There is limited information regarding the clinical characteristics associated with HD access-related ESBL-Kp bacteremia in MHD patients. Most of the patients with bacteremia in the present study were elderly, malnourished, and had a history of severe illness and prolonged hospitalization. These patients were also critically ill, as determined by PBS, and had high prevalence rates of significant underlying diseases and ICU stay at the time of the onset of bacteremia; therefore, they had a high mortality rate(36/57, 63.2%). Although broad-spectrum antibiotic treatment prior to the onset of bacteremia was also highly prevalent, its contribution to the acquisition of ESBL infection and effect on patient outcome were not analyzed; this might contribute to an epidemiological bias. Only 36.8% of these critically ill patients received empiric effective antibiotics within 5 days after the first positive blood culture for ESBL-Kp, which may have contributed to the high mortality rate.
Previous studies have demonstrated vascular access accounts for 48–73% of bacteremia in HD patients [2]. In the present study, both longer LOS and a lower serum albumin level were associated with high mortality in patients with CRB. Prolonged hospitalization has been recognized as a risk factor for ESBL infection in prior studies, which reported a mean time to acquisition of ESBL-Kp bacteremia of more than 1 month [13]. Hypoalbuminemia was found to increase the likelihood of a recurrent episode of CRB among patients treated for an initial CRB [1]. In the present study, the duration of catheter-dependent HD before bacteremia was on an average longer than 1 month, and catheter-dependent HD ≥ 30 days was a significant independent risk factor for increased mortality by multivariate analysis. These findings suggest that shortening the duration of catheter-dependent HD may decrease the probability of CRB secondary to ESBL-producing bacteria and improve the prognosis. It is not surprising to find that higher PBS was independently associated with increased mortality. There was also a trend toward a longer ICU stay at the time of bacteremia in the deceased group. Because MHD patients with HD access-related ESBL-Kp bacteremia were mostly immunocompromised and critically ill, their mortality rate was determined by these parameters, which reflected the severity of the septicemia.
For ESBL infections, there are both a higher clinical failure rate [14] and mortality rate [13] associated with cephalosporin treatment. Furthermore, ESBL-producing bacteria are frequently resistant to many classes of beta-lactam and non-beta-lactam antibiotics, including cefepime [15], beta-lactam/beta-lactamase inhibitor combinations, fluoroquinolones [16], and aminoglycosides [17]. The emergence of multi-drug resistance in these virulent pathogens has significantly hampered the effort to devise effective empiric or directed antibiotic treatment regimens, and is associated with high treatment failure rates. Unfortunately, most of our patients initially received ineffective empiric antibiotics, including extended-spectrum cephalosporins, which increased the difficulty of further treatment and led to a high treatment failure and mortality rates.
Although carbapenems have been recommended for the treatment of infections caused by ESBL-producing organisms, extensive use of these antibiotics may result in the outbreak of infections related to carbapenem-resistant strains such as Acinetobacter baumanii[18], Pseudomonas aeruginosa[19], and Stenotrophomonas maltophilia[20], and it poses challenging infection-control issues. Flomoxef is unique among cephamycins in having a difluoromethylthio-acetamido group at position 7, which improves its in vitro activity against ESBL-producing Enterobacteriaceae [6, 21]. Flomoxef was also shown to be as clinically effective as a carbapenem for the treatment of flomoxef-susceptible ESBL-Kp bacteremia in terms of clinical outcome and comparable results of time-kill studies regardless of the inoculum size of 105 or 107 cfu/mL [9]. Although this study was limited by its retrospective design and small sample size, it provides insight into the possibility of using a cephamycin for infections caused by ESBL-producing bacteria. However, the efficacy of these agents for the treatment of HD access-related ESBL-Kp bacteremia in MHD patients is still unclear.
The use of effective antibiotics such as carbapenems during the 5-day period after the onset of bacteremia due to an ESBL-producing organism has been reported to be associated with lower mortality [22]. In the present study, treatment with effective antibiotics within 5 days after the onset of bacteremia and the use of carbapenems improved the prognosis in patients with CRB. The choice of antibiotics is critical, in the light of our finding that treatment with flomoxef was an independent risk factor for increased mortality in these vulnerable patients by multivariate analyses. The lower percentage of patients receiving effective empiric antibiotics may reflect our collective unawareness of the significance of these emerging strains and the very limited information regarding this issue.