Clinical manifestations and treatment outcomes for patients with Pseudomonas endocarditis.

OBJECTIVES: To investigate clinical outcomes of patients with Pseudomonas endocarditis and identify factors associated with treatment failure. METHODS: Adult patients meeting definitive Duke's criteria for Pseudomonas endocarditis at 11 hospitals were identified between May 2000 and February 2024. Failure was defined as death or microbiological failure by day 42. First-line therapy consisted of cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam alone or in combination. RESULTS: Forty-eight patients met inclusion criteria; 29% were persons who inject drugs and 13% were organ transplant recipients. Pseudomonas aeruginosa was the causative species in 98% of cases. Patients who experienced 42 day cure were more likely to be initially managed with first-line ß-lactam agents compared with those who experienced clinical failure (97% versus 62%, P = 0.004). Treatment with first-line ß-lactams was associated with shorter time to treatment initiation and a lower likelihood of infection due to MDR Pseudomonas spp. In the univariate model, patients who experienced 90 day mortality were more likely to have prosthetic valve endocarditis (57% versus 24%, P = 0.02), an intracardiac complication (36% versus 9%, P = 0.04) and a higher median (IQR) Pitt bacteraemia score [2.5 (2-3.8) versus 1 (0-2), P = 0.048]. Combination therapy did not improve clinical outcomes but did increase the rate of adverse effects resulting in drug discontinuation compared with monotherapy, (21% versus 0%, P = 0.08). CONCLUSIONS: This is the largest study of Pseudomonas endocarditis to date. We identified improved clinical outcomes when cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam were used for initial treatment. We did not identify a clinical benefit for combination treatment.

Clinical outcomes of baloxavir versus oseltamivir in immunocompromised patients.

BACKGROUND: Neuraminidase inhibitors, including oseltamivir, are the treatment standard for influenza. Baloxavir, a novel antiviral, demonstrated comparable outcomes to oseltamivir in outpatients with influenza. Baloxavir was equally effective as oseltamivir in a retrospective study of hospitalized patients with influenza at our institution. However, the efficacy of baloxavir in immunocompromised patients is unclear. METHODS: We conducted a retrospective cohort study of immunocompromised adult patients hospitalized with influenza A who received baloxavir from January 2019 to April 2019 or oseltamivir from January 2018 to April 2018. Demographic and clinical outcomes were assessed. Primary outcomes were time from antiviral initiation to resolution of hypoxia and fever. Secondary outcomes were length of stay (LOS), intensive care unit (ICU) care, ICU LOS, and 30-day mortality. RESULTS: Of 95 total patients, 52 received baloxavir and 43 received oseltamivir. Other than younger age (57.5 vs. 65; p = .035) and longer duration between vaccination and symptom onset (114 vs. 86 days; p = .001) in the baloxavir group, baseline characteristics did not differ. H1 was the predominant subtype in the baloxavir group (65.3%) versus H3 in the oseltamivir group (85.7%). When comparing baloxavir to oseltamivir, there was no significant difference in median time from antiviral initiation to resolution of hypoxia (59.9 vs. 42.5 h) and to resolution of fever (21.6 vs. 26.6 h). There were no differences in secondary outcomes. CONCLUSION: Baloxavir was not associated with longer time to resolution of hypoxia or fever in comparison to oseltamivir. Results must be taken in context of variations in seasonal influenza subtype and resistance rates.

Outcomes of pregnant women exposed to Sotrovimab for the treatment of COVID-19 in the BA.1 Omicron predominant era (PRESTO).

BACKGROUND: Sotrovimab, a monoclonal antibody with efficacy against SARS-CoV-2 including certain Omicron variants, has been used in treatment of mild-moderate COVID-19. Limited data exists regarding its use in pregnant women. METHODS: Electronic medical record review of pregnant COVID-19 patients treated with sotrovimab from 12/30/21 - 1/31/22 (Yale New Haven Health Hospital System [YNHHS]) was performed. Included were pregnant individuals ≥ 12 years, weighing ≥ 40 kg, with positive SARS-CoV-2 test (within 10 days). Those receiving care outside YNHHS or receiving other SARS-CoV-2 treatment were excluded. We assessed demographics, medical history, and Monoclonal Antibody Screening Score (MASS). The primary composite clinical outcome assessed included emergency department (ED) visit < 24 h, hospitalization, intensive care unit (ICU) admission, and/or death within 29 days of sotrovimab. Secondarily, adverse feto-maternal outcomes and events for neonates were assessed at birth or through the end of the study period, which was 8/15/22. RESULTS: Among 22 subjects, median age was 32 years and body mass index was 27 kg/m2. 63% were Caucasian, 9% Hispanic, 14% African-American, and 9% Asian. 9% had diabetes and sickle cell disease. 5% had well-controlled HIV. 18%, 46%, and 36% received sotrovimab in trimester 1, 2, and 3, respectively. No infusion/allergic reactions occurred. MASS values were < 4. Only 12/22 (55%) received complete primary vaccination (46% mRNA-1273; 46% BNT162b2; 8% JNJ-78,436,735); none received a booster. CONCLUSIONS: Pregnant COVID-19 patients receiving sotrovimab at our center tolerated it well with good clinical outcomes. Pregnancy and neonatal complications did not appear sotrovimab-related. Though a limited sample, our data helps elucidate the safety and tolerability of sotrovimab in pregnant women.

Immunomodulatory Agents for Coronavirus Disease-2019 Pneumonia.

Morbidity and mortality from COVID-19 is due to severe inflammation and end-organ damage caused by a hyperinflammatory response. Multiple immunomodulatory agents to attenuate this response have been studied. Corticosteroids, specifically dexamethasone, have been shown to reduce mortality in hospitalized patients who require supplemental oxygen. Interleukin-6 antagonist, tocilizimab, and Janus kinase inhibitors have also been shown to reduce mortality. However, patients who have severe pulmonary end-organ damage requiring mechanical ventilation or extracorporeal membrane oxygenation appear not to benefit from immunomodulatory therapies. This highlights the importance of appropriate timing to initiate immunomodulatory therapies in the management of severe COVID-19 disease.

Mucocutaneous Leishmaniasis in a Pregnant Immigrant.

Cutaneous leishmaniasis is a parasitic infection that causes significant maternal morbidity, and even fetal mortality, during pregnancy, yet there are limited therapeutic options. Here, we report a case of leishmaniasis in a pregnant immigrant with exuberant mucocutaneous lesions with favorable response to liposomal amphotericin B.

Combination Therapy of Chloramphenicol and Daptomycin for the Treatment of Infective Endocarditis Secondary to Multidrug Resistant Enterococcus faecium.

A 38-years-old female with an aortic valve replacement presented to an outside hospital (OSH) with fevers and malaise. Blood cultures revealed VRE which was resistant to linezolid, resistant to ampicillin, non-susceptible to daptomycin (MIC of 8 mcg/mL), and exhibited susceptibility to gentamicin. The patient was therefore initiated on intravenous (IV) daptomycin 6 mg/kg q24h and gentamicin IV 1 mg/kg q8h. However, after 14 days of therapy with daptomycin and gentamicin, the patient was transferred to our institution for the management of cardiogenic shock and hypoxemic respiratory failure. Given the concern for treatment failure, her antimicrobial regimen was changed to IV chloramphenicol 12.5 mg/kg every 6 hours with IV daptomycin 10 mg/kg every 48 hours given an estimated creatinine clearance of 30 mL/minutes. In vitro susceptibilities for chloramphenicol were performed which confirmed susceptibility. A transesophageal echocardiogram revealed a possible abscess at the left coronary cusp and aortic valve dehiscence. The patient underwent aortic valve replacement with aortic root reconstruction. The aortic valve culture grew VRE susceptible to linezolid but resistant to ampicillin and doxycycline. The patient was deemed clinically cured after 42 days of combination therapy with daptomycin and chloramphenicol. After 6 years of follow-up, the patient has not had a recurrent VRE infection. To our knowledge, this is the first case of endocarditis secondary to VRE that was successfully managed with the combination of daptomycin and chloramphenicol.

Rectal screening for azole non-susceptible Candida species in patients undergoing liver transplantation.

INTRODUCTION: Candidiasis is the most common invasive fungal infection in solid organ transplant recipients, and liver transplant (LT) recipients are at heightened risk. We hypothesized that pre-transplant screening for azole non-susceptible Candida (ANSC) allows for tailored antifungal prophylaxis to reduce the incidence of post-LT ANSC infection. METHODS: We performed a retrospective chart review of adult (age ≥18 years) patients who underwent LT at Yale New Haven Hospital from April 2019 to March 2021. Screening for ANSC, defined as Candida glabrata or Candida krusei, was performed using a rectal swab prior to or at the time of LT. RESULTS: During the study period, ANSC screening was performed in 47 patients who underwent a total of 48 LTs, with 46/48 (96%) primary LTs and two re-transplantations. Ten of 48 screened cases (21%) had ANSC-positive rectal swabs. Only seven of 10 ANSC-colonized patients received appropriate antifungal prophylaxis (i.e., anidulafungin), and one of these seven patients developed candidemia within 30 days of LT. The median number of candidiasis risk factors was one, and 29% of the cohort had two or more risk factors. DISCUSSION: Routine ANSC screening of LT candidates may assist in selecting appropriate antifungal prophylaxis but may be insufficient to prevent infection in those with multiple risk factors for Candida infection.

An outbreak of SARS-CoV-2 on a transplant unit in the early vaccination era.

BACKGROUND: Solid organ transplant recipients are at increased risk of COVID-19-associated morbidity and mortality. AIMS: We describe a nosocomial outbreak investigation on an immunocompromised inpatient unit. METHODS: Patients positive for SARS-CoV-2 were identified. An epidemiologic investigation was assisted with whole genome sequencing of positive samples. RESULTS: Two patients were identified as potential index cases; one presented with diarrhea and was initially not isolated, and the other developed hypoxemia on hospital day 18 before testing positive. Following identification of a SARS-CoV-2 cluster, the unit was closed and all patients and staff received surveillance testing revealing eight additional positive patients and staff members. Whole genome sequencing confirmed an outbreak. Enhanced infection prevention practices mitigated further spread. Asymptomatic patients with COVID-19 were successfully treated with bamlanivimab. DISCUSSION: Preventing SARS-CoV-2 outbreaks in transplant units poses unique challenges as patients may have atypical presentations of COVID-19. Immunocompromised patients who test positive for SARS-CoV-2 while asymptomatic may benefit from monoclonal antibody therapy to prevent disease progression. All hospital staff members working with immunocompromised patients should be promptly encouraged to follow infection prevention behaviors and receive SARS-CoV-2 vaccination. CONCLUSION: SARS-CoV-2 outbreaks on immunocompromised units can be mitigated through prompt identification of cases and robust infection prevention practices.

Nocardia thailandica Brain Abscess in an Immunocompromised Patient.

OBJECTIVES: Successful treatment for Nocardia thailandica is not well elucidated in the literature. To the best of our knowledge, N. thailandica has not yet been described in the medical literature to cause central nervous system (CNS) infection from brain abscess. We report the case of an immunocompromised patient who underwent successful treatment to treat his brain abscess caused by N. thailandica. METHODS: After failing medical therapy, the patient underwent a craniotomy, and tissue was sent for culture. Upon identification by 16S rDNA sequencing, the organism causing infection was identified to be N. thailandica. RESULTS: Based on susceptibilities, the patient was treated with IV ceftriaxone 2 grams daily for five months. The patient demonstrated clinical and radiological improvement which persisted to 7 months after initiation of therapy. CONCLUSIONS: To the best of our knowledge, this is the first documented case of a brain abscess due to N. thailandica which was successfully treated. Due to the location of the infection, ceftriaxone was chosen because of optimal CNS penetration. Ceftriaxone monotherapy demonstrated clinical and radiographic treatment success resulting in the successful treatment of this infection.

Pharmacists leadership in a medication shortage response: Illustrative examples from a health system response to the COVID-19 crisis.

As medication experts, clinical pharmacists play an active and dynamic role in a medication shortage response. Supplementing existing guidelines with an actionable framework of discrete activities to support effective medication shortage responses can expand the scope of pharmacy practice and improve patient care. Dissemination of best practices and illustrative, networked examples from health systems can support the adoption of innovative solutions. In this descriptive report, we document the translation of published shortage mitigation guidelines into system success through broad pharmacist engagement and the adaption and implementation of targeted strategies. The profound, wide-reaching medication shortages that accompanied the coronavirus disease 2019 (COVID-19) pandemic are used to highlight coordinated but distinct practices and how they have been combined to expand the influence of the pharmacy enterprise.

Renal and Hepatic Toxicity Analysis of Remdesivir Formulations: Does What Is on the Inside Really Count?

It has been postulated that the injectable solution formulation of remdesivir could be more nephrotoxic than the lyophilized powder since it contains twice as much sulfobutylether-ß-cyclodextrin (SBECD). Therefore, we evaluated 1,000 hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received remdesivir lyophilized powder or solution. A logistic regression model accounting for baseline confounders identified that neither the use of the injectable solution (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.49 to 2.29; P = 0.901) nor a creatinine clearance of <30 ml/min at the time of remdesivir initiation (OR, 1.39; 95% CI, 0.51 to 3.5; P = 0.499) was significantly associated with acute kidney injury. Regarding hepatoxicity, there was no significant difference in early discontinuation of remdesivir due to abnormal liver function tests between patients who received the lyophilized powder versus those who received solution (0.9% versus 2.3%, P = 0.09).

A Novel Dosing Strategy of Ceftolozane/Tazobactam in a Patient Receiving Intermittent Hemodialysis.

We describe the case of a 54-year-old male receiving intermittent hemodialysis (iHD) who was found to have Pseudomonas aeruginosa bacteremia secondary to osteomyelitis of the calcaneus bone. The patient was clinically cured without recurrence using a ceftolozane/tazobactam (CTZ) dosing strategy of 100/50 mg every 8 hours (standard dosing) and 1000/500 mg thrice weekly following iHD. Utilizing a susceptibility breakpoint of ≤4 µg/mL for P. aeruginosa, the T > MIC for standard dosing and the 1000/500-mg thrice-weekly following iHD regimen were calculated to be 92.7% and 94.1%, respectively. Ceftolozane total body clearance for the standard q 8 h dosing and the 1000/500-mg thrice-weekly following iHD regimen were calculated to be 0.196 L/h and 0.199 L/h, respectively. To our knowledge, this is the first report to illustrate the administration of CTZ at a dose of 1000/500 mg thrice weekly following iHD.

Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19.

We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical SARS-CoV-2 infection. Disease severity was based on maximum oxygen requirement during hospital stay to maintain SpO2 > 93% (moderate, 0-3 L NC; severe, 4-6 L NC or non-rebreather; critical, HFNC, NIPPV, or MV). All patients were treated using the institution's treatment algorithm, which included consideration of tocilizumab for severe and critical disease. The most common cytokine elevations among all patients included IL-6, sIL2R, IFN-γ, and IL-10; patients who received tocilizumab had higher incidence of IL-6 and sIL2R elevations. Pre-tocilizumab IL-6 levels increased with disease severity (p = .0151). Both IL-6 and sIL2R levels significantly increased after administration of tocilizumab in all severity groups; IL-10 levels decreased in severe (p = .0203), but not moderate or critical, patients after they received tocilizumab. Cluster analysis revealed association between higher admission IL-6, sIL2R, and CRP levels and disease severity. Mean IL-6, sIL2R, and D-dimer were associated with mortality, and tocilizumab-treated patients with elevated IL-6, IL-10, and D-dimer were more likely to also receive glucocorticoids. Accessible clinical cytokine panels may be useful for monitoring response to treatment in COVID-19. The increase in sIL2R post-tocilizumab, despite administration of glucocorticoids, may indicate the need for combination therapy in order to modulate more than one hyperinflammatory pathway in COVID-19. We also discuss the role of cytokines as potential biomarkers for use of adjunct glucocorticoid therapy.

Evaluation of the negative predictive value of methicillin-resistant Staphylococcus aureus nasal swab screening in patients with acute myeloid leukemia.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs are utilized to guide the discontinuation of empiric MRSA therapy. In multiple studies, MRSA nasal swabs have been shown to have a negative predictive value (NPV) of ~99% in non-oncology patients with pneumonia and other infections. We evaluated the performance characteristics of a negative MRSA nasal swab in the acute myeloid leukemia (AML) populaion to determine its NPV. DESIGN: Retrospective chart review. PATIENTS: This study included adult AML patients with a suspected infection and a MRSA nasal swab collected between 2013 and 2018. METHODS: MRSA nasal swab and culture-documented infections were identified to determine the sensitivity, specificity, NPV, and positive predictive value of the MRSA nasal swabs. RESULTS: In total, 194 patients were identified, and 484 discrete encounters were analyzed. Overall, 468 (97%) encounters had a negative MRSA nasal swab upon admission with no cultured documented MRSA infection during their hospitalization. However, 3 encounters (0.6%) had a negative MRSA nasal swab with a subsequent cultured documented MRSA infection during their admission. Identified infections were bacteremia (n = 2) and confirmed pneumonia (n = 1). MRSA nasal swab had a sensitivity of 62% (95% CI, 0.24-0.91), specificity of 98% (95% CI, 0.96-0.99), positive predictive value of 38% (95% CI, 0.21-0.6), and NPV of 99% (95% CI, 0.98-1). CONCLUSIONS: A negative MRSA nasal swab has a 99% NPV for subsequent MRSA infections in AML patients with no prior history of MRSA colonization or infection. Based on these findings, a negative MRSA nasal swab can help guide de-escalation of empiric MRSA antibiotic therapy.

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort.

Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) of <30 ml/min and an eCrCl of ≥30 ml/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl of <30 ml/min were older {median, 80 years (interquartile range [IQR], 63.8 to 89) versus 62 (IQR, 54 to 74); P < 0.001}, were more likely to be on vasopressors on the day of remdesivir administration (30% versus 12.7%; P = 0.003), and were more likely to be mechanically ventilated during remdesivir therapy (27.5% versus 12.4%; P = 0.01) than those with an eCrCl of ≥30 ml/min. Despite these confounders, there was no significant difference in the frequency of EOT AKI (5% versus 2.3%; P = 0.283) or early discontinuation due to abnormal liver function tests (LFTs) (0% versus 3.9%; P = 0.374). Of the 5% of patients who developed EOT AKI on remdesivir with an eCrCl <30 ml/min, no cases were attributable to remdesivir administration per the treating physician. Comparable safety outcomes were observed when 1:1 nearest neighbor matching was applied to account for baseline confounders. In conclusion, remdesivir administration was not significantly associated with increased EOT AKI in patients with an eCrCl of <30 ml/min compared to patients with an eCrCl of ≥30 ml/min.