scholarly journals Risk Factors for Treatment Failure of Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections

2013 ◽  
Vol 57 (11) ◽  
pp. 5394-5397 ◽  
Author(s):  
Yanina Dubrovskaya ◽  
Ting-Yi Chen ◽  
Marco R. Scipione ◽  
Diana Esaian ◽  
Michael S. Phillips ◽  
...  
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Klebsiella Pneumoniae ◽  
Renal Insufficiency ◽  
Treatment Failure ◽  
Clinical Cure ◽  
Polymyxin B ◽  
Antimicrobial Treatment ◽  
Carbapenem Resistant

ABSTRACTPolymyxins are reserved for salvage therapy of infections caused by carbapenem-resistantKlebsiella pneumoniae(CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline,in vitrosynergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.

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

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.

Machine Learning Algorithms to Predict the Mortality of Carbapenem Resistant Klebsiella Pneumoniae bacteremia

2019 ◽  
Author(s):  
Qiqiang Liang ◽  
Fang Qian ◽  
Yibing Chen ◽  
Zhijun Xu ◽  
Zhijiang Xu ◽  
...  
Keyword(s):  
Machine Learning ◽  
Risk Factors ◽  
Septic Shock ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Severe Thrombocytopenia ◽  
Acute Renal Injury ◽  
High Risk Factors ◽  
Carbapenem Resistant ◽  
Logical Regression

Abstract Purpose To establish mortality prediction models in 14 days of Carbapenem-Resistant Klebsiella Pneumoniae bacteremia using Machine learning.Materials and Methods It is a single-center retrospective study. We collect the relevant clinical information of all patients with Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) bacteremia in the past 5 years using the local database. Data analysis and verification are carried out by multiple logical regression, decision tree, random forest, support vector machine (SVM), and XGBoost.Result This study includes 187 patients with 40 related variables. In multiple logical regression, acute renal injury (P=0.003), Apache II score (P=0.036), immunodeficiency (P=0.025), severe thrombocytopenia (P=0.025) and septic shock (P=0.044) are the high-risk factors for 14 days mortality of CRKP bloodstream infections. According to the importance of those parameters, risk scoring is established to predict the survival rate of CRKP bacteremia. The analysis of the five models, with 70% training set and 30% test set, show the comprehensive performance of random forest (AUROC=0.953, precision=91.85%) is slightly better than that of XGBoost (AUROC=0.912, precision=86.41%) and SVM (AUROC=0.936, precision=79.89%) in predicting 14-day mortality of CRKP bacteremia. The multiple logical regression model (AUROC=0.825, precision=81.52%) is the second, and the decision tree model (AUROC=0.712, precision=79.89%) is not very ideal.Conclusion Machine learning has good performances in predicting 14-day mortality of CRKP bacteremia than multiple logical regression. Acute renal injury, severe thrombocytopenia, and septic shock are the high-risk factors of CRKP bacteremia mortality.

scholarly journals Comparative Effectiveness of Aminoglycosides, Polymyxin B, and Tigecycline for Clearance of Carbapenem-Resistant Klebsiella pneumoniae from Urine

2011 ◽  
Vol 55 (12) ◽  
pp. 5893-5899 ◽  
Author(s):  
Michael J. Satlin ◽  
Christine J. Kubin ◽  
Jill S. Blumenthal ◽  
Andrew B. Cohen ◽  
E. Yoko Furuya ◽  
...  
Keyword(s):  
New York ◽  
Klebsiella Pneumoniae ◽  
Urine Culture ◽  
Active Agent ◽  
Polymyxin B ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Tract Infections

ABSTRACTCarbapenem-resistantKlebsiella pneumoniae(CRKP) is an increasingly common cause of health care-associated urinary tract infections. Antimicrobials within vitroactivity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort (n= 41), compared to 64% in the polymyxin B (P= 0.02;n= 25), 43% in the tigecycline (P< 0.001;n= 21), and 36% in the untreated (P< 0.001;n= 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10;P= 0.003), tigecycline (OR, 0.08;P= 0.001), and untreated (OR, 0.14;P= 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when activein vitro, was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.

scholarly journals In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types

2021 ◽  
Vol 12 ◽  
Author(s):  
Jocelyn Qi-Min Teo ◽  
Nazira Fauzi ◽  
Jayden Jun-Yuan Ho ◽  
Si Hui Tan ◽  
Shannon Jing-Yi Lee ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Apparent Difference ◽  
Initial Inoculum ◽  
Carbapenem Resistant ◽  
Limited Effectiveness ◽  
Sequence Types

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.

scholarly journals Efficacy of Ceftazidime-Avibactam Versus Polymyxin B and Risk Factors Affecting Clinical Outcomes in Patients With Carbapenem-Resistant Klebsiella pneumoniae Infections a Retrospective Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Fang ◽  
Hui Li ◽  
Min Zhang ◽  
Guochao Shi ◽  
Mengying Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Klebsiella Pneumoniae ◽  
Polymyxin B ◽  
Therapeutic Effects ◽  
Bacterial Eradication ◽  
Factors Affecting ◽  
Carbapenem Resistant ◽  
All Cause Mortality ◽  
Cox's Regression

Background: The worldwide outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become an urgent public health problem. High mortality and lack of effective treatments further pose new challenges to control this infection. However, studies about the evaluation of available antibiotics for CRKP infection are limited. The present study aimed to compare the efficacy of polymyxin B versus ceftazidime-avibactam (CAZ/AVI) in Chinese patients with CRKP infections and to identify risk factors affecting 7-day bacterial eradication and 28-day all-cause mortality.Methods: From January 8, 2018, to July 6, 2020, a total of 115 adult CRKP infected patients from two tertiary teaching hospitals in Shanghai, China were enrolled based on the inclusion and exclusion criteria. By reviewing electronic medical records of these patients, demographic and clinical data were extracted. The selected patients were divided into polymyxin B and CAZ/AVI groups according to primary antibiotic exposure to compare therapeutic effects. Binary logistic and cox’s regression analysis were performed to identify risk factors for 7-day bacterial eradication and all-cause mortality.Results: One hundred and five patients were treated with polymyxin B (67.8%) or CAZ/AVI (32.2%). Patients in the CAZ/AVI group had significantly lower rates of 28-day mortality (8.1 vs 29.5%, p = 0.013), higher microbiological eradication and 28-day clinical success. Multivariate analysis showed that Charlson comorbidity index (≥3) and prior antibiotic use within 90 days were independent risk factors for poor microbiological eradication. Cox’s regression analysis indicated that the length of hospitalization after CRKP infection and baseline creatinine clearance negatively affected 28-day mortality.Conclusion: CAZ/AVI was more effective than polymyxin B and appeared to be a promising drug for CRKP infection, especially for critically ill patients.

scholarly journals In Vitro Activity of Ceftazidime-Avibactam against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Fangyou Yu ◽  
Jingnan Lv ◽  
Siqiang Niu ◽  
Hong Du ◽  
Yi-Wei Tang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Experience ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Antimicrobial Treatment ◽  
In Vitro Activity ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant

ABSTRACT Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains have emerged while antimicrobial treatment options remain limited. Herein, we tested the in vitro activity of ceftazidime-avibactam and other comparator antibiotics against 65 CR-hvKp isolates. Ceftazidime-avibactam, colistin, and tigecycline are highly active in vitro against CR-hvKp isolates (MIC90, ≤1 μg/ml), including K. pneumoniae carbapenemase 2 (KPC-2)-producing ST11 CR-hvKp. On the basis of previous clinical experience and the in vitro data presented herein, we posit that ceftazidime-avibactam is a therapeutic option against CR-hvKp infections.

scholarly journals Effect of N-Acetylcysteine Administration on 30-Day Mortality in Critically Ill Patients with Septic Shock Caused by Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii: A Retrospective Case-Control Study

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 271
Author(s):  
Alessandra Oliva ◽  
Alessandro Bianchi ◽  
Alessandro Russo ◽  
Giancarlo Ceccarelli ◽  
Francesca Cancelli ◽  
...  
Keyword(s):  
Septic Shock ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Retrospective Case ◽  
Icu Patients ◽  
Saps Ii ◽  
Carbapenem Resistant ◽  
Saps Ii Score ◽  
Definitive Therapy

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab) represent important cause of severe infections in intensive care unit (ICU) patients. N-Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties, showing also in-vitro antibacterial activity. Aim was to evaluate the effect on 30-day mortality of the addition of intravenous NAC to antibiotics in ICU patients with CR-Kp or CR-Ab septic shock. A retrospective, observational case:control study (1:2) in patients with septic shock caused by CR-Kp or CR-Ab hospitalized in two different ICUs was conducted. Cases included patients receiving NAC plus antimicrobials, controls included patients not receiving NAC. Cases and controls were matched for age, SAPS II, causative agent and source of infection. No differences in age, sex, SAPS II score or time to initiate definitive therapy were observed between cases and controls. Pneumonia and bacteremia were the leading infections. Overall, mortality was 48.9% (33.3% vs. 56.7% in cases and controls, p = 0.05). Independent risk factors for mortality were not receiving NAC (p = 0.002) and CR-Ab (p = 0.034) whereas therapy with two in-vitro active antibiotics (p = 0.014) and time to initial definite therapy (p = 0.026) were protective. NAC plus antibiotics might reduce the 30-day mortality rate in ICU patients with CR-Kp and CR-Ab septic shock.

scholarly journals In Vitro Double and Triple Bactericidal Activities of Doripenem, Polymyxin B, and Rifampin against Multidrug-Resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli

2010 ◽  
Vol 54 (6) ◽  
pp. 2732-2734 ◽  
Author(s):  
Carl Urban ◽  
Noriel Mariano ◽  
James J. Rahal
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Carbapenem Resistant ◽  
Bactericidal Activities

ABSTRACT In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.

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