Management of infection in the post-cardiac-transplant patient

In reviewing our post-transplant experience with infection in 192 cardiac transplant patients, we have noticed a pattern. During the first month following transplantation, the patient seldom has an opportunistic infection, but is in danger of nosocomial infection (84 episodes in 57 patients). These include wound infection, and infections of the lungs, blood, and urinary tract. After the first month, and for the duration of the first year following transplantation, nosocomial infections become less common and opportunistic infections dominate (176 episodes in 111 patients). Although viruses are the most common opportunistic pathogens (100 infections in 111 patients), bacteria, fungi, and parasites are the most serious threats, especially when they affect the lungs. We relate our experience in prophylaxis, diagnosis, and treatment throughout the first year following transplant.     

Infectious complications after kidney transplantation: a single-center experience

Infectious complications after renal transplantation are associated with significant morbidity and mortality. The prevalence of infections in transplant recipients varies from country to country. This study sought to assess the overall incidence of post-transplant infectious complications at our research center in Iran, compared with other centers in the world. Between 2002 and 2004, 179 renal transplantations were performed in our center. Of these, 142 were studied and followed for 1 year. Immunosuppressive regimens were cyclosporine, mycophenolate mofetil, and prednisolone. The overall incidence of infections was 54.2%. The most common sites of infections were the urinary tract (41.5%) and the respiratory tract (6.3%). The most frequent causes of infections were Klebsiella (24%) and cytomegalovirus (CMV) (17.6%). Wound infection occurred in 4.9% of the patients. Three (2.1%) patients developed hepatitis C and 2 (1.4%) had mycobacterial infections. There was no case of Pneumocystis pneumonia. Overall mortality was 7.7%. Infection-related mortality was 3.5%. In conclusion, this study identifies infections as the cause of morbidity and mortality in the post-transplant period. There was a low incidence of tuberculosis (<2% yearly) and a high incidence of CMV disease in our recipients.     

Hospitalizations for fungal infections after renal transplantation in the United States

Abstract: Fungal infections in renal transplant recipients have not been studied in a national population. Therefore, 33,420 renal transplant recipients in the United States Renal Data System from 1 July 1994 to 30 June 1997 were analyzed in a retrospective registry study of hospitalized fungal infections (FI). FI were most commonly associated with secondary diagnoses of esophagitis (68, 23.9%), pneumonia (57, 19.8%), meningitis (23, 7.6%), and urinary tract infection (29, 10.3%). Opportunistic organisms accounted for 95.4% of infections, led by candidiasis, aspergillosis, cryptococcosis, and zygomycosis. Most fungal infections (66%) had occurred by six months post-transplant, but only 22% by two months. In logistic regression analysis, end-stage renal disease due to diabetes, duration of pre-transplant dialysis, maintenance tacrolimus and allograft rejection were associated with FI. In Cox regression analysis, recipients with FI had a relative risk of mortality of 2.88 (95% CI=2.22–3.74) compared to all other recipients. Among FI, zygomycosis and aspergillosis were independently associated with both increased patient mortality and length of hospital stay. Most fungal infections in renal transplant recipients were opportunistic, occurred later than previously reported, and were associated with greatly decreased patient survival. Recipients with diabetes, prolonged pre-transplant dialysis, rejection, and tacrolimus immunosuppression should be considered high risk for FI.     

肾移植合并感染性疾病178例临床分析

目的　探讨肾移植患者术后感染时间、种类和病原体分布情况及现行抗排异和预防感染措施的效果。方法　对 178例肾移植患者的临床资料进行 6个月～ 2年的回顾性分析。结果　 178例患者中合并感染性疾病 5 5例 (3 0 .9% )。肺炎、尿路感染、乙型肝炎病毒 (HBV)、巨细胞病毒 (CMV)及单纯疱疹病毒 (HSV)感染的发生率分别为 9.5 5 %、5 .65 %、4.49%、2 .2 5 %和 3 .3 7% ;革兰阴性杆菌 (GNB)、真菌、HBV、CMV及HSV是肾移植患者最常见的病原体。肺炎、尿路感染和单纯疱疹多发生在移植后 1～ 6个月 ,乙型肝炎和CMV感染多见于移植术 6个月后。外周血白细胞、中性粒细胞及T淋巴细胞CD+ 4 /CD+ 8比值在感染组和非感染组比较差异有显著性 (P <0 .0 1)。环孢霉素 (CSA)、强的松 (Pred)、硫唑嘌呤 (AZA)及雷公藤多甙 (T) (方案CPAT)的抗排异方案和抗菌素的预防治疗可降低移植患者感染率。结论　肾移植患者各系统的感染率增加 ,通过实施有效的措施 ,其发生率可下降     

Cancer incidence after immunosuppressive treatment following kidney transplantation

Cancer incidence is increased in renal transplant recipients due to immunosuppressant treatment that should be maintained to prevent and treat acute rejection. Use of new and very potent immunosuppressants has made it possible to reduce acute rejection incidence and improve renal graft survival, although increase of infections and post-transplant neoplasms have become clearer. On the other hand, renal transplant candidates who remain on dialysis have a greater prevalence of neoplasms than the age-matched general population, either because the neoplasm was the cause of their renal failure (multiple myeloma or kidney or urinary tract cancers) or because their renal disease entails a risk for cancer development (acquired cystic disease or analgesic nephropathy). Practically, all de novo neoplasms have a greater incidence in renal transplant patients. Cutaneous neoplasms are the most prevalent in renal transplant recipients and their incidence increases with transplant time. Post-transplant lymphoproliferative diseases are more frequent in patients who receive greater immunosuppression (antithymocyte/antilymphocyte globulin or OKT3) or are infected de novo by Epstein Barr Virus (EBV) through the transplanted kidney. Kaposi's sarcoma has a high incidence in the renal transplanted population, does not appear in the general population, and is related with Human Herpes Virus 8 (HHV-8) infections. The incidence of tumors in non-functioning native kidneys is especially high in renal transplant due to the presence of acquired cystic disease or analgesic nephropathy. Gold standards of post-transplant de novo renal neoplasm prevention are modulating immunosuppression and avoiding exposure to sunlight and to different oncogenic viruses (EBV, cytomegalovirus, hepatitis B and C viruses).     

Infection in the renal transplant recipient

The incidence of infection in the renal transplant patient is directly related to the net immunosuppressive effect achieved and the duration of time over which this therapy is administered. A second major factor in the causation of infections in this population is the nosocomial hazards to which these patients are exposed, ranging from invasive instrumentation to environmental contamination with Aspergillus species, Legionella pneumophila, Pseudomonas aeruginosa and other microbial pathogens. Careful surveillance is necessary to identify and eliminate such nosocomial sources of infection. The major types of infection observed can be categorized according to the time period post-transplant in which they occur: postsurgical bacterial infection in the first month after transplantation; opportunistic infection, with cytomegalovirus playing a major role, and transplant pyelonephritis in the period one to four months post-transplant; and a mixture of conventional and opportunistic infections in the last post-transplant period. Conventional infection in this late period occurs primarily in patients with good renal function who are receiving minimal immunosuppressive therapy; opportunistic infection occurs primarily in patients with poor renal function who are receiving higher levels of immunosuppression.     

A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis

PURPOSE: To determine the efficacy of long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for prevention of bacterial infection following renal transplantation, the absorption of TMP-SMZ in transplant patients, the effects of prophylaxis on the microflora, and the cost-benefit of prophylaxis. PATIENTS AND METHODS: One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial. RESULTS: Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p less than 0.001) and significantly fewer bacterial infections during the transplant hospitalization after removal of a urethral catheter (0.76 versus 1.88 per 100 days, p less than 0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p less than 0.001). During the transplant hospitalization, a daily dose of 320/1,600 mg was highly effective for prophylaxis whereas 160/800 mg daily gave unexpectedly low blood levels and was effective only for prevention of urinary tract infections after catheter removal. Prophylaxis was most effective in prevention of infections of the urinary tract (24 versus 54, p less than 0.005) and bloodstream (one versus nine, p less than 0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p less than 0.001), enterococci (six versus 22, p = 0.006), or Staphylococcus aureus (one versus nine, p = 0.01). Prophylaxis did not prevent urinary tract infection associated with urethral catheters in the early posttransplant period, but after catheter removal, reduced the risk of urinary tract infection threefold (p less than 0.001). No significant differences in colonization by TMP-SMZ-resistant gram-negative bacilli were identified between the two groups; patients given TMP-SMZ were, paradoxically, less likely to become colonized by candida, probably because of less exposure to antibiotics for treatment of infection. Recipients of prophylaxis did not have a higher rate of infection caused by TMP-SMZ-resistant bacteria or Candida; however, their infections were more likely to be caused by resistant bacteria than infections in patients in the placebo group (62% versus 18%, p less than 0.001). CONCLUSIONS: Prophylaxis with TMP-SMZ, which is well tolerated, significantly reduces the incidence of bacterial infection following renal transplantation, especially infection of the urinary tract and bloodstream, can provide protection against Pneumocystis carinii pneumonia, and is cost-beneficial. Subnormal absorption of TMP-SMZ in the early posttransplant period mandates 320/1,600 mg daily for optimal benefit. Prophylaxis has little discernible effect on the microflora.     

Infektion nach Nierentransplantation

Complications due to infections after renal transplantation may be persistent from dialysis time (hepatitis, HIV), transmitted by the transplant (hepatitis, HIV, rabies, cytomegalovirus, Epstein-Barrvirus) or may be acquired from the transplantation (contamination of organ preservation solution, septicemia by central venous catheter, early urinary tract infection and wound and lymphocele infection). Thus, early infections are mainly urinary tract infections, herpes virus 1 and 2, cytomegalovirus and polyoma BK virus. Early as well as delayed infections are urinary tract infections, diarrhea, infections of the respiratory tract, polyoma BK virus (2 years post-transplantation), cytomegalovirus, Epstein-Barr virus and Varicella zoster virus infection, Pneumocystis jirovecii pneumonia, nocardiosis, tuberculosis (reactivation), hepatitis E as well as fungal infections. The spiral development of increasing immunological recipient risks, more and more potent immunosuppressive regimens and increasing infectious complications should be counteracted by effective monitoring of immune function and thus minimization of immunosuppression and finally by developing methods for recipient tolerance.     

Urinary tract infection associated with ureteral stents in renal transplantation

OBJECTIVES: In the mid 1980s, ureteral stents were used in renal transplantation when ureteral injury had occurred. Subsequently, it was shown that routine ureteral stent placement at the time of transplantation reduced urological complications. We carried out a chart review on renal transplant patients and noted which patients developed urinary tract infections (UTIs) with stents in place, and whether these infections ultimately affected transplant outcome. We sought to distinguish subgroups of patients who were more likely to develop infection and to identify the optimum time for stent removal. PATIENTS AND METHODS: We performed a retrospective chart review of 213 patients who underwent renal transplantation in 1994 and 1995. Adequate follow-up information was available on 167 patients with intraoperative stent placement. Of these 167 patients, 4 patients expired and 8 required transplant nephrectomy due to complications unrelated to the stent. RESULTS: In total, 35 patients (22.6%) developed a post-operative UTI. One infection occurred during the first week following transplant, 3 developed within 2 weeks, and importantly, the remaining 32 infections occurred more than 2 weeks after transplant. An increase in infections in diabetics (25.7%) as compared to other transplant recipients (20.2%) was noted. Patients with cadaveric renal transplants are also at higher risk of UTI (24%) compared to those with living related donors (15%). CONCLUSION: The use of ureteral stents is safe, but is associated with a UTI rate of 22.6%. To reduce infection rates, we recommend stent removal within 14 days and earlier if possible, particularly in diabetic patients who have received a cadaveric renal transplant.     

Infectious risk factors in the immunosuppressed host

A survey of 194 renal transplant recipients was undertaken to clarify factors of importance in the genesis of infections in the immunosuppressed host. The need for high dose prednisone therapy and the occurrence of hyperglycemia were significantly greater in patients with fatal and nonfatal post-transplant infections than in patients without such infection. Being over 40 years of age at the time of transplantation and the presence of leukopenia were occasionally significantly associated with infectious death after transplantation. Renal failure was associated with infectious death in some transplant recipients; this association likely reflected the use of high dose immunosuppressive agents to treat refractory rejection. Hypogammaglobulinemia, azathioprine therapy (at the dosage level studied) and the sex and race of the recipient, the type of underlying renal disease, nephrectomy, splenectomy and thymectomy were not associated with post-transplant infectious death.There was a marked diminution in infection and infectious death after 1965. We postulate that this decline was due to two factors: (1) the accumulation of extensive experience with post-transplant infections leading to a more aggressive diagnostic and therapeutic approach in recent transplant recipients with infection, and (2) a decrease in the use of high dose prednisone therapy and of the occurrence of hyperglycemia in recent transplant recipients. The more frequent use of related donor kidneys and the introduction of antilymphocyte globulin permitted less use of high dose prednisone therapy in transplant recipients after 1965.     

Stand der Nierentransplantation im Jahr 2012

Triple immunosuppression including a calcineurin inhibitor, mycophenolic acid and steroids remains the standard of care after (renal) transplantation, while steroid-free immunosuppression and calcineurin inhibitor-free (mTOR inhibitor or belatacept-based) therapies are increasingly being used. In several transplant centers induction therapy with basiliximab or antilymphocyte globulin/antithymocyte globulin (ATG/ALG) is routinely used. Impairment of renal graft function necessitates a thorough investigation, often including a renal core biopsy and imaging studies for the assessment of vascular perfusion to allow adequate treatment for, e.?g. humoral, antibody-mediated rejection or polyomavirus type BK (BKV) nephropathy. Long-term survival of patients with functioning graft is largely determined by cardiovascular mortality. Therefore, aggressive preventive and therapeutic strategies are required in cardiovascular high-risk transplant patients. This comprises blood pressure control <140/90?mmHg, with calcium channel blocker, diuretic, angiotensin-converting enzyme (ACE) inhibitor, beta blocker as agents of first choice, statin treatment (fluvastatin, pravastatin most intensely studied), diabetes treatment (target HbA1c at 7%), avoidance of inadequate post-transplantation weight gain and nicotine abstinence. Tumor risk is increased 4-fold, especially skin tumors, post-transplant lymphoproliferative disorders (PTLD) and renal/bladder cancer. Besides standard tumor prevention protocols as suggested for the general population, regular dermatological and ultrasound studies (liver when viral hepatitis is present, native kidneys) are recommended. High-dose immunosuppression increases the risk of infection especially within the first 6 months. Transplantation-associated infections (catheter, wound, pneumonia, urinary tract infections with urinary bladder catheterization), de novo infections or endogeneous reactivation of viral infections, i.e. with herpes viruses (HSV, VZV, CMV) are most frequent. Due to the medical complexity of transplantation patients, an interdisciplinary approach and a close collaboration between transplant center and the primary care nephrologist is needed.     

Effect of time after transplantation on microbiology of urinary tract infections among renal transplant recipients

Abstract: We evaluated the microbiology of renal transplant recipients hospitalized with urinary tract infections over a 10-year period. While gram-negative organisms were seen most frequently (73%), the median time to infection post transplantation was shorter in patients infected with gram-positive organisms (9.0 vs. 44.7 months).     

The challenge of urinary tract infections in renal transplant recipients

Urinary tract infections (UTI) are an important cause of morbidity and mortality in renal transplant patients. These infections are quite common, and the goal of care is to identify and reduce risk factors while providing effective prophylaxis and treatment. Better understanding of long‐term outcomes from these infections has led to the distinctions among UTI, recurrent UTI, and asymptomatic bacteriuria (ASB), and that each requires a different therapeutic approach. Specifically, new research has supported the perspective that asymptomatic bacteriuria should not be treated. Symptomatic UTI, on the other hand, requires intervention and remains an ongoing challenge for infectious disease clinicians. Many bacteria species are responsible for UTI in renal transplant patients, and in recent years there has been a global rise in infection caused by bacteria with newly acquired antibacterial resistance genes. Many renal transplant patients who experience UTI will also have multiple recurring episodes, which likely has a distinct pathophysiological mechanism leading to chronic colonization of the urinary tract. In these cases, long‐term management includes bacterial suppression, which aims to reduce rather than eliminate bacteria to levels below the threshold for symptomatic infection. This review will address the current understanding of UTI epidemiology, pathogenesis, and risk factors in the renal transplant community, and also focus on current prevention and treatment strategies for patients who face an environment of increasingly antibiotic‐resistant bacteria.     

Late onset Pneumocystis pneumonia in renal transplantation after long-term immunosuppression with belatacept

Abstract: Interference with T-cell function increases the risk of infections, especially during the early post-transplant period. Belatacept, a costimulation blocker, is currently being tested in phase III clinical trials. Here we report a renal transplant recipient who received belatacept and developed severe Pneumocystis jirovecii pneumonia (PCP) with fatal superinfections 4 years post transplant. Cytomegalovirus infection preceded PCP, which typically occurs in overimmunosuppressed patients, but has not yet been reported under T-cell costimulation blockade in transplant patients. This case illustrates the possibility of excessive immunosuppression even with a lymphocyte-specific regimen.     

Urinary tract infections and chronic renal failure

The paper briefly summarizes issues related to urinary tract infections in adults: predispositions and risk factors, classification, assessment of pathogenicity of bacterial agents, the role of bacteriuria and leucocyturia, interpretation of findings, treatment principles and an association with chronic renal failure. Urinary tract infections are the second most frequent infectious disease in the population. They most often affect women of childbearing potential and then seniors of both sexes who have multiple risk factors. Escherichia coli and Staphylococcus saprophyticus are the most pathogenic towards urinary tract; they are responsible for 85% and 10-15% of cases of acute uncomplicated urinary infections, respectively. Chronic pyelonephritis, a chronic interstitial nephritis, is the fourth most frequent cause of chronic renal failure. Chronic renal failure is a risk factor for the development of urinary infections due to metabolic disorders resulting in secondary immunodeficiencywith a disorder of all components of immunity. In patients with chronic renal failure, urinary tract infections occur most frequently after kidney transplantation when graft pyelonephritis is a life-threatening complication. Therefore, urinary tract infection prevention with co-trimoxazole once daily over at least 6 months is recommended in renal allograft recipients.     

Iatrogenic emphysematous pyelonephritis in a renal transplant patient

Abstract: Emphysematous pyelonephritis (EPN) is a rare condition that typically occurs in patients with diabetes mellitus, urinary tract obstruction, or immunosuppression such as solid organ transplant recipients. It has high mortality and frequently requires nephrectomy to achieve cure, although percutaneous drainage has been reported to be successful in some patients. We report a renal transplant recipient with underlying diabetes mellitus who developed iatrogenic EPN. The patient initially presented with dyspnea and was admitted for cardiac evaluation. There was no evidence of urinary tract infection at the time of admission. The patient developed high‐grade fever 3 days after admission. Despite intravenous (IV) antibiotic therapy, the patient developed acute renal failure requiring hemodialysis. Studies revealed Klebsiella bacteremia and EPN. We believe that urinary tract infection was precipitated by urinary bladder catheterization performed on the day of admission. Despite 2 weeks of IV antibiotic therapy, infection persisted with progressive extension of gas into the perinephric space on repeat imaging. The patient underwent a transplant nephrectomy with subsequent clinical recovery. This case illustrates that antibiotics alone are often inadequate to cure and preserve renal function in EPN despite immediate therapy. Furthermore, this patient underscores the risk of serious infection precipitated by urinary bladder catheterization in immunocompromised patients.     

Antibody-coated bacteria as an indicator of the site of urinary tract infection in renal transplant recipients receiving immunosuppressive agents.

Distinguishing an infection in the upper urinary tract from one in the lower urinary tract is especially important in renal transplant patients. Although the presence of antibody-coated bacteria in the urine has been shown by others to be a reliable indication of an infection in the upper urinary tract, it was not known whether sufficient antibody to coat the bacteria would be produced in a renal transplant recipient undergoing immunosuppression. We used a fluorescent test for detecting antibody-coated bacteria in the urine to follow 80 renal transplant patients prospectively for six months. Antibody-coated bacteria were detected in specimens from four patients with a clinical picture compatible with, or histopathologic evidence of, pyelonephritis. The origin of bacteriuria in a fifth patient was indeterminate both clinically and by the fluorescent antibody test. Twenty-three other patients with bacteriuria without clinical or histopathologic evidence of pyelonephritis had negative tests for antibody-coated bacteria. One patient with pyelonephritis in her own end-stage kidney had persistent bacteriuria with a negative fluorescent antibody test. Her transplanted kidney, however, was not infected.     

A serological investigation of BK virus and JC virus infections in recipients of renal allografts

BK virus (BKV) and JC virus (JCV) infections were evaluated in a serological study of 496 renal transplant recipients and their donors. A seropositive donor increased the rate of primary and reactivation infections with BKV and of primary infections with JCV. BKV infection rates were not influenced by the source of the renal allograft (cadaver versus living related donor); however, primary JCV infections occurred more often in recipients of seropositive cadaveric kidneys. Reactivated JCV infections occurred less frequently in patients treated with antilymphocyte preparation. BKV and JCV infections in renal transplant recipients may be caused either by reactivation of the recipient's latent virus or by virus from the donor kidney. These infections are, however, not associated with adverse outcome (death, high serum creatinine level, or loss of renal function) in the recipient in the early post-transplant period.     

Urinary tract infections due to Candida albicans

Infection of the urinary tract due to Candida albicans is an uncommon but well-described complication of modern therapeutics. Despite the rarity of this infection, culture of properly collected urine yielding C. albicans requires an explanation. The significance of systemic factors in the defense of the urinary tract against candidal infection is unknown, but secretions from the prostate gland in men and from periurethral glands in women have been reported to be fungistatic. In addition, growth of Candida at sites on mucous membranes may be suppressed by other normal flora. Conditions that predispose to candiduria include diabetes mellitus, antibiotic and corticosteroid therapy, as well as factors such as local physiology and disturbance of urine flow. Lower urinary tract candidiasis is usually the result of a retrograde infection, while renal parenchymal infection most often follows candidemia. In addition to asymptomatic candiduria, recognized clinical forms of candidal urinary tract infections include bladder infection, renal parenchymal infection, and infections associated with fungus ball formation. Unfortunately, clinical criteria alone are insufficient to distinguish reliably among these clinical types. If the urine is found to contain candidal organisms, the condition of the patient should be considered for determination of appropriate therapy. When infection is thought to be confined to the bladder, patients without indwelling bladder catheters should be considered for flucytosine therapy. For patients requiring indwelling bladder catheterization, irrigation with amphotericin B is usually successful. Although flucytosine alone may be useful for renal parenchymal candidal infection, iv amphotericin B alone or the combination of amphotericin B and flucytosine is indicated when systemic candidiasis cannot be excluded.     

Cefotaxime therapy of serious infections with multiresistant gram-negative bacilli

33 patients with serious gram-negative bacillary infections were treated with cefotaxime. In patients with normal renal function the dose varied between 1.5 to 4 g/day. 17 patients had urinary tract infections, 5 respiratory tract infections, 1 combined urinary tract infection and respiratory tract infection, and 10 miscellaneous infections. 16 patients had septicemia. 25 infections were due to pathogens resistant in vitro to ampicillin, cephalothin, gentamicin and/or tobramycin. 15 infections had failed to respond to ampicillin, cefazolin, gentamicin or tobramycin therapy. 32/33 patients responded favourably to cefotaxime (cure or improvement) but 4 patients developed superinfection with cefotaxime-resistant bacteria. No evidence of nephrotoxicity was observed except for a transient moderate rise in creatinine in one patient.