A Multicenter Retrospective Study Evaluating Intravenous to Oral Antibiotic Stepdown for Uncomplicated Streptococcal Bacteremia.

Background: The purpose of this study was to compare the efficacy and safety of intravenous (IV) versus oral (PO) stepdown therapy for uncomplicated streptococcal bacteremia. Methods: This multicenter, retrospective study included adult patients with uncomplicated streptococcal bacteremia between 1 July 2019 and 1 July 2022. Patients who received IV therapy for the full treatment course were compared to patients who transitioned to PO therapy after initial IV therapy. The primary outcome was clinical success, defined as absence of infection recurrence, infection-related readmission, and infection-related mortality at 90 days. Secondary outcomes included microbiological success, length of stay (LOS), and IV line-associated complications. Results: Of 238 patients included, 47.1% received PO stepdown therapy. Clinical success occurred in 94.4% and 94.6% in the IV only and PO stepdown groups, respectively (P = .946). Patients who transitioned to PO therapy received a median duration of IV therapy of 3.9 days (interquartile range, 2.9-7.3 days). Line complications were more frequent in the IV only group, primarily driven by catheter-related infections (7.2% vs 0%, P = .002). LOS was significantly shorter in the PO stepdown group (5.5 vs 9.2 days, P < .001). Conclusions: Patients transitioned to PO antibiotics for uncomplicated streptococcal bacteremia had similar rates of clinical success compared to patients who received only IV therapy. With consideration of infectious source, severity of illness, and comorbidities, PO stepdown following initial IV antibiotics for uncomplicated streptococcal bacteremia in select patients is a reasonable approach that may result in decreased LOS and line-related complications.

An Unexpectedly High Incidence of Invasive Fungal Diseases in Solid Organ Transplant Recipients Taking Belatacept for Organ Rejection Prophylaxis: A Single-Center Retrospective Cohort Study.

Among solid organ transplant recipients taking belatacept, 15% developed invasive fungal diseases. The most common invasive fungal diseases were aspergillosis (56%) and candidiasis (22%). The infected cohort was more likely to receive basiliximab, undergo lung transplantation, or identify as White. Higher rates of aspergillosis were seen in this lung cohort than previously reported.

Microbiology of infection-related complications after transrectal ultrasound-guided prostate biopsy.

INTRODUCTION: The objective of this study was to describe the incidence, microbiology, and risk factors related to infectious complications after transrectal prostate biopsies. METHODS: This was a single-center, retrospective cohort study of patients undergoing prostate biopsies. Throughout the study period, the institutional standard for antibiotic prophylaxis was cephalexin and ciprofloxacin. Due to the desire to limit fluoroquinolone use, the ciprofloxacin duration of therapy was reduced from 48 to 24 hours in the middle of the study period. The primary outcome was the incidence of infection-related complications, defined as a urinary tract infection or bacteremia within 30 days post-procedure. RESULTS: A total of 1471 transrectal prostate biopsies were included. All patients received antibiotic prophylaxis, with 86.1% (1268/1472) of patients receiving both ciprofloxacin and cephalexin. The incidence of infection-related complications was 1.6% (24/1471). Four patients experienced bacteremia, all of which were due to E. coli and all of these patients had received antibiotic prophylaxis with an active antibiotic. The use of ciprofloxacin was associated with a lower risk of infection-related complications (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07, 0.55). Bacteriuria within one year prior to the procedure was associated with increased risk of infection-related complications (OR 4.77, 95% CI 1.34, 16.93). Four (0.3%) patients experienced an antibiotic-related adverse event. CONCLUSIONS: We observed a low rate of infection-related complications and antibiotic-related adverse events in the setting of antibiotic prophylaxis with ciprofloxacin and cephalexin for 24 hours, without pre-procedure rectal culture screening. Investigation into procedural or host factors may uncover opportunities to further reduce infection-related complications.

When is vancomycin prophylaxis necessary? Risk factors for MRSA surgical site infection.

Background: The 2022 SHEA/IDSA/APIC guidance for surgical site infection (SSI) prevention recommends reserving vancomycin prophylaxis to patients who are methicillin-resistant Staphylococcus aureus (MRSA) colonized. Unfortunately, vancomycin prophylaxis remains common due to the overestimation of MRSA risk and the desire to cover MRSA in patients with certain healthcare-associated characteristics. To optimize vancomycin prophylaxis, we sought to identify risk factors for MRSA SSI. Methods: This was a single-center, case-control study of patients with a postoperative SSI after undergoing a National Healthcare Safety Network operative procedure over eight years. MRSA SSI cases were compared to non-MRSA SSI controls. Forty-two demographic, medical, and surgical characteristics were evaluated. Results: Of the 441 patients included, 23 developed MRSA SSIs (rate = 5.2 per 100 SSIs). In the multivariable model, we identified two independent risk factors for MRSA SSI: a history of MRSA colonization or infection (OR, 9.0 [95% CI, 1.9-29.6]) and hip or knee replacement surgery (OR, 3.8 [95% CI, 1.3-9.9]). Hemodialysis, previous hospitalization, and prolonged hospitalization prior to the procedure had no measurable association with odds of MRSA SSI. Conclusions: Patients with prior MRSA colonization or infection had 9-10 times greater odds of MRSA SSI and patients undergoing hip and knee replacement had 3-4 times greater odds of MRSA SSI. Healthcare-associated characteristics, such as previous hospitalization or hemodialysis, were not associated with MRSA SSI. Our findings support national recommendations to reserve vancomycin prophylaxis for patients who are MRSA colonized, as well as those undergoing hip and knee replacement, in the absence of routine MRSA colonization surveillance.

Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020.

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

Impact of the sequential implementation of a pharmacy-driven methicillin-resistant Staphylococcus aureus (MRSA) nasal-swab ordering policy and vancomycin 72-hour restriction protocol on standardized antibiotic administration ratio (SAAR) data for antibiotics used for resistant gram-positive infections.

OBJECTIVE: Vancomycin is often initiated in hospitalized patients; however, it may be unnecessary or continued for longer durations than needed. Oversight of all vancomycin orders may not be feasible with widespread prescribing and strategies to enlist other clinicians to serve as stewards of vancomycin use are needed. We implemented 2 sequential interventions: a protocol in which the pharmacist orders MRSA nasal swab followed by a protocol requiring approval from pharmacists to continue vancomycin for >72 hours. METHODS: In this single-center, retrospective, quasi-experimental study, we evaluated vancomycin use after implementation of a pharmacy-driven MRSA nasal-swab ordering protocol and a vancomycin 72-hour restriction protocol. The primary outcome was the change in the standardized antibiotic administration ratio (SAAR) for antibacterial agents for resistant gram-positive infections. We also evaluated the impact on antibiotic utilization. RESULTS: Following the MRSA swab protocol, the SAAR decreased from 1.26 to 1.13 (P < .001; 95% confidence interval [CI], 1.16-1.25). After the 72-hour approval process, the SAAR was 0.96 (P < .001; 95% CI, 1.0-1.12). Vancomycin utilization decreased from 138.9 to 125.3 days of therapy per 1,000 patient days following the MRSA swab protocol (P < .001) and to 112.7 (P < .001) following the 72-hour approval protocol. Interrupted time-series analysis identified a similar rate of decline in utilization following the 2 interventions (-0.3 and -0.5; P = .16). Both interventions combined resulted in a significant reduction (-1.5; P < .001). CONCLUSION: Implementation of a pharmacist-driven MRSA nasal-swab ordering protocol, followed by a 72-hour approval protocol, was associated with a significant reduction in the SAAR for antibiotics used in the treatment of resistant gram-positive infections and a reduction in vancomycin utilization. Leveraging the oversight of primary service clinical pharmacists through these protocols proved to be an effective strategy.

Infectious complications of car T-cell therapy: A longitudinal risk model.

BACKGROUND: CAR T-cell therapy, where a patient's own T cells are re-engineered to express a receptor to a target of interest, is becoming an increasingly utilized cancer-directed therapy. There are significant toxicities that contribute to a novel state of immunocompromise, leading to new patterns of infectious complications that require further detailed study. METHODS: We created a single-center cohort of adult recipients of CD19-directed CAR T-cell therapy and assessed infectious outcomes, supportive care received, toxicities, and markers of immune function up to 2 years following CAR T-cell therapy. Descriptive statistics were used as appropriate for analysis. We additionally conducted time-to-event analysis assessing time-to-first infection with either log-rank testing or Cox regression with univariate analysis, before including significant predictors into a multivariate Cox model of time to infection. RESULTS: We identified 73 patients who received CD19-directed CAR T-cell therapy who predominantly had diffuse large B-cell lymphoma. Within 30 days of cell infusion, bacterial and Candida infections were the most common, with 64% of infections due to these organisms. Between 30 days and 2 years postinfusion, respiratory viruses and pneumonia were the most frequent infections, with 68% of infections due to these etiologies. Receipt of tocilizumab, development of immune effector cell-associated neurotoxicity syndrome (ICANS), or lower neutrophil count were associated with quicker onset of infection in a multivariate Cox model. CONCLUSIONS: Respiratory viruses remain an important infectious complication of CAR T-cell therapy following the first year. The model may be a useful tool to identify patients at the highest risk of infection.

Current and Emerging Therapies for COVID-19 in Lung Transplantation.

Purpose of Review: The landscape of the coronavirus disease 2019 (COVID-19) pandemic has rapidly changed over the past 3 years. Paralleling this evolution, the scientific and medical communities have reported many novel findings relating to the infection's epidemiology, transmission, diagnosis, and treatment. We review pertinent studies of COVID-19 therapeutics with an emphasis on their application to lung transplant recipients. Recent Findings: Agents that have been well-studied for treating COVID-19 include antivirals (remdesivir, nirmatrelvir/ritonavir, molnupiravir), monoclonal antibodies, and immunomodulators (for example, corticosteroids and tocilizumab). Summary: Remdesivir remains an essential therapy for managing mild-moderate COVID-19. Though highly efficacious for mild-moderate COVID-19 for outpatient therapy, ritonavir-boosted nirmatrelvir has limited use in lung transplant recipients due to significant drug-drug interactions. Monoclonal antibodies, though useful, are the most affected by the emergence of new viral variants.

Chronic aseptic meningitis caused by enterovirus in a humorally immunosuppressed adult patient presenting with sensorineural hearing loss: a case report.

BACKGROUND: Enterovirus has been described as a cause of aseptic meningitis in humorally immunosuppressed patients. CASE PRESENTATION: A 67-year-old female with a history of mantle cell lymphoma on rituximab therapy presented with subacute hepatitis, myalgias, and sensorineural hearing loss several months after an initial febrile illness. She was diagnosed with enterovirus infection by CSF PCR as a unifying etiology of her presentation, representing an unusual presentation of disease. DISCUSSION AND CONCLUSIONS: This patient's unique presentation and clinical course presents important implications in the care of similarly immunosuppressed patients with cryptic complaints.

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.

Febrile Neutropenia Syndromes in Children: Risk Factors and Outcomes of Primary, Prolonged, and Recurrent Fever.

BACKGROUND: The approach to recurrent febrile neutropenia (FN) in children with cancer has not been sufficiently addressed and was cited as a research gap in the International Pediatric Fever and Neutropenia (IPFNP) Guideline 2017. METHODS: Retrospective medical record review for all pediatric cancer patients with a diagnosis of FN was performed. Variables were collected at 2 different time sets (at day 1 and day 4 of presentation). Three FN syndromes have been defined based on the duration and time course of the fever: (1) primary: fever resolved before 96 hours and did not follow with recurrent fever; (2) prolonged fever: episodes failing to defervesce after at least 96 hours of antibacterial therapy; (3) recurrent fever: a new episode of fever >72 hours after resolution of the initial fever when a patient remained neutropenic and on antibiotics or if a fever developed within 1 week after antibiotic discontinuation. These entities were compared with define risk factors and adverse outcomes associated with recurrent fever. RESULTS: A total of 633 FN episodes (FNEs) were identified in 268 patients. Each FNE was classified as primary (n=453, 71.5%), prolonged (n=119, 18.7%), or recurrent (n=61, 9.7%). In multivariable analysis, acute myelogenous leukemia (odds ratio [OR]=4.6, 95% confidence interval [CI]: 2.95-7.24), allogeneic stem cell transplant (SCT) (OR=4.9, 95% CI: 2.61-7.35), absolute lymphocyte count <300/mm3 (OR=3.8, 95% CI: 1.30-5.02), prior neutropenia of ≥10 days, (OR=3.95, 95% CI: 1.70-5.93) and hypotension (OR=3.65, 95% CI: 1.30-5.86) on day 1 of presentation were all associated with an increased risk of recurrent fever when compared with primary fever. In subset analysis for only the high-risk FN group, hypotension (OR=3.2, 95% CI: 1.80-4.96), prior neutropenia ≥10 days (OR=2.55, 95% CI: 1.40-6.22), and absolute lymphocyte count <300/mm3 at presentation (OR=2.6, P=0.03, 95% CI: 2.65-7.12) were associated with an increased risk of recurrent fever when compared with high-risk FN not developing recurrent fever. Allogeneic SCT (OR=5.9, 95% CI: 2.65-7.12) and prior neutropenia ≥10 days (OR=2.11, 95% CI: 1.25-9.32) were significantly associated with recurrent fever when compared with prolonged fever. Invasive fungal disease was a more common etiology with recurrent fever compared with primary and prolonged fever (P=0.001 and 0.01, respectively). Recurrent fever episodes were more likely to be admitted to the pediatric intensive care unit (OR=3, 95% CI: 1.27-6.23) and had a higher 30-day mortality (OR=8, 95% CI: 1.87-71.85) when compared with primary fever. CONCLUSIONS: Knowledge of risk factors for recurrent fever may enable the early detection infection-related complications of this high-risk group, and possible improved approaches to treatment resulting in decreased morbidity and mortality.

Impact of a structured interview on beta-lactam reaction documentation quality.

Incomplete documentation of ß-lactam reactions often leads to inappropriate antibiotic prescribing. The objective of this study was to evaluate the impact of a structured interview on the quality of ß-lactam reaction documentation. After 203 interviews, documentation of the core components of a ß-lactam reaction improved (48% vs 1%; P < .001).

Remdesivir Use in the Setting of Severe Renal Impairment: A Theoretical Concern or Real Risk?

BACKGROUND: Remdesivir (RDV) is US FDA approved for coronavirus disease 2019 (COVID-19) but not recommended in severe renal impairment (SRI, Creatinine clearance <30mL/min or requiring renal replacement therapy). Few studies have evaluated RDV in patients with SRI. METHODS: Hospitalized patients who received RDV between 1 May 2020 and 31 October 2020 were analyzed in a retrospective chart review. We compared incident adverse events (AEs) in patients with and without SRI, including hepatotoxicity, nephrotoxicity, any reported AE, mortality, and length of stay. RESULTS: Of a total of 135 patients, 20 had SRI. Patients with SRI were significantly older (70 vs 54 years, P = .0001). The incidence of possible AEs was 30% among those with SRI vs 11% without (P = .06). Liver function test (LFT) elevations occurred in 10% vs 4% (P = .28), and serum creatinine (SCr) elevations in 27% vs 6% (P = .02) of patients with SRI vs without, respectively. LFT and SCr elevations were not attributed to RDV in either group. Mortality and length of stay were consistent with historical controls. CONCLUSIONS: RDV AEs occurred infrequently and overall were not significantly different between those with and without SRI. While more of patients with SRI experienced SCr elevations, 3 (75%) patients had acute kidney injury prior to RDV. The use of RDV in this small series of patients with SRI appeared to be relatively safe, and the potential benefit outweighed the theoretical risk of liver or renal toxicity. Additional studies are needed to confirm this finding.

COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia.

Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the mortality of coronavirus disease 2019 (COVID-19). The IL-6 receptor-blocking monoclonal antibody tocilizumab has been repurposed for COVID-19, but prospective trials and dose-finding studies in COVID-19 have not yet fully reported. We conducted a single-arm phase II trial of low-dose tocilizumab in nonintubated hospitalized adult patients with COVID-19, radiographic pulmonary infiltrate, fever, and C-reactive protein (CRP) ≥ 40 mg/L. We hypothesized that doses significantly lower than the emerging standards of 400 mg or 8 mg/kg would resolve clinical and laboratory indicators of hyperinflammation. A dose range from 40 to 200 mg was evaluated, with allowance for one repeat dose at 24 to 48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Thirty-two patients received low-dose tocilizumab, with the majority experiencing fever resolution (75%) and CRP decline consistent with IL-6 pathway abrogation (86%) in the 24-48 hours following drug administration. There was no evidence of a relationship between dose and fever resolution or CRP decline over the dose range of 40-200 mg. Within the 28-day follow-up, 5 (16%) patients died. For patients who recovered, median time to clinical recovery was 3 days (interquartile range, 2-5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (16%) patients. Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with COVID-19. Results of this trial provide rationale for a randomized, controlled trial of low-dose tocilizumab in COVID-19.

Investigating the impact of a ß-lactam allergy label on preoperative antibiotic prophylaxis administration.

OBJECTIVE: Surgical site infection (SSI) is a common postprocedure complication that may be prevented by adhering to established recommendations, including administration of preoperative antibiotic prophylaxis. Patients with a ß-lactam allergy (BLA) label have an increased risk of SSI. We sought to evaluate the appropriateness of preoperative antibiotic prophylaxis in patients labeled with a BLA compared those without a BLA. METHODS: This was a single-center, retrospective, matched cohort study of adult patients who underwent a clean or clean-contaminated knee replacement, abdominal hysterectomy, colorectal surgery, or coronary artery bypass graft (CABG). Patients with a BLA label were matched to patients without a BLA label based on procedure, age, and body mass index (BMI). The primary end point was the rate of appropriate preoperative antibiotic prophylaxis, including antibiotic selection and timing prior to incision. RESULTS: In total, 260 patients were included. Knee replacement (38%) was the most common procedure, followed by abdominal hysterectomy (25%), colorectal surgery (18%), and CABG (18%). Appropriate preoperative antibiotic prophylaxis was higher among patients without a BLA (76% vs 37%; P < .001). Among patients with a mild-to-moderate reaction or intolerance, 29 (53%) received antibiotics that would have been appropriate only if the patient had had a severe BLA. Patients with a BLA were more likely to have had an antibiotic omitted from the prophylactic regimen (44% vs 4%; P < .001). CONCLUSION: Patients with a BLA were more likely to receive inappropriate preoperative antibiotic prophylaxis, attributed to misinterpretation of BLA labels and antibiotic omissions. Optimizing antibiotic prophylaxis among patients with BLAs remains an area of opportunity to prevent SSIs.

Three-Tiered COVID-19 Cohorting Strategy and Implications for Memory-Care.

An outbreak of SARS-CoV-2 in a skilled nursing facility (SNF) can be devastating for residents and staff. Difficulty identifying asymptomatic and presymptomatic cases and lack of vaccination or treatment options make management challenging. We created, implemented, and now present a guide to rapidly deploy point-prevalence testing and 3-tiered cohorting in an SNF to mitigate an outbreak. We outline key challenges to SNF cohorting.

Clinical Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Tests for Diagnosing Coronavirus Disease 2019.

Utilizing 34 348 severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) nucleic acid amplification test (NAAT) results from 2 health systems, we estimated the clinical sensitivity of a single SARS-CoV-2 NAAT. We found that SARS-CoV-2 NAAT has 82%-97% sensitivity for diagnosing coronavirus disease 2019 among symptomatic patients.

COVIDOSE: Low-dose tocilizumab in the treatment of Covid-19.

Background Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the high mortality of coronavirus disease 2019 (Covid-19). Tocilizumab, an IL-6 receptor blocking monoclonal antibody, has been repurposed for Covid-19, but prospective trials and dose-finding studies in Covid-19 are lacking. Methods We conducted a phase 2 trial of low-dose tocilizumab in hospitalized adult patients with Covid-19, radiographic pulmonary infiltrate, fever, and C-reactive protein (CRP) >= 40 mg/L who did not require mechanical ventilation. Dose cohorts were determined by a trial Operations Committee, stratified by CRP and epidemiologic risk factors. A range of doses from 40 to 200 mg (low-dose tocilizumab) was evaluated, with allowance for one repeat dose at 24-48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Outcomes were compared with retrospective controls with Covid-19. Correlative studies evaluating host antibody response were performed in parallel. Findings A total of 32 patients received low-dose tocilizumab. This cohort had improved fever resolution (75.0% vs. 34.2%, p = 0.001) and CRP decline (86.2% vs. 14.3%, p < 0.001) in the 24-48 hours following drug administration, as compared to the retrospective controls (N=41). The probabilities of fever resolution or CRP decline did not appear to be dose-related in this small study (p=0.80 and p=0.10, respectively). Within the 28-day follow-up, 5 (15.6%) patients died. For patients who recovered, median time to clinical recovery was 3 days (IQR, 2-5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (15.6%) patients. Correlative biological studies demonstrated that tocilizumab-treated patients produced anti-SARS-CoV-2 antibodies comparable to controls. Interpretation Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with Covid-19. Results of this trial and its correlative biological studies provide rationale for a randomized, controlled trial of low-dose tocilizumab in Covid-19.