Nocardiosis in transplant recipients Lebeaux, D.; Morelon, E.; Suarez, F. ...
European journal of clinical microbiology & infectious diseases,
05/2014, Letnik:
33, Številka:
5
Journal Article
Recenzirano
Nocardiosis is a rare opportunistic infection caused by
Nocardia
spp., an aerobic actinomycete, that mainly affects patients with cell-mediated immunity defects, such as transplant recipients. ...Despite recent progress regarding
Nocardia
identification and changes in taxonomic assignment, many challenges remain for the diagnosis or management of nocardiosis. This opportunistic infection affects 0.04 to 3.5 % of patients with solid organ or hematopoietic stem cell transplantation, depending on the organ transplanted, cytomegalovirus (CMV) infection, corticosteroids dose and calcineurin inhibitors level. Nocardiosis diagnosis relies on appropriate clinical, radiological and microbiological workup that includes the sampling of an accessible involved site and molecular microbiology tools. In parallel, extensive clinical and radiological evaluations are mandatory, including brain imaging, even in the absence of neurological signs. In transplanted patients, differential diagnosis is challenging, with co-infections reported in 20 to 64 % of cases. As the antibiotic susceptibility pattern varies among species, the antimicrobial regimen before species identification should rely on the association of antibiotics active on all species of
Nocardia
. Bactericidal antibiotics are required in cases of severe or disseminated disease. Furthermore, in transplant recipients, combination therapy is difficult to manage because of cumulative toxicity and interactions with immunosuppressive agents. Because of a high recurrence rate, antibiotic therapy should be prescribed for 6 to 12 months.
Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious ...therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to
, 13.5% to varicella-zoster virus, 5.5% to
, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for
) or absent (
). M/ME caused by Enterobacteria,
or filamentous fungi were associated with high and early mortality (50%-70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.
Anti‐HLA donor‐specific antibodies (DSAs) cause acute and chronic antibody‐mediated rejection (AMR). However, the clinical relevance of anti‐HLA‐C antibodies remains unclear. We evaluated the ...clinical relevance of the presence of anti‐HLA‐C DSA at day 0 in renal transplant recipients. In this retrospective, case‐controlled study, 608 patients who underwent kidney transplantation between August 2008 and March 2012 were screened for the presence of isolated anti‐HLA‐C DSA at day 0. A total of 22 renal transplant recipients were selected and followed for a period of 1 year. AMR was classified according to the Banff classification. The 22 patients were compared with 88 immunized patients. Acute AMR was diagnosed in six patients (27.3%). The median level of DSA at day 0 was 1179 (530–17 941). The mean fluorescence intensity in the anti‐C group was 4966 (978–17 941) in the AMR group and 981 (530–8012) in the group of patients without AMR. Acute AMR was diagnosed less frequently in the 88 immunized individuals (9.1%) than in the DSA anti‐C group (p = 0.033). The level of DSA at day 0 was predictive for AMR (p = 0.017). Patients with a high level of pretransplant anti‐HLA‐C DSAs are likely to develop acute AMR during the first year after transplantation.
In this retrospective, case‐controlled study of renal transplant recipients, the authors demonstrate that patients with a high level of pretransplant anti‐HLA‐C donor‐specific antibodies are likely to develop acute antibody‐mediated rejection during the first year after transplantation.
In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report ...the case of a renal transplant recipient who developed severe cryptococcal meningitis‐associated IRIS 1 week after immunosuppression reduction. High‐dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor‐α (TNF‐α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.
A renal transplant recipient with steroid‐resistant cryptococcal meningitis‐associated immune reconstitution inflammatory syndrome experiences neurological improvement under adalimumab, a human monoclonal tumor necrosis factor‐alpha.
Background. Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors ...for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients. Methods. We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis. Results. One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2–244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio OR, 6.11; 95% confidence interval CI, 2.58–14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17–6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03–1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02–1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00–1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms. Conclusions. We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.
Despite the dramatic decrease in opportunistic infections after the introduction of highly active antiretroviral therapy, Pneumocystis jirovecii pneumonia remains the major AIDS related infection in ...France.
The clinical, radiological and microbiological diagnosis is usually easily made in HIV-infected patients. The preferred treatment is high dose trimethoprim-sulfamethoxazole, in association with steroids in cases of severe hypoxaemia. This has led to a dramatic reduction in mortality in these patients. Prophylactic treatment is mandatory in highly immunosuppressed patients (CD4 counts<200/μL) whose viraemia is not well controlled by antiretroviral therapy.
Whether PCR-based diagnosis would be useful for HIV-infected patients is a matter of debate, as is also the clinical significance of P. jirovecii colonization. The best alternative regimens for treating P. jirovecii pneumonia in cases of treatment failure or severe intolerance to trimethoprim-sulfamethoxazole are not clearly defined.
In the context of universal HIV testing and recent guideline recommendations to start antiretroviral therapy early in the course of HIV infection, the frequency of P. jirovecii pneumonia should continue to decline in France.
Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence ...of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB.
We performed this multicentre, randomized, open-label trial in kidney transplant recipients who had ASB and were ≥2 months post-transplantation. We randomly assigned participants to receive antibiotics or no therapy. The primary outcome was the incidence of symptomatic UTI over the subsequent 12 months.
One hundred and ninety-nine kidney transplant recipients with ASB were randomly assigned to antibiotics (100 participants) or no therapy (99 participants). There was no significant difference in the occurrence of symptomatic UTI between the antibiotic and no-therapy groups (27%, 27/100 versus 31%, 31/99; univariate Cox model: hazard ratio 0.83, 95%CI: 0.50–1.40; log-rank test: p 0.49). Over the 1-year study period, antibiotic use was five times higher in the antibiotic group than in the no-therapy group (30 antibiotic days/participant, interquartile range 20–41, versus 6, interquartile range 0–15, p < 0.001). Overall, 155/199 participants (78%) had at least one further episode of bacteriuria during the follow-up. Compared with the participant's baseline episode of ASB, the second episode of bacteriuria was more frequently caused by bacteria resistant to clinically relevant antibiotics (ciprofloxacin, cotrimoxazole, third-generation cephalosporin) in the antibiotic group than in the no-therapy group (18%, 13/72 versus 4%, 3/83, p 0.003).
Applying a screen-and-treat strategy for ASB does not reduce the occurrence of symptomatic UTI in kidney transplant recipients who are more than 2 months post-transplantation. Furthermore, this strategy increases antibiotic use and promotes the emergence of resistant organisms.
Background. Solid organ transplant (SOT) recipients are at risk of nocardiosis, a rare opportunistic bacterial infection, but prognosis and outcome of these patients are poorly defined. Our ...objectives were to identify factors associated with 1-year mortality after nocardiosis and describe the outcome of patients receiving short-course antibiotics (≤120 days). Methods. We analyzed data from a multicenter European case-control study that included 117 SOT recipients with nocardiosis diagnosed between 2000 and 2014. Factors associated with 1-year all-cause mortality were identified using multivariable conditional logistic regression. Results. One-year mortality was 10-fold higher in patients with nocardiosis (16.2%, 19/117) than in control transplant recipients (1.3%, 3/233, P < .001). A history of tumor (odds ratio OR, 1.4; 95% confidence interval CI, 1.1–1.8), invasive fungal infection (OR, 1.3; 95% CI, 1.1–1.5), and donor age (OR, 1.0046; 95% CI, 1.0007–1.0083) were independently associated with 1-year mortality. Acute rejection in the year before nocardiosis was associated with improved survival (OR, 0.85; 95% CI, 0.73–0.98). Seventeen patients received short-course antibiotics (median duration 56 24–120 days) with a 1-year success rate (cured and surviving) of 88% and a 5.9% risk of relapse (median follow-up 49 6–136 months). Conclusions. One-year mortality was 10-fold higher in SOT patients with nocardiosis than in those without. Four factors, largely reflecting general medical condition rather than severity and/or management of nocardiosis, were independently associated with 1-year mortality. Patients who received short-course antibiotic treatment had good outcomes, suggesting that this may be a strategy for further study.
To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT).
We performed a multinational case-control study that retrospectively ...recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy.
We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07–179.46; p 0.009) was identified as an independent risk factor for late IPA.
More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.
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