Posttransplantation Infectious Complications and Vaccinations

Posttransplantation Infectious Complications and Vaccinations

Camille Nelson Kotton

Joanna M. Schaenman

Phuong-Thu T. Pham


  • General considerations

    • All kidney transplant candidates should receive vaccinations for hepatitis B, pneumococcus, and other standard vaccinations appropriate for age and presence of endstage kidney disease.

    • Household members, close contacts, and health care workers should also be fully immunized.

    • Vaccinations using inactivated or killed microorganisms, components, and recombinant moieties are safe for transplant recipients.

    • Live vaccines are contraindicated posttransplant.

    • Seasonal influenza vaccine (injectable) is safe and effective; both quadrivalent and high-dose trivalent can be used.

    • Ensuring adequate response to hepatitis B vaccination is important to prevent transmission of donor-derived infection (from organ or blood donors).

  • Timing of vaccinations

    • Vaccinations should be administered ≥4 weeks before transplant to achieve optimal response and to minimize the possibility of live vaccine-derived infection in the posttransplant period.

    • Vaccinations during the first 3 months after transplantation may result in suboptimal response and protection because of heavy immunosuppression. Most centers restart vaccinations 6 to 12 months after transplantation, 3 months posttransplant for influenza during outbreaks.

  • Recommended vaccinations before and after transplantation are shown in Table 13-1.1


  • Destinations—look up country of destination for travel medicine recommendations


  • Information on immunocompromised hosts and travel


    TABLE 13-1 Recommended Vaccinations Before and After Transplant


    Before transplant

    After transplanta ≥3 mo posttransplant





    Should be administered ≥4 wk prior to transplant/onset of immunosuppression



    See comments.

    Diphtheria and tetanus: booster every 10 y

    Varicella-live (Varivax)



    Should be administered ≥4 wk prior to transplant if nonimmune



    Inactivated polio

    For travelers to endemic areas (eg, some parts of Asia, Africa)

    Haemophilus influenzae type b



    Especially important for patients who have undergone splenectomy

    Inactivated influenza vaccine




    All patients who are >3 mo posttransplant should receive seasonal influenza vaccine.

    May be administered in the immediate posttransplant period during an outbreak

    Pneumococcal conjugate PCV13



    For those who have not received either pneumococcus vaccine, PCV13 should be administered first, followed 8 wk later by PPSV23.

    Patients who have already received one dose of PPSV23 should receive PCV13 at least 1 y after PPSV23.

    Pneumococcal polysaccharide PPSV23



    Recommended posttransplant if not administered pretransplant. Patients who have already received one dose of PPSV23 should receive an additional dose 5 y after the first dose of PPSV23.

    Hepatitis A



    Recommended posttransplant if not administered pretransplant.

    For travelers to endemic areas, men who have sex with men, other risks factors

    Hepatitis B



    Recommended posttransplant if not administered pretransplant. High dose often more effective than standard dose; can accelerate series if needed before transplant

    Monitor titers for response to vaccination and repeat vaccination series if needed.

    Human papillomavirus



    Nonpregnant female candidates aged 11-26 y, males aged 11-21 y

    Neisseria meningitides (both quadrivalent and group B vaccines)



    Recommended for patients before/after splenectomy, those with functional asplenia, with properdin terminal component deficiencies or receiving eculizumab therapy

    Others: military members, travelers to high-risk areas, college freshman living on campus

    Zoster-nonlive viral particle (Shingrix)



    Recommended over Zostavax; limited safety data patients posttransplant, contains adjuvant, moderately reactogenic

    Zoster-live (Zostavax)



    Should be administered ≥4 wk prior to transplantc/onset of immunosuppression

    Abbreviations: PCV13, pneumococcal conjugate vaccine; PPSV23, pneumococcal polysaccharide vaccine.

    a Live vaccines are contraindicated posttransplant.

    b Vaccinations <3 months posttransplant may result in suboptimal response and protection.

    c If inadvertently given within 4 weeks before transplant, consult infectious disease specialist and administer acyclovir to prevent reaction of vaccine-strain virus.

  • Traveler’s diarrhea

    • Transplant patients traveling abroad should bring ciprofloxacin or azithromycin for self-treatment in case of severe or bloody travel-related diarrhea.


  • Donor-derived infections

  • Recipient-related risks

    • Net state of immunosuppression: intensity and duration of immunosuppression

    • Surgical instrumentation, wound, abdominal fluid collections

    • Underlying medical risks (eg, diabetes mellitus, uremia)

    • Increased patient age

    • Hypogammaglobulinemia: Although prospective controlled trials are lacking, currently available literature suggests that posttransplant monitoring of immunoglobulin G (IgG) levels and Ig replacement therapy may reduce infection rates in patients with hypogammaglobulinemia (especially IgG <400 mg/dL).2,3

    • Neutropenia and leukopenia

      • Drug-induced (see chapter 2): thymoglobulin, mycophenolate mofetil (MMF), azathioprine, sirolimus, valganciclovir, trimethoprim-sulfamethoxazole, dapsone, or possible idiosyncratic drug-drug reaction

      • The use of granulocyte colony-stimulating factor (GCSF) is considered safe and effective in kidney transplant recipients.

    • Infections with immunomodulating viruses

  • Environmental exposures: nosocomial, immediate living surrounding, endemic/epidemic, colonization, travel


Both the type and occurrence of infections in the immunocompromised transplant recipient follow a timetable pattern (Table 13-2).4,5 However, the timing of infections may be altered by intensity of immune suppression, use of antimicrobial prophylaxis, and patient exposures.4,5 All transplant recipients should be counseled to minimize environmental exposure (primarily avoidance of pigeon droppings and areas of active building construction).

  • Month 1 after transplantation

    • Donor- and recipient-derived infections with common nosocomial bacterial microorganisms and Candida species predominate.

    • Most bacterial infections involve wounds, catheters, and drainage sites.

    • Aspiration pneumonia and urinary tract infections (UTIs) are common.

    • UTI preventive measures: early urethral catheter removal and antibiotic prophylaxis

    • Infections caused by multidrug-resistant bacteria are center specific.

  • Month 1 to 6 after transplantation

    • Unconventional or opportunistic infections secondary to immunosuppression are most common.

    • Viral infections

      • Common viral infections including cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), and hepatitis C virus (HCV) may occur de novo or reactivation of latent disease.

      • Community-acquired respiratory viruses are a common hazard.

      • Viral infections may further impair immunity and increase the risk for additional opportunistic infections.

      • BK virus (BKV) infection is an important cause of allograft loss (discussed later).

    • Fungal infections

      • Repeated courses of antibiotics and corticosteroid therapy increase the risk of fungal infections.

  • After 6 months

    • Patients can be arbitrarily divided into three categories in terms of infection risks:

      • Category 1 (70%-80% of patients) consists of patients with satisfactory or good allograft function, on relatively low doses of immunosuppressants, and no history of chronic viral infection.

        • image The risk of infection is similar to that of the general population.

        • image Community-acquired respiratory viruses constitute the major infective agents.

        • image Opportunistic infections are unusual unless environmental exposure has occurred.

      • Category 2 (approximately 10% of patients) consists of those with chronic viral infection (eg, HBV, HCV, CMV, EBV, BKV, papillomavirus).

        • image In the setting of immunosuppression, chronic viral infections may accelerate disease progression or give rise to associated complications (eg, liver cirrhosis with HBV and HCV, BK nephropathy [BKN], posttransplant lymphoproliferative disease [EBV], or squamous cell carcinoma [papillomavirus]). The advent of the direct-acting anti-HCV antiviral agents should result in a decrease in the incidence of chronic HCV infection and cirrhosis.

      • Category 3 (approximately 10% of patients) consists of those who experience multiple rejection episodes requiring repeated exposure to potent immunosuppression.

        • image These patients are the most likely to develop chronic viral infections and superinfection with opportunistic infections.

      TABLE 13-2 Timetable of Infections

      Time after transplant

      Infectious agents

      Comments Preventive measures

      Month 1

      Bacterial (sites and sources)

      Urinary tract



      Surgical wound or intra-abdominal sources (lymphoceles, hematomas, urine leak)

      Vascular access or instrumentation (catheters, drains, urinary stents)

      Anatomic or functional genitourinary tract abnormalities (ureteral stricture, vesicoureteric reflux, neurogenic bladder)

      Clostridium difficile or center-specific multidrug-resistant species


      Uncommon except for HSV


      Candida species predominate (recipient pretransplant colonization or donor derived).

      Organisms transmitted with donor organs

      Common nosocomial bacterial pathogens and Candida species predominate.

      Risk can be mitigated by appropriate prophylaxis (see Tables 13-3 and 13-4).

      Minimize or avoid environmental exposure at all time after transplant (primarily avoidance of pigeons and areas of active building construction).

      Month 1-6


      CMV, HSV, VZV, EBV, HBV, HCV,a BK virus (exogenous infection or reactivation of latent disease due to immunosuppression)

      Others: HHV-6, HHV-7, influenza, parainfluenza, RSV, adenovirus


      Aspergillus species, Cryptococcus, agents of mucormycosis


      Recurrent urinary tract infections or pyelonephritis

      Nocardia, Listeria, Mycobacterium species (tuberculous and nontuberculous), Legionella


      Pneumocystis jiroveci, Toxoplasma, and Strongyloides species

      Unconventional or opportunistic infections due to immunosuppression

      Risk can be mitigated by appropriate prophylaxis (see Tables 13-3 and 13-4).

      Minimize or avoid environmental exposure (noted above).

      More than 6 mo posttransplant

      Stable patients on low-dose immunosuppressants Community-acquired respiratory and GI viral pathogens

      History of multiple rejection episodes requiring intensification of immunosuppression

      Viral infections (invasive CMV such as CMV colitis or pneumonitis, VZV, parvovirus B19), late opportunistic infections (Pneumocystis, Cryptococcus, Listeria, nocardiosis), tuberculosis

      Persistent infections: HBV, HCV,a papillomavirus, BK virus

      Geographically restricted (eg, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis)

      Deep-seated infections (eg, osteomyelitis, paravertebral abscess). Predisposing risk factors: chronic skin infections, long-standing poorly controlled diabetes, peripheral vascular disease

      Associated with malignancies: EBV (PTLD), papillomavirus (squamous cell carcinoma), HSV (cervical cancer), HHV-8 (Kaposi sarcoma)

      Infection risks associated with duration and intensity of immunosuppression and epidemiologic exposures

      Minimize or avoid environmental exposure (noted above).

      Abbreviations: CMV, cytomegalovirus; EBV, Epstein-Barr virus; GI, gastrointestinal; HBV, hepatitis B virus; HCV, hepatitis C virus; HHV-6, human herpes virus 6; HHV-7, human herpes virus 7; HHV-8, human herpes virus 8; HSV, herpes simplex virus; PTLD, posttransplant lymphoproliferative disease; RSV, respiratory syncytial virus; VZV, varicella zoster virus.

      a Incidence should decrease with the use of the newer interferon- and ribavirin-free anti-HCV protease inhibitor combination therapy.

      TABLE 13-3 Posttransplantation Antimicrobial Prophylaxis




      Pneumocystis jirovecii

      First line: trimethoprim-sulfamethoxazole (TMP-SMX) × 6-12+ moa (lifelong in some, especially thoracic organs)

      Second line (sulfa allergies)b: atovaquone, dapsone, or aerosolized pentamidine

      TMP-SMX also reduces the incidence of Toxoplasma gondii, Listeria monocytogenes, and Nocardia asteroides and reduces the incidence of UTI in kidney transplant recipients.

      Check glucose-6-phosphate dehydrogenase prior to initiation of dapsone.

      Be aware of the risk of methemoglobinemia on dapsone.


      Nystatin S&S or fluconazolec

      Fluconazole recommended in high-risk recipients (eg, simultaneous pancreas-kidney or simultaneous liver-kidney transplant recipients, history of coccidioidomycosis, or patients who live in endemic areas)


      Acyclovir, valganciclovir, ganciclovir (see Table 13-5)

      Acyclovir for HSV and VZV prophylaxis for patients not on CMV prophylaxis

      Abbreviations: CMV, cytomegalovirus; HSV, herpes simplex virus; UTI, urinary tract infection; VZV, varicella zoster virus.

      a Restart trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis × 3 months after any Solu Medrol pulse or antibody treatment. Duration of prophylactic therapy may vary among centers (see chapter 2).

      b Listed in order of preference. Consider adding fluoroquinolones or other agents for antibacterial activity for higher risk recipients.

      c We advocate lifelong therapy in patients with history of coccidioidomycosis or in those who live in endemic areas.

    • Other considerations

      • New infections occurring after 6 months often reflect recent exposures (eg, Listeria monocytogenes [dietary exposure], Lyme disease [tick exposure], and malaria [travelers to endemic areas]).6

Suggested antimicrobial prophylactic therapy in kidney transplant recipients is shown in Table 13-3.


May 8, 2019 | Posted by in NEPHROLOGY | Comments Off on Posttransplantation Infectious Complications and Vaccinations

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