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Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta.

Chronic laryngitis commonly presents with dysphonia, and infectious causes include tuberculosis and endemic mycoses. We present a 58-year-old female with laryngitis for 5 years, fevers, chills, fatigue, malaise, myalgias, anterior neck pain, and night sweats after multicontinent exposure. Bronchoscopy cultures were negative. Bilateral microflap excision of vocal fold lesions demonstrated thickened epithelium and a deep vocal fold mass. Biopsy showed necrotizing granulomatous inflammation with acid-fast bacilli. Mycobacterium kansasii was identified. Treatment led to improvement in dysphonia, systemic symptoms, and vocal fold irritation. To our knowledge, this is the first case of isolated nontuberculous mycobacterial vocal fold infection. Laryngoscope, 129:2534-2536, 2019.

BackgroundClostridium difficile infection (CDI) can cause severe morbidity in transplant recipients; the effects of probiotic therapy in this population are unknown.MethodsSingle-center, retrospective chart review of lung and liver transplant recipients between January 2003 and December 2009 with po

Background. Cytomegalovirus (CMV) viremia that is resistant or refractory to the standard antiviral therapy still constitutes a major threat to high-risk transplant recipients. In addition, multiple CMV recurrences may lead to neutropenia because of repeated courses of therapy with ganciclovir derivatives. Leflunomide, a drug for rheumatoid arthritis, has been reported to have anti-CMV activity. This study reports on its use in 17 transplant recipients with complex CMV syndromes who had failed or were intolerant to other therapies. Methods. Single-center, retrospective study. Clinical data were extracted from the electronic medical record. CMV DNA viral loads were performed by quantitative hybrid capture assay. Results. Leflunomide was initiated after a median of three episodes of CMV viremia, with a mean peak viral load of 245,826 copies/mL. Initial clearance of CMV viremia was observed in 14 of 17 patients (82%), and 9 of 17 (53%) patients achieved a long-term suppression of CMV recurrences. Higher peak viral load and higher viral load at the start of leflunomide therapy were associated with failure to suppress viremia. The duration ofleflunomide therapy ranged from 1 to 24 months (median 3.5 months, interquartile range 2.6-7 months), and the mean time to an undetectable CMV-DNA was 1.9 months. Adverse effects included diarrhea (35%), anemia (18%), and increased liver function tests (12%). Conclusions. Leflunomide, alone or in combination, has potential utility in treatment of complex CMV syndromes and in long-term suppression of viremia. The optimal duration of therapy and the balance of risks and benefits are not yet known.

Background Many clinical scenarios have been encountered by patients who developed histoplasmosis after receiving a solid organ transplant at a large transplant center in an endemic area. Methods Cases of posttransplantation histoplasmosis were identified by use of multiple methods, including reviews of microbiology test results, transplant databases, and billing codes. Data were obtained retrospectively. Descriptive statistics were used. Results During the 1997-2007 study period, 3436 patients received a solid organ transplant, and 38 patients were identified as having posttransplantation histoplasmosis. Of these 38 patients, 9 were excluded from our study because the diagnosis was solely clinical. Of the remaining 29 patients, 14 had posttransplantation histoplasmosis (incidence, 1 case per 1000 person-years); 14 showed histologic evidence of histoplasmosis in the recipient or donor tissue, which was encountered unexpectedly at the time of transplantation; and 1 had histoplasmosis before receiving the transplant. Of the 14 patients who developed histoplasmosis after transplantation, 5 were heart transplant recipients, 3 were lung transplant recipients, 3 were kidney transplant recipients, 1 was a liver transplant recipient, 1 was a pancreas transplant recipient, and 1 was a kidney-pancreas transplant recipient. The median time from transplantation to diagnosis was 17 months (interquartile range, 8.1-46 months), and the median time from onset of symptoms to diagnosis 3 weeks (interquartile range, 1.9-6.5 weeks). All recipients had disseminated disease. The most common treatment was amphotericin B and itraconazole. All were cured, or still on treatment, but symptom-free. Of the 14 patients who had an explanted organ or donor tissue that showed histologic evidence of histoplasmosis, 13 (93%) were lung transplant recipients, and 1 (7%) was a liver transplant recipient. None of these patients developed active histoplasmosis, but all received prophylactic treatment. Finally, 1 patient had histoplasmosis before transplantation; he was treated with itraconazole 3 months before and after transplantation, and he did well. Conclusions In conclusion, posttransplantation histoplasmosis is rare (1 case per 1000 transplant-person-years; 95% confidence interval, 0.6-1.7), even in endemic areas. Prognosis is good but requires protracted therapy. Patients with latent infection did not develop posttransplantation histoplasmosis when prophylaxis was used.

Infection is a major comorbidity after ventricular assist device (VAD) placement. Defects in cellular immunity have been reported after VAD placement. However, to our knowledge, quantitative immunoglobulin G (IgG) level determination and the impact of hypogammaglobulinemia (HGG) on infections after VAD implantation have not been evaluated before.A total of 76 patients (mean age, 53 years) underwent VAD implantation as a bridge to transplantation and had IgG levels determined as a baseline before transplantation. Patients were divided into 2 groups according to IgG level: Control Group (n = 56, IgGor = 700 mg/dl) and HGG Group (n = 20, IgG700 mg/dl). Infection outcome during the VAD course and after transplantation was analyzed in relation to the IgG level.Baseline characteristics were similar in both groups. The incidence of bacteremia (14/20 [70%] vs 18/56 [32%], p = 0.0032) and major infection (19/20 [95%] vs 31/56 [56%], p = 0.0009) were significantly increased in the HGG Group compared with the Control Group. After transplantation, the episodes of rejection were similar in both groups and survival was similar. The HGG Group experienced more cytomegalovirus infections compared with the Control Group (9/20 [45%] vs 9/56 [16%], p = 0.009).VAD patients with HGG are at increased risk of infections. After transplantation, these patients also experience increased cytomegalovirus infections. A randomized preemptive IgG replacement trial may be warranted in the future to determine if this intervention will alleviate the risk of infection.

Background Increasing interest has focused on possible viral triggers of cardiac allograft vasculopathy. Although much interest has centered on cytomegalovirus, it has recently been noted that donor hepatitis C seropositivity is associated with risk for accelerated vasculopathy. The current study hypothesized that hepatitis B (HBV) might be associated with accelerated vasculopathy. Methods Sixty-six patients who received heart transplants between September 1998 and July 2000 were analyzed by intravascular ultrasound within 6 weeks and again at 12 months after transplantation. These patients were divided into 2 groups: the HBV Group ( n = 13) in which either the donor or recipient was seropositive for hepatitis B core antibody (HBcAb), and a Control Group ( n = 53) in which neither donor nor recipient was positive for HBcAb. Results Baseline characteristics of the 2 groups were similar. The HBV Group had significant increase in the change in average intimal area (1.59 ± 1.4 vs 0.46 ± 0.4 mm 2 , p = 0.01) per mm length of the vessel compared with controls. Allograft vasculopathy at 1 year (defined as largest maximal intimal thickness increase of ≥0.50 mm) occurred in 46% of the HBV group compared with 24% of the control group ( p = 0.05). When measured as an average maximal intimal thickness increase of >0.30 mm, allograft vasculopathy at 1 year occurred in 31% of the HBV Group compared with 5% of Controls ( p = 0.01). Conclusions These preliminary results suggest that HBV seropositivity in donor or recipient may be associated with an increased risk for cardiac allograft vasculopathy.

Background Lung transplant recipients are susceptible to complications from influenza infection. Antibody responses to influenza vaccination have been shown to be decreased in lung transplant recipients. Cellular immune mechanisms serve an important role in influenza clearance. The cellular immune response to influenza vaccination has not been studied in transplant populations. Methods Interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels to the three viral antigens included in the 1999 to 2000 influenza vaccine were measured before and 4 weeks post-vaccination in 43 lung transplant recipients and 21 healthy adult controls. Results Interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels did not increase from pre- to post-vaccination in the lung transplant group. Both pre- and post-cytokine levels were lower in the transplant group compared to the control group. Pre- and post-granzyme B levels did not differ significantly between the groups. The T-helper response in the control group varied with the different viral strains. A correlation between acute rejection episodes and the absence of both azathioprine and mycophenolate was found. Conclusions Influenza vaccination does not stimulate a cell-mediated immune response in lung transplant recipients as judged by interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels. Alternative prevention strategies may be needed.

It is possible, but unproven, that hepatitis C (HCV) infection accelerates atherosclerosis. We evaluated the hypothesis that donor HCV seropositivity predicts mortality and the development of coronary vasculopathy in cardiac transplant recipients.Thirty-four cardiac transplant recipients who were seronegative for HCV at the time of transplantation received hearts from HCV-seropositive donors. We compared the mortality and the incidence of vasculopathy in this group of patients (study group) with a group of 183 successive heart transplant recipients (control group) with no evidence of HCV in the donor or in the recipient.After transplantation, 75% of the HCV-seronegative patients who received hearts from HCV-seropositive donors had detectable and persistent viremia (presence of HCV-RNA by reverse-transcription polymerase chain reaction). After a mean follow-up of 4.2 +/- 1.9 years, mortality was 2.8-fold greater in the study group than in controls (95% confidence interval [CI], 1.3-5.7; p = 0.006). The risk of having any vasculopathy after a mean follow-up of 3.4 +/- 1.6 years and after adjustment for other significant risk factors was 3-fold greater (hazards ratio, 3.08; 95% CI 1.52-6.20; p = 0.001) in the HCV group compared with controls. The risk of developing advanced vasculopathy was much greater in the study group compared with controls (hazard ratio, 9.4; 97% CI, 3.3-26.6; p =0.0001). The risk of mortality (p = 0.005) and vasculopathy (p =0.0001) was greatest in patients with combined donor HCV seropositivity and the presence of antibodies against donor B cells by flow cytometry.We conclude that donor hepatitis-C virus seropositivity is an independent risk factor for increased mortality and for the development of accelerated allograft vasculopathy after cardiac transplantation. These observations may have implications for the use of HCV-positive donors in heart transplant recipients.

Background. Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. Objective. To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center. Methods. Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. Results. Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R–), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3×/week) IV ganciclovir for prophylaxis. Conclusions. GCV-R CMV is associated with CMV D+/R– status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.

Atherosclerotic coronary artery disease is multifactorial, but several lines of evidence implicate infection as a potential contributing factor. Chlamydia pneumoniae has the most compelling data, with Helicobacter pylori and cytomegalovirus also implicated. Clinical trials of antibiotics to decrease coronary events are underway. Until the results are available, however, we advise against prescribing antibiotics for this purpose.

Hypogammaglobulinemia (HGG) has been reported after solid organ transplantation and is noted to confer an increased risk of opportunistic infections.In this study, we sought to assess the relationship between severe HGG to infection and acute cellular rejection following heart transplantation.Between February 1997 and January 1999, we retrospectively analyzed the clinical outcome of 111 consecutive heart transplant recipients who had immunoglobulin G (IgG) level monitoring at 3 and 6 months post-transplant and when clinically indicated.Eighty-one percent of patients were males, mean age 54 +/- 13 years, and the mean follow-up period was 13.8 +/- 5.7 months. Patients had normal IgG levels prior to transplant (mean 1137 +/- 353 mg/dl). Ten percent (11 of 111) of patients developed severe HGG (IgG350 mg/dl) post-transplant. The average time to the lowest IgG level was 196 +/- 125 days. Patients with severe HGG were at increased risk of opportunistic infections compared to patients with IgG350 mg/dl (55% [6 of 11] vs. 5% [5 of 100], odds ratio = 22.8, p0.001). Compared to patients with no rejection, patients who experienced three or more episodes of rejection had lower mean IgG (580 +/- 309 vs. 751 +/- 325, p = 0.05), and increased incidence of severe HGG (33% [7 of 21] vs. 2.8% [1 of 35], p = 0.001). The incidence of rejection episodes per patient at 1 year was higher in patients with severe HGG compared to patients with IgG350 (2.82 +/- 1.66 vs. 1.36 +/- 1.45 episodes/patient, p = 0.02). The use of parenteral steroid pulse therapy was associated with an increased risk of severe HGG (odds ratio = 15.28, p0.001).Severe HGG after cardiac transplantation may develop as a consequence of intensification of immunosuppressive therapy for rejection and hence, confers an increased risk of opportunistic infections. IgG level may be a useful marker for identifying patients at high risk.

Proven clinical efficacy of protease-sparing regimens (PSR) has been shown. Concerns exist about broad applicability of these regimens in advanced naïve patients. Recent reports have associated a rise in liver enzymes with nevi rapine; however, no data exist with efavirenz.17 consecutive antiretroviral-naïve HIV patients were started on a PSR with efavirenz plus two nucleoside reverse transcriptase inhibitors. Baseline liver enzymes, serum CD38, CD4, and HIV viral load data were collected. Correlation between change in viral load and immune reconstitution on therapy were compared to baseline laboratory values.All patients had a mean viral load decrease of2 logs, including patients with low initial CD4% or high viral load, and there was no increase of liver enzymes observed at a median follow-up of 42 weeks (range 17-78). There was a perfect correlation between the change in viral load and the initial viral load (p.0001, r = 1.00) including patients with viral loador =100,000 copies/mL and CD4 countor =50 (n = 5). Even patients with low initial CD4 had a significant percentage increase in CD4 count (p.0002, r = 0.7880). CD38% showed a positive correlation with change in viral load (p =.046, r = 0.522).All patients experienced a mean viral load decrease of2 logs (88% less than 400 copies/mL and 35% less than 20 copies/mL). There were no observed increases in liver enzymes. Patients with low CD4 counts, high initial viral load, or high CD38 expression still experienced a significant change in viral load.

Background: The recent development of powerful agents such as mycophenolate mofetil and tacrolimus has altered current regimens for the prevention and treatment of allograft rejection. Questions have been raised about these newer regimens in terms of susceptibility to opportunistic infections and effects on host defenses. Severe hypogammaglobulinemia has been infrequently described in solid organ transplant recipients, but has been recently noted in six heart transplant recipients at one center, of whom five were receiving a combination of tacrolimus, mycophenolate mofetil, and prednisone. Methods: Case summaries of six recent heart transplant recipients with total immunoglobulin G (IgG) levels of less than 310 mg/dl, five of whom had cytomegalovirus (CMV) infection and three of whom had multiple infections including Nocardia, invasive Trichophyton, and Acinetobacter bacteremia. Previous literature was reviewed with the aid of a Medline search using the search terms hypogammaglobulinemia; kidney, liver, heart, lung, and organ transplantation; mycophenolate mofetil; tacrolimus; cyclosporine; azathioprine; and nocardiosis. Results: We here report six cardiac transplant recipients seen over a period of one year who were found to have immunoglobulin G levels of 310 mg/dl or below (normal: 717–1400 mg/dl). The first five patients were diagnosed because of evaluation for infections; the sixth, who was asymptomatic with an IgG level of 175, was found during screening for hypogammaglobulinemia instituted as a result of these first five patients. All six patients had received steroid pulses for rejection; all received mycophenolate mofetil; and 5/6 had been switched from cyclosporine to tacrolimus because of steroid-resistant rejection. Transient neutropenia (absolute neutrophil count less than 1000) was observed in 2/6; 3/6 had received OKT3 therapy for refractory rejection. These six patients were treated with a combination of antimicrobials, immunoglobulin replacement, and decrease in immunosuppressive therapy. Conclusions: The finding of unexpected hypogammaglobulinemia and concomitant infectious complications in six heart transplant recipients highlights a possible complication in a subset of patients receiving newer immunosuppressive agents. A larger prospective study is underway to determine risk factors for development of post-transplant hypogammaglobulinemia and to assess pre-transplant immune status of these recipients. Monitoring of immunoglobulin levels in high-risk patients receiving intensified immunosuppressive therapy for rejection may help to prevent infectious complications.

Aspergillus native valve endocarditis in patients who have not had cardiac surgery is uncommon. We report 3 cases and review 58 other adult patients reported in the English-language literature. Sixty-seven percent of the patients had underlying immunosuppression. The clinical features were fever (74%), embolic episodes (69%), a new or changing heart murmur (41%), and sudden visual loss (13%). Patients with mural endocarditis were more often immunosuppressed, especially due to solid organ transplants, but had lower frequency of heart murmurs and embolic episodes. Echocardiography revealed a vegetation in 78% of all the cases in which it was performed. Examination and culture of biopsy material often helped to establish a diagnosis of Aspergillus infection. Twenty-five patients had an antemortem diagnosis. These patients received a mean cumulative amphotericin B dose of 27 mg/kg. Twenty percent (3/15) of patients who received combined surgical and medical therapy survived, compared to none of those who received medical therapy alone (p = 0.08). Patients who survived were not immunosuppressed. We conclude that native valve aspergillus infective endocarditis is uniformly fatal without surgical intervention and antifungal therapy.

Histoplasmosis is a common cause of systemic mycosis in areas of the United States where it is endemic. Central nervous system and genitourinary histoplasmosis is rare, especially in immunocompetent hosts. We describe a case of disseminated histoplasmosis in a normal host that was associated with cerebral and prostatic histoplasmosis presenting as fever of undetermined origin, weight loss, and severe debilitating altered mental status. The patient subsequently developed acute renal failure that manifested as obstructive uropathy during antifungal therapy with amphotericin B. Transurethral resection of the prostate resulted in improved renal function during continuation of amphotericin B therapy. Pathological analysis of the prostate revealed necrotizing granulomas with intralesional fungal organisms. Blood and urine cultures were positive for Histoplasma capsulatum. Diagnostic issues and management are discussed. Treatment resulted in return of normal cognitive and motor function. This case is compared with the 8 previously reported cases of H. capsulatum prostatitis.

Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.

Therapeutic and diagnostic aspiration of Echinococcus granulosus liver cysts, but not pulmonary cysts, are increasingly being performed. Documented herein is the utility of percutaneous drainage and of albendazole treatment in a patient with a large recurrent, isolated, pulmonary echinococcal cyst for whom traditional therapy would have resulted in severe morbidity. Therapeutic options and possible complications are discussed.

Background: Influenza vaccination may be less immunogenic in transplant recipients than in healthy people. Influenza A (H1N1) and B circulating viruses during the 2007-2008 epidemic were different from those contained in that season’s vaccine. In that epidemic, influenza vaccine effectiveness against culture-confirmed influenza was 44%. Objective: To describe clinical, immunological, and virological characteristics of 18 transplant recipients who developed influenza during the 2007-08 epidemic despite influenza vaccination (tx-vac-flu), and compare them to 6 transplant recipients who developed influenza in the absence of influenza vaccination (tx-no vac-flu), 12 previously healthy people who developed influenza (healthy-flu), and 13 transplant recipients who received influenza vaccination and did not develop influenza (tx-vac-no flu). Methods: Case ascertainment was through microbiology and electronic medical records. A case of influenza was defined by a clinical presentation of an influenza-like illness, plus a positive influenza A or B multiplex real time polymerase chain reaction (Prodesse, Inc. Waukesha, WI) on a nasopharyngeal swab. Results: Of the 36 patients with influenza, 22 had influenza A, and 15 had influenza B (1 transplant recipient had both serotypes simultaneously). Types of transplant were lung (11), hematopoietic stem cell (8), heart (7), liver (3), kidney (3), kidney + pancreas (3), liver + kidney (1), and liver + pancreas (1). Patients in the tx-vac-flu group were significantly older than patients in the tx-no vac-flu group [median 61 vs. 50.5 year, (P=0.02), the healthy-flu group [median 49.5 years (P=0.04)], and the tx-vac-no flu group [median 53 years (P=0.02)]. Influenza occurred 1,410 (261-3,467) days {median [interquartile (IQR) range]} after transplant in the tx-vac-flu group, compared to 175 (40-1,064] days in the tx-no vac-flu group (P=0.18). Influenza occurred 114 days (median [IQR 99-137]) after vaccination in the tx-vac-flu group. Immunoglobulin G levels and immune function assay levels were not significantly different between the 3 transplant groups. There were no statistically significant differences in the incidence of fever, headache, cough, rhinorrhea, sore throat, malaise, shortness of breath, exposure to contacts with similar symptoms, presence of infiltrates on chest roentgenograms, or the estimated influenza viral loads among the 3 groups who had influenza. Patients in the tx-vac-flu group were treated with oseltamivir significantly more frequently than the healthy-flu group [94% vs. 50% (P=0.0006)], but not the tx-no vac-flu group [100% (P=0.7)]. Duration of treatment with oseltamivir was not significantly different among the 3 groups who had influenza. Patients in the tx-vac-flu group had concomitant infections significantly more frequently than the healthy-flu group [44% vs. 8% (P=0.043)], but not the tx-no vac-flu group. Patients in the tx-vac-flu group developed pneumonia, and were hospitalized for management of influenza significantly more frequently than patients in the healthy-flu group (P=0.031 and P=0.00007; respectively). Only one patient (6%) in the tx-vac-flu group and none in the tx-no vac-flu or healthy-flu groups required admission to an intensive care unit and mechanical ventilation following influenza. No patients died as a result of influenza. Conclusions: Influenza vaccination did not alter clinical presentation of influenza in transplant recipients, but these patients were hospitalized and developed pneumonia more frequently than healthy people. Transplant recipients who developed influenza despite influenza vaccination were not more immunosuppressed than transplant recipients who were vaccinated and did not develop influenza. Transplant recipients who developed influenza despite influenza vaccination were more likely to have concomitant infections than healthy people with influenza.

BACKGROUND Staphylococcus aureus bacteremia (SAB) is an important cause of morbidity and mortality. Herein, we describe the incidence, clinical characteristics, and outcomes of SAB after solid organ transplantation (SOT) and compare these features with non-SOT controls. METHODS In a single-center retrospective study, blood cultures positive for S. aureus were obtained from January 1, 2000, to December 31, 2008. Chart review was performed on all SOT recipients with SAB. The social security death index was used to determine all-cause mortality. RESULTS Seventy of 2959 patients with SAB were SOT recipients (26 lung, 19 liver, 18 kidney, and seven heart). The overall attack rate of SAB in SOT was 22.9/1000 transplant patients. Early-onset SAB (≤ 90 days) was more frequent in liver recipients (79%), when compared with kidney recipients (17%). All-cause 30-day and 1-year mortality rates were 6% and 28% in SOT, respectively. Pneumonia as a source was associated with an increased 30-day mortality (18% vs. 2%, P = 0.04). Comparing SOT versus non-SOT controls, methicillin resistance was more frequent (86% vs. 52%, P < 0.0001), and duration of bacteremia was longer (mean 3.8 vs. 1.6 days, P < 0.01). SOT status was independently associated with lower risk of 30-day mortality (risk ratio [RR]: 0.37, P = 0.02). CONCLUSIONS In our cohort of SOT recipients, SAB was less common than previously reported and surprisingly had lower 30-day mortality, when compared with non-SOT. In SOT recipients, pneumonia as a source of SAB in SOT is associated with an increased 30-day mortality.

Toxoplasmosis is a common, largely asymptomatic infection. Early reports of acquired disease noted frequent dermatologic manifestations, whereas recent reviews of toxoplasmosis stress the lymphadenopathic presentation of the disease. We report the case of a patient with acute toxoplasmosis associated with a prominent macular and papular rash involving the palms and soles. We have reviewed the literature on dermatologic manifestations of acute acquired toxoplasmosis to underscore the importance of considering toxoplasmosis in the differential diagnosis of febrile illnesses with varied dermatologic presentations.

Purpose of review Hypogammaglobulinemia may develop as a result of a number of immune deficiency syndromes that can be devastating. This review article explores the risk of infection associated with hypogammaglobulinemia in solid organ transplantation and discusses therapeutic strategies to alleviate such a risk. Recent findings Hypogammaglobulinemia is associated with increased risk of opportunistic infections, particularly during the 6-month posttransplant period when viral infections are most prevalent. The preemptive use of immunoglobulin replacement results in a significant reduction of opportunistic infections in patients with moderate and severe hypogammaglobulinemia. Summary Monitoring immunoglobulin G levels may aid in clinical management of solid organ transplant recipients. The preemptive use of immunoglobulin replacement may serve as a new strategy for managing solid organ transplant recipients with hypogammaglobulinemia.

Background: The isolation of a pathogen is vital in the diagnosis and treatment of a device infection. A swab culture, despite poor sensitivity, is the most common method used in specimen collection. Objective: To determine the relative value of swab and tissue specimen cultures in patients with implantable cardiac pacemakers and defibrillators. Design: Prospective patient cohort study. Setting: A 1,000-bed tertiary referral center in Cleveland, Ohio. Patients: Consecutive patients with implantable cardiac pacemaker or defibrillator presenting for lead extraction from October 1, 2000 to March 31, 2001. Methods: Tissue and swab cultures were prospectively collected during pacemaker and implantable defibrillator surgeries that required lead extraction. Clinical manifestations, microbiology, and echocardiographic data were recorded in patients with and without a clinical diagnosis of device system infection. Results: Seventy-one patients with implantable pacemaker (n = 49, 69%), implantable defibrillator (n = 18, 25%), or both devices (n = 4, 6%) requiring lead extraction had pocket swab and tissue cultures for analysis. Infection was evident clinically in 35 (49%) of the patients and absent in the remainder. The most common bacteria isolated were coagulase-negative Staphylococcus (37%) and Staphylococcus aureus (10%). Patients with clinical infection had positive cultures more frequently (P = 0.002) by pocket tissue culture (n = 24, 69%) than by swab culture (n = 11, 31%). However, patients without clinical infections had positive cultures at similar rates by pocket tissue culture (n = 10, 28%) and by swab culture (n = 8, 22%; P = 0.48). Patients without clinical infection were not treated with other than perioperative antibiotics, and did not develop clinical infections. Conclusion: Pocket tissue cultures are more effective than pocket swab cultures for the isolation and identification of the infectious pathogens in cardiac device infections. Positive cultures by pocket swab or tissue cultures in the absence of clinical signs and symptoms of infection does not imply infection or the need for specific therapy.

West Nile virus (WNV) infections are potentially life threatening in immunocompromised hosts. Currently, the best diagnostic test is serology. Reverse-transcriptase polymerase chain reaction (RT-PCR) testing has a role, but, because WNV is a cell-associated neurotropic virus, RT-PCR results are frequently negative even in cases of active infection. We present a case in which serology results were persistently negative because the patient was immunocompromised following lymphoma treatment. The role of humoral immunity in resolution of WNV is also discussed.

Background Heart transplantation represents a significant life-saving and increased quality-of-life intervention for patients with refractory cardiac failure. Successful transplantation requires continuous immunosuppression to avoid immune rejection. Unfortunately, persistent viral infections in donors may be transmitted to recipients in the process of heart transplantation. With the severe shortage of available organs and significant waiting list mortality there is a rationale for considering use of organs from donors with evidence of prior hepatitis B and/or hepatitis C infection. Methods Published literature articles were searched using Medline, PaperChase and further review of references in relevant articles on issues related to hepatitis B and hepatitis C and heart transplantation. Results Donor and recipient testing for hepatitis B and hepatitis C is important for relative risk assessment. Nucleic acid testing for hepatitis B DNA and hepatitis C RNA represent emerging technologies, which may add valuable information to traditional serologic testing. Conclusions Heart transplant recipient risk may be modified by vaccination against hepatitis B before transplantation. There is currently no available vaccine for hepatitis C. Recently described effective treatments for hepatitis B and hepatitis C provide further rationale for reconsideration of using hearts from donors with evidence of hepatitis B and/or hepatitis C infection.

Background Comprehensive international travel preparation often requires several vaccines. Up to 90% of adults have some fear of injections, mostly due to injection-related pain. Pediatric studies with routine vaccines have shown topical anesthetic EMLA cream (lidocaine and prilocaine, Astra Pharmaceuticals, Inc.) and the topical vapocoolant Fluori-Methane (dichlorodifluoromethane and trichlorodifluoromethane, Gebauer Co.) to be equally effective in reducing pain from vaccinations. EMLA cream is expensive and requires a 60-min application, while Fluori-Methane (FM) is immediate in onset of action and inexpensive. Skin anesthesia begins at 10°C. Fluori-Methane can briefly cool the skin to 0°C. Methods We studied the effectiveness of topical vapocoolant on adult clients at our international travel clinic in a randomized, controlled trial of topical FM vs. cold (4°C) saline placebo. Using a preset randomization table, participants served as their own controls, receiving placebo/control or active agent (participant blinded) in one arm (left or right), and a similar number of vaccines in the untreated arm. Vaccines were administered according to a set protocol per arm to minimize the risk of bias. Pain was measured using a modified McGill present pain intensity (PPI) pain index. Subjects rated their pain immediately and at 5min on a six-level scale, noting treated and untreated arms separately. A questionnaire was completed on intervention preferences. Sample size was predetermined to achieve 90% statistical power estimating 25% efficacy (minimum n = 172). Results One hundred and eighty-five participants were enrolled; 93 FM and 92 cold saline placebo. FM-treated arms had a significant reduction in immediate pain compared to untreated arms (pain scale mean 2.2 vs. 3.1; p < .0001), and compared to placebo (mean 2.2 vs. 2.8; p < .01). Delayed pain at 5min was not affected by FM or control (mean 1.9 vs. 2.0) compared to no intervention (pain scale 1.9). The intervention preference questionnaire indicated that participants did not find FM therapy uncomfortable. They would choose FM therapy in the future, over a cream, especially if a wait was involved. Conclusion The topical vapocoolant Fluori-Methane is an effective, quick, preferred, inexpensive agent for reducing vaccine-associated injection pain for international travel clients.

Background We have previously shown that the preemptive use of cytomegalovirus (CMV) immunoglobulin (Ig) replacement (CytoGam) decreases the incidence of opportunistic infections in cardiac transplant recipients with severe hypogammaglobulinemia. However, the impact of Ig replacement in moderately hypogammaglobulinemic patients is unknown. Methods Periodic monitoring of the IgG levels was done in 300 heart transplant recipients. Moderate hypogammaglobulinemia (IgG, 350–500 mg/dl) developed in 56 patients (18.6%). Thirty-three patients declined randomization but agreed to have their IgG levels monitored. Twenty-three patients were randomized to placebo ( n = 10) or CytoGam ( n = 13) at 105 ± 63 days after transplantation. Results The baseline characteristics were similar. A significant reduction in CMV infection was noted in the CytoGam Group compared with the Placebo Group (15.4% [2/13] vs 60% [6/10], p = .039). Among patients who declined randomization, CMV infection developed in 13 (39.4%) of 33, and 6 (46.1%) of the 13 progressed to severe hypogammaglobulinemia. A trend for reduction in the average episodes of ≥grade 2 rejection during the 6-month period after randomization was noted in the CytoGam group (0.4 ± 0.6 vs 1.4 ± 1.3, p = 0.065). Conclusions The preemptive use of CytoGam decreases the incidence of CMV infection in patients with moderate hypogammaglobulinemia. A larger randomized study is needed to substantiate these results.

First identified in the United States in 1999, West Nile virus caused approximately 3,500 infections in the late summer and fall of 2002. The virus is predominantly transmitted by mosquitoes, and the risk of infection through blood product transfusion is believed to be low. We present a case of West Nile virus encephalitis transmitted by red blood cell transfusion at the time of coronary artery bypass grafting that resulted in the patient's death. Individuals undergoing procedures with high blood product transfusion requirements, such as cardiac surgery or organ transplantation, may be at higher risk of this nosocomial infection during epidemics.

Objective:To determine the accuracy and cost-effectiveness of a polymerase chain reaction (PCR) for detecting nasal carriage ofStaphylococcus aureusdirectly from clinical specimens.Cross-Sectional Study:This occurred in a tertiary-care hospital in Cleveland, Ohio, and included 239 consecutive patients who were scheduled for a cardiothoracic surgical procedure. Conventional cultures and a PCR for S.aureusfrom nasal swabs were used as measurements.Cost-Effectiveness Analysis:Data sources were market prices and Bureau of Labor Statistics. The time horizon was the maximum period for availability of culture results (3 days). Interventions included universal mupirocin therapy without testing; initial therapy, with termination if PCR negative (treat-PCR); initial therapy, with termination if culture negative (treat-culture); treat PCR-positive carriers (PCR-guided treatment); and treat culture-positive carriers (culture-guided treatment). The perspective was institutional and costs and the length of time to treatment were outcome measures.Results:Sixty-seven (28%) of the 239 swabs grewS. aureus.Rapid PCR was 97.0% sensitive and 97.1% specific for the detection of S.aureus.For populations with prevalences of nasalS. aureuscarriage of up to 50%, the PCR assay had negative predictive values of greater than 97%. PCR-guided treatment had the lowest incremental cost-effectiveness ratio ($1.93 per additional day compared with the culture strategy). Among immediate treatment strategies, treat-PCR was most cost-effective. The universal therapy strategy cost $38.19 more per additional day gained with carrier identification compared with the PCR strategy.Conclusion:Rapid real-time PCR is an accurate, rapid, and cost-effective method for identifyingS. aureuscarriers for preoperative intervention.

Hypogammaglobulinemia (HGG) in solid organ transplant (SOT) patients confers an increased risk of opportunistic infections and poorer outcomes. Severe HGG (IgG350 mg/dL) after heart transplantation may follow intensification of immunosuppressive therapy and the resultant increased risk of opportunistic infections, particularly cytomegalovirus (CMV) disease. Evaluation of the effects of replacement therapy using intravenous immunoglobulin (CMV-IGIV, CytoGam) was conducted in cardiac transplant recipients and the data matched with a historical control group. Patients with severe HGG who received pre-emptive replacement therapy had significantly fewer opportunistic infections (P0.001) and episodes of rejection (gradeor = 3; P = 0.03 and gradeor = 2; P = 0.04) compared with the control group.

The purpose of this study was to evaluate the humoral immune response to influenza vaccination in lung transplant recipients. Antibody levels to the three viral antigens included in the 1999-2000 trivalent influenza vaccine (A/Sydney/5/97-like (H3N2), A/Beijing262/95-like (H1N1), and B/Yamanashi/16/ 98) were measured before and 4 weeks postvaccination in 43 lung transplant recipients and 21 healthy adult controls. The ability to develop protective antibody levels, a serological response, and the magnitude of change in levels were assessed. The humoral immune response to influenza vaccination was significantly lower in the transplant group for all three viral antigens. To A/Sydney, 95% of the control group and 40% of the transplant group developed protective levels (p=0.0009); to A/Beijing, 71% of the control group and 30% of the transplant group developed protective levels (p=0.004); and to B/Yamanashi, 48% of the control group and 19% of the transplant group developed protective levels (p=0.02). Those receiving cyclosporine had lower antibody responses when compared to those receiving tacrolimus (r=-0.3056, p=0.0463). The humoral immune response to influenza vaccination in lung transplant recipients is poor. Lung transplant recipients receiving cyclosporine may have a lower antibody response than those receiving tacrolimus. Alternative prevention strategies may be needed.

Vaccination is recommended for overseas travelers, children, older adults, transplant recipients, patients with chronic liver disease, and others at risk.

Objective To examine the safety and the immunologic and virologic consequences of corticosteroid use in HIV-1 infection. Methods A randomized, double-blinded, placebo-controlled trial of corticosteroid administration in 41 patients with advanced HIV-1 infection. Patients had a baseline median CD4 cell count of 131 x 10(6) cells/l at enrollment and 85% had a history of opportunistic infection. All but one of the patients had been taking stable antiretroviral regimen, including a protease inhibitor in 36, for a median duration of 158 days. Patients were randomized to 8 weeks of prednisone 0.5 mg/kg daily or placebo. Results No AIDS-defining events occurred; two patients in each group developed oral candidiasis, and two patients on prednisone developed mild herpes simplex flares. None who developed oral candidiasis or herpes simplex was receiving prophylaxis and each responded promptly to therapy. In the prednisone group, two patients developed hyperglycemia and one diabetic increased insulin requirements. CD4 cell counts and plasma HIV-1 RNA levels did not change, but plasma tumor necrosis factor alpha levels and CD38+ CD8+ cells decreased significantly in those taking prednisone. Conclusion Short-term prednisone administration is well tolerated and reasonably safe in advanced HIV-1 disease and decreases immune activation without effects on HIV-1 RNA levels or CD4 cell counts. These results suggest that, in stable HIV-1 disease, these immune activation markers are more likely consequences of but not inducers of HIV-1 replication.

We report the case of a patient with Crohn's disease and recurrent pneumonia for over 3 years before the discovery of an occult ileopulmonary fistula and review five other cases in the literature. Patients often present with chronic cough productive of feculent sputum, pleuritic chest pain, and signs of pulmonary consolidation that fail to respond completely to antibiotic therapy. Mixed enteric flora is cultured from sputum and bronchial washings in most cases. Bronchoscopy findings range from chronic bronchial inflammation to feculent material in the airways. Barium enema is often diagnostic. Surgery and Crohn's-specific therapy are key components of curative therapy.

Each year millions of people travel overseas, where they may come into contact with infectious diseases unfamiliar to citizens of the industrialized world. Reviewing the potential risks, and how to avoid them, greatly enhances the chances of an uneventful trip. This article contains specific recommendations including recipes for oral rehydration solutions that travelers can prepare.

THE IMPACT OF CYTOGAM ON CARDIAC TRANSPLANT RECIPIENTS WITH MODERATE HYPOGAMMAGLOBULINEMIA M.H. Yamani, R.C. Starling, R. Avery, S. Mawhorter, A. McNeil, N.B. Ratliff, D. Cook, D. Pelegrin, P. Colosimo, K. Kiefer, R. Hobbs, D. Taylor, P. McCarthy, J.B. Young, Cardiovascular Medicine; Infectious Disease; Anatomic Pathology; Allogen Laboratory; CardioThoracic Surgery, Cleveland Clinic Foundation, Cleveland, OH

Pediatric patients hospitalized at Strong Memorial Hospital, Rochester, New York, between April 1, 1985, and November 7, 1986, who received ceftriaxone were identified by daily examination of pharmacy records. Hospital records were retrospectively reviewed, and patients who completed antibiotic therapy with ceftriaxone as outpatients were identified. Primary physicians were contacted by telephone to verify duration of therapy, determine office versus home administration of ceftriaxone, and identify complications or problems. Parents were also contacted by telephone, and a questionnaire used to obtain information about drug-related complications, relapse or recurrence, impact of home versus hospital treatment, and their acceptance of outpatient therapy. Costs related to antibiotic therapy were based on 1986 pharmacy charges, which include a fixed dispensing fee of $3.40 per dose. As an estimate of minimum daily hospital costs, the $250 room fee for a standard semiprivate room at SMH was used. The cost for home therapy was based on the $51 visiting nurse service fee for basic evaluation and administration of medication in Monroe County, New York.

OUTPATIENT ADMINISTRATION OF CEFTRIAXONE TO COMPLETE TREATMENT FOR SERIOUS BACTERIAL INFECTIONS