scholarly journals 1316. Pharmacokinetic/Pharmacodynamic Analyses of Cefiderocol in Critically Ill Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S669-S670
Author(s):  
Takayuki Katsube ◽  
Nao Kawaguchi ◽  
Yuko Matsunaga ◽  
Mari Ariyasu ◽  
Tsutae Den Nagata ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Clinical Cure ◽  
Drug Exposure ◽  
Survival Rates ◽  
Panel Member ◽  
Research Support ◽  
Review Panel ◽  
Gram Negative ◽  
Wide Range

Abstract Background Cefiderocol (CFDC), a novel siderophore cephalosporin, has demonstrated potent antibacterial activity against a wide range of Gram-negative bacteria including carbapenem-resistant strains. We aimed to evaluate relationships between drug exposure and outcomes in critically ill patients. Methods Sparse pharmacokinetic (PK) samples at steady state from critically ill patients with pneumonia, bloodstream infection/sepsis, or complicated urinary tract infection receiving CFDC in two Phase 3 studies were analyzed. Percent time of dosing interval of free drug concentration exceeding the minimum inhibitory concentration (MIC) in plasma and epithelial lining fluid (ELF) (%fT>MIC and %fT>MIC,ELF, respectively) were determined for 60 (CREDIBLE-CR; NCT02714595) and 97 patients (APEKS-NP; NCT03032380), using a 3-compartment population PK model. The %fT>MIC,ELF was calculated for 125 pneumonia patients based on an intrapulmonary PK model. Relationships between %fT>MIC, %fT>MIC,ELF and clinical and microbiological outcomes at test of cure (TOC), or mortality at Day 28 were assessed. Results The median (90th percentile) MICs of Gram-negative pathogens in the PK/pharmacodynamic (PD) analyses were 0.25 (4) µg/mL (CREDIBLE-CR) and 0.25 (2) µg/mL (APEKS-NP), respectively. Individual plasma %fT>MIC was 100% in ≥95% of patients in each study, and estimated %fT>MIC,ELF was 100% in 89.3% (25/28 pneumonia patients; CREDIBLE-CR) and 97.9% (95/97 pneumonia patients; APEKS-NP). Clinical cure rates and survival rates in patients with 100% fT>MIC or %fT>MIC,ELF were similar between the two studies (Table). No PK/PD relationships between %fT>MIC, %fT>MIC,ELF and clinical cure, microbiological eradication, or survival were identified in either study because high %fT>MIC or %fT>MIC,ELF was achieved in all patients. Table. Clinical cure and survival rates in patients with 100% fT>MIC or %fT>MIC,ELF in CREDIBLE-CR and APEKS-NP studies Conclusion PK/PD relationship was not identified between CFDC plasma or ELF exposure and clinical or microbiological outcomes, or mortality as high %fT>MIC and %fT>MIC,ELF were achieved, suggesting the recommended dosing regimen of 2 g q8h or renally adjusted dosage (including augmented renal clearance), infused over 3 hours, provides sufficient exposure to CFDC in critically ill patients. Disclosures Takayuki Katsube, PhD, Shionogi & Co., Ltd. (Employee) Nao Kawaguchi, BPharm, Shionogi & Co., Ltd. (Employee) Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee) Simon Portsmouth, MD, Shionogi Inc. (Employee) David Paterson, Accelerate (Speaker’s Bureau)BioMerieux (Speaker’s Bureau)BioMerieux (Advisor or Review Panel member)Entasis (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Merck (Grant/Research Support)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Shionogi & Co., Ltd. (Grant/Research Support)VenatoRx (Advisor or Review Panel member) Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Grant/Research Support)Merck (Grant/Research Support)Shionogi Inc. (Consultant) Roger Echols, MD, Shionogi Inc. (Consultant) Toshihiro Wajima, PhD, Shionogi & Co., Ltd. (Employee)

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia

2016 ◽  
Vol 32 (8) ◽  
pp. 487-493 ◽  
Author(s):  
Jessica L. Elefritz ◽  
Karri A. Bauer ◽  
Christian Jones ◽  
Julie E. Mangino ◽  
Kyle Porter ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Clinical Cure ◽  
Statistical Significance ◽  
Cohort Analysis ◽  
Kidney Injury ◽  
Multidrug Resistant ◽  
High Dose ◽  
Loading Dose ◽  
Gram Negative

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

scholarly journals 785. Distribution and Associated Mortality in Carbapenem-Resistant Gram-Negative Bacilli in Japan: A Multicenter Study From Multi-Drug Resistant Organisms Clinical Research Network (MDRnet)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S489-S490
Author(s):  
Sho Saito ◽  
Aki Sakurai ◽  
Kohei Uemura ◽  
Yasufumi Matsumara ◽  
Ryota Hase ◽  
...  
Keyword(s):  
Panel Member ◽  
Mortality Rates ◽  
Research Network ◽  
Drug Resistant ◽  
Survival Curves ◽  
Research Support ◽  
Review Panel ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Kaplan Meier

Abstract Background Carbapenem-resistant gram-negative bacilli (CRGNB) are increasingly reported around the world as a cause of serious infections. However, the epidemiology and clinical course of patients with CRGNB in Japan is not well understood. Methods We prospectively collected CR cases from 4/2019 to 9/2020 in Multi-Drug Resistant organisms clinical research network (MDRnet) consisting of 5 tertiary care facilities in Japan. We looked for all CRGNB, and all unique patients with CR Enterobacterales, CR nonfermenting gram-negative bacilli (NFGNB) and CR Aeromonas sp. isolation were included. Carbapenem resistance was tested by agar dilution method and defined based on the CLSI criteria for each species. Infections were determined by NHSN protocols. Results In total, 156 patients (30 Enterobacterales, 119 NFGNB, 7 Aeromonas spp.) were included (11 Enterobacter spp., 11 Klebsiella spp., 86 Pseudomonas aeruginosa, 29 Stenotrophomonas maltophilia, 7 Aeromonas spp.). Acinetobacter sp. was not detected. Isolation sites were sputum (n = 12) and urine (n = 7) in Enterobacterales, sputum (n = 62) and blood (n = 18) in NFGNB, and blood (n = 6) in Aeromonas spp. The median age and male ratio of the patients were 68 years [IQR: 53-74] and 19 (63.3%) in Enterobacterales, 72 years [IQR: 60-79] and 70 (58.8%) in NFGNB and 78 years [IQR: 54-83] and 2 (28.6%) in Aeromonas spp. Ten (33.3%) patients with Enterobacterales, 55 (46.2%) patients with NFGNB, and 6 (85.7%) patients with Aeromonas spp. were infected cases. The others were considered as colonized. There were no patients with ICU stay or intubation in Enterobacterales, while 5 (4.2%) and 4 (3.4%) patients were in ICU and intubated in NFGNB, and 2 patients were in ICU and intubated in Aeromonas spp., respectively. All-cause 30-day mortality rates were 10% in Enterobacterales, 16.8 % in NFGNB and 28.6% in Aeromonas spp. In the infected patients, 3 patients (30%) with Enterobacterales, 12 patients (21.8%) with NFGNB and 1 patient (16.7%) with Aeromonas spp. died within 30 days after isolation. Flow diagram outlining the characteristics of the patients and species in this study. Kaplan-Meier survival curves of patients with carbapenem resistant Enterobacterales Kaplan-Meier survival curves of patients with carbapenem resistant nonfermenting gram-negative bacilli Conclusion Mortality rates were high in infected cases of CR Enterobacterales, CR NFGNB and CR Aeromonas spp. Carbapenem-resistant Acinetobacter spp. was not detected, which differed from the CR epidemiology in Europe, the United States, and other Asian countries. Disclosures Sho Saito, n/a, Shionogi (Grant/Research Support) David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Yohei Doi, MD, PhD, AstraZeneca (Speaker's Bureau)bioMerieux (Consultant)FujiFilm (Advisor or Review Panel member, Speaker's Bureau)Gilead (Consultant)GSK (Consultant)Meiji (Consultant)MSD (Consultant)Shionogi (Consultant) Yohei Doi, MD, PhD, Astellas (Individual(s) Involved: Self): Grant/Research Support; AstraZeneca (Individual(s) Involved: Self): Speakers' bureau; bioMerieux (Individual(s) Involved: Self): Consultant, Speakers' bureau; Chugai (Individual(s) Involved: Self): Consultant; Entasis (Individual(s) Involved: Self): Consultant; FujiFilm (Individual(s) Involved: Self): Advisor or Review Panel member; Gilead (Individual(s) Involved: Self): Consultant; GSK (Individual(s) Involved: Self): Consultant; Kanto Chemical (Individual(s) Involved: Self): Grant/Research Support; MSD (Individual(s) Involved: Self): Speaking Fee; Pfizer (Individual(s) Involved: Self): Grant/Research Support; Shionogi (Individual(s) Involved: Self): Grant/Research Support, Speakers' bureau; Teijin Healthcare (Individual(s) Involved: Self): Speakers' bureau; VenatoRx (Individual(s) Involved: Self): Consultant

scholarly journals Impact of Combination Antimicrobial Therapy on Mortality Risk for Critically Ill Patients with Carbapenem-Resistant Bacteremia

2015 ◽  
Vol 59 (7) ◽  
pp. 3748-3753 ◽  
Author(s):  
Stephanie N. Bass ◽  
Seth R. Bauer ◽  
Elizabeth A. Neuner ◽  
Simon W. Lam
Keyword(s):  
Blood Culture ◽  
Combination Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Survival Rates ◽  
Gram Negative ◽  
Risk Of Death ◽  
Carbapenem Resistant ◽  
Gram Negative Bacteremia

ABSTRACTThere are limited treatment options for carbapenem-resistant Gram-negative infections. Currently, there are suggestions in the literature that combination therapy should be used, which frequently includes antibiotics to which the causative pathogen demonstratesin vitroresistance. This case-control study evaluated risk factors associated with all-cause mortality rates for critically ill patients with carbapenem-resistant Gram-negative bacteremia. Adult patients who were admitted to an intensive care unit with sepsis and a blood culture positive for Gram-negative bacteria resistant to a carbapenem were included. Patients with polymicrobial, recurrent, or breakthrough infections were excluded. Included patients were classified as survivors (controls) or nonsurvivors (cases) at 30 days after the positive blood culture. Of 302 patients screened, 168 patients were included, of whom 90 patients died (53.6% [cases]) and 78 survived (46.4% [controls]) at 30 days. More survivors received appropriate antibiotics (antibiotics within vitroactivity) than did nonsurvivors (93.6% versus 53.3%;P< 0.01). Combination therapy, defined as multiple appropriate agents given for 48 h or more, was more common among survivors than nonsurvivors (32.1% versus 7.8%;P< 0.01); however, there was no difference in multiple-agent use whenin vitroactivity was not considered (including combinations with carbapenems) (87.2% versus 80%;P= 0.21). After adjustment for baseline factors with multivariable logistic regression, combination therapy was independently associated with decreased risk of death (odds ratio, 0.19 [95% confidence interval, 0.06 to 0.56];P< 0.01). These data suggest that combination therapy with multiple agents within vitroactivity is associated with improved survival rates for critically ill patients with carbapenem-resistant Gram-negative bacteremia. However, that association is lost ifin vitroactivity is not considered.

scholarly journals 1285. Outcomes in Patients with Gram-Negative Bacteremia from Phase 2 and Phase 3 Clinical Trials of Cefiderocol, a Novel Siderophore Cephalosporin

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S658-S658
Author(s):  
David PatersonDavid PatersonMasahiro Kinoshita ◽  
Kiichiro Toyoizumi ◽  
Yuko Matsunaga ◽  
Roger Echols
Keyword(s):  
Missing Data ◽  
Clinical Studies ◽  
Drug Evaluation ◽  
Panel Member ◽  
Blood Cultures ◽  
Source Control ◽  
Sufficient Information ◽  
Research Support ◽  
Review Panel ◽  
Gram Negative

Abstract Background Cefiderocol (CFDC) is the first siderophore cephalosporin approved (US and EU) for a broad range of infections caused by Gram-negative (GN) bacteria, including carbapenem-resistant Enterobacterales (ENT) and non-fermenters (NFs). Bacteremia is a serious manifestation of GN infection and understanding how well an antibiotic works to clear the bacteremia is an important part of drug evaluation. Methods All completed clinical studies for CFDC development were used to identify patients with GN bacteremia. Information collected included the primary infection site, species identification and antibiotic susceptibility, post randomization blood cultures and clinical and bacteremia outcome. In patients with missing data (blood cultures) clinical response of cure was used to impute microbiological eradication. Indeterminate responses resulted from a combination of missing data and clinical failure, including death prior to test of cure (TOC). Results Three clinical studies randomized 900 patients (CFDC 552; comparators 348) of whom 84 (CFDC 52; comparators 32) had GN bacteremia at baseline (Table). Bacteremia rate by study was CREDIBLE-CR 25.3%, APEKS-cUTI 6.2%, APEKS-NP 6.0%. Escherichia coli (29), Klebsiella pneumoniae (23) and Acinetobacter spp (21) were most frequent species. Sources included urinary tract (31), lung (22), unknown (10), IV line (8), intraabdominal (6), or other (7). Persistence of bacteremia at TOC was seen in 2/52 (3.8%) CFDC and 2/32 (6.2%) control patients (Table), usually due to lack of source control. Clinical outcomes varied by study and infection source and were often confounded (indeterminate response). Eradication in patients with ENT at TOC was determined for 27/39 (69%) for CFDC and 16/23 (70%) for controls, and for 9/16 (56%) for CFDC and 10/11 (91%) for controls in patients with NFs, respectively. Table. Clinical and bacteremia microbiological outcomes per patient at TOC. Conclusion Post-treatment negative blood cultures were inconsistently collected, especially in APEKS-NP and -cUTI, however, negative blood cultures on therapy without recurrence was seen in 96% of CFDC patients with sufficient information. A dedicated clinical trial in GN bacteremia (GAME CHANGER; NCT03869437) is ongoing and will better delineate microbiological outcomes. Disclosures David Paterson, Accelerate (Speaker’s Bureau)BioMerieux (Speaker’s Bureau)BioMerieux (Advisor or Review Panel member)Entasis (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Merck (Grant/Research Support)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Shionogi & Co., Ltd. (Grant/Research Support)VenatoRx (Advisor or Review Panel member) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Yuko Matsunaga, MD, Shionogi Inc. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant)

β-Lactam pharmacodynamics in Gram-negative bloodstream infections in the critically ill

2019 ◽  
Author(s):  
Gloria Wong ◽  
Fabio Taccone ◽  
Paola Villois ◽  
Marc H Scheetz ◽  
Nathaniel J Rhodes ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Blood Stream Infection ◽  
Bloodstream Infections ◽  
Positive Outcome ◽  
Classification And Regression Tree ◽  
Gram Negative ◽  
Cart Analysis

Abstract Objectives To determine the β-lactam exposure associated with positive clinical outcomes for Gram-negative blood stream infection (BSI) in critically ill patients. Patients and methods Pooled data of critically ill patients with mono-microbial Gram-negative BSI treated with β-lactams were collected from two databases. Free minimum concentrations (fCmin) of aztreonam, cefepime, ceftazidime, ceftriaxone, piperacillin (co-administered with tazobactam) and meropenem were interpreted in relation to the measured MIC for targeted bacteria (fCmin/MIC). A positive clinical outcome was defined as completion of the treatment course or de-escalation, without other change of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation. Drug exposure breakpoints associated with positive clinical outcome were determined by classification and regression tree (CART) analysis. Results Data from 98 patients were included. Meropenem (46.9%) and piperacillin/tazobactam (36.7%) were the most commonly prescribed antibiotics. The most common pathogens were Escherichia coli (28.6%), Pseudomonas aeruginosa (19.4%) and Klebsiella pneumoniae (13.3%). In all patients, 87.8% and 71.4% achieved fCmin/MIC ≥1 and fCmin/MIC >5, respectively. Seventy-eight patients (79.6%) achieved positive clinical outcome. Two drug exposure breakpoints were identified: fCmin/MIC >1.3 for all β-lactams (predicted difference in positive outcome 84.5% versus 15.5%, P < 0.05) and fCmin/MIC >4.95 for meropenem, aztreonam or ceftriaxone (predicted difference in positive outcome 97.7% versus 2.3%, P < 0.05). Conclusions A β-lactam fCmin/MIC >1.3 was a significant predictor of a positive clinical outcome in critically ill patients with Gram-negative BSI and could be considered an antibiotic dosing target.

scholarly journals 1298. Population Pharmacokinetics of Ceftazidime-avibactam among Critically-ill Patients with and without Receipt of Continuous Renal Replacement Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S663-S664
Author(s):  
Ellen G Kline ◽  
Minh Hong T Nguyen ◽  
Erin K McCreary ◽  
Brett Wildfeuer ◽  
Josh Kohl ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Panel Member ◽  
Pharmacokinetic Parameters ◽  
Intermittent Hemodialysis ◽  
Review Panel ◽  
Research Grant

Abstract Background 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)

scholarly journals 1291. PROVE (Retrospective Cefiderocol Chart Review) Study of Real-World Outcomes and Safety in the Treatment of Patients with Gram-negative Bacterial Infections in the US and Europe

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S734-S735
Author(s):  
Stephen Marcella ◽  
Teena Chopra ◽  
Teena Chopra ◽  
Jose A Vazquez ◽  
Steven Smoke ◽  
...  
Keyword(s):  
Real World ◽  
Chart Review ◽  
Research Study ◽  
Panel Member ◽  
Research Support ◽  
Review Panel ◽  
Clinical Resolution ◽  
Gram Negative ◽  
Study Investigator ◽  
Review Study

Abstract Background Gram-negative bacterial resistance is a global health problem. Limited treatment options exist, especially for carbapenem resistant (CR) pathogens containing metallo-β-lactamases (MBLs) and multidrug resistant non-lactose fermenting bacteria. Cefiderocol (CFDC) retains activity against resistant strains. We describe the objectives, design, and early results of PROVE, a real world retrospective study of CFDC use. Methods PROVE is a multi-center, chart review study of CFDC use for resistant Gram-negative infections (GNI). Cases were eligible if they received ≥ 72 hrs of CFDC. Demographics, comorbidity, pathogen, infection site, and treatment course were assessed. Outcomes included all-cause 14-day and inpatient mortality and length of stay (LOS). Clinical resolution was defined by documentation that clinical signs and/or symptoms had resolved or improved without relapse. Results 24 patients who were treated with CFDC at 2 sites were included to date. Median age was 48 years (Range: 19 - 69 years); 33% were female. The most common comorbidity was diabetes (n=7, 29%). Median total ICU LOS was 36 days. Targeted treatment of documented GNI without preceding failure of prior therapy accounted for 71% of CFDC use. Empirical and salvage treatments accounted for 4% and 25% respectively (Table 1). Median time from admission to 1st CFDC dose was 21 days. Acinetobacter baumannii and Pseudomonas aeruginosa accounted for &gt; 75% of isolates (Fig.1). 92% of patients had CR isolates; &gt; 50% were respiratory. Sensitivity to CFDC was tested in 58% of which 71% were sensitive. All-cause 14-day post-CFDC mortality was 13% (95% CI: 2, 27) and overall hospital mortality 25% (95% CI: 6, 44). Clinical resolution was reached in 54% (95% CI: 33, 76). Median post-CFDC LOS was 40 days. Outcomes were stratified by key covariates (Table 2). Conclusion We present initial data for real world use of CFDC for resistant GNI. Patients were complex with multiple comorbidities, some hospitalized for long periods before their index GNI. Outcomes largely reflect this patient population. Additional data are needed to determine the optimal role of CFDC. PROVE offers an opportunity to see how CFDC is being utilized in various settings as well as a first look at key, real world outcomes. Disclosures Stephen Marcella, MD, MPH, Shionogi, Inc (Employee) Steven Smoke, PharmD, Karius (Advisor or Review Panel member)Shionogi (Scientific Research Study Investigator, Advisor or Review Panel member) Ryan K. Shields, PharmD, MS, Shionogi (Consultant, Research Grant or Support) David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member)

Follow-up blood cultures in Gram-negative bacilli bacteremia: are they needed for critically ill patients?

2020 ◽  
Vol 86 (5) ◽  
Author(s):  
Martina Spaziante ◽  
Alessandra Oliva ◽  
Giancarlo Ceccarelli ◽  
Francesco Alessandri ◽  
Francesco Pugliese ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Blood Cultures ◽  
Gram Negative

scholarly journals 1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S798-S799
Author(s):  
Nicolo Cabrera ◽  
Truc T Tran ◽  
Travis J Carlson ◽  
Faris Alnezary ◽  
William R Miller ◽  
...  
Keyword(s):  
Research Study ◽  
Clinical Success ◽  
Significant Proportion ◽  
Scientific Research ◽  
Panel Member ◽  
Multidrug Resistant ◽  
Outcome Data ◽  
Research Support ◽  
Gram Negative ◽  
Study Investigator

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited. Methods Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed. Results 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related. Conclusion We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

scholarly journals 1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S534-S535
Author(s):  
Charlotte-Paige M Rolle ◽  
Vu Nguyen ◽  
Kiran Patel ◽  
Dan Cruz ◽  
Federico Hinestrosa ◽  
...  
Keyword(s):  
Older Adults ◽  
Drug Interactions ◽  
Real World ◽  
Research Study ◽  
Panel Member ◽  
Median Number ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Hiv 1

Abstract Background Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results. Methods This retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA&lt; 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA&lt; 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study. Results 306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA&lt; 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations. Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 Conclusion In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

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