DIFFERENTIAL DIAGNOSIS OF INFECTION FOLLOWING RENAL TRANSPLANTATION Infecti...

DIFFERENTIAL DIAGNOSIS OF INFECTION FOLLOWING RENAL TRANSPLANTATION

Infectious episodes are the leading event of morbidity and mortality during the early post-transplant stage, almost > 80 % of TRs (transplant recipients) may experience at least one infectious episode through the 1^st year. Infection as well as graft malfunction induced by rejection are both closely related to the magnitude of the immunosuppressive burden.

The main risk factor for post-transplant infectious episodes is highly related to the magnitude of overall immunosuppression administrated in the induction therapy, maintenance immunosuppression as well as that given for the management of acute rejection and particular immunosuppressive agent per se. Moreover, the behavior of the post-transplant opportunistic infection   may be altered via the traditional use of the prophylactic antimicrobials given for Pneumocystis carinii (P. jirovecii) and CMV (cytomegalovirus). These alterations have been changed due to the advent of the newly presented clinical syndromes (e.g. polyoma allograft nephropathy) and owing to infection caused by resistant organisms to antimicrobial management.

The newly admitted quantitative molecular and the antigen-dependent micro-biologic testing can now identify the previously unrecognized transplant-related infections, e.g., lymphocytic choriomeningitis viral infection. These lab tests can be also applied in the control of the common infections, e.g., CMV and EBV (Epstein-Barr virus). Variable factors, however, may influence the magnitude of risk of infection intensity that may include:

1]     Three different sources are currently can induce post-transplant infection:

·        Environment-induced exposure,

·        Reactivated previous latent infection, or

·        Currently active infection transmission via the donated graft (very rare).

2]     Indwelling catheter placement.

3]     Impact of nutrition and metabolic effectors, e.g., uremic mille and hyperglycemia out of control.

4]     Viral-related immunomodulation can be induced by CMV, EBV, HBV, HCV, and HIV.

5]     Module of dialysis before transplantation.

6]     PD (peritoneal dialysis) may be associated with a significant risk of post-operative infectious episodes in comparison to HDX (hemodialysis).

 

There is a tendency of different types of infectious agents to be presented in a generally temporal pattern during the post-transplantation period. The impact of the newly introduced immunosuppressive medications upon these temporal tendencies still uncertain. To achieve a prompt differential diagnosis of the post-transplant infectious episodes, it is wise to follow the timing of their post-transplant presentation.

 

EARLY POSTTRANSPLANT INFECTION 

The 1^st month post-operative may show the traditional infections after surgery, similar to that observed in patients with no immunosuppression performing similar surgeries. Usually bacterial or fungal agents that cause wound sepsis, bacterial pneumonias, and bacterial/fungal infection involving the urinary or PD catheter, or a central venous access. Rarely, bacterial and/or fungal agents can be transmitted via an infected graft, despite donors were strictly screened for any latent contamination.

However, opportunistic infection e.g., Pneumocystis carinii and Nocardia asteroids, are rarely observed in this timing despite the heavy burden of immunosuppression administrated to the recipient to manage the acute rejection episodes. This notion indicates that the duration of immunosuppression exposure has a robust impact on the risk for post-transplant opportunistic infection to a large extent.

 

ONE TO SIX MONTHS AFTER TRANSPLANTATION

Infections in this stage with the immunomodulating viral agents e.g., CMV in particular, are most common. These group of organisms may induce many clinical syndromes, however, their immunomodulating impact may result in opportunistic infection predisposition, examples may include Pneumocystis jiroveci (P. carinii), pneumonias, Listeria species, and Aspergillus fumigates. Other common infections that can be seen in this stage may include HBV, HBV, Herpes simplex, Herpes zoster, Mycobacterium TB, and EBV, these agents can be complicated by the PTLD (lymphoproliferative disorders) evolution, as well as recurrent or relapsed UTI infection. 

 

LATE POSTTRANSPLANTATION

The late period after transplantation (> 6 mo post-transplant) is characterized by stability in allograft function with established maintenance on a minimal doses of immunosuppression. So, infectious episodes in this period is often simulates that observed in the general population (e.g., influenza infection, pneumococcal pneumonias, UTI, etc). Nevertheless, almost 10-15 % of TRs may experience chronic viral infection that may become clinically manifest by time e.g., CMV chorioretinitis, PTLD due to EBV, HCV/HBV hepatitis, and HIV infection.

A minority of TRs (5-15 %) with multiple episodes of acute rejection and a higher burden of immunosuppression may experience devastating opportunistic infections with serious morbidity and mortality e.g., Pneumocystis carinii, Listeria monocytogenes, and Nocardia asteroids.

 

ANTIMICROBIAL PROPHYLAXIS

Several recommendations have been admitted for routine prophylactic antimicrobial administration to TRs:

1]    Prophylactic antibiotic (AB) with broad spectrum ABs to prevent surgical wound infection in the Perioperative period. TMP/SMX can be given

to prevent UTI, sepsis, Pneumocystis jiroveci infection and Nocardia species.

2]    Doses of TMP/SMX must be adjusted considering allograft function. The traditional dose equals one DS tablet per day if SCr is < 2-3 mg/dL (176 - 264 µmol/L), and one DS tablet EOD or one single strength tablet daily if SCr is > 3 mg/dL (>264 µmol/L). However, low dosage means lower protection. Prophylaxis for almost one y in normal urinary tracts.

3]    Nevertheless, indefinite prophylaxis may be offered for TRs with recurrent UTI, anatomic UT aberrations, or a neurogenic UB.

4]    Allergic TRs to TMP/SMX can be managed by an oral quinolone, e.g. ciprofloxacin to guard against UTI.

5]    A robust prophylaxis against Pneumocystis with atovaquone 1500 mg/day or a nebulized pentamidine 300 mg/month.  

6]    Oral dapsone for Pneumocystis prevention is generally not advised, due to a higher prevalence of hemolytic anemia in TRs.

7]    Anti-CMV prophylactic measures is mandated in many clinical situations.

8]    Prevention of primary infection in CMV-negative TRs of CMV-positive donors is mandatory as well as prevention of reactivated infection in CMV-positive TRs receiving OKT3 in particular.

N.B. This Blogger is created to declare the possibility of infection after renal transplantation.

REFERENCES

1. Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357:2601.
2. Johnson DW, Isbel NM, Brown AM, et al. The effect of obesity on renal transplant outcomes. Transplantation 2002; 74:675.
3. Kamath NS, John GT, Neelakantan N, et al. Acute graft pyelonephritis following renal transplantation. Transpl Infect Dis 2006; 8:140.
4. Torre-Cisneros J, Castón JJ, Moreno J, et al. Tuberculosis in the transplant candidate: importance of early diagnosis and treatment. Transplantation 2004; 77:1376.
5. Lee I, Barton TD, Goral S, et al. Complications related to dapsone use for Pneumocystis jirovecii pneumonia prophylaxis in solid organ transplant recipients. Am J Transplant 2005; 5:2791.