates of renal function in assessed patients at an American Burn Association-verified burn center. All thermally injured burn patients with a CrCl-12 result were included. ARC was defined as a CrCl-12 >130 ml/min. Cockcroft-Gault, modification of diet in renal disease (MDRD), and CKD-EPI-2021 estimates were calculated. Over 13 months, 163 CrCl-12 results were collected in 68 patients at a median of 9 days from admission with an average value of 160 ml/min. The median total body surface area (total body surface area [TBSA]%) was 17.25%. ARC prevalence was 70.6% with an incidence of 66.3% in all CrCl-12 assessments. Those with ARC were less likely to have heart failure, P = .007. Age, TBSA%, and trauma were not different between those with or without ARC. ARC incidences in those with TBSAs of ≥20%, <20%, or <10%, were 70.5%, 58.6%, and 76.7%, respectively. Agreement of Cockcroft-Gault, MDRD, and CKD-EPI-2021 to CrCl-12 was moderate to weak and frequently failed to identify ARC. ARC is common in burn patients, regardless of TBSA%. Widely accepted estimations of renal function may be incorrect resulting in under-dosing of medications. Additional research is required to identify burn patients at greatest risk for ARC and subsequent dosing strategies to maintain pharmacologic efficacy without unduetoxicity.

Kimyrsa, An Oritavancin-Containing Product: Clinical Study and Review of Properties.

Background: There is a need for improved antibiotic formulations for the treatment of acute bacterial skin and soft structure infection (ABSSSI), especially with the rise of antimicrobial resistance among Gram-positive bacteria. A new formulation of oritavancin was developed to reduce intravenous infusion volume (from 1000 mL to 250 mL), shorten infusion time (from 3 hours to 1 hour), and provide pharmacies with flexibility in oritavancin preparation (from 5% dextrose in sterile water to either normal saline or 5% dextrose in sterile water) compared with the current formulation. Methods: A total of 102 adult patients with a diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen were randomized 1:1 to receive either the new formulation of oritavancin or the current formulation. After a single 1200-mg intravenous infusion of oritavancin, the relative area-under-the-curve exposure of the new formulation and current formulation groups were compared. Safety and tolerability of the new formulation were assessed for treatment-emergent adverse events, serious adverse events, and changes to laboratory parameters. Results: The area under the curve for 0 hour to 72 hours postdose was very similar in the new formulation group compared with the current formulation group. No differences in treatment-emergent adverse events were observed between the current and new formulation groups, and all treatment-emergent adverse events were consistent with the known safety profile of the current formulation. Conclusions: The new formulation of oritavancin with reduced volume and duration of intravenous infusion demonstrates a safety profile and pharmacokinetics similar to that of the original formulation.

Real-World Use of Tedizolid Phosphate for 28 Days or More: A Case Series Describing Tolerability and Clinical Success.

Tedizolid has activity against Gram-positive pathogens as well as Mycobacterium spp and Nocardia spp. Real-world evidence supporting long-term tolerability and clinical success of tedizolid is lacking. Prolonged tedizolid therapy (median, 188 days; interquartile range, 62-493 days) appeared to be well tolerated in 37 patients (8.1% experienced adverse effect leading to discontinuation). Clinical success was 81.3% in those evaluated.

Comparison of Sequential Dalbavancin With Standard-of-Care Treatment for Staphylococcus aureus Bloodstream Infections.

Background: Dalbavancin (DAL) is a long-acting lipoglycopeptide with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). This study investigates DAL as sequential therapy in S. aureus bloodstream infections (BSIs). Methods: We conducted a retrospective cohort study from 2014 to 2021 comparing sequential DAL with standard-of-care therapy (SoC) for S. aureus BSI. The primary outcome was 90-day clinical failure (90-day all-cause mortality or 90-day recurrence). Secondary outcomes were incidence of acute kidney injury, creatinine phosphokinase elevations, catheter-related thrombosis, and hospital-acquired infections. Analyses were adjusted using inverse probability of treatment weighting (IPTW). Results: Overall, 225 patients (45 DAL, 180 SoC) were included. DAL patients had a higher incidence of community-acquired infection and persons who use drugs; SoC patients had more comorbidities and a longer duration of bacteremia. MRSA incidence was similar between the DAL and SoC groups. The median length of stay was 16 days among DAL recipients compared with 24 days among SoC recipients. Central catheter placement was 17.8% compared with 57.2% in the SoC group. Ninety-day clinical failure occurred in 13.3% and 18.3% of participants in the DAL and SOC groups, respectively. In IPTW-adjusted analysis, sequential DAL was not associated with 90-day clinical failure (adjusted odds ratio, 0.94; 95% CI, 0.333-2.32). Conclusions: This study provides preliminary evidence that select patients with S. aureus BSI treated with sequential DAL have similar clinical failure rates, with significant reductions in catheter placement and hospital length of stay compared with SoC. Further prospective evaluation is needed.

Clinical Pharmacokinetics and Pharmacodynamics of Dalbavancin.

Dalbavancin is a synthetic lipoglycopeptide that exerts its antimicrobial activity through two distinct modes of action, inhibition of cell wall synthesis and an anchoring mechanism. Compared with previous glycopeptide antibiotics, dalbavancin demonstrates improved antibacterial potency against Gram-positive organisms and a long half-life of approximately 1 week, which is longer in tissues (e.g., skin, bone) than plasma. These factors facilitated the development of single-dose or once-weekly dosing regimens to treat acute bacterial skin and skin structure infections (ABSSSI). Dalbavancin exhibits dose-proportional pharmacokinetics and is highly protein bound (93%). Despite being highly protein bound, it has a steady-state volume of distribution >10 L and distributes widely into the skin, bone, peritoneal space, and epithelial lining fluid, but not cerebrospinal fluid. Dalbavancin elimination occurs via a combination of renal (approximately 45%) and non-renal clearance, with dose adjustments recommended only in patients with a creatinine clearance <30 mL/min not receiving any form of dialysis. The established pharmacokinetic/pharmacodynamic index associated with bacterial kill is free area under the concentration-time curve over the minimum inhibitory concentration (fAUC/MIC), with a goal 24-h fAUC/MIC of at least 27.1 for Staphylococcus aureus infections. Recent data suggest usefulness in the treatment of infections beyond ABSSSI, with convenient dosing and redosing strategies for complicated infections requiring extended treatment durations. Additional studies are needed to confirm these preliminary findings.