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.

Serratia endocarditis: antimicrobial management strategies and clinical outcomes.

OBJECTIVES: The incidence of Serratia endocarditis is increasing, yet optimal treatment has not been defined. Our objective was to investigate the outcomes of patients with Serratia endocarditis by treatment strategy. METHODS: We reviewed adult patients with definitive Serratia endocarditis at two independent health systems between July 2001 and April 2023. Combination therapy was defined as receipt of ≥2 in vitro active agents for ≥72 h. RESULTS: Seventy-five patients were included; 64% (48/75) were male and 85% (64/75) were people who inject drugs. Compared with monotherapy, receipt of combination therapy was associated with lower rates of microbiological failure (0% versus 15%, P = 0.026) and 90 day all-cause mortality (11% versus 31%, P = 0.049). Antimicrobial discontinuation due to an adverse event was more common among patients receiving combination therapy compared with monotherapy (36% versus 8%, P = 0.058). CONCLUSIONS: In the largest series of Serratia endocarditis to date, combination antibiotic treatment was associated with improved outcomes. However, larger, prospective studies are warranted.

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.

Dosing implications for liposomal amphotericin B in pregnancy.

Liposomal amphotericin B (LAmB) is used in the treatment of opportunistic fungal and parasitic infections, including leishmaniasis. Given its lack of known teratogenicity in pregnancy, LAmB is a preferred agent for treatment for these patients. However, significant gaps remain in determining optimal dosing regimens for LAmB in pregnancy. We describe the use of LAmB for a pregnant patient with mucocutaneous leishmaniasis (MCL) using a dosing strategy of 5 mg/kg/day for days 1-7 using ideal body weight followed by 4 mg/kg weekly using adjusted body weight. We reviewed the literature for LAmB dosing strategies, particularly dosing weight, in pregnancy. Of the 143 cases identified in 17 studies, only one reported a dosing weight, in which ideal body weight was used. Five Infectious Diseases Society of America guidelines in total discussed the use of amphotericin B in pregnancy but no guidelines included recommendations for dosing weight. This review describes our experience in using ideal body weight for dosing LAmB in pregnancy for the treatment of MCL. Use of ideal body weight may minimize risk of adverse effects to the fetus compared to the use of total body weight while maintaining efficacy for treatment of MCL in pregnancy.

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.

Genetic and Epidemiologic Analyses of an Outbreak of Pneumocystis jirovecii Pneumonia Among Kidney Transplant Recipients in the United States.

BACKGROUND: Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. METHODS: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. RESULTS: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. CONCLUSIONS: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.

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.

Three is a crowd: Clinical outcomes of a twice daily versus a thrice daily metronidazole dosing strategy from a multicenter study.

This was a multicenter, retrospective study of patients with anaerobic bacteremia comparing metronidazole 500 mg every 8 h versus 500 mg every 12 h. Of 782 patients reviewed, 85 met inclusion criteria. There was no significant difference in mortality, length of stay, or escalation of therapy between dosing strategies.