Carbapenem‐resistant Klebsiella pneumoniae vertebral osteomyelitis in a renal transplant recipient treated with ceftazidime‐avibactam

Ceftazidime‐avibactam (CAZ‐AVI) is a novel cephalosporin beta lactamase inhibitor combination that has shown activity against carbapenem‐resistant Enterobactericeae. Data are limited on its utilization in the treatment of carbapenem‐resistant Klebsiella pneumoniae osteomyelitis in solid organ transplant patients. We describe a case report on the use of CAZ‐AVI in the treatment of vertebral osteomyelitis in a renal transplant recipient.     

Aspergillus vertebral osteomyelitis after simultaneous kidney–pancreas transplantation

Abstract: Aspergillus osteomyelitis is a rare complication of invasive aspergillosis after organ transplantation. This is the report of a 46‐year‐old man who underwent a simultaneous pancreas and kidney transplantation, complicated by an Aspergillus osteomyelitis and diskitis of the lumbar spine. Prompt diagnosis with needle biopsy, followed by antifungal therapy using caspofungin, a new antifungal agent recommended for the treatment of refractory aspergillosis, in combination with amphotericin B and an early surgical intervention led to clinical resolution of the infection. Reported cases of spinal aspergillosis after transplantation are reviewed in terms of clinical presentation, risk factors, therapeutic options, and outcome.     

Aspergillus thyroiditis in a renal transplant recipient mimicking subacute thyroiditis

Y. Solak, H. Atalay, A. Nar, O. Ozbek, K. Turkmen, S. Erekul, S. Turk. Aspergillus thyroiditis in a renal transplant recipient mimicking subacute thyroiditis.
Transpl Infect Dis 2011: 13: 178–181. All rights reserved Abstract: Fungal pathogens are increasingly encountered after renal transplantation. Aspergillus causes significant morbidity and mortality in transplant patients. Fungal thyroiditis is a rare occurrence owing to unique features of the thyroid gland. Most cases are caused by Aspergillus species and have been described in immunocompromised patients. Presentation may be identical with that of subacute thyroiditis, in which hyperthyroidism features and painful thyroid are the prominent findings. Diagnosis can be ascertained by fine‐needle aspiration of thyroid showing branching hyphae of Aspergillus. We describe a renal transplant patient who developed Aspergillus thyroiditis as part of a disseminated infection successfully treated with voriconazole.     

Severe Aspergillus endocarditis in a lung transplant recipient with a five‐year survival

B. Philippe, D. Grenet, P. Honderlick, E. Longchampt, B. Dupont, C. Picard, M. Stern. Severe Aspergillus endocarditis in a lung transplant recipient with a five‐year survival
Transpl Infect Dis 2010: 12: 273–276. All rights reserved Abstract: We report the case of a patient with cystic fibrosis who underwent lung transplant and developed Aspergillus endocarditis and cutaneous relapse. Long‐term survival was achieved with surgical and prolonged antifungal treatment. This case report emphasizes the recommendation of life‐long antifungal treatment in transplant recipients who survive an episode of fungal endocarditis.     

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991–92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community‐acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre‐intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high‐risk solid organ transplant patients.     

Mycobacterium abscessus pulmonary infection complicated with vertebral osteomyelitis in a heart transplant recipient: case report and literature review

Infections produced by Mycobacterium abscessus are emerging in immunosuppressed patients, such as solid organ transplant recipients. We report the first case, to our knowledge, of a vertebral osteomyelitis caused by M. abscessus in a heart transplant recipient, and review the risk factors, manifestations, and therapeutic approaches to this uncommon disease.     

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.     

Non-contiguous multifocal vertebral osteomyelitis caused by Serratia marcescens

Abstract

Serratia marcescens is a common nosocomial infection but a rare cause of osteomyelitis and more so of vertebral osteomyelitis. Vertebral osteomyelitis caused by this organism has been reported in few studies. We report a case of S. marcescens vertebral discitis and osteomyelitis affecting multiple non-contiguous vertebras. Although Staphylococcus aureus is the most common cause of vertebral osteomyelitis, rare causes, such as S. marcescens, need to be considered, especially when risk factors such as intravenous heroin use, post-spinal surgery and immunosuppression are present. Therefore, blood culture and where necessary biopsy of the infected region should be undertaken to establish the causative organism and determine appropriate antibiotic susceptibility. Prompt diagnosis of S. marcescens vertebral osteomyelitis followed by the appropriate treatment can achieve successful outcomes.     

Management of voriconazole hepatotoxicity in a lung transplant patient

S. Belaiche, M. Roustit, P. Bedouch, S. Quetant, C. Saint‐Raymond, C. Pison. Management of voriconazole hepatotoxicity in a lung transplant patient.
Transpl Infect Dis 2011: 13: 309–311. All rights reserved Abstract: Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We report the case of a 46‐year‐old female lung transplant outpatient diagnosed with persistent pulmonary Aspergillus colonization (>50 colonies of Aspergillus terreus) 3 months after lung transplantation. Oral voriconazole 200 mg twice a day (b.i.d) was initiated shortly after diagnosis. Two days after voriconazole initiation, alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) were normal or slightly elevated (79, 37, and 21 UI/L, respectively). Ten days after the first voriconazole administration, these values started to increase. Maximum levels were reached after 20 days for ALP (369 UI/L) and at around 30 days for ALT and AST (223 and 188 UI/L, respectively). Instead of discontinuing antifungal therapy, it was decided to reduce the voriconazole dose to 100 mg b.i.d. This asymptomatic progressive cholestatic hepatitis resolved, and 10 days after dose reduction ALP, ALT, AST were at 136, 53, and 28 UI/L, respectively. Finally, therapeutic drug monitoring revealed adequate voriconazole plasma trough concentrations (0.98 mg/L) 30 days after dose reduction and no more colonies of Aspergillus were observed. Voriconazole‐induced hepatotoxicity is a well known dose‐dependent adverse drug reaction. This experience confirms the appropriateness of voriconazole dose reduction instead of therapy interruption in dose‐dependent moderate liver toxicity. Voriconazole therapeutic drug monitoring before and after dose reduction may help to avoid drug accumulation and inappropriately low drug exposure, respectively.     

Vertebral osteomyelitis and endocarditis of a pacemaker lead due to Granulicatella (Abiotrophia) adiacens

Systemic infection due to Granulicatella (formerly Abiotrophia), a species of nutrition-deficient gram-positive cocci, is rare. We present the case of a 68-year-old diabetic male who presented with back pain and a history of fever and chills. Imaging studies revealed vertebral osteomyelitis of the Th 10/11 region. Transesophageal echocardiography disclosed a vegetation adjacent to the pacemaker lead and blood cultures grew Granulicatella adiacens. A diagnosis of vertebral osteomyelitis and endocarditis due to G. adiacens was made and the patient improved with bed rest and medical treatment alone. Granulicatella ssp. should always be part of the differential diagnosis of fastidious bacteria in vertebral osteomyelitis and endocarditis. Received: June 6, 2001 · Revision accepted: February 16, 2002 A. Woywodt (corresponding author)     

Unsuspected osteomyelitis is frequent in persistent diabetic foot ulcer and better diagnosed by MRI than by 18F-FDG PET or 99mTc-MOAB

Aim. Prevalence, optimal diagnostic approach and consequences of clinically unsuspected osteomyelitis in diabetic foot ulcers are unclear. Early diagnosis of this infection may be crucial to ensure correct management. Methods. We conducted a prospective study in 20 diabetic patients with a chronic foot ulcer (>8 weeks) without antibiotic pretreatment and without clinical signs for osteomyelitis to assess the prevalence of clinically unsuspected osteomyelitis and to compare the value of magnetic resonance imaging (MRI), ¹⁸F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) and ^99mTc‐labelled monoclonal antigranulocyte antibody scintigraphy (^99mTc‐MOAB). Those with suggestive scans underwent bone biopsy for histology (n = 7). Results. Osteomyelitis was confirmed by biopsy in seven of the 20 clinically unsuspected foot ulcers. Presence of osteomyelitis was not related to age, ulcer size, ulcer duration, duration of diabetes or HbA1c. C‐reactive protein was slightly elevated in patients with osteomyelitis (35.1 ± 16.0 mg L^?1 vs. 12.2 ± 2.6 mg L^?1 in patients with and without osteomyelitis respectively; P = 0.07). MRI was positive in six of the seven patients with proven osteomyelitis, whereas ¹⁸F‐FDG PET and ^99mTc‐MOAB were positive only in (the same) two patients. Of the seven patients with osteomyelitis, five had lower limb amputation and in one patient the ulcer was persisting after 24 months of follow‐up. In contrast, of the 13 patients without detectable signs of osteomyelitis on imaging modalities only two had lower limb amputation and two persisting ulcers. Conclusions. Clinically unsuspected osteomyelitis is frequent in persisting foot ulcers and is a high risk factor for adverse outcome. MRI appears superior to ¹⁸F‐FDG PET and ^99mTc‐MOAB in detecting foot ulcer‐associated osteomyelitis and might be the preferred imaging modality in patients with nonhealing diabetic foot ulcers.     

Peripheral blood smear findings in a kidney transplant recipient with disseminated histoplasmosis and elevated Aspergillus galactomannan

We report a case of disseminated histoplasmosis in a renal transplant recipient who presented with a nodular pulmonary lesion and elevated serum and bronchoalveolar lavage (BAL) Aspergillus galatomannan. This almost led to an erroneous diagnosis of invasive aspergillosis since the donor respiratory tract was known to be colonized with Aspergillus terreus. However, distinctive intracelluar Histoplasma yeasts on peripheral blood smear led to early diagnosis and appropriate treatment. The cross‐reactivity between Aspergillus galactomannan and Histoplasma antigen is discussed further.     

Aspergillus endocarditis in lung transplant recipients: case report and literature review

M. Lázaro, A. Ramos, P. Ussetti, A. Asensio, R. Laporta, E. Muñez, I. Sánchez‐Romero, E. Tejerina, R. Burgos, V. Moñivas, A. Varela. Aspergillus endocarditis in lung transplant recipients: case report and literature review.
Transpl Infect Dis 2011: 13 : 186–191. All rights reserved Abstract: We present a case of endocarditis caused by Aspergillus in a lung transplant (LT) patient and review 6 previously reported cases. All cases were caused by Aspergillus fumigatus. Five patients (71%) were transplanted due to cystic fibrosis. None of the patients had any previously known valvular heart disease. The time that elapsed between LT surgery and the diagnosis of Aspergillus endocarditis was 8±6 months. Large peripheral emboli were observed in 6 patients (85%); blood cultures were negative in all. Transthoracic echocardiography did not detect the presence of vegetations in 3 patients (43%); the vegetations measured >1.5 cm in all cases. Five patients (71%) died from disseminated disease. Both survivors underwent combined therapy with antifungal drugs and surgical treatment.     

Antigen detection in the diagnosis and management of a patient with probable cerebral aspergillosis treated with voriconazole

This report describes the diagnosis and management of a 16‐year‐old boy who developed neurological signs and symptoms suggestive of cerebral aspergillosis following a haploidentical bone marrow transplant. A new sandwich enzyme‐linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan circulating antigens (Platelia Aspergillus, Sanofi Diagnostic Pasteur, France) was used on serum and cerebrospinal fluid to obtain a presumptive diagnosis and to monitor the course of the disease. Having failed conventional therapy with amphotericin B, the patient received compassionate treatment with voriconazole for a period of 37 days. High levels of voriconazole were observed in both serum and cerebrospinal fluid (CSF), with a trend toward accumulation. After 7 days a marked improvement in the patient’s neurological symptoms was noted, and ELISA data indicated a corresponding decrease in Aspergillus galactomannan levels in both serum and CSF. Voriconazole was well tolerated, with only transient increases in ALT/AST recorded during therapy. Although the patient survived the acute Aspergillus infection, he subsequently died of an unrelated infection.     

Fatal Fusarium infection manifesting as osteomyelitis following previous treatment with amphotericin B in a multi‐visceral transplant: Case report and review of Fusarium infections in solid organ transplantation

Invasive fusariosis in solid organ transplant is uncommon and usually presents as localized infection with favorable outcomes compared to hematologic malignancies or bone marrow transplants. We report the first case of Fusarium osteomyelitis in a patient following multi‐visceral transplant and review Fusarium in organ transplant recipients and Fusarium bone and joint infections. Our case underscores the importance of early recognition and multidisciplinary approach to treatment and highlights potential failure to eradicate with amphotericin B monotherapy.     

Late aspergilloma of a renal allograft without need for operative management: a case report and review of the literature

Aspergillus infection localized to the renal allograft is a rare and potentially life‐threatening infection and typically requires a combination of operative and medical management. We report the case of a renal allograft aspergilloma in a renal transplant patient presenting 2 years post transplant, successfully managed non‐surgically. To our knowledge, this is the first report of a patient presenting with an allograft aspergilloma so long after transplantation and being successfully managed with antifungal therapy alone.     

Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases

X. Yu, F. Han, J. Wu, Q. He, W. Peng, Y. Wang, H. Huang, H. Li, R. Wang, J. Chen. Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases.
Transpl Infect Dis 2011: 13: 385–391. All rights reserved Abstract: Nocardiosis is a rare but life‐threatening opportunistic infection, especially in immune compromised patients, including kidney transplant recipients. Primary pulmonary infection is the most common clinical pattern, and can easily result in disseminated Nocardia infection if treatment therapy is not adequate at the beginning. In this article, we report a new case of disseminated nocardiosis (lungs, skin, and pericardium) after renal allograft transplantation. We also review the English literature published from 1980 to 2010 and analyze the clinical characteristics of nocardiosis in kidney transplant recipients.     

Cerebral phaeohyphomycosis caused by Bipolaris spicifera after heart transplantation

L. Rosow, J.X. Jiang, T. Deuel, M. Lechpammer, A.A. Zamani, D.A. Milner, R. Folkerth, F.M. Marty, S. Kesari. Cerebral phaeohyphomycosis caused by Bipolaris spicifera after heart transplantation.
Transpl Infect Dis 2011: 13: 419–423. All rights reserved Abstract: Phaeohyphomycosis is an increasingly recognized cause of brain abscess in both immunocompetent and immunocompromised hosts. We report a case of cerebral phaeohyphomycosis in a 55‐year‐old male heart transplant recipient caused by Bipolaris spicifera. We review the literature regarding the pathogenesis, epidemiology, diagnosis, and management of infections with dematiaceous fungi.     

Infections of the central nervous system in transplant recipients

Central nervous system (CNS) infections, accounting for 4–29% of CNS lesions in transplant recipients, are a significant post‐transplant complication. Focal CNS infectious lesions or brain abscesses have been documented in 0.36–1% of the transplant recipients. Mycelial fungi, particularly Aspergillus, are by far the most frequent etiologies of post‐transplant brain abscesses. Bacteria, with the exception of Nocardia, are rarely associated with brain abscesses in transplant recipients. Time of onset and concurrent extraneural lesions have implications relevant towards invasive diagnostic procedures in transplant recipients with brain abscesses. Meningoencephalitis in transplant recipients is predominantly due to viruses, e.g., herpesviruses, and less frequently due to Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus. Despite a wide, and at times perplexing array of opportunistic pathogens that can cause CNS infections, the temporal association of the infection with the time elapsed since transplantation, risk factors, clinical manifestations, and neuroimaging characteristics of the lesion can allow a reasoned and rational approach towards the recognition, diagnosis, and appropriate management of CNS infections in transplant recipients.     

Cerebellar abscess caused by Listeria monocytogenes in a liver transplant patient

Brain abscesses are a rare but serious complication and have been documented in transplant recipients. Aspergillus is by far the most frequent etiology of post‐transplant brain abscesses. Bacteria, apart from Nocardia, have a low association with brain abscesses in transplant recipients. We report herein the case of a 52‐year‐old man who had undergone orthotopic liver transplantation (OLT) for end‐stage liver disease and hepatocellular carcinoma secondary to chronic hepatitis, and who developed a cerebellar abscess (CA) from Listeria monocytogenes. Three months after transplantation, he presented with a 1‐week history of headache and vomiting. Computed tomography scan of the brain revealed a space‐occupying lesion in the right cerebellum, which was further confirmed by magnetic resonance imaging. Emergency surgery was planned because of pressure effect on the surrounding structures. The patient recovered smoothly from the surgery. To our knowledge, no reports of Listeria CA following OLT have been published in the English literature. This case shows that, although extremely rare, L. monocytogenes may cause CA in liver transplant recipients, and clinicians should be aware of this, so that prompt diagnosis and treatment can be instituted before serious brain damage can occur.