|Year : 2022 | Volume
| Issue : 5 | Page : 98-105
Expert group opinion for respiratory infections in solid organ transplant recipients in South Asia
P Prasannakumar1, Ashwini B Gadde2, Shyam B Bansal2, Priscilla Rupali1
1 Infectious Diseases Training and Research Center, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Nephrology and Renal Transplant Medicine, Medanta Kidney and Urology Institute, Gurugram, Haryana, India
|Date of Submission||10-Sep-2021|
|Date of Acceptance||21-Feb-2022|
|Date of Web Publication||18-Oct-2022|
Dr. Priscilla Rupali
Infectious Diseases Training and Research Center, Christian Medical College, Vellore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Respiratory infections are among the most common and serious infections after solid organ transplantation (SOT). Infections within a month after transplant are usually donor-derived or bacterial infections related to surgical infections or ventilator associated. Infections between 1–6 months after SOT are mostly opportunistic due to various viruses, or fungal infections. After 6 months of transplantation usually community acquired infections predominate, however it is not uncommon to find opportunistic fungal and viral infections in this period. The signs and symptoms of these infections are often mitigated in SOT recipients, so a high index of suspicion is required along with microbiological or tissue diagnosis early in the course to timely treat these infections. Thorough screening for common infections and endemic infections is required in donor and recipients before transplantation to reduce the risk of infections in posttransplant period. Finally, a longer duration of treatment and prophylaxis is required for adequately treat these infections and prevent the relapse.
Keywords: Pneumonia, respiratory infections, solid organ transplant, South Asia
|How to cite this article:|
Prasannakumar P, Gadde AB, Bansal SB, Rupali P. Expert group opinion for respiratory infections in solid organ transplant recipients in South Asia. Indian J Transplant 2022;16, Suppl S1:98-105
|How to cite this URL:|
Prasannakumar P, Gadde AB, Bansal SB, Rupali P. Expert group opinion for respiratory infections in solid organ transplant recipients in South Asia. Indian J Transplant [serial online] 2022 [cited 2022 Dec 9];16, Suppl S1:98-105. Available from: https://www.ijtonline.in/text.asp?2022/16/5/98/358666
| Introduction|| |
Infections and rejections are the most common reasons for hospitalization after solid organ transplantation (SOT). Infections that occur early are related either to the surgery itself or they are donor derived. Infections that occur remotely after transplantation are either due to reactivation of viruses or to environmental exposures in the community. Vaccinations and antimicrobial prophylaxis can influence the etiology of respiratory infections in this group of patients.
Respiratory infections lead to significant mortality and morbidity following SOT. Lungs are exposed to toxic insult from underlying disease, infection, chemotherapy, and radiation. Decreased mucociliary clearance, altered function of phagocytes/macrophages, neutropenia, immunosuppressives and environmental exposures contribute to respiratory infections. The incidence in kidney transplant recipients varies from 2.9% to 30%., In addition, if a patient has been hospitalized prior to transplant it is likely that airways have been colonized with hospital acquired pathogens and that is likely to influence the etiology and outcome as well.
Allograft rejection requiring a high dose of immunosuppression can also lead to an increased risk of infection. A dynamic assessment of infectious risk can be done following transplant based on the time after transplant and possible dose of immunosuppressives being received, [Table 1].
|Table 1: Common time table and etiology of respiratory infections in solid organ transplantation recipients|
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| Risk of Pulmonary Infections in Solid Organ Transplantation Recipients|| |
The risk depends on pre transplant factors which may be recipient or donor-related, intraoperative factors, and posttransplant factors while in the hospital or later in the community. These factors can be modified by pre transplant evaluation assessing risk, providing prophylaxis, vaccinating against vaccine preventable diseases as well as following appropriate infection control practices pre transplant, during and after transplantation.
Pretransplant factors in the recipient include underlying disease requiring transplantation, nutritional level of the host and colonization by multi-drug resistant (MDR) organisms and HCV positivity. Donor related pre transplant factors include donor derived infections (DDI) like cytomegalovirus (CMV), Epstein–Barr virus (EBV), tuberculosis (TB), hepatitis B, hepatitis C, HIV and Toxoplasmosis if missed in screening. However, unexpected DDI could include Histoplasma spp., lymphocytic choriomeningitis virus, herpes simplex virus (HSV), West Nile virus, unknown bacteremia or viremia at the time of organ procurement. These could lead to development of pneumonia in the recipient at a later date.
Intraoperative factors like an unexpected event during surgery like injury to phrenic, vagus or recurrent laryngeal nerve can affect the pulmonary toilet and lead to pneumonia.
Among the posttransplant factors, prolonged endotracheal intubation and technical problems related to the vascularity and function of the allograft may affect graft viability which can predispose to infection. Later on, net state of immunosuppression and exposure to community viruses and aspergillus contamination could also be risk factors for respiratory infections.
| Risk Mitigation Strategies to Prevent Pulmonary Infections in Solid Organ Transplantation Recipients|| |
The Assessment of risk followed by mitigation strategies such as provision of prophylaxis or vaccination is paramount to prevent life-threatening infections.
Solid organ transplant recipients wait for unpredictable periods before a donor organ is available and hence this period should be used to boost immunity as much as possible. As far as possible most vaccinations should be initiated pretransplant, however, if this was not done immunization can be done 3–6 months' posttransplant when a period of maintenance immunosuppression is achieved. Immunoglobulin (Ig) levels may be used as a surrogate marker for initiation of immunization. If a live donor transplant is planned it is recommended that routine adult vaccinations and boosters are planned. In addition, a concept of “ring vaccination” for close family and friends of the SOT recipient is advisable.
Efforts to boost the immune response after vaccination include using a higher dose of the vaccine as is commonly advised in Hepatitis B and Influenza or an extra booster dose.
Usual recommended pre-transplant vaccinations to prevent respiratory infections include:
- Annual Inactivated quadrivalent influenza vaccination
- Conjugate Pneumococcal vaccination (Prevenar-13) followed Pneumovax 23, 8 weeks later following a prime boost strategy to ensure a robust immune response
- COVID-19 vaccinations: At present, the vaccinations available in India include CovishieldTM (ChAdO × 1 nCoV-19 recombinant) an adenoviral vectored vaccine; Covaxin® which is a whole virion inactivated vaccine, Sputnik V (Gam-COVID-Vac) again an adenoviral 5, 26 vectored vaccine. The latest vaccine approved in India for use in <18 years of age includes the ZyCoV-D DNA vaccine. Ideally, the patient should be fully vaccinated before undergoing any organ transplantation. In case of urgency one dose should be taken at least 2 weeks before the transplantation. The subsequent dose should be given 1–6 months after transplantation
- Other vaccines recommended as per usual include Tdap, Inactivated polio vaccine (IPV-recommended in pediatric patients), haemophilus influenzae b recommended only for pediatric solid organ transplants and adult lung transplants, meningococcal conjugate vaccine only recommended in endemic areas, hepatitis B vaccine (usually preferred pre transplant but could be given posttransplant as well
- Live viral vaccines such as Measles Mumps Rubella and Varicella Zoster virus (VZV) vaccines are usually not recommended peri transplant or posttransplant and a booster should be considered before considerable organ failure has set in pre-transplant. The live vaccine should be given minimum 4 weeks before transplantation.
Usually, no prophylaxis is required pretransplant except what is dictated pretransplant by underlying disease and previous infections. Surgical prophylaxis may be used for the transplant surgery to prevent surgical site infections (SSI) as per institutional protocols. In some cases, for example, lung or intestine there may be the colonization of the tract and that may require pre, peri and postoperative prophylaxis.
Routine SSI prophylaxis is advised. Isoniazid prophylaxis is advised to prevent posttransplant TB if the recipient is PPD positive, however, this is not a universal practice in South Asia to do PPD in asymptomatic patients, as chances of hepatotoxicity are high. In liver transplants in most cases, the decision is based on the degree of liver dysfunction and may be initiated after the liver transplant.
Fluconazole prophylaxis is recommended for a month posttransplant surgery in liver, small intestine, multi-visceral, and pancreas transplantation. Anti-mould prophylaxis/treatment of recipient or donor lungs may be required as they may be colonized by Aspergillus and require to prevent the development of aspergillus tracheobronchitis at the anastomotic site. The usual regimen includes either Inhaled Amphotericin B or Voriconazole at prophylactic doses.
Pneumocystis jirovecii pneumonia prophylaxis
This is usually advised at discharge from the hospital for a period of 6–12 months as it is likely that the recipient will be on maintenance immunosuppression by then.
The incidence of CMV is dependent on the serostatus of the donor and recipient and the transplant performed. Valganciclovir is routinely recommended for a period of 3–6 months in all SOT. In lung transplants, CMV-specific Ig along with Valganciclovir may be recommended in case of D+/R-serostatus, especially in lung transplantation.
| Screening Recommendations (Adopted from ASTID Guidelines for Solid Organ Transplantation)|| |
- Medical history: Routine assessment of previous infections, vaccinations, travel, occupational exposures, and high-risk behavior
- Bacterial infection of the respiratory tract should have documented appropriate treatment with evidence of infection control prior to organ donation
- For lung donors, bronchoscopy with cultures should be performed and appropriate antibiotics initiated in the recipient to cover recovered bacteria
- Avoid donation from a donor with possible TB. Most centers would routinely perform a chest X-ray and living donors should undergo PPD testing or Interferon Gamma release assay testing if there is a high suspicion of TB. A chest radiography to be performed routinely by all irrespective of the PPD/IGRA test with a documentation of whether there is a history of previous TB
- Donors who are predisposed to cryptococcal infection (e.g., end stage liver disease/chronic liver disease, rheumatological disorder, sarcoidosis, steroid or immunosuppressant therapy) or who have an undiagnosed cause for meningoencephalitis or pulmonary nodules or fever of unknown origin should screen for cryptococcal infection
- Screening for donor viral infections using serology or molecular assays should be routinely done.
- The underlying condition of the recipient
- Cystic fibrosis patients have risk of colonization with MDR organisms such as Pseudomonas and/or Burkholderia or fungi such as Aspergillus spp
- Screening for colonizers and previous respiratory infections in lung transplant recipients
- Screening for colonization methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, carbapenem-resistant Enterobacterales is recommended in liver and intestinal transplantation, however, selective digestive decontamination is not recommended
- All recipients should have an evaluation performed to rule out active TB – Chest X-ray. PPD/IGRA have little value in highly endemic region like India and should be performed only if there is a high suspicion of TB or history of close contact
- Screening for endemic mycoses, parasitic infection (strongyloidiasis, Toxoplasma), viral previous viral infections (CMV, EBV, HIV, HCV, HBV) should be performed (detailed in chapter on screening).
| Clinical Presentation|| |
Symptoms and signs are often attenuated after transplant due to the immunosuppressive state and hence mild but persistent symptoms should not preclude a complete evaluation. Fever, cough with expectoration suggest an alveolar process, pleuritic chest pain indicates a pleuritic process or a parenchymal process originating in the pleura. Hemoptysis can indicate a necrotic lung parenchymal process or an angioinvasive disease. Interstitial processes on the other hand, present only with breathlessness and cough with a scanty expectoration. Weight loss, anorexia, and a general feeling of being unwell should always prompt a full and careful evaluation.
| Diagnosis|| |
Initial evaluation is based on Imaging is often helpful towards a differential diagnosis but invasive tests using a combination of conventional and advanced molecular techniques are often required to make a firm etiologic diagnosis.
| Imaging|| |
A computer tomography (CT) scan of thorax with high-resolution cuts along with a good detailed history can often help narrow down a differential diagnosis. Other tests which may find utility include bronchoscopy with bronchoalveolar lavage, endobronchial ultrasound (US) (for visualization of bronchial tree). Guided biopsies of infected tissue whether obtained by open surgical techniques or via endobronchial US or transbronchial lung needle aspiration or biopsy should be explored for a confirmatory diagnosis.
| Differential Diagnosis of Fever with Lung Infiltrates|| |
- Consolidation (focal parenchymal) with acute presentation: Usually due to bacterial infection such as Streptococcus pneumoniae, Klebsiella pneumoniae, Legionella pneumophila, S. aureus, but it can sometimes be due to pulmonary embolism or hemorrhagealso
- Consolidation (focal parenchymal) with sub-acute presentation: Invasive pulmonary aspergillosis, pulmonary TB, nocardiosis, P. jirovecii, HSV, VZV, drug associated pulmonary infiltrates
- Interstitial infiltrates: Viral pneumonias– CMV, influenza, respiratory syncytial virus (RSV), EBV, parainfluenza, Fungi- P. jirovecii, Bacteria– Mycobacterium tuberculosis, Nocardia spp
- Pulmonary nodules (micro or macronodules or mixed): These may be produced by bacteria and fungi. Bacterial nodules may be produced by M. tuberculosis, Rhodococcus equi, Nocardia spp. while fungal nodules may be produced by Aspergillus spp, Mucor spp or endemic fungi prevalent in that region
- Parenchymal infiltrates with effusion or empyema: May occur due to necrotizing bacterial infections like S. aureus, Klebsiella pneumoniae, oral anaerobes, M. tuberculosis
- Parenchymal infiltrates with lymphadenopathy: These may occur due to M. tuberculosis, endemic fungi and Nocardia spp.
Due to attenuation of clinical symptoms and signs in this category of immunosuppressed patients, generally, a high index of suspicion needs to be maintained to arrive at a diagnosis. The routine microbiologic tests of gram stains and cultures for bacterial infections from a well-expectorated sputum sample are usually not useful as there is a significant lack of inflammation. Occasionally, induced sputum or bronchoalveolar lavage specimens with bacterial and fungal cultures maybe useful. Biomarkers may provide a supportive role for diagnosis of bacterial and fungal infections however, US or CT-guided biopsies or open lung biopsies may often be required for a confirmatory diagnosis.
| Microbiological Evaluation|| |
While imaging techniques can show a particular pattern, tissue obtained by invasive or noninvasive means is paramount toward making a diagnosis. A confirmatory microbiologic diagnosis either by conventional or molecular diagnostic techniques is essential for definitive therapy in these immunosuppressed individuals. Routine stains such as Gomori Methenamine silver (GMS), Wright-Giemsa stains, Diff-Quik (Modifed Wright's) stain, Ziehl–Neelsen and Calcofluor stains on open lung biopsy tissue samples are routinely advised to detect fungi, nocardia or mycobacteria. In case of respiratory viral infections diagnosis is often made based by qualitative or quantitative polymerase chain reaction (PCR) on nasopharyngeal swabs or lower respiratory specimen samples. Systemic viral infections are often diagnosed based on serial rise in quantitative viral PCRs or antibody titers on serology tests.
Alveolar (diffuse bilateral parenchymal) infiltrates
Blood cultures, sputum gram stain and cultures, sputum acid-fast bacilli (AFB) smears and cultures, Sputum potassium hydroxide stain for fungus, fungal C/S, and Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsies.
Interstitial (ground-glass opacities or mixed micronodular) infiltrates
Direct immunofluorescence for P. jirovecii, Quantitative CMV PCR, Modified AFB smear and culture to identify Nocardia spp., special stains for Legionella and Mycoplasma, Bronchoscopy with BAL and transbronchial lung biopsies for bacterial, viral, fungal, and AFB stains and cultures.
Bacterial and fungal biomarkers such as Procalcitonin, Galactomannan and beta D glucan (BDG) cannot be used to rule out the diagnosis of bacterial or fungal infections. They can be used to support a diagnosis and provide prognostic value, especially with regard to the stoppage of antimicrobials. Others like C-reactive protein are nonspecific with elevation occurring in both infectious and noninfectious inflammatory conditions.
Procalcitonin synthesis is induced by bacterial endotoxins, cytokines induced by inflammation due to infection like tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β) and IL-6. In contrast, procalcitonin production is not induced in viral infections. This allows differentiation between bacterial and viral infections and optimal antibiotic usage.
Beta D glucan
1,3 BDG is a polysaccharide which is abundant in the cell wall of most fungi except Blastomyces dermatitidis, Cryptococcus spp. and the Zygomycetes spp. This is a chromogenic quantitative immunoassay designed to detect BDG in ng/ml by measuring activation of factor G. A positive test does not always indicate a definitive diagnosis of invasive candidiasis although it may occasionally suggest a deep-seated invasive candidiasis when blood cultures are negative. It is imperative that interpretation should be guided by clinical and microbiological picture. This assay has a high sensitivity and low specificity and thus a high negative predictive value suggesting that its utility lies in stoppage of antifungal agents in intensive care settings where the likelihood of an invasive candidiasis is lower.
Galactomannan is a polysaccharide which is a constituent of Aspergillus cell wall. The galactomannan enzyme immunoassay (EIA) uses an optical density readout and a positive result is expressed as an OD index cut off value of ≥ 0.5 as suggestive of invasive Aspergillosis. In a meta-analysis conducted in immunocompromised individuals revealed that the sensitivity for Galactomannan EIA was 82% and specificity was 81% and a further sub group analysis suggested that it performed better in those who had a hematological malignancy on chemotherapy or underwent a peripheral blood stem cell transplantation. It had a limited utility in solid organ transplant recipients.
PCR and Microarray techniques have revolutionized the diagnosis of infections in SOT as most often the organisms are not easily detectable due to a lack of host immune response or if present at a low colony count. Respiratory viral panels are available for detection of various respiratory viruses. 16sRNA for bacteria and 18sRNA or the internal transcribed spacer regions of fungal ribosomal DNA for fungal infections can help make a microbiological diagnosis and thus help with targeted antimicrobial therapy. Other platforms like the matrix-assisted laser desorption ionization time-of-flight mass spectrometry can also help towards a quicker diagnosis thus helping with institution early appropriate antimicrobial therapy.
| Treatment|| |
In the absence of India specific data, it is often challenging for Indian physicians when faced with infections in this group of immunocompromised patients. Knowledge of the timeline of infections, taking into account the degree of immunosuppression and possible epidemiologic exposures can often help narrow down a differential diagnosis and in turn help with targeted investigations and treatment. While starting treatment is easy it is often difficult to stop treatment as in the presence of longstanding immunosuppression a longer duration with or without secondary prophylaxis may be required.
Early posttransplant phase
In the immediate posttransplant period, respiratory infections may be due to health care associated pneumonia due to multi resistant bacterial pathogens or systemic viral or fungal pathogens transmitted via the donor. Hence a preliminary diagnostic evaluation should take these etiologies into consideration. Generally, no empirical antibacterial treatment is advised unless there are features of sepsis or septic shock in which case a broad-spectrum antibiotic is chosen based on possible pathogens based on the type of transplant, type of health care setting and risk factors.
Late posttransplant phase
In this phase, possible pathogens include those acquired as a result of potential exposure in the community either due to habitat, occupation, pets or other individuals or due to reactivation of infections due to cumulative effects of immunosuppression. Generally, the same principle is followed here as well where it is prudent to obtain a confirmatory diagnosis prior to initiation of antimicrobial therapy.
If antibacterial treatment started, principles of antimicrobial stewardship should be kept in mind to determine choice, route and duration of therapy. If antivirals or antifungals started, duration may be determined by the level of immunosuppression and resolution of clinical picture.
| Specific Infections|| |
Incidence of M. tuberculosis in SOT recipients is 30–100 times higher with TB being a reactivation rather than a primary infection. The incidence of TB in India in maintenance hemodialysis is 8.7% and in renal allograft recipients was 12.3% in a study from South India. The risk factors for posttransplant TB are older age, lung transplantation, uncontrolled diabetes mellitus, chronic liver disease, concomitant infections, longer pre transplant hemodialysis, induction with T cell depleting antibodies and previous H/O TB. A randomized controlled trial has shown that the administration of Isoniazid decreases the risk of developing TB posttransplant with no effect on overall mortality but there is substantially increased risk of hepatotoxicity.
Respiratory viral infections
RSV, influenza, parainfluenza, rhinovirus (PIV), adenovirus, and human metapneumovirus (hMPV), human coronavirus and human bocavirus are common causative organisms of pneumonia in SOT whereas human herpesviruses (HSV1, HSV2), and VZV are less common causes of pneumonia in SOT recipients. While RSV and influenza do commonly occur in winter, rhinovirus and parainfluenza virus can occur at any season. Rhinovirus, bocavirus and coronavirus can cause severe infections only if they co-infect with other pathogens and they usually don't cause lower respiratory tract infection. In contrast hMPV and PIV can have similar LRTI and mortality rate as Influenza and RSV infections.
Respiratory syncytial virus
Lung transplant recipients are at a high risk of developing RSV related morbidity and mortality among the solid organ transplants. The risk factors include younger age, infection soon after transplant, preexisting lung disorder and recent rejection. RSV can cause simple upper respiratory tract infection to severe pneumonia and bronchiolitis obliterans. Aerosolized ribavirin in combination with RSV IVIG or palivizumab can be used in RSV infection in SOT patients.
CMV commonly causes acute pneumonia in lung transplant recipients in the absence of prophylaxis, whereasbronchiolitis obliterans occurs as a subacute to chronic manifestation. In other solid organ transplants, commonest manifestation of CMV induced tissue invasive disease is gastrointestinal, followed by retinitis, nephritis, pancreatitis or hepatitis. In most of the Indian solid organ transplant settings (most of the data is based on kidney and liver), the CMV serostatus is D+/R+ varies from 70% to 90%. Reactivation was encountered in 1.7 of kidney transplant and 21% of liver transplant recipients. CMV has a number of indirect effects as well, some of which include atherosclerosis and coronary artery disease in heart transplantation, bronchiolitis obliterans in lung transplantation, vanishing bile duct disease in liver transplantation and various vascular events in any SOT. In addition, the immunomodulatory effects of CMV also results in increased risk of concurrent bacterial, viral and fungal infection followed by IV ganciclovir and oral valganciclovir are preferred first choices whereas foscarnet and cidofovir are reserved for ganciclovir resistant CMV.
Influenza can cause severe disease in solid transplant patients especially in lung transplant patients in which severe influenza ranges from 16% to 20% of those infected with an attributable mortality rate of 4% to 8%. Neuraminidase inhibitors especially oseltamivir is the drug of choice. Though early prompt virus specific therapy will yield better results, influenza therapy should be offered at any point of illness in SOT patients as even delayed therapy has shown benefit. All SOT patients should receive inactivated influenza vaccine after 2 months of transplant and thereafter every year but the live attenuated influenza vaccine is contraindicated after SOT.
There is a probable risk of transmission of SARS CoV-2 from a donor to the recipient as viral RNA is detected in organs that can be transplanted e.g., lung, heart, kidney and liver. Hence donor screening is strongly recommended prior to transplantation. If a donor is found positive, transplantation should be deferred from 4 to 12 weeks (depending upon the severity) after recovery of donorto reduce the risk of transmission to recipient. In case a lung transplant is planned from a deceased donor, sampling from upper and lower respiratory tract for SARS Co-V-2 PCR is recommended to ensure negativity. Among the recipients, transplantation should be deferred till symptom resolution and for a minimum of 3–4 weeks from infection as far as possible as SARS Co-V-2 viral RNA shedding can continue for a median of 20 days. Recipients who develop moderate to severe disease are required to wait for minimum of 8–12 weeks before accepting for transplantation. In addition, if transplantation is not emergent, it may be prudent to obtain two negative SARS CO-V-2 PCR tests. It is prudent to vaccinate both recipients and donors before SOT to reduce the infection and severity as mortality is high in SOT recipients.
Invasive aspergillosis incidence varies among solid organ transplant individuals with lung transplant patients are at higher risk while kidney and pancreas transplant are at lower risk and the risk factors include degree of immunosuppression, environmental exposure and co-viral infections especially CMV. Aspergillus colonization and tracheobronchitis are commonly seen in lung transplant patients and needs to be addressed promptly to prevent progression and subsequent dissemination. Pulmonary aspergillosis may present with mildrespiratory symptoms and even lacks any specific radiological features. The gold standard of diagnosis is histopathology showing tissue invasion and the same tissue culture growing aspergillus but if not feasible then a composite assessment of clinical feature, radiographic images, galactomannan assay and culture should be used to make diagnosis. Voriconazole is the drug of choice.
Pulmonary zygomycetes and aspergillosis may have similar clinical and radiological presentation thus tissue and culture diagnosis are always necessary. Amphotericin B is the drug of choice. Pulmonary cryptococcus is also seen in SOT patients other than HIV patients. Most of them may have acute presentation including respiratory failure. Serum cryptococcal antigen test is less sensitive in isolated pulmonary cryptococcus thus requiring tissue biopsy and culture. The principle of management is same as in HIV patients and Amphotericin B and 5-Flucytosine followed by fluconazole are the drug of choice. Scedosporium and endemic mycosis can cause pulmonary disease but they are rare in Indian settings.
P. jirovecii pneumonia has traditionally had a high incidence among lung and combined heart-lung transplantation varying from <10% to 40% in various studies however it has increasingly become uncommon due to the widespread use of Co-trimoxazole prophylaxis. Risk factors described in kidney transplant recipients include acute graft rejection and development of CMV infection. Chest X-ray may be normal or reveal bilateral interstitial infiltrates sparing the peripheries. A high-resolution CT thorax may have higher sensitivity for the diagnosis. Direct staining of respiratory secretions (either induced sputum or bronchoalveolar lavage) with immunofluorescent monoclonal antibody stains is now the mainstay of diagnosis. GMS, Wright Giemsa stains are more or less given up as they have poor sensitivity and specificity. BDG a pan-fungal biomarker issensitive (>95%) but is not specific. Breakthrough infections while on Co-trimoxazole prophylaxis are rare. Co-trimoxazole remains the drug of choice for treatment of Pneumocystis pneumonia even today.
| Summary|| |
Infections after SOT depend on the “net state of immunosuppression” and epidemiologic exposures. Causes are wide and varied and are often modified by prophylactic strategies and vaccinations pre and post transplantation. Due to the attenuation of clinical symptoms and signs, invasive procedures with microbiological cultures and molecular techniques are often required for a confirmatory diagnosis. An appropriate pre transplant evaluation with the requisite vaccinations could to a large extent modify the course of relevant infections after transplantation leading to improved morbidity and survival.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Dharnidharka VR, Stablein DM, Harmon WE. Post-transplant infections now exceed acute rejection as cause for hospitalization: A report of the NAPRTCS. Am J Transplant 2004;4:384-9.
Green M. Introduction: Infections in solid organ transplantation. Am J Transplant 2013;13 Suppl 4:3-8.
Fishman JA; AST Infectious Diseases Community of Practice. Introduction: Infection in solid organ transplant recipients. Am J Transplant 2009;9 Suppl 4:S3-6.
Awan AA, Niu J, Pan JS, Erickson KF, Mandayam S, Winkelmayer WC, et al.
Trends in the causes of death among kidney transplant recipients in the United States (1996-2014). Am J Nephrol 2018;48:472-81.
Khoury JA, Brennan DC. Infectious complications in kidney transplant recipients: Review of the literature. Saudi J Kidney Dis Transpl 2005;16:453-97.
] [Full text]
Singh N, Chang FY, Gayowski T, Wagener M, Marino IR. Fever in liver transplant recipients in the intensive care unit. Clin Transplant 1999;13:504-11.
Tveit DJ, Hypolite IO, Poropatich RK, Hshieh P, Cruess D, Hawkes CA, et al.
Hospitalizations for bacterial pneumonia after renal transplantation in the United States. J Nephrol 2002;15:255-62.
Cisneros JM, Muñoz P, Cisneros JT, Gurgui M, Hernandez MJ, Aguado JM, et al.
Pneumonia after heart transplantation: A multiinstitutional study. Clin Infect Dis 1998;27:324-31.
Timsit JF, Sonneville R, Kalil AC, Bassetti M, Ferrer R, Jaber S, et al.
Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients. Intensive Care Med 2019;45:573-91.
Malinis M, Boucher HW; AST Infectious Diseases Community of Practice. Screening of donor and candidate prior to solid organ transplantation – Guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant 2019;33:e13548.
Aguado JM, Silva JT, Fernández-Ruiz M, Cordero E, Fortún J, Gudiol C, et al.
Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations. Transplant Rev (Orlando) 2018;32:36-57.
Gottlieb J, Schulz TF, Welte T, Fuehner T, Dierich M, Simon AR, et al.
Community-acquired respiratory viral infections in lung transplant recipients: A single season cohort study. Transplantation 2009;87:1530-7.
Pneumonia Infection in Organ Transplant Recipients – Infectious Disease and Antimicrobial Agents. Available from: http://www.antimicrobe.org/t35.asp
. [Last accessed on 2020 Dec 09].
Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M, et al.
Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab 1994;79:1605-8.
Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, et al.
Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001;164:396-402.
Gilbert DN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010;48:2325-9.
Theel ES, Doern CD. β-D-glucan testing is important for diagnosis of invasive fungal infections. J Clin Microbiol 2013;51:3478-83.
Tissot F, Lamoth F, Hauser PM, Orasch C, Flückiger U, Siegemund M, et al.
β-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med 2013;188:1100-9.
Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al.
Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis 2016;62:e1-50.
Leeflang MM, Debets-Ossenkopp YJ, Wang J, Visser CE, Scholten RJ, Hooft L, et al.
Galactomannan detection for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst Rev 2015;2015:CD007394.
Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: A meta-analysis. Clin Infect Dis 2006;42:1417-27.
Azoulay E, Russell L, Van de Louw A, Metaxa V, Bauer P, Povoa P, et al.
Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Med 2020;46:298-314.
Carugati M, Morlacchi LC, Peri AM, Alagna L, Rossetti V, Bandera A, et al.
Challenges in the diagnosis and management of bacterial lung infections in solid organ recipients: A narrative review. Int J Mol Sci 2020;21:1221.
Sundaram M, Adhikary SD, John GT, Kekre NS. Tuberculosis in renal transplant recipients. Indian J Urol 2008;24:396-400.
] [Full text]
John GT. Infections after renal transplantation in India. Indian J Nephrol 2003;13:14. [Full text]
John GT, Thomas PP, Thomas M, Jeyaseelan L, Jacob CK, Shastry JC. A double-blind randomized controlled trial of primary isoniazid prophylaxis in dialysis and transplant patients. Transplantation 1994;57:1683-4.
Kim YJ, Boeckh M, Englund JA. Community respiratory virus infections in immunocompromised patients: Hematopoietic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. Semin Respir Crit Care Med 2007;28:222-42.
Kute VB, Vanikar AV, Shah PR, Gumber MR, Patel HV, Godara SM, et al
. Post-renal transplant cytomegalovirus infection: Study of risk factors. Transplant Proc 2012;44:706-9.
Varghese J, Subramanian S, Reddy MS, Shanmugam N, Balajee G, Srinivasan V, et al.
Seroprevalence of cytomegalovirus in donors & opportunistic viral infections in liver transplant recipients. Indian J Med Res 2017;145:558-62.
] [Full text]
Vincent E. Facing the facts: The indirect effects of cytomegalovirus. Transplantation 2007;84:S7-10.
Razonable RR, Humar A; AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplantation. Am J Transplant 2013;13 Suppl 4:93-106.
Arthurs SK, Eid AJ, Pedersen RA, Kremers WK, Cosio FG, Patel R, et al.
Delayed-onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation. Clin Infect Dis 2008;46:840-6.
Paulsen GC, Danziger-Isakov L. Respiratory viral infections in solid organ and hematopoietic stem cell transplantation. Clin Chest Med 2017;38:707-26.
von Lilienfeld-Toal M, Berger A, Christopeit M, Hentrich M, Heussel CP, Kalkreuth J, et al.
Community acquired respiratory virus infections in cancer patients – Guideline on diagnosis and management by the infectious diseases working party of the German society for haematology and medical oncology. Eur J Cancer 2016;67:200-12.
Odongo FC, Azevedo LS, Neto ED, Yeh-Li H, Caiaffa H, Pierrotti LC. Clinical characteristics and outcomes of influenza A infection in kidney transplant recipients: A single-center experience. Transplant Proc 2016;48:2315-8.
Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al.
Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020;323:1843-4.
Azzi Y, Bartash R, Scalea J, Loarte-Campos P, Akalin E. COVID-19 and solid organ transplantation: A review article. Transplantation 2021;105:37-55.
Silveira FP, Husain S. Fungal infections in solid organ transplantation. Med Mycol 2007;45:305-20.
Singh N, Husain S. Aspergillus
infections after lung transplantation: Clinical differences in type of transplant and implications for management. J Heart Lung Transplant 2003;22:258-66.
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al.
Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15.
Vilchez RA, Irish W, Lacomis J, Costello P, Fung J, Kusne S. The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center. Medicine (Baltimore) 2001;80:308-12.
Skiada A, Pavleas I, Drogari-Apiranthitou M. Rare fungal infectious agents: A lurking enemy. F1000Res 2017;6:1917.
Fishman JA. Prevention of infection due to Pneumocystis carinii
. Antimicrob Agents Chemother 1998;42:995-1004.
Lee SH, Huh KH, Joo DJ, Kim MS, Kim SI, Lee J, et al.
Risk factors for Pneumocystis jirovecii
pneumonia (PJP) in kidney transplantation recipients. Sci Rep 2017;7:1571.
Karageorgopoulos DE, Qu JM, Korbila IP, Zhu YG, Vasileiou VA, Falagas ME. Accuracy of b-D-glucan for the diagnosis of Pneumocystis jirovecii
pneumonia: A meta-analysis. Clin Microbiol Infect 2013;19:39-49.