- Infections are a major cause of death for kidney transplant patients, accounting for around 15-20% of post-transplant mortality. The most common infections are cytomegalovirus (CMV) and Pneumocystis pneumonia (PCP). - CMV infection and disease are still frequent despite prophylaxis and preemptive treatment. PCP is now rare due to universal long-term prophylaxis. Bacterial pneumonia also occurs in around 5% of kidney transplant recipients and carries a high mortality risk, especially for nosocomial infections. - Vaccination of transplant candidates and recipients is important for prevention of pneumonia. However, live vaccines should generally be avoided in transplant patients for the

2. PNEUMONIA IN
TRANSPLANT PATIENTS

4. INFECTION IN THE KIDNEY TRANSPLANT PATIENT'S
• Increasingly potent immunosuppressive agents have dramatically reduce rejection rates at the same
time increasing susceptibility of patients to opportunistic infection and cancers.
• Early years of transplantation infection occurred in 80% of cases and was cause of death in 40% of
cases. Recent statistics show still about 15 to 20 % of death post Kt is due to Infections.
• Infections are a common cause of morbidity and mortality after transplantation, and infections rank
second as the cause of death in patients with allograft function. The rate of first infections in the initial
years after kidney transplantation is 45.0 per 100 patient-years of follow-up, as estimated using
Medicare claims data collected by the U.S. Renal Data System
• transplant recipients may not manifest typical signs and symptoms of infection, diagnoses may be
confounded.
• death with a functioning kidney graft (DWFG) is a major cause of graft loss after renal transplantation,
occurring in 10–40% of transplants

5. Sood Int Urol Nephrol (2010) 42:929–934

6. CHANGING TIMELINE OF INFECTIONS AFTER
ORGAN TRANSPLANTATION
Fishman Jay. n engl j med 357;25 December 20, 2007

7. CMV INFECTIONS
• Cytomegalovirus (CMV) infection is the most common opportunistic infection in kidney transplant
recipients, occurring in 8% of patients
• Risk factors for the development of CMV include donor seropositivity (especially if the recipient is
seronegative), use of induction immunosuppression (T cell–depleting antibodies), simultaneous kidney-
pancreas transplantation, older donors (60 years), presence of allograft rejection, and concurrent
infection from other viruses.
• CMV infection is defined as evidence of CMV replication regardless of symptoms
• CMV disease requires both evidence of infection as well as symptoms, including viral syndrome with
fever or malaise, leukopenia, thrombocytopenia, or evidence of tissue invasion
• CMV infection may occur as primary infection, reinfection (both donor-derived),or reactivation of latent
recipient infection. Donor-derived infections are the most common.
SM Arend Clinical Infectious Diseases 1996;22:920-5

8. Fishman Jay. n engl j med 357;25 December 20, 2007

9. CMV PROPHYLAXIS AND TREATMENT
• Administration of antiviral agent to at risk post-transplant patients before the onset of infection
(prophylaxis) or when infection has been identified (pre-emptive)has been studied and found to be
effective at reducing the incidence of CMV disease
• randomized, controlled trial published in 2008 comparing oral ganciclovir chemoprophylaxis with viral
load monitoring in kidney transplant recipients revealed improved graft survival in those who received
ganciclovir chemoprophylaxis.
• prophylaxis is generally recommended for the highest-risk recipients. early studies showed benefit with
oral or intravenous acyclovir, this has been shown to be inferior to ganciclovir . valganciclovir has
replaced ganciclovir because of the lower pill burden, better bioavailability, and reduced availability of
oral ganciclovir
• blood products maybe a source of CMV infection in CMV D-/R- recipient, whenever possible, these
patients should receive CMV-negative blood and leukodepleted blood during or after transplantation.
• Treatment of established CMV disease requires a multi-factorial approach, including reduction of
immunosuppressive agents, antiviral agents, and in some cases adjuvant therapy

10. PCP
• Historically, P. jiroveci (formerly known as P. carinii) was an important cause of severe pulmonary infections
during the first 3–6 months after transplantation.
• Currently, because of universal prophylaxis during the first 6–12 months after transplantation, this
infection is now rare and the overall incidence rate of P. jiroveci pneumonia (PCP) in kidney transplant
recipients is 0.8 case per 1000 person after completion of 1 year of prophylaxis.
• PCPis associated with a 29%–50% mortality rate in kidney transplant recipients
• typical presentation of PCP includes fever, cough, shortness of breath, and hypoxia out of proportion to
physical and radiologic findings.
• Diagnosis relies on identification of the organism in induced sputum, bronchoalveolar lavage, or
transbronchial biopsy sample. Elevated LDH or even better Beta-d-Glycan in cases with no microbiological
confirmation. (Borstnar S et al. Transplant Proc 2013)
Transmission can occur from patients with PCP but also from asymptomatic hosts that can be transiently
infected with Pneumocystis (colonization)
J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

11. ATTACK RATE OF PNEUMOCYSTIS PNEUMONIA (PCP)
IN TRANSPLANT RECIPIENTS. ADAPTED FROM
RODRIGUEZ ET AL.
Iriart X et al. J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

12. NUMBER OF REJECTION TREATMENTS ADMINISTERED
TO 15 RENAL TRANSPLANT RECIPIENTS WITH PCP AND
95 CONTROLS.
Arent SM Et al.. Clinical Infectious Diseases
1996;22:920-5

13. CMV STATUS VERSUS PCP
CMV infection increased the risk of PCP fivefold, irrespective of
rejection treatments
Arent SM Et al.. Clinical Infectious Diseases
1996;22:920-5

14. IMMUNOSUPPRESSIVE REGIMENS REPORTED WITHIN THE UNITED STATES RENAL
DATA SYSTEM ANALYSES. A TOTAL OF 32,757 MEDICARE PRIMARY ADULT
RECIPIENTS OF A KIDNEY TRANSPLANT BETWEEN 2000 AND 2004.
Iriart X et al. J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

15. IDENTIFICATION OF CYTOMEGALOVIRUS (CMV) AS A
RISK FACTOR FOR PNEUMOCYSTIS PNEUMONIA (PCP)
IN CASE-CONTROL STUDIES.
Iriart X et al. J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

16. NUMBERS OF PNEUMOCYSTIS PNEUMONIA (PCP) DIAGNOSED WITH
TRADITIONAL DIAGNOSTIC METHODS ACCORDING TO THE TYPE OF
SAMPLES.
Iriart X et al. J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

17. DIAGNOSING PCP BEYOND MICROSCOPY- PCP DIAGNOSES HAVE BEEN
EXCELLENT, PARTICULARLY IN ASSAYS DIRECTED AT MSG AND MTLSU RRNA
GENES , WITH SENSITIVITIES FROM 93% TO 100% AND SPECIFICITIES HIGHER
THAN THOSE OBSERVED FOR STANDARD PCR (83%–100%).
Iriart X et al. J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

18. PCP TREATMENT AND PROPHYLAXIS
• Optimal treatment includes high-dose trimethoprim-sulfamethoxazole (15–20 mg/kg per day) in divided
doses or intravenous pentamidine (4 mg/kg per day) for 14–21 days. Potential alternative agents
include atovaquone for mild to moderate PCP or the combination of clindamycin and pyrimethamine. In
patients with hypoxia (partial pressure of oxygen in the alveoli,70 mmHg on room air), corticosteroids
should be coadministered with antimicrobial agents
• prophylaxis for a minimum of 6–12 months after transplantation is recommended; longer courses may
be indicated in patients requiring prolonged higher doses of immunosuppression. Trimethoprim-
sulfamethoxazole is the preferred prophylactic agent; for patients who are intolerant or allergic,
alternatives include dapsone, atovaquone, or inhaled pentamidine (although there is a higher rate of
breakthrough PCP with pentamidine.
• NNT for prophylactic TMP SMZ 1:19 (cochrane database syst rev 2014)

19. TREATMENT AND PROPHYLAXIS PCP
Iriart X et al. J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

20. TREATMENT AND PROPHYLAXIS PCP
Iriart X et al. J. Fungi 2015, 1, 293-331; doi:10.3390/jof1030293

21. PNEUMONIA IN SOT
• Likewise, bacterial pneumonia occurs in 15% of cardiac, 9% of liver and 4-6% of kidney transplant
recipients (4, 17, 74, 109). In
• recent cohort studies of predominantly liver and kidney transplant recipients, overall mortality was
between 21 and 35%, however, mortality differences between nosocomial and community acquired
infection were extreme at 58% compared to 8%, respectively
• Mechanical ventilation and nosocomial infection increase the risk for death
• solid organ transplant patients, the sensitivity of bronchoalveolar lavage for obtaining microbiological
diagnosis has been reported to be between 58% and 69% (15, 97). The sensitivity is highest for the
detection of PCP (90%) (103) and lower for mycobacterial and fungal infections (50%
Infectious Disease & anti microbial Agents 2010-2011. Nina S

22. VACCINATIONS
• It is especially important to make sure that transplant candidates are immunized with pneumococcal
vaccine, hepatitis B virus(HBV) vaccine, and influenza vaccine . Patients who are not immune to varicella
should also be vaccinated, with completion of the series a minimum of 2–4weeks before
transplantation
• Per KDIGO guide-lines, all kidney transplant recipients should be given inactivated vaccines and live
vaccines should be avoided in all but exceptional circumstances.
• Because of the potential blunting of the immune response related to high-dose immunosuppression in
the first 6 months after transplant, it is recommended that routine vaccination be delayed for the first 6
months.
• influenza vaccine has been considered to be an exception to the 6-month recommendation; this vac-
cine can be given at 1 month after transplantation in pandemic situations or as early as 3 months based
on the timing of transplantation relative to the onset of the influenza season
Clin J Am Soc Nephrol 7: 2058–2070, 2012. doi:
10.2215/CJN.04410512

23. Long, B, koftman A. Emergency
Physicians Monthly Jan 2017

24. PULMONARY INFECTION ALGORITHM