Clinical Characteristics and Associated Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bloodstream Infection
by
, , , , , and
Jin Young Ahn
1,†, 
Sang Min Ahn
1,†,
Jung Ho Kim
1,
Su Jin Jeong
1,
Nam Su Ku
1,
Jun Yong Choi
1,
Joon Sup Yeom
1 and
Je Eun Song
2,* 1
Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
2
Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang 10380, Republic of Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Microorganisms 2023, 11(5), 1121; https://doi.org/10.3390/microorganisms11051121
Submission received: 30 March 2023
/
Revised: 24 April 2023
/
Accepted: 24 April 2023
/
Published: 25 April 2023
(This article belongs to the Special Issue Bacterial Pathogens Associated with Bacteremia)
Abstract
:Background: Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae (CRE) significantly influences patient morbidity and mortality. We aimed to identify the characteristics, outcomes, and risk factors of mortality in adult patients with CRE bacteremia and elucidate the differences between carbapenemase-producing (CP)-CRE BSI and non-CP-CRE BSI. Methods: This retrospective study included 147 patients who developed CRE BSI between January 2016 and January 2019 at a large tertiary care hospital in South Korea. The patient demographic characteristics and clinical and microbiological data including the Enterobacteriaceae species and carbapenemase type were obtained and analyzed. Results: Klebsiella pneumoniae was the most commonly detected pathogen (80.3%), followed by Escherichia coli (15.0%). In total, 128 (87.1%) isolates were found to express carbapenemase, and most CP-CRE isolates harbored blaKPC. The 14-day and 30-day mortality rates for CRE BSI were 34.0% and 42.2%, respectively. Higher body mass index (odds ratio (OR), 1.123; 95% confidence interval (CI), 1.012–1.246; p = 0.029), higher sequential organ failure assessment (SOFA) score (OR, 1.206; 95% CI, 1.073–1.356; p = 0.002), and previous antibiotic use (OR, 0.163; 95% CI, 0.028–0.933; p = 0.042) were independent risk factors for the 14-day mortality. A high SOFA score (OR, 1.208; 95% CI; 1.081–0.349; p = 0.001) was the only independent risk factor for 30-day mortality. Carbapenemase production and appropriate antibiotic treatment were not associated with high 14- or 30-day mortality rates. Conclusions: Mortality from CRE BSI was related to the severity of the infection rather than to carbapenemase production or antibiotic treatment, showing that efforts to prevent CRE acquisition rather than treatment following CRE BSI detection would be more effective at reducing mortality.
1. Introduction
Enterobacteriaceae are causative organisms of approximately 30% of healthcare-associated infections [1]. Recently, increased multidrug resistance of Enterobacteriaceae to carbapenems has become a worldwide concern [2,3,4,5]. In Korea, multidrug-resistant organisms, including Enterobacteriaceae, pose a tremendous clinical and economic burden [6,7]. Although the rate of carbapenem resistance in bloodstream infections (BSIs) caused by Enterobacteriaceae is low (1.2% for Klebsiella pneumoniae (KPN)), the rate of carbapenem resistance in hospital-acquired BSIs is high; this value can reach up to 4.3% in patients treated in intensive care units (ICUs) [8]. Particularly, BSIs caused by carbapenem-resistant Enterobacteriaceae (CRE) significantly impact patient morbidity and mortality [9,10]. A study conducted in Israel found that a longer length of hospital stay increased the rate of antimicrobial-resistant Gram-negative bacteria in BSI and was associated with higher mortality rates [11]. CRE are classified into carbapenemase-producing CRE (CP-CRE) and non-carbapenemase-producing CRE (non-CP-CRE) based on the mechanism underlying the acquisition of carbapenem resistance. However, there is a lack of studies comparing the characteristics and outcomes between CP-CRE BSI and non-CP-CRE BSI. Furthermore, there is a scarcity of information about management strategies and antibiotic treatment [12].
Furthermore, the resistance of CRE to most other classes of antibiotics in addition to carbapenems has severely limited treatment options. Despite attempts to use various antibiotic combinations and the development of new antibiotics to treat CRE infections, a consensus has not been reached on the optimal treatment regimen. Therefore, identifying the risk factors for mortality in patient management is imperative to identify high-risk patients. Understanding the burden of antimicrobial resistance and identifying and targeting the pathogen is important [13]. Moreover, management strategies for CRE, which include patient isolation, vary across countries based on epidemiology and resistance patterns, and research on the characteristics and prognosis of CRE-induced BSI in Korea is lacking.
Therefore, we aimed to identify the characteristics and outcomes of patients with CRE BSI and elucidate the risk factors for mortality in adult patients with CRE BSI. We also investigated whether the clinical characteristics and prognosis differ between CP-CRE BSI and non-CP-CRE BSI.
2. Methods
2.1. Study Design and Population
This was a retrospective observational cohort study performed in Seoul, Korea, at a 2500-bed tertiary care multi-specialty university hospital with a 105-bed ICU. The patients included in this study were older than 18 years (mean age 61.79 years) and hospitalized with CRE BSI between January 2016 and January 2019. In total, 147 patients were inducted in this study (36, 47, 59, and 5 in 2016, 2017, 2018, and 2019, respectively). The microbiological data from blood culture samples were obtained retrospectively from the laboratory information system records for the specified period. All the patients were included for analysis only once, at their first CRE isolation, although CRE was isolated from some patients multiple times during the study period. This study was approved by the institutional review board of the Yonsei University Health System Clinical Trials Center, and the protocol adhered to the tenets of the Declaration of Helsinki. Since the study was retrospective and the study participants were anonymized, the institutional review board waived the requirement for written consent from the patients.
2.2. Data Collection and Parameter Definition
The collected data included patient demographic characteristics such as age, sex, and body mass index (BMI). The clinical and microbiological variables for which data were collected included vital signs, underlying disease, route of infection, the severity of illness (classified using the sequential organ failure assessment (SOFA) score and Pitt bacteremia score), duration from admission to BSI diagnosis, previous antibiotic use, antimicrobial therapy regimen to treat the CRE infection, isolated pathogens, the presence and the type of carbapenemase of the bacterial isolate, and the antimicrobial susceptibility of the bacterial isolate.
CRE BSI was defined as the presence of CRE in one or more blood cultures. BSI diagnosis was defined as the date of the first blood culture test that isolated CRE. Antimicrobial susceptibility tests were performed based on standard guidelines provided by the Clinical and Laboratory Standard Institute (CLSI) in M100-S25 [14]. Based on minimum inhibitory concentration (MIC) values, we defined CRE as isolates with MIC values ≥4 µg/mL for doripenem, imipenem, meropenem, and ≥2 µg/mL for ertapenem. If the Enterobacteriaceae isolate was resistant to carbapenem, we performed the modified Hodge test (MHT) and designated it as CP-CRE when the isolate with positive MHT had any carbapenemase gene in the multiplex PCR. CP-CRE were defined as CRE isolates that produced any carbapenemase including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), GES, Verona integron-encoded metallo-β-lactamase (VIM), or oxacillinase (OXA)-48-like (OXA-48).
Comorbidities were defined according to the International Classification of Diseases, 10th Revision. The primary focus of the BSI was classified according to the Centers for Disease Control and Prevention/National Healthcare Safety Network surveillance criteria [15]. Neutropenia was defined as an absolute neutrophil count of >500 cells/μL. Corticosteroid use was noted only if the patient had recently received 30 mg of prednisone daily for at least 7 days or 20 mg/day for 14 days in the previous 30 days. Receipt of immunosuppressants was defined as the use of any immunosuppressive drug (e.g., cyclosporine or antineoplastic chemotherapy) in the previous 30 days. Previous exposure to various antibiotic agents was also noted. Exposure to a specific antimicrobial agent was considered significant in our analysis only if it had been administered for at least three consecutive days within a month before the CRE BSI onset. Antimicrobial therapy was considered appropriate if the causative microorganisms were susceptible to at least one of the administered antimicrobial agents after the identification of Gram-negative organisms in the blood culture. Exposure to various risk factors was taken into consideration for the analysis only if it had occurred before the development of the CRE BSI.
2.3. Statistical Analysis
The primary and secondary endpoints were all-cause 14- and 30-day mortality rates, respectively. SPSS (version 25.0; IBM Corporation, Armonk, NY, USA) was used for all the statistical analyses. Categorical variables were analyzed using the chi-squared test or Fisher’s exact test. Continuous variables were analyzed using an independent samples t-test or a Mann–Whitney U test. Logistic regression analysis was used to assess the effect of independent variables on the risk. A two-tailed p-value <0.05 was considered significant. All variables with p-values <0.05 in the univariate analysis were included in the multiple logistic regression models that were used to identify the risk factors for mortality after the CRE BSI onset.
3. Results
3.1. Clinical Characteristics of CRE Bloodstream Infections
The demographic and clinical characteristics of the patients with CRE BSI are shown in Table 1. The mean age was 61.79 years and 60.5% (89/147) of patients were male. The median duration from admission to BSI diagnosis was 18 days (interquartile range (IQR), 5–57 days), and 42% (46/147) of the patients had a condition requiring their admission to the ICU at the time of CRE BSI diagnosis. Most CRE BSI cases were due to CP-CRE (87.1%, 128/147); however, 12.9% (19/147) were due to non-CP-CRE. Pneumonia (31.3%) and catheter-related BSI (27.9%) were the most common sources of infection. The mean SOFA score at the time of BSI diagnosis was 5.74 ± 4.31, and the mean Pitt bacteremia score was 2.19 ± 2.27. Most patients (83%) were previously exposed to broad-spectrum antibiotics and 45.6% had a history of carbapenem use. KPN was the most common pathogen (80.3%, 118/147), followed by Escherichia coli (15.0%, 22/147) and Enterobacter sp. (6.1%, 9/147). Most of the CP-CRE isolates harbored blaKPC (87.5%, 112/128), followed by blaNDM (10.9%, 14/128). The 14-day and 30-day mortality rates for the CRE BSI were 34.0% (50/147) and 42.2% (62/147), respectively.
3.2. CP-CRE and Non-CP-CRE Bloodstream Infections
The baseline characteristics of the patients such as age, sex, and BMI did not differ significantly between the CP-CRE BSI and non-CP-CRE BSI groups (Table 1). Similarly, the time of BSI diagnosis during hospitalization, predisposing factors, or severity of BSI did not significantly differ between the two groups. However, catheter-related BSIs were significantly more common in the non-CP-CRE BSI group than in the CP-CRE BSI group (63.2%, 12/19 vs. 22.7%, 29/128) (p < 0.001). Pneumonia tended to be more common in the CP-CRE BSI group (although the difference was not significant), and the number of patients with underlying chronic lung disease was significantly higher in the CP-CRE BSI group (p = 0.025). The number of patients with prior carbapenem use was high in the CP-CRE BSI group (p = 0.08), although the difference was not statistically significant. The proportion of BSIs due to KPN was significantly high in the CP-CRE BSI group (85.2% (109/128) vs. 47.4% (9/19)) (p < 0.001).
Table 2 shows the distribution of the MICs of carbapenems and aminoglycosides for the isolated CRE. The proportion of CRE isolates with ertapenem MIC ≥8 µg/mL and meropenem/imipenem MIC ≥16 µg/mL was significantly higher in the CP-CRE BSI group than in the non-CP-CRE BSI group (91.2% vs. 57.9%, p < 0.001 for ertapenem and 83.1% vs. 7.7%, p < 0.001 for meropenem/imipenem). In the non-CP-CRE BSI group, 61.5% of the isolates were susceptible (MIC ≤ 1) to meropenem or imipenem, and 30.8% were not susceptible but had a meropenem/imipenem MIC <8 µg/mL, which was lower than that observed in the CP-CRE BSI group. The CP-CRE BSI group also had a significantly higher proportion of gentamicin-resistant isolates compared to the non-CP-CRE BSI group (75.0% vs. 16.7%, p < 0.001).
3.3. Associated Factors for 14- and 30-Day Mortality in CRE Bloodstream Infections
The factors associated with mortality in CRE BSI are presented in Table 3 and Table 4. Univariate analysis showed that patients who died within 14 days of CRE BSI diagnosis had a higher BMI (p = 0.003), higher rate of prophylactic antibiotic use (p = 0.020), higher presence of shock (p < 0.001), acute kidney injury (p = 0.012), higher SOFA score (p < 0.001), higher Pitt bacteremia score (p < 0.001), and a higher rate of previous antibiotic use (p = 0.037) than the survivors did (Table 3). The mean BMI was 22.15 ± 4.48 kg/m2, but the number of patients with a BMI > 25 kg/m2 was higher among the non-survivors than among the survivors (38.0% vs. 17.5%) (p = 0.006). Furthermore, 9 out of the 10 patients with a BMI > 30 kg/m2 were in the non-survivor group (p < 0.001). Multivariate logistic regression analysis showed that higher BMI (odds ratio (OR), 1.123; 95% CI, 1.012–1.246; p = 0.029), higher SOFA score (OR, 1.206; 95% CI, 1.073–1.356; p = 0.002), and previous antibiotic use (OR, 0.163; 95% CI, 0.028–0.933; p = 0.042) were independently associated with the 14-day mortality in CRE BSI (Table 3).
Univariate analysis showed that patients who died within 30 days of a CRE BSI diagnosis had higher BMI (p = 0.003), higher rates of presence of shock (p < 0.001) and acute kidney injury (p = 0.002), higher SOFA score (p < 0.001), higher Pitt bacteremia score (p < 0.001), and a higher rate of previous antibiotic use (p =0.043) and were more likely to have a urinary tract infection as a source of infection (p = 0.026) compared to the survivors (Table 3). In contrast, multivariate logistic regression analysis showed that only a higher SOFA score (OR, 1.208; 95% CI, 1.081–1.349; p = 0.001) was an independent risk factor for 30-day mortality (Table 4). Interestingly, carbapenemase production, carbapenemase genotype, isolated pathogen, use of specific antibiotics for CRE, and appropriate antibiotic use did not show statistically significant correlations with the 14- or 30-day mortality.
4. Discussion
Carbapenem-resistant Gram-negative organisms, including CRE, CR Pseudomonas aeruginosa (CRPA), and CR Acinetobacter baumannii (CRAB), pose a major global threat in the 21st century [16,17]. A 2021 study by Hovan et al. involving 155 patients with CRE BSI showed that KPN accounted for the highest proportion of cases (46.6%, 69/146) with KPC being the predominant carbapenemase in the CP-CRE group (92%, 81/88) [18]. According to a nationwide epidemiological study in Korea, the most frequent causative agents of BSI was KPN (69%), followed by Enterobacter sp. (10%) and E. coli (8%) [14]. Non-CP-CRE tends to occur sporadically owing to antibiotic selection pressure, whereas the plasmid-associated horizontal spread of CP-CRE within hospitals has also been reported [19,20,21]. In this study, most of the CP-CRE BSI cases were caused by KPC-producing KPN (85.2%, 109/128), whereas KPN accounted for 47% (9/19) of the non-CP-CRE BSI cases. This suggests that most CRE BSI cases in the hospital where this study was conducted may have been caused by the in-hospital transmission of CPE, leading to colonization. Further studies are required to confirm this conclusion including whole-genome sequencing of the CPE strains to determine the clonality. Furthermore, various diagnostic methods are being investigated for the rapid diagnosis of multidrug-resistant organisms, which plays an important role in preventing transmission [22,23,24,25].
A meta-analysis by Falagas et al. showed that the mortality attributed to CRE infection varied from 26 to 44%, and the mortality rate was higher in CRE-infected patients than in carbapenem-susceptible Enterobacteriaceae (CSE)-infected patients (relative ratio (RR), 2.05, 95% confidence interval (CI), 1.56–2.69) [26]. A case-control study by Zarkotou et al. showed that infection mortality was 34%. Older age, APACHE II score at infection onset, and inappropriate antibiotic treatment were independent predictors of mortality. [27]. In this study, the 30-day mortality rate was >40% and was significantly related to the severity of infection at the time of the BSI (measured using the SOFA score and Pitt bacteremia score), and mortality. However, the 14-day and 30-day mortality rates were not significantly associated with appropriate antibiotic use. Of the 50 patients who died within 14 days, 34% (17/40) died within 3 days because of severe sepsis, making it difficult to assess the effectiveness of antibiotics in these cases. Nevertheless, no significant difference was observed between the survivors and non-survivors with regard to the use of amikacin, colistin, or combination therapy with colistin and carbapenem. The percentage of broad-spectrum antibiotics administered before the onset of infection was significantly higher in the mortality group. This suggests that in critically ill patients with a long history of broad-spectrum antibiotic use, CRE BSI developed into a breakthrough BSI that could not be improved with susceptible antibiotics alone. The presence of difficult-to-treat resistance, defined as resistance to all first-line antibiotics in Gram-negative BSI, is associated with decreased survival rates because of the challenge of finding an effective antibiotic to treat it [28]. Clinicians are prescribing a wide range of treatment regimens in their current practice with no proven efficacy and potential side effects, as available studies do not provide clear recommendations on the type and number of agents to be used in combination [29]. Furthermore, the recommended antibiotics for treating KPC-producing CP-CRE BSI such as ceftazidime-avibactam or cefiderocol [30,31] are not available in Korea. In another Korean study dealing with CRPA and CRAB BSI, carbapenem resistance was an independent risk factor for treatment failure regardless of the appropriateness of empiric antibiotics [32]. Caution is needed when Korean national studies conclude that appropriate antibiotic use is not associated with reduced mortality.
In this study, there was no significant difference between the CP-CRE group and the non-CP-CRE group, except for catheter-related BSIs as the source of infection and underlying lung disease. The non-CP-CRE group showed a diverse range of strains, suggesting that there was no clonal spread and that the infection occurred sporadically, unlike the CP-CRE group. In this study, we observed a significant difference between the groups in the MIC values of carbapenem, with the CP-CRE BSI group showing higher MIC values. These findings are consistent with that of a study by Tamma et al., which reported that CP-CRE pathogens are more likely to have meropenem MICs of ≥16 μg/mL than non-CP-CRE isolates (38% vs. 2%), thus contributing to higher mortality in the CP-CRE BSI group compared to that of the non-CP-CRE BSI group [33]. In a study of CRPA infections by Reyes et al., patients with CP-CRPA infections had higher 30-day mortality than those with non-CP-CRPA infections [34]. However, in this study, we did not observe any differences in mortality between the patients with CP-CRE BSI and non-CP-CRE BSI. This finding is consistent with the fact that the use of susceptible antibiotics at this hospital was not significantly associated with mortality. A Korean study in 2020 also found no significant difference in the 14-day mortality between CP-CRE BSI and non-CP-CRE BSI. These conflicting results highlight the need for further research to develop effective treatment strategies for CRE infection.
In our study, higher BMI was an independent risk factor for 14-day mortality. Obesity has been associated with an increased risk of nosocomial infection and sepsis events [35,36]. However, information on the impact of obesity on the outcomes of patients with sepsis is lacking. Obese patients may have insufficient blood antibiotic concentrations or fluid resuscitation compared to patients with a normal BMI [37]. In our study, the mean BMI was < 25 kg/m2 but the number of patients with BMI > 25 kg/m2 was higher among the non-survivors than among the survivors (38% vs. 17.5%) (p = 0.006). Moreover, 90% (1/9) of the patients with a BMI > 30 kg/m2 were in the non-survivor group (p < 0.001).
This study has several limitations, such as the relatively short study period, a limited number of CRE BSI cases, and retrospective design, which may have introduced bias or confounding factors. One of the fundamental limitations of retrospective studies is the inability to accurately determine whether the identified microorganisms are true pathogens. To minimize this bias, our study focused only on BSIs. Additionally, we did not perform a phylogenetic analysis to identify the clonality of the CP-CRE isolates in this study. Despite these limitations, we have analyzed the clinical characteristics and prognostic differences between the CP-CRE and non-CP-CRE isolates, focusing on clinically significant infections that cause BSI. Furthermore, the diversity of the patient population contributes to the generalizability of our findings. Additionally, we have emphasized the importance of infection control measures to prevent CRE acquisition and the need for further research to identify effective prevention strategies. Given the high mortality rate of CRE BSI and the difficulty in improving prognosis through antibiotic treatment alone, our findings provide valuable information for clinical management.
In conclusion, most of the CRE BSIs reported in this study were due to CP-CRE. However, the mortality due to CRE BSIs was not significantly associated with carbapenemase production or the antibiotic treatment regimen but rather with the severity of the infection. Therefore, infection control efforts to prevent CRE acquisition would be a more cost-effective approach to reducing patient mortality.
Author Contributions
All the authors contributed to the preparation of this manuscript, including its review and editing, and have approved the final version for submission. All the authors had full access to all the data in the study and were responsible for the decision to submit the manuscript for publication. Conceptualization, J.Y.A. and J.E.S. Data curation, J.Y.A. Formal analysis, J.Y.A., J.H.K., J.Y.C. and J.S.Y. Validation, S.J.J. and N.S.K. Writing—original draft, S.M.A. and J.E.S. Writing—review and editing, J.E.S. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was approved by the Institutional Review Board of Severance Hospital and the requirement for written informed consent was waived.
Informed Consent Statement
Not applicable.
Data Availability Statement
Data will be available upon justified request.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Sikora, A.; Zahra, F. Nosocomial Infections. In StatPearls; StatPearls Publishing LLC.: Treasure Island, FL, USA, 2021. [Google Scholar]
- Sligl, W.I.; Dragan, T.; Smith, S.W. Nosocomial Gram-negative bacteremia in intensive care: Epidemiology, antimicrobial susceptibilities, and outcomes. Int. J. Infect. Dis. 2015, 37, 129–134. [Google Scholar] [CrossRef] [PubMed]
- Jean, S.S.; Harnod, D.; Hsueh, P.R. Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front. Cell Infect. Microbiol. 2022, 12, 823684. [Google Scholar] [CrossRef]
- Zhang, Z.; Sun, Z.; Tian, L. Antimicrobial Resistance Among Pathogens Causing Bloodstream Infections: A Multicenter Surveillance Report Over 20 Years (1998–2017). Infect. Drug Resist. 2022, 15, 249–260. [Google Scholar] [CrossRef] [PubMed]
- Marimuthu, K.; Venkatachalam, I.; Khong, W.X.; Koh, T.H.; Cherng, B.P.Z.; Van La, M.; De, P.P.; Krishnan, P.U.; Tan, T.Y.; Choon, R.F.K.; et al. Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore. Clin. Infect. Dis. 2017, 64 (Suppl. S2), S68–S75. [Google Scholar] [CrossRef] [PubMed]
- Seo, H.; Lee, S.C.; Chung, H.; Ra, S.H.; Sung, H.; Kim, M.N.; Jung, J.; Kim, S.-H.; Lee, S.-O.; Choi, S.-H.; et al. Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia. Int. J. Antimicrob. Agents 2020, 56, 106126. [Google Scholar] [CrossRef]
- Song, K.H.; Kim, C.J.; Choi, N.K.; Ahn, J.; Choe, P.G.; Park, W.B.; Kim, N.J.; Choi, H.J.; Bae, J.Y.; Kim, E.S.; et al. Clinical and economic burden of bacteremia due to multidrug-resistant organisms in Korea: A prospective case control study. J. Glob. Antimicrob. Resist. 2022, 31, 379–385. [Google Scholar] [CrossRef]
- Kim, D.; Yoon, E.J.; Hong, J.S.; Choi, M.H.; Kim, H.S.; Kim, Y.R.; Uh, Y.; Shin, K.S.; Shin, J.H.; Park, J.S.; et al. Major Bloodstream Infection-Causing Bacterial Pathogens and Their Antimicrobial Resistance in South Korea, 2017–2019: Phase I Report from Kor-GLASS. Front. Microbiol. 2021, 12, 799084. [Google Scholar] [CrossRef]
- Satlin, M.J.; Chen, L.; Patel, G.; Gomez-Simmonds, A.; Weston, G.; Kim, A.C.; Seo, S.K.; Rosenthal, M.E.; Sperber, S.J.; Jenkins, S.G.; et al. Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States. Antimicrob. Agents Chemother. 2017, 61, e02349-16. [Google Scholar] [CrossRef]
- Xu, L.; Sun, X.; Ma, X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann. Clin. Microbiol. Antimicrob. 2017, 16, 18. [Google Scholar] [CrossRef]
- Nutman, A.; Wullfhart, L.; Temkin, E.; Feldman, S.F.; Schechner, V.; Schwaber, M.J.; Carmeli, Y. Hospital-Onset Bloodstream Infections Caused by Eight Sentinel Bacteria: A Nationwide Study in Israel, 2018–2019. Microorganisms 2022, 10, 1009. [Google Scholar] [CrossRef]
- Zhu, J.; Li, Q.; Li, X.; Kang, J.; Song, Y.; Song, J.; Yin, D.; Duan, J. Successful control of the first carbapenem-resistant Klebsiella pneumoniae outbreak in a Chinese hospital 2017–2019. Antimicrob. Resist. Infect. Control 2020, 9, 91. [Google Scholar] [CrossRef] [PubMed]
- Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022, 399, 629–655. [CrossRef] [PubMed]
- Patel, J.B. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement; Document M100-S25; Clinical and Laboratory Standard Institute: Wayne, NY, USA, 2015. [Google Scholar]
- Horan, T.C.; Andrus, M.; Dudeck, M.A. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am. J. Infect. Control 2008, 36, 309–332. [Google Scholar] [CrossRef] [PubMed]
- Falcone, M.; Tiseo, G.; Carbonara, S.; Marino, A.; Di Caprio, G.; Carretta, A.; Mularoni, A.; Mariani, M.F.; Maraolo, A.E.; Scotto, R.; et al. Mortality attributable to bloodstream infections caused by different carbapenem-resistant Gram negative bacilli: Results from a nationwide study in Italy (ALARICO Network). Clin. Infect. Dis. 2023, ciad100. [Google Scholar] [CrossRef] [PubMed]
- Pogue, J.M.; Zhou, Y.; Kanakamedala, H.; Cai, B. Burden of illness in carbapenem-resistant Acinetobacter baumannii infections in US hospitals between 2014 and 2019. BMC Infect. Dis. 2022, 22, 36. [Google Scholar] [CrossRef]
- Hovan, M.R.; Narayanan, N.; Cedarbaum, V.; Bhowmick, T.; Kirn, T.J. Comparing mortality in patients with carbapenemase-producing carbapenem resistant Enterobacterales and non-carbapenemase-producing carbapenem resistant Enterobacterales bacteremia. Diagn. Microbiol. Infect. Dis. 2021, 101, 115505. [Google Scholar] [CrossRef] [PubMed]
- Navon-Venezia, S.; Chmelnitsky, I.; Leavitt, A.; Schwaber, M.J.; Schwartz, D.; Carmeli, Y. Plasmid-mediated imipenem-hydrolyzing enzyme KPC-2 among multiple carbapenem-resistant Escherichia coli clones in Israel. Antimicrob. Agents Chemother. 2006, 50, 3098–3101. [Google Scholar] [CrossRef]
- Bratu, S.; Brooks, S.; Burney, S.; Kochar, S.; Gupta, J.; Landman, D.; Quale, J. Detection and spread of Escherichia coli possessing the plasmid-borne carbapenemase KPC-2 in Brooklyn, New York. Clin. Infect. Dis. 2007, 44, 972–975. [Google Scholar] [CrossRef]
- Hossain, A.; Ferraro, M.J.; Pino, R.M.; Dew, R.B., 3rd; Moland, E.S.; Lockhart, T.J.; Thomson, K.S.; Goering, R.V.; Hanson, N.D. Plasmid-mediated carbapenem-hydrolyzing enzyme KPC-2 in an Enterobacter sp. Antimicrob. Agents Chemother. 2004, 48, 4438–4440. [Google Scholar] [CrossRef]
- Caméléna, F.; Péan de Ponfilly, G.; Pailhoriès, H.; Bonzon, L.; Alanio, A.; Poncin, T.; Lafaurie, M.; Dépret, F.; Cambau, E.; Godreuil, S.; et al. Multicenter Evaluation of the FilmArray Blood Culture Identification 2 Panel for Pathogen Detection in Bloodstream Infections. Microbiol. Spectr. 2023, 11, e0254722. [Google Scholar] [CrossRef]
- Gill, C.M.; Rajkotia, P.; Roberts, A.L.; Tenover, F.C.; Nicolau, D.P. Directed carbapenemase testing is no longer just for Enterobacterales: Cost, labor, and workflow assessment of expanding carbapenemase testing to carbapenem-resistant P. aeruginosa. Emerg. Microbes Infect. 2023, 12, 2179344. [Google Scholar] [CrossRef] [PubMed]
- Gu, D.; Yan, Z.; Cai, C.; Li, J.; Zhang, Y.; Wu, Y.; Yang, J.; Huang, Y.; Zhang, R.; Wu, Y. Comparison of the NG-Test Carba 5, Colloidal Gold Immunoassay (CGI) Test, and Xpert Carba-R for the Rapid Detection of Carbapenemases in Carbapenemase-Producing Organisms. Antibiotics 2023, 12, 300. [Google Scholar] [CrossRef] [PubMed]
- Ong, S.W.X.; Hon, P.Y.; Wee, S.S.H.; Chia, J.W.Z.; Mendis, S.; Izharuddin, E.; Lin, R.J.; Chia, P.Y.; Sim, R.C.S.; Chen, M.I.-C.; et al. Accuracy of a Rapid Multiplex Polymerase Chain Reaction Plus a Chromogenic Phenotypic Test Algorithm for Detection of Extended-Spectrum β-Lactamase and Carbapenemase-Producing Gram-Negative Bacilli in Positive Blood Culture Bottles. Clin. Infect. Dis. 2022, 74, 1850–1854. [Google Scholar] [CrossRef] [PubMed]
- Falagas, M.E.; Tansarli, G.S.; Karageorgopoulos, D.E.; Vardakas, K.Z. Deaths attributable to carbapenem-resistant Enterobacteriaceae infections. Emerg. Infect. Dis. 2014, 20, 1170–1175. [Google Scholar] [CrossRef] [PubMed]
- Zarkotou, O.; Pournaras, S.; Tselioti, P.; Dragoumanos, V.; Pitiriga, V.; Ranellou, K.; Prekates, A.; Themeli-Digalaki, K.; Tsakris, A. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin. Microbiol. Infect. 2011, 17, 1798–1803. [Google Scholar] [CrossRef] [PubMed]
- Kadri, S.S.; Adjemian, J.; Lai, Y.L.; Spaulding, A.B.; Ricotta, E.; Prevots, D.R.; Palmore, T.N.; Rhee, C.; Klompas, M.; Dekker, J.P.; et al. Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents. Clin. Infect. Dis. 2018, 67, 1803–1814. [Google Scholar] [CrossRef]
- Savoldi, A.; Carrara, E.; Piddock, L.J.V.; Franceschi, F.; Ellis, S.; Chiamenti, M.; Bragantini, D.; Righi, E.; Tacconelli, E. The role of combination therapy in the treatment of severe infections caused by carbapenem resistant gram-negatives: A systematic review of clinical studies. BMC Infect. Dis. 2021, 21, 545. [Google Scholar] [CrossRef]
- Tamma, P.D.A.S.; Bonomo, R.A.; Mathers, A.J.; van Duin, D.; Clancy, C.J. Infectious Diseases Society of America Antimicrobial-Resistant Treatment Guidance: Gram-Negative Bacterial Infections; Version 1.1.; Infectious Diseases Society of America: Chicago, IL, USA, 2022. [Google Scholar]
- Paul, M.; Carrara, E.; Retamar, P.; Tängdén, T.; Bitterman, R.; Bonomo, R.A.; de Waele, J.; Daikos, G.L.; Akova, M.; Harbarth, S.; et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine). Clin. Microbiol. Infect. 2022, 28, 521–547. [Google Scholar] [CrossRef]
- Lee, C.M.; Kim, Y.J.; Jung, S.I.; Kim, S.E.; Park, W.B.; Choe, P.G.; Kim, E.S.; Kim, C.-J.; Choi, H.J.; Lee, S.; et al. Different clinical characteristics and impact of carbapenem-resistance on outcomes between Acinetobacter baumannii and Pseudomonas aeruginosa bacteraemia: A prospective observational study. Sci. Rep. 2022, 12, 8527. [Google Scholar] [CrossRef]
- Tamma, P.D.; Goodman, K.E.; Harris, A.D.; Tekle, T.; Roberts, A.; Taiwo, A.; Simner, P.J. Comparing the Outcomes of Patients with Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin. Infect. Dis. 2017, 64, 257–264. [Google Scholar] [CrossRef]
- Reyes, J.; Komarow, L.; Chen, L.; Ge, L.; Hanson, B.M.; Cober, E.; Herc, E.; Alenazi, T.; Kaye, K.S.; Garcia-Diaz, J.; et al. Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): A prospective cohort study. Lancet Microbe. 2023, 4, e159–e170. [Google Scholar] [CrossRef] [PubMed]
- Dossett, L.A.; Dageforde, L.A.; Swenson, B.R.; Metzger, R.; Bonatti, H.; Sawyer, R.G.; May, A.K. Obesity and site-specific nosocomial infection risk in the intensive care unit. Surg. Infect. 2009, 10, 137–142. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.E.; Griffin, R.; Judd, S.; Shapiro, N.I.; Safford, M.M. Obesity and risk of sepsis: A population-based cohort study. Obesity 2013, 21, E762–E769. [Google Scholar] [CrossRef] [PubMed]
- Trivedi, V.; Bavishi, C.; Jean, R. Impact of obesity on sepsis mortality: A systematic review. J. Crit. Care 2015, 30, 518–524. [Google Scholar] [CrossRef]
Table 1.
Clinical characteristics of patients with carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) and non-CP-CRE bloodstream infections.
Table 1.
Clinical characteristics of patients with carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) and non-CP-CRE bloodstream infections.
| Characteristics | Total (n = 147) | Non-CP-CPE (n = 19) | CP-CRE (n = 128) | p-Value |
|---|---|---|---|---|
| Age | 61.79 ± 12.73 | 61.42 ± 8.88 | 61.84 ± 13.23 | 0.893 |
| Age > 65 | 58 (39.5) | 8 (42.1) | 50 (39.1) | 0.806 |
| BMI | 22.15 ± 4.48 | 23.32 ± 5.11 | 21.97 ± 4.37 | 0.221 |
| Male | 89 (60.5) | 14 (73.7) | 75 (58.6) | 0.314 |
| Admission to bacteremia (day) (median, IQR) | 18 (5–57) | 67 (1.5–15.5) | 11 (6–60.75) | 0.436 |
| Infection source | ||||
| UTI | 14 (9.5) | 2 (10.5) | 12 (9.4) | 0.873 |
| Pneumonia | 46 (31.3) | 2 (10.5) | 44 (34.4) | 0.060 |
| SSTI | 7 (4.8) | 0 (0) | 7 (5.5) | 0.595 |
| CRBSI | 41 (27.9) | 12 (63.2) | 29 (22.7) | <0.001 |
| IAI | 26 (17.7) | 2 (10.5) | 24 (18.8) | 0.528 |
| Underlying comorbidity | ||||
| HTN | 60 (40.8) | 8 (42.1) | 52 (40.6) | 1.000 |
| DM | 52 (35.4) | 6 (31.6) | 46 (35.9) | 0.801 |
| Cardiovascular disease | 42 (28.6) | 7 (36.8) | 35 (27.3) | 0.420 |
| Lung disease | 40 (27.2) | 1 (5.3) | 39 (30.5) | 0.025 |
| Renal disease | 29 (19.7) | 3 (15.8) | 26 (20.3) | 0.767 |
| Solid cancer | 56 (38.1) | 11 (57.9) | 45 (35.2) | 0.076 |
| Hematologic disease | 22 (15.0) | 3 (15.8) | 19 (14.8) | 1.000 |
| SOT | 34 (23.1) | 4 (21.1) | 30 (23.4) | 1.000 |
| HSCT | 8 (5.4) | 1 (5.3) | 7 (5.5) | 1.000 |
| Rheumatologic disease | 9 (6.1) | 2 (10.5) | 7 (5.5) | 0.605 |
| Liver disease | 22 (15.0) | 1 (5.3) | 21 (16.4) | 0.309 |
| Predisposing factor | ||||
| Neutropenia | 31 (21.1) | 3 (15.8) | 28 (21.9) | 0.578 |
| Steroid | 45 (30.6) | 5 (26.3) | 40 (31.3) | 0.793 |
| Oral prophylactic antibiotics | 27 (18.4) | 3 (15.8) | 24 (18.8) | 1.000 |
| Immunosuppressant | 47 (32.0) | 7 (36.8) | 40 (31.3) | 0.793 |
| Chemotherapy | 34 (23.1) | 4 (21.1) | 30 (23.4) | 1.000 |
| Pressure sore | 19 (12.9) | 0 | 19 (14.8) | 0.134 |
| Operation | 32 (21.8) | 3 (15.8) | 29 (22.7) | 0.571 |
| Previous broad-spectrum antibiotics | 122 (83.0) | 15 (78.9) | 107 (83.6) | 0.743 |
| Carbapenem use | 67 (45.6) | 5 (26.3) | 62 (48.4) | 0.086 |
| Procedures | ||||
| Foley catheter | 97 (66.0) | 10 (52.6) | 87 (68.0) | 0.188 |
| Central venous catheter | 111 (75.5) | 14 (73.7) | 97 (75.8) | 0.843 |
| Ventilator care | 38 (25.9) | 4 (21.1) | 34 (26.6) | 0.609 |
| Drainage catheter | 57 (38.8) | 6 (31.6) | 51 (39.8) | 0.490 |
| Severity | ||||
| ICU care | 62 (42.2) | 7 (36.8) | 55 (43.0) | 0.632 |
| ICU duration (days) (median, IQR) | 21.5 (6.25–31.5) | 23.5 (11.5–41.5) | 20.5 (5.5–28) | 0.916 |
| Shock | 63 (42.9) | 8 (42.1) | 55 (43.0) | 1.000 |
| Acute kidney injury | 41 (27.9) | 5 (26.3) | 36 (28.1) | 1.000 |
| SOFA score | 5.74 ± 4.31 | 5.21 ± 3.90 | 5.82 ± 4.38 | 0.567 |
| Pitt bacteremia score | 2.19 ± 2.27 | 2.47 ± 2.89 | 2.13 ± 2.15 | 0.549 |
| Pathogen | ||||
| Klebsiella pneumoniae | 118 (80.3) | 9 (47.4) | 109 (85.2) | <0.001 |
| Escherichiae coli | 22 (15.0) | 3 (15.8) | 19 (14.8) | 1.000 |
| Enterobacter spp. | 9 (6.1) | 7 (36.8) | 2 (1.6) | <0.001 |
| Carbapenemase | ||||
| KPC | 112 (87.5) | |||
| OXA | 1 (0.8) | |||
| NDM | 14 (10.9) | |||
| Outcomes | ||||
| Mortality (14 days) | 50 (34.0) | 8 (42.1) | 42 (32.8) | 0.445 |
| Mortality (30 days) | 62 (42.2) | 11 (57.9) | 51 (39.8) | 0.212 |
BMI: body mass index; UTI: urinary tract infection; SSTI: skin and soft tissue infection; CRBSI: catheter-related bloodstream infection; IAI: intra-abdominal infection; IQR: interquartile range; HTN: hypertension; DM: diabetes mellitus; SOT: solid organ transplantation; HSCT: hematopoietic stem cell transplantation; ICU: intensive care unit; SOFA: sequential organ failure assessment.
Table 2.
Differences in the distributions of the minimum inhibitory concentration values between carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) and non-CP-CRE bloodstream infections.
Table 2.
Differences in the distributions of the minimum inhibitory concentration values between carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) and non-CP-CRE bloodstream infections.
| Antimicrobial Agent | Number (%) | p-Value | |
|---|---|---|---|
| CP-CRE BSI Group (n = 128) | Non-CP-CRE BSI Group (n = 19) | ||
| Ertapenem | <0.001 | ||
| MIC ≤ 0.5 | 1 (0.8) | ||
| 0.5 < MIC <2 | 1 (5.3) | ||
| 2 ≤ MIC < 4 | 1 (0.8) | 2 (10.5) | |
| 4 ≤ MIC < 8 | 9 (7.2) | 5 (26.3) | |
| MIC ≥ 8 | 114 (91.2) | 11 (57.9) | |
| Meropenem/Imipenem | <0.001 | ||
| MIC ≤ 1 | 2 (1.6) | 8 (61.5) | |
| 1 < MIC < 4 | 2 (1.6) | 1 (7.7) | |
| 4 ≤ MIC < 8 | 2 (1.6) | 3 (23.1) | |
| 8 ≤ MIC < 16 | 15 (12.1) | ||
| MIC ≥ 16 | 103 (83.1) | 1 (7.7) | |
| AMK → Amikacin | 0.196 | ||
| S (MIC ≤ 16) | 121 (94.5) | 16 (88.9) | |
| I (16 < MIC < 64) | 3 (2.3) | ||
| R (MIC ≥ 64) | 4 (3.1) | 2 (11.1) | |
| Gentamicin | <0.001 | ||
| S (MIC ≤ 4) | 31 (24.2) | 14 (77.8) | |
| I (4 < MIC < 16) | 1 (0.8) | 1 (5.6) | |
| R (MIC ≥ 16) | 96 (75.0) | 3 (16.7) | |
BSI: bloodstream infection; MIC: minimum inhibitory concentration.
Table 3.
Clinical characteristics of the survivors and non-survivors with carbapenem-resistant Enterobacteriaceae bacteremia according to 14-day and 30-day mortality.
Table 3.
Clinical characteristics of the survivors and non-survivors with carbapenem-resistant Enterobacteriaceae bacteremia according to 14-day and 30-day mortality.
| 14-Day Mortality | 30-Day Mortality | |||||
|---|---|---|---|---|---|---|
| Survivors (n = 97) | Mortality (n = 50) | p-Value | Survivors (n = 85) | Mortality (n = 62) | p-Value | |
| Age | 60.98 ± 12.50 | 63.36 ± 13.15 | 0.458 | 60.53 ± 13.14 | 63.52 ± 12.03 | 0.736 |
| Male | 60 (61.9) | 29 (58.0) | 0.650 | 49 (57.6) | 40 (64.5) | 0.495 |
| BMI | 21.23 ± 3.68 | 23.41 ± 5.15 | 0.003 | 21.23 ± 3.68 | 23.41 ± 5.15 | 0.003 |
| Admission to bacteremia (median, IQR) | 3.5 (3–56) | 11 (7.5–59) | 0.841 | 33.5 (3–52) | 3.5 (7–68.5) | 0.841 |
| CPE | 86 (88.7) | 42 (84.0) | 0.425 | 77 (90.6) | 51 (82.3) | 0.137 |
| Infection source | ||||||
| UTI | 12 (12.4) | 2 (4.0) | 0.101 | 12 (14.1) | 2 (3.2) | 0.026 |
| Pneumonia | 29 (29.9) | 17 (34.0) | 0.611 | 25 (29.4) | 21 (33.9) | 0.565 |
| SSTI | 4 (4.1) | 3 (6.0) | 0.613 | 3 (3.5) | 4 (6.5) | 0.411 |
| CRBSI | 26 (27.1) | 15 (30.0) | 0.682 | 23 (27.1) | 18 (29.0) | 0.792 |
| IAI | 16 (16.5) | 10 (20.0) | 0.598 | 13 (15.3) | 13 (21.0) | 0.373 |
| Underlying comorbidity | ||||||
| HTN | 39 (40.2) | 21 (42.0) | 0.834 | 32 (37.6) | 28 (45.2) | 0.360 |
| DM | 38 (39.2) | 14 (28.0) | 0.179 | 29 (34.1) | 23 (37.1) | 0.709 |
| Cardiovascular disease | 23 (23.7) | 19 (38.0) | 0.069 | 19 (22.4) | 23 (37.1) | 0.051 |
| Chronic lung disease | 26 (26.8) | 14 (28.0) | 0.877 | 24 (28.2) | 16 (25.8) | 0.744 |
| Chronic renal disease | 20 (20.6) | 9 (18.0) | 0.705 | 17 (20.0) | 12 (19.4) | 0.923 |
| Solid cancer | 41 (42.3) | 15 (30.0) | 0.147 | 33 (38.8) | 23 (37.1) | 0.831 |
| Hematologic disease | 12 (12.4) | 10 (20.0) | 0.219 | 12 (54.5) | 10 (16.1) | 0.736 |
| HSCT | 5 (5.2) | 3 (6.0) | 0.831 | 5 (5.9) | 3 (4.8) | 0.783 |
| SOT | 24 (24.7) | 10 (20.0) | 0.518 | 23 (27.1) | 11 (17.7) | 0.186 |
| Rheumatologic disease | 5 (5.2) | 4 (8.0) | 0.495 | 4 (4.7) | 5 (8.1) | 0.402 |
| Chronic liver disease | 14 (14.4) | 8 (16.0) | 0.801 | 13 (15.3) | 9 (14.5) | 0.896 |
| Predisposing conditions | ||||||
| Neutropenia | 21 (21.6) | 10 (20.0) | 0.816 | 20 (23.5) | 11 (17.7) | 0.396 |
| Steroid use | 29 (29.9) | 16 (32.0) | 0.793 | 28 (32.9) | 17 (27.4) | 0.473 |
| Prophylactic antibiotics | 22 (22.7) | 5 (10.0) | 0.060 | 21 (24.7) | 6 (9.7) | 0.020 |
| Immunosuppressant | 33 (34.0) | 14 (28.0) | 0.458 | 31 (36.5) | 16 (25.8) | 0.171 |
| Chemotherapy | 26 (26.8) | 8 (16.0) | 0.141 | 22 (25.9) | 12 (19.4) | 0.354 |
| Pressure sore | 13 (13.4) | 6 (12.0) | 0.810 | 12 (14.1) | 7 (11.3) | 0.614 |
| Surgery | 24 (24.7) | 8 (16.0) | 0.224 | 22 (25.9) | 10 (16.1) | 0.157 |
| Severity | ||||||
| ICU care | 38 (39.2) | 24 (48.0) | 0.305 | 31 (36.5) | 31 (50.0) | 0.101 |
| ICU duration | 8.75 ± 17.22 | 14.66 ± 38.74 | 0.203 | 8.52 ± 16.96 | 13.84 ± 35.75 | 0.232 |
| Shock | 28 (28.9) | 35 (70.0) | <0.001 | 25 (29.4) | 38 (61.3) | <0.001 |
| Acute kidney injury | 19 (19.6) | 22 (44.0) | 0.002 | 17 (20.0) | 24 (38.7) | 0.012 |
| SOFA score | 4.63 ± 4.07 | 7.90 ± 3.98 | <0.001 | 4.47 ± 3.99 | 7.48 ± 4.15 | <0.001 |
| Pitt bacteremia score | 1.60 ± 1.87 | 3.25 ± 2.55 | <0.001 | 1.53 ± 1.89 | 3.04 ± 2.44 | <0.001 |
| Previous antibiotics use | 76 (78.4) | 46 (92.0) | 0.037 | 66 (77.6) | 56 (90.3) | 0.043 |
| Carbapenem | 43 (44.3) | 24 (48.0) | 0.672 | 36 (42.4) | 31 (50.0) | 0.358 |
| Quinolone | 19 (19.6) | 14 (28.0) | 0.247 | 16 (18.8) | 17 (27.4) | 0.217 |
| Cephalosporin | 28 (28.9) | 16 (32.0) | 0.694 | 25 (29.4) | 19 (30.6) | 0.872 |
| Pathogen | ||||||
| Klebsiella pneumoniae | 78 (80.4) | 40 (80.0) | 0.953 | 68 (80.0) | 50 (80.6) | 0.923 |
| Escherichia coli | 15 (15.5) | 7 (14.0) | 0.814 | 13 (15.3) | 9 (14.5) | 0.896 |
| Enterobacter spp. | 6 (6.2) | 3 (6.0) | 0.965 | 6 (7.1) | 3 (4.8) | 0.579 |
| KPC genotype | 76 (78.4) | 36 (72.0) | 0.392 | 67 (78.8) | 45 (72.6) | 0.380 |
| Antibiotics treatment | ||||||
| Appropriate antibiotic use | 73 (76.0) | 25 (75.8) | 0.974 | 64 (76.2) | 34 (75.6) | 0.936 |
| Amikacin in S | 51 (53.1) | 16 (48.5) | 0.645 | 45 (53.6) | 22 (48.9) | 0.612 |
| Carbapenem | 73 (76.0) | 24 (72.7) | 0.704 | 64 (76.2) | 33 (73.3) | 0.720 |
| Carbapenem (prolonged infusion) | 10 (10.4) | 3 (9.1) | 0.827 | 10 (11.9) | 3 (6.7) | 0.346 |
| Tigecycline | 4 (4.2) | 4 (12.1) | 0.102 | 4 (4.8) | 4 (8.9) | 0.354 |
| Colistin | 32 (33.3) | 13 (39.4) | 0.529 | 28 (33.3) | 17 (37.8) | 0.614 |
| Carbapenem/colistin combination | 27 (28.1) | 12 (36.4) | 0.374 | 24 (28.6) | 15 (33.3) | 0.575 |
BMI: body mass index; CPE: carbapenemase-producing Enterobacteriaceae; UTI: urinary tract infection; SSTI: skin and soft tissue infection; CRBSI: catheter-related bloodstream infection; IAI: intra-abdominal infection; IQR: interquartile range; HTN: hypertension; DM: diabetes mellitus; SOT: solid organ transplantation; HSCT: hematopoietic stem cell transplantation; ICU: intensive care unit; SOFA: sequential organ failure assessment.
Table 4.
Multivariate analysis of the risk factors of 14-day and 30-day mortality due to carbapenem-resistant Enterobacteriaceae bacteremia.
Table 4.
Multivariate analysis of the risk factors of 14-day and 30-day mortality due to carbapenem-resistant Enterobacteriaceae bacteremia.
| Characteristics | Univariate Analysis | Multivariate Analysis | ||
|---|---|---|---|---|
| Unadjusted OR (95% CI) | p-Value | Adjusted OR (95% CI) | p-Value | |
| 14-day mortality | ||||
| Age | 1.015 (0.987–1.044) | 0.283 | 1.037 (0.993–1.083) | 0.105 |
| BMI | 1.128 (1.039–1.225) | 0.04 | 1.123 (1.012–1.246) | 0.029 |
| CPE | 0.672 (0.251–1.794) | 0.427 | 1.176 (0.297–4.651) | 0.817 |
| SOFA score | 1.201 (1.100–1.311) | <0.001 | 1.206 (1.073–1.356) | 0.002 |
| Previous antibiotics use | 3.178 (1.026–9.839) | 0.045 | 0.163 (0.028–0.933) | 0.042 |
| Amikacin treatment | 0.830 (0.376–1.833) | 0.646 | 1.522 (0.573–4.041) | 0.399 |
| Carbapenem treatment | 0.840 (0.342–2.063) | 0.84 | 1.595 (0.534–4.760) | 0.403 |
| Colistin treatment | 1.378 (0.616–3.081) | 0.435 | 1.187 (0.432–3.266) | 0.739 |
| 30-day mortality | ||||
| Age | 1.019 (0.992–1.047) | 0.162 | 1.037 (0.998–1.079) | 0.066 |
| BMI | 1.123 (1.035–1.217) | 0.005 | 1.095 (0.994–1.207) | 0.067 |
| CPE | 0.482 (0.181–1.280) | 0.143 | 0.505 (0.144–1.770) | 0.286 |
| Urinary tract infection | 0.203 (0.044–0.942) | 0.026 | 0.270 (0.031–2.393) | 0.240 |
| SOFA score | 1.192 (1.093–1.301) | <0.001 | 1.194 (1.068–1.335) | 0.002 |
| Previous antibiotics use | 2.687 (1.004–7.191) | 0.049 | 3.005 (0.739–12.214) | 0.124 |
| Amikacin treatment | 0.829 (0.402–1.711) | 0.612 | 0.654 (0.267–1.604) | 0.354 |
| Carbapenem treatment | 0.859 (0.375–1.970) | 0.72 | 0.760 (0.269–2.145) | 0.604 |
| Colistin treatment | 1.263 (0.598–2.665) | 0.540 | 0.812 (0.313–2.104) | 0.668 |
BMI: body mass index; CPE: carbapenemase-producing Enterobacteriaceae; SOFA: sequential organ failure assessment; OR: odds ratio; CI: confidence interval.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Ahn, J.Y.; Ahn, S.M.; Kim, J.H.; Jeong, S.J.; Ku, N.S.; Choi, J.Y.; Yeom, J.S.; Song, J.E. Clinical Characteristics and Associated Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bloodstream Infection. Microorganisms 2023, 11, 1121. https://doi.org/10.3390/microorganisms11051121
AMA Style
Ahn JY, Ahn SM, Kim JH, Jeong SJ, Ku NS, Choi JY, Yeom JS, Song JE. Clinical Characteristics and Associated Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bloodstream Infection. Microorganisms. 2023; 11(5):1121. https://doi.org/10.3390/microorganisms11051121
Chicago/Turabian StyleAhn, Jin Young, Sang Min Ahn, Jung Ho Kim, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Joon Sup Yeom, and Je Eun Song. 2023. "Clinical Characteristics and Associated Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bloodstream Infection" Microorganisms 11, no. 5: 1121. https://doi.org/10.3390/microorganisms11051121
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
