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.

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.

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.

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.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Eosinophilic Syndromes Associated With Daptomycin Use: Re-exposure Hypersensitivity Pneumonitis and Prior Peripheral Eosinophilia.

Background: Daptomycin pulmonary eosinophilia (DPE) has been well described in case reports and reporting from the Food and Drug Administration. We report 3 eosinophilic syndromes associated with daptomycin use. Methods: This is a retrospective review of all patients who received daptomycin (inpatient or outpatient) from 2010 to 2020 at the Veterans Affairs Portland Healthcare System. Patients who developed DPE while receiving daptomycin were evaluated to determine risk factors. Data collected included daptomycin dose and duration, body mass index, creatinine clearance, and peripheral eosinophilia. Results: Of 330 patients who received daptomycin, 81.5% developed a peripheral eosinophilia, with 109 (33%) developing peripheral eosinophilia ≥5%. Fifty-one (16%) met criteria for DPE. Primary DPE occurred in 38 of the 51 patients with a median 26 days of treatment, and 49% had peripheral eosinophilia ≥5%. Re-exposure DPE occurred in the other 13 patients and occurred a median of 3 days after initiation of daptomycin. The presence of an elevated peripheral eosinophilia of ≥5% during daptomycin usage was significantly associated with primary (odds ratio [OR], 2.23; 95% CI, 1.2-4.09; P = .008) and re-exposure DPE (OR, 12; 95% CI, 1.6-103; P = .003). All patients recovered after withdrawal of daptomycin without complications. Conclusions: There are 3 daptomycin eosinophilic syndromes: peripheral eosinophilia, primary DPE occurring about 4 weeks into therapy, and re-exposure DPE. Elevated peripheral eosinophilia ≥5% was a risk factor for both primary and re-exposure DPE, but still identified about half the cases. Peripheral eosinophilia should be carefully monitored during daptomycin treatment, and clinicians should be aware that prior eosinophilia may predict an acute pulmonary reaction upon daptomycin re-exposure.

Strategies for the implementation of a nasal decolonization intervention to prevent surgical site infections within the Veterans Health Administration.

As part of a multicenter evidence-based intervention for surgical site infection prevention, a qualitative study was conducted with infection control teams and surgical staff members at three Department of Veterans Affairs Healthcare Systems in the USA. This study aimed to identify strategies used by nurses and other facility champions for the implementation of a nasal decolonization intervention. Site visit observations and field notes provided contextual information. Interview data were analyzed with inductive and deductive content analysis. Interview data was mapped to the Expert Recommendations for Implementing Change (ERIC) compilation of implementation strategies. These strategies were then considered in the context of power and relationships as factors that influence implementation. We found that implementation of this evidence-based surgical site infection prevention intervention was successful when nurse champions drove the day-to-day implementation. Nurse champions sustained implementation strategies through all phases of implementation. Findings also suggest that nurse champions leveraged the influence of their role as champion along with their understanding of social networks and relationships to help achieve implementation success. Nurse champions consciously used multiple overlapping and iterative implementation strategies, adapting and tailoring strategies to stakeholders and settings. Commonly used implementation categories included: "train and educate stakeholders," "use evaluative and iterative strategies," "adapt and tailor to context," and "develop stakeholder interrelationships." Future research should examine the social networks for evidence-based interventions by asking specifically about relationships and power dynamics within healthcare organizations. Implementation of evidence-based interventions should consider if the tasks expected of a nurse champion fit the level of influence or power held by the champion. Trial registration: ClinicalTrials.gov, identifier: NCT02216227.

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.

Effect of Frequency of Changing Point-of-Use Reminder Signs on Health Care Worker Hand Hygiene Adherence: A Cluster Randomized Clinical Trial.

Importance: Although hand hygiene (HH) is considered the most effective strategy for preventing hospital-acquired infections, HH adherence rates remain poor. Objective: To examine whether the frequency of changing reminder signs affects HH adherence among health care workers. Design, Setting, and Participants: This cluster randomized clinical trial in 9 US Department of Veterans Affairs acute care hospitals randomly assigned 58 inpatient units to 1 of 3 schedules for changing signs designed to promote HH adherence among health care workers: (1) no change; (2) weekly; and (3) monthly. Hand hygiene rates among health care workers were documented at entry and exit to patient rooms during the baseline period from October 1, 2014, to March 31, 2015, of normal signage and throughout the intervention period of June 8, 2015, to December 28, 2015. Data analyses were conducted in April 2018. Interventions: Hospital units were randomly assigned into 3 groups: (1) no sign changes throughout the intervention period, (2) signs changed weekly, and (3) signs changed monthly. Main Outcomes and Measures: Hand hygiene adherence as measured by covert observation. Interrupted time series analysis was used to examine changes in HH adherence from baseline through the intervention period by group. Results: Among 58 inpatient units, 19 units were assigned to the no change group, 19 units were assigned to the weekly change group, and 20 units were assigned to the monthly change group. During the baseline period, 9755 HH opportunities were observed at room entry and 10 095 HH opportunities were observed at room exit. During the intervention period, a total of 15 855 HH opportunities were observed at room entry, and 16 360 HH opportunities were observed at room exit. Overall HH adherence did not change from baseline compared with the intervention period at either room entry (4770 HH events [48.9%] vs 3057 HH events [50.1%]; P = .14) or exit (6439 HH events [63.8%] vs 4087 HH events [65.2%]; P = .06). In units that changed signs weekly, HH adherence declined from baseline at room entry (-1.9% [95% CI, -2.7% to -0.8%] per week; P < .001) and exit (-0.8% [95% CI, -1.5% to 0.1%] per week; P = .02). No significant changes in HH adherence were observed in other groups. Conclusions and Relevance: The frequency of changing reminder signs had no effect on HH rates overall. Units assigned to change signs most frequently demonstrated worsening adherence. Considering the abundance of signs in the acute care environment, the frequency of changing signs did not appear to provide a strong enough cue by itself to promote behavioral change. Trial Registration: ClinicalTrials.gov Identifier: NCT02223455.

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.

Improving fluoroquinolone use in the outpatient setting using a patient safety initiative.

We analyzed the impact of a fluoroquinolone patient safety initiative on the weekly fluoroquinolone prescription rate in Veterans Affairs community-based outpatient clinics. We observed a significant initial but unsustained reduction. Such an initiative can function as an antimicrobial stewardship intervention; however, strategies to promote sustainability should be explored.