Year : 2007 | Volume
: 18 | Issue : 4 | Page : 594--598
Fatal Hemorrhagic Intracranial TB in a Renal Transplant Recipient despite INH Prophylaxis
Nasrulla Abutaleb1, Abdulmunaem Obaideen2, Abdulmajeed Hamza1, M Zakaria3, Hisham Afifi3, Sammera Fallata4, Seddiq Younis1, Muhalab Adem1,
1 Department of Nephrology, North West Armed Forces Hospital, Tabuk, Saudi Arabia
2 Department of Radiology, North West Armed Forces Hospital, Tabuk, Saudi Arabia
3 Department of Surgery, North West Armed Forces Hospital, Tabuk, Saudi Arabia
4 Department of Internal Medicine, North West Armed Forces Hospital, Tabuk, Saudi Arabia
Consultant Nephrologist, King Fahad Specialist Hospital, P.O. Box 15215, Dammam-31444
A 50-year-old ESRD who received LUR renal graft abroad. Since transplanted, he remained dependent on hemodialysis. The patient received steroid pulse therapy twice for rejecrion. Nonspecific bilateral lung infiltrate were noted on admission CXR, which stimulated the search for TB. The patient suddenly lost consciousness during his hospital stay. Intracranial hemorrhage was drained and tissue staining revealed heavy loads of tuberculus (TB) bacilli. The patient died two weeks later from septic shock with multi-organ failure.
|How to cite this article:|
Abutaleb N, Obaideen A, Hamza A, Zakaria M, Afifi H, Fallata S, Younis S, Adem M. Fatal Hemorrhagic Intracranial TB in a Renal Transplant Recipient despite INH Prophylaxis.Saudi J Kidney Dis Transpl 2007;18:594-598
|How to cite this URL:|
Abutaleb N, Obaideen A, Hamza A, Zakaria M, Afifi H, Fallata S, Younis S, Adem M. Fatal Hemorrhagic Intracranial TB in a Renal Transplant Recipient despite INH Prophylaxis. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2022 Nov 27 ];18:594-598
Available from: https://www.sjkdt.org/text.asp?2007/18/4/594/36518
We report here the development of fatal intracranial hemorrhage secondary to tuberculosis (TB) that occurred despite our early introduction of isoniazed (INH) prophylaxis.
This is a 50-year-old man who presented to our hospital for the first time one month after receiving living unrelated renal transplant abroad. The underlying etiology of his renal failure was unknown. The patient was a heavy smoker, malnourished, and emaciated. Since the operation, the patient remained dependent on hemodialysis because of delayed graft function. He also had received two courses of five-day empirical IV methylprednisolone anti-rejection therapy without allograft biopsy; one at the transplant center abroad and the other in the referring hospital.
After admission to our hospital, we switched the patient from cyclosporine (CSA) to tacrolimus (0.15 mg/kg/day initially) and obtained renal graft biopsy, which revealed evidence of cellular rejection. Tacrolimus blood level was maintained around 9-10 mg/L. In addition, the patient was maintained on oral prednisolone 15 mg/day, and mycophenolate mofetil (MMF) 750 mg BID.
Nonspecific bilateral lung infiltrate were noted on admission CXR [Figure 1] that stimulated the search for TB. This infiltrate cleared completely on empirical cefepime therapy within 4-5 days of admission [Figure 2]. Sputum was negative for TB was negative and we did not pursue bronchos-copy since the CXR findings had cleared. INH was then started within a week of patient's admission. In addition large peri-nephric hematoma of the allograft was documented and aspirated also early after admission [Figure 3]. Pseudomonas spp. grew in the aspirate culture. Ciprofloxacin was then added. Cefepime was later replaced by tazocin (pipracillin/tazobactam) as later urine culture grew also Pseudomonas spp. that was multi-drug resistant (MDR); sensitive only to tazocin. Repeated aspirations from the perinephric collection were attempted as suggested by surgical consultation; the hematoma was largely organized and only few milliliters could be aspirated in each attempt. Surgical exploration and/or catheter drainage of the hematoma were not contemplated by the surgeons. Cultures from the subsequent aspirates remained negative. The course of the patient was also complicated by cytomegaloviral (CMV) infection with transient leucopenia.
One month after the patient's admission to our hospital, he developed fever for the first time associated with minor opacities in mid zones on CXR. We switched ciprofloxacin to IV moxifloxacin and added Itraconazle 200mg/d empirically. The patient refused both bronchoscopy and liver/bone marrow biopsy/ aspirate that were considered to rule out TB despite ongoing INH and Quinolone antibiotics.
Two weeks later, the patient suddenly lost consciousness. Intracranial hemorrhage was diagnosed by brain computerized tomography (CT) scan, and it was drained surgically. However, the tissue staining revealed heavy loads of TB bacilli. The patient was initiated on anti-TB therapy (4 drugs), systemic antifungal and anti-pseudomonas antibiotic therapy within the first 24-36 hours after the occurrence of the CNS complication. The patient required tracheal intubation.
Despite our intensive management, aspergillous spp. was grown from the tracheal aspirate and from the thyroid gland. The patient developed suppurative thyroiditis one week after the intracranial event [Figure 4]. Blood culture grew MDR pseudomonas spp. with the same sensitivity pattern of pseudomonas that grew from urine culture two weeks after admission. The patient was already on tazocin immediately after the intracranial catastrophe. In addition, we discontinued the immunosuppressive (IS) therapy.
However, the condition of the patient deteriorated and he expired two weeks later from septic shock with multi-organ failure.
Despite refrain ing from further high dosed pulse steroids, and lim iting changes of IS to tacrolimus as a rescue therapy, this patient died because of opportunistic infections.
INH prophylaxis and concomitant flouroquinolone therapy that has also strong antiTB effect, failed to prevent the dissemination of TB in this patient. The protection offered by INH is not perfect. Most studies reported a general protection in the range of 60 to 90%. Among immunocompromised lupus patients, INH efficacy was found around 82% in one study.  Agarwal et al  concluded from a randomized controlled study on Indian renal transplant patients with high background TB incidence (25.8%) that the risk ratio of TB in renal transplant patients on INH versus control group was 0.36 (95% CI, 0.10-1.32); the difference was, however, not statistically significant (P=0.12). However, Sayiner et al  reported 100% prevention of TB in Turkish renal transplant patients with low background TB incidence (4.1%). Though flouroquinolons were administered for their antibacterial action, their anti-TB effect was expected to support the prophylactic action of INH and help preventing TB flare up.
An occult TB disease at the time of initiating INH prophylaxis can not be ruled out in many patients including our index patient. Clinically, however, there was no evidence of active TB upon starting INH prophylactic therapy. However, as we received the patient more than a month after transplant surgery, INH initiation might have been relatively late. The search for TB was limited to repeated sputum smears, tuberculin skin test and CXR. Plans for bronchoscopy and possibly gastric aspirate studies were not entertained with the prompt clearance of CXR opacities shortly after admission
It is obvious that malnutrition, under-dialysis, CMV disease, IS therapy especially the two initial empirical IV methylprednisolone courses prior to our admission and even possible INH resistance have all contributed to the development of TB in this patient. CMV infection has clearly predisposed this patient to develop both disseminated TB and invasive aspergilosis. John GT et al reported risk ratio of 2.35 for TB exerted by infections as CMV, HBV and or HCV.  CMV caused a 5-fold increased risk of systemic mycoses.  Furthermore, combined tacrolimus and MMF therapy was associated with earlier TB development in renal transplant patients in a retrospective study. 
Considering brain CT examination in the evaluation of isolated fever in IS patients may be prudent even in the absence of CNS symptom or signs. Occult intracranial infection may initially manifest itself by unexplained fever. In addition, sudden intracranial hemorrhage can still be associated with intracranial TB infection in this population.
The MDR Pseudomonas septicemia that developed after intubation has likely originated from the peri-graft collection or the urinary tract. Medical therapy combined with the repeated aspirations did not seem to have eradicated completely the peri-graft infection.
Similarly, antifungal therapy with itraconazole also failed to prevent the development of aspergillous infection despite discontinuing all drugs that interfere with gastric acidity and so with itraconazole absorption.
Other risk factors in this case included the absence of pre-transplant work up, noncompliance to dialysis therapy, and malnutrition.
We conclude that our reported patient developed pseudomonas, TB and aspergillosis infection post transplantation despite appropriate prophylactic and therapeutic measures. Aggressive IS therapy especially in emaciated uremic patients is most likely inappropriate.
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