Pneumonia In Transplant Recipients Research Articles

Atypical pneumonia testing in transplant recipients.

The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T-cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre-defined criteria. A cost analysis of diagnostic testing was performed. Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1-year post-transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings.

Cytomegalovirus (CMV) DNA quantification in bronchoalveolar lavage fluid of immunocompromised patients with CMV pneumonia.

Cytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA-approved PCR assay (Cobas® AmpliPrep/Cobas TaqMan® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656000 IU/mL yielded 100% sensitivity and specificity among biopsy-proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/106 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients.

A Mouse Model of Interstitial Pneumonitis Induced by Murine Cytomegalovirus Infection after Allogeneic Skin Transplantation

We investigated the effect of murine cytomegalovirus (MCMV) on interstitial pneumonia in transplant recipients in an experimental skin allograft model. Skin transplantation between C57BL/6J and BALB/c mice was performed in the presence or absence of cyclosporin A treatment. Flow cytometry showed that the number of CD4+ and CD8+ cells and the level of IFN-γ decreased significantly in the groups treated with cyclosporin A. We either mock-infected or infected the mice with MCMV by intranasal administration and monitored pathophysiological behavior and body weight. The infected mice were sacrificed at different days postinfection for histology, immunohistochemistry, and molecular biological evaluations. Interstitial pneumonitis was observed in positive control groups as well as in experimental group that received cyclosporin A, a skin transplant, and infected with the highest dose of virus (105 PFU). Transmission electronic microscopy demonstrated the presence of herpes virus particles. MCMV DNA and glycoprotein B were demonstrated in the epithelial cells of the lung tissue in those animals by in situ hybridization and immunohistochemistry, respectively. Our data demonstrated the establishment of a mouse model of interstitial pneumonitis via MCMV infection after allogeneic skin transplantation.

Pharmacology and clinical use of foscarnet

Foscarnet, licenced by Astra pharmaceutical products, is a pyrophosphate analogue that selectively inhibits replication of viruses in infected cells. It inhibits in vitro the replication of all herpes viruses, including human cytomegalovirus (HCMV) at concentrations of 100 to 300 μmol/l and has a dose-related inhibitory effect on HIV-1 virus, influenza virus and hepatitis B virus. It does not require intra-cellular phosphorylation for antiviral activity. Oral bioavailability of foscarnet is low (12–22%), and foscarnet must be administered intravenously. It is mainly eliminated unchanged by the kidneys. Mean half-life in plasma ranges from 3.4 to 5 h. For acute therapy, the currently recommended regimen is 60 mg/kg t.i.d. or 90–100 mg/kg b.i.d. In AIDS patients, foscarnet is an effective treatment of HCMV retinitis. Healing or stabilisation of lesions is obtained in 85–95% of patients after 2 weeks or 3 weeks therapy. For HCMV gastrointestinal disease, complete or partial response rates of 57–95% have been reported with foscarnet. The optimal maintenance dosage of foscarnet necessary in CMV infections in AIDS patients remains to be clearly established. Data from small samples size studies have shown that foscarnet decreased significantly circulating levels of HIV antigen in AIDS patients with HCMV disease. Foscarnet is an effective treatment for acyclovir-resistant herpes simplex virus and for acyclovir-resistant varicella-zoster virus (40 mg/kg every 8 h). In patients with immunosuppression not HIV-related HCMV infections, particularly interstitial pneumonia in transplant recipients, experience with foscarnet is limited. The major adverse effect of foscarnet is reversible renal dysfunction, due to acute tubular toxicity. In may be partially prevented by hyperhydratation during the treatment. Fluctuations in serum calcium and phosphore levels, with both increase and decrease are also frequent adverse reactions. Most clinical symptoms are related to decrease in ionized calcium levels. Hyperphosphatemia, a clinically benign phenomenom, reflects the incorporation of foscarnet in bone. Penile ulcerations have been described and may result from mococutaneous direct toxicity of foscarnet eliminated in urine. Although relapses frequently occur after a few months of maintenance therapy, foscarnet that shows a marked activity against HCMV in vitro, has allowed important progress in therapy of HCMV infections in AIDS patients.

Legionella pneumonia in transplant recipients: a cluster of cases of eight years' duration

Infection with Legionella is often encountered in immunosuppressed patients, especially in recipients of renal allografts. From January 1985 until April 1993 14 cases of nosocomial legionella pneumonia were diagnosed (four by culture, 10 by serological methods) on the surgical transplantation unit of Innsbruck University Hospital. All isolates from patients and from the building's hot water were found to be Legionella pneumophila serogroup 1. They were indistinguishable from each other by monoclonal antibody subtyping and restriction fragment length polymorphism pattern and thus indicated a series of infections originating from the same source during a period of more than 8 years. Repeated efforts to control Legionella by raising the temperature in the hot water lines failed to bring permanent success. Replacing the central hot water supply with small electric water heaters installed in the patient rooms on the transplant ward now seems to have reduced the incidence of legionellosis on this unit. However, further infections occurring in transplant patients in other surgical departments in the same building indicate that a major renovation of the whole surgical building's hot water system is necessary.

Prevention and treatment of cytomegalovirus pneumonia in transplant recipients.

The prevention of cytomegalovirus (CMV) infection in individuals at the highest risk, such as CMV-seronegative recipients of allogeneic bone marrow transplants or of CMV-positive solid organ transplants, involves the use of blood products obtained from CMV-seronegative donors or the use of filtered blood products. In addition, the use of ganciclovir is becoming increasingly important as an early means of preventing serious disease. The options for use of ganciclovir include conventional prophylaxis early after engraftment or preemptive use after documented infection. Evidence is reviewed for selected use of this drug in only the highest-risk subjects to avoid unnecessary adverse effects. The optimal use of ganciclovir in specific patient groups needs to be evaluated, and general recommendations that fit all groups cannot be made at this time. Although the use of intravenous immunoglobulin (IVIG) in transplantation remains controversial, there is increasing evidence to support a recommendation of the use of IVIG as general support for the allogeneic bone marrow transplant recipient and of CMV antibody-enriched immunoglobulin in selected renal transplant recipients. For the treatment of CMV-associated pneumonitis, it is recommended that ganciclovir and IVIG be used in combination for the bone marrow transplant recipient and that ganciclovir be used with or without IVIG in patients in other transplantation groups.