Objectives: Infection is a common cause of morbidity and mortality after kidney transplant. Based on the well-documented successes of reducing infections with decolonization of patients in intensive care units, we began a universal immediate posttransplant decolonization program for all kidney transplant recipients. Herein, we report safety and efficacy of this decolonization program.
Materials and Methods: We compared a consecutive cohort of kidney transplant recipients who underwent universal decolonization (intervention group) with a cohort of transplant patients from an era immediately prior to this practice (control group). Universal decolonization included daily chlorhexidine body wash and nasal mupirocin ointment.
Results: Seventy-eight patients who underwent universal decolonization were compared with 43 patients in the control group. Ten microbiologically proven infections (8.3%) occurred in the 30 days after discharge: 7 (9%) in the intervention group and 3 (7%) in the control group. Forty-five transplant recipients (37.2%) were readmitted in the 30 days after discharge: 31 (39.7%) in the intervention group and 14 (32.6%) in the control group. No patients in the intervention group had adverse drug events from mupirocin and chlorhexidine use.
Conclusions: A universal decolonization protocol was successfully implemented and was well tolerated by all patients. Despite successful implementation, we did not observe any significant differences in infection rates between treated patients and historical controls.
Key words : Infection prevention, Intensive care unit, Renal transplant
Infection is a common cause of morbidity and mortality after kidney transplant (KT). Despite careful pretransplant screening of donors and recipients, as well as vaccination and immuno-prophylaxis, pre-venting infection in the early transplant period remains challenging. Kidney transplant recipients are at high risk of developing infections in the post-transplant period. Risk factors for infection include previous multidrug-resistant (MDR) pathogen exposure, reduction in effective immunity secondary to immunosuppression, central venous catheters, and surgical wounds.1
Decolonization with intranasal mupirocin and chlorhexidine bathing has been used to reduce transmission and to prevent infection from Staphylococcus aureus carriers.2-4 The broad antimicrobial activity of chlorhexidine makes it attractive for preventing hospital-acquired infection by lowering bacterial concentrations on the body surface.5-7 Universal decolonization strategies have been shown to decrease the incidence of bloodstream infections in the intensive care unit (ICU).8 To our knowledge, there are no studies evaluating universal decolonization in KT recipients in the peritransplant period. It is important to know whether universal decolonization is safe and whether it reduces infection incidence in this population. Here, we describe our 2-year experience with universal decolonization in the peri-KT period.
Materials and Methods
This retrospective cohort study included patients seen at a tertiary KT referral center (Hahnemann University Hospital, Philadelphia, PA, USA), which performs an average of 40 KTs per year. We compared a consecutive cohort of KT recipients who underwent universal decolonization with a cohort of historical controls (from March 2012 to October 2013) who were not decolonized. Regular training on the decolonization procedure was provided to the nursing staff and transplant team. The decolonization inter-vention was implemented by the transplant floor nursing director, transplant infectious disease physician, transplant pharmacist, and medical staff. The phase-in period was from November 2013 through February 2014, and the 22-month intervention period was from March 2014 through January 2016. Any patient who underwent KT during the intervention period was included in the study, irrespective of whether the patient had a history of MDR organism (defined as resistant to 3 or more antimicrobial classes) colonization or infection.
During the study period, patients at our center received a standard immunosuppression protocol, which included an interleukin 2 receptor blocker or antithymocyte globulin induction, calcineurin inhibitor-based immunosuppression, mycophenolate, and steroid taper. Prophylaxis included therapy to prevent Pneumocystis jiroveci pneumonia for 6 months and valganciclovir to prevent Cytomegalovirus infection depending on risk of infection. Patient demographics, cause of end-stage kidney disease, presence of pretransplant diabetes, comorbid con-ditions, and history of MDR infection were obtained from electronic medical records.
Perioperative antibiotic prophylaxis consisted of 1 dose of cefazolin (2 g). Universal decolonization included twice-daily nasal mupirocin ointment (2%, Bactroban, GlaxoSmithKline, Research Triangle Park, NC, USA) and daily 4% chlorohexidine body wash during the entire hospital stay. If a patient was discharged earlier than 5 days, he/she completed a total of 5 days of decolonization after discharge. Contact precaution policies were identical, and infection control policies were unchanged during the period. The result of nasal screening was obtained on admission, performed using polymerase chain reaction assay (by Gene Xpert MTB/RIF, Cepheid Inc., Sunnyvale, CA, USA) and available within 2 hours.
The primary outcome was microbiologically proven clinical infection rate within 30 days of transplant. Secondary outcomes included 30-day rates of Staphylococcus infection, hospital readmission, and adverse events related to the decolonization procedure.
Means and medians were used to describe continuous variables. Proportions were used to describe categorical variables. We used t test or Wilcoxon rank-sum test to compare continuous variables and the chi-square test to compare categorical variables across groups. Data were analyzed using the Statistical Package for the Social Sciences (version 24, SPSS, Chicago, IL, USA).
Seventy-eight patients who underwent universal decolonization were compared with 43 patients in the control group. In the overall cohort, the median age was 52 years (interquartile range, 40-61 y). Of total patients, 94 (77.7%) received a deceased-donor KT and 13.2% had a history of infection or colo-nization with an MDR organism. On routine nasal screening, only 2.6% patients were positive for methicillin-resistant Staphylococcus aureus. As shown in Table 1, significantly more patients who received decolonization were on dialysis at the time of KT than controls (97.1% vs 82.5%; P = .01).
For the primary outcome, the 30-day rate of microbiologically proven infection after discharge was 9% (7 patients) in the decolonization group versus 7% (3 patients) in the control group (P = 1.0). There were 4 cases of Enterococcus infection and 2 cases of Pseudomonas species, Citrobacter species, Clostridium difficile, and polymicrobial infection. The most common infections posttransplant were urinary tract infection (6 cases) followed by wound infection (3 cases). The control group had the only case of Staphylococcus aureus infection in the overall cohort. As shown in Table 2, no patients in the overall cohort developed bacteremia within 30 days of transplant. Thirty-day readmission rate was 39.7% (31 patients) in the decolonization group and 32.6% (14 patients) in the control group (P = .43). No patients in the decolonization group reported any adverse drug events from Mupirocin or Chlorhexidine.
In our cohort of KT recipients, a significant number of patients had a history of infection or colonization with MDR organisms. A universal decolonization protocol was successfully implemented and was well tolerated. After implementation, we did not observe any clinically significant differences in infection rates in decolonized patients versus historical controls.
Universal decolonization of patients in the ICU has been shown to reduce methicillin-resistant clinical cultures and bloodstream infections with any pathogen more effectively than targeted deco-lonization or screening and isolation.8 Climo and associates also found that daily bathing with chlorhexidine-impregnated washcloths significantly reduced primary bloodstream infections.5 Decreased microorganism burden on the body surface may have resulted in reduced infection. Because patients in the ICU often have central venous catheters and are at high risk of developing hospital-acquired infections, universal decolonization is a strategy that can be easily implemented.
There are a number of potential reasons that a decolonization strategy that works effectively in the ICU did not have a similar effect for KT recipients. For instance, the most common infections in our cohort were urinary tract infection and wound-related infection. Rather than decolonization of the body surface, minimizing urinary catheter use, using appropriate preoperative antimicrobials, and direct wound care may be more effective strategies in preventing infections during the post-KT period. Of note, no one in our cohort developed a bloodstream infection within 30 days of transplant. Furthermore, the brief hospital course (median of 7 days) may be too short of a period to become colonized with an MDR pathogen.
The universal decolonization process itself offered valuable anecdotal observations about the imple-mentation of infection control principles within our population. We found that universal decolonization was feasible and safe. Patients, nursing staff, and the transplant team were all motivated to help implement these measures. We also noted that attention to these measures also helped reinforce the importance of other components of our infection control protocols. Unlike ICU patients who are often sedated and intubated, most KT patients were awake and able to participate in the decolonization process. We found that patients and their families were accepting of this initiative after the rationale was explained.
Although we did not find that universal deco-lonization led to a significant drop in the rates of either infections or readmissions for KT recipients, the strategy still needs to be evaluated in liver, heart, and lung transplant recipients, who often face a higher risk of bacteremia and/or a higher likelihood of extended ICU stays. It has been shown that an active surveillance strategy with contact isolation and nasal decolonization in liver transplant patients decreased Staphylococcus infection rate by 10-fold.9 By extending currently available universal deco-lonization protocols beyond the ICU stay in solid-organ transplant recipients, hospital infection rates might fall.
A number of significant limitations to this study should be considered. First, this is a retrospective study that utilized historical controls; these control patients may have been different from patients in the decolonization group in undocumented ways. Second, the small sample size may have limited our ability to detect differences between the deco-lonization and control groups. Lastly, risk factors for infections, including diabetes mellitus, obesity, delayed graft function, and immunosuppression factors, were not adjusted due to the limited sample size.
We found that a universal decolonization protocol can be implemented and tolerated in the early posttransplant period. Despite successful imple-mentation, we did not observe any significant differences in rates of either infection or readmission compared with historical controls. We believe that further studies are warranted, particularly in other types of solid-organ recipients.
DOI : 10.6002/ect.2018.0341
From the 1Division of Infectious Diseases and HIV Medicine, the
Nephrology, and the 3Department of Surgery, Drexel University College of
Medicine, Philadelphia, Pennsylvania, USA
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare. This work was presented at IDWeek 2016 (New Orleans, LA, USA) in October 2016.
*Current address of A. Doyle: Division of Nephrology, University of Virginia, Charlottesville, VA, USA.
Corresponding author: Dong Heun Lee, 245 North 15th Street, Philadelphia, PA 19102, USA
Phone: +1 215 762 4697
Table 1. Characteristics of the Kidney Transplant Population and Outcomes
Table 2. Characteristics of Patients Who Developed Microbiologically Proven Clinical Infection Within 30 Days of Transplant