Janis E. Blair

Coccidioidomycosis in Solid Organ Transplantation

Coccidioidomycosis is an endemic fungal infection of the southwestern United States. Normally a self-limited infection in healthy hosts, coccidioidomycosis can become a serious complication in patients who have had solid organ transplantation. Among patients whose solid organ transplantation was complicated by coccidioidomycosis, the infection has a variety of clinical presentations. Disseminated disease is common and has substantial morbidity. Patients at risk for coccidioidal infection should be identified so that antifungal prophylactic therapy can be initiated. Treatment options include amphotericin B or azoles. Secondary prophylaxis is recommended because relapse is frequent.

A randomized, prospective, double-blinded evaluation of selective bowel decontamination in liver transplantation.

Background. Bacterial infection is a frequent, morbid, and mortal complication of liver transplantation. Selective bowel decontamination (SBD) has been reported to reduce the rate of bacterial infection after liver transplantation in uncontrolled trials, but benefits of this intervention have been less clear in controlled studies. Methods. Eighty candidates for liver transplantation were randomly assigned in a double-blinded fashion to an SBD regimen consisting of gentamicin 80 mg+polymyxin E 100 mg+nystatin 2 million units (37 patients) or to nystatin alone (43 patients). Both treatments were administered orally in 10 ml (increasing to 20 ml, according to predefined criteria), four times daily, through day 21 after transplantation. Anal fecal swab cultures were performed on days 0, 4, 7, and 21. Rates of infection, death, and charges for medical care were assessed from day 0 through day 60. Results. More than 85% of patients in both treatment groups began study treatment more than 3 days before transplantation. Rates of infection (32.4 vs. 27.9%), death (5.4 vs. 4.7%), or charges for medical care (median

Bacterial, mycobacterial, and protozoal infections after liver transplantation-Part I

194,000 vs.

Voriconazole Use for Endemic Fungal Infections

163,000) were not reduced in patients assigned to SBD. On days 0, 4, 7, and 21, growth of aerobic gram-negative flora in fecal cultures of patients assigned to SBD was significantly less than that of patients taking nystatin alone; growth of aerobic gram-positive flora, anaerobes, and yeast was not significantly different. Conclusion. Routine use of SBD in patients undergoing liver transplantation is not associated with significant benefit.

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis

Infection is one of the leading causes of morbidity and mortality in liver transplant recipients. More than two-thirds of liver transplant recipients have infection in the first year after transplantation, and infection is the leading cause of death in these patients.1 In addition, release of cytokines during the infection may have other indirect and negative effects, including allograft injury, opportunistic superinfection, and malignancy.1 The risk of infection in liver transplant recipients is determined by the intensity of exposure to infectious agents (hospital or community sources) and the overall immunosuppression level. This “net state of immunosuppression”2 is influenced by the dose, duration, sequence, and choice of immunosuppressive medications, underlying immune deficiencies, the presence of neutropenia or lymphopenia, mucocutaneous barrier integrity, the presence of necrotic tissue, ischemia or fluid collection, metabolic conditions such as diabetes mellitus, and the activity of immunomodulating viruses.2 After solid organ transplantation, there are 3 time periods when specific infections are likely to occur. The patient’s susceptibility to infection during these periods is strongly influenced by surgical factors, the level of immunosuppression and environmental exposure, and the dose, duration, and types of prophylaxis.3,4 Figure 1 depicts an infection time line of typical organisms after solid organ transplantation. During the first period, the month immediately after transplantation, most infections are related to technical or surgical issues and complications. Exposure to infectious agents through prolonged hospitalization before transplantation or during postoperative care may also result in infection. Bacterial and candidal wound infections, urinary infections, catheter-related infections, pneumonias, and Clostridium difficile colitis predominate during this period, and the etiologic organisms are similar to hospital-acquired infections common in other surgical patients.4,5 Although its incidence has markedly diminished with prophylaxis, reactivated human herpesvirus 1 (herpes simplex virus) is also a common viral illness in this time frame. The next period encompasses the second through sixth posttransplant months. During this time, infections from opportunistic organisms predominate as a result of cumulative immunosuppression. Typical infectious organisms of this period include cytomegalovirus, Pneumocystis jiroveci, and Aspergillus species. Other viruses (human herpesvirus 6, hepatitis B and C, human herpesvirus 3 [varicella-zoster virus], and others), fungi (Cryptococcus, Histoplasma, and Coccidioides species), and bacteria (Nocardia species, Listeria species, or Mycobacterium tuberculosis) may also be seen.4 From approximately the seventh to 12th posttransplant months and beyond, most recipients acquire infections such as influenza, urinary tract infections, and community-acquired pneumonias, which are similar to the infections acquired by patients who have not received transplants.4,6,7 Reactivation of human herpesvirus 3 may manifest as herpes zoster, and although it is uncommon, cytomegalovirus infections can occur. Three notable scenarios may enhance patient susceptibility to opportunistic infections, including (1) acute organ rejection necessitating increased immunosuppression therapy, (2) retransplantation, which “restarts” the immunosuppression and infection time line, and (3) chronic viral infections such as human immunodeficiency virus or hepatitis B or C.4 Kusne et al.8 studied 101 consecutive liver transplantation patients for 1 year or longer. The patients received antibiotics for wound prophylaxis for 5 days and nystatin for antifungal prophylaxis for 30 days. No prophylaxis was administered for pneumocystic or viral infections. Figure 2 shows the timing of all severe infections and separately profiles the rates of bacterial, fungal, viral, and protozoal infections. The majority of infections occurred within 6 months of transplantation. Abbreviations: OLT, orthotopic liver transplantation; VRE, vancomycin-resistant enterococci. From the Division of Infectious Diseases, Mayo Clinic, Scottsdale, AZ. Received September 7, 2005; accepted September 13, 2005. Address reprint requests to: Janis E. Blair, MD, Division of Infectious Diseases, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ 85259. Copyright

Facilitated peer mentorship: a pilot program for academic advancement of female medical faculty.

ABSTRACT In a retrospective review of 24 patients with histoplasmosis, blastomycosis, or coccidioidomycosis treated with voriconazole (most for salvage therapy), the outcome was favorable (improved or stable) for 22 (95.8%) within 2 months of starting voriconazole and for 20 (83.3%) at the last follow-up. Prospective studies are required to determine its role in the treatment of endemic mycoses.

Donor-Derived Fungal Infections in Organ Transplant Recipients: Guidelines of the American Society of Transplantation, Infectious Diseases Community of Practice†

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patients individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

Viral and fungal infections after liver transplantation — Part II

BACKGROUND In the United States, female physicians working in academic medical practices are less likely to achieve the academic rank of associate professor or professor than are male physicians of comparable seniority. Lack of mentoring has been suggested as a possible contributor to this difference. METHODS In this paper, we describe a facilitated peer mentorship pilot program that was developed to meet the unique needs of women faculty. Experienced female physicians acted as facilitators to a group of junior women who served as their own peer mentors. Outcome measures for the program included comparison of a pretest and a posttest completed by the peer mentor participants, a skills acquisition survey, published papers, and academic advancement of participants. RESULTS All the peer participants realized increased academic activity in the form of published papers and promotion in academic rank, skills acquisition, and enthusiasm for continuance of the program. CONCLUSIONS This new model of facilitated peer mentorship demonstrated success in a small-scale pilot program. Expansion of this program and other creative solutions to the lack of mentoring for women may result in greater numbers of women achieving academic advancement.

Treatment of Refractory Coccidioidomycosis With Voriconazole or Posaconazole

Donor‐derived fungal infections can be associated with serious complications in transplant recipients. Most cases of donor‐derived candidiasis have occurred in kidney transplant recipients in whom contaminated preservation fluid is a commonly proposed source. Donors with cryptococcal disease, including those with unrecognized cryptococcal meningoencephalitis may transmit the infection with the allograft. Active histoplasmosis or undiagnosed and presumably asymptomatic infection in the donor that had not resolved by the time of death can result in donor‐derived histoplasmosis in the recipient. Potential donors from an endemic area with either active or occult infection can also transmit coccidioidomycosis. Rare instances of aspergillosis and other mycoses, including agents of mucormycosis may also be transmitted from infected donors. Appropriate diagnostic evaluation and prompt initiation of appropriate antifungal therapy are warranted if donor‐derived fungal infections are a consideration. This document discusses the characteristics, evaluation and approach to the management of donor‐derived fungal infections in organ transplant recipients.

Coccidioidomycosis After Renal Transplantation in an Endemic Area

Viral and fungal infections in liver transplant recipients are important to recognize and treat early because of their association with substantial morbidity and mortality. Some viruses, such as cytomegalovirus and human herpesvirus 6, have immunomodulatory properties and can facilitate other infections, including fungal infections. Cytomegalovirus has long been recognized as an important virus in transplantation, but in the past decade other viruses have also received attention in the medical literature because of their association with particular clinical syndromes. Although human herpesvirus 6 has been associated with fever, rash, and encephalitis, a direct cause‐and‐effect relationship is still lacking. Human herpesvirus 8 has been found to be the cause of Kaposi sarcoma. Molecular techniques (e.g., pp65 antigenemia and polymerase chain reaction) that have been introduced for routine diagnosis of viruses have facilitated the diagnosis of asymptomatic viral infections and the institution of preemptive therapy. Nonetheless, the diagnosis of invasive fungal infections in liver transplant recipients is often delayed and thus associated with high mortality. Despite the use of new antifungal agents in clinical practice and the reduced incidence of fungal infections because of antifungal prophylaxis regimens, mortality has not decreased. Future patient outcomes may improve with early identification of patients who have risk factors for invasive fungal infections and with the development of new molecular diagnostic techniques for early detection. Liver Transpl 12:2–11, 2006.