Extended-Spectrum β-Lactamases and Clinical Outcomes: Current Data

Abstract

Nosocomial infections caused by extended-spectrum b-lactamase (ESBL)-producing gram-negative bacteria complicate therapy and limit treatment options. However, the clinical significance of infections caused by ESBL-producing bacteria remains unclear. A critical examination of the literature provides divergent views of the effect of ESBL carriage on morbidity and mortality and suggests that ESBL production may have its most marked effect on ceftazidime. Effective strategies for the empirical and directed treatment of infections caused by ESBL-producing pathogens include the use of carbapenems and, possibly, the fourth-generation cephalosporin cefepime. Studies indicate that the use of cefepime to treat serious nosocomial infections (e.g., bacteremia, pneumonia, and urinary tract infections) is associated with high rates of microbiological and clinical success. The probability of attaining time above the minimum inhibitory concentration targets of at least 70% of the dosing interval, an important pharmacodynamic indicator of clinical success, is higher with cefepime than with other antimicrobials against Escherichia coli and Klebsiella pneumoniae strains exhibiting ESBL phenotypes. However, for non-ESBL-producing strains, there is no difference in the time above the minimum inhibitory concentration between ceftazidime and cefepime. When used appropriately in institutional settings, cefepime reduces the overall use of cephalosporins, thereby decreasing selection pressure for presumptive ESBL-producing pathogens.Infections caused by multidrug-resistant bacteria expressing extended-spectrum b-lactamases (ESBLs) pose serious challenges to clinicians. Because ESBL-producing bacteria are resistant to a broad range of b-lactams, including third-generation cephalosporins, nosocomial infections caused by these organisms complicate therapy and limit treatment options [1]. In addition, patients infected with ESBL-producing bacteria may have a higher mortality rate and may require longer hospital stays because they are generally sicker and have received more antibiotics than patients who are not infected with ESBL-producing strains. Nevertheless, the clinical significance of infections caused by ESBL-producing bacteria remains unclear, primarily because few prospective studies have been designed specifically to evaluate clin- ical outcomes among a statistically meaningful number of patients [2,3]. Studies of this kind are essential for developing consensus guidelines (which are not currently available) for the treatment of infection due to ESBL-producing bacilli.A critical examination of the literature provides divergent views of the role of ESBL carriage in death and suggests that ESBL production may have its most marked effect on ceftazidime, but this could be a geographic or enzyme-specific variation [3,4]. The present review summarizes recent reports in the medical literature related to the clinical significance of ESBL expression and describes strategies for the treatment of infections caused by ESBL-producing pathogens. ...

TheKlebsiella pneumoniaeYfgL (BamB) lipoprotein contributes to outer membrane protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, andin vivovirulence

“…The non-specificity of K. pneumoniae for adherence to various host tissues is not surprising, given that this pathogen causes several kinds of infections, including pneumonia, bacteremia, urinary tract infection, and PLA. [1][2][3] Strains with the K1 and K2 capsular types have been identified as the predominant virulent types and are prevalent in K. pneumoniae PLA. 4,10 Moreover, brain and eyes are immune privileged sites; once these tissues are invaded by pathogens, brain and eyes would be highly susceptible to infection.…”

“…[1][2][3][4] Recently, community-acquired pyogenic liver abscess (PLA) caused by K. pneumoniae has emerged, with 10-13% of PLA patients also exhibiting metastatic meningitis and/or endophthalmitis. [4][5][6][7][8][9][10] Mortality rates are 10% for those with K. pneumoniae PLA alone, and 30-40% among those with metastatic meningitis.…”

Isolation, Phenotypic Characterization and Prevalence of ESBL-Producing Escherichia Coli and Klebsiella Species from Orthopedic Wounds in National Orthopedic Hospital Enugu (NOHE), South East Nigeria

“…ESBLs have been found in a great number of different bacterial species, but more frequently in Escherichia coli and Klebsiella pneumonia [2]. There have also been reports of the growing concern of the Enterobacteriaceae and Pseudomonas spp producing ESBLs among nosocomial and also community-acquired infections [3]. Wounds occur in countless ways and vary broadly in severity.…”

Successful Treatment of a Patient with Ventriculoperitoneal Shunt-Associated Meningitis Caused by Extended-Spectrum <i>β</i>-Lactamase-Producing <i>Klebsiella pneumoniae</i>

“…Effective antimicrobial agents for infections caused by ESBL-producers are carbapenems (Ramphal and Ambrose 2006). Meropenem is recommended by the Infectious Diseases Society of America (IDSA) treatment guidelines for meningitis, especially when the causative pathogens are ESBL-producing gram-negative bacilli (Tunkel et al 2004).…”

“…The IDSA guideline recommends a 21-day antimicrobial therapy for aerobic gram-negative bacilli related meningitis (Tunkel et al 2004). Timely and appropriate treatment is important to reduce mortality and morbidity of infections caused by ESBL-producing organisms (Ramphal and Ambrose 2006).…”