Predictors of mortality and clinical characteristics among carbapenem-resistant or carbapenemase-producing Enterobacteriaceae bloodstream infections in Spanish children

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging problem in the paediatric population worldwide with high mortality rates in bloodstream infection (BSI). Objectives To evaluate predictors of 30 day mortality in CRE BSI in a paediatric cohort. Methods A retrospective observational single-centre study (December 2005–August 2018) was conducted. Cases of CRE BSI in children 0 to 16 years were included. Microbiological identification (MALDI Biotyper) and antimicrobial susceptibility testing (Vitek2® and MicroScan panel NBC44) according to EUCAST breakpoints were performed. PCR OXVIKP® was used to confirm carbapenemase genes (OXA-48, VIM, KPC, NDM). Demographic characteristics, underlying diseases, source of bacteraemia, antimicrobial therapy and outcomes were collected from medical records. Survival analysis to establish predictors of 30 day mortality was performed. Results Thirty-eight cases were included; 76.3% were hospital-acquired infections and 23.7% related to healthcare. All patients had at least one underlying comorbidity and 52.6% were recipients of an organ transplant. VIM carbapenemase was the predominant mechanism (92.1%). Previous CRE colonization or infection rate was 52.6%. Intestinal tract (26.3%) and vascular catheter (21.1%) were the most common sources of infection. Crude mortality within 30 days was 18.4% (7/38); directly related 30 day mortality was 10.5%. Conditions associated with an increment in 30 day mortality were intensive care admission and inadequate empirical therapy (P < 0.05). Combination-antibiotic targeted treatment and a low meropenem MIC were not related to improved survival. Conclusions CRE BSI mortality rate is high. The most important factor related to 30 day survival in our CRE BSI cohort in children was empirical treatment that included at least one active antibiotic.

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PREDICTORS OF MORTALITY AND CLINICAL CHARACTERISTICS AMONG CARBAPENEM-RESISTANT OR CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE BLOODSTREAM INFECTION IN SPANISH CHILDREN

10.1101/2020.05.14.20097188 ◽

2020 ◽

Author(s):

Maria Fatima Ara Montojo ◽

Luis Escosa Garcia ◽

Marina Alguacil ◽

Nieves Seara ◽

Carlos Zozaya ◽

...

Keyword(s):

Bloodstream Infection ◽

Pediatric Population ◽

Empiric Therapy ◽

Carbapenem Resistant ◽

Crude Mortality ◽

Single Center Study ◽

Sources Of Infection ◽

Underlying Diseases ◽

Hospital Acquired ◽

Carbapenem Resistant Enterobacteriaceae

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are a growing problem in pediatric population worldwide with high mortality rates (18.5-52%) in bloodstream infection (BSI). Objectives: The aim of this study is to evaluate predictors of 30-day mortality in CRE BSI in a pediatric cohort. Methods: Retrospective observational single-center study (December 2005 - August 2018) was conducted. CRE BSI in children 0 to 16 years were included. Microbiological identification (MALDI Biotyper) and antimicrobial susceptibility testing (Vitek2 and MicroScan panel NBC44) according to current EUCAST breakpoints were performed. PCR OXVIKP was used to confirm carbapenemases genes (OXA-48, VIM, KPC, NDM). Demographic characteristics, underlying diseases, source of bacteremia, antimicrobial therapy and outcomes were collected from medical records. Survival analysis to establish predictors of 30 day-mortality was performed. Results: Thirty-eight cases were included, 76.3% hospital-acquired infections and 23.7% related to healthcare. All patients had underlying comorbidity and 52.6% had received a transplant. VIM-carbapenemase was the predominant mechanism (92%). Previous CRE colonization or infection rate was 52.6%. Gut (26%) and vascular catheter (21%) were the predominant sources of infection. Crude mortality within 30 days was 18.4% (7/38); directly related 30-day mortality was 10.5%. Conditions associated with an increment in 30-day mortality were intensive care admission and inadequate empiric therapy (p<0.05). Combination antibiotic targeted treatment and a low meropenem MIC were not related to improved survival. Conclusions: CRE BSI mortality rate is high. The most important factor related to 30-day survival in our CRE BSI cohort in children was success in empiric treatment with at least one active antibiotic.

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Aminoglycosides for Treatment of Bacteremia Due to Carbapenem-Resistant Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02638-15 ◽

2016 ◽

Vol 60 (5) ◽

pp. 3187-3192 ◽

Cited By ~ 23

Author(s):

Ryan K. Shields ◽

Cornelius J. Clancy ◽

Ellen G. Press ◽

M. Hong Nguyen

Keyword(s):

Klebsiella Pneumoniae ◽

Successful Treatment ◽

Chronic Health Evaluation ◽

Apache Ii ◽

Health Evaluation ◽

Success Rates ◽

Content Type ◽

Carbapenem Resistant ◽

Sources Of Infection ◽

Underlying Diseases

ABSTRACTAminoglycoside treatment of carbapenem-resistant (CR)Klebsiella pneumoniaebacteremia was associated with a 70% rate (23/33) of 30-day survival. Successful treatment was associated with sources of bacteremia amenable to reliable aminoglycoside pharmacokinetics (P= 0.037), acute physiology and chronic health evaluation II (APACHE II) scores of <20 (P= 0.16), and nonfatal underlying diseases (P= 0.015). Success rates were 78% and 100% if ≥2 and all 3 factors were present, respectively. Clinicians may consider the use of aminoglycosides against CRK. pneumoniaebacteremia if strains are susceptible and the sources of infection are amenable to reliable pharmacokinetics.

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Healthcare-Associated Infections: Enterobacteriaceae Bloodstream Infections in the ICU Settings

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.805 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s246-s247

Author(s):

Marta KŁOS ◽

Monika Pomorska-Wesołowska ◽

Dorota Romaniszyn ◽

Agnieszka Chmielarczyk ◽

Jadwiga Wojkowska-Mach

Keyword(s):

Drug Resistance ◽

Hospital Care ◽

Empirical Therapy ◽

Bloodstream Infections ◽

High Rate ◽

Diffusion Method ◽

Resistance Testing ◽

High Level ◽

Healthcare Associated ◽

Hospital Acquired

Background: Bloodstream infections (BSIs) are one of the most frequently observed hospital-acquired infections (HAIs). Objectives: We aimed to describe the epidemiology and drug resistance of hospital-acquired Enterobacteriaceae BSIs and to check for any correlation with the type of hospital care. Methods: In 2015–2018, 333 Enterobacteriaceae isolates were collected from hospitalized internal medicine and surgical patients. The drug-resistance testing was conducted according to the EUCAST recommendations, using the disc-diffusion method to determine resistance to penicillin, cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and sulfamethoxazole with trimethoprim. Tests confirming the presence of extended-spectrum β-lactamases (ESBLs) and KPC, NDM, and OXA-48 carbapenemases were performed. We determined the minimum inhibitory concentration (MIC) values (mg/L) for selected antibiotics. To detect the resistance genes, a single PCR reaction, a multiplex PCR, and a real-time PCR were conducted. Results: The prevalence rate of Enterobacteriaceae bacilli in BSIs was 23.5%. Penicillin resistance remained at a very high level of almost 100%, with only the piperacillin-tazobactam resistance remaining at 19%–22%. The same was true for cephalosporins: the bacilli have only shown a high susceptibility to cefoperazone with sulbactam (4%–14% of them were resistant). Ciprofloxacin (53%–62%) and sulfamethoxazole with trimethoprim (48–55%) have proven highly resistant. Carbapenems were the only antibiotics with susceptibility at 98%–99%. No difference was found between the types of hospital care (surgical vs nonsurgical) and the levels of antimicrobial resistance in the studied Enterobacteriaceae isolates (Table 1). Conclusions: The high prevalence of Enterobacteriaceae bacilli in BSI is particularly worrying, as is the high rate of resistance to cephalosporins and aminoglycosides, which are often used in the empirical therapy. Unfortunately, our results indicate the need to base the empirical therapy on carbapenems.Funding: This work was supported by a grant from Jagiellonian Univerity Medical School (No. N41/DBS/000053)Disclosures: None

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Ceftobiprole Perspective: Current and Potential Future Indications

Antibiotics ◽

10.3390/antibiotics10020170 ◽

2021 ◽

Vol 10 (2) ◽

pp. 170 ◽

Cited By ~ 1

Author(s):

Tommaso Lupia ◽

Carlo Pallotto ◽

Silvia Corcione ◽

Lucio Boglione ◽

Francesco Giuseppe De Rosa

Keyword(s):

Bacterial Infections ◽

Life Experiences ◽

Real Life ◽

Empirical Therapy ◽

Bloodstream Infections ◽

Clinical Situation ◽

Community Acquired Pneumonia ◽

Severe Infections ◽

Hospital Acquired Pneumonia ◽

Hospital Acquired

Ceftobiprole combines an excellent spectrum for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) pathogens, with a low/medium MDR risk, and the β-lactams’ safety in frail patients admitted to the hospital in internal medicine wards which may be at high risk of adverse events by anti-MRSA coverage as oxazolidinones or glycopeptides. We aimed to report the available evidence regarding ceftobiprole use in pneumonia and invasive bacterial infections, shedding light on ceftobiprole stewardship. The clinical application and real-life experiences of using ceftobiprole for bloodstream infections, including infective endocarditis, are limited but nevertheless promising. In addition, extended-spectrum ceftobiprole activity, including Enterococcus faecalis, Enterobacteriaceae, and Pseudomonas aeruginosa, has theoretical advantages for use as empirical therapy in bacteremia potentially caused by a broad spectrum of microorganisms, such as catheter-related bacteremia. In the future, the desirable approach to sepsis and severe infections will be administered to patients according to their clinical situation, the intrinsic host characteristics, the susceptibility profile, and local epidemiology, while the “universal antibiotic strategy” will no longer be adequate.

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Assessment of mortality-related risk factors and effective antimicrobial regimens for the treatment of bloodstream infections caused by carbapenem-resistant Enterobacterales

10.21203/rs.3.rs-397946/v1 ◽

2021 ◽

Author(s):

Liang Chen ◽

Xiudi Han ◽

YanLi Li

Keyword(s):

Risk Factors ◽

Mortality Risk ◽

Empirical Therapy ◽

Bloodstream Infections ◽

Antimicrobial Treatment ◽

Source Control ◽

Teaching Hospitals ◽

Treatment Regimens ◽

Carbapenem Resistant ◽

Related Risk

Abstract Background Bloodstream infections (BSIs) attributable to carbapenem-resistant Enterobacterales (CRE-BSIs) are dangerous and a major cause of mortality in clinical settings. This study was therefore designed to define risk factors linked to 30-day mortality in CRE-BSI patients and to examine the relative efficacy of different antimicrobial treatment regimens in affected individuals. Methods Data pertaining to 187 CRE-BSI cases from three teaching hospitals in China collected between January 2018 and June 2020 were retrospectively analyzed. Results For the 187 analyzed patients in this study, the 30-day mortality of CRE-BSI was 41.7% (78/187). Multivariate logistic regression analyses revealed that Pitt score [odd ratio (OR) 5.313, 95% confidence interval (CI) 3.209–8.797, P < 0.001], immunocompromised status (OR 4.605, 95% CI 1.629–13.020, P = 0.004), meropenem minimum inhibitory concentration (MIC) ≥ 8 mg/L (OR 3.736, 95% CI 1.091–12.795, P = 0.036), source control of infection (OR 0.316, 95% CI 0.117–0.854, P = 0.023), and appropriate empirical therapy (OR 0.129, 95% CI 0.027–0.625, P = 0.011) were independent predictors of CRE-BSI patient 30-day mortality. After controlling for potential confounding factors, relative to ceftazidime-avibactam (CAZ-AVI) treatment, combination therapies including CAZ-AVI (OR 1.287, 95% CI 0.124–13.403, P = 0.833) were not related to any significant change in patient mortality risk, whereas 30-day mortality risk was higher for patients administered other antimicrobial regimens (OR 12.407, 95% CI 1.684–31.430, P = 0.011). When patients were treated with antimicrobial regimens not containing CAZ-AVI, combination therapy (OR 0.239, 95% CI 0.077–0.741, P = 0.013) was related to a decreased 30-day mortality risk relative to monotherapy treatment. Conclusion The mortality-related risk factors and relative antimicrobial regimen efficacy data demonstrated in this study may guide the management of CRE-BSI patients.

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Antimicrobial Resistance in Enterobacterales Bacilli Isolated from Bloodstream Infection in Surgical Patients of Polish Hospitals

International Journal of Microbiology ◽

10.1155/2021/6687148 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

M. Kłos ◽

M. Pomorska-Wesołowska ◽

D. Romaniszyn ◽

J. Wójkowska-Mach ◽

A. Chmielarczyk

Keyword(s):

Drug Resistance ◽

Surgical Site Infection ◽

High Resistance ◽

Antimicrobial Agents ◽

Empirical Therapy ◽

Bloodstream Infections ◽

Surgical Patients ◽

Site Infection ◽

M Gene ◽

Hospital Acquired

Background and Aims. Bloodstream infections (BSIs) are one of the most frequently observed hospital-acquired infections (HAIs). We sought to describe the epidemiology and drug resistance secondary Enterobacterales BSIs in surgical patients and check for any correlation with the type of hospital ward. Materials and Methods. This multicenter (13 hospitals in southern Poland) laboratory-based retrospective study evaluated adults diagnosed with BSI secondary to surgical site infection (SSI) hospitalized in 2015–2018; 121 Enterobacterales strains were collected. The drug resistance was tested according to the EUCAST recommendations. Tests confirming the presence of extended-spectrum β-lactamases (ESBLs) and bla resistance genes were carried out. The occurrence of possible clonal epidemics among K. pneumoniae strains was examined. Results. The prevalence of Enterobacterales in secondary BSI was 12.1%; the most common strains were E. coli (n = 74, 61.2%) and Klebsiella spp. (n = 33, 27.2%). High resistance involved ampicillin and ampicillin/sulbactam (92, 8–100%), fluoroquinolones (48–73%), and most cephalosporins (29–50%). Carbapenems were the antimicrobials with the susceptibility at 98%. The prevalence of ESBL strains was 37.2% (n = 45). All the ESBL strains had blaCTX-M gene, 26.7% had the blaSHV gene, and 24.4% had blaTEM gene. The diversity of Klebsiella strains was relatively high. Only 4 strains belonged to one clone. Conclusions. What is particularly worrying is the high prevalence of Enterobacterales in BSI, as well as the high resistance to antimicrobial agents often used in the empirical therapy. To improve the effectiveness of empirical treatment in surgical departments, we need to know the epidemiology of both surgical site infection and BSI, secondary to SSI. We were surprised to note high heterogeneity among K. pneumoniae strains, which was different from our previous experience.

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Epidemiology and Outcomes of Bloodstream Infections in HIV-Patients during a 13-Year Period

Microorganisms ◽

10.3390/microorganisms8081210 ◽

2020 ◽

Vol 8 (8) ◽

pp. 1210

Author(s):

E. Franceschini ◽

Antonella Santoro ◽

Marianna Menozzi ◽

Erica Bacca ◽

Claudia Venturelli ◽

...

Keyword(s):

Bloodstream Infections ◽

Mortality Rates ◽

Multidrug Resistant ◽

People Living With Hiv ◽

Coagulase Negative Staphylococci ◽

Carbapenem Resistant ◽

Distribution Family ◽

Living With Hiv ◽

Hospital Acquired ◽

Single Center Observational Study

No data on antibiotic resistance in bloodstream infection (BSI) in people living with HIV (PLWH) exist. The objective of this study was to describe BSI epidemiology in PLWH focusing on multidrug resistant (MDR) organisms. A retrospective, single-center, observational study was conducted including all positive blood isolates in PLWH from 2004 to 2017. Univariable and multivariable GEE models using binomial distribution family were created to evaluate the association between MDR and mortality risk. In total, 263 episodes (299 isolates) from 164 patients were analyzed; 126 (48%) BSI were community-acquired, 137 (52%) hospital-acquired. At diagnosis, 34.7% of the patients had virological failure, median CD4 count was 207/μL. Thirty- and 90-day mortality rates were 24.2% and 32.4%, respectively. Thirty- and 90-day mortality rates for MDR isolates were 33.3% and 46.9%, respectively (p < 0.05). Enterobacteriaceae were the most prevalent microorganisms (29.8%), followed by Coagulase-negative staphylococci (21.4%), and S. aureus (12.7%). In BSI due to MDR organisms, carbapenem-resistant K. pneumoniae and methicillin-resistant S. aureus were associated with mortality after adjustment for age, although this correlation was not confirmed after further adjustment for CD4 < 200/μL. In conclusion, BSI in PLWH is still a major problem in the combination antiretroviral treatment era and it is related to a poor viro-immunological status, posing the question of whether it should be considered as an AIDS-defining event.

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Clinical Characteristics of Bloodstream Infections Due to Ampicillin-Sulbactam-Resistant, Non-Extended- Spectrum-β-Lactamase-ProducingEscherichia coliand the Role of TEM-1 Hyperproduction

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00797-10 ◽

2010 ◽

Vol 55 (2) ◽

pp. 495-501 ◽

Cited By ~ 24

Author(s):

Rebecca I. Waltner-Toews ◽

David L. Paterson ◽

Zubair A. Qureshi ◽

Hanna E. Sidjabat ◽

Jennifer M. Adams-Haduch ◽

...

Keyword(s):

Bloodstream Infection ◽

Organ Transplant ◽

Empirical Therapy ◽

Bloodstream Infections ◽

Plasmid Copy Number ◽

Plasmid Copy ◽

Ulcer Disease ◽

E Coli ◽

Extended Spectrum ◽

High Level

ABSTRACTAmpicillin-sulbactam is commonly used as an empirical therapy for invasive infections whereEscherichia coliis a potential pathogen. We evaluated the clinical and microbiologic characteristics of bloodstream infection due toE. coli, with focus on cases that were nonsusceptible to ampicillin-sulbactam and not producing extended-spectrum β-lactamase (ESBL). Of a total of 357 unique bacteremic cases identified between 2005 and 2008, 111 (31.1%) were intermediate or resistant to ampicillin-sulbactam by disk testing. In multivariate analysis, a history of liver disease, organ transplant, peptic ulcer disease, and prior use of ampicillin-sulbactam were independent risk factors for bloodstream infection with ampicillin-sulbactam-nonsusceptibleE. coli. Among cases that received ampicillin-sulbactam as an empirical therapy, an early clinical response was observed in 65% (22/34) of susceptible cases but in only 20% (1/5) of nonsusceptible cases. Among 50 ampicillin-sulbactam-resistant isolates examined, there was no clonal relatedness and no evidence of production of inhibitor-resistant TEM (IRT). Instead, the resistance was attributed to hyperproduction of TEM-1 β-lactamase in the majority of isolates. However, promoter sequences ofblaTEM-1did not predict resistance to ampicillin-sulbactam. While the plasmid copy number did not differ between representative resistant and susceptible isolates, the relative expression ofblaTEM-1was significantly higher in two of three resistant isolates than in three susceptible isolates. These results suggest high-levelblaTEM-1expression as the predominant cause of ampicillin-sulbactam resistance and also the presence of yet-unidentified factors promoting overexpression ofblaTEM-1in these isolates.

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Assessment of mortality-related risk factors and effective antimicrobial regimens for the treatment of bloodstream infections caused by carbapenem-resistant Enterobacterales

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00698-21 ◽

2021 ◽

Author(s):

Liang Chen ◽

Xiudi Han ◽

YanLi Li ◽

Minghui Li

Keyword(s):

Risk Factors ◽

Mortality Risk ◽

Empirical Therapy ◽

Bloodstream Infections ◽

Antimicrobial Treatment ◽

Source Control ◽

Teaching Hospitals ◽

Treatment Regimens ◽

Carbapenem Resistant ◽

Related Risk

Background Bloodstream infections (BSIs) attributable to carbapenem-resistant Enterobacterales (CRE-BSIs) are dangerous and a major cause of mortality in clinical settings. This study was therefore designed to define risk factors linked to 30-day mortality in CRE-BSI patients and to examine the relative efficacy of different antimicrobial treatment regimens in affected individuals. Methods Data pertaining to 187 CRE-BSI cases from four teaching hospitals in China collected between January 2018 and December 2020 were retrospectively analyzed. Results For the 187 analyzed patients in this study, the 30-day mortality of CRE-BSI was 41.7% (78/187). Multivariate logistic regression analyses revealed that Pitt score, immunocompromised status, meropenem minimum inhibitory concentration (MIC) ≥ 8 mg/L, absence of source control of infection and appropriate empirical therapy were independent predictors of CRE-BSI patient 30-day mortality. After controlling for potential confounding factors, relative to ceftazidime-avibactam (CAZ-AVI) treatment, combination therapies including CAZ-AVI ( OR 1.287, 95% CI 0.124 - 13.403, P = 0.833) were not related to any significant change in patient mortality risk, whereas 30-day mortality risk was higher for patients administered other antimicrobial regimens ( OR 12.407, 95% CI 1.684 - 31.430, P = 0.011). When patients were treated with antimicrobial regimens not containing CAZ-AVI, combination therapy ( OR 0.239, 95% CI 0.077 - 0.741, P = 0.013) was related to a decreased 30-day mortality risk relative to monotherapy treatment. Conclusion The mortality-related risk factors and relative antimicrobial regimen efficacy data demonstrated in this study may guide the management of CRE-BSI patients.

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Risk factors and outcomes for carbapenem-resistant Klebsiella pneumoniae bacteremia in onco-hematological patients

The Journal of Infection in Developing Countries ◽

10.3855/jidc.11189 ◽

2019 ◽

Vol 13 (05) ◽

pp. 357-364 ◽

Cited By ~ 1

Author(s):

Jianling Liu ◽

Haichen Wang ◽

Ziyan Huang ◽

Xiaoyan Tao ◽

Jun Li ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Klebsiella Pneumoniae ◽

Empirical Therapy ◽

Carbapenem Resistance ◽

Bloodstream Infections ◽

Observation Study ◽

Hematological Patients ◽

Carbapenem Resistant ◽

Independent Risk Factors

Introduction: Carbapenem-resistant Klebsiella pneumoniae (KP) serves as a major threat to onco-hematological patients, resulting in great morbidity and mortality. The purpose of our study was to identify the risk factors for KP bloodstream infections (BSIs) and mortality in onco-hematological patients. Methodology: A retrospective observation study was conducted on KP BSIs in the onco-hematology departments at Xiangya hospital from January 2014 to September 2018. Multivariate analysis was employed to identify the independent risk factors for carbapenem-resistant (CR) KP BSIs and related mortality. Results: A total of 89 strains of KP were analyzed in our study, in which 20 strains were CRKP. The only risk factor for CRKP BSI was carbapenem exposure within 30 days before the onset of BSIs (HR 25.122). The 30-day mortality was 24.7%. CRKP caused more mortality than carbapenem-susceptible KP (55.0% vs 15.9%, P = 0.001). In the multivariate analysis, unresolved neutropenia (HR 16.900), diarrhea (HR 3.647) and RDW > 14% (HR 6.292) were independent risk factors for mortality, and appropriate empirical therapy (HR 0.164) was protective against mortality. Conclusions: Our findings showed that carbapenem resistance was spreading in our setting, and a precise combination of antibiotics covering the common pathogen is crucial to improving patient survival.

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