Clinical Outcomes Associated with Polymyxin B Dose in Patients with Bloodstream Infections Due to Carbapenem-Resistant Gram-Negative Rods

ABSTRACTThere is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been defined. The purpose of this retrospective study was to evaluate the relationship between PMB dose and clinical outcomes. We included patients with bloodstream infections (BSIs) due to carbapenem-resistant Gram-negative rods who received ≥48 h of intravenous PMB. The objective was to evaluate the association between PMB dose and 30-day mortality, clinical cure at day 7, and development of acute kidney injury (AKI). A total of 151 BSIs were included. The overall 30-day mortality was 37.8% (54 of 151), and the median PMB dosage was 1.3 mg/kg (of total body weight)/day. Receipt of PMB dosages of <1.3 mg/kg/day was significantly associated with 30-day mortality (46.5% versus 26.3%;P= 0.02), and this association persisted in multivariable analysis (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.05 to 1.81;P= 0.04). Eighty-two percent of patients who received PMB dosages of <1.3 mg/kg/day had baseline renal impairment. Clinical cure at day 7 was not significantly different between dosing groups. AKI was more common in patients receiving PMB dosages of ≥250 mg/day (66.7% versus 32.0%;P= 0.03), and this association persisted in multivariable analysis (OR = 4.32; 95% CI = 1.15 to 16.25;P= 0.03). PMB dosages of <1.3 mg/kg/day were administered primarily to patients with renal impairment, and this dosing was independently associated with 30-day mortality. However, dosages of ≥250 mg/day were independently associated with AKI. These data support the use of PMB without dose reduction in the setting of renal impairment.

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Clinical Experience with High-Dose Polymyxin B against Carbapenem-Resistant Gram-Negative Bacterial Infections—A Cohort Study

Antibiotics ◽

10.3390/antibiotics9080451 ◽

2020 ◽

Vol 9 (8) ◽

pp. 451

Author(s):

Yiying Cai ◽

Hui Leck ◽

Ray W. Tan ◽

Jocelyn Q. Teo ◽

Tze-Peng Lim ◽

...

Keyword(s):

Cohort Study ◽

Bacterial Infections ◽

Kidney Injury ◽

Polymyxin B ◽

Population Pharmacokinetic ◽

High Dose ◽

Pharmacokinetic Studies ◽

Gram Negative ◽

Carbapenem Resistant ◽

Median Daily Dose

Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340–34,884 IU/kg/day) and 14 days (IQR, 7–28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6–13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00–1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03–4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.

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165. Cefiderocol Treatment for Serious Infections Caused by Carbapenem-resistant Bacteria: Post-hoc Analysis of Outcomes by Pathogen in the CREDIBLE-CR Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.475 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S212-S212

Author(s):

Yuko Matsunaga ◽

Mari Ariyasu ◽

Miki Takemura ◽

Yoshinori Yamano ◽

Kiichiro Toyoizumi ◽

...

Keyword(s):

Clinical Cure ◽

Carbapenem Resistance ◽

Bloodstream Infections ◽

Resistant Bacteria ◽

Open Label ◽

Gram Negative ◽

Mitt Population ◽

Carbapenem Resistant ◽

Serious Infections ◽

Tract Infections

Abstract Background The efficacy and safety of cefiderocol (CFDC), a novel siderophore cephalosporin, for the treatment of serious infections due to carbapenem-resistant (CR) Gram-negative pathogens was assessed in the CREDIBLE-CR study. The current analysis evaluated clinical and microbiological outcomes by baseline CR pathogen. Methods An open-label, prospective, randomised 2:1, Phase 3 study (CREDIBLE-CR; NCT02714595) was conducted in adult patients with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, bloodstream infections or sepsis, and complicated urinary tract infections caused by CR Gram-negative pathogens. Patients received either intravenous (IV) CFDC 2g, q8h, 3-h infusion, or IV best available therapy (BAT: up to 3 drugs in combination), for 7–14 days (extendable to 21 days). Clinical and microbiological outcomes were assessed in the CR microbiological intent-to-treat (CR-MITT) population by CR pathogen, baseline MIC and by mechanism of carbapenem resistance at test of cure (TOC). Only summary statistics were collected. Results In the CR-MITT population (CFDC N=80; BAT N=38), Acinetobacter baumannii (46.3% and 44.7%), Klebsiella pneumoniae (33.8% and 31.5%), and Pseudomonas aeruginosa (15% and 26%) were the most frequent pathogens in CFDC and BAT arms, respectively. For all CR pathogens, clinical cure rates were achieved in 52.5% in the CFDC arm and 50.0% in the BAT arm at TOC; rates were similar between treatment arms by baseline CR pathogen (Table 1). Numerically higher clinical cure and microbiological outcomes were observed with CFDC for Enterobacterales (Table 1), especially against NDM-producing bacteria or those with porin-channel mutations (Table 1). CFDC MIC values ranged between ≤0.03 and 4 μg/mL, except for one pathogen (Table 2). Microbiological outcomes for CR A. baumannii, CR K. pneumoniae, and CR P. aeruginosa at TOC by baseline MICs of ≤4 μg/mL ranged between 0–40%, 0–100%, and 0–100%, respectively; at MIC ≤4 μg/mL, clinical and microbiological outcomes were equal (Table 2). Conclusion CFDC, via a novel mechanism of entry and its stability against β-lactamases, was effective against serious infections caused by CR pathogens with various resistance mechanisms or baseline MIC values. Disclosures Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee)

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Clinical and epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infections in a tertiary hospital in China

10.21203/rs.3.rs-153263/v2 ◽

2021 ◽

Author(s):

Zhiwen Cui ◽

Lirui Wang ◽

Wei Chang ◽

Minghui Li ◽

Yuexia Li ◽

...

Keyword(s):

Kidney Injury ◽

Bloodstream Infections ◽

Polymyxin B ◽

Apache Ii Score ◽

Klebsiella Pneumonia ◽

Drainage Fluid ◽

Carbapenem Resistant ◽

Significant Difference ◽

Epidemiological Characteristics ◽

Antimicrobial Regimen

Abstract Background：The infections due to carbapenem-resistant Klebsiella pneumonia (CR-KP) have become an important problem. The aim of the study is to evaluate the clinical and epidemiological characteristics of CR-KP. Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. Hemopathy, age (>60 years), tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression showed that survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B. But there was not statistically significant difference between carbapenems plus tigecycline and carbapenems plus polymyxin B. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens. Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.

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2262. Ceftazidime–Avibactam vs. Polymyxin B in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1940 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S774-S774 ◽

Cited By ~ 1

Author(s):

Jamie John ◽

Brian Nelson ◽

Nenad Macesic

Keyword(s):

Clinical Cure ◽

Bloodstream Infections ◽

Pharmacokinetic Profile ◽

Polymyxin B ◽

Development Of Resistance ◽

Carbapenem Resistant ◽

Statistical Measures ◽

Multivariable Regression ◽

Tract Infections ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Background Pharmacotherapy for carbapenem-resistant Enterobacteriaceae (CRE) infections is limited. There is a paucity of evidence to guide optimal management of CRE infections. Ceftazidime–avibactam, a novel cephalosporin/β-lactamase inhibitor, may be a reasonable alternative to colistin for CRE infections, but data on polymyxin B (PB) are lacking. Given the improved pharmacokinetic profile of PB compared with colistin, we sought to evaluate clinical and microbiological outcomes of patients treated with CAZ-AVI vs. PB for CRE infections. Methods We conducted retrospective cohort study in adult patients treated with CAZ-AVI or PB for a CRE infection between June 2010 and August 2018. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included clinical cure, microbiological cure, and development of resistance. Endpoints were analyzed using standard statistical measures. The influence of clinical variables other than antimicrobial therapy was assessed in a multivariable regression analysis. Results The study included 117 patients, with 42 patients receiving CAZ-AVI and 75 receiving PB. Respiratory and urinary tract infections were most common, occurring in 37.6% and 20.5% of patients, respectively. Bloodstream infections occurred in 45 (35.9%) patients. In the CAZ-AVI group, there were 9 deaths (21.4%), compared with 19 deaths (25.3%) in the PB group (P = 0.653). No statistically significant differences were found in clinical cure or microbiologic cure between CAZ-AVI and PB. PB was associated with a higher incidence of nephrotoxicity (19% vs. 43%; P = 0.048). After adjustment for duration of therapy, combination therapy, and initial WBC, use of PB was not an independent predictor of mortality. Conclusion No statistically significant differences between CAZ-AVI and PB were found in clinical or microbiologic outcomes in this cohort of patients treated for CRE infection. Further studies are necessary to confirm these preliminary findings to optimize clinical practice. Disclosures All authors: No reported disclosures.

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Faculty Opinions recommendation of Effect of differences in MIC values on clinical outcomes in patients with bloodstream infections caused by gram-negative organisms treated with levofloxacin.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158817.620056 ◽

2009 ◽

Author(s):

Larry Bush ◽

Maria Perez

Keyword(s):

Clinical Outcomes ◽

Bloodstream Infections ◽

Gram Negative ◽

Gram Negative Organisms

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Healthcare-Associated Laboratory-Confirmed Bloodstream Infections—Species Diversity and Resistance Mechanisms, a Four-Year Retrospective Laboratory-Based Study in the South of Poland

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052785 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2785

Author(s):

Agnieszka Chmielarczyk ◽

Monika Pomorska-Wesołowska ◽

Dorota Romaniszyn ◽

Jadwiga Wójkowska-Mach

Keyword(s):

Bloodstream Infections ◽

Diagnostic Techniques ◽

Resistance Mechanisms ◽

Infection Prevention And Control ◽

The South ◽

Coagulase Negative Staphylococci ◽

Aminoglycoside Resistance ◽

Gram Negative ◽

Maldi Tof ◽

Carbapenem Resistant

Introduction: Regardless of the country, advancements in medical care and infection prevention and control of bloodstream infections (BSIs) are an enormous burden of modern medicine. Objectives: The aim of our study was to describe the epidemiology and drug-resistance of laboratory-confirmed BSI (LC-BSIs) among adult patients of 16 hospitals in the south of Poland. Patients and methods: Data on 4218 LC-BSIs were collected between 2016–2019. The identification of the strains was performed using MALDI-TOF. Resistance mechanisms were investigated according to European Committee on Antimicrobial Susceptibility Testing, EUCAST recommendations. Results: Blood cultures were collected from 8899 patients, and LC-BSIs were confirmed in 47.4%. The prevalence of Gram-positive bacteria was 70.9%, Gram-negative 27.8% and yeast 1.4%. The most frequently isolated genus was Staphylococcus (50% of all LC-BSIs), with a domination of coagulase-negative staphylococci, while Escherichia coli (13.7%) was the most frequent Gram-negative bacterium. Over 4 years, 108 (2.6%) bacteria were isolated only once, including species from the human microbiota as well as environmental and zoonotic microorganisms. The highest methicillin resistant Staphylococcus aureus (MRSA) prevalence was in intensive care units (ICUs) (55.6%) but S. aureus with resistance to macrolides, lincosamides and streptogramins B (MLSB) in surgery was 66.7%. The highest prevalence of E. faecalis with a high-level aminoglycoside resistance (HLAR) mechanism was in ICUs, (84.6%), while E. faecium-HLAR in surgery was 83.3%. All cocci were fully glycopeptide-sensitive. Carbapenem-resistant Gram-negative bacilli were detected only in non-fermentative bacilli group, with prevalence 70% and more. Conclusions: The BSI microbiology in Polish hospitals was similar to those reported in other studies, but the prevalence of MRSA and enterococci-HLAR was higher than expected, as was the prevalence of carbapenem-resistant non-fermentative bacilli. Modern diagnostic techniques, such as MALDI-TOF, guarantee reliable diagnosis.

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Impact of empirical antibiotic regimens on mortality in neutropenic patients with bloodstream infection presenting with septic shock

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01744-21 ◽

2021 ◽

Author(s):

Mariana Chumbita ◽

Pedro Puerta-Alcalde ◽

Carlota Gudiol ◽

Nicole Garcia-Pouton ◽

Júlia Laporte-Amargós ◽

...

Keyword(s):

Risk Factors ◽

Septic Shock ◽

Kidney Injury ◽

Bloodstream Infections ◽

Gram Positive ◽

Gram Negative ◽

Neutropenic Patients ◽

Prospective Cohorts ◽

Independent Risk Factors ◽

The Impact

Objectives: We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. Methods: Multicenter retrospective study (2010-2019) of two prospective cohorts comparing BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Results: Of 1563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% vs 15%, p<0.001). Gram-negative bacilli caused 81% of episodes with septic shock; gram-positive cocci, 22%; and Candida species 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical β-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% vs 51%, p=0.002). Age >70 years (OR 2.3, 95% CI 1.2-4.7), IEAT for Candida spp. or gram-negative bacilli (OR 3.8, 1.3-11.1), acute kidney injury (OR 2.6, 1.4-4.9) and amikacin as the only active antibiotic (OR 15.2, 1.7-134.5) were independent risk factors for mortality, while combination of β-lactam and amikacin was protective (OR 0.32, 0.18-0.57). Conclusions: Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.

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Disease Severity Is an Independent Risk Factor of Mortality and Outcomes in Critically Ill Patients With Carbapenem-resistant Klebsiella Pneumoniae Bloodstream Infections: a 5-year Retrospective Analysis

10.21203/rs.3.rs-658252/v1 ◽

2021 ◽

Author(s):

Yuzhen Qiu ◽

Wen Xu ◽

Yunqi Dai ◽

Ruoming Tan ◽

Jialin Liu ◽

...

Keyword(s):

Risk Factors ◽

Septic Shock ◽

Klebsiella Pneumoniae ◽

Critically Ill Patients ◽

Bloodstream Infections ◽

Polymyxin B ◽

Mortality Rates ◽

Carbapenem Resistant ◽

All Cause Mortality ◽

Independent Risk Factors

Abstract Background: Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are associated with high morbidity and mortality rates, especially in critically ill patients. Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment.Methods: We retrospectively analyzed 87 patients with CRKP-BSIs (between July 2016 and June 2020) to identify the independent risk factors for 28-day all-cause mortality. The therapeutic efficacies of tigecycline-and polymyxin B-based therapies were analyzed.Results: The 28-day all-cause mortality and in-hospital mortality rates were 52.87% and 67.82%, respectively, arising predominantly from intra-abdominal (56.32%) and respiratory tract infections (21.84%). A multivariate analysis showed that 28-day all-cause mortality was independently associated with the patient’s APACHE II score (p = 0.002) and presence of septic shock at BSI onset (p = 0.006). All-cause mortality was not significantly different between patients receiving tigecycline- or polymyxin B-based therapy (55.81% vs. 53.85%, p = 0.873), and between subgroups mortality rates were also similar. Conclusions: Critical illness indicators (APACHE II scores and presence of septic shock at BSI onset) were independent risk factors for 28-day all-cause mortality. There was no significant difference between tigecycline- and polymyxin B-based therapy outcomes. Prompt and appropriate infection control should be implemented to prevent CRKP infections.

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Clinical Characteristics of Carbapenem-Resistant Klebsiella Pneumoniaee Infections In A Tertiary Hospital In China

10.21203/rs.3.rs-636758/v1 ◽

2021 ◽

Author(s):

Zhiwen Cui ◽

Lirui Wang ◽

Wei Chang ◽

Minghui Li ◽

Yuexia Li ◽

...

Keyword(s):

Survival Time ◽

Sofa Score ◽

Clinical Characteristics ◽

Bloodstream Infections ◽

Polymyxin B ◽

Apache Ii ◽

Apache Ii Score ◽

Drainage Fluid ◽

Carbapenem Resistant ◽

Antimicrobial Regimen

Abstract Background：The infections due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) have become an important problem. The aim of the study is to evaluate the clinical characteristics of CR-KP.Methods: A retrospective cohort study has been made on all patients presenting with CR-KP infections. 615 patients with CR-KP humor infections diagnosed were identified. 135 patients who did not meet the requirements were excluded. Clinical characteristics, antimicrobial regimens, and outcomes of patients have been analyzed.Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. Logistics regression analysis showed that hemopathy, age (>60 years), solid tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression was performed in APACHE II score, SOFA score, lymphocyte absolute value (LYM) and survival time. Survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. Finally, we investigated different antimicrobial regimens for CR-KP infections. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens.Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.

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