This study was presented in part at the 2012 Annual Meeting of the American Transplant Congress in Boston, MA.
Impact of pretransplant rifaximin therapy on early post–liver transplant infections
Article first published online: 26 MAR 2014
© 2014 American Association for the Study of Liver Diseases
Volume 20, Issue 5, pages 544–551, May 2014
How to Cite
Esfeh, J. M., Hanouneh, I. A., Koval, C. E., Kovacs, C., Dalal, D. S., Ansari-Gilani, K., Confer, B. D., Eghtesad, B., Zein, N. N. and Menon, K. V. N. (2014), Impact of pretransplant rifaximin therapy on early post–liver transplant infections. Liver Transpl, 20: 544–551. doi: 10.1002/lt.23845
- Issue published online: 25 APR 2014
- Article first published online: 26 MAR 2014
- Accepted manuscript online: 3 FEB 2014 09:42AM EST
- Manuscript Accepted: 27 JAN 2014
- Manuscript Received: 15 SEP 2013
Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period. Liver Transpl 20:544–551, 2014. © 2014 AASLD.
Liver transplantation (LT) is currently the standard of care for both acute and chronic liver failure. After LT, patients need lifelong immunosuppression for the prevention of rejection; however, immunosuppression is associated with an increased risk of infection. Additionally, intensive care unit (ICU) stay during the immediate posttransplant period increases the risk of infection for many of these patients. Infectious complications are the leading cause of morbidity and mortality in this patient population, especially in the first 30 days after transplantation when patients are at risk for donor-derived, recipient-derived, and surgical infections. Bacterial (especially due to gram-negative bacteria) and fungal wound and blood stream infections, urinary infections, pneumonias, and Clostridium difficile–associated diarrhea and colitis are the most troublesome infectious complications after LT with an estimated frequency of 20% to 80%. These infections increase the length of the hospital stay and costs and are the main causes of death after LT.[3-5] The majority of these post-LT infections (75%) occur in the first month after surgery.[6-9] The endogenous microbial flora in the oropharynx, stomach, and intestines play a major role in causing these infections. A number of risk factors for early bacterial infections (EBIs) after LT have been identified, and they include renal failure, hemodialysis, the length of the transplant surgery, the total number of blood product units given during surgery, and the length of the ICU stay.
The benefits of the administration of intestinal decontamination to sick patients admitted to the ICU have been shown in multiple studies.[11-14] However, its universal use in LT candidates is controversial, and data showing a benefit from intestinal decontamination before LT are not robust.[4, 15] Most of these studies have used quinolones and/or nystatin to control the endogenous flora because these contribute the most to posttransplant infections.
Rifaximin (Xifaxan), a nonsystemically absorbed antibiotic, was initially approved by the Food and Drug Administration for the treatment of traveler's diarrhea. In 1998, it received orphan drug status from the US Food and Drug Administration to be used for the treatment of hepatic encephalopathy. It is a semisynthetic, nonsystemically absorbed rifamycin-based antibiotic with an additional pyridoimidazole ring limiting the drug's effect on the gastrointestinal tract. Rifaximin has activity against aerobic and anaerobic gram-positive and gram-negative bacteria.[17, 18] Rifaximin is currently widely used for the treatment of hepatic encephalopathy. To date, no study has determined the effect of rifaximin therapy in the pre-LT period on EBIs and fungal infections within the first 30 days after LT.
The aims of our study were (1) to determine the effect of rifaximin therapy in the pretransplant period on bacterial and fungal infections within the first 30 days after LT and (2) to determine the risk factors for EBIs after LT.
PATIENTS AND METHODS
All adult patients (age ≥ 18 years) who underwent LT at the Cleveland Clinic between January 2009 and July 2011 were included in the study. Patients receiving concurrent antibiotics other than pretransplant protocol antibiotics, those with human immunodeficiency virus infections (according to both enzyme-linked immunosorbent assays and western blot tests), and those with a history of systemic malignancy (not including hepatocellular carcinoma) were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. In our study, 48 hours of therapy was used as the inclusion criterion in order to ensure adequate intraluminal concentrations of rifaximin. This was based on the study by Gruttadauria et al., who showed that in patients undergoing colorectal surgery, preoperative treatment with rifaximin for 48 to 72 hours reduced fecal counts of both aerobic and anaerobic bacteria. The standard dosage of rifaximin for the treatment of hepatic encephalopathy was 550 mg taken orally every 12 hours. The institutional review board of the Cleveland Clinic approved the study.
Immunosuppression induction therapy at our institution consisted of 2 doses of an interleukin-2 receptor antagonist (basiliximab). The main immunosuppressive agent used after LT was a calcineurin inhibitor. When side effects prevented the full therapeutic dose of the calcineurin inhibitor from being used, mycophenolate mofetil was added. Corticosteroids were generally discontinued 21 days after surgery.
Mild episodes of acute cellular rejection were treated with an increase in the dose of the calcineurin inhibitor, whereas moderate and severe rejection (defined as a rejection activity index > 5) was managed with intravenous corticosteroids.
All patients who underwent orthotopic LT, regardless of the cytomegalovirus (CMV) serum status, were treated with 2 weeks of valganciclovir prophylaxis followed by acyclovir for the remaining 3 months. Preemptive therapy with CMV DNA monitoring was then initiated every 2 weeks for the first year. CMV viremia was determined with CMV DNA polymerase chain reaction and was recorded as copies per milliliter. Patients who developed CMV viremia were treated with intravenous ganciclovir or oral valganciclovir.
Demographic data included the age, sex, ethnicity, etiology of the underlying liver disease, and Model for End-Stage Liver Disease (MELD) score. Variables that were possible risk factors for early infections were divided into 3 broad categories:
- Pretransplant risk factors (1-month preoperative period): diabetes mellitus, chronic obstructive pulmonary disease, renal failure (creatinine level > 2.5 mg/dL for more than 7 days) with or without the need for hemodialysis, ICU admission with or without the need for mechanical ventilation, and previous LT.
- Intraoperative risk factors: length of transplant surgery, total number of packed red blood cell (PRBC) units given during surgery, type of biliary anastomosis (duct-to-duct versus Roux-en Y), donor age, and donor CMV status.
- Posttransplant risk factors: multiorgan transplantation, immunosuppression, acute allograft rejection, number of acute rejection episodes, type of treatment administered for acute rejection, length of the ICU stay, mechanical ventilation and its duration, vasopressor requirements, readmission to the ICU, retransplantation (in the first 7 days after LT), renal failure, need for hemodialysis, and postoperative complications (including bleeding and biliary strictures).
Infection Episode Definition
An infection was diagnosed only if strict clinical and microbiological data were present. Bacterial infections were defined according to the American Society of Transplantation recommendations for reporting infectious complications of organ transplantation during immunosuppression trials:
- Infections meeting criteria for uncomplicated cystitis, pyelonephritis, or perinephric abscesses were considered to be genitourinary infections.
- Infected intra-abdominal fluid collections and frank peritonitis were classified as intra-abdominal infections if appropriate criteria were met. To be reported as an intra-abdominal abscess, a fluid collection must have been identified radiographically or at laparotomy with positive cultures obtained in a sterile fashion. Cultures of externalized drains were deemed inadequate for documenting infections because of concerns about colonization.
- A lower respiratory tract infection was recognized if a positive sputum culture, a bronchoalveolar lavage culture, or a lung biopsy specimen was obtained with at least 1 of the following symptoms: cough, hemoptysis, fever, dyspnea, radiographic infiltrates on computed tomography or a chest X-ray, or new-onset pleuritic chest pain.
- Invasive fungal infections were defined according to the revised criteria proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus group. Those classified as proven were considered to be invasive fungal infections, whereas those meeting criteria for possible infections were discarded.
A univariate analysis was performed to assess differences between the subjects who took rifaximin and those who did not. Student t tests or nonparametric Wilcoxon rank-sum tests were used to compare continuous factors, and Pearson chi-square tests were used for categorical variables. In addition, a time-to-event analysis was performed to study the occurrence of post-LT infections as well as survival. The follow-up time was defined as the time between LT and the occurrence of an event or the last follow-up visit if there was no infection. Kaplan-Meier plots were constructed, and log-rank tests were used to compare the rifaximin groups. Also, univariate and multivariate Cox regressions were performed to evaluate factors associated with the occurrence of post-LT infections. An automated, stepwise, variable selection method performed on 1000 bootstrap samples was used to choose the final multivariate model; the use of rifaximin was included in the models, and all other factors were considered for inclusion. Variables with an inclusion rate of 15% or higher were kept in the model. P < 0.05 was considered statistically significant. All analyses were performed with SAS 9.2 (SAS Institute, Cary, NC) and R 2.13.1 (R Foundation for Statistical Computing, Vienna, Austria).
The records of 351 patients who underwent LT between January 2009 and July 2011 were reviewed. Eighty-three of the recipients (23.6%) were excluded from the study because they had concurrently received antibiotics other than pretransplant protocol antibiotics or had a definite diagnosis of human immunodeficiency virus and/or systemic malignancy (other than hepatocellular carcinoma). The remaining 268 patients (76.4%) with a follow-up period of at least 30 days were included in the study. Among them, 71 (26.5%) were identified to be on rifaximin for at least 2 days before surgery (the rifaximin group). The remaining 197 patients (73.5%) made up the non-rifaximin group.
LT recipients in both groups received protocolized surgical prophylaxis in the form of ampicillin-sulbactam (Unasyn; 3 g every 6 hours for 24 hours). Those who were allergic to penicillin received vancomycin (1 g every 12 hours for 24 hours) and ciprofloxacin (400 mg intravenously every 12 hours for 24 hours).
The demographic and clinical characteristics of the patients are shown in Table 1. The 2 groups were comparable with respect to age, sex, race, and MELD score (the mean score was less than 30 for both groups) at the time of transplantation. Tacrolimus was the primary immunosuppressant for the majority of the patients (98%).
|Factor||Missing (n)||No Rifaximin (n = 197)||Rifaximin (n = 71)||P Value|
|Age at LT (years)a||4||53.2 ± 15.4||55.3 ± 9.8||0.29|
|Sex: male [n (%)]||0||129 (65.5)||53 (74.6)||0.16|
|Race: Caucasian [n (%)]||26||151 (86.3)||60 (89.6)||0.5|
|Pre-LT diabetes mellitus [n (%)]||6||50 (26.2)||28 (39.4)||0.04|
|Pre-LT chronic obstructive pulmonary disease [n (%)]||5||4 (2.1)||2 (2.8)||0.72|
|Pre-LT renal failure: creatinine > 2.5 mg/dL [n (%)]||5||20 (10.4)||12 (16.9)||0.15|
|Etiology, nonexclusive [n (%)]|
|Hepatitis C virus||5||72 (37.5)||24 (33.8)||0.58|
|Hepatitis B virus||5||11 (5.7)||2 (2.8)||0.33|
|Alcohol||5||20 (10.4)||8 (11.3)||0.84|
|Nonalcoholic steatohepatitis||5||24 (12.5)||21 (29.6)||0.001|
|Hepatocellular carcinoma||5||76 (39.6)||13 (18.3)||0.001|
|Primary biliary cirrhosis/primary Sclerosing Cholangitis||5||27 (14.1)||6 (8.5)||0.22|
|Cryptogenic||5||9 (4.7)||3 (4.2)||0.87|
|MELD scorea||7||21.3 ± 4.9||22.5 ± 6.7||0.11|
|Pretransplant ascites based on ultrasound [n (%)]||13||114 (62.0)||52 (73.2)||0.09|
|Dialysis before LT [n (%)]||6||12 (6.3)||8 (11.4)||0.16|
|ICU admission 1 month before LT [n (%)]||5||4 (2.1)||6 (8.5)||0.02|
|Days on rifaximina||0||-||163 ± 16|
|Number of LT procedures [n (%)]||5||0.32|
|1||185 (96.3)||67 (94.4)|
|2||7 (3.6)||3 (4.2)|
|Combined liver-kidney transplant [n (%)]||5||11 (5.7)||5 (7.0)||0.69|
|Combined liver-heart transplant [n (%)]||5||3 (1.6)||0 (0.0)||0.29|
|Combined liver-lung transplant [n (%)]||5||2 (1.0)||0 (0.0)||0.39|
|Length of LT surgery (hours)a||13||9.4 ± 1.7||9.5 ± 1.7||0.67|
Patients on rifaximin at the time of transplantation were more likely to have nonalcoholic steatohepatitis as a cause for cirrhosis. In addition, a pretransplant diagnosis of diabetes mellitus, admission to the ICU 1 month before transplantation, a higher number of units of PRBCs given during surgery, and an absence of acute allograft rejection after LT were more common in the rifaximin group. Patients in the rifaximin group were found to have had a longer ICU stay after LT, an increased rate of dialysis after transplantation, more vasopressor utilization in the ICU, and a longer period of mechanical ventilation after surgery. The need for ICU readmission and red blood cell transfusions at the time of LT were also increased (Table 2).
|Factor||Missing (n)||No Rifaximin (n = 197)||Rifaximin (n = 71)||P Value|
|ICU stay after LT (days)a||10||4.3 ± 4.7||10.7 ± 13.5||<0.001|
|Dialysis after LT [n (%)]||6||7 (3.5)||13 (21.7)||<0.001|
|Need for pressor in ICU [n (%)]||8||31 (15.5)||28 (46.7)||<0.001|
|Mechanical ventilation (days)||8||1.00 (1.00-1.00)||1.00 (1.00-3.5)||<0.001|
|Donor age (years)a||9||51.2 ± 13||49.8 ± 15||0.3|
|CMV status: seropositive donor/seronegative recipient [n (%)]||7||21 (10.6)||8 (11.2)||0.43|
|Urgent repeat LT in first 7 days after LT [n (%)]||10||2 (1.0)||4 (6.8)||0.1|
|Bile leak after LT [n (%)]||7||2 (1.00)||1 (1.7)||0.67|
|Portal vein thrombosis [n (%)]||7||2 (1.00)||0 (0.0)||0.44|
|Intra-abdominal bleeding [n (%)]||7||13 (6.5)||10 (16.7)||0.06|
|Biliary stricture [n (%)]||7||7 (3.5)||6 (10.0)||0.42|
|Repeat ICU stay [n (%)]||7||3 (1.5)||9 (15.0)||<0.001|
|PRBCs at LT (U)||12||4.0 (2.0-5.0)||4.5 (4.0-6.0)||0.006|
|Type of biliary derivation [n (%)]||11||0.6|
|Duct-to-duct||177 (88.5)||49 (86.0)|
|Roux-en-Y||23 (11.5)||8 (14.0)|
|Cyclosporine [n (%)]||11||3 (1.5)||3 (5.1)||0.11|
|Tacrolimus [n (%)]||11||194 (98.0)||58 (98.3)||0.87|
|Mycophenolate mofetil [n (%)]||11||171 (86.4)||50 (84.7)||0.75|
|Azathioprine [n (%)]||11||1 (0.51)||1 (1.7)||0.57|
|Steroids [n (%)]||11||195 (98.5)||59 (100.0)||0.34|
|Sirolimus [n (%)]||15||12 (6.2)||1 (1.7)||0.17|
|Rejection after LT [n (%)]||19||17 (8.9)||1 (1.7)||0.07|
|Rejection episodes (n)||253||1.00 (1.00-1.00)||1.00 (1.00-1.00)||0.79|
|Treatment of rejection, if applicable [n/N (%)]||0||0.8|
|Steroids||16/17 (94.1)||1/1 (100.0)|
|Steroids + mycophenolate mofetil||1/17 (5.9)||0/1 (0.0)|
Among the 268 recipients, 60 (22.4%) suffered either bacterial or fungal infections within the first 30 days after transplantation. Demographic and preoperative characteristics of the LT recipients with or without the development of EBIs are shown in Table 3. The most common EBIs were intra-abdominal infections (88.3%). These included peritonitis, subhepatic abscesses, and intra-abdominal abscesses. Other common infections were posttransplant bacteremia (10.9%), genitourinary infections (6.16%), colitis and/or gastroenteritis (3.23%), skin and soft tissue infections (4.25%), intra-abdominal infections (4.27%), lower respiratory tract infections (3.32%), and invasive fungal infections (1.7%). The identified infectious agents are shown in Table 4.
|Factor||Missing (n)||No Early Infection (n = 208)||Early Infection (n = 60)||P Value|
|Age at LT (years)a||4||53.5 ± 14.0||54.7 ± 14.6||0.55|
|Sex: male [n (%)]||0||137 (65.9)||45 (75.0)||0.18|
|Race: Caucasian [n (%)]||26||165 (86.8)||46 (88.5)||0.76|
|Pre-LT diabetes mellitus [n (%)]||6||59 (29.2)||19 (31.7)||0.71|
|Pre-LT chronic obstructive pulmonary disease [n (%)]||5||6 (3.0)||0 (0.0)||0.18|
|Pre-LT renal failure: creatinine > 2.5 mg/dL [n (%)]||5||22 (10.8)||10 (16.7)||0.22|
|Etiology, nonexclusive [n (%)]|
|Hepatitis C virus||5||73 (36.0)||23 (38.3)||0.74|
|Hepatitis B virus||5||11 (5.4)||2 (3.3)||0.51|
|Alcohol||5||24 (11.8)||4 (6.7)||0.26|
|Nonalcoholic steatohepatitis||5||35 (17.2)||10 (16.7)||0.92|
|Hepatocellular carcinoma||5||74 (36.5)||15 (25.0)||0.1|
|Primary biliary cirrhosis/primary sclerosing cholangitis||5||24 (11.8)||9 (15.0)||0.51|
|Cryptogenic||5||10 (4.9)||2 (3.3)||0.6|
|MELD scorea||7||21.4 ± 5.0||22.4 ± 6.8||0.24|
|Pretransplant ascites based on ultrasound [n (%)]||13||127 (64.5)||39 (67.2)||0.7|
|Dialysis before LT [n (%)]||6||12 (5.9)||8 (13.3)||0.058|
|ICU admission 1 month before LT [n (%)]||5||5 (2.5)||5 (8.3)||0.04|
|Rifaximin at LT [n (%)]||0||53 (25.5)||18 (30.0)||0.48|
|Days on rifaximina||0||179.1 ± 177.0||115.4 ± 103.3||0.15|
|Number of LT procedures [n (%)]||5||<0.001|
|1||199 (98.0)||53 (88.3)|
|2||3 (1.5)||7 (11.7)|
|4||1 (0.49)||0 (0.0)|
|Simultaneous liver-kidney transplant [n (%)]||5||8 (3.9)||8 (13.3)||0.007|
|Simultaneous liver-heart transplant [n (%)]||5||1 (0.49)||2 (3.3)||0.07|
|Simultaneous liver-lung transplant [n (%)]||5||0 (0.0)||2 (3.3)||0.009|
|Length of LT surgery (hours)a||13||9.4 ± 1.7||9.7 ± 1.8||0.25|
|Isolated Microorganism||No Rifaximin (n = 197)||Rifaximin (n = 71)|
|Enterobacteriaceae||32 (16.2)||11 (15.8)|
|Pseudomonas aeruginosa||18 (9.1)||6 (8.9)|
|Other gram-negative bacteria||76 (38.8)||30 (41.6)|
|Clostridium difficile||13 (6.4)||4 (6.1)|
|Methicillin-resistance Staphylococcus aureus||12 (6.3)||4 (5.9)|
|Vancomycin-resistant Enterococcus faecium||7 (3.8)||3 (3.6)|
|Other gram-positive bacteria||39 (19.4)||13 (18.1)|
There was no significant difference in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48). This did not change after adjustments for baseline confounders, including the length of the ICU stay, the length of the surgery, the need for vasopressors in the ICU, the duration of mechanical ventilation, the number of blood transfusion units at the time of surgery, and the use of azathioprine and mycophenolate mofetil after transplantation. There was no difference in drug resistance between the 2 groups. There was also no difference in fungal infections between the 2 groups.
After 30 days of follow-up, the survival rates were estimated to be 98% for patients who were on rifaximin and 97% for patients who were not on rifaximin (P = 0.36; Fig. 1). Post-LT survival was, therefore, not affected by treatment with rifaximin at the time of LT. The mortality rate was, however, higher for patients who developed EBIs after transplantation versus those who did not (P = 0.03).
Factors found to be significantly associated with infections early after orthotopic LT included an ICU admission 1 month before LT, previous LT, liver-kidney or liver-lung transplantation, a longer ICU stay, a need for post-LT dialysis, vasopressor use in the ICU, more days on mechanical ventilation, a need for urgent re-LT, intra-abdominal bleeding, biliary strictures, readmission to the ICU, and the number of red blood cell transfusions during transplantation. Independent risk factors for EBIs were noted to include pressor use in the ICU and the length of the ICU stay after LT (Table 5). For every additional day in the ICU after LT, the hazard of having an infection increased by 6%.
|Factor||Odds Ratio (95% CI)||P Value|
|Rifaximin at the time of LT||0.99 (0.47-2.1)||0.98|
|Need for pressor in ICU||3.1 (1.4-6.6)||0.004|
|Post-LT ICU stay (days)||1.07 (1.00-1.1)||0.035|
|Mechanical ventilation (days)||0.97 (0.79-1.2)||0.78|
|Length of LT surgery (hours)||1.07 (0.88-1.3)||0.5|
|PRBCs (U)||1.04 (0.94-1.1)||0.43|
Despite the declining incidence of EBIs after LT, infections still remain major postoperative complications. The rate of early bacterial and fungal infections in our study was 22.4%, which is within the range mentioned in previous studies.[3-5] More importantly, EBIs were associated with increased mortality, and their prevention will help to improve the outcomes of LT. However, efforts at using different antibiotics for the purpose of intestinal decontamination have shown conflicting results.
Gorensek et al. showed in a cohort study that selective bowel decontamination with a combination of norfloxacin and nystatin was well tolerated and highly effective in reducing early gram-negative and fungal infections after transplantation. However, 2 different studies by San-Juan et al. and Zwaveling et al. found no significant protective effects from norfloxacin or ciprofloxacin against the development of bacterial infections. This was confirmed by a more complicated prophylactic regimen in a randomized clinical trial.[24, 25] A recent study by Sun et al. showed a protective effect of rifaximin against posttransplant EBIs in more severely ill LT recipients with no increase in multidrug-resistant bacterial infections.
In our study, we assessed the drug resistance of infecting organisms and did not detect a shift to infectious organisms outside rifaximin's reported spectrum of activity. This is important because it overrides the argument against using rifaximin for fear of the emergence of clinically significant antimicrobial resistance. However, we did not screen for the resistance of colonizing organisms. Thus, more deliberate and prolonged surveillance might be necessary to detect the possible emergence of resistance in the setting of rifaximin use.
It is also important to note that rifaximin was used only in the pretransplant period and was not continued after transplantation. It is unknown whether continuing the administration of rifaximin in the immediate postoperative period can decrease the rate of early bacterial and fungal infections after LT.
A number of risk factors have been found to be associated with EBIs after LT, and these include hemodialysis, the length of the transplant surgery, the total amount of blood product units given during surgery, and the length of the ICU stay. In our study, we found that the use of pressor support in the ICU and the length of stay in the ICU were independently associated with the risk of EBIs after LT. Our findings about the association of the use of pressor support and the length of the ICU stay with EBIs may be inherently related to the fact that these were sicker patients needing additional support after LT. Such patients may, therefore, benefit from close monitoring for infections and early treatment.
Some drawbacks of the present study deserve consideration. First, this was a retrospective study with all its inherent biases. Second, early bacterial and fungal infections in this study were defined by the isolation of a microorganism (bacterial or fungal) and/or a positive culture within the first 30 days after LT. Although the majority of studies[4, 26, 27] have included an isolated microorganism or a positive culture as an important and even obligatory component of the definition of an infection episode, it is possible that patients with infections who had negative cultures may have been missed. This was more important for patients who were incapable of complaining about the symptoms used to guide diagnostic evaluations and could have led to a falsely low recorded number of EBIs. However, because the rates of EBIs in our study were similar to those found in other reports, it is unlikely that major infectious episodes were missed in the current study. All patients on rifaximin had hepatic encephalopathy in our study. Patients in the rifaximin group, therefore, appeared to be sicker overall, and the groups were not evenly matched.
In conclusion, the use of rifaximin in the pre-LT period did change the rates of bacterial and fungal infections in the first 30 days after LT; importantly, resistant bacterial and fungal infections were not seen.
- 4for Spanish Network of Infection in Transplantation/Spanish Network for Research in Infectious Diseases. Selective intestinal decontamination with fluoroquinolones for the prevention of early bacterial infections after liver transplantation. Liver Transpl 2011;17:896-904., , , , , , et al.;
- 7for AST Infectious Diseases Community of Practice. Multiply resistant gram-positive bacteria methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus (MRSA, VISA, VRSA) in solid organ transplant recipients. Am J Transplant 2009;9(suppl 4):S41-S49.;
- 14Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial. Am J Respir Crit Care Med 2002;166:1029-1037., , , , , , et al.
- 17A new use for Xifaxan. Nurse Pract 2011;36:8-9..
- 20for AST ID Working Group on Infectious Disease Monitoring. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant 2006;6:262-274., ;
- 21for European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus group. Clin Infect Dis 2008;46:1813-1821., , , , , , et al.;
- 27for RESITRA Network, Spain. Incidence, clinical characteristics and risk factors of late infection in solid organ transplant recipients: data from the RESITRA study group. Am J Transplant 2007;7:964-971., , , , , , et al.;
early bacterial infection
intensive care unit
Model for End-Stage Liver Disease
packed red blood cell