An outbreak of hospital-acquired Klebsiella pneumoniae bacteraemia, including strains producing extended-spectrum β-lactamase

doi:10.1053/jhin.2000.0862

Journal of Hospital Infection

Volume 47, Issue 1, January 2001, Pages 53-59

https://doi.org/10.1053/jhin.2000.0862 Get rights and content

Abstract

This study describes the clinical outcome of an outbreak of extended-spectrum β-lactamase producingKlebsiella pneumoniae (ESBL-KP) bacteraemia. Ninety-two episodes of hospital-acquired K. pneumoniae bacteraemia were studied, 49 ESBL-KP and 43 non-ESBL-KP, from May 1993 to June 1995. Of these, 44 (90%) episodes of ESBL-KP vs. 20 (46%) episodes of non-ESBL-KP occurred in intensive care unit (ICU) patients. The incidence of K. pneumoniae bacteraemia (mainly due to ESBL-KP) increased in the ICU during the outbreak. A significant association was found between intravascular catheter-related bacteraemia and isolation of ESBL-KP [27 (56%) in the ESBL-KP group vs. 13 (30%) in the non-ESBL-KP group;P= 0.01]. The worst prognostic features were identified as age > 65 years (P= 0.02), septic shock (P< 0.001) and secondary bacteraemia (P= 0.04). High rates of resistance to β-lactam/β-lactamase inhibitors observed in our ESBL-KP isolates, as well as variable activity of aminoglycosides, restricts the empirical use of these antibiotics. Carbapenems should be the treatment of choice since they are uniformly active against these strains. Our study shows that ESBL-KP bacteraemia occurring in an epidemic ICU setting is mainly catheter-related. We did not find ESBL strains to be associated with a significantly poor outcome.

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Klebsiella pneumoniae is among the most common antibiotic-resistant pathogens causing nosocomial infections. Additionally, it is a leading cause of neonatal sepsis and childhood mortality across the globe. Despite its clinical importance, we are only beginning to understand how the mammalian adaptive immune system responds to this pathogen. Further, many studies investigating potential K. pneumoniae vaccine candidates or alternative therapies have been launched in recent years. Here, we review the current state of knowledge on the adaptive immune response to K. pneumoniae infections and progress towards developing vaccines and other therapies to combat these infections.
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
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.
Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?
2017, Journal of Hospital Infection
Citation Excerpt :
We found no evidence for initial appropriate empiric antibiotic therapy being associated with ICU mortality or length of stay. Our findings are in line with several recent studies that did not find an association between inappropriate antibiotic therapy and mortality [20–30]. A recent prospective evaluation of empiric antibiotic therapy and mortality in ten English acute hospitals did not find an association between inappropriate empiric antibiotic therapy and mortality at seven days (adjusted OR: 0.82; 95% CI: 0.35–1.94) or 30 days (adjusted OR: 0.92; 95% CI: 0.50–1.66) [20].
Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy.
To evaluate these associations while adjusting for potential time-varying confounding using methods from the causal inference literature.
Patients who stayed more than two days in two general ICUs in England between 2002 and 2006 were included in this cohort study. Marginal structural models with inverse probability weighting were used to estimate the mortality and discharge associated with Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic therapy on these outcomes.
Among 3411 ICU admissions, 195 (5.7%) ICU-acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU death [cause-specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10–1.99] and a reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54–0.80). Appropriate empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08; 95% CI: 0.59–1.97) or discharge (HR: 0.91; 95% CI: 0.63–1.32).
ICU-acquired Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU mortality. Furthermore, the daily discharge rate was also lower after acquiring infection, even when adjusting for time-varying confounding using appropriate methodology. No evidence was found for a beneficial modifying effect of appropriate empiric antibiotic therapy on ICU mortality and discharge.
Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish society of infectious diseases and clinical microbiology
2015, Enfermedades Infecciosas y Microbiologia Clinica
Citation Excerpt :
The risk of nosocomial infection caused by ESBL-producers varies greatly according to the local epidemiology, even to a ward level. On the basis of local epidemiology and according to studies performed in Spain, individual risk factors include previous duration of hospital stay, exposure to invasive procedures (mainly mechanical ventilation), previous antibiotics (mainly cephalosporins and fluoroquinolones) and previous colonisation with these microorganisms.73–77 Predictive scores have not been developed.
The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum β-lactamases and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial.
Clinically relevant questions were selected and the literature was reviewed for each of them. The information from the selected articles was extracted and recommendations were provided and graded according to the strength of the recommendations and quality of the evidence. The document was opened to comments from the members from the Spanish Society of Infectious Diseases and Clinical Microbiology, which were considered for inclusion in the final version.
Evidence-based recommendations are provided for the use of microbiological techniques for the detection of extended-spectrum β-lactamases and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for invasive/severe infections caused by these organisms. The absence of randomised controlled trials is noteworthy; thus, recommendations are mainly based on observational studies (that have important methodological limitations), pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified.
La diseminación de Enterobacteriaceae multirresistentes en relación con la producción de β-lactamasas de espectro extendido y carbapenemasas es un importante problema de salud pública en todo el mundo. Tanto el diagnóstico microbiológico como el tratamiento de estas infecciones son complicados y controvertidos.
Los autores seleccionaron preguntas clínicamente relevantes, realizándose una revisión de la literatura para cada una de ellas; se obtuvo información de los artículos seleccionados y se realizaron recomendaciones que se clasificaron de acuerdo con la fuerza de la recomendación y la calidad de la evidencia. El documento estuvo abierto para los comentarios de los socios de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, los cuales se consideraronpara su inclusión en la versión final.
Se proporcionan recomendaciones basadas en la evidencia para el uso de técnicas microbiológicas cara a la detección de β-lactamasas de espectro extendido y carbapenemasas en Enterobacteriaceae, y para el tratamiento antimicrobiano de las infecciones graves o invasivas causadas por estos microorganismos. Es llamativa la ausencia de ensayos aleatorizados, por lo que las recomendaciones se basan principalmente en estudios observacionales que tienen importantes limitaciones metodológicas, modelos farmacocinéticos y farmacodinámicos, y datos de estudios en animales. Además, se identificaron áreas prioritarias para la investigación futura.
Multidrug-resistant bacteria in travellers hospitalized abroad: Prevalence, characteristics, and influence on clinical outcome
2012, Journal of Hospital Infection
Worldwide, the burden of multidrug-resistant bacteria (MDR) is increasing, especially in the hospital setting.
To explore characteristics and clinical relevance of MDR obtained from travellers transferred from hospitals abroad.
This retrospective study included patients transferred from hospitals abroad to the University Hospital Zurich, Switzerland, who routinely underwent admission screening for possible colonization with meticillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase-producing bacteria (ESBL) and multidrug-resistant Gram-negative bacteria (MR Gram negative).
Forty-six (17%) of 259 subjects were found to be colonized with MDR and nine (3.5%) patients to be infected. Thirty-three (12%) patients were colonized with one bacterial species, 12 (4.6%) with two, and three (1.2%) were colonized with three different bacterial species. In total, 36 ESBL, 21 MR Gram-negative and three MRSA isolates were detected. Escherichia coli (N = 18, 30%), Klebsiella pneumoniae (N = 14, 23%) and Acinetobacter baumannii (N = 14, 23%) were most frequently isolated. The most common sites of detection were skin (97%) and respiratory tract (41%). Being colonized contributed to an increased length of ICU stay [median (range): 8 (1–35) vs 3.5 (1–78) days; P = 0.011]. In-hospital mortality in patients colonized with MDR (10.9%) was higher than in uncolonized patients (2.3%, P = 0.018). Being colonized with MDR was associated with death (adjusted odds ratio: 5.176; 95% confidence interval: 1.325–20.218).
A substantial proportion of patients transferred from abroad are colonized with MDR, a fact which is associated with poor clinical outcome.
Infections caused by multidrug resistant organisms are not associated with overall, all-cause mortality in the surgical intensive care unit: The 20,000 foot view
2012, Journal of the American College of Surgeons
Resistant pathogens are increasingly common in the ICU, with controversy regarding their relationship to outcomes. We hypothesized that an increasing number of infections with resistant pathogens in our surgical ICU would not be associated with increased overall mortality.
All ICU-acquired infections were prospectively identified between January 1, 2000 and December 31, 2009 in a single surgical ICU. Crude in-hospital, all-cause mortality data were obtained using a prospectively collected ICU database. Trends in rates were compared using linear regression.
A total of 799 resistant pathogens were identified (257 gram-positive, 542 gram-negative) from a total of 3,024 isolated pathogens associated with 2,439 ICU-acquired infections. The most frequently identified resistant gram-positive and -negative pathogens (defined as resistant to at least 1 major class of antimicrobials) were methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, respectively. Pathogens were most commonly isolated from the lung, blood, and urine. The crude mortality rate declined steadily from 2000 to 2009 (9.4% to 5.4%; equation for trend y = −0.11x + 8.26). Linear regression analysis of quarterly rates revealed a significant divergence in trends between increasing total resistant infections (equation for trend y = 0.34x + 13.02) and percentage resistant infections (equation for trend y = 0.36x + 18.66) when compared with a decreasing mortality (p = 0.0003, p < 0.0001, respectively).
Despite a steady rise in the proportion of resistant bacterial infections in the ICU, crude mortality rates have decreased over time. The rates of resistant infections do not appear to be a significant factor in overall mortality in our surgical ICU patients.

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^f1: Author for correspondence: Dr C. Peña, Infectious Disease Service, Hospital de Bellvitge, University of Barcelona, E-08907 L'Hospitalet de Llobregat, Barcelona, Spain. Fax: 34-93-2607637; E-mail:[email protected]

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Journal of Hospital Infection

Abstract

References (19)

Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistantKlebsiella pneumoniae

Lancet

Risk factors forfaecal carriage of Klebsiella pneumoniae producing extended-spectrum β-lactamases in the intensive care unit

J Hosp Infect

Klebsiella bacteremia

Arch Intern Med

Nosocomial outbreak of Klebsiella pneumoniae resistant to late-generation cephalosporins

Ann Intern Med

Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center

Clin Infect Dis

Outbreak of multiply resistant Enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition

Clin Infect Dis

Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum b-lactamases

Antimicrob Agents Chemother

Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation

J Infect Dis

Detection of extended broad-spectrum β-lactamases in Enterobacteriaceae in four French hospitals

Eur J Clin Microbiol Infect Dis

Cited by (86)

Klebsiella pneumoniae: adaptive immune landscapes and vaccine horizons

Associated factors and clinical outcomes of bloodstream infection due to extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae during febrile neutropenia

Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish society of infectious diseases and clinical microbiology

Multidrug-resistant bacteria in travellers hospitalized abroad: Prevalence, characteristics, and influence on clinical outcome

Infections caused by multidrug resistant organisms are not associated with overall, all-cause mortality in the surgical intensive care unit: The 20,000 foot view

Regular ArticleAn outbreak of hospital-acquired Klebsiella pneumoniae bacteraemia, including strains producing extended-spectrum β-lactamase

Abstract

Lancet

J Hosp Infect

Klebsiella bacteremia

Arch Intern Med

Nosocomial outbreak of Klebsiella pneumoniae resistant to late-generation cephalosporins

Ann Intern Med

Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center

Clin Infect Dis

Outbreak of multiply resistant Enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition

Clin Infect Dis

Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum b-lactamases

Antimicrob Agents Chemother

Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation

J Infect Dis

Detection of extended broad-spectrum β-lactamases in Enterobacteriaceae in four French hospitals

Eur J Clin Microbiol Infect Dis

Regular Article
An outbreak of hospital-acquired Klebsiella pneumoniae bacteraemia, including strains producing extended-spectrum β-lactamase