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.

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.

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.

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.

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.

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.

Universal molecular Clostridioides difficile screening and overtreatment in solid organ transplant recipients.

BACKGROUND: Screening for Clostridioides difficile (CD) colonization can be performed using molecular testing to identify the presence of microbial DNA of the toxin gene. Colonization rates for hospitalized patients are as high as 20% and may be considerably higher in solid organ transplant (SOT) recipients. Treatment for CD should be based on clinical disease and not colonization, yet clinicians may misinterpret a positive CD screen resulting in overtreatment. OBJECTIVES: The objective of this analysis is to determine how often positive CD screens resulted in inappropriate treatment with oral vancomycin. METHODS: Clostridioides difficile screens were performed using the Xpert C difficile assay (Cepheid), a nucleic acid amplification testing method utilizing polymerase chain reaction (PCR), on peri-rectal swabs for newly admitted patients. This was a single-center cohort study of adult patients with CD screens hospitalized between July 2015 and November 2018. The primary outcome was the rate of inappropriate oral vancomycin treatment in all patients and in SOT recipients, defined as therapy in the absence of diarrhea. RESULTS: Of the 47 076 total CD screens reviewed, 1,921 were positive. In the SOT cohort, 58 of 329 screens were positive (4.1% vs 17.9%, P < .01). Of all patients with a positive CD screen, 20.1% (386/1921) were treated with oral vancomycin within 48 hours of swab collection. In the SOT cohort, 39.6% (23/58) with positive CD screens were treated with oral vancomycin within 48 hours. Of the SOT patients who received oral vancomycin, 39% (9/23) did not have true CD infection. CONCLUSION: Solid organ transplant recipients were more likely to have CD colonization detected by peri-rectal screening than the general inpatient population. SOT and non-SOT patients were treated with oral vancomycin at similar rates in response to the positive screen. Nearly half of the oral vancomycin use in SOT recipients was likely overtreatment, but this finding is limited by the low number of patients in this cohort.

Reducing medication errors involving antiretroviral therapy with targeted electronic medical record modifications.

Medication errors are common among HIV-infected patients on anti-retroviral therapy (ART), especially when transitioning to the inpatient setting. In previous studies, medication error rates among hospitalized patients on ART have been reported to exceed 50%. When patients receiving ART are admitted to the hospital, medication errors can be prevented through optimization of administration instructions and dosing defaults in order-entry screens in the electronic medical record (EMR). We sought to evaluate the impact of EMR modifications (defaulted doses, frequencies, and administration instructions) implemented to improve the order-entry process and reduce errors. All adult patients admitted between 10/1/2010-3/31/2012 (pre-EMR modification) and 10/1/2013-3/31/2014 (post-EMR modification) that continued on ART upon admission were included. The primary outcome was the overall rate of medication errors identified through review by the antimicrobial stewardship program (ASP). We also characterized the types of medication errors identified during the two time periods. Following EMR modifications, the medication error rate identified through ASP review was reduced from 50.2% to 28.2% (P < 0.01). The number of medication related errors relating to dosage (regimens requiring dose optimization, renal dose adjustment, and dose timing) were reduced by 22% (P < 0.01). Modifications at the anti-retroviral medication order-entry screens in the EMR significantly reduced medication errors, particularly with respect to dosing and dose timing.

Moxifloxacin versus levofloxacin for antibacterial prophylaxis in acute leukemia patients.

OBJECTIVE: The primary endpoint of this study was to determine the incidence of febrile neutropenia among patients receiving either moxifloxacin or levofloxacin for antibacterial prophylaxis. Secondary endpoints were number of documented infections and in-hospital mortality in patients who develop febrile neutropenia. METHODS: A single-center retrospective cohort analysis at a large tertiary care academic medical center was conducted. This study included adult acute leukemia patients (age ≥18 years old) who received inpatient antibacterial prophylaxis (moxifloxacin or levofloxacin) from 1 July 2012 to 1 October 2014. Patients were excluded from the study if they were treated with antimicrobial therapy in the preceding five days or admitted to the hospital with neutropenic fever. Fisher's exact test was used for categorical data and Mann-Whitney test for continuous data. Logistic regression analysis was used to determine risk factors for febrile neutropenia. RESULTS: Eighty-five patients were included in the final analysis with 40 patients who received moxifloxacin and 45 patients who received levofloxacin. Baseline characteristics were similar between the two groups. Twenty-two patients experienced febrile neutropenia requiring intravenous antibiotics in the moxifloxacin group and 30 patients in the levofloxacin group (P = 0.190). Age and duration of neutropenia appeared to predict for febrile neutropenia; however, after multivariate analysis, longer duration of neutropenia was shown to be the best predictor for febrile neutropenia with an odds ratio of 4.69 (95% CI, 1.697-12.968). Both groups had similar rates of documented infections and in-hospital morality. CONCLUSION: Moxifloxacin and levofloxacin showed similar rates of febrile neutropenia when used for neutropenic antibacterial prophylaxis in acute leukemia patients.

Misdiagnosis of Bordetella bronchiseptica Respiratory Infection as Bordetella pertussis by Multiplex Molecular Assay.

Multiplex polymerase chain reaction (PCR) tests are useful for the rapid detection of pathogens, though diagnostic challenges may arise. We report 2 immunocompromised patients with Bordetella bronchiseptica respiratory infection misdiagnosed as Bordetella pertussis using PCR, including discussion of transmission, diagnostic testing, clinical implications, and infection control considerations.

Multicentre study of posaconazole delayed-release tablet serum level and association with hepatotoxicity and QTc prolongation.

Objectives: The association of posaconazole serum concentrations and toxicity is unclear. An assessment of whether levels obtained with the delayed-release tablet (DRT) formulation are correlated with abnormal liver function test (LFT) results and/or QTc prolongation was undertaken. Methods: This was a multicentre, retrospective, observational study of adult patients with cancer between 26 November 2013 and 14 November 2014. Patients were included if they received posaconazole DRT with a posaconazole level obtained between days 5 and 14. Clinical data, including demographics, hepatotoxic medications, posaconazole levels, LFTs and QTc intervals, were obtained. Association of factors with changes in LFTs and QTc prolongation was assessed using linear and logistic regression. Results: One hundred and sixty-six study patients were included. The median posaconazole level was 1250 (range 110-4220) ng/mL and the median time until level was 6 (range 5-14) days. There was a statistically significant increase in AST ( P < 0.001), ALT ( P < 0.001), alkaline phosphatase (ALK) ( P < 0.001), total bilirubin (TBILI) ( P < 0.001) and QTc ( P = 0.05) from baseline. Posaconazole levels were not associated with increases in AST [ß (SE) = -0.33 (2.2), P = 0.88], log ALT [ß (SE) = -0.02 (0.03), P = 0.63], ALK [ß (SE) = 2.2 (2.9), P = 0.46] and TBILI [ß (SE) = -0.01 (0.04), P = 0.88]. For each additional hepatotoxic medication, there was a mean change in TBILI of 0.13 mg/dL ( P = 0.02) and ALK of 7.1 U/L ( P = 0.09). No statistically significant association between posaconazole level and QTc interval prolongation was found. Conclusions: We did not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered.

Impact of a clinical pathway on appropriate empiric vancomycin use in cancer patients with febrile neutropenia.

Objectives Febrile neutropenia management guidelines recommend the use of vancomycin as part of an empiric antimicrobial regimen when specific criteria are met. Often, vancomycin use among patients with febrile neutropenia is not indicated and may be over utilized for this indication. We sought to evaluate the impact of implementing a febrile neutropenia clinical pathway on empiric vancomycin use for febrile neutropenia and to identify predictors of vancomycin use when not indicated. Methods Adult febrile neutropenia patients who received initial therapy with an anti-pseudomonal beta-lactam with or without vancomycin were identified before (June 2008 to November 2010) and after (June 2012 to June 2013) pathway implementation. Patients were assessed for appropriateness of therapy based on whether the patient received vancomycin consistent with guideline recommendations. Using a comorbidity index used for risk assessment in high risk hematology/oncology patients, we evaluated whether specific comorbidities are associated with inappropriate vancomycin use in the setting of febrile neutropenia. Results A total of 206 patients were included in the pre-pathway time period with 35.9% of patients receiving vancomycin therapy that was inconsistent with the pathway. A total of 131 patients were included in the post-pathway time period with 11.4% of patients receiving vancomycin inconsistent with the pathway ( p = 0.001). None of the comorbidities assessed, nor the comorbidity index score were found to be predictors of vancomycin use inconsistent with guideline recommendations. Conclusion Our study has demonstrated that implementation of a febrile neutropenia pathway can significantly improve adherence to national guideline recommendations with respect to empiric vancomycin utilization for febrile neutropenia.

Repeated Blood Cultures in Pediatric Febrile Neutropenia: Would Following the Guidelines Alter the Outcome?

BACKGROUND: The Infectious Diseases Society of America (IDSA) guidelines recommend collecting blood cultures for the first 3 days of febrile neutropenia (FN) in the clinically stable oncology patient with persistent fevers. Nonetheless, many physicians send daily blood cultures beyond 3 days, and the impact of that practice is uncertain. PROCEDURE: We reviewed pediatric FN episodes from July 2009 to May 2014 at University of Chicago Comer Children's Hospital. For each positive culture, we determined if it was a pathogen or a contaminant. We reviewed episode and patient demographics to identify risk factors for subsequent positive blood cultures in the setting of an initially negative culture. RESULTS: We identified 381 episodes of FN in 162 patients. Of those, 87 had a positive blood culture on day 1 (21.0% incidence of bacteremia). Of 294 episodes with a negative blood culture on day 1, six (2.04%, 95% confidence interval [CI] 0.42-3.67) had a positive culture after day 3. Of those, three were pathogens (1.02%, 95%CI -0.14 to 2.18), and only one was found in a hemodynamically stable patient (0.34%, 95%CI -0.33 to 1.01) with new mucositis. In the other two patients, Escherichia coli was isolated from blood cultures after day 10 in the setting of significant hemodynamic changes. Risk factor analysis performed in stable patients yielded nonsignificant results. CONCLUSIONS: Of 294 FN episodes with an initial negative blood culture, only one episode of bacteremia occurred without hemodynamic changes past day 3, supporting the IDSA guidelines to discontinue blood cultures in stable FN patients after day 3.

Hepatic Failure in a Patient Receiving Itraconazole for Pulmonary Histoplasmosis-Case Report and Literature Review.

Severe cases of itraconazole-induced hepatotoxicity have been reported; however, these events are thought to occur very rarely. The available literature is comprised largely of individual case reports and small series that do not report the itraconazole serum concentration at the time of the severe adverse event or apply an objective scale to assess probability of the event being related to drug exposure. We report a case of severe hepatotoxicity after 6 months of itraconazole therapy for histoplasmosis, resulting in acute hepatic failure (aspartate transaminase >20× and alanine transaminase >15× upper limit normal), in the setting of therapeutic serum concentrations (5 mg/mL). Both the Naranjo probability scale and the Roussel Uclaf causality assessment method were used to assess the probability of a causality relationship showing a "probable" and "highly probable" association with itraconazole exposure, respectively. The available literature describing severe hepatotoxicity resulting in hepatic failure associated with itraconazole is also reviewed.

Candida dubliniensis Pneumonia: A Case Report and Review of Literature.

Candida dubliniensis is an uncommon species of Candida which has been implicated in fungal pneumonia only very rarely. We present the case of a 75-year-old man with laryngeal cancer undergoing chemotherapy on broad-spectrum antibiotics and tuberculosis therapy with blood and endotracheal cultures positive for C. dubliniensis. Subsequent autopsy was performed with postmortem lung cultures positive for C. dubliniensis and lung histopathology demonstrating an invasive fungal infection. Molecular analysis of the lung tissue confirmed the identity of the fungi as C. dubliniensis. Since its discovery as a pathogen in the oral cavities of HIV-positive patients, C. dubliniensis has been identified in a wide spectrum of clinical scenarios and anatomic locations but manifests only rarely as pneumonia. This report represents a novel case of C. dubliniensis pneumonia confirmed by culture, histopathology, and molecular identification.

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.

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.

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 recommendation 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 (UTI) 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.

Fidaxomicin versus oral vancomycin for Clostridioides difficile infection among patients at high risk for recurrence based on real-world experience.

INTRODUCTION: Clostridioides difficile infection (CDI) is a common nosocomial infection and is associated with a high healthcare burden due to high rates of recurrence. In 2021 the IDSA/SHEA guideline update recommended fidaxomicin (FDX) as first-line therapy. Our medical center updated our institutional guidelines to follow these recommendations, prioritizing FDX use among patients at high risk for recurrent CDI (rCDI). METHODS: This pre- post- quasi-experimental study included patients with a presumptive diagnosis of CDI at risk for recurrence (age >/= 65 years, immunocompromised, severe CDI) that received vancomycin (VAN) or FDX between October 2019 to October 2022. Patients who received bezlotoxumab, had fulminant CDI, or received <10 days of the same antibiotic for their full treatment course were excluded. Patients were evaluated for rCDI within 8 weeks of completion of therapy, subsequent episodes of CDI within 12 months, and CDI-related admissions within 30 days. RESULTS: Of 397 CDI regimens evaluated, 196 received VAN and 201 received FDX. Rates of rCDI (9.2% vs 10%, P = 0.86), subsequent CDI within 12 months of therapy completion of therapy (19.4% vs 26%, P = 0.12) and 30-day CDI-related readmissions (3% vs 4.5%, P = 0.6) were similar between patients who received VAN versus FDX. CONCLUSION: Outcomes were similar between patients treated with FDX and VAN for the treatment of CDI among those at high risk for rCDI, using our outlined criteria. Although we observed a trend toward lower rates of rCDI among immunocompromised patients, this finding was not significant. Further investigation is needed to determine which patients with CDI may benefit from FDX.

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.