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  • McCreary, Erin K  (12)
  • 1
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 75, No. 10 ( 2020-10-01), p. 3023-3028
    Kurzfassung: Isavuconazole is a triazole antifungal available in IV and capsule formulation. Prescribing information states that capsules should not be chewed, crushed, dissolved or opened because the drug was not studied in this manner. However, considering the pharmacokinetics of the capsules, we theorized opening and sprinkling the contents into an enteral feeding tube (EFT) would result in adequate absorption and systemic concentrations of isavuconazole. Objectives To determine whether patients receiving isavuconazonium sulphate capsules via EFT would achieve clinical blood concentrations of isavuconazole. Methods Nineteen solid organ and HCT recipients receiving isavuconazole via EFT for prevention or treatment of invasive fungal infection (IFI) were prospectively identified at four academic medical centres in the USA. Patients were included in this evaluation if they received isavuconazole via EFT for at least 5 days and therapeutic drug monitoring (TDM) was performed. Results TDM was performed after a median of 7 days (range 6–17) following EFT administration and 15 days (range 7–174) of isavuconazole therapy overall. Median isavuconazole concentration was 1.8 μg/mL (range 0.3–5.2). Median isavuconazole concentrations in patients with or without prior IV administration were 1.8 μg/mL (range 0.3–5.2) and 2.2 μg/mL (range 0.8–3.6; P = 0.896), respectively. Concentrations achieved with the EFT route were similar to or greater than the corresponding concentrations via the IV route in six patients who had TDM performed during both routes of administration. Conclusions It is reasonable to consider opening isavuconazonium sulphate capsules and administering the contents enterally for prevention and treatment of IFI.
    Materialart: Online-Ressource
    ISSN: 0305-7453 , 1460-2091
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 1467478-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S6-S7
    Kurzfassung: IFI is a significant complication following lung transplant (LT). VOR was universal antifungal px in our LT program from 2004 to October 2015, at which time px was changed to ISA. We compared the efficacy and tolerability of VOR vs. ISA px in LTR. Methods We reviewed all LTR from September 2013 to February 2018 who received VOR or ISA Px. The standard duration of px was 3 or 4 months following basiliximab and alemtuzumab induction, respectively. All patients were followed for ≥1 years post-Tx. IFI was defined by revised EORTC/MSG criteria. Results In total, 310 LTR were included, 149 and 161 of whom received ISA and VOR px, respectively. There was no difference in demographics, underlying diseases, single vs. double LT, or induction therapy (alemtuzumab vs. basiliximab) between the 2 groups. At 1-year after LT, 9% (14) and 8% (13) of patients in ISA and VOR groups developed IFI, respectively (P = 0.5). 5% (7) and 3% (5) of patients developed breakthrough (BT) IFI during ISA and VOR px, respectively (P = 0.6; Figure 1, P = 0.4, Kaplan-–Meier). ISA BT included pneumonia (PNA, 2), endobronchial IFI (2), mediastinitis (1), chest wall IFI (1), and candidemia (1). ISA BT patients were infected with Aspergillus fumigatus (3; 2 with ISA MIC = 0.5 µg/mL, 1 MIC = 1 µg/mL), black mould (1), and yeasts (3; 2 C. glabrata, 1 C. albicans). VOR BT IFI included PNA (2), endobronchial IFI (1), empyema (1), and chest wall IFI (1). VOR BT IFIs were due to A. ustus, A. niger, A. lentulus, black mould, and Rhizopus spp (1 each). All Aspergillus VOR BT isolates exhibited VOR MIC ≥2 µg/mL. Patients with IFI were more likely to have positive pre-LT respiratory fungal culture (P = 0.01) and grade ≥3 ischemic reperfusion injury (IRI) post-LT (P = 0.01). VOR and ISA were prematurely discontinued in 53% (85) and 14% (21) of patients due to adverse events, respectively (P 〈 0.0001). Hepatotoxicity was more common with VOR (22%, 35) than ISA (5%, 7) (P 〈 0.0001). IFI was an independent risk factor for death at 1 year (Figure 2, P 〈 0.0001, Kaplan–Meier). Conclusion ISA was as effective as VOR in preventing IFI in LTR, and significantly better tolerated. Pre-LT fungal culture positivity and grade ≥3 IRI post-LT were risk factors for the development of IFI. IFI within 1-year post-LT had a significant impact on mortality Disclosures Fernanda P. Silveira, MD, MS, FIDSA, Ansun: Grant/Research Support; Qiagen: Grant/Research Support; Shire: Grant/Research Support; Whiscon: Grant/Research Support.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Kurzfassung: An ASP is mandated for all hospitals and requires extensive resources with multidisciplinary collaboration. We measured the impact of implementing real-time decision support software (ILUM Insight) within our ASP. Methods Our ASP has relied on prior authorization since 2002 and focused audit and feedback since 2015. In August 2021 we implemented to bring actionable data to front-line stewards. ILUM provides real-time notifications, organizes communications, and tracks patient-and provider-level data. We hypothesized that ILUM would increase the efficiency of ASP workflow and result in decreased antimicrobial utilization. We compared data 6 months before (8/20 – 1/21) and after (8/21 – 1/22) implementation. There were no significant staffing changes during either period. Results Existing notifications within ILUM were tailored to local practices, including alerts with intervention for positive blood cultures, antibiotic de-escalation, and bug-drug mismatches. New notifications were built for restricted antimicrobials, antibiotic timeouts, and MRSA screening. ASP pharmacists and physicians received training in July and November, respectively. A breakdown of all notifications received during the post-implementation period is provided in Fig 1. With increased ILUM usage, the number of interventions made by our ASP increased while missed opportunities decreased (Fig 2.). During the same time period, ASP communications rose from 205 to 1200 per month. Comparing pre- and post-implementation periods, antimicrobial days of therapy (DOT) per 1,000 patient days (PD) decreased by 14.5% from a median of 969 to 846 per month (Fig 3;P=0.002). Antimicrobial expenditures were decreased by a median 21% per month during the post-intervention period compared to baseline. Among patients prescribed antimicrobials during an index admission, 30-day re-admissions decreased from 330 to 262 and re-admissions associated with re-ordering of antimicrobials decreased from 235 to 182 (Fig 4). Conclusion Custom-designed, task-specific software improves the efficiency of daily ASP workflow and significantly decreased antimicrobial utilization without the need for additional ASP team members. Disclosures Ryan K. Shields, PharmD, MS, Infectious Disease Connect: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support J Ryan Bariola, MD, Infectious Disease Connect: Salary support|Merck: Grant/Research Support Caley Yakemowicz, n/a, Infectious Disease Connect: Employee Courtney Simonick, n/a, Infectious Disease Connect: Stocks/Bonds Riaan Erwee, na, Infectious Disease Connect: Employee Erin K. McCreary, PharmD, Infectious Disease Connect: Advisor/Consultant Rima Abdel-Massih, MD, Infectious Disease Connect: Co founder and Chief Medical Officer|Infectious Disease Connect: Ownership Interest.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S627-S627
    Kurzfassung: Despite increasing recognition of aspergillosis complicating severe influenza and its associated high fatality in Europe, incidence and features of the disease in the United States are unknown. Methods We reviewed all influenza cases requiring ICU admission from 2009 to 2019 at our center. Results 262 patients with influenza required ICU admission. 4% (10) developed IFI at median 2d after influenza diagnosis. 80% (8/10) of patients with IFI were infected with influenza A vs. 88% (221/252) without IFI. 20% were on steroids at the time of IFI diagnosis. 70% of IFI required mechanical ventilation. Types of IFI were pneumonia (70%, 6 Aspergillus and 1 Wangiella), endobronchial IFI (20%, 1 each with Aspergillus and Lictheimia), and Coccidioides fungemia (10%). 4% (10) of patients were fungal colonized, but did not have IFI (5 A. fumigatus, 1 A. terreus, 4 Penicillium). CT findings of IFI included nodules (4), cavitation (3), and ground-glass opacities (2). Serum galactomannan (GM) was positive in 3 (43%). Median time to antifungal therapy (AF) was 2 days. Triazoles were prescribed to all 7 patients with aspergillosis. Posaconazole and amphotericin B were AF for patients with Wangiellaand Lichteimia, respectively. Patients with C. immitis fungemia died before AF. Median duration of AF was 60 days among survivors. Patients with IFI required acute hemodialysis more frequently than colonized patients (60% vs. 0%, P = 0.01). 30-day mortality was 60% (6/10) and 20% 92/10) in patients with IFI and colonization, respectively (P = 0.2). Patients with IFI had significantly higher in-hospital and 60-day mortality than those without IFI (Fig 1, P = 0.009). Conclusion Our rate of post-influenza IFI (4%) was lower than reported in Europe (~15%), which might stem from a lack of systematic BAL GM testing at our center, over-reliance on GM to make diagnoses in Europe, and/or differences in pt populations and clinical practices in treating severe influenza. IFI and fungal colonization rates were similar at our center, highlighting the importance of using well-defined criteria to define disease. Given the high mortality of post-influenza IFI, priority should be given to defining risk factors that might identify patients for targeted AF prophylaxis. In using AF, it is important to recognize that Aspergillus is not the only cause of IFI. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 3 ( 2021-08-02), p. 416-426
    Kurzfassung: Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. Methods A single-center, retrospective study of patients who received isavuconazole (September 2015–February 2018) or voriconazole (September 2013–September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. Results Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion  & gt;7 units at transplant. Bronchial necrosis  & gt;2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). Conclusions Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.
    Materialart: Online-Ressource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2002229-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S768-S768
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S768-S768
    Kurzfassung: M/V demonstrates in vitro activity against KPC-producing CRE, but real-world clinical experience is limited. Methods Patients treated for 〉 48 hours with M/V for CRE infections were included. Success was defined as improved symptoms, absence of recurrent infection, and survival at 30 days. Microbiologic failures (MF) were defined as isolation of the same species post-treatment (tx). KPC and ompK36 mutations were detected by sequencing of PCR products. Results 19 patients were included; 58% were men; median age was 53. 11% were transplant recipients and median Charlson score was 3 (range: 0–10). Infection types included bacteremia (n = 7), pneumonia (6; 5 ventilator-associated), soft tissue (2), tracheobronchitis (2), intra-abdominal (1), and pyelonephritis (1). 68% of patients were in the ICU; median APACHE II and SOFA scores were 18 (7–40) and 4 (1–13), respectively. CR pathogens included K. pneumoniae (14), K. oxytoca (2), E. coli (2), and C. freundii (1); 89% harbored KPC, including KPC-2 (6), KPC-3 (10), and KPC-3 with a D179Y mutation (1). All were susceptible to M/V (median MIC = 0.03 µg/mL [0.015–0.12]). Median duration of tx was 8 days (3 – 28); 89% received monotherapy. Success and survival rates at 30d were 63% and 89%, respectively. Failures were due to death (2), recurrent infection (2), worse symptoms (2), and persistent bacteremia (1). Success rates for bacteremia and pneumonia were 57% and 67%, respectively. MF within 90 days occurred in 32% due to K. pneumoniae (5) or E. coli (1). MF were classified as intra-abdominal abscess (3), pneumonia (1), and respiratory (1) or urinary (1) colonization. The median time to MF was 32 days (15 – 67). M/V MICs were increased ≥8-fold against 67% (4/6) of recurrent isolates. 1 pt developed intra-abdominal infection due to M/V non-susceptible KPC-3 K. pneumoniae isolate (MIC = 8) following a 12-day of M/V; the recurrent isolate differed from the parent by an IS5 insertion in the ompK36 gene promoter. M/V was well-tolerated, 1 patient developed eosinophilia. Conclusion In this cohort of critically-ill patients with CRE infection, tx with M/V yielded outcomes comparable to prior cohorts treated with ceftazidime–avibactam. M/V non-susceptibility emerged in 1 isolate. Our findings require validation in future studies. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP)
    Kurzfassung: Necrotizing soft tissue infections (NSTIs) are life-threatening infections. The aim of this study is to evaluate the safety of clindamycin plus vancomycin versus linezolid as empiric treatment of NSTI. Methods Retrospective, single-center, quasi-experimental study of patients admitted from June 1, 2018 to June 30, 2019 (pre-intervention) and May 1, 2020 to October 15, 2021 (post-intervention). Patients who received surgical management within 24 hours of NSTI diagnosis and at least one dose of linezolid or clindamycin were included. The primary endpoint was death at 30 days. The secondary outcomes included rates of acute kidney injury (AKI) and Clostridioides difficile infection (CDI). Results 274 patients were identified by admission diagnosis code for NSTI or Fournier’s Gangrene; 164 patients met the inclusion criteria. Sixty-two matched pairs were evaluated. There was no difference in rates of 30-day mortality (8.06% vs. 6.45%, HR 1.67 95%CI (0.32, 10.73), p = 0.65). There was no difference in CDI (6.45% vs. 1.61%, HR Inf 95%CI (0.66, Inf), p = 0.07) but more AKI in the pre-intervention group (9.68% vs. 1.61%, HR 6 95% CI (0.73, 276), p = 0.05). Conclusions In this small, retrospective, single-center, quasi-experimental study, there was no difference in 30-day mortality in patients receiving treatment with clindamycin plus vancomycin versus linezolid in combination with standard gram-negative and anaerobic therapy and surgical debridement for the treatment of NSTI. A composite outcome of death, AKI, or CDI within 30 days was more common in the clindamycin plus vancomycin group.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2020-12-31), p. S663-S664
    Kurzfassung: Ceftazidime-avibactam (CAZ-AVI) is used to treat multidrug-resistant infections. There are limited pharmacokinetic (PK) data among critically-ill patients (pts) and no dosing recommendations for those receiving continuous renal replacement therapy (CRRT). Methods We conducted a PK study of CAZ-AVI among pts with and without CRRT. Serial blood samples were collected at 0 (pre-dose), 2, 4, 6, and 8 hours after CAZ-AVI administration. All doses were infused over 2h. Samples were centrifuged and plasma stored at -80°C until analysis by a Shimadzu Nexera XD UHPLC with a Shimadzu 8045 MS. Transitions were monitored in positive mode for CAZ (m/z 274.05 & lt; 80.05) and negative mode for AVI (264.00 & lt; 95.90). The assay was reproducible and linear over a range of 0.1 – 20 µg/mL for AVI and 1 – 200 µg/mL for CAZ. non-compartmental analyses were used. Results 96 plasma samples from 20 pts were included in the study. Median age was 56 years (range: 31 – 74), 55% were male, and 90% were in the ICU at the time of collection. CZA dosing regimens included 2.5g IV q 8h (n=15), 1.25g IV q 8h (n=2), 0.94g IV q 24h (n=1), and 0.94g IV q 48h (n=2). 7 pts received CRRT (median blood and dialysate flow rates were 250 mL/min and 2.5 L/h, respectively; 86% received 2.5g IV q 8h) and 2 pts received intermittent hemodialysis (iHD). Among remaining pts, median creatinine clearance (CrCl) by Cockcroft-Gault was 91ml/min (range: 37 – 168 ml/min). PK values for CAZ and AVI are shown in the Table. Individual concentration-time profiles for patients receiving 2.5g IV q 8h are shown in the Figure. For patients receiving 2.5g IV q8h, CAZ and AVI median (IQR) AUCs were 525.6 hr*µg/ml (403.2, 762.0) and 83.7 (57.3, 129.5), respectively. For those on CRRT receiving the same dose, CAZ and AVI median (IQR) AUCs were 450.2 (450.0, 558.4) and 102.4 (100.7, 142.3), respectively. CAZ pharmacodynamics (PD) targets of 100% fT & gt; 1x and 4x MIC were achieved in 90% and 55% of pts, respectively. AVI PD targets of 100% fT & gt; 1 and 2.5µg/mL were achieved in 100% and 80% of pts, respectively. Treatment-emergent adverse events were not reported in any case. Ceftazidime and avibactam pharmacokinetic parameters among critically-ill patients Conclusion Among this cohort of critically-ill pts, CAZ and AVI exposures varied; however, most pts achieved PD targeted exposures, including those patients receiving CRRT and a standard dosing regimen of 2.5g IV q 8h. Disclosures Erin K. McCreary, PharmD, Entasis (Advisor or Review Panel member)Summit (Advisor or Review Panel member) Ryan K. Shields, PharmD, MS, Allergan (Advisor or Review Panel member, Research Grant or Support)Entasis (Advisor or Review Panel member)Melinta (Research Grant or Support)Menarini (Consultant)Merck (Advisor or Review Panel member, Research Grant or Support)Shionogi (Advisor or Review Panel member, Research Grant or Support)Summit (Advisor or Review Panel member)Tetraphase (Research Grant or Support)Venatorx (Advisor or Review Panel member, Research Grant or Support)
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. 12 ( 2020-12-01)
    Kurzfassung: We report a case of multidrug-resistant Pseudomonas aeruginosa meningitis treated with ceftolozane-tazobactam with concomitant therapeutic drug monitoring of plasma and cerebral spinal fluid. The data suggest that ceftolozane-tazobactam may be an option for select central nervous system infections; however, treatment decisions should be interpreted on a case-by-case basis.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 71, No. 3 ( 2020-07-27), p. 667-671
    Kurzfassung: Twenty patients with carbapenem-resistant Enterobacteriaceae infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam–nonsusceptible, ompK36 porin mutant Klebsiella pneumoniae.
    Materialart: Online-Ressource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 2002229-3
    Standort Signatur Einschränkungen Verfügbarkeit
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