Bacterial and fungal infections in renal allograft recipients

With the increase of short-term survival, a greater number of patients have had optimal results also in the long term, which is leading to a gradual but progressive change in focus of the clinicians to different problems such as the quality of life of transplant patients, and the increased incidence of infective and neoplastic complications linked to the state of immunosuppression induced by antirejection therapy. With the aim of evaluating infective complications in patients undergoing solid-organ transplantation it is necessary to completely understand the complexity of the transplantation problem and to briefly look at the general principles of transplantology. I will begin by briefly examining the terminology, the various ways in which transplantation can be classified, and the principles that guide the choice and evaluation of the donor. Finally there will be a brief evaluation of transplantation problems such as rejection reactions and immunosuppressive therapy. I will introduce and explain in the following chapters the complex panorama of the infective complications of transplant patients. In fact even if the increase in and the success of organ transplantation are the result of progress obtained in the fields of surgery, diagnosis and treatment, the management of infective complications underlines the necessity for monitoring, prevention and adequate prophylaxis in clinical practice. Monitoring and prevention have become the principal aims of follow-up in transplant recipients and begin in the pre-transplantation period to continue well after the transplantation. The aim of this study was to evaluate the infective state of patients undergoing renal transplantation and combined renal-pancreas transplantations at the transplantation centre of the University Hospital of Catania subdivided in two phases : first I evaluated the infective state of the patients, both donors and recipients, before transplantation in order to detect acute and chronic infective processes and the eventual risk of activation of latent infections. Then, in the post-transplantation period, the infective state of the patients was monitored initially every month for the first three months after transplantation and then once every three months. This microbiological monitoring identified, prevented and rapidly treated infections in the patients undergoing transplantation at our centre, with the aim of safeguarding both the graft and the transplanted patient. Moreover, considering the relative difficulty, for example an accurate diagnosis of invasive fungal infections (IFI), it was fundamentally important to be able to find laboratory markers that could differentiate the subject most at risk and initiate, based on clinical conditions, an eventual pre-emptive therapy or prophylaxis. This monitoring was performed by 1 November 2007 to 30 June 2010 the incidence and time to appearance of infective complications were evaluated in a population of 101 organ transplantation recipients (84 from cadavers and 17 from live donors, average age 44 years) having undergone transplantation for a single kidney, double kidney or kidney/pancreas combination. Microbiological and virological investigations were carried out: by means of various examinations culture exams, serum exams, PCR. In particular the biological samples examined were: pharyngeal swab, nasal swabs and analysis of the organ transport liquid, colonisation studies by means of swabs (oropharyngeal, cutaneous, right and left nasal) and basic serum investigations for the identification of anti-Candida (mycelial phase) antibodies respectively in bacteriology and mycology. A significative result was obtained from the examination of the transport liquid from the 84 samples examined; in 46 (54%) there was the presence of at least one microorganism. In all the recipients undergoing antibiotic therapy bacteremia did not develop that could be attributed to the transport liquid. These results confirm that, even if a high risk of organ loss and death of patients was reported in previous studies, above all by gram-negative microorganisms such as Escherichia coli, the contamination of the donor was not a contraindication for transplantation if prophylactic antibiotic therapy was initiated before transplantation. On the other hand, the incidence of fungal contamination is from 2 to 10%. There are no guidelines for vascular prevention or for complications from fungal infections of the donor or of contamination of the transport liquid. Various studies have underlined the need for nephrectomy of the organ as prophylaxis when the transport liquid is found to be contaminated. In conclusion the analysis of the transport liquid before transplantation is useful for the identification of recipients at high risk of infections and can be used as pre-emptive therapy. The bacteriological analysis of both nasal and pharyngeal swabs did not give significative results as most cases isolated were commensal bacteria while results significative were shown for urinary infections. In particular from this study it can be seen that Escherichia coli and Klebsiella pneumoniae were the bacterial species that are still the principal etiological agent of infections, both nosocomial and community of the urinary tract. The antibiotics that were the most active against E. coli and K. pneumoniae were amikacin and imipenem that inhibited all the sampled strains. Particular attention was paid to 10 patients from March to September 2009: three patients developed bacteraemia, seven patients developed symptomatic UTIs, due to the presence of fever, urgency, frequency, dysuria, and supra-pubic tenderness, caused by K. pneumoniae that showed a pattern of resistance to multiple antibiotics. These microorganisms were characterised to determine the mechanisms responsible for antibiotic resistance by means of specific phenotypic tests (double disc for ESBLs) and molecular techniques for the amplification of resistance genes (DNA extraction, PCR). Moreover, to evaluate the type of diffusion inside the hospital these strains underwent molecular typing by means of Pulsed Field Gel Electroforesis (PFGE). The ten strains belonged to two different clones, A and B, moreover, clone A was an MDR clone resistant to all àƒ àƒ àƒ àƒ àƒ àƒ à,²-lactams and amikacin, piperacillin/tazobactam and ciprofloxacin. Clone B was susceptible to amikacin and ciprofloxacin. Subtle differences in the bla gene content were observed between both clones, demonstrating that lateral gene transfer drives the diffusion of many antibiotic resistance genes. These clones had never been isolated before and were responsible, for the first time, for severe upper UTIs with difficult resolution: one failure and one relapse. Finally, UTIs remain the most frequent infections among renal transplant recipients. Until recently infections were sustained by susceptible microrganisms in which complete resolution of infections was easily obtained; the increase of potentially life-threatening multi-resistant strains now emerging in hospital settings for renal transplant recipients has changed the severity of infections and the corresponding outcome. The implementation of control measures, focusing on hand hygiene and appropriate urinary catheter manipulation through educational programs and contact isolation procedures were able to limit the spread of resistance clones in the renal transplantation unit. Therefore it is mandatory to continue epidemiological surveillance of transplantation units in order to tailor a correct therapy to maintain antibioticspotent, such as carbapenem, which are losing their potency. Of the 101 patients monitored 57(56%) were colonized in at least one of the investigated sites, generally, in all the sites investigated, 123 species were found: 64(52%) in the respiratory tract(oral-pharyngeal swab/sputum) and 59(48%) in urine. In particular in both sites the most frequently isolated species was C. albicans. Therefore, even if C.albicans was the most frequently isolated species it appears that in the respiratory tract the species have a greater distribution with respect to urine.