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To evaluate whether mediastinitis/deep sternal wound infection (Med/DSWI) is more common in ventricular assist device (VAD) with delayed sternal closure (DSC) compared to VAD with primary sternal closure (PSC).A literature search was done over the last four decades for studies that addressed this comparison.Two studies met our inclusion criteria, and their results are contradictory. The first study compared 184 VAD recipients with PSC to 180 VAD recipients with DSC. There was no difference in VAD-related infections between DSC and PSC (15% vs. 16%, respectively; odds ratio = 0.965, 95% confidence interval [CI] = 0.525-1.635). The second study compared 464 VAD recipients with PSC to 94 VAD recipients with DSC. The rate of surgical site infection was higher in the DSC patients (12.5% vs. 1.4%, respectively; odds ratio = 10.1; 95% CI = 3.8-27.0). DSC was identified as an independent risk factor for postoperative mortality, but no detailed infection information was given.There is no clear evidence of the association between DSC, compared to PSC, and Med/DSWI. Therefore, DSC is not an absolute indication for extended systemic antibiotic prophylaxis. The decision to extend the duration of systemic antibiotic prophylaxis should be made on a case-by-case basis, in collaboration with an infectious disease specialist.

Background Tenosynovitis is an uncommon manifestation of disseminated infection with Coccidioides fungal species. Most experts treat this infection with combined surgical debridement and antifungal medication. The aim of our study was to examine the outcomes of patients with coccidioidal tenosynovitis of the hand and wrist. Methods We retrospectively searched for the records of patients with coccidioidal tenosynovitis of the hand and wrist at our institution. between 1987 and 2013. We also conducted a review of the literature from 1950 to 2014 to identify additional cases. Results We identified 9 cases of coccidioidal tenosynovitis of the hand and wrist at our institution, along with 5 other cases found in a review of the literature. The relapse rate was high overall (50%) and was higher after discontinuation of antifungal therapy (71%) in both immunocompromised and immunocompetent patients. Results of serologic testing were not predictive of relapse. Conclusions A treatment strategy for coccidioidal tenosynovitis should focus on long-term administration of antifungal agents.

Breast fungal infections are rare in nonlactating women. The present report is the first to describe a necrotizing cutaneous breast fungal infection. A 50-year-old woman with a remote history of breast cancer and autologous tissue reconstruction presented with a progressive cutaneous necrotic infection one year after implant augmentation of the reconstruction. Multiple eschars developed on the left breast, and pathological examination of debrided tissue revealed numerous fungal hyphae invading the epidermis, dermis and adipose tissue of the breast. Fungal cultures yielded Bipolaris species. She was treated with voriconazole. Five months later, the patient presented with an eschar on her back, indicative of disseminated disease. Bipolaris species are dematiaceous fungi; cutaneous or disseminated infections with Bipolaris species have rarely been reported in immunocompetent patients. Unresectable or recurrent lesions should be treated with antifun-gals. Cutaneous necrotizing breast fungal infections should be considered in patients who do not respond to antibacterial therapy.

Summary As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995–2003) and E2, (2004–2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while ‘other’ dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival.

Convalescence is prolonged, regardless of whether the patient receives treatment., In Arizona, USA, primary pulmonary coccidioidomycosis accounts for 15%–29% of community-acquired pneumonia. To determine the evolution of symptoms and changes in laboratory values for patients with mild to moderate coccidioidomycosis during 2010–2012, we conducted a prospective 24-week study of patients with primary pulmonary coccidioidomycosis. Of the 36 patients, 16 (44%) were men and 33 (92%) were White. Median age was 53 years, and 20 (56%) had received antifungal treatment at baseline. Symptom scores were higher for patients who received treatment than for those who did not. Median times from symptom onset to 50% reduction and to complete resolution for patients in treatment and nontreatment groups were 9.9 and 9.1 weeks, and 18.7 and 17.8 weeks, respectively. Median times to full return to work were 8.4 and 5.7 weeks, respectively. One patient who received treatment experienced disseminated infection. For otherwise healthy adults with acute coccidioidomycosis, convalescence was prolonged, regardless of whether they received antifungal treatment.

Discrete nodules developed on the leg of a 27-year-old immunosuppressed woman after an allogeneic stem cell transplant. Biopsy and culture grew Legionella pneumophila serogroup 8. On day 7 of azithromycin treatment, respiratory distress and abnormal liver transaminases developed, and the patient died on day 14. Review of the medical literature identified 19 reports of Legionella species-associated skin or soft tissue infections (total of 20 patients, 13 with confirmed infection). Manifestations of the 13 confirmed cases included erythematous macular rash (n = 7), erythema after thoracentesis (n = 1), abscess formation (n = 4), respiratory symptoms (n = 6), and abnormal chest radiographs (n = 8). Six required surgical exploration and débridement, and 7 were immunocompromised. Rash and respiratory infection improved with antibiotics in 10, but 3 died. Immunosuppression may predispose transplant recipients to Legionella infections. Diagnostic biopsies may facilitate appropriate treatment.

In endemic regions, coccidioidomycosis causes substantial morbidity and mortality for patients receiving solid organ transplants. We aimed to demonstrate the effect of antifungal coccidioidal prophylaxis in heart transplant (HT) recipients. We retrospectively reviewed the electronic health records of all patients who received HTs between October 19, 2005, and December 13, 2014. We collected information regarding antifungal regimens and determined whether patients subsequently developed infections. Our 174-person cohort all received antifungal prophylaxis for at least 6 months (mean follow-up, 53.8 months). One proven and one probable coccidioidal infection (each, 0.6%) occurred during the study period. The incidence of coccidioidomycosis was 0.6% at 1 year and 2.3% at 5 years. No cases of proven coccidioidomycosis occurred within 2 years after transplantation. No patients developed disseminated disease, and no sentinel events were attributed to coccidioidomycosis. Both fluconazole and voriconazole were well tolerated. In the absence of intolerance or contraindication, we suggest continuing a universal antifungal prophylactic regimen with fluconazole for at least 6-12 months in HT recipients residing in a coccidioidomycosis-endemic area. This article is protected by copyright. All rights reserved.

Background. Infection is a serious complication of left ventricular assist device (LVAD) therapy. Published data regarding LVAD-associated infections (LVADIs) are limited by single-center experiences and use of nonstandardized definitions. Methods. We retrospectively reviewed 247 patients who underwent continuous-flow LVAD implantation from January 2005 to December 2011 at Mayo Clinic campuses in Minnesota, Arizona, and Florida. LVADIs were defined using the International Society for Heart and Lung Transplantation criteria. Results. We identified 101 episodes of LVADI in 78 patients (32%) from this cohort. Mean age (± standard deviation [SD]) was 57±15 years. The majority (94%) underwent Heartmate II implantation, with 62% LVADs placed as destination therapy. The most common type of LVADIs were driveline infections (47%), followed by bloodstream infections (24% VAD related, and 22% non-VAD related). The most common causative pathogens included gram-positive cocci (45%), predominantly staphylococci, and nosocomial gram-negative bacilli (27%). Almost half (42%) of the patients were managed by chronic suppressive antimicrobial therapy. While 14% of the patients had intraoperative debridement, only 3 underwent complete LVAD removal. The average duration (±SD) of LVAD support was 1.5±1.0 years. At year 2 of follow-up, the cumulative incidence of all-cause mortality was estimated to be 43%. Conclusion. Clinical manifestations of LVADI vary on the basis of the type of infection and the causative pathogen. Mortality remained high despite combined medical and surgical intervention and chronic suppressive antimicrobial therapy. Based on clinical experiences, a management algorithm for LVADI is proposed to assist in the decision-making process.

Summary Objective Primary pulmonary coccidioidomycosis can often be associated with hypersensitivity symptoms treatable with a short course of palliative corticosteroids. Long-term use of corticosteroids is a known risk factor for severe or disseminated infection but the effects of short-term use are not known. Methods A retrospective review was conducted of immunocompetent patients with acute pulmonary coccidioidomycosis who received systemic corticosteroids for relief of coccidioidal-related symptoms. Age- and sex-matched controls were also reviewed. Predetermined end-points were assessed. Results Seventy-four patients met inclusion criteria for the corticosteroid-treated group, and 74 controls were identified. Cumulative corticosteroid (prednisone-equivalent) doses were 10 mg→3,600 mg (mean = 206 mg; median = 120 mg). Corticosteroids were prescribed most commonly for rash 43/74 [58%] or asthma/wheezing/cough 30/74 [41%]. Coccidioidal-related hospitalization occurred in 19 patients in the corticosteroid group vs. 22 in the control group ( P = .58). Coccidioidal-related symptoms resolved within a mean of 19 weeks (median = 8 weeks [range = 2–208 weeks]) vs. 32.3 weeks (median = 8 weeks [range = 1–1040 weeks]) in the corticosteroid and control groups ( P = .38). Relapse of symptoms occurred in 12% of both groups ( P > .99). Extrapulmonary dissemination occurred in 3% vs. 4.0% ( P > .99) in the corticosteroid and control groups, respectively. Conclusion This study found no adverse effects of short-term corticosteroid therapy for early symptomatic treatment in acute pulmonary coccidioidomycosis.

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

Coccidioidomycosis is a common infection in the desert southwestern USA; approximately 3 % of healthy persons in Arizona alone become infected annually. Coccidioidomycosis may be severe in immunocompromised persons, but experience among patients with solid organ cancer has not been fully described. Therefore, we aimed to describe the clinical courses of patients whose cancers were complicated by coccidioidomycosis at our institution, which is located in an area with endemic Coccidioides. To do so, we conducted a retrospective review from January 1, 2000, through December 31, 2014, of all patients with breast, colorectal, or ovarian cancer whose cancer courses were complicated by coccidioidomycosis. We identified 17,576 cancer patients; 14 (0.08 %) of these patients met criteria for proven or probable coccidioidomycosis diagnosed within the first 2 years after the cancer diagnosis. All of these patients had primary pulmonary coccidioidomycosis, none had relapsed prior infection, and 1 had possible extrapulmonary dissemination. Five had active coccidioidal infection during chemotherapy, 1 of whom was hospitalized for coccidioidal pneumonia. All were treated with fluconazole, and all improved clinically. Eleven did not require prolonged courses of fluconazole. There were no clearly demonstrated episodes of relapsed infection. In conclusion, coccidioidomycosis was not a common complication of breast, colorectal, or ovarian cancers in patients treated at our institution, and it was not commonly complicated by severe or disseminated infection.

Summary Objectives To describe the demographics, clinical manifestations, treatment, and outcomes of patients with pulmonary alveolar proteinosis (PAP) who developed an opportunistic infection with Nocardia spp., mycobacteria or fungal pathogens. Methods A case of PAP and Nocardia spp. brain abscess is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of PAP and opportunistic infections between 1950 and July, 2010. Results Seventy five cases were reviewed. Thirty two patients (43%) had nocardial infection, 28 (37%) mycobacterial infection, and 15 (20%) fungal infection. Thirty nine patients (65%) were male. Seventeen patients (23%) were immunosuppressed. Twenty patients (27%) were active smokers. PAP was the initial diagnosis in 19 patients (33%), while infection presented first in 23 patients (40%); 16 patients (27%) had a concurrent diagnosis of PAP and infection. The average interval between PAP diagnosis and an opportunistic infection was 16 months. Lungs were the most common site of infection; extra-pulmonary infection was present in 27 patients (32%). Thirty nine patients (57%) survived through the follow-up period, while 31 died. Conclusions Opportunistic infections can either precede or follow a diagnosis of PAP. PAP should be considered in apparently immunocompetent patients who present with an opportunistic infection and diffuse alveolar infiltrates.

Coccidioidomycosis results from infection with Coccidioides species endemic to the southwestern United States. The mobile US population has resulted in incremental cases being found throughout the world. The fungal infection can result in pulmonary sequelae, including nodules, cavities, and complications requiring treatment by the thoracic surgeon.A retrospective chart review was conducted of 1,496 patients with coccidioidomycosis treated at our institution (January 1998 to December 2008) to identify those requiring surgery.Of the 1,496 patients, 86 (6%; mean age, 58 years [range, 18 to 81], 48 women) underwent operations. Radiographs revealed 59 nodules, 18 cavities, 2 infiltrates, and 7 complications of disease (e.g., effusion, pneumothorax, and empyema). Of the 86 patients, 40% underwent resection for persistent symptoms or disease progression despite adequate antifungal therapy. One third of the operations were performed by video-assisted thoracoscopic surgery. Morbidity, 21% (18 patients), and in-hospital mortality, 2% (2 patients), were greater after resection for cavitary lesions with resultant complications versus for nodular disease: 41% versus 12% (por = 0.002) and 8% versus 0% (p0.005). Prolonged air leaks or bronchopleural fistulas were the most common complications (13 patients). Postoperative antifungal therapy was administered to 42% of patients (89% of cavitary and complicated). There were no cases of recurrence at follow-up (mean, 24 months).Surgical intervention was indicated for only a few patients, most commonly for diagnostic dilemmas involving nodular disease, symptomatic nonresponsive cavitary disease, or complications. Prolonged air leaks were the main cause of morbidity. Resection should result in symptom resolution and long-term freedom from recurrence.

BACKGROUND Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. METHODS In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. RESULTS Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P < .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. CONCLUSIONS The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

The number of cases of tuberculosis (TB) in the United States declined by 45% between 1993 and 2006. This decline occurred disproportionately among United States–born persons (66%) compared to foreign-born individuals, among whom the number of cases actually increased by 5%. In solid-organ transplant recipients, the incidence of Mycobacterium tuberculosis (MTB) infection worldwide ranges between 0.35% and 15%, depending on the level of endemicity. This rate can be 36to 74-fold greater than that in the general population. The majority of MTB cases after transplantation represent reactivation of latent tuberculosis infection (LTBI), although acquisition of primary TB infection posttransplant and transmission of MTB via the transplanted organ are infrequent possibilities. Active TB in the posttransplantation setting can pose a number of challenges: atypical presentation leading to a delay in diagnosis, therapy associated with drug interactions and toxicities, graft rejection, and formidable morbidity and mortality. This is of particular concern in both patients with end-stage liver disease awaiting liver transplantation and liver transplant recipients, given the hepatotoxicity of several anti-TB medications and their associated drug interactions with immunosuppressants. In this issue of Liver Transplantation, Holty et al. present a systematic review and meta-analysis of TB in liver transplant recipients. They included cases of active MTB infection following liver transplantation as well as transplant candidates or recipients who received 6 months of therapy for LTBI prior to transplantation. The prevalence of active TB in liver transplant recipients was 1.3%. Extrapulmonary infection was seen in 67%, multiorgan involvement was seen in 27%, and 31% died. Tuberculin skin test (TST) results were as follows: a) Among 38 cases of posttransplant active TB with known pretransplant TST status, 37% were TST-positive, 53% were negative, and 11% were anergic; among 17 of these patients who had a posttransplant TST, only 35% were positive. b) In 3 studies with 2972 patients who underwent liver transplantation, 31% of the patients had a pretransplant TST, and 13% of these were positive. None of the TST-positive patients who received isoniazid therapy for at least 6 months developed active TB, whereas 7 TST-positive patients developed active disease without such therapy (mean follow-up, 54 months). Short-term mortality in patients with active posttransplant TB was 31%, with 65% of deaths directly attributed to MTB infection. Because reactivation of LTBI represents the majority of posttransplant cases of active TB, it is prudent to screen and identify such patients before transplantation for consideration of appropriate therapy for LTBI. Until recently, TST was the only test available for LTBI diagnosis. As noted previously, TST was notoriously insensitive: 64% of patients with posttransplant active TB were either TST-negative or anergic prior to transplantation, and 65% of patients had a negative posttransplant TST in the setting of active TB. TST has

Background. Coccidioidomycosis is an endemic fungal infection of the southwestern United States that causes considerable morbidity and mortality in transplant recipients, often as the result of reactivated infection. Methods. A retrospective review of the medical records of 47 patients with prior coccidioidomycosis who underwent solid organ transplantation (18 liver, 24 kidney, 3 pancreas, and 2 combined organ) at our tertiary care academic medical center. Results. Of 47 transplant recipients with a history of coccidioidomycosis, 44 had quiescent infection at transplantation. Of the three with active coccidioidomycosis at transplantation, two were taking azole prophylaxis and had no further coccidioidal infection after transplantation. One of the three had positive serologic findings identified only on the day of transplantation, and prophylaxis was initiated a few hours after surgery along with immunosuppression; nevertheless, the treatment course was complicated by disseminated coccidioidomycosis. Seven patients did not initiate or self-discontinued prophylaxis; one patient who discontinued prophylaxis experienced recurrent pulmonary infection. Conclusions. For patients undergoing transplantation in an area endemic for coccidioidomycosis, we recommend routine evaluation for evidence of prior infection and initiation of azole prophylaxis. For our patients with quiescent infection, azoles suppressed any recrudescent coccidioidomycosis after transplantation. The selection of patients who would benefit from prophylaxis and the optimal dose and duration of such prophylaxis should be studied further.

Zygomycetes are ubiquitous fungi that can cause invasive disease associated with high mortality. We report 10 solid organ transplant recipients with zygomycosis (incidence 2 per 1000) and reviewed 106 cases in the English-language literature. These included renal (n = 73), heart (n = 16), lung (n = 4), heart/lung (n = 2), liver (n = 19) and kidney/pancreas (n = 2) transplant recipients. All patients were receiving immunosuppression and the vast majority steroids. The clinical presentation included rhino-sino-orbital (n = 20), rhinocerebral (n = 16), pulmonary (n = 28), gastrointestinal (n = 13), cutaneous (n = 18), renal (n = 6) and disseminated disease (n = 15). Most frequently isolated genera were Rhizopus (73%) followed by Mucor (13%). The overall mortality was 49%. While rhino-sino-orbital disease had the best prognosis, rhinocerebral disease had high mortality (93%) comparable to disseminated disease. A favorable outcome was associated with limited, surgically accessible disease and early surgical intervention along with amphotericin B administration.

JC virus (JCV), BK virus (BKV) and simian virus 40 (SV40) are deoxyribonucleic acid (DNA) viruses, members of the family Polyomaviridae. These viruses establish persistent infections, and reactivate from latency in their host under immunosuppression. During the last few years there has been recognition of the morbidity related to polyomaviruses, particularly BKV in kidney transplant recipients. More importantly, recent studies indicate the potential implication of JCV, BKV, and SV40 in renal dysfunction among nonrenal organ transplant patients. Polyomaviruses are tumor-inducing viruses and animal models have provided evidence of the oncogenicity of these pathogens. Although data are not conclusive, molecular studies suggest an association of BKV and SV40 with malignancies among solid organ transplant patients. As new and potent immunosuppressive agents are introduced into clinical practice, it is believed that the incidence of polyomavirus-related diseases in organ transplantation might increase. This review evaluates the biologic and epidemiologic features of these 3 viruses, the data regarding their infections in nonkidney organ transplant patients and describes future directions in the management and research of these opportunistic pathogens. Liver Transpl 12:1457-1463, 2006. © 2006 AASLD.

Serious infection due to strains of Pseudomonas aeruginosa that exhibit resistance to all common antipseudomonal antimicrobials increasingly is a serious problem. Colistin was used as salvage therapy for 23 critically ill patients with multidrug-resistant P. aeruginosa infection. Twenty-two patients who had septic shock (n=14) and/or renal failure (n=21) received mechanical ventilatory support at baseline. The most common types of infection were pneumonia (n=18) and intra-abdominal infection (n=5). Colistin was administered for a median of 17 days (range, 7-36 days). Seven patients died during therapy, at a median of 17 days (range, 4-26 days) after initiation of treatment. A favorable clinical response was observed in 14 patients (61%); only 3 patients experienced relapse. Bacteremia was the only significant factor associated with treatment failure (P=.02). One patient manifested diffuse weakness that resolved after temporary cessation of colistin therapy. Colistin provides an important salvage therapeutic option for patients with otherwise untreatable serious P. aeruginosa infection.

Clostridium innocuum is a relatively antimicrobial resistant, frequently misidentified anaerobe that has only rarely been associated with bacteremia. A 38-year-old female with chronic hepatitis C underwent a second kidney transplant operation. Two weeks after surgery a computed tomography scan of the abdomen showed a heterogeneous hematoma with pockets of gas adjacent to the allograft, which extended into the pelvis and left abdominal wall, associated with low-grade fever. An anaerobic blood culture grew a Clostridium initially identified as C. subterminale and later re-identified as C. innocuum. At abdominal exploration liquefied blood was evacuated, and the patient completed a course of antibiotics and recovered. C. innocuum should be considered as a cause of gas-producing anaerobic infection in transplant patients. Because C. innocuum is frequently misidentified by the use of commercial anaerobic identification kits, its true incidence in serious infections is likely underestimated.

Invasive aspergillosis (IA) in liver transplant recipients is associated with poor response rates and a very high mortality rate, despite administration of therapy with conventional amphotericin B. We conducted a single-center, retrospective study to compare the outcome of liver transplant recipients with IA who received amphotericin B lipid complex (ABLC) or conventional amphotericin B. IA was present in 12 ABLC-treated patients (definite, 4; probable, 8) and 29 amphotericin B recipients (definite, 11; probable, 18) in the historical cohort. The 60-day mortality rate was lower in the ABLC cohort: 4 (33%) of 12 patients versus 24 (83%) of 29 patients (P=.006). Only 1 of 4 ABLC recipients with definite IA died, compared with all 11 in the amphotericin B group. Sixty-day survival probability curves was significantly lower in the amphotericin B cohort (P=.008). ABLC therapy was the only independent mortality-protective variable (odds ratio, 0.31; 95% confidence interval, 0.07-0.44; P=.02). First-line or early salvage therapy for IA with ABLC was associated with significantly improved survival relative to a comparable historical group treated with amphotericin B.

To discern whether the characteristics and outcome of invasive aspergillosis in liver transplant recipients have evolved during the past decade, 26 patients who underwent transplantation during 1990-1995 (known as "the earlier cohort") were compared with 20 patients who underwent transplantation during 1998-2001 (known as "the later cohort"). Twenty-three percent of the Aspergillus infections in the earlier cohort occurredor =90 days after transplantation, compared with 55% of such infections in the later cohort (P=.026). The earlier cohort was significantly more likely to have disseminated infection (P=.034) and central nervous system (CNS) involvement (P=.0004) than was the later cohort. The mortality rate was significantly higher for the earlier cohort (92%) than for the later cohort (60%; P=.012). Only disseminated infection (not the year of transplantation) approached statistical significance as an independent predictor of outcome. In the current era, invasive aspergillosis occurs later in the posttransplantation period, is less likely to be associated with CNS infection, and is associated with a lower mortality rate, compared with invasive aspergillosis in the early 1990s.

(Sca) is a ubiquitous filamentous fungus capable of causing invasive disease. We reviewed our electronic microbiology records and the English-language literature. Between 1976 and December 1999 we identified 23 solid organ transplant recipients with Sca infection, 7 of which occurred between December 1987 and December 1999 at our institution. Overall incidence was 1 per 1,000 patients, with a trend of higher incidence in patients receiving lung transplants compared with other transplant organs (p = 0.06). The 23 patients included liver (4), kidney (8), heart (8), lung (2), and heart/lung (1) recipients. Male to female ratio was 19:4, and the mean age was 46 +/- 12 (SD) years. Fungal infection was diagnosed at a median of 4 months (range, 0.4-156 mo) after transplant. The clinical presentation included disseminated disease ( 8), skin lesions (3), lung disease (5), endophthalmitis (1), meningitis (1), brain abscess with or without extension to eye (3), fungal mycotic aneurysm (1), and sinusitis (1). Seven (30%) patients had intravascular infection, and 11 (48%) patients had central nervous system involvement. Antifungal therapy was accompanied by surgical debridement in 9 cases. Three additional patients were found to have airway colonization only and received itraconazole prophylaxis, without evidence of disease. Of 22 patients with known outcome, 16 (72.7%) died. Five of 6 patients who survived had localized infections: skin lesions (n = 3), sinus fungus ball (n = 1), and solitary lung nodule (n = 1). All patients with disseminated disease and 10 of 11 patients with central nervous system disease died. An exception was 1 patient with a brain abscess, successfully treated with voriconazole and surgical drainage. Sca infection is rare but is associated with high mortality. Early diagnosis by culture is important because Sca is resistant to amphotericin B, routinely used in the empiric therapy of invasive fungal infections. Treatment with the combination of an antifungal and surgery may have a better outcome. Voriconazole promises to be an effective antifungal agent. Cultures positive for Sca should not be ignored, and long-term antifungal prophylaxis in candidates and transplant recipients should be considered.

A 52-year-old-white male underwent double lung transplantation for severe emphysema due to alpha-1-antitrypsin deficiency and heavy tobacco use. Following a postoperative course complicated by renal insufficiency, pulmonary emboli, and Clostridium difficile colitis, he was discharged in stable condition. Two months later, he was admitted to a local hospital with a fever, abdominal pain, diarrhea, nausea, and dyspnea. Computerized tomography (CT) of the chest revealed bilateral pleural effusions. Sigmoidoscopy was grossly normal but biopsy demonstrated cytomegalovirus (CMV) colitis, and the patient was placed on intravenous ganciclovir. Over the next week, he became progressively hypoxemic and was transferred to the University of Pittsburgh Medical Center (post-transplant day 81) for further evaluation. His medications on transfer included: ganciclovir, prednisone, tacrolimus, dapsone, fluconazole, ondansetron, lansoprazole, digoxin, and coumadin.

1. Recurrent and de novo malignancies are the second leading causes of late death in liver transplant recipients, following age-related cardiovascular complications. 2. The increased incidence of de novo malignancies in liver transplant recipients compared with the general population reflects their demographic makeup, known preexistent risk factors for cancer, greater rate of chronic viral infection, and actions of exogenous immunosuppression. 3. The greatest incidence of de novo malignancies is seen in cancers associated with chronic viral infections, such as Epstein-Barr virus-associated posttransplant lymphoproliferative disease, and skin cancers, including squamous cell carcinoma and Kaposi's sarcoma. 4. Although a greater incidence of such malignancies as oropharyngeal malignancy and colorectal cancer was noted, there did not appear to be an increased risk for liver transplant recipients matched for age, sex, and length of follow-up using modified life-table technique and Surveillance Epidemiology End Result data with a similar at-risk group. However, they may present with more advanced stages of disease. 5. An increased incidence of de novo cancers in chronically immunocompromised liver transplant recipients demands careful long-term screening protocols to help facilitate diagnosis at an earlier stage of disease.

The aim of this study was to review the characteristics and outcome of 21 patients with invasive mucormycosis treated with amphotericin B colloidal dispersion (ABCD) in five phase I and phase II studies. Mucormycosis is an increasing concern in immunocompromised patients, in whom mortality exceeds 60%. The standard treatment has been amphotericin B combined with surgical debridement. Twenty-one patients with invasive mucormycosis treated with ABCD, a lipid complex of amphotericin B and cholesteryl sulfate, were identified. Patients were given ABCD on the basis of pre-existing renal insufficiency, development of nephrotoxicity during amphotericin B therapy, or fungal infection that failed to respond to amphotericin B. Response could be evaluated in 20 patients, all of whom had bone marrow or organ transplantation, haematologic malignancies, or diabetes. Infection was disseminated in six patients and localised to the sinuses, lower respiratory tract, or skin in the other patients. ABCD was given at a mean dose of 4.8 mg/kg per infusion for a mean duration of 37 days. Twelve of 20 patients responded to ABCD therapy. Response rates were similar when patients were treated with ABCD alone (4/7) and ABCD combined with surgery (8/13), with more complete response obtained in the latter group. No difference in response rate was observed in leukaemic patients (3/5) or transplant recipients (6/10) compared to diabetics (3/5). No renal or hepatic toxicity was observed. These results compare favourably with the results of standard treatment and suggest that ABCD combined with surgery may be a useful therapy in patients with mucormycosis.

Background . Ventricular assist devices (VAD) are currently approved for use as a bridge for transplantation. Although reports have suggested acceptable rates of survival of patients with VAD, there is little information regarding the mechanism and etiology of bacteremia in these patients. Methods . We prospectively followed patients who underwent VAD implantation and developed bacteremia during VAD support at the University of Pittsburgh Medical Center. Relapsing bacteremia was defined as at least two episodes of positive blood cultures with a genetically related organism on 2 different days. Species identification and susceptibility testing were performed on all isolates. Pulse field gel electrophoresis was performed on selected blood and VAD isolates. Results . Between January 1998 and August 1999, 3 patients with VAD developed relapsing bacteremia, which was treated with full courses of antibiotic agents, 2 of whom also developed VAD endocarditis. All 3 patients had documented driveline or device pocket infections with these isolates. Consecutive blood and VAD isolates were found to be genetically related within each patient. Conclusions . These patients with bacteremia after VAD implantation had relapse due to the same strain, which may have originated from indolent driveline infection. Endovascular infection in this setting is difficult to eradicate with antibiotic agents and carries a high mortality. These patients should be considered to have priority for orthotopic heart transplantation.

Background. The aim of the study was to assess the incidence of cytomegalovirus (CMV) infection and disease in adult liver transplant recipients, using routine preemptive therapy guided by the pp65 antigenemia test. Methods. Antigenemia was monitored weekly after liver transplantation (OLTX) for the first 3 months, and once a month for another 3 months. CMV seronegative recipients were treated preemptively for the first positive antigenemia. Seropositive recipients were treated only when their antigenemia count reached a threshold of ≥100 positive cells per 200,000 leukocytes. Results. A total of 144 patients were included between June 1994 and April 1995, of which 137 (95%) were primary OLTX. The percentage of positive antigenemia and CMV disease was 55 and 8%, respectively. Seventy-eight (54%) patients were protocol-monitored for the entire follow-up (group 1) and received appropriate preemptive therapy, although 66 (46%) patients had protocol violation by having missed blood samples or blood drawn at unscheduled times (group 2). Using Cox's proportional hazards model, patients with a first antigenemia count of >11 leukocytes had a significantly higher rate of CMV disease compared to patients with an antigenemia count ≤11 leukocytes (RR=7.3, 95% confidence interval=2.2 to 24.5). In a multivariate Cox regression analysis, adjustments were made to control for: group 1 versus group 2, use of OKT3, and serology risk categories. This analysis showed that the relative rate of CMV disease was still significantly higher among patients with antigenemia count >11 leukocytes (adjusted RR=4.9, 95% confidence interval=1.3 to 18.1). The estimated cost of preemptive therapy was less than that of prophylaxis with i.v. (14-day course) or oral (90-day course) ganciclovir. Conclusions. Preemptive therapy guided by pp65 antigenemia is a useful and cost effective strategy for prevention of CMV disease.

Background In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. Methods We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. Results The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. Conclusions This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation. (Liver Transpl 2005;11:1295–1297.)

Invasive fungal infections are a significant complication of solid organ transplantation. Here we report the first case of concurrent invasive pulmonary fungal infection caused by Aspergillus fumigatus and Mucor species in a heart transplant recipient. Polymicrobial mold infection is rare but should be considered in solid organ transplant recipients who fail to respond to initial antifungal therapy targeting a single organism. It is also of interest that in addition to potent immunosuppression and prolonged voriconazole therapy, possible airway fungal colonization following hurricane Katrina cleaning efforts might have contributed to this dual invasive mold infection.

We describe a thymidine-dependent small-colony variant of Staphylococcus aureus associated with left ventricular assist device infection and prosthetic valve and pacemaker endocarditis.

Background. Coccidioidomycosis is an airborne infection caused by the fungus Coccidioides, which is endemic to the southwestern United States. Cell-mediated immunity is required for the control of this infection, and some patients such as organ transplant recipients, who lack such immunity, have a high risk of severe, disseminated, or relapsed infection with high mortality. Previously latent coccidioidal infection can reactivate after transplantation. Antifungal prophylaxis has substantially decreased the risk of reactivated coccidioidomycosis after transplantation in these patients. Methods. We conducted a retrospective review of all patients with coccidioidomycosis who underwent solid organ transplantation at our center to identify factors for recrudescent coccidioidomycosis (despite antifungal prophylaxis) after transplantation. Results. Between June 1999 and June 2009, 100 patients with previous coccidioidomycosis underwent solid organ transplantation at our institution. Ninety-four (94%) received anticoccidioidal prophylaxis after transplantation. The six patients who did not receive such prophylaxis did not experience reactivated coccidioidomycosis. Five patients who received anticoccidioidal prophylaxis experienced reactivated infection. All five patients survived with further antifungal treatment. Among patients who experienced recrudescent infection despite antifungal prophylaxis, African American race was an identified risk factor. Pretransplant dissemination may be a risk factor for reactivated coccidioidomycosis, but this finding was not statistically significant. Whether nonadherence to prophylaxis played a small or large role is uncertain. Conclusions. Antifungal prophylaxis effectively suppressed recrudescent coccidioidomycosis after solid organ transplantation for the large majority of patients with a history of coccidioidomycosis before transplantation. Strict lifelong adherence to antifungal prophylaxis is imperative.

Zygomycetes, ubiquitous fungi found in the environment, are well known to be pathogenic in immunocompromised patients, including those with diabetes mellitus, leukemia, lymphoma, solid tumors, acute or chronic renal failure, gastrointestinal or liver disease, organ transplantation, and kwashiorkor.lm3 Mucormycosis is a well-recognized clinical term referring to diseases caused by organisms in the order Mucorales and the class Zygomycetes. Certain predisposing conditions appear to be more commonly associated with certain clinical syndromes of mucormycosis. Rhinocerebral mucormycosis is most commonly found in patients with diabetes mellitus and has been associated with a high mortality ratee4 Blitzer reported a 50% mortality rate for paranasal sinus mucormycosis; however, when analyzed according to decade, survival increased to 70% in cases reported from 1970 to 1979 compared with prior years. 5 A review of 33 cases of mucormycosis at Johns Hopkins Hospital revealed a 6% survival rate before 1970 and 73% after 1970.” This impact is felt to be secondary to prompt diagnosis, aggressive surgical debridement, treatment with amphotericin B, and correction of underlying metabolic abnormalities.

The clinical characteristics and neuropathological findings of 22 organ transplant recipients with CNS aspergillosis were reviewed. Thirteen patients had liver, six kidney, two heart and one had cluster transplants. The most frequent neurological symptoms were alteration of mental status (86%), seizures (41%) and focal neurological deficits (32%). Meningeal signs were less common (19%). Aspergillus spp invasion of the blood vessels with subsequent ischaemic or haemorrhagic infarcts, and solitary or multiple abscesses were the predominant neuropathological findings. The lungs were the probable portal of entry; however, isolated CNS aspergillosis was seen in two patients. Antemortem diagnosis of the infection was made in half of the patients. Concomitant diabetes mellitus was noted in 59% of the patients and bacterial or other severe infections in 86%. No specific clinical or pathological pattern could be identified among patients with different types of organ transplants. In addition CNS aspergillosis was preceded by organ rejection and the need for intense immunosuppression and retransplantation in the majority of the patients.

Background Rhino-orbital-cerebral disease is a significant manifestation of zygomycosis in solid organ transplant (SOT) recipients. However, its characteristics and outcome are not well addressed. Methods SOT recipients with zygomycosis as per the European Organization for Research and Treatment in Cancer and the Mycoses Study Group criteria in a cohort study at our centers published previously and those identified with a PubMed search from the 1950s to November 2009 were studied. Patients with mycosis involving the sinuses, orbits, or central nervous system (CNS) were included. Results Patients comprised a total of 90 SOT recipients with rhino-orbital-cerebral zygomycosis, including 13 in our cohort and 77 in the literature. CNS disease occurred in 57% (51 of 90). Overall mortality was 52.3% (46 of 88), and the mortality in patients with CNS disease was 73.5% (36 of 49). In logistic regression analysis, older age (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04-1.21, P=0.002) was associated with a higher mortality rate, whereas lipid formulations of amphotericin B compared with amphotericin B deoxycholate (OR 0.09, 95% CI 0.02-0.50, P=0.006) and surgery (OR 0.12, 95% CI 0.01-0.94, P=0.043) were independently associated with an improved survival even when controlled for CNS involvement and the era of diagnosis of disease. Conclusions Rhino-orbital-cerebral zygomycosis, particularly CNS disease, is associated with substantial mortality rate in SOT recipients. Older age is a significant risk factor for mortality, whereas lipid formulations of amphotericin B and surgery improved outcomes.

Fifty-eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra-pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2-11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain.

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.

Background In August 2002, fever and mental-status changes developed in recipients of organs from a common donor. Transmission of West Nile virus through organ transplantation was suspected. Methods We reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. Persons who donated blood to the organ donor and associated blood components were identified and tested for West Nile virus. Results We identified West Nile virus infection in the organ donor and in all four organ recipients. Encephalitis developed in three of the organ recipients, and febrile illness developed in one. Three recipients became seropositive for West Nile virus IgM antibody; the fourth recipient had brain tissue that was positive for West Nile virus by isolation and nucleic acid and antigen assays. Serum specimens obtained from the organ donor before and immediately after blood transfusions showed no evidence of West Nile virus; however, serum and plasma samples obtained at the time of organ recovery were positive on viral nucleic acid testing and viral culture. The organ donor had received blood transfusions from 63 donors. A review of blood donors and follow-up testing identified one donor who had viremia at the time of donation and who became seropositive for West Nile virus IgM antibodies during the next two months. Conclusions Our investigation of this cluster documents the transmission of West Nile virus by organ transplantation. Organ recipients receiving immunosuppressive drugs may be at high risk for severe disease after West Nile virus infection. Blood transfusion was the probable source of the West Nile virus viremia in the organ donor. (N Engl J Med 2003;348:2196–2203).

A 51-year-old man developed fever and back pain 2 months after orthotopic liver transplantation for end-stage liver disease secondary to chronic hepatitis C infection. CT scan demonstrated destructive lesions in T12 suggestive of osteomyelitis. Aspiration biopsy of the vertebra revealed granulomatous inflammation and yeast forms; culture yielded Candida albicans. The patient improved with intravenous amphotericin B and 5-fluorocytosine and did not require surgical intervention. Candida osteomyelitis is a rare condition and to our knowledge it has not been reported before in liver transplant recipients. Awareness of this potential complication may shorten the delay in making the definitive diagnosis, which in turn may increase the likelihood of a response without sequela.

Background Although influenza and parainfluenza viruses commonly cause respiratory tract infections in the community, their incidence and clinical implications in adult lung transplant recipients have received little attention. Methods We performed a retrospective cohort study of influenza and parainfluenza viral infections in adult lung transplant recipients at the University of Pittsburgh Medical Center. Results Between January 1989 and March 1999, 39 cases (single-lung 25, double-lung 14) of influenza or parainfluenza respiratory viral infection were identified at a mean of 1.7 years (SD+/-1.4) after transplantation. The mean length of admission was 7 days. The cases included 15 patients with influenza (A, 11; B, 4) and 24 with parainfluenza (para1, 7; para2, 2; para3, 15). The median age at diagnosis was 48 years; there were 19 females and 20 males. Symptoms were reported in 30 patients and lasted for a median of 7 days before admission. These included cough (64%), shortness of breath (56%), and temperature elevation (33%). Chest infiltrates were seen in 14 (36%) patients, and 5 (13%) of them required intubation and mechanical ventilation. Viral pneumonia was diagnosed in 10 (5 influenza and 5 parainfluenza) patients, and concurrent bacterial pneumonia occurred in 4 patients. Transbronchial biopsy was performed in 36 patients, of whom 23 (64%) showed some degree of acute allograft rejection. Conclusion Influenza and parainfluenza respiratory viral infections are associated with significant morbidity in adult lung transplant recipients. Active vaccination programs and the development of new antiviral agents active against these viruses are important for prevention.

Background: Nocardia is responsible for infection in both normal and immunocompromised hosts. Organ transplant recipients are increasingly recognized as a sub-group of immunocompromised patients in whom nocardia is an important pathogen. The frequency of nocardia in organ transplant recipients varies between 0.7% and 3%. Nocardia infection has largely been reported in heart, kidney and liver transplant recipients. Presentations of nocardia in lung transplant recipients have been restricted primarily to case reports. The present study reviews the clinical and epidemiologic characteristics of nocardia infection in lung transplant recipients at our institution. Methods: A retrospective cohort study of 473 lung transplant recipients from January 1991 to November 2000 was done at a university hospital. Patient demographics, immunosuppressive regimen at the time of isolation of nocardia species, use of trimethoprim–sulfamethoxazole for Pneumocystis carinii prophylaxis, rejection episodes in the preceding 6 months, concurrent pathogens, site of infection, radiologic findings and treatment and outcome were recorded. Results: Nocardia infection was found in 2.1% (10 of 473) of our lung transplant recipients. Median time of onset was 34.1 months after transplantation. Nocardia species included N farcinica in 30% (3 of 10), N nova in 30% (3 of 10), N asteroides complex in 30% (3 of 10) and N brasiliensis in 10% (1 of 10) of patients. Post-transplant diabetes was present in 50% (5 of 10) of patients. The primary indication for lung transplantation was emphysema in 40% (4 of 10). Native lung involvement was noted in 75% (3 of 4) of patients with single lung transplant. Breakthrough nocardia infection were noted in 6 patients who were receiving trimethoprim–sulfamethoxazole prophylaxis for P carinii pneumonia; all breakthrough isolates remained susceptible to trimethoprim–sulfamethoxazole. Overall mortality was 40% (4 of 10). All patients (3 of 3) with infection due to N farcinica, except 1 (1 of 7) with infection due to other nocardia species, died. Seventy-five percent (3 of 4) of deaths were attributable to nocardia infection. Conclusions: Nocardia infection tended to involve the native lung in single lung transplant recipients. Trimethoprim–sulfamethoxazole for P carinii prophylaxis at the doses given was not protective against nocardiosis in these patients. Infection with N farcinica was associated with poor outcome. Thus, species identification and extended courses of antibiotics based on antimicrobial susceptibility testing are important in management of these patients.

Purpose To determine the incidence of acute respiratory failure (ARF) in non-AIDS patients with pulmonary cryptococcosis (PC). Design Retrospective cohort study. Setting University of Pittsburgh Medical Center, Pittsburgh, PA. Subjects All patients in whom PC without HIV infection was diagnosed between February 1989 and March 1999. Results Thirty-three patients with PC were identified, and 11 of those patients (33%) developed ARF and comprised the study group. Underlying diseases included solid-organ transplant recipients (seven patients; 64%) and other underlying medical conditions (four patients; 36%). The most common symptoms were cough, shortness of breath, and temperature elevation. Extrapulmonary involvement was seen in six patients (meningitis, four patients; peritonitis, one patient; laryngeal mass, one patient). Six of the 11 patients (55%) died. Conclusion ARF may develop in one third of non-AIDS patients with PC. This clinical syndrome is associated with the dissemination to extrapulmonary sites and high mortality rates. PC should be recognized as a possible cause of respiratory failure in non-AIDS patients.

We describe a case of acute invasive sinusitis due to an unusual moniliaceous fungus, Trichoderma longibrachiatum Rifai 1969 (a member of the class Hyphomycetes), in a small bowel and liver transplant recipient treated with tacrolimus (FK-506) and prednisone. The patient was successfully treated with surgical debridements and amphotericin B followed by oral itraconazole.

Objective: To determine the incidence, clinical presentation, and outcome and confounding factors associated with the development of a brain abscess in solid organ transplant recipients. Design: A 14-year retrospective survey. Setting: A single, multiorgan, academic transplantation center. Patients: A total of 2380 liver transplant recipients, 1650 kidney transplant recipients, and 598 heart, heart-lung, or lung transplant recipients of all ages (pediatric and adult) were included. All patients were given cyclosporine-based immunosuppression during this period. Main Outcome Measure: A brain abscess was determined to be present if there was histological and/or microbiological confirmation of a brain lesion seen by a computed tomographic scan. A brain abscess was considered suspicious if radiographic findings were seen in the clinical setting of neurologic symptoms and fever without histological or microbiological confirmation. Results: A brain abscess developed in a total of 28 patients (0.61%) of the total study population. The frequency of brain abscess according to organ type was as follows: 0.63%, liver; 0.36%, kidney; and 1.17%, heart and heart-lung. The overall mortality was 86%. Complicating factors associated with fungal ( Candida and Aspergillus sp) abscess formation included major subsequent operations, retransplantations, antirejection therapy, associated bacteremia or viremia, and multiorgan failure. The lung was the primary site of dissemination in 18 patients. Low-dose prophylactic amphotericin was ineffective in preventing a fungal brain abscess in 10 high-risk patients. Because of the ineffective therapy and the deadly nature of established fungal abscesses, full-dose antifungal therapy and reduced immunosuppression were warranted on identification of a high-risk clinical setting. Nonfungal abscesses ( Nocardia and Toxoplasma sp) occurred in healthy graft recipients long after transplantation. The existing medical therapy is usually effective in these patients, provided that rapid tissue diagnosis is established. Conclusions: The epidemiological features of brain abscess formation after solid organ transplantation suggest 2 populations of patients exist that differ in timing, clinical setting, and response to therapy. For the chronically immunosuppressed outpatient, an established abscess should be empirically treated with sulfonamides until tissue diagnosis is confirmed. On the other hand, the acutely immunosuppressed posttransplant recipient, with defined risk factors, should receive full-dose therapy with amphotericin B and concomitantly lowered immunosuppression. Arch Surg. 1997;132:304-310