Breakthrough SARS-CoV-2 infections among recipients of tixagevimab-cilgavimab prophylaxis: A citywide real-world effectiveness study.

There are limited real-world data on the effectiveness of tixagevimab-cilgavimab as pre-exposure prophylaxis of COVID-19. We describe lessons learned when coordinating data collection and identifying breakthrough SARS-CoV-2 infections among patients across indications and institutions in a major US city. The Chicago Department of Public Health requested patient-level tixagevimab-cilgavimab administration data from all prescribing providers in Chicago, for treatments December 8, 2021 through June 30, 2022. Records were matched to COVID-19 vaccinations and laboratory-confirmed SARS-CoV-2 infections through December 31, 2022. Due to difficulty collecting data from all providers, targeted follow-up was conducted to improve completeness on key variables (demographics, vaccination status, clinical indication for prophylaxis). Over half of reported tixagevimab-cilgavimab administrations were to patients residing outside Chicago. Five hundred forty-four Chicago residents who received at least one dose of tixagevimab-cilgavimab were included in this analysis. Most were age 50 years or older (72%), Black non-Latinx (33%) or White non-Latinx (29%), and fully vaccinated (80%). Seventy-five patients (14%) had laboratory-confirmed COVID-19. Patients with and without breakthrough infections were demographically similar. Clinical indication was missing for >95% of cases, improved to 64% after follow-up; the most frequently specified was hematologic malignancy (10%). Severe outcomes were uncommon: 16% had documented COVID-19-related hospitalizations, one death was identified. Tixagevimab-cilgavimab recipients in Chicago had a lower rate of severe SARS-CoV-2 infection than reported among other untreated high-risk patients, including during predominance of non-neutralizing variants. Improving stakeholder collaboration is essential for generation of real-world effectiveness data, informing pandemic preparedness and optimizing use of medical countermeasures.

Using antibiotics wisely.

PURPOSE OF REVIEW: This review will describe role of shorter antibiotic therapies, early switch from intravenous to oral therapy, and artificial intelligence in infectious diseases. RECENT FINDINGS: There is evidence that shorter courses of antibiotics are noninferior to standard durations of therapy. This has been demonstrated with Enterobacterales bacteremia that can be treated with 7 days of therapy, community acquired pneumonia with 3 days and ventilator associated pneumonia with just 7 days of antibiotic therapy. The conversion from intravenous to oral therapy in treating bacteremia, endocarditis and bone and joint infections is safe and effective and reduces line complications and costs. Also, for clean surgical procedures only one dose of antibiotic is needed, but it should be the most effective antibiotic which is cefazolin. This means avoiding clindamycin, removing penicillin allergies where possible for improved outcomes. Finally, the role of artificial intelligence to incorporate into using antibiotics wisely is rapidly emerging but is still in early stages. SUMMARY: In using antibiotics wisely, targeting such as durations of therapy and conversion from intravenous antibiotic therapy to oral are low hanging fruit. The future of artificial intelligence could automate a lot of this work and is exciting but needs to be proven. VIDEO ABSTRACT: http://links.lww.com/COID/A50.

Scedosporium infection disseminated "from toe to head" in allogeneic stem cell transplant recipient: a case report.

BACKGROUND: Scedosporium is a lesser-known non-Aspergillus genus of mold that can present in unsuspecting ways. If overlooked, it may disseminate and cause high mortality in high-risk allogeneic stem cell transplant recipients. CASE PRESENTATION: This case report describes a 65-year-old patient with Acute Myeloid Leukemia who underwent an allogeneic hematopoietic stem cell transplant after a period of prolonged neutropenia with fluconazole prophylaxis. She suffered severe debility with altered mentation from a S. apiospermum infection which likely disseminated from a toe wound to the lung and central nervous system. She was successfully treated with liposomal amphotericin B and voriconazole, but faced a prolonged recovery from physical and neurologic sequela. CONCLUSIONS: The case highlights the importance of adequate anti-mold prophylaxis in high-risk patients, and the value of a thorough physical examination in this patient population, with particular attention to skin and soft tissue findings.

White paper on antimicrobial stewardship in solid organ transplant recipients.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fits-all" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Non-toxigenic Vibrio cholerae in an autologous stem cell and renal transplant recipient.

A patient with a renal transplant after an autologous stem cell transplant for multiple myeloma developed non-toxigenic Vibrio cholerae diarrhea after travel to Mexico. This is a rare cause of diarrhea in transplant recipients, and the patient had not had pre-travel counseling. This case reflects the lack of referral of transplant recipients for travel infectious disease review before overseas travel and the role of the live attenuated cholera vaccine.

Cryptococcosis in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of cryptococcosis in the pre- and post-transplant period. The current update now includes a discussion of cryptococcosis, which is the third most common invasive fungal infection in SOT recipients. Infection often occurs a year after transplantation; however, early infections occur and donor-derived infections have been described within 3 months after transplant. There are two main species that cause infection, Cryptococcus neoformans and C gattii. Clinical onset may be insidious, but headaches, fevers, and mental status changes should warrant diagnostic testing. The lateral flow cryptococcal antigen assay is now the preferred test from serum and cerebrospinal fluid due to its rapidity, accuracy, and cost. A lumbar puncture with measurement of opening pressure is recommended for patients with suspected or proven cryptococcosis. Lipid amphotericin B plus 5-flucytosine is used as initial treatment of meningitis, disseminated infection, and moderate-to-severe pulmonary infection, followed by fluconazole as consolidation therapy. Fluconazole is effective for mild-to-moderate pulmonary infection. Immunosuppression reduction as part of management may lead to immune reconstitution syndrome that may resemble active disease.

Clinical Outcomes of Oral Suspension versus Delayed-Release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections.

Posaconazole is used for prophylaxis for invasive fungal infections (IFIs) among patients with hematologic malignancies. We compared the incidence of breakthrough IFIs and early discontinuation between patients receiving delayed-release tablet and oral suspension formulations of posaconazole. This was a retrospective cohort study of patients receiving posaconazole between 1 January 2010 and 30 June 2016. We defined probable or proven breakthrough IFIs using the European Organization for Research and Treatment of Cancer (EORTC) criteria. Overall, 547 patients received 860 courses of posaconazole (53% received the oral suspension and 48% received the tablet); primary indications for prophylaxis were acute myeloid leukemia (69%), graft-versus-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indications between patients receiving the different formulations. The incidence and incidence rate of probable or proven IFIs were 1.6% and 3.2 per 10,000 posaconazole days, respectively. There was no significant difference in the rate of IFIs between suspension courses (2.8 per 10,000 posaconazole days) and tablet courses (3.7 per 10,000 posaconazole days) (rate ratio = 0.8, 95% confidence interval [CI] = 0.3 to 2.3). Of the 14 proven or probable cases of IFI, 8/14 had posaconazole serum concentrations measured, and the concentrations in 7/8 were above 0.7 µg/ml. Posaconazole was discontinued early in 15.5% of courses; however, the frequency of discontinuation was also not significantly different between the tablet (16.5%) and oral suspension (14.6%) formulations (95% CI for difference = -0.13 to 0.06). In conclusion, the incidence of breakthrough IFIs was low among patients receiving posaconazole prophylaxis and not significantly different between patients receiving the tablet formulation and those receiving the oral suspension formulation.

Disseminated, persistent, and fatal infection due to the vaccine strain of varicella-zoster virus in an adult following stem cell transplantation.

Live attenuated varicella vaccine is recommended for healthy individuals who are susceptible to varicella. Although the vaccine is safe, effective, and used worldwide, serious adverse events have been reported, mainly in immunocompromised patients who subsequently recovered. Here, we describe the fatality of an immunocompromised patient who received the varicella vaccine. His medical history provides a cautionary lens through which to view the decision of when vaccination is appropriate. A middle-aged man with non-Hodgkin lymphoma received chemotherapy and a stem cell transplant. He was vaccinated 4 years post-transplantation, despite diagnosis of a new low-grade lymphoma confined to the lymph nodes. Within 3 months of vaccination, he developed recurrent rashes with fever, malaise, weakness, hepatitis, weight loss, and renal failure. The syndrome was eventually determined to be associated with persistent disseminated zoster caused by the vaccine virus. This case illustrates a circumstance when a live viral vaccine should not be used.

Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: implications for the management of immunosuppression.

BACKGROUND: Risk factors including how changes in immunosuppression influence the occurrence of immune reconstitution syndrome (IRS) in solid organ transplant (SOT) recipients with cryptococcosis have not been fully defined. METHODS: SOT recipients with cryptococcosis were identified and followed for 12 months. IRS was defined based on previously proposed criteria. RESULTS: Of 89 SOT recipients, 13 (14%) developed IRS. Central nervous system (CNS) disease (adjusted odds ratio [AOR], 6.23; P = .03) and discontinuation of calcineurin inhibitor (AOR, 5.11; P = .02) were independently associated with IRS. Only 2.6% (1/13) of the patients without these risk factors developed IRS compared with 18.8% (6/32) with 1 risk factor, and 50% (6/12) with both risk factors (χ(2) for trend, P = .0001). Among patients with CNS disease, those with neuroimaging abnormalities (P = .03) were more likely to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia. Graft rejection after cryptococcosis was observed in 15.4% (2/13) of the patients with IRS compared with 2.6% (2/76) of those without IRS (P = .07). CONCLUSIONS: We determined variables that pose a risk for IRS and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis.

Review of rapid diagnostic tests used by antimicrobial stewardship programs.

Rapid microbiologic tests provide opportunities for antimicrobial stewardship programs to improve antimicrobial use and clinical and economic outcomes. Standard techniques for identification of organisms require at least 48-72 hours for final results, compared with rapid diagnostic tests that provide final organism identification within hours of growth. Importantly, rapid microbiologic tests are considered "game changers" and represent a significant advancement in the management of infectious diseases. This review focuses on currently available rapid diagnostic tests and, importantly, the impact of rapid testing in combination with antimicrobial stewardship on patient outcomes.

Use of electronic health records and clinical decision support systems for antimicrobial stewardship.

Electronic health records (EHRs) and clinical decision support systems (CDSSs) have the potential to enhance antimicrobial stewardship. Numerous EHRs and CDSSs are available and have the potential to enable all clinicians and antimicrobial stewardship programs (ASPs) to more efficiently review pharmacy, microbiology, and clinical data. Literature evaluating the impact of EHRs and CDSSs on patient outcomes is lacking, although EHRs with integrated CDSSs have demonstrated improvements in clinical and economic outcomes. Both technologies can be used to enhance existing ASPs and their implementation of core ASP strategies. Resolution of administrative, legal, and technical issues will enhance the acceptance and impact of these systems. EHR systems will increase in value when manufacturers include integrated ASP tools and CDSSs that do not require extensive commitment of information technology resources. Further research is needed to determine the true impact of current systems on ASP and the ultimate goal of improved patient outcomes through optimized antimicrobial use.

Clinical outcomes of a veterans affairs outpatient antimicrobial treatment program.

OBJECTIVES: The outpatient parenteral antibiotic therapy (OPAT) program of the Portland Veterans Affairs Medical Center (PVAMC), which has a self-administration model, is staffed by visiting nurses from a specialist infusion company. This study evaluates the clinical outcomes of these patients. METHODS: This study was a retrospective chart review of 262 patients at PVAMC who had received OPAT between 2007 and 2009. Patients were included only if they received ongoing care at PVAMC. The data collected included conditions and organisms being treated and types and durations of antibiotics used. Clinical cure was defined as documented cure at the end of treatment and 90 days post-OPAT. RESULTS: One hundred ninety patients of 262 were analyzed. The mean age was 63.2 years. Diabetes was the main comorbid factor (17%). The most common indications for OPAT were osteomyelitis (38%), urinary tract infection (23%), and skin and soft tissue infection (12.6%). Mixed bacterial culture (26%) and Staphylococcus aureus (31%) were the most common organisms treated. Vancomycin was the most frequently used antibiotic (26%) followed by ceftriaxone (12%). The median duration of OPAT was 30 days. The rate of clinical cure at end of treatment observed for all infections treated was 78%, which then decreased to 58% at 90 days post-OPAT (P < 0.001). Patients with diabetes and osteomyelitis had an increased risk of relapse at 90 days post-OPAT on multivariate analysis (P = 0.025). CONCLUSIONS: An OPAT program using a self-administration model treating patients who were military veterans had successful outcomes. Patients with diabetes and osteomyelitis had worse clinical outcomes 90 days after the completion of OPAT therapy.

Shorter antibiotic courses in the immunocompromised: the impossible dream?

BACKGROUND: A growing number of studies have demonstrated similar outcomes with shorter courses of antibiotics for bacterial infections. Immunocompromised patients are frequently excluded from these studies despite anticipated benefits associated with shortening antibiotic courses (including lower risks of antibiotic toxicity, Clostridioides difficile infection, drug-resistant pathogens, and microbiome alterations). OBJECTIVES: To critically review the literature that assesses shorter antibiotic courses in immunocompromised patients, specifically among solid organ transplant recipients and neutropenic fever (NF) syndromes among patients on antineoplastic chemotherapy and undergoing haematopoietic cell transplant. SOURCES: References were identified through searches of PubMed, Embase, MEDLINE, and clinical guidelines documents. CONTENT: Among organ transplant recipients, the majority of studies assessing outcomes associated with shorter antibiotic courses have been retrospective but have demonstrated similar rates of clinically relevant endpoints. Patients with high- and low-risk NF have been well-studied, including enrolment in randomized studies, albeit with heterogeneous patient populations and outcomes assessed. Clinical improvement-guided adoption of shorter courses has been associated with fewer antibiotic days and similar rates of fever recurrence and mortality. IMPLICATIONS: Similar to studies demonstrating efficacy in immunocompetent patients, shorter antibiotic courses should be considered for immunocompromised hosts with presumed bacterial infections. Organ recipients and patients with NF syndromes should be prioritized for study in randomized controlled clinical trials assessing shorter course therapy.

Implementation of a Prevention Bundle to Decrease Rates of Staphylococcus aureus Surgical Site Infection at 11 Veterans Affairs Hospitals.

Importance: While current evidence has demonstrated a surgical site infection (SSI) prevention bundle consisting of preoperative Staphylococcus aureus screening, nasal and skin decolonization, and use of appropriate perioperative antibiotic based on screening results can decrease rates of SSI caused by S aureus, it is well known that interventions may need to be modified to address facility-level factors. Objective: To assess the association between implementation of an SSI prevention bundle allowing for facility discretion regarding specific component interventions and S aureus deep incisional or organ space SSI rates. Design, Setting, and Participants: This quality improvement study was conducted among all patients who underwent coronary artery bypass grafting, cardiac valve replacement, or total joint arthroplasty (TJA) at 11 Veterans Administration hospitals. Implementation of the bundle was on a rolling basis with the earliest implementation occurring in April 2012 and the latest implementation occurring in July 2017. Data were collected from January 2007 to March 2018 and analyzed from October 2020 to June 2023. Interventions: Nasal screening for S aureus; nasal decolonization of S aureus carriers; chlorhexidine bathing; and appropriate perioperative antibiotic prophylaxis according to S aureus carrier status. Facility discretion regarding how to implement the bundle components was allowed. Main Outcomes and Measures: The primary outcome was deep incisional or organ space SSI caused by S aureus. Multivariable logistic regression with generalized estimating equation (GEE) and interrupted time-series (ITS) models were used to compare SSI rates between preintervention and postintervention periods. Results: Among 6696 cardiac surgical procedures and 16 309 TJAs, 95 S aureus deep incisional or organ space SSIs were detected (25 after cardiac operations and 70 after TJAs). While the GEE model suggested a significant association between the intervention and decreased SSI rates after TJAs (adjusted odds ratio, 0.55; 95% CI, 0.31-0.98), there was not a significant association when an ITS model was used (adjusted incidence rate ratio, 0.88; 95% CI, 0.32-2.39). No significant associations after cardiac operations were found. Conclusions and Relevance: Although this quality improvement study suggests an association between implementation of an SSI prevention bundle and decreased S aureus deep incisional or organ space SSI rates after TJAs, it was underpowered to see a significant difference when accounting for changes over time.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Genotypic resistance testing creates new treatment challenges: two cases of oxacillin-susceptible methicillin-resistant Staphylococcus aureus.

Oxacillin-susceptible, mecA-positive Staphylococcus aureus isolates create a treatment challenge for the clinician. In this article, we describe two cases of bacteremia from isolates that carried the mecA gene but were susceptible to oxacillin (oxacillin-susceptible methicillin-resistant S. aureus [OS-MRSA]). DNA microarray analysis was used to characterize these isolates as a mecA-positive, clonal complex 5, pediatric strain and a mecA-positive, clonal complex 8, USA300 strain.

Rifampin combination therapy for nonmycobacterial infections.

The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.