Infections in Solid Organ Transplant Recipients

Pre-transplantation Factors

The specific organ that is transplanted is the most important determinant of the location of infection, especially during the first 3 postoperative months. The chest, abdomen, and urinary tract are the most common sites of infection after thoracic, liver, and kidney transplantation, respectively. Explanations for these site-specific infections include local ischemic injury and bleeding, as well as potential intraoperative contamination. The underlying condition causing organ failure also can lead to an increased risk for developing infection after SOT. For example, cystic fibrosis (CF) predisposes to pseudomonal and fungal infections after lung transplantation. Palliative surgery, such as for cardiac, biliary, and urologic conditions, before transplantation increases the technical difficulty of the transplant procedure, enhancing the risk of subsequent infection. In addition, the severity of disease at the time of transplantation correlates with the risk of postoperative morbidity and mortality. Long-standing malnutrition predisposes children to infection; attempts to correct nutritional deficits with parenteral alimentation carry attendant risks for catheter-associated infection. Finally, mechanical ventilation while awaiting transplantation increases the risk of colonization and infection with nosocomial pathogens, many of which have multidrug resistance.

Age is an important determinant of both susceptibility to and severity of infection after transplantation. Young children undergoing transplantation can experience greater disease severity with certain viruses, such as respiratory syncytial virus (RSV) or parainfluenza virus (PIV) compared with older recipients. Likewise, primary infection with cytomegalovirus (CMV) or Epstein–Barr virus (EBV), more common in young children, is associated with worse outcomes compared with reactivation of disease. ^, By contrast, other pathogens, such as Cryptococcus species, rarely are found before young adulthood. Younger age at the time of transplantation also is associated with an increased rate of infection during the first few years after transplantation. Finally, young children who are not fully immunized remain susceptible to vaccine-preventable infections or receive vaccination after transplantation, when their ability to mount an immune response may be hampered by immunosuppression.

Donated Organ Considerations

Transplant recipients can acquire pathogens from their donors who have active or latent infections at the time of organ procurement. Examples include CMV, EBV, Toxoplasma gondii , Histoplasma spp., West Nile virus (WNV), hepatitis B (HBV) and C viruses (HCV), and HIV. ^{, ,} Screening to preclude donors with HIV or active HBV infection is standard practice, whereas HCV-positive donors are often used for HCV-positive recipients and in more recent years even for HCV-negative recipients. Similarly, HBV core antibody positive donors sometimes are used in individual cases. Bacteria or fungi colonizing the donor’s respiratory tract can cause disease after lung transplantation. Similarly, unrecognized infection with bacteria, fungi, viruses, or parasites in the blood or organ being transplanted in the donor creates a risk to any recipient. In the US, unanticipated infections that may be of donor origin are reported to the Organ Procurement and Transplant Network (OPTN) safety portal for evaluation by the ad hoc disease transmission advisory committee (DTAC) to help improve overall transplant safety.

Intraoperative Factors

Operative factors unique to each SOT procedure can predispose to infection. For example, the type of biliary reconstruction used in liver transplantation influences the likelihood of developing an infectious complication. Surgical events during the operation also alter the risk of infection. Injury to the phrenic, vagal, or recurrent laryngeal nerves affect pulmonary toilet, predisposing a lung transplant recipient to pneumonia. Additional factors, including prolonged operative time, contamination of the operative field, and bleeding at or near surgical sites, also increase the risk of postoperative infections.

Post-transplantation Factors

Immunosuppression is the greatest risk factor for infection following transplantation. Although immunosuppressive regimens evolve to achieve more specific control of rejection with less impairment of immune function, all current regimens interfere with host defenses. Treatment of rejection exacerbates this risk, as does use of antilymphocyte preparations or other biologic agents. ^, As newer immunosuppressive agents are introduced, clinicians must be alert for known and unknown infectious risks, as well as the manifestations of those infections.

Immunosuppression generally is divided into induction therapy and maintenance therapy. Induction therapy commonly results in depletion of T-cells and possibly other immune functions for weeks to months. Maintenance therapies are intended to prevent long-term rejection of the transplanted organ and impair T-cell function, though not to the degree observed in induction. If rejection occurs, immunosuppression similar to induction therapies are often needed ( Table 95.1 ).

Technical problems after transplantation are major risk factors for infectious complications. Common post-transplant complications include thrombosis of the hepatic artery, which predisposes to hepatic abscesses and bloodstream infection (BSI) after liver transplantation; vesicoureteral reflux, which predisposes to graft pyelonephritis in renal transplant recipients; ^, and mediastinal bleeding requiring re-exploration, which predisposes to mediastinitis and BSI in thoracic organ transplant recipients.

Indwelling cannulas pose a significant risk for infection after transplantation. Central venous catheters are a risk for BSI; urethral catheters predispose to urinary tract infection (UTI); and prolonged endotracheal intubation is associated with pneumonia.

Nosocomial exposures constitute the final group of posttransplant risk factors. All transplant recipients are at risk for transfusion-associated pathogens. Children undergoing transplantation during the winter often are exposed nosocomially to common viruses (e.g., RSV, influenza virus), as well as novel viruses such as severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2). Areas of the hospital undergoing construction may have contamination with pathogenic fungi, such as Aspergillus species, which increase the risk of invasive fungal disease after SOT. Finally, nosocomial transmission of multiple drug-resistant bacteria predisposes to infection with these pathogens.