Posttransplantation Infectious Complications and Vaccinations



Posttransplantation Infectious Complications and Vaccinations


Camille Nelson Kotton

Joanna M. Schaenman

Phuong-Thu T. Pham



VACCINATIONS



  • 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


INTERNATIONAL TRAVEL VACCINATION RECOMMENDATIONS/WEBSITE



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



    • https://wwwnc.cdc.gov/travel/destinations/list/


  • Information on immunocompromised hosts and travel



    • https://wwwnc.cdc.gov/travel/yellowbook/2018/advising-travelers-with-specific-needs/immunocompromised-travelers









    TABLE 13-1 Recommended Vaccinations Before and After Transplant


















































































    Vaccines


    Before transplant


    After transplanta ≥3 mo posttransplant


    Commentsb


    Measles-mumps-rubella


    Yes


    No


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


    Diphtheria-tetanuspertussis


    Yes


    See comments.


    Diphtheria and tetanus: booster every 10 y


    Varicella-live (Varivax)


    Yes


    No


    Should be administered ≥4 wk prior to transplant if nonimmune


    Poliovirus


    Yes


    Inactivated polio


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


    Haemophilus influenzae type b


    Yes


    Yes


    Especially important for patients who have undergone splenectomy


    Inactivated influenza vaccine


    Yes


    Yes


    Annually


    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


    Yes


    Yes


    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


    Yes


    Yes


    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


    Yes


    Yes


    Recommended posttransplant if not administered pretransplant.


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


    Hepatitis B


    Yes


    Yes


    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


    Yes


    Yes


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


    Neisseria meningitides (both quadrivalent and group B vaccines)


    Yes


    Yes


    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)


    Yes


    Yes


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


    Zoster-live (Zostavax)


    Yes


    No


    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.


RISK FACTORS FOR POSTTRANSPLANTATION INFECTIOUS COMPLICATIONS



  • 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



TIMETABLE OF POSTTRANSPLANTATION INFECTIOUS COMPLICATIONS

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


      Respiratory


      Bacteremia


      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


      Viral


      Uncommon except for HSV


      Fungal


      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


      Viral


      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


      Fungal


      Aspergillus species, Cryptococcus, agents of mucormycosis


      Bacterial


      Recurrent urinary tract infections or pyelonephritis


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


      Parasitic


      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























      Prophylaxis


      Regimen


      Comments


      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.


      Fungal


      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)


      CMV


      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.


RECURRENT URINARY TRACT INFECTION WORKUP AND MANAGEMENT

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

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