Management of Infection in Patients With Kidney Transplant

General Risk Factors for Infection

Sources of infection among renal transplant recipients (RTRs) include reactivation of latent infection in recipients, donor-derived infections, and de novo posttransplant infections, which can include immediate postoperative, nosocomial, and community-acquired infections. Underlying comorbidities such as malnutrition, diabetes, obesity, or cirrhosis also may increase the overall risk of infection. Factors directly related to the transplant, including the hospitalization, surgical procedure, and need for supportive equipment such as urinary catheters, endotracheal tubes, and central lines, provide further potential sources of infection. Postoperatively, intensive immunosuppressive therapy is used to prevent acute rejection and preserve renal graft function. The level and duration of immunosuppression correlates with increased risk of developing opportunistic infections. Thus, despite advances in management of immunosuppression, a fine balance exists between the quantity of immunosuppression needed to prevent rejection and the superimposed risk of infection. Infection in immunocompromised hosts carries a broad spectrum of potential pathogens and atypical presentations of infection compared with the general population.

Pretransplant Evaluation

Because of the infectious risks of transplantation and the resultant immunosuppression, pretransplant evaluations for donors and recipients are completed to minimize these risks. Pretransplant evaluations and management may vary across transplant centers. A thorough medical history including travel, prior infections, environmental exposures, and immunization history should be obtained. Common testing includes serology for cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), Human T-Cell Lymphotropic Virus (HLTV) 1 and 2, Rapid Plasma Reagin/ Venereal Disease Research Laboratory (RPR/VDRL), hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Further screening and treatment may be completed based on exposure risks for latent tuberculosis, Strongyloides spp., Trypanosoma cruzi, Coccidioides spp., Histoplasma spp., and West Nile virus. Pretransplant vaccinations may reduce morbidity and mortality because of these pathogens and often include pneumococcal; seasonal influenza; combined tetanus, diphtheria, and pertussis; varicella and zoster viruses; measles, mumps, and rubella; human papillomavirus (age dependent); and hepatitis A and B.

Early Period (During the First Month)

Infections occurring during the first month after transplantation usually are related to the transplant. Complications resulting from the surgery, including prolonged ischemic time and leakage or strictures of urinary and vascular anastomoses, increase risk for superficial and deep surgical site infections with nosocomial pathogens. The most common infections after kidney transplant are urinary tract infections and can occur shortly after the procedure. Urine cultures from donor and recipient are obtained immediately before the transplantation, and typically the recipient receives a course of antibiotics directed at these pathogens guided by susceptibility testing. Other nosocomial infections, including pneumonia, central venous catheter–related infections, and Clostridium difficile infection can be seen during this time. Reactivation of herpes simplex or varicella zoster viruses (HSV or VZV) also may manifest during this early period in the absence of antiviral prophylaxis because of the effects of the stress of the transplantation and immunosuppression. Unusual donor-derived infections, including free-living amoeba, lymphocytic choriomeningitis virus (LCMV), rabies virus, and West Nile virus, have been reported during this period or shortly thereafter, and should be considered if the patient develops unexplained signs, symptoms, or laboratory findings concerning for these processes.

Middle Period (Between 1 and 6 Months)

Opportunistic infections occur commonly between months 1 and 6 after transplantation and often are caused by reactivation of latent infections. Most centers use trimethoprim-sulfamethoxazole for prophylaxis against Pneumocystis jiroveci, which also offers protection against infections resulting from Listeria spp., Nocardia spp., Toxoplasma spp., and some urinary and gastrointestinal pathogens. However, if this is not prescribed or taken, all of the aforementioned infections can be seen. Viral infections are also common, and most patients receive antiviral prophylaxis to prevent reactivation of HSV and VZV, but cytomegalovirus (CMV) infection can be problematic in at-risk patients. Other viral infections, including BK virus, adenovirus, and EBV also can occur during this time. Reactivation of tuberculosis or endemic/dimorphic fungi (Histoplasma capsulatum, Coccidioides immitis, and Blastomyces dermatitidis) also should be considered in patients with the appropriate clinical scenario and exposure.

Late (After 6 Months)

Patients who require treatment for rejection continue to be at risk for opportunistic infections while they require intensive immunosuppression. In the absence of rejection, infections occurring 6 months or more posttransplantation are, for the most part, similar to those seen in the general community. Depending on donor and recipient serostatus and duration of antiviral prophylaxis, delayed infections resulting from herpesviruses also can occur, primarily because of reactivation of latent infection in recipient or primary infection transmitted via the allograft.

Bacterial Infections

Bacterial infections account for a large proportion of posttransplant complications and include but are not limited to upper and lower urinary tract infection (UTI), bloodstream infection, pneumonia, meningitis, and deep and superficial wound infections. Because of deceased donors or pending recipients may have been hospitalized preceding donation, drug-resistant organisms (methicillin resistant staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE)) must be considered for any bacterial infection. Treatment for bacterial infections should be guided by drug penetration of the site of infection, local antibiograms, and susceptibility testing. Duration of therapy depends on source control, presence of concurrent infections (e.g., bloodstream infection), and clinical response.

Urinary Tract Infection

UTIs are the most common bacterial infection in renal transplant recipients, present in approximately one third of patients, and make up 50% to 75% of posttransplant infections. Infection can range from simple cystitis to ascending infection with renal abscess, lobar nephronia, and pyelonephritis with concurrent bloodstream infection. Recurrent infections may indicate anatomic complications or retained nidus of infection. Symptoms may be similar to those in the general population, with hematuria, dysuria, suprapubic, or low back pain. However, the allograft often is located in the pelvis; thus pain in the lower abdomen may indicate upper tract infection involving the allograft, which occurs more readily in this population because of the shortened ureter. Female gender, advanced age, preceding time on dialysis, urinary tract abnormalities (anatomic, catheter, and stent presence), cadaveric donor kidney, comorbidities such as diabetes, graft function, graft rejection, and other infections may increase the risk for posttransplant UTI.

Common bacterial urinary pathogens in RTRs include the Enterobacteriaceae flora of the recipient ( Escherichia coli, Proteus spp., Klebsiella spp.) . Pseudomonas aeruginosa and other nosocomial pathogens such as Enterococcus species are also common. Controversy remains in the literature regarding whether UTIs result in increased risk for allograft dysfunction or rejection. Asymptomatic bacteruria is common, and persistent bacteruria has been associated with allograft infection and acute rejection in some, but not all, studies. However, demonstrable reduction in symptomatic UTIs via treatment of asymptomatic bacteruria is lacking in the literature. Because of the controversies remaining in the literature, consensus on treatment of asymptomatic bacteruria has not been reached, but some transplant programs use this practice. Patients receiving TMP-SMZ for Pneumocystic jiroveci prophylaxis may have lower risk of asymptomatic bacteruria and UTI.

Bacterial Pneumonia

Bacterial pneumonia may arise from a diverse spectrum of pathogens from community and nosocomial exposures. Clinical manifestations of pneumonia may be subtler initially and require clinicians to maintain a high level of suspicion. Diagnostic workup should consist of respiratory samples (sputum, nasal swab for viral pathogens, tracheal secretions, and/or bronchoalveolar lavage [BAL]). Urine streptococcal and legionella antigens are also appropriate. Blood cultures should be drawn in the setting of sepsis to ascertain concomitant bloodstream infection and possible metastatic sites of infection, because this may alter antimicrobial choices and duration of therapy. S. aureus, Pseudomonas, and the enteric gram-negative bacilli account for the majority of cases in the nosocomial setting, and these organisms should be covered empirically in patients with pneumonia until culture data is available. S. pneumoniae is the most common community-acquired bacterial respiratory pathogen in patients greater than 6 months from transplantation, with no augmented immunosuppression for rejection. Legionella remains a potential sporadic and epidemic pathogen, and clinicians must recognize the need for atypical coverage with macrolide or quinolone. Empiric antimicrobial therapy should be based on exposure risks, antibiograms, and individual patient issues (allergies, drug interactions, comorbidities) and tailored appropriately on susceptibilities. Please refer to published guidelines for further detail.