Risk factors for bloodstream infection caused by extended-spectrum β-lactamase–producing Escherichia coli and Klebsiella pneumoniae: A focus on antimicrobials including cefepime

doi:10.1016/j.ajic.2015.02.030

American Journal of Infection Control

Volume 43, Issue 7, 1 July 2015, Pages 719-723

https://doi.org/10.1016/j.ajic.2015.02.030 Get rights and content

Highlights

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We conduct a 5-year retrospective case-case-control study at a Detroit hospital.
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We identify risk factors for bloodstream infections caused by extended-spectrum β-lactamase–producing Escherichia coli or Klebsiella pneumoniae.
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Those predictors include central venous catheter, prior β-lactam therapy, and prior cefepime therapy.
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Prior antimicrobial therapy was the strongest unique risk factor.
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Predictor of bloodstream infection caused by nonextended-spectrum β-lactamase–producing pathogens was foley catheter insertion.

Background

Extended-spectrum β-lactamase (ESBL)–producing pathogens represent increasing challenges to physicians because of rising prevalence, high mortality, and challenging treatment. Identifying high risks and early appropriate therapy is critical to favorable outcomes.

Methods

This is a 5-year retrospective case-case-control study performed at the Detroit Medical Center on adult patients with bloodstream infection (BSI) caused by ESBL-producing and non-ESBL–producing Escherichia coli or Klebsiella pneumoniae, each compared with uninfected controls. Data were collected from December 2004-August 2009. Multivariate analysis was performed using logistic regression.

Results

Participants included 103 patients with BSI caused by ESBL-producing pathogens and 79 patients with BSI caused by pathogens that did not produce ESBLs. The mean age of patients in the ESBL group was 67 years; of the patients, 51% were men, 77% were black, and 38% (n = 39) died in hospital. The mean age of patients in the non-ESBL group was 58 years; of the patients, 51% were men, 92% were black, and 22% (n = 17) died in hospital. On multivariate analysis, predictors of BSI caused by ESBL-producing pathogens included central venous catheter (odds ratio [OR], 29.4; 95% confidence interval [CI], 3.0-288.3), prior β-lactam–/β-lactamase–inhibitor therapy (OR, 28.1; 95% CI, 1.99-396.5), and prior cefepime therapy (OR, 22.7; 95% CI, 2.7-192.4). The only risk factor for BSI caused by non-ESBL–producing pathogens was urinary catheter insertion (OR, 18.2; 95% CI, 3.3-100.3).

Conclusion

Prior antimicrobial therapy, particularly with β-lactam, was the strongest unique risk factor for BSI caused by ESBL-producing E coli or K pneumoniae.

Section snippets

Study design

Two retrospective case-control studies were performed at the Detroit Medical Center (DMC) health care system between December 2004 and August 2009. With >2,200 inpatient beds, the 8- hospital DMC health care system serves as a tertiary referral hospital for Southeast Michigan. Institutional review boards at DMC and Wayne State University approved this study prior to data collection.

Study population

The study population was identified by querying the DMC’s Clinical Microbiology Laboratory, which handles >500,000

Demographics

Of the ESBL BSI cases, 103 were included, including 18 caused by E coli, 84 caused by K pneumoniae, and 1 caused by both E coli and K pneumoniae. There were 103 uninfected controls matched to the ESBL cases. There were 79 susceptible BSI cases, 15 with BSI caused by E coli, and 64 with BSI caused by K pneumoniae, and 79 uninfected controls were matched to these susceptible cases. Information regarding patient demographics, clinical characteristics, outcomes, and prior antibiotic exposure for

Discussion

Although third-generation cephalosporins have been widely recognized as risk factors for ESBL-producing pathogens, this is the first study to our knowledge to identify exposure to cefepime, a fourth-generation cephalosporin, as a unique and independent predictor for BSI caused by ESBL-producing Enterobacteriaceae. Although cefepime has increased activity against and stability to ESBLs compared with third-generation cephalosporins, they are not as active or stable as the carbapenems.

In this

Conclusion

This article demonstrates that, from a hospital formulary perspective, use of cefepime as a workhorse antimicrobial has a similar impact on ESBL risk, as does use of piperacillin-tazobactam. Infection prevention, particularly with regard to central line care, and antimicrobial stewardship efforts geared toward limiting the duration of broad-spectrum empirical agents, including cefepime and BLABLI combinations, are likely to be effective and appropriate methods to prevent and manage infections

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Risk factors and diagnostic markers for Escherichia coli bloodstream infection in older patients
2021, Archives of Gerontology and Geriatrics
Citation Excerpt :
Infection with ESBL+ E. coli not only increases the cost of hospitalization, but also prolongs the length of stay (Leistner et al., 2014). In this study, previous exposure to cephems and drainage tube placement were identified as independent risk factors for infection with ESBL+ E. coli, and this is in keeping with previous reports (Chopra et al., 2015; Pascual et al., 2015; Zhang et al., 2019). Thus, production of ESBL in E. coli is associated with multiple factors, which mainly include invasive procedures and prior antibiotic exposure.
To investigate risk factors for Escherichia coli (E. coli) bloodstream infection (BSI) in older patients and the diagnostic accuracy of laboratory parameters.
The electronic medical records of patients aged 60 years and above who were admitted with a serious condition were extracted. Propensity score matching (PSM) was used to ensure that the included patients had similar baseline clinical features. Multiple regression analysis was used to identify risk factors for E. coli BSI and extended-spectrum β-lactamase (ESBL)-producing E. coli BSI. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic utility of relevant laboratory indicators.
After PSM, 508 patients were included: 254 patients with E. coli BSI and 254 control patients. Bile duct stone (adjusted odds ratio [aOR] 5.131), kidney stone (aOR 3.678), and urinary system infection (aOR 3.173) were independent risk factors for E. coli BSI. Prior exposure to cephems (aOR 3.782) and drainage tube placement (aOR 2.572) were independent risk factors for ESBL-producing E. coli BSI. Serum procalcitonin (PCT) yielded the highest area under the curve (0.783) and the best cut-off value (1.3 ng/ml).
Bile duct stone, kidney stone, and urinary system infection must be detected and treated early, in order to prevent E. coli BSI in older patients. Further, administration of cephems and invasive procedures must be undertaken with caution, in order to reduce the risk of BSI with ESBL-producing E. coli. Finally, serum PCT level has potential as diagnostic marker for E. coli BSI in older individuals.
Non-intravenous carbapenem-sparing antibiotics for definitive treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamase (ESBL) or AmpC β-lactamase: A propensity score study
2019, International Journal of Antimicrobial Agents
Citation Excerpt :
In a metanalysis [3], use of empirical quinolones (oral or i.v.) for ESBL Enterobacteriaceae bacteraemia was associated with a higher mortality than carbapenems, but mortality was similar when quinolones were used as definitive therapy. Some studies have shown prior exposure to fluoroquinolones or β-lactams to be independent risk factors for ESBL-producing or carbapenem-resistant Enterobacteriaceae infections [31,32]. Taking this into consideration, other non-i.v. treatments such as SXT or fosfomycin could be a better option for definitive therapy.
Carbapenems are considered the treatment of choice for extended-spectrum β-lactamase (ESBL)- or AmpC β-lactamase-producing Enterobacteriaceae bacteraemia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. This study compared the 30-day mortality and clinical failure associated with the use of carbapenems versus alternative non-intravenous antibiotics for the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia. This 12-year retrospective study (2004–2015) included all patients with bacteraemia due to ESBL/AmpC-producing Enterobacteriaceae at a Spanish hospital. Given the lack of randomisation of initial therapies, a propensity score for receiving carbapenems was calculated. There were 1115 patients with a first episode of bacteraemia due to Escherichia coli or Klebsiella pneumoniae, of which 123 (11.0%) were ESBL/AmpC-positive. There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (trimethoprim/sulfamethoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared with the carbapenem group, patients treated with an alternative regimen had a shorter hospital stay [median (IQR) 7 (5–10) days vs. 12 (9–18) days; P < 0.001]. Use of an alternative non-intravenous therapy did not increase mortality (OR = 0.27, 95% CI 0.05–1.61; P = 0.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95 (95% CI 0.94–26.01; P = 0.059). Alternative non-intravenous carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia, allowing a reduction in carbapenem use. Use of trimethoprim/sulfamethoxazole in this series showed favourable results.
A retrospective analysis of risk factors and outcomes in patients with extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infections
2019, Journal of Global Antimicrobial Resistance
Citation Excerpt :
Data from the CHINET Antimicrobial Resistance Surveillance Program showed that the detection rate of ESBL-producing E. coli in China increased from 38.9% in 2005 to 55.8% in 2014, which is similar to that seen in other countries [2,19]. Previous studies have shown that ESBL-producing E. coli is primarily derived from UTIs, whereas the current study showed abdominal infection to be the primary origin; this may be related to the high number of patients with hepatobiliary surgery in the current hospital [20]. In agreement with previous studies, multivariate analysis of risk factors for ESBL-producing E. coli in the current study showed that UTI was an independent risk factor, with 13.5% of patients having a history of urinary catheterization.
Risk factors and outcomes associated with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) bloodstream infections (BSI) are not yet fully understood.
This was a retrospective analysis of patients with E. coli BSI treated over a 4-year period. The characteristics of bacteremia caused by ESBL-producing versus non-ESBL-producing E. coli were compared. Factors influencing mortality were also assessed.
Of 554 eligible patients, 58.9% developed ESBL-producing E. coli. Multivariate analysis showed that urinary tract infections, stomach tube catheterization, and prior cephalosporin exposure were independent risk factors for the emergence of ESBL-producing E. coli BSI. No significant differences in 30-day mortality were seen in patients with BSI caused by ESBL-producing or non-ESBL-producing E. coli (11.1% vs. 9.2%; P = 0. 642). Factors independently associated with a higher risk of mortality were previous carbapenem exposure, high APACHE II score, and respiratory tract origin.
This study showed that prior UTIs and previous cephalosporin exposure represent significant risk factors for the development of ESBL-producing E. coli BSI. Previous carbapenem exposure, high APACHE II score, and a respiratory tract origin were seen to be independent mortality risk factors in patients with E. coli BSI.
Associated factors and clinical outcomes of bloodstream infection due to extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae during febrile neutropenia
2019, International Journal of Antimicrobial Agents
Citation Excerpt :
In contrast to other studies [24,25], previous admission, by itself, was not associated with ESBL-positive bacteremia in our cohort. Interestingly, only a few studies suggested the use of CVC during bacteremia to be associated with ESBL infection [26,27]. In our cohort, CVC was an independent risk factor for ESBL-positive bacteremia, although CRBSI was diagnosed in only one patient.
Patients with neutropenia are vulnerable to serious infections. During the last decade, increased prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae has affected immunocompromised patients. We conducted a single-center case–control study to evaluate factors associated with ESBL-positive bacteremia among neutropenic patients, and its clinical impact. The study included adult patients with hematologic or oncologic diseases diagnosed with ESBL-positive and ESBL-negative Escherichia coli or Klebsiella pneumoniae bacteremia during febrile neutropenia between January 2010 and October 2017 at the Shaare Zedek Medical Center, Jerusalem, Israel. Analyses included risk factors for ESBL-positive bacteremia, appropriateness of empiric antibiotics, mortality, length of stay, and intensive care unit (ICU) admission. Univariate and multivariate models were constructed. The cohort (80 patients), consisted of 54 ESBL-negative and 26 ESBL-positive Gram-negative bacteremia. Multivariate analysis suggested ESBL-positive bacteremia to be associated with long-term central venous catheter (CVC) (odds ratio (OR), 8.7; 95% confidence interval (CI), 1.6–48.1; P=0.01], index culture obtained 48 h post-admission (OR, 3.6; 95% CI, 1–12.3; P=0.04), and exposure to previous antimicrobial therapy (OR, 12.6; 95% CI, 2.1–74; P<0.01). There were no significant differences between groups with regard to length of stay, ICU admission, or mortality rates. Mortality was associated with high Pitt bacteremia score but not inappropriate empirical therapy. Previous antimicrobial therapy, long-term CVC, and hospital-acquired bacteremia were associated with ESBL bacteremia. Neutropenic patients with ESBL bacteremia have increased morality due to other factors than ESBL status. These findings should be validated in other centers and with larger populations.
Risk factors and molecular epidemiology of extended-spectrum β-lactamase-producing Klebsiella pneumoniae in Xiamen, China
2017, Journal of Global Antimicrobial Resistance
Citation Excerpt :
Previous studies have shown that previous use of antibiotics is a risk factor for ESBL-KP infection [14,15]; in particular, patients exposed to third-generation cephalosporins have an increased risk for this infection [2,6,16]. An additional study even revealed that exposure to cefepime, a fourth-generation cephalosporin, is a unique and independent predictor of ESBL-KP infection [17]. However, some researchers have suggested that the cephalosporin class is not independently associated with ESBL bloodstream infection [18].
The aim of this study was to evaluate the risk factors for pneumonia due to extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) and to analyse the molecular epidemiology of ESBL-KP in Xiamen, China.
A case–control study was conducted at Zhongshan Hospital from January 2014 to August 2015. Medical records of patients with nosocomial pneumonia caused by K. pneumoniae were collected. A total of 40 cases with ESBL-KP infection and 90 controls with non-ESBL-KP infection were included. The sequence types (STs) of the 40 ESBL-KP strains were determined by multilocus sequence typing (MLST).
Univariate analysis primarily revealed an association between the following seven risk factors and ESBL-KP infection (P < 0.10): length of hospitalisation; use of cephalosporins; use of quinolones; presence of a nasogastric tube; presence of an intravenous catheter; mechanical ventilation; and cerebrospinal fluid drainage. Furthermore, multivariate analysis revealed that use of cephalosporins and presence of a nasogastric tube were independent risk factors for ESBL-KP infection (P < 0.05), with adjusted odds ratios of 3.473 [95% confidence interval (CI) 1.105–10.911; P = 0.033] and 2.488 (95% CI 1.083–5.715; P = 0.032), respectively. MLST identified 28 STs. The main STs were ST23 (10.0%) and ST37 (10.0%); three novel STs were identified.
Use of cephalosporins and presence of a nasogastric tube are independent risk factors for ESBL-KP infection. In addition, the discovery of three novel STs serves as a reminder to continuously monitor outbreaks of ESBL-KP infection.
Analysis of infections among patients with historical culture positive for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae: Is ESBL-targeted therapy always needed?
2023, Antimicrobial Stewardship and Healthcare Epidemiology

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Major articleRisk factors for bloodstream infection caused by extended-spectrum β-lactamase–producing Escherichia coli and Klebsiella pneumoniae: A focus on antimicrobials including cefepime

Highlights

Background

Methods

Results

Conclusion

Section snippets

Study design

Study population

Demographics

Discussion

Conclusion

Int J Antimicrob Agents

Int J Infect Dis

J Microbiol Immunol Infect

National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2003, issued August 2003

Am J Infect Control

Clinical and economic impact of bacteremia with extended- spectrum-beta-lactamase-producing Enterobacteriaceae

Antimicrobial Agents Chemother

Costs of bloodstream infections caused by Escherichia coli and influence of extended-spectrum-beta-lactamase production and inadequate initial antibiotic therapy

Antimicrobial Agents Chemother

Bloodstream infections caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae: risk factors, molecular epidemiology, and clinical outcome

Antimicrobial Agents Chemother

Risk factors for and clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae

Infect Control Hosp Epidemiol

Major article
Risk factors for bloodstream infection caused by extended-spectrum β-lactamase–producing Escherichia coli and Klebsiella pneumoniae: A focus on antimicrobials including cefepime