Nocardia infection in lung transplant recipients

Nocardia is a well-recognized pathogen in immunocompromised hosts, but the incidence of Nocardia infections in lung transplant recipients is not well defined. A chart review from 1990 to 2007 at Clarian Hospital Lung Transplant Center and Indiana University Medical Center revealed Nocardia infections in four of 410 lung transplant recipients despite prophylaxis. All infections were confined to lung and occurred at a median time of 315 d after transplantation. Nocardia nova was isolated in two patients, Nocardia farcinica in one, and unspecified Nocardia sp. in one. Nocardia isolates were susceptible to trimethoprim sulfa (TMP/SMX). Our data suggest that the dose of TMP/SMX, commonly used for Pneumocystis prophylaxis is not protective for Nocardia. Contrary to historic data reporting 40% mortality, none of the patients in our study died because of Nocardia. Nocardia infection is an under-recognized entity in lung transplant recipients, and the optimal duration of therapy and prophylaxis are unclear.     

Recurrent Pneumocystis carinii colonization in a heart-lung transplant recipient on long-term trimethoprim-sulfamethoxazole prophylaxis.

INTRODUCTION: In the setting of organ transplantation, prior to prophylaxis, Pneumocystis carinii pneumonia (PCP) had been a common clinical problem, particularly in heart-lung and lung recipients who receive long-term immunosuppressive therapy to prevent allograft rejection. Continuous oral trimethoprim-sulfamethoxazole (TMP-SMX) has been highly effective in preventing PCP in these patients. REPORT: In this paper we report a case of recurrent Pneumocystis carinii infection in a chronic (> 15 years) heart-lung allograft recipient on long-term TMP-SMX prophylaxis. Twice, in 1995 and again in 1998, Pneumocystis carinii infection was diagnosed by bronchoalveolar lavage (BAL), in the same patient, despite continued oral TMP-SMX (960 mg TMP/4800 mg SMX per week) prophylaxis. The subject was not lymphopenic (his CD4 count was 569/mm3) and there was no associated deterioration in pulmonary function, nor evidence of hypoxemia. CONCLUSION: This case demonstrates that asymptomatic Pneumocystis carinii lung infections may recur in chronic heart-lung transplant recipients who take standard oral PCP prophylaxis.     

Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii infections in heart-lung and lung transplantation--how effective and for how long?

Pneumocystis carinii pneumonia (PCP) is a common clinical problem in the setting of organ transplantation, particularly in heart-lung and lung allograft recipients. Without prophylactic measurements, the incidence of P carinii pneumonia can reach up to 88% of heart-lung transplant recipients. We conducted a retrospective analysis of the Stanford heart-lung and lung transplant experience in order to assess the efficacy of the prophylactic therapy and to try to define the duration of therapy necessary for prevention. During a 9-year period 82 heart-lung and 13 single-lung transplants were performed. Of the patients not on prophylaxis therapy 27% (13 patients) developed P carinii infection as compared with 0% of patients on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. The incidence of PCP infection peaked between 3 and 6 months posttransplantation. No case of infection was observed before the 7th week posttransplant. PCP was more common following induction immunosuppression with OKT3 as compared with RATG (P less than 0.05). All cases of infections later than one year posttransplant were associated with recent increase in the immunosuppression regimen with high-dose corticosteroids for treatment of acute or chronic (obliterative bronchiolitis) rejection. Although our study is retrospective and based on various immunosuppressive and diagnostic technique periods, it seems that TMP-SMX is highly effective in preventing PCP infections in heart-lung and lung transplant recipients. Twelve months of therapy is probably a sufficient length of therapy if immunosuppressive therapy is stable. However, whenever augmentation in the immunosuppression regimen is indicated, prophylactic therapy should promptly be restarted.     

Nocardia farcinica brain abscess in a patient without immunocompromise

Brain abscess has an incidence of 1 per 100,000 in developed countries and a mortality rate of 10%. Cerebral infections with Nocardia farcinica have a mortality of up to 90%. Nocardial species are important pathogens in immunocompromised hosts, but infections in immunocompetent patients are extremely rare. We report a case of primary brain abscess with N. farcinica in a patient without immunosuppression, which was treated with surgery and a one-year course of oral moxifloxacin.     

Invasive Pneumococcal Infections in Adult Lung Transplant Recipients

An increased risk of invasive pneumococcal infection (IPI) has been described among kidney or heart transplant recipients, but the epidemiology of IPI among lung transplant recipients has not been previously reported. We undertook a single center, retrospective cohort study to define the incidence, timing, clinical, and microbiologic features of IPI in lung transplant patients. Fourteen out of 220 recipients (6.4%) developed IPI at a median of 1.3 years after transplantation (incidence rate: 22.7 cases per 1000 person-years). All patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis, and 10 (71%) had TMP-SMX-resistant isolates. All isolates were from the 23 valent polysaccharide vaccine-associated serogroups. The high incidence of IPI in lung transplant recipients is similar to that reported in kidney and heart recipients. Alternative prevention strategies, including use of the conjugated pneumococcal vaccine, should be explored in future studies.     

Infection in renal transplant recipients

Renal transplant recipients are susceptible to infection by a wide array of pathogens. Impaired inflammatory responses due to immunosuppressive therapies suppress clinical and radiologic findings engendered by microbial invasion. As a result, patients are often minimally symptomatic and evaluation and diagnosis are delayed. Specific microbiologic diagnosis is essential both for the optimization of antimicrobial therapy and to avoid unnecessary drug toxicities. Differential diagnosis is guided by knowledge of organisms commonly involved in infection in immunocompromised hosts and understanding of the limitations of prophylactic strategies. The risk of infection in the organ transplant recipient is determined by the interaction between the individual's epidemiologic exposures and net state of immunosuppression. Epidemiology includes environmental exposures in the community and hospital, organisms derived from donor tissues and latent infections activated in the host during immune suppression. The net state of immune suppression is determined by the interaction of all factors contributing to infectious risk. Routine antimicrobial prophylaxis is aimed at common infections and unique risk factors in individual patient groups. This includes trimethoprim-sulfamethoxazole (for Pneumocystis, Toxoplasma, most Nocardia and Listeria, common urinary pathogens), perioperative (eg, anti-fungal prophylaxis for pancreas transplants), or antiviral (for herpesviruses in high risk recipients).     

Nocardial infection in a renal transplant recipient on tacrolimus and mycophenolate mofetil.

Infection with Nocardia spp. is an uncommon but important cause of morbidity and mortality in organ transplant recipients. Cotrimoxazole prophylaxis against urinary tract infection and Pneumocystis carinii pneumonia in these patients usually prevents nocardial infection also. We report the case of a patient on tacrolimus and mycophenolate mofetil who developed drug-induced diabetes mellitus followed by nocardial brain infection. This infection occurred despite conventional cotrimoxazole prophylaxis. Physicians should be aware that newer, more potent and more diabetogenic immunosuppressive regimens may increase the risk of opportunistic infections such as nocardiosis, even in the presence of "adequate" antimicrobial preventive measures.     

Hypercalcemia and suppressed PTH levels in a renal transplant patient infected with Pneumocystis carinii

Pneumocystis carinii pneumonia is a serious and relatively common complication of immunosuppressive therapy. In immunocompromised patients, P. carinii pneumonia can cause significant morbidity and mortality. Another common complication, typically seen in the subpopulation of renal transplant recipients, is hypercalcemia. The prevalence of hypercalcemia varies, reaching as high as 71%. We report the case of a renal transplant recipient who developed P. carinii pneumonia and hypercalcemia, the latter being resolved after the successful treatment of the former. We argue that there is a causal relationship between P. carinii pneumonia and hypercalcemia in renal transplant recipients. In immunocompromised patients, pulmonary infection accompanied by hypercalcemia should raise the suspicion of P. carinii pneumonia.     

Pulmonary infections in cardiac transplant patients: modes of diagnosis, complications, and effectiveness of therapy

Eighteen serious pulmonary infections have been encountered in 10 of 16 surviving cardiac transplant recipients. Fourteen of 18 infections (78%) occurred within the first six months after transplant and the remaining 4 (22%) after the first six months (p less than 0.05). There was no correlation between the number of rejections per patient and propensity toward infection. Transtracheal aspiration or percutaneous lung aspiration established the diagnosis in all but two episodes. Percutaneous lung aspiration appeared more accurate as a diagnostic tool but was associated with 6 complications in 13 attempts (46%), while no complications occurred in 17 attempts with transtracheal aspiration (p less than 0.05). Five of the 10 patients had multiple episodes of pulmonary infection; 2 of these 5 (40%) had concurrent infections. Nocardia organisms were encountered most frequently, accounting for 7 of 18 (39%) infections; 6 of 10 patients (60%) were infected with Nocardia at some point after transplant. Nine of 10 patients (90%) were cured of infection. Eight are still alive without evidence of infection. We conclude from these data that pulmonary infection is common in transplant recipients, that early definitive diagnosis, in spite of the potential complications, is warranted, and that cure of infection and long-term survival are possible if treatment is timely and aggressive.     

Pneumocystis jirovecii Pneumonia in Liver Transplant Recipients: A Systematic Review

BackgroundPneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients.MethodsWe searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms “liver transplantation” and “pneumocystis.” Our search yielded 60 articles, 35 of which were used for our review.ResultsP. jirovecii pneumonia (PJP) has an incidence of 1%–11% in liver transplant recipients without prophylaxis and mortality rates of 7%–88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%–3%. The duration of its use varies from 3 months to 1 year after the liver transplantation.ConclusionsPJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.     

Tuberculosis in Renal Transplant Recipients: A Brazilian Center Registry

Renal transplant recipients receiving immunosuppression show an increased risk for developing opportunistic infections, such as tuberculosis (TB). TB represents the major cause of morbidity and mortality in the world, mainly in underdeveloped countries. The aim of this study was to analyze the incidence of TB and its presentation among renal transplant recipients over 20 years.

Patients and Methods

This retrospective analysis included medical records of renal transplant recipients from January 1984 to April 2007.

Results

Among 1342 renal transplant recipients, 31 received treatment for TB due to clinical disease (n = 23) or prophylaxis (n = 8). The overall incidence of TB was 1.71%, which was diagnosed at 53 ± 49 months posttransplantation. The indications for TB prophylaxis were a previous history of TB (n = 6) or direct contact with a TB carrier (n = 1). The most common clinical presentation was extrapulmonary (n = 13). The classical treatment was effective in 16 cases. However, 7 cases of resistant TB required ethambutol added to therapy. Adverse events of treatment included liver toxicity (n = 1) and peripheral neuropathy (n = 1). Three patients died due to TB-related complications. Graft loss was observed in 3 patients after cessation of TB treatment. None of the patients on prophylaxis developed clinical disease.

Conclusions

TB incidence was significantly greater among renal transplant recipients compared with the local population, with a higher incidence of extrapulmonary disease. TB prophylaxis in selected cases was effective, avoiding new infections.     

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups. Received: 14 April 1998 Received after revision: 24 September 1998 Accepted: 18 December 1998     

Voriconazole Prophylaxis in Lung Transplant Recipients

Lung transplant recipients have one of the highest rates of invasive aspergillosis (IA) in solid organ transplantation. We used a single center, nonrandomized, retrospective, sequential study design to evaluate fungal infection rates in lung transplant recipients who were managed with either universal prophylaxis with voriconazole (n = 65) or targeted prophylaxis (n = 30) with itraconazole ± inhaled amphotericin in patients at high risk (pre- or posttransplant Aspergillus colonization [except Aspergillus niger ]). The rate of IA at 1 year was better in lung transplant recipients receiving voriconazole prophylaxis as compared to the cohort managed with targeted prophylaxis (1.5% vs. 23%; p = 0.001). Twenty-nine percent of cases in the targeted prophylaxis group were in patients colonized with A. niger who did not receive itraconazole. A threefold or higher increase in liver enzymes was noted in 37–60% of patients receiving voriconazole prophylaxis as compared to 15–41% of patients in the targeted prophylaxis cohort. Fourteen percent in the voriconazole group as compared to 8% in the targeted prophylaxis group had to discontinue antifungal medications due to side effects. Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients. Regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity.     

Delay of CMV infection in high-risk CMV mismatch lung transplant recipients due to prophylaxis with oral ganciclovir

Cytomegalovirus (CMV) is a common opportunistic infection in lung transplant recipients. Despite the use of early post-operative intravenous ganciclovir, most high-risk patients develop CMV infection. We conducted this retrospective study to determine the efficacy of extended CMV prophylaxis with oral ganciclovir in high-risk, donor-positive-recipient-negative, lung recipients. All patients initially received 3 months of intravenous ganciclovir and CMV hyperimmune globulin. Clinical outcomes in all CMV mismatch patients undergoing lung transplant surviving at least 3 months were included (n = 42). Since 1998, 14 patients received no oral ganciclovir prophylaxis (group 1) and 28 patients received indefinite oral ganciclovir after completion of intravenous therapy (group 2). In those patients receiving oral ganciclovir, the prevalence of post-transplant CMV infection was significantly reduced over the first 180 d post-transplant (50% in group 1 vs. 4% in group 2; p < 0.001). Although some CMV events were observed with additional follow-up in group 2, there remained a significantly greater freedom from CMV infection by Kaplan-Meier analysis in group 2 as compared with group 1, with over 30 months follow-up time in each group (log-rank, p = 0.02). A moderate rate of drug discontinuation was observed in group 2, and no severe drug-related events occurred. In high-risk lung transplant recipients, CMV prophylaxis with intravenous ganciclovir, followed by indefinite oral ganciclovir, significantly delays and reduces post-transplant CMV infections. A larger prospective randomized study is needed to confirm the benefits of oral ganciclovir on CMV prevention.     

Following Universal Prophylaxis with Intravenous Ganciclovir and Cytomegalovirus Immune Globulin, Valganciclovir is Safe and Effective for Prevention of CMV Infection Following Lung Transplantation

We prospectively determined the safety and efficacy of valganciclovir for prevention of cytomegalovirus (CMV) in at-risk (donor positive/recipient negative [D+/R-] or R+) lung transplant recipients. We also determined the length of prophylaxis required to significantly decrease both CMV infection and disease. Consecutive lung transplant recipients surviving >30 days (n = 90) received combination prophylaxis with intravenous (i.v.) ganciclovir (GCV) 5 mg/kg/day and cytomegalovirus immune globulin (CMV-IVIG) followed by valganciclovir (450 mg twice-daily) to complete 180, 270 or 365 days of prophylaxis. This group was compared to a historical group (n = 140) who received high-dose oral acyclovir following i.v. GCV and CMV-IVIG. CMV disease was significantly lower in patients receiving valganciclovir compared to acyclovir (2.2% vs. 20%; p < 0.0001). Freedom from CMV infection and disease was significantly greater (p < 0.02) in patients receiving 180, 270 or 365 days of prophylaxis (90%, 95% and 90%, respectively) compared to those receiving 100-179 days (64%) or < 100 days (59%). No patient receiving valganciclovir died during the study. Following prophylaxis with i.v. GCV and CMV-IVIG, valganciclovir is safe and effective for prevention of CMV infection and disease in at-risk lung transplant recipients. The required length of prophylaxis was at least 180 days.     

Nocardia farcinica brain abscess: clinical and specific radiological findings and management. Report of two cases in immunononcompromised patients

Nocardia spp. cerebral abscesses are rare and usually occur in immunocompromised patients. We report two recent cases of cerebral abscesses due to Nocardia farcinica in immunocompetent patients and review the literature about diagnosis and therapeutic issues. Outcome was good for the two patients following an early identification of the bacteria. Stereotactic biopsy was performed in one case and craniotomy with excision of the abscess in the other case. In both cases, complete identification of the bacteria could be achieved, followed by prolonged antibiotic therapy. Exposure to the germ (mainly telluric) is often difficult to suspect from the past medical history of the patient. Diagnosis is also unexpected. Despite the typically and characteristic aspect on CT and MRI, specific identification and anti-microbial sensitivity profiles are necessary to optimize treatment. In some rare cases, unusual species like Nocardia farcinica, can be resistant to numerous antibiotics requiring adjustments of medical management. Early identification of the bacteria is necessary to achieve good outcome in immunocompetents patients.     

A heart transplant recipient lost due to Pneumocystis jiroveci pneumonia under trimethoprim-sulfamethoxazole prophylaxis: case report

Infections in solid-organ transplant recipients are the most important causes of morbidity and mortality. A primary goal in organ transplant is the prevention or effective treatment of infection, which is the most common life-threatening complication of long-term immunosuppressive therapy. A 21-year-old woman who underwent heart transplant 3 years previous owing to dilated cardiomyopathy was referred to our hospital with symptoms of high fever and cough. The patient's history revealed that she had received a trimethoprim-sulfamethoxazole double-strength tablet each day for prophylactic purposes. On chest radiograph, pneumonia was detected, and in broncho-alveolar lavage sample, Pneumocystis jiroveci cysts were found. After diagnosing P. jiroveci pneumonia, trimethoprim-sulfamethoxazole was initiated at 20 mg/kg/d including intravenous trimethoprim in divided dosages every 6 hours. On the sixth day of therapy, she died in intensive care unit. In solid-organ transplant recipients, although antipneumocystis prophylaxis is recommended within the first 6 to 12 months after transplant, lifelong prophylaxis is also used in several settings. In addition, the physician should keep in mind that P. jiroveci pneumonia may develop in solid organ recipients, despite trimethoprim-sulfamethoxazole prophylaxis.     

Comparison of DNA amplification and immunofluorescence for detecting Pneumocystis carinii in patients receiving immunosuppressive therapy.

Two studies were performed to compare the sensitivity of DNA amplification with immunofluorescence for the detection of Pneumocystis carinii in asymptomatic normal and immunosuppressed subjects receiving no anti-Pneumocystis chemoprophylaxis. In the first study, immunofluorescence and silver stains were used to examine 12 induced sputa and 12 bronchoalveolar lavage specimens from 24 normal control subjects; induced sputa from 20 renal transplant recipients; and induced sputa from 11 patients with fibrosing alveolitis. All specimens were negative for P carinii using both stains, apart from one renal patient in whom 2 P carinii cysts were seen by immunofluorescence alone. In the second study, DNA amplification and immunofluorescence were used to examine induced sputa from 3 groups of 10 control, renal, and heart/lung transplant recipients. All 30 specimens were negative for P carinii by immunofluorescence. However, 3 renal and 2 heart/lung patients were positive for P carinii by DNA amplification alone. One of these patients developed P carinii pneumonia 6 weeks after sputum induction. DNA amplification is a more sensitive technique than immunofluorescence for detecting P carinii. P carinii colonization occurs in asymptomatic organ transplant recipients, but not in normal individuals.     

Simkania negevensis in bronchoalveolar lavage of lung transplant recipients: a possible association with acute rejection

BACKGROUND: Simkania negevensis is a novel organism closely related to chlamydiae. The organism has been associated with community acquired pneumonia and acute exacerbation of chronic obstructive pulmonary disease. The prevalence and pathogenic potential of S. negevensis is not known in lung transplant recipients. METHODS: In this multicenter study comparative analysis of bronchoalveolar lavage (BAL) in lung transplants (Tx) and kidney Tx, immunocompromised and nasopharyngeal (NP) washes of immunocompetent patients was done. The BAL specimens were tested by nested polymerase chain reaction (PCR) for C. pneumoniae and S. negevensis. Selected S. negevensis positive PCR cases were confirmed by culture. RESULTS: In the initial 41 BAL samples S. negevensis was detected in 97.5% (40/41) of lung transplant recipients as compared to 14.1% (1/7) in other organ transplant recipients (P<0.0001). In the sequential samples of 19 lung transplant recipients, 59% (24/41) had concomitant positive PCR and rejection as compared to 30% (3/10) who had negative PCR but had rejection (P=0.16). S. negevensis infection had hazard ratio of 3.29 (95% CI: 0.73-14.76; P=0.11) for developing acute rejection. CONCLUSION: S. negevensis is highly prevalent in liver Tx recipients and may be associated with acute rejection.     

Syndrome of Inappropriate Antidiuretic Hormone Secretion Complicating Systemic Nocardiosis in a Renal Transplant Recipient: A Case Report

Background

Infection by Nocardia species is an uncommon cause of severe clinical syndromes, particularly in immunocompromised patients, and solid-organ transplantation is the most common underlying condition. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been described thus far in lung and stem cell transplants with systemic nocardiosis.