Anne V. Hall

Infection imaging with radiopharmaceuticals in the 21st century

Infection continues to be a major cause of morbidity and mortality worldwide. Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections such as abscesses, osteomyelitis, septic arthritis, endocarditis, and infections of prosthetic devices. Established techniques such as radiolabelled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals, such as radiolabelled anti-infectives (e.g. 99mTc- ciprofloxacin). In addition to aiding early diagnosis of infection, through serial imaging these agents might prove very useful in monitoring the response to and determining the optimum duration of anti-infective therapy. This article reviews the current approach to infection imaging with radiopharmaceuticals and the future direction it might take.

Native valve Aspergillus endocarditis complicating lung transplantation.

We present 2 cases of Aspergillus endocarditis occurring in lung transplant recipients, both of whom were treated with early surgical intervention and triazole anti-fungal agents. Neither had evidence of airway colonization/infection with Aspergillus post-transplant, suggesting hematogenous spread of fungi at the time of surgery as a possible mechanism of infection. One case was successfully treated and discharged from the hospital, but, despite initial recovery, death occurred 10 months later due to a recurrence of Aspergillus endocarditis. Aspergillus endocarditis should be considered a relapsing disease and survivors of the condition should receive ongoing anti-fungal therapy.

Fungal infection in cardiothoracic transplant recipients: outcome without systemic amphotericin therapy

Transplant recipients require immunosuppression to prevent allograft rejection, placing them at risk of opportunistic infections including fungal infection. Difficulties in managing fungal infections include: establishing diagnosis, poor treatment response, drug interactions and toxicity. We report our single centre experience of treating fungal infections using systemic non‐Amphotericin current generation antifungals. Patients receiving inpatient antifungal therapy from September 2005 to December 2010 were identified from pharmacy records. Fungal infections were retrospectively classified according to European Organization for Research and Treatment of Cancer (EORTC) criteria. Treatment outcomes were classified in a manner similar to those used in clinical trials. Two hundred and forty‐nine recipients received antifungal treatment, 204 lungs and 45 hearts. One hundred and one patients received Voriconazole, 82 Caspofungin and 65 received both agents. One patient was unsuccessfully treated with additional Amphotericin. Treatment duration varied from 1.5 to 12 weeks. One hundred and sixty‐five patients had a complete response, 24 had a partial response and in 60 patients treatment was unsuccessful. The response to systemic non‐Amphotericin based antifungal therapy was high. We propose that diagnostic criteria without positive identification of a fungus allow treatment to be started early with few clinically relevant side effects.

Radiological resolution of cavitating Aspergillus fumigatus infection following treatment with oral voriconazole in two lung transplant recipients

Invasive aspergillosis is the most common invasive mould infection worldwide [1]. Fungal infections with Aspergillus species are a particular threat to lung transplant recipients because the transplanted organ is continuously exposed to these ubiquitous pathogens. In the transplanted lung, Aspergillus can simply colonize the airway, cause tracheobronchitis or invasive pulmonary aspergillosis (IPA). In one case series these complications occurred in 26%, 4% and 5% of lung transplant recipients respectively. Although IPA infections are infrequent, they can be rapidly progressive and often fatal with a mortality rate of 73% [2]. Diagnosis is difficult and in order to standardize comparisons of response to treatment, disease is defined according to European Organisation for Research and Treatment of Cancer (EORTC) guidelines [3]. The response to treatment is often poor and the optimal duration of treatment is uncertain. We present two cases of cavitatory lung disease secondary to A. fumigatus infection in ambulatory lung transplant recipients. The condition responded to outpatient treatment with oral voriconazole over a 6–9-month period. The duration of treatment was decided based on outpatient radiological surveillance of the lung disease. We then discuss the drugs currently available in the management of IPA. The first case is a 51-year-old lady who had undergone bilateral sequential single lung transplantation in January 1997 for bronchiectasis because of recurrent childhood respiratory infections (which infections is unknown). The patient remained in good health for 4 years. In September 2001, she suffered an episode of grade A2 acute rejection that was treated with 1 g methylprednisolone once daily for 3 days followed by a reducing dose of oral prednisolone. Her cyclosporin maintenance levels were increased in an attempt to prevent further episodes of rejection. Three months later, the patient was admitted to hospital with increasing exertional dyspnoea and a severe deterioration in her spirometry. At bronchoscopy, the appearance of the airways was consistent with tracheobronchitis, and large volumes of creamy secretions were present. A chest radiograph showed a cavitating lesion in the right upper lobe. High resolution computerized tomography (HRCT) thorax (Fig. 1a) showed at least three cavitating lesions, two in the right upper lobe and one in the left upper lobe with areas of soft tissue within the cavities. Aspergillus fumigatus was isolated from sputum. Treatment with voriconazole 200 mg orally twice daily was commenced. As the patient felt well and was ambulatory she was discharged on treatment with continuing oral voriconazole. The patient had regular 8-weekly follow-up HRCTs that demonstrated progressive improvement in the size of the cavities. After 9 months of treatment with oral voriconazole, HRCT (Fig. 1b) demonstrated diminution of the fungal cavities towards nodular scars and the treatment with oral voriconazole was stopped. The second case is a 25-year-old man who underwent heart–lung transplantation for cystic fibrosis (CF) in early 1999. He was not colonized with Aspergillus prior to surgery. Postoperatively he developed early cyclosporin neurotoxicity and was thus switched to tacrolimus. 30 months post-transplantation, the patient was investigated due to worsening spirometry and a diagnosis of Bronchiolitis Obliterans was made. He underwent total lymphoid irradiation for chronic rejection and 36 months post-transplantation he underwent plasmaphoresis and 4 weeks of Rituximab therapy as the presence of class II human lymphocyte antigen (HLA) donor-specific antibody was demonstrated. The deterioration in the patient’s lung function subsequently stabilized. 48 months posttransplantation the patient was admitted from outpatient clinic as his chest radiograph showed new cavitating lesions in both lung fields. Clinically the patient felt well and his respiratory function was stable. HRCT (Fig. 1c) showed multiple cavities scattered around both upper lobes, the apical segment of the left lower lobe, and the lateral and medial segments of the right lower lobe. Transbronchial biopsies showed chronic Bronchiolitis Obliterans and Broncheo-alveolar lavage subsequently grew Aspergillus species. The patient was started on oral voriconazole and discharged from hospital. The patient was followed up regularly. HRCT (Fig. 1d) 5 months post-diagnosis of IPA shows marked resolution of the cavities and the pericavity fungal granulomas in both

Imaging Bacterial Infection with a Radiolabelled Antibiotic

The bio-physiological basis of nuclear medicine imaging is related to the disease process and it has been further developed - this time the target is bacteria and the disease state is infection. It is often than an inflammation may be due to bacterial infection. Conditions like osteomyelitis or endocarditis where long term antibiotic therapy would be appropriate require that the specific presence of a bacterial infection is demonstrated as the cause of inflammation. The available radiopharmaceuticals: Ga-67 citrate, Tc-99m or In-111 human immune globulin, Tc-99m antigranulocyte antibodies or binding peptides or Tc-99m/In-111 labelled leucocytes offer little help to provide this specific information. To address this issue, a search was pursued for an agent which would bind to living bacteria and that can be radiolabelled. This has resulted in development of Tc-99m Infection by Solanki et al [1].