Bloodstream Infections Among Transplant Recipients: Results of a Nationwide Surveillance in Spain1

Authors


  • 1

    The results of this article were presented in part at the 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Washington, D.C. 2005. Abstract #K-1563.

* Corresponding author: Asunción Moreno, amoreno@clinic.ub.es

Abstract

Bloodstream infections (BSIs) are a major cause of morbidity and mortality in transplant recipients. The aim of this study is to describe the incidence, microbiology and outcomes of BSIs in transplant recipients in Spain. The Spanish Network for Research on Infection in Transplantation (RESITRA) is formed by 16 centers with transplant program in Spain. The incidence and characteristics of BSIs in transplant patients were obtained prospectively from the cohort. We included 3926 transplant recipients (2935 solid organ and 991 hematopoietic stem cell transplants). Overall, 730 episodes of BSIs were recorded with an incidence rate ranging from 3 episodes per 10 000 transplant days in kidney recipients to 44 episodes per 10 000 transplant days in allogeneic hematopoietic stem cell transplantation (HSCT). The most frequent sources were intravascular catheters and the most frequent microorganisms isolated were coagulase-negative staphylococci. Crude mortality of BSIs was 7.8%, being highest in liver recipients (16%). Multidrug resistant nonfermentative gram-negative BSIs had significantly worse prognosis than those caused by their susceptible counterparts (p = 0.015), but no differences were found between resistant and susceptible gram-negative enteric bacilli, S. aureus or Candida spp. BSIs are still a major concern in transplant recipients. The increasing isolations of multiresistant microorganisms represent a challenge for the next years.

Background

Solid-organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) are currently considered standard procedures for the treatment of end-stage organ diseases and high-risk hematological malignancies. Since the beginning of the transplant programs, a progressive improvement in the prevention and management of the infections in this group of patients has been achieved, and this has been noteworthy for severe bloodstream infections (BSIs). However, the emergence of resistant pathogens and the widespread use of antibacterial and antifungal prophylaxis could lead to a change in the etiologic agents and thus to alterations in the prophylactic and empiric antimicrobial therapy used for suspected BSIs.

BSIs remain a major cause of mortality in SOT (1–3) and HSCT transplant recipients (4). The mortality can reach 50% when bacteremia is accompanied with septic shock (5). As a consequence of BSIs, patients require a prolongation in hospital stay and incur the costs associated with the hospitalization and treatment. It has been estimated the cost for care of BSI in the post renal-transplant setting is $48 400 in the United States (6).

The aim of this study was to determine the incidence, main characteristics, the microbiological features and impact of resistant bacteria emergence, and the factors associated to mortality in a large cohort of SOT and HSCT patients in Spain.

Methods

Study population

The characteristics of the Spanish Network for Research on Infection in Transplantation (RESITRA) had been described elsewhere (7,8), Briefly, RESITRA is a Network formed by 16 Hospitals in Spain with transplant programs (SOT and HSCT). It was created in April 2003 to prospectively evaluate the characteristics of transplantation in our setting, especially focusing on the incidence and features of infections in this group of patients. Pre-, peritransplant, and follow-up (2 years after transplant) data were prospectively recorded into an online database. Major events such as infection, rejection episodes, graft-versus-host disease and other complications (major surgery, medical complications, etc.) were recorded into specifically designed data collection form, according to the predefined definitions published in the RESITRA web site (http://www.resitra.retics.net/web/index.asp). Data collection is made through PDF e-forms, which are sent to an SQL-server database located in the RESITRA web site (http://www.resitra.retics.net). Data exploration is made through managerial and statistical databases generated from the SQL-server database after a validating process managed by each hospital coordinator. A young investigator in each Hospital was responsible for data collection and introduction into the database. Data were revised by a senior investigator previously to the final validation. From April to July 2003, research tools were created and implemented, and at the end of July 2003, the first patients were recruited. Patients were included in the study from July 2003 to April 2005.

Definitions

i) BSI: We considered bacteremia or fungemia to be significant according to the CDC criteria: (9) the isolation of a microorganism other than skin contaminants (diphteroids, Bacillus spp. or coagulase-negative staphylococci) in one culture with the presence of signs of infection (chills, fever, hypotension), or the isolation of a microorganism in two consecutive cultures associated with signs of infection. Systemic inflammatory response syndrome (SIRS) was diagnosed by the presence of at least two of the following criteria: temperature >38°C or <36°C, heart rate >90 ppm, tachypnea (>20 bpm, hyperventilation or PC02 < 32 mmHg) or altered white blood cell (WBC) counts (>12 × 109/L or <4 × 109/L or >10 nonsegmented neutrophils on differential count) (10). Severe sepsis was diagnosed when BI was associated with SIRS and organ dysfunction (renal failure, respiratory failure or need for mechanical ventilation) (10). Septic shock was diagnosed in patients with SIRS and hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities (10).

ii) Antibiotic resistance: For Staphylococcus aureus, resistance was evaluated in those strains resistant to methicillin. Enteric gram-negative bacilli resistance was categorized in those strains with phenotypic resistance to third-generation cephalosporins. As there is no widely accepted definition for multidrug resistance in Pseudomonas aeruginosa and Acinetobacter baumanii isolates (11), we include in this category those isolates susceptible only to colistin. In the case of Candida spp isolates, Candida krusei and Candida glabrata were considered potential fluconazole-resistant candidemias.

Statistical analysis

Categorical variables are summarized as percentages and compared using the chi-square or Fisher's exact test when appropriate. Incidence rates are expressed as number of events per 10 000 transplant days. Associations are given as an odds ratio with a confidence interval established at 95%. Survival analysis was performed by survival tables and graphically represented by actuarial survival curves. Differences between survival curves were calculated using the Wilcoxon test. A backward stepwise logistic regression model was used to identify the independent predictors for mortality. Those variables with a p-value <0.30 were introduced in the model. A two-sided p-value <0.05 was considered to be significant. All statistics were performed with the SPSS statistical package (version 12.0; SPSS, Inc., Chicago, IL).

Results

Cohort epidemiology and incidence of BSIs

In the study period, 3926 transplant recipients were included (2935 solid organ and 991 hematopoietic stem cell transplants), of which kidney was the most frequent, followed by liver and autologous stem cell transplantation (Table 1 and 2). Overall, 730 episodes of BSI were recorded, 321 in SOT and 409 in HSCT. The incidence of BSI by type of transplantation are summarized in Tables 1 and 2. BSIs were more frequent in allogeneic than in autologous HSCT, and the incidence was higher in HSCT than in SOT (p < 0.001)(Figure 1).

Table 1.  Main characteristics of the recipients of a SOT with BIs, according to the type of transplantation
 KidneyLiverHeartLungPancreas
  1. 1Within 30 days before or after the bloodstream infection episode.

Transplants performed1400 (48%)1012 (34%)291 (10%)167 (6%)65 (2%)
Number of BSI episodes121134321717
Number of patients102105241413
Ratio BSI episodes/patients1.21.31.31.21.3
Incidence by episodes8.6%13.2%11%10.2%26.1%
Incidence by patients7.3%10.4%8.2%8.4%20%
Incidence rate13.0044.8444.1436.20815.231
Source
 Catheter-related25/21%40/30%14/44%12/71%4/23%
 Urinary47/39%4/3%1/3%0/-0/-
 Pulmonary1/1%8/6%3/9%4/23%0/-
 Biliary0/-8/6%0/-0/-0/-
 Abdominal nonbiliary2/2%14/10%0/-0/-2/12%
 Surgical wound5/4%11/8%3/9%0/-1/6%
 Unknown32/26%46/34%9/28%1/6%8/47%
Microbiology
 Gram-negative75/62%59/44%13/41%3/17%5/29%
 Gram-positive39/32%62/46%19/59%11/65%10/59%
 Ratio GP/GN0.521.071.463.662.00
 Anaerobes3/2.5%8/6%0/-0/-1/6%
 Fungemia6/5%5/4%1/3%3/17%2/12%
 Candidemia6/5%5/4%1/3%3/17%2/12%
 Polymicrobial4/4%4/3%1/3%0/-2/12%
Late onset BI (>6 months)8 (6.6%)6 (4.7%)01 (6%)5 (28%)
 Candidemia01 (17%)000
 Gram-negative5 (62.5%)2 (33%)002 (40%)
 Gram-positive3 (37.5%)3 (50%)01 (100%)3 (60%)
Leukopenia10/8%19/14.5%1/3%2/13%4/29%
Septic shock7/6%30/23%5/16%2/12%3/18%
Severe sepsis
 Renal failure37/31%33/25%5/16%1/6%3/18%
 Respiratory failure5/4%25/19%6/19%4/23.5%0/-
 Mechanical ventilation3/2%17/13%4/12.5%4/23.5%0/-
Acute rejection116 (13%)21 (16%)2 (6%)2 (12%)4 (24%)
Surgical reoperation25 (21%)33 (26%)3 (9%)2 (12%)6 (35%)
CMV infection3 (2.5%)8 (6%)1 (3%)3 (18%)1 (6%)
CMV disease9 (7%)8 (6%)01 (6%)0
Crude mortality5/4%21/16%1/3%2/12%1/6%
Related mortality2/2.5%14/10%1/3%1/6%1/6%
Table 2.  Main characteristics of the recipients of a HSCT with BIs, according to the type of transplantation
 AllogeneicAutologous
  1. 1The incidence rate is expressed as number of BSIs per 10 000 transplant days.

  2. 2Within 30 days before or after the bloodstream infection episode.

  3. 3The case of fungemia other than Candida spp was an isolation of Scedosporium prolificans.

Transplants performed423 (43%)568 (57%)
Number of BSI episodes245164
Number of patients179148
Ratio BSI episodes/patients1.41.3
Incidence by episodes57.9%28.9%
Incidence by patients42.3%26%
Incidence rate14411322125
Cause for HSCT
 Acute leukemia112 (63%)44 (30%)
 Lymphoma32 (18%)49 (33%)
 Other causes35 (19%)55 (37%)
GVHD during BI
 Grade I20 (8%)
 Grade II19 (8%)
 Grade III6 (2%)
 Grade IV5 (2%)
Severe neutropenia (< 500 cells/mm3) during BI224 (53%)110 (67%)
CMV infection240 (16%)0
CMV disease212 (5%)0
Source
 Catheter-related106/44%69/42%
 Urinary9/4%1/1%
 Pulmonary14/6%9/5.5%
 Unknown99/41%77/47%
 Septic shock24/10%9/5.5%
Severe sepsis
 Renal failure13/5%7/4%
 Respiratory failure21/9%10/6%
 Mechanical ventilation11/5%5/3%
Microbiology
 Gram-negative96/39%55/33%
 Gram-positive147/60%112/68%
 Ratio GP/GN1.532.04
 Anaerobes3/1%4/3%
 Fungemia11/4.5%31/1%
 Candidemia10/4%1/1%
 Polymicrobial18/7%9/5.5%
Late onset BI (>6 months)13 (5%)16 (10%)
 Candidemia2 (15%)0
 Gram-negative4 (31%)9 (56%)
 Gram-positive7 (54%)7 (44%)
Crude mortality19/11%8/5%
Related mortality15/6%5/3%
Figure 1.

Incidence rate of bacteremia according to the type of transplantation.

Around 60% of all BSIs occurred within 1 month posttransplantation (Figure 2A). The incidence in the subsequent months was around 10% in all groups. Late-onset BSIs (more than 180 days posttransplant) represented 6% of all BSIs (49 cases).

Figure 2.

Percentage of bacteremia (A) and percentage of deaths in patients with BSIs (B) according to the posttransplant timeline.

Microbiological features and source of infection

With the exception of recipients of kidney transplants, gram-positive infections were the most frequent etiologic agents for all groups. The ratio of gram-positive (GP) to gram-negative (GN) infections was the highest in lung transplant recipients (GP/GN ratio 3.66). The incidence of candidemia was highly variable, ranging from 1% in autologous HSCT to 17% in lung transplant recipients.

Coagulase-negative staphylococci were the most frequent microorganism isolated (37%), followed by E. coli (17%). Nonfermentative gram-negative bacilli represented 15% of all isolates. Staphylococcus aureus only accounted for 5% of all bacteremias (Table 3).

Table 3.  Microbiological isolates by type of transplantation
 TotalKidneyLiverPancreasHeartLungAllo-HSCTAuto-HSCT
  1. CoNS = coagulase-negative staphylococci.

CoNS284 (37%)27 (22%)35 (25%)  5 (26%)  9 (27%)10 (59%)111 (42%)87 (50%)
E. coli127 (17%)38 (30%)15 (11%)1 (5%)  5 (15%)   41 (15.5%)27 (16%)
A. baumanii60 (8%)4 (3%)19 (14%)  3 (16%) 1 (3%) 2 (12%)19 (7%)12 (7%) 
Pseudomonas spp47 (6%)17 (14%)  9 (6.5%)1 (5%)1 (6%)15 (6%)4 (2%)
Enterococcus spp46 (6%)6 (5%) 13 (9.5%) 4 (22%) 3 (9%)1 (6%)15 (6%)4 (2%)
S. aureus37 (5%)4 (3%)10 (7%) 1 (5%)  7 (21%)   9 (3.5%)  6 (3.5%)
Klebsiella spp29 (4%)7 (5%)  9 (6.5%) 2 (6%) 6 (2%)5 (3%)
Candida spp28 (4%)6 (5%)5 (4%)  2 (10%) 1 (3%)  3 (18%)10 (4%)  1 (0.5%)
Enterobacter spp19 (2%)5 (4%)4 (3%)1 (5%) 1 (3%) 5 (2%)  3 (1.5%)
Streptococcus viridans11 (1%)1 (1%)1 (1%)   4 (1.5%)5 (3%)
Bacteroides spp9 (1%)1 (1%)7 (5%)1 (5%)
S. maltophilia7 (1%)1 (1%) 1 (3%)   4 (1.5%)  1 (0.5%)
Corynebacterium spp7 (1%)1 (1%)   2 (0.5%)4 (2%)
S. pneumoniae6 (1%)1 (1%)1 (1%)   2 (0.5%)2 (1%)
Others51 (6%)7 (5%)  9 (6.5%) 3 (9%)  20 (7.5%)12 (7%) 
Total768125138193317263173

Cephalosporin resistance was recognized in 14.5% of all enteric bacilli (Figure 3). Nearly 10% of nonfermenting gram-negative bacilli had multiple antibiotic resistance (being only sensitive to colistin). Methicillin-resistant S. aureus accounted for 16% of all S. aureus isolated. Nearly half of all Candida spp isolated were presumed to be resistant to fluconazole (C. glabrata or C. krusei).

Figure 3.

Percentage of multiresistant isolates compared with their susceptible counterparts.

Central venous catheters were the most frequent source for BSIs in all groups except kidney transplant recipients where the urinary tract predominated as the source.

Risk factors for mortality

Mortality was near 3-fold higher in liver and lung SOT and allogeneic HSCT than in the other transplant groups.

In at least 117 (16%) of cases, BSI was associated with septic shock or severe sepsis (renal or respiratory failure and need for mechanical ventilation). Overall, septic shock and severe sepsis were more frequent in liver recipients.

Regarding antibiotic resistance, only BSIs caused by multiple resistant nonfermentative bacilli (in comparison with susceptible strains) were associated with mortality (Table 4). No association with mortality was found in patients with cephalosporin-resistant gram-negative bacilli, methicillin-resistant S. aureus or presumed fluconazole-resistant Candida spp in comparison with BSIs caused by their susceptible counterparts.

Table 4.  Related deaths of multiresistant isolates compared with their susceptible counterparts
MicroorganismRelated deathsp
  1. 1Include extended spectrum betalactamase producers and chromosomic resistance (AMPc).

  2. 2Include Pseudomonas aeruginosa and Acinetobacter baumanii isolates.

Enteric bacilli
 Cephalosporin-susceptible12/144 (8.3%)NS
 Cephalosporin-resistant12/24 (8.3%) 
Non-fermentative bacilli:2
 Susceptibles8/83 (9.6%)0.015
 Multi-drug resistant4/9 (44%) 
Staphylococcus aureus:
 Methicillin-susceptible2/31 (6.5%)NS
 Methicillin-resistant0/6 
Candida spp:
 Fluconazole-susceptible1/15 (6.6%)NS
 Fluconazole-resistant1/13 (7.7%) 

We found no differences in the percentage of deaths according to the onset of BIs in the posttransplant timeline in SOT recipients (Figure 2B). However, mortality related to BIs in HSCT recipients was higher after the second month posttransplant (p = 0.0015)(Figure 2B).

In the multivariate analysis of the risk factors for mortality in SOT recipients (Table 5), BSIs in liver transplant recipients, the presence of septic shock and the need for mechanical ventilation were independently associated with higher mortality.

Table 5.  Risk factors for mortality in SOT recipients with BIs
 Unadjusted ORAdjusted OR (CI 95%)
ORCI 95%p
  1. 1Within 30 days before or after the bloodstream infection episode.

  2. 2Including biliary source, abdominal nonbiliary source and surgical-wound source.

One-year age increment1.000.98–1.030.9700
Male gender0.550.26–1.140.1090
Type of SOT 
 Liver3.151.46–6.780.00343.30 (1.21–9.00)
 Kidney0.340.14–0.850.0207
 Pancreas1.130.25–5.130.8791
 Heart0.270.04–2.010.1993
 Lung1.200.26–5.520.8108
Immunosuppressive regimen
 Tacrolimus-based0.840.39–1.800.644
 Cyclosporin-based1.040.45–2.440.925
 Use of mofetil mycophenolate0.550.26–1.180.126
CMV infection/disease10.190.03–1.500.0746
Acute rejection10.220.03–1.690.1040
Surgical reoperation11.290.53–3.150.5752
BI after 6 months posttransplant1.640.45–5.920.4525
Source0.630.26–1.510.3007
 Catheter-related0.320.08–1.390.1297
 Urinary7.002.4–21.10.0009
 Pulmonary1.660.64–4.300.3015
 Abdominal20.960.43–2.160.9156
 Unknown1.940.92–4.130.0833
Gram-negative BI0.540.25–1.180.1205
Gram-positive BI0.530.08–3.810.5329
Candidemia3.401.40–8.500.0031
Leukopenia45.314.20–144.0<0.0015.00 (1.79–13.9)
Septic shock5.602.6–12.3<0.001
Renal failure26.811.1–64.9<0.001
Respiratory failure33.012.9–84.7<0.00113.7 (4.42–42.4)
Need for mechanical ventilation 

In the multivariate analysis of the risk factors for mortality in HSCT recipients (Table 6), the presence of septic shock, respiratory failure and the need for mechanical ventilation were associated with higher mortality, while catheter-related BSI was associated with lower mortality.

Table 6.  Risk factors for mortality in HSCT recipients with BIs
 Unadjusted ORAdjusted OR (CI 95%)
ORCI 95%p
  1. HSCT = hematopoietic stem cell transplant; GVHD = graft-versus-host disease; BI = bloodstream infection.

One-year age increment0.990.98–1.020.8070
Male gender1.080.50–2.300.8507
Allogeneic transplantation1.640.70–3.840.2514
Myeloablative regimen0.620.30–1.280.1916
Cause for HSCT
 Acute leukemia0.820.40–1.800.6137
 Lymphoma1.330.56–3.130.5175
 Other causes0.970.40–2.370.9534
GVHD during episode3.011.31–6.890.0070
BI after 6 months posttransplant1.720.48–6.080.3977
Source0.050.01–0.3<0.0001  0.08 (0.01–0.91)
 Catheter-related3.750.76–18.600.0837
 Urinary7.92.9–21.5<0.0001  
 Pulmonary2.010.91–4.440.0811
 Unknown2.701.22–5.990.0115
Gram-negative BI0.200.10–0.500.0011
Gram-positive BI2.710.57–12.880.1942
Candidemia1.600.65–3.930.3007
Neutrophil count < 500 cell/mm351.719.8–135.3<0.0001  9.85 (2.81–34.6)
Septic shock36.913.1–103.7<0.0001  
Renal failure71.826.3–196.6<0.0001  6.80 (1.50–31.1)
Respiratory failure74.221.4–257.4<0.0001  8.11 (1.21–54.5)
Need for mechanical ventilation 

Discussion

Despite the use of antimicrobial prophylaxis against opportunistic infections in individuals treated with intensive immunosuppressive regimens, conventional bacteria remain a cause of potential life-threatening infections among transplant recipients. As our results show, BSI is still of concern in the transplant population with incidence rates ranging from 7.3% in kidney to 42.3% in allogeneic stem-cell transplant recipients.

As reported in previous studies (12), a shift toward gram-negative BSIs in HSCT recipients still persists (global ratio GP/GN 1.72 compared with ratios of 3.3 in the early 1990s) (13). However, gram-positive bacteria remain the most frequent agents of BSIs, and are probably associated with the use of intravascular catheters. In renal transplant recipients, whose length of hospital stay is shorter, gram-negative BIs from urinary tract source predominates. Among all sources, intravascular catheter-related is the most frequent and more preventable source BSI in all groups except in kidney transplantation. The isolation of Staphylococcus aureus and Candida spp due to catheter infection was lower than in the studies performed in the 90s (14), and this could reflect a better prophylaxis management. Because the evidence-based procedures recommended by the CDC (15) (hand-washing, the use of full-barrier precautions during the insertion of central venous catheters avoiding the femoral site, cleaning the skin with chlorhexidine, and removing unnecessary catheters) can diminish the risk of catheter-related bacteremia in the intensive-care unit setting (16), efforts for applying these measures in our transplant population are required.

About 14% of E. coli, Klebsiella spp and Enterobacter spp isolates were resistant to third-generation cephalosporins. However, the isolation of these multidrug resistant enterobacteria was not associated with higher mortality. These emerging bacteria could lead to the use of carbapenems for the empiric treatment of suspected gram-negative infections. Neither the isolation of methicillin-resistant S. aureus nor fluconazole-resistant Candida spp was associated with a worse prognosis. BSIs caused by multiple antibiotic-resistant Pseudomonas aeruginosa or Acinetobacter baumanii were associated with higher mortality. The increase of multiple drug resistant bacteria of nosocomial acquisition is probably an emerging worldwide phenomenon, as recent studies show (17). In the case of Pseudomonas spp and Acinetobacter spp this antibiotic resistance often leaves colistin as the only active drug for the treatment of these infections. In the transplant population, the use of colistin, a polymixin discovered in 1947 (18), could be associated with a higher risk of nephrotoxicity due to underlying renal impairment, the use of concomitant nephrotoxic medications such as calcineurin inhibitors, hypotension associated with medical and surgical procedures, and other related factors. Colistin renal toxicity is greater in subjects with previous renal impairment (19). Nevertheless, this drug must be used promptly when invasive infections with these bacteria are microbiologically confirmed.

Candidemia in transplant patients must have special considerations. While the incidence of candidemia in HSCT remains between 3%–and 4% in all patients (4,20), in SOT patients represents 8%. In thoracic transplantation, the incidence of candidemia has been reported to be 0.27% in heart and 1.8% in lung transplantation (21). The available data on candidemia in pancreatic transplantation is scarce. One recent study reviewed outcomes in 72 patients who underwent combined kidney-pancreas transplantation with construction of a systemic venous/enteric exocrine enteric-drainage system. In this study only one patient had a C. krusei BSI (22). In our series, two patients with pancreas transplantation had candidemia. Whether pancreas recipients are at higher risk of developing candidemia must be confirmed with larger series. In our population, about 46% of cases of candidemia are due to potentially fluconazole-resistant species (C. krusei and C. glabrata). These data must be taken into account when considering antifungal prophylaxis in transplant patients. In the case of pancreas and lung transplantation where the recipient has an implanted intravascular device, empirical antifungal therapy against Candida spp must be considered, since yeast represents more than 10% of isolates. In these cases, antifungal drugs with activity against fluconazole-resistant Candida spp are the drugs of choice (amphotericin B, new azoles or echinocandins).

BSIs crude mortality in our series ranged from 4% (related mortality 2.5%) in kidney to 16% (related mortality 10%) in liver recipients. In HSCT recipients, mortality due to bacteremia was higher in the later periods of the posttransplant (especially between the second to sixth month) in comparison with the mortality in the first month. However, BI occurring after the 6 months posttransplant was not an independent variable associated with mortality in the multivariate analysis. The development of septic shock, respiratory failure or the need for mechanical ventilation were independent variables associated with higher risk of mortality in HSCT recipients; on the other hand, catheter-related BIs was associated with lower mortality. In SOT recipients, liver transplantation, the development of septic shock or the need for mechanical ventilation were independent variables associated with mortality. Except for the higher mortality of BIs in liver transplant recipients, the rest of independent variables associated with mortality in SOT and HSCT recipients were those associated with severe sepsis and septic shock. Appropriate preventive measures and judicious use of empirical antimicrobial therapy when dealing with a transplant recipient with a high suspicion of a BSI may contribute to reducing lower the high mortality associated with this complication.

Two aspects must limit the ability to generalize these results to the transplant population. The antibiotic or antifungal susceptibility patterns of the microorganisms isolated may be widely different depending on the hospital institutions. Thus, physicians must adapt the empirical treatments to their own bacterial or fungal isolates. On the other hand, it is difficult to find independent variables associated with mortality when the analysis combine such heterogeneous populations (even if HSCT and SOT patients are separated). Probably, each type of transplant has its owns predictors of mortality. However, its difficult to analyze the predictors for each type of transplantation due to the large sample size required.

In conclusion, BSIs are still a major concern in transplant recipients. We detected a significant percentage multidrug-resistant bacteria and fungi as a cause of BSIs in our patient population. These data may portend changes in the choices of empiric antimicrobial agents when faced with a transplant recipient with a suspected BSI. A reduction in fatal outcomes associated with these infections is a challenge for the future.

Acknowledgments

This work was supported by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, ‘Fondo de Investigación Sanitaria’ (FIS PI050315), Spanish Network of Infection in Transplantation (RESITRA G03/075), and Spanish Network for the Research in Infectious Diseases (REIPI 06/0008).

All authors have no conflict of interest.

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