A prospective analysis of the incidence of and risk factors for opportunistic infections in patients with inflammatory bowel disease

Background

Immunosuppressants lead to an increased risk of infection, but few prospective studies have assessed the incidence of opportunistic infections in inflammatory bowel disease (IBD) patients, a high proportion of whom are treated with immunosuppressants. The aim of this study was to assess the age distribution of Japanese IBD patients with opportunistic infections and the risk factors associated with these infections.

Methods

A multicenter, prospective study of 570 IBD patients was conducted. The patients were followed for up to 12 months to identify any new infections. The incidence of opportunistic infections and the age distribution of patients with these infections were analyzed. We carried out a case–control study in which 2 non-infected IBD patients were selected as controls for each case (infected IBD patient); the effect of medications on the infection rate was also examined.

Results

Fifty-two (9.1 %) of 570 IBD patients developed opportunistic infections. Herpes simplex virus and herpes zoster virus infections were observed in 29 and 16 patients, respectively. No cases of active tuberculosis were observed. The incidence of opportunistic infections in patients aged 50 years or over was significantly higher than that in the other age groups (p = 0.01). The use of steroids (p = 0.02), thiopurine (p < 0.01), and immunosuppressant combination therapy (p < 0.01) was associated with an increased rate of opportunistic infections. However, the use of infliximab was not associated with an increased rate of opportunistic infections (p = 0.62). Multivariate analysis indicated that the use of thiopurine was an independent risk factor for opportunistic infections (p < 0.01).

Conclusions

Age ≥50 years and the use of immunosuppressants are risk factors for opportunistic infections in patients with IBD. In our cohort, tuberculosis was not seen as a complication of immunosuppressant therapy.     

Systemic nocardiosis following allogeneic bone marrow transplantation

Abstract: Five cases of systemic Nocardia infection were diagnosed among 301 allogeneic bone marrow transplant recipients. A sixth case included in this report received her transplant at another institution. The cumulative annual incidence rate of this infection was 1.75%. All patients had been treated previously for acute graft-versus-host disease (GVHD). At the time of diagnosis of systemic Nocardia infection, a median of 198 (range 148–1121) days after transplantation, all patients had extensive chronic GVHD and were taking 2 to 3 immunosuppressive medications. Prior to diagnosis of Nocardia infection patients had experienced multiple opportunistic infections, including infections with Mycobacterium avium-intracellulare, Pneumocystis carinii , and cytomegalovirus antigenemia. Treatment with trimethoprim-sulfamethoxazole (TMP-SMX), ceftriaxone, or carbapenem antibiotics resulted in a median survival of 219 days from the time of diagnosis and an actuarial 1-year survival of 40%. All patients who received more than 2 weeks of therapy were cured of their infections. Notably, 5/6 patients in this cohort were unable to take TMP-SMX because of myelosuppression. In comparison with randomly selected control patients, the use of pentamidine for prevention of P. carinii infection was associated with a marginal increase in the risk of Nocardia infection. We postulate that the use of TMP-SMX may be of benefit in the prophylaxis of infections other than P. carinii in patients with chronic GVHD.     

Factors predictive of disease progression and death in AIDS-related Kaposi's sarcoma

Background   The natural history of Kaposi's sarcoma (KS) is poorly documented. We attempted to identify factors predictive of progression and survival in HIV-infected patients with KS and CD4⁺ cell counts greater than 100/μL.
Patients and Methods   We studied retrospectively 78 HIV-infected patients diagnosed as having KS between 1989 and 1995. The following variables were assessed as potential predictors of progression and death, in a Cox proportional hazards model: age, sex, ethnic group, transmission group, site of the first KS lesions, duration of KS, concomitant opportunistic infections or malignancies, antiretroviral drug therapy (excluding protease inhibitors), antiherpes treatments, neutrophil counts, CD4⁺ and CD8⁺ cell counts, plasma HIV load, p24 antigenaemia, β₂-microglobulinaemia and immunoglobin A and G serum levels.
Results   During a median follow-up of 22 months (3–81 months), KS progressed in 66 of the 78 patients. The median survival time after progression was 68 months (9–126 months). Multivariate analysis identified only visceral KS, a high neutrophil count and a high serum immunoglobulin (Ig) level as independent predictors of progression ( P  < 0.05). Previous and concomitant opportunistic diseases ( P  = 0.003) and low CD4⁺ cell counts ( P  = 0.013) were independently associated with shorter survival; in contrast KS therapy did not independently influence survival.
Conclusion   Progression of KS is predicted by markers of KS severity, while overall survival is best predicted by markers of immunodeficiency (opportunistic diseases and the CD4⁺ cell count).     

T cell depletion utilizing CD34(+) stem cell selection and CD3(+) addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients

CD34‐selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft‐versus‐host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post‐transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34‐selected 8–10/10 human leucocyte antigen (HLA)‐matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n = 13) or non‐malignant (n = 6) diseases. T cells were added back to achieve total dose 1·0–2·5 × 10⁵ CD3⁺/kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade II–IV aGVHD, limited chronic GVHD (cGVHD), and extensive cGVHD were 15·8%, 23·3%, and 0%, respectively. One patient developed PTLD. One‐year infection‐related mortality was 5·6%. T cell immune reconstitution was delayed. One‐year overall survival was 82·3%. Five patients with malignant disease ultimately died from progressive disease. CD34‐selected MUD PBSCT using a defined dose of T cell add‐back resulted in high rates of engraftment and low risk of grade II–IV aGVHD, early transplantation‐related mortality, and extensive cGVHD.     

Prevalence and outcome of fungal infection in patients with severe acute pancreatitis

Background and Aim:  To study the prevalence of risk factors and outcome of fungal infections in patients with severe acute pancreatitis.
Methods:  Fifty consecutive patients with severe acute pancreatitis were investigated for evidence of fungal infection by weekly culture of body fluids and aspirate from pancreatic/peripancreatic tissue and samples collected at necrosectomy. All patients were managed as per a standard protocol. Patients with documented fungal infection were treated with intravenous amphotericin or fluconazole. Data were analyzed using SPSS software (version 13), and risk factors for fungal infection and mortality were determined.
Results:  Fungal infection was documented in 18 (36%) of 50 patients with Candida albicans (the commonest species). The incidence of fungal infection steadily increased with increasing duration of hospital stay. Those with fungal infection more often had evidence of respiratory failure ( P  = 0.031) and hypotension ( P  = 0.031) at admission, prolonged hospital stay > 4 weeks ( P  = 0.034), longer duration of antibiotics ( P  = 0.003), received total parenteral nutrition ( P  = 0.005), and required mechanical ventilation ( P  = 0.001) in contrast to those without fungal infection. The logistic regression analysis found the independent risk factors for fungal infection to be antibiotic therapy for > 4 weeks and hypotension at hospitalization. Of the 18 patients with fungal infection, 13 were administered intravenous antifungals; eight of these patients survived, while the five who did not receive antifungals died.
Conclusion:  Fungal infection was detected in 36% of our patients. The independent risk factors associated with it were hypotension at hospitalization and prolonged antibiotic therapy. Antifungal therapy improved their chances of survival.     

Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incidence at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell- depleted marrows ( P  = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts <3% prior to transplant ( P  = n.s.). However, relapse incidence differed significantly in patients with non-T-cell-depleted transplants and high basophil counts (> 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group ( P  = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy.     

Common community acquired infections and subsequent risk of chronic lymphocytic leukaemia

Emerging evidence supports a role for immune-related factors in the causation of chronic lymphocytic leukaemia (CLL). Using the population-based U.S. Surveillance Epidemiology and End Results-Medicare database, 10 171 elderly CLL patients and 122 531 frequency-matched controls were identified in order to evaluate several community acquired infections associated with subsequent CLL risk. Odds ratios (ORs) were adjusted for gender, age, race, calendar year and number of physician claims. CLL risk was increased following Medicare claims for sinusitis (OR = 1·11; 95% CI = 1·05–1·17), pharyngitis (OR = 1·15; 1·08–1·22), bronchitis (OR = 1·14; 1·08–1·19), pneumonia (OR = 1·17; 1·11–1·24), influenza (OR = 1·10; 1·01–1·19), cellulitis (OR = 1·08; 1·02–1·14) and herpes zoster (OR = 1·26; 1·15–1·37). Associations with pneumonia and cellulitis remained significant when the 5-year period before diagnosis/control selection was excluded. CLL risk increased with increasing severity/frequency of pneumonia ( P  = 0·005), cellulitis ( P  < 0·001) and herpes zoster ( P  < 0·001). Our findings suggest that common infections may play a role in CLL aetiology. Alternatively, the associations might reflect an underlying immune disturbance present several years prior to CLL diagnosis.     

Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma

Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) have been reported after autologous transplantation (AT) for lymphoma. It is not clear whether myeloablative therapy used in conjunction with autologous transplantation contributes to the development of MDS/AML or whether the conventional chemotherapy preceding the transplant, and administered over a prolonged period, causes these secondary malignancies. To address this issue, we examined 188 patients with multiple myeloma (MM) who had received AT. 71 patients with no more than one cycle of standard chemotherapy were enrolled in our Total Therapy program, designed to avoid exposure to alkylating agents prior to peripheral blood stem cell mobilization (group 1). The median duration of pre-transplant therapy in group 1 was 7.6 months and significantly shorter than the 24 months of 117 patients (group 2) with more prolonged conventional therapy ( P  = 0.0001). All seven patients developing MDS post-transplantation belonged to group 2 ( P  = 0.02); the median durations from initial therapy and first transplant were 66 months (range 38–86) and 24 months (range 9–39), respectively. Our findings provide evidence that prolonged standard-dose alkylating agent therapy prior to transplantation, rather than autotransplant-supported myeloablative treatment, is associated with development of MDS/AML. Stem cell damaging alkylator treatment should be avoided, not to compromise PBSC collection, but also to reduce the risk of treatment-related MDS/AML.     

Primary cutaneous fungal infection after solid-organ transplantation: report of five cases and review.

Solid-organ transplant recipients who are receiving immunosuppressive therapy are at increased risk of acquiring opportunistic infections, particularly fungal infections. We present the cases of five liver transplant recipients who developed primary cutaneous opportunistic fungal infections that remained localized to the skin. These cases are compared with 27 previously reported cases of primary cutaneous fungal infections. In these previously reported cases, administration of systemic antifungal medications, including amphotericin B, ketoconazole, griseofulvin, and miconazole, resulted in a 71% survival rate. Medical and surgical therapy together resulted in an 86% survival rate, and surgical excision resulted in a 100% survival rate. Thus, regardless of the age of the patient, type of immunosuppressive therapy, clinical presentation, or organisms involved, surgical excision yielded the highest cure rate. When possible, surgical excision should be performed on solid-organ transplant recipients who acquire opportunistic fungal infections.     

Phaeohyphomycosis due to Alternaria species in transplant recipients

R.D. Boyce, P.J. Deziel, C.C. Otley, M.P. Wilhelm, A.J. Eid, N.L. Wengenack, R.R. Razonable. Phaeohyphomycosis due to Alternaria species in transplant recipients.
Transpl Infect Dis 2010: 12: 242–250. All rights reserved Abstract: Alternaria species are members of a heterogenous group of dematiaceous fungi that rarely cause opportunistic infections in transplant recipients. During a 20‐year period from 1989 to 2008, 8 solid organ transplant recipients (63% males; median age, 48 years) developed Alternaria species infections at the Mayo Clinic. All patients were highly immunocompromised as evidenced by their receipt of multiple transplants, treatment of acute and chronic allograft rejection, and occurrence of other opportunistic infections. All patients presented with non‐tender erythematous or violaceous skin papules, nodules, or pustules in exposed areas of the extremities. No case of visceral dissemination was observed. Itraconazole was the most common drug used for treatment, although voriconazole, posaconazole, and caspofungin could potentially be useful based on our limited clinical data and in vitro antifungal susceptibility testing. One patient was treated with voriconazole, while another patient who was refractory to itraconazole had rapid resolution of lesions after the addition of caspofungin. Attempts at antifungal therapy alone were unsuccessful; all patients eventually required surgical excision of lesions. In conclusion, Alternaria species are rare but increasingly recognized opportunistic infections among highly immunocompromised transplant recipients. Wide excisional surgery combined with prolonged systemic antifungal therapy and reduction in immunosuppressive regimens provided the best chance of cure. Although itraconazole remains the most common drug for treatment, this case series highlights the potential clinical utility of caspofungin, voriconazole, and posaconazole as alternative regimens.     

Cryptococcal meningitis: an analysis among 5521 consecutive organ transplant recipients

Abstract: Cryptococcal meningitis has been reported to be an important cause of morbidity and mortality in renal transplant recipients. However, additional studies of recipients of other organ transplants suggested that these patients might be at low risk for cryptococcal meningitis. We examined the incidence and clinical features of cryptococcal meningitis among different groups of organ transplant patients at the University of Pittsburgh Medical Center. From January 1989 through July 1999, 28 patients were diagnosed with cryptococcal meningitis among 5521 transplant recipients. These included liver (11/2539), heart (8/372), kidney (7/2122), lung (1/432), and small bowel (1/56) recipients. The incidence of cryptococcal meningitis was higher in heart and small bowel recipients compared to other transplant populations ( P  = 0.005). The cryptococcal meningitis-related mortality in transplant recipients was 50% and was associated with altered mental status ( P  = 0.001), absence of headache ( P  = 0.02), and liver failure ( P  = 0.002). Multivariable analysis indicated that liver failure was the only independent risk factor for poor prognosis ( P  = 0.043). All cases of liver failure occurred among liver transplant recipients. Cryptococcal meningitis is associated with significant mortality among organ transplant recipients. The presence of allograft failure in liver transplant recipients with cryptococcal meningitis may be an indicator of poor prognosis in this patient population.     

Opportunistic infections complicating solid organ transplantation with alemtuzumab induction

Opportunistic infections remain a common complication of solid organ transplantation. Despite significant changes in immunosuppression and infectious diseases prophylaxis, data are limited on the contemporary epidemiology and outcomes of opportunistic infections. Alemtuzumab, a potent lymphocyte‐depleting antibody, has been used with increased frequency in solid organ transplant recipients in the last decade. A literature review was performed to summarize the current understanding of the epidemiology, risk factors, and outcomes of opportunistic infections complicating solid organ transplantation with and without alemtuzumab induction therapy. Areas where data are limited regarding opportunistic infections in solid organ transplantation with alemtuzumab induction are indicated.     

Infections during induction therapy of childhood acute lymphoblastic leukemia--no association to mannose-binding lectin deficiency

OBJECTIVES: Infection during the induction phase of childhood acute lymphoblastic leukemia (ALL) is a major cause of morbidity and mortality. Several studies have indicated that genetically determined low serum levels of mannose-binding lectin (MBL), a component of innate immunity, are associated with increased risk for infections in patients receiving chemotherapy. Thus, these patients have been proposed to be candidates for MBL replacement therapy. METHODS: In a population-based cohort of 137 children with ALL treated at a single pediatric hematology-oncology center with an almost identical chemotherapy regimen, we studied the relationship between polymorphisms in the MBL gene (MBL2) and the MBL2 promoter and the risk of infections during the first 50 d of induction therapy. RESULTS: No increased frequency of infection was seen for the children with genotypes encoding serum low levels of MBL. A higher incidence of fever (P < 0.004), infectious events (P = 0.025), days with neutropenia (P < 0.001) and a higher frequency of antimicrobial therapy (P = 0.0007) were seen in the young age group (<2.5 yr) compared with the older age group (> or =2.5 yr), independent of the MBL genotype. CONCLUSIONS: MBL deficiency did not influence the frequency of infections in children receiving induction chemotherapy for ALL, not even in the youngest children (<2.5 yr) whom we found to have the highest risk for infections.     

Effect of interferon α-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis

Aim:  The objective of this study was to elucidate the long-term effects of interferon (IFN)α-2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C.
Methods:  A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN-α-2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis.
Results:  A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non-SVR patients ( P  = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years ( P  = 0.006), advanced histological staging ( P  = 0.033), non-SVR to IFN therapy ( P  = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of ≧ 40 IU/L after the combination therapy ( P  = 0.021).
Conclusions:  These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development.     

Occurrence of graft‐versus‐host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT

Background

The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune‐mediated graft‐versus‐leukaemia effects. Previous studies have suggested a strong association between graft‐versus‐host disease (GVHD) occurrence and graft‐versus‐leukaemia effects after allogeneic hematopoietic cell transplantation.

Methods

Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient‐year within sequential 90‐day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time‐dependent covariate.

Results

The study included data from 1068 patients given single (n  = 567) or double (n  = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II–IV acute (HR = 0.8, P  = 0.1) and chronic (HR = 0.65, P  = 0.1) GVHD decreased relapse risk. However, grade II–IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P  = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P  < 0.001) and late (HR = 4.9, P  < 0.001) mortality after UCBT.

Conclusions

The occurrence of grade II–IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft‐versus‐leukemia effect of GVHD.

     

Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections

It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group ( n  = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients ( n  = 34) treated with AmB ( P  = 0.09); P  = 0.03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis ( P  = 0.05 and P  = 0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P  = 0.03). More patients on AmB had a >100% increase of their baseline serum creatinine ( P  < 0.001).
The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.     

Infections after lung transplantation

Despite advances in prophylaxis and therapy, infections remain a major source of morbidity and mortality after lung transplantation. Lung transplant recipients are at increased risk for both community-acquired and nosocomial pathogens, which may develop at various time points. The risk of infections increases with the intensity of immunosuppression. Careful assessment of the recipient is essential to assure adequate prophylactic or preemptive therapy. Aggressive prophylaxis for some infections (e.g., cytomegalovirus) has substantially reduced the prevalence of serious infections due to this organism. Tuberculin-positive individuals should be treated with prophylactic isoniazid to reduce the chance for reactivation of tuberculosis following transplantation. Myriad opportunistic pathogens (including various viruses, bacteria, fungi, etc.) may complicate transplantation, owing to the effects of multiagent immunosuppressive therapy. This review addresses the salient pathogens that may infect organ transplant recipients, and discusses strategies to prevent or treat specific pathogens in this highly susceptible patient population.     

Severe infections after allogeneic peripheral blood stem cell transplantation: a matched-pair comparison of unmanipulated and CD34+ cell-selected transplantation

BACKGROUND AND OBJECTIVES: T-cell depletion of the graft delays immune recovery following allogeneic peripheral blood stem cell transplantation (PBSCT), but it is not clear whether it actually increases the risk of severe infections after the transplant. DESIGN AND METHODS: We have compared the occurrence of severe infections following 162 CD34+ cell-selected allogeneic PBSCT and 162 unmanipulated PBSCT (CD34+ and UM groups, respectively) from HLA-identical siblings. RESULTS: The probability of infection-related mortality (IRM) was 22% in the UM group and 31% in the CD34+ group (log-rank, p=0.2). In multivariate analyses only the use of fluconazole prophylaxis showed a protective effect on IRM in the whole set of patients, while in both transplant groups the most significant factor was the development of moderate-to-severe graft-versus-host disease (GVHD). The probability of developing cytomegalovirus (CMV) infection was 42% in the UM group and 59% in the CD34+ group (p=0.002), with no differences in CMV disease (10% and 9%, respectively). Multivariate analysis of CMV infection identified three variables associated with a higher risk in the whole set of patients: CMV positive serostatus, CD34+ transplant group and recipient age above 40 years. The development of moderate-to-severe GVHD was a significant factor only in the UM group. Disseminated varicella-zoster virus infection was more common in the CD34+ group (19% and 12%, p=0.05), as were early (< 30 days post-transplant) severe bacterial infections (28% vs 14%, p=0.002). Invasive fungal infections and pneumonias of unknown origin did not differ between groups. INTERPRETATION AND CONCLUSIONS: Our results do not show a significant increase in the risk of dying from an opportunistic infection with CD34+-PBSCT, but the risk of CMV infection is increased, with no differences in CMV disease or mortality attributable to CMV. There is an additive effect on IRM of developing moderate-to-severe GVHD (acute or chronic) following CD34+-PBSCT, and in this subset of patients maximum efforts for the prevention and early treatment of opportunistic infections should be pursued.     

Rapidly growing non‐tuberculous mycobacterial infection in a renal transplant patient after alemtuzumab induction

Renal transplant recipients are at high risk of developing opportunistic infections particularly in the first 6 months after transplantation. Organisms causing such infections include rapidly growing non‐tuberculous mycobacteria (NTM). Lymphocytes have a central role in combating mycobacterial infections. The use of lymphocyte‐depleting agents, such as alemtuzumab, in the renal transplant population has increased in recent years. A case of multifocal osteomyelitis caused by one of the NTM, Mycobacterium chelonae, in a renal transplant recipient, after alemtuzumab induction, is presented.     

Mycobacterial infection after renal transplantation in a Western population

Abstract:  Mycobacterial infection is a serious opportunistic infection in renal transplant recipients. The incidence is higher in developing than in developed Western countries. This study is a single-centre retrospective review of the records of 2502 renal transplant recipients in Belgium. Fourteen cases of mycobacterial infection (9 Mycobacterium tuberculosis and 5 atypical mycobacterial infection) were diagnosed. The time interval between transplantation and diagnosis was 64 ± 80 months (mean ± SD, range 5–188) for M. tuberculosis and 92 ± 75 months (range 14–209) for atypical mycobacterial infection. The localisation of M. tuberculosis was pulmonary/pleural in 67% and extrapulmonary in 33%. The atypical mycobacterial infections were located in skin, tendons, and joints. Eight patients received IV prednisolone pulse therapy for acute rejection long before the time of mycobacterial infection. The initial antimycobacterial therapy consisted of a combination of isoniazid, rifampicin, and ethambutol in all patients. In patients with M. tuberculosis infection, a good response to antimycobacterial therapy was obtained. In patients with atypical mycobacterial infection, initial treatment was successful in 3 out of 5 patients, in 1 patient recurrence was diagnosed and in another patient, who is still under treatment at present, the initial treatment was adjusted after identification of the atypical mycobacterium and its antibiogram.
The incidence of mycobacterial infection after renal transplantation did not increase with newer immunosuppressive therapy. The major risk factor is the total dose of corticosteroids. All patients responded well without major reductions in immunosuppressive therapy. Chemoprophylaxis for high-risk patients still is recommended.