A. Famulari

Incidence of Urinary Tract Infections Caused by Germs Resistant to Antibiotics Commonly Used After Renal Transplantation

BACKGROUND The inadequate utilization of antibiotics is responsible for the development of urinary tract infections (UTI) after renal transplantation (RT), through the induction of resistance to the antibiotics themselves. The purpose of this study was to evaluate the incidence of resistance to cefotaxime (CEF) and trimethoprim/sulfamethoxazole (TMP-SMX), routinely used for surgical perioperative prophylaxis and prevention of Pneumocystis carinii, respectively. MATERIALS AND METHODS We enrolled all adult patients having received an RT from 2001 to 2006 and having a minimum follow-up of 6 months. Urine cultures (UC) were routinely performed at every outpatient clinic control and whenever required by the onset of significant clinical signs/symptoms. UTI was diagnosed by the presence of a positive UC. The endpoint of the study was the emergence of bacterial strains resistant to either CEF or TMP/SMX. RESULTS We recorded 169 UTI in 76 patients (38 men/38 women, 33%) over a mean follow-up of 779.9+/-523.3 days. Thirty-nine patients (51%) developed more than 1 UTI episode. When gram-negative bacteria were considered, 102/144 (70.8%) tests showed resistance to TMP/SMX, while data were available in about only 7 gram-positive infections (5/7, 71%). CEF was tested less frequently with 21/43 (49%) germs resistant to this molecule. CONCLUSIONS The onset of bacterial resistance to either TMP/SMX or CEF is frequent after RT. A wiser stricter utilization of antibiotics is mandatory. Standard antibiotic protocols should be revised.

Fatal hemorrhage in two renal graft recipients with multi-drug resistant Pseudomonas aeruginosa infection.

Abstract: Pseudomonas aeruginosa (PA) infections occurring after renal transplantation (RT) represent a potentially life‐threatening complication. We present 2 cases of early death following RT in which PA was transmitted, possibly from the donor to the recipients, despite preoperative cultures that were negative. The donor had developed PA‐related bilateral pneumonia while in the intensive care unit. However, after appropriate antibiotic therapy, no signs of infection were present at the time of organ retrieval and cultures were negative. Both recipients received a renal graft from the same donor and developed multi‐drug resistant (MDR)‐PA infections with bacterial phenotypes and resistances similar to the donor. The first recipient died 9 days after RT from rupture of a false aneurysm of the external iliac artery, caused by a fully thickened PA‐related arteritis. The second recipient died postoperatively on day 10 after rupture of an aneurysm in the right vertebral artery. Our experience shows that MDR‐PA infection early after RT may be a catastrophic event. Specific anti‐PA antibiotic therapy in RT patients during the perioperative period is recommended in the case of PA infection in the donor, even after apparent successful therapy with negative cultures.

A case of coloboma in a newborn to a woman taking mycophenolate mofetil in pregnancy after kidney transplantation.

Recently, mycophenolate mofetil (MMF) has been introduced in the immunosuppressive strategy after kidney transplantation. Recently, the existence of a MMF associated embriopathy has been hypothesized, namely, multiple craniofacial malformations. Only 1 report has described chorioretinal coloboma. We report a case of woman who used MMF throughout pregnancy after kidney transplantation. Her newborn developed coloboma of the right eye associated with an ocular cyst without any other malformation. The other drugs used by our patient are not considered teratogenic. Therefore, it seems reasonable to conclude a causal relationship between MMF and the malformation observed in this newborn.

A Systematic Review of Two Different Trimetoprim–Sulfamethoxazole Regimens Used to Prevent Pneumocystis jirovecii and No Prophylaxis at All in Transplant Recipients: Appraising the Evidence

BACKGROUND The aim of this study was to clarify the potential advantages of a low-dose regimen of trimethoprim-sulfamethoxazole prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP) in transplant recipients (80/400 mg/d every day or 160/800 mg/d every other day) with those obtained from the full-dose prophylaxis (160/800 mg/d every day) or no prophylaxis. METHODS Prospectively randomized and retrospectively case controlled studies were selected. RESULTS Four studies matched the inclusion criteria-2 randomized and 2 case controls-for a total of 570 patients. The pneumonia incidence was 0% after full-dose prophylaxis (0/181), 1% after the low-dose regimen (1/105), and 11% with no prophylaxis (31/284). Pneumonia occurrences were significant lower between the full-dose prophylaxis versus the no prophylaxis group (0% vs 11%; P < .001), and between the low-dose and no prophylaxis groups (1% vs 11%; P < .001). There was no difference between patients receiving the full-dose prophylaxis versus the low-dose regimen (0% vs 1%; P = NS). CONCLUSIONS The low-dose gives similar results as the full-dose regimen for the prevention of PJP and seems a feasible, safe option for transplanted patients.

De Novo Autoimmune Hepatitis Following Liver Transplantation : A Case Report

De novo autoimmune hepatitis (AIH), a rare disorder first described in 1998, appears in patients with liver transplants due to autoimmune and nonautoimmune etiologies. De novo AIH occurs in 2.5% to 3.4% of allografts; children seem to have a predilection for this syndrome. We have present herein a case of a liver allograft recipient who developed chronic hepatitis associated with autoimmune features outlining the clinical course, liver histology, and response to treatment.

Regenerative Medicine Applied to Solid Organ Transplantation: Where Do We Stand?

The objective of regenerative medicine (RM) and Tissue Engineering (TE) is to create living functional tissues to repair or replace tissues or organ functions. This field holds the promise of regenerating damaged tissues and organs in the body. It has the potential to solve the problems of organ shortage and of toxicities deriving from life-long immunosuppression. In fact, cells in the regenerated organ would match those of the patient, from whom they would normally be derived. In the past decade, RM/TE has achieved striking results which are of interest to the transplant community. However, major roadblocks on the avenue to full success include the need for a deeper understanding of cell biology and of interactions with the extracellular matrix. We are presently not able to grow and expand cells indefinitely and safely in various scenarios where RM/TE may be indicated. The production of adequately vascularized scaffolds to optimize nutrients and oxygen delivery, assessment of the viability and function of the cells in the bioengineered construct, and the costs remain areas of scientific research.

Kidney Transplantation From Older Donors

BACKGROUND The use of kidneys from older donors has become generally accepted and increasingly common, despite the knowledge that donor age is a well-known risk factor for graft failure. AIM To review our experience with the utilization of kidneys from donors older than 60 years. PATIENTS AND METHODS Among two hundred eight patients, 32 (group A) received an organ obtained from a donor older than 60 years. The organs were age-matched with a maximum gap of 20 years between donors and recipients. Organs from older donors were assigned to recipients presenting a body mass index lower than that of the donor. The primary end point was patient and graft survival. Secondary endpoints were incidences of delayed graft function and of acute rejection episodes as well as renal function at 3 months and yearly. RESULTS The two groups were comparable in terms of demographic features, indications for transplantation, comorbidities, as well as cold and warm ischemia times. The Mean lengths of follow up were 31.4 ± 20.3 months and 30.3 ± 20.1 months, respectively. Graft and patient survivals were comparable. Mean creatinine values at the study intervals were significantly lower among group B who received grafts from younger donors. The incidence of delayed graft function and acute rejection episodes were similar: 15.6% (5/32) versus 20.5% (36/176; P=0.35) and 15.6% (5/32) and 12.1% (21/167; P=0.136) in groups A and B, respectively. CONCLUSIONS Donor age older than 60 years showed a negative impact on kidney function. Though, given the escalating disparity between organ supply and demand, this precious source of organs cannot be neglected. We need better ways to use the available organs.

Clinical Operational Tolerance After Kidney Transplantation: A Short Literature Review

The clinical era of solid organ transplantation started with a renal transplantation (RT) performed between identical twins in Boston in 1954. The patient did not receive any immunosuppression, thus representing the very first case of operational tolerance (Tol). However, more than half a century later, we must admit the inadequacy of our knowledge regarding such a fundamental aspect of transplant immunology, as demonstrated by the fact that Tol has never been achieved in an intention-to-treat protocol. Herein we aim to shortly review the worldwide experience on clinical operational Tol after RT. Thus far, reports on successful cases of Tol after RT have been anecdotal: the largest series included no more than 10 individuals. We will understand that Tol can develop even in the presence of either HLA mismatches or blood group incompatibility at baseline, in the presence of anti-HLA antibodies during follow-up, as well as in patients having experienced acute rejection. Despite the lack of robust evidence, the fact that Tol is often accidentally discovered by transplant physicians during follow-up in noncompliant patients justifies the hypothesis that the real number of Tol cases might be much higher than currently reported.

One-shot versus multidose perioperative antibiotic prophylaxis after kidney transplantation: A randomized, controlled clinical trial

BACKGROUND There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for renal transplant recipients. Some studies have reported that irrigation of the wound at the time of closure without systemic antibiotics may suffice to minimize the risk for surgical site infection (SSI), but many centers still use long-term, multidose regimens in which antibiotics are administered until removal of foreign bodies occur, such as the urethral catheter, drain and central line. METHODS We designed a prospective, randomized, multicenter, controlled trial to compare a single dose versus a multidose regimen of systemic antibiotic prophylaxis in adult, nondiabetic, non-morbidly obese patients undergoing renal transplantation. The primary endpoint was the incidence of SSI; the assessment of other infection in the first postoperative month was the secondary endpoint. RESULTS Two hundred five patients were enrolled and randomized to receive either a single (n = 103) or multidose antibiotic regimen (n = 102) for prophylaxis. The incidences of SSI and urinary tract infection were similar in both groups. CONCLUSION As the dramatic increase in antibiotic resistance has mandated the implementation of global programs to optimize the use of antibiotic agents in humans, we believe that the single dose regimen is preferred, at least in nondiabetic, non-morbidly obese, adult renal transplant recipients.

Cytomegalovirus and Gastric Cancer After Renal Transplantation: A Possible Interplay

We herein have described a case of de novo gastric cancer in a renal transplant recipient with a concomitant diagnosis of gastrointestinal cytomegalovirus (CMV) disease. We hypothesize that CMV, through causing an imbalance between cell proliferation and cell death, functions as the causative agent for the progression of the gastric tumor in this case after gastric colonization. To the best of our knowledge, this is the second such case ever reported of such kind and may represent a platform for investigations aimed at understanding the possible interplay between CMV and gastric cancer.