Multidrug Resistant Gram‐Negative Bacteria in Solid Organ Transplant Recipients

The incidence of colonization and infection with multidrug resistant Gram-negative bacteria has been increasing throughout the world (1,2). Although there are limited data regarding this in transplant recipients, these patients typically are among those at higher risk for infections and it is therefore, likely that colonization and infection with resistant Gram-negative organisms are increasing in transplant recipients as well. In transplant recipients, these organisms have been most frequently described in nosocomial settings and in patients with cystic fibrosis (CF). However, with the growing trend toward infections with resistant organisms in community-acquired infections in nontransplant patients, it is anticipated that more resistant bacterial infections may be acquired more frequently outside the hospital environment in the future. Reports in transplant patients include, but are not limited to the presence of extended spectrum beta-lactamase (ESBL) producing, AmpC beta-lactamase producing enteric Gram-negative bacteria, and resistant Acinetobacter infections in abdominal organ, renal and lung transplant recipients, as well as resistant Pseudomonas and Burkholderia infections in lung transplant candidates and recipients. The sites of infection have been diverse and have included the urinary tract, lower respiratory tract, intra-abdominal, bloodstream and wounds. Multidrug resistance (MDR) is defined as resistance to all antibiotics tested in at least two of the three following classes: fluoroquinolones, b-lactams and aminoglycosides. Pan-resistance (PR) is defined as resistance to all licensed, routinely available antibacterials. ESBL-producing bacteria, carbapenem-resistant Klebsiella pneumoniae and MDR Acinetobacter: There are no recent surveys to define the incidence of colonization and infection with ESBL-producing Gram-negative organisms; it appears likely that there is significant worldwide variation in their prevalence. Surveillance data from 1998 and 2001, in liver and intestinal transplant recipients, suggest that these organisms may commonly colonize the gastrointestinal tract in these patients with colonization rates of 31% for ESBL-producing Klebsiella in intestinal transplant recipients and 67% for ESBL-producing E. coli in an adult liver transplant unit (3,4). In a 2008 survey of beta-lactamase producing Gram-negative infections in transplant recipients, 43% of E. coli and Klebsiella isolates were beta-lactam resistant (5). Sporadic nosocomial outbreaks have been reported involving patients in intensive care units, as well as in liver and renal transplant units (3,6– 8). Although Linares and colleagues report increased morbidity associated with ESBL-producing and Amp C betalactamase Gram-negative organisms in a population of renal transplant recipients, the majority of studies do not report worse outcomes in patients with ESBL-producing Gram-negative pathogens when compared with those of patients with more susceptible organisms (5). MDR Acinetobacter infections have been reported in lung transplant recipients; the actual incidence of these infections is unknown (9). MDR Acinetobacter infections may be associated with increased mortality in transplant recipients, especially in critically ill surgical patients (10). Carbapenemresistant Klebsiella pneumoniae have been increasingly reported as a cause of nosocomial infections associated with significant morbidity and mortality. Although no specific association with organ transplantation has been noted, risk factors have included antibiotic exposure (especially to fluoroquinolones) and ICU stay, both of which are common in transplant recipients (11).