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
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.
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
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.
Category 2 (approximately 10% of patients) consists of those with chronic viral infection (eg, HBV, HCV, CMV, EBV, BKV, papillomavirus).
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.
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
Symptomatic UTIs with pyuria and positive urine cultures: Treatment is indicated.
Asymptomatic bacteriuria without pyuria: no clear need to treat. However, some centers may choose to treat in the first few months after transplant as a cautionary measure.
Evaluation of recurrent UTIs
Rule out urinary retention: Measure postvoid residuals (by ultrasound or catheter); if elevated (>100 mL), may need intermittent catheterization or other measures
Preventive measures
Avoid constipation. Refer to gastroenterologist as needed.
Educate patients in measures to avoid recurrent UTIs (Table 13-4).Stay updated, free articles. Join our Telegram channel
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