Unilateral leg pain caused by cryptococcal myositis: An unusual presentation of disseminated cryptococcosis in a kidney transplant recipient.

Cryptococcal disease is a rare but often serious infection in solid organ transplant recipients, commonly presenting as meningitis and pneumonia but can rarely cause myositis. We report the case of a 43-year-old female kidney transplant recipient with two previous graft failures requiring re-transplantations who presented with a 1-month duration of worsening unilateral leg pain, swelling, and shortness of breath. Blood cultures isolated Cryptococcus neoformans. A calf biopsy was performed and histopathology revealed myonecrosis with yeast forms consistent with Cryptococcus spp. Liposomal amphotericin B (LamB) was administered. Her course was complicated by hypoxemic respiratory failure with development of ground glass opacities on chest imaging. Work-up revealed bacterial and C neoformans pneumonia and probable Pneumocystis jirovecii pneumonia (PJP) She received trimethoprim-sulfamethoxazole and LamB and was discharged on fluconazole. Shortly thereafter she was re-admitted with confusion, septic shock, and multi-organ failure. Work-up revealed PJP with subsequent development of cryptococcal meningitis. Despite aggressive management, she expired. Disseminated cryptococcal infection may manifest as myositis. Presence of cryptococcal infection is a marker of severe net state of immunosuppression (IS), hence, presence of other opportunistic infections is likely. Early recognition of cryptococcal infection, institution of targeted therapy, and IS reduction are important to improve overall survival.

Clinical and epidemiological characterization of histoplasmosis cases in a nonendemic area, Connecticut, United States.

We performed a retrospective analysis of histoplasmosis cases diagnosed at our institution in New Haven, Connecticut, from 2005 to 2015. Among 12 cases of active histoplasmosis, seven were immunosuppressed and five had human immunodeficiency virus (HIV). Eleven patients reported travel to potentially endemic areas at a median of 105 days prior to presentation; travel to the Caribbean was most common (n = 6). Median time to diagnosis from symptom onset and first Histoplasma antigen testing were 41 and 28 days, respectively. Consistent with reports from other non-endemic areas, our findings suggest that the epidemiology of histoplasmosis may differ in Connecticut, potentially contributing to delayed diagnoses.

Fatal case of cutaneous-sparing orolaryngeal zoster in a renal transplant recipient.

Herpesvirus infections in solid organ transplant (SOT) recipients are a significant cause of morbidity and mortality. We report a case of herpes zoster (HZ) in a kidney transplant recipient while receiving belatacept, a CTLA-4 inhibitor that prevents acute rejection. The patient presented with oropharyngolaryngeal mucosal lesions that subsequently disseminated resulting in pneumonitis and meningo-encephalitis. Very late-onset HZ can occur and can present atypically in SOT recipients. Delayed recognition and treatment may result in poor outcomes, as illustrated by this case.

Fungal Mycotic Aneurysm of the Internal Carotid Artery Associated with Sphenoid Sinusitis in an Immunocompromised Patient: A Case Report and Review of the Literature.

In immunocompromised patients, invasive molds such as Aspergillus and Mucor can lead to locally aggressive angioinvasive infections that are often life-threatening. A particularly devastating complication is the development of a fungal mycotic aneurysm resulting from invasion of the arterial wall. Due to anatomic contiguity, the sphenoid sinus provides potential access for these fungi, which often colonize the respiratory sinuses, into the cavernous sinus and internal carotid artery (ICA), thus leading to the formation of ICA aneurysms. The ideal treatment of fungal ICA aneurysms includes a combination of surgical debridement and long-term effective antifungal therapy, but the role of endoscopic resection and the duration of antimicrobials are poorly defined. Here, we present the case of a 71-year-old immunocompromised patient who developed an ICA mycotic aneurysm, associated with a proven invasive fungal infection (presumptively Mucorales) of the sphenoid sinuses, as defined by EORTC/MSG criteria, and who survived after undergoing coil embolization with parent vessel sacrifice of the aneurysm in combination with liposomal amphotericin B. We also review the literature for published cases of invasive fungal sphenoid sinusitis associated with mycotic aneurysms of the ICA and provide a comparative analysis .

Added Diagnostic Utility of Clinical Metagenomics for the Diagnosis of Pneumonia in Immunocompromised Adults.

BACKGROUND: In the evaluation of community-acquired pneumonia, 30% to 60% of cases remain undiagnosed, despite extensive conventional microbiologic testing (CMT). Clinical metagenomics (CM) is an unbiased pathogen detection method that can increase diagnostic yield. RESEARCH QUESTION: Does adding clinical metagenomics to conventional microbiologic testing improve the diagnostic yield for pneumonia in immunocompromised adults? STUDY DESIGN AND METHODS: We performed a noninterventional prospective study of immunocompromised adults with pneumonia who underwent bronchoscopy and BAL over 2 years. CMT was performed per standard of care. A commercial CM test was performed on residual BAL fluid. Final microbiologic diagnoses were based on CMT vs CMT + CM. Final clinical diagnoses for CMT and CMT + CM were made based on laboratory results in conjunction with clinical and radiologic findings. Hypothetical impact of CMT + CM on management and antimicrobial stewardship was also assessed. RESULTS: A total of 30 immunocompromised adult patients (31 episodes of pneumonia) were included. Final microbiologic diagnoses were made in 11 cases (35%) with the use of CMT and in 18 cases (58%) with the use of CMT + CM. Bacterial pneumonia was diagnosed in five cases (16%) by CMT and in 13 cases (42%) by CMT + CM; fungal pneumonia was diagnosed in six cases (19%) by CMT and in seven cases (23%) by CMT + CM, and viral pneumonia was diagnosed in two cases (6%) by CMT and in five cases (16%) by CMT + CM. The hypothetical impact of CMT + CM on management was deemed probable in one case, possible in eight cases, and unlikely in two cases, whereas the impact on antimicrobial stewardship was possible in 13 cases and unlikely in seven cases. Final clinical diagnoses were made in 20 of 31 cases (65%) based on CMT and in 23 of 31 cases (74%) based on CMT + CM. INTERPRETATION: CMT + CM increased diagnostic yield in immunocompromised adults with pneumonia from 35% to 58%, mostly by the detection of additional bacterial causes but was less useful for fungal pneumonia.

Emerging Microbiology Diagnostics for Transplant Infections: On the Cusp of a Paradigm Shift.

In light of the heightened risk for infection associated with solid organ and hematopoietic stem cell transplantation, rapid and accurate microbiology diagnostics are essential to the practice of transplant clinicians, including infectious diseases specialists. In the last decade, diagnostic microbiology has seen a shift toward culture-independent techniques including single-target and multiplexed molecular testing, mass-spectrometry, and magnetic resonance-based methods which have together greatly expanded the array of pathogens identified, increased processing speed and throughput, allowed for detection of resistance determinants, and ultimately improved the outcomes of infected transplant recipients. More recently, a newer generation of diagnostics with immense potential has emerged, including multiplexed molecular panels directly applicable to blood and blood culture specimens, next-generation metagenomics, and gas chromatography mass spectrometry. Though these methods have some recognized drawbacks, many have already demonstrated improved sensitivity and a positive impact on clinical outcomes in transplant and immunocompromised patients.

Gomori Methenamine Silver Stain on Bronchoalveolar Lavage Fluid Is Poorly Sensitive for Diagnosis of Pneumocystis jiroveci Pneumonia in HIV-Negative Immunocompromised Patients and May Lead to Missed or Delayed Diagnoses.

CONTEXT.­: Direct visualization of Pneumocystis jiroveci organisms, using Gomori methenamine silver (GMS) staining in bronchoalveolar lavage fluid (BAL), is a historical gold standard that has been widely used for the diagnosis of P jiroveci pneumonia (PJP). However, the stain may be less sensitive in human immunodeficiency virus (HIV)-negative immunocompromised patients owing to a lower burden of organisms. OBJECTIVES.­: To assess the sensitivity of the GMS stain on BAL fluid for the diagnosis of PJP in HIV-negative immunocompromised patients as compared to HIV-positive patients. DESIGN.­: We conducted a retrospective review from 2012 to 2018 to identify immunocompromised patients (≥18 years old) who underwent bronchoscopy with BAL GMS staining for the diagnosis of PJP. To assess for sensitivity, we sought to identify BAL GMS-positive cases and BAL GMS-negative cases of PJP. The BAL GMS-negative cases were categorized into proven and probable PJP. RESULTS.­: We identified 45 adult immunocompromised patients with proven and probable PJP, including 24 HIV-negative (11 BAL GMS-positive and 13 BAL GMS-negative) and 21 HIV-positive cases (all were BAL GMS-positive). The sensitivity of BAL GMS for the diagnosis of PJP in HIV-negative immunocompromised patients was 11 of 24 (46%) versus 21 of 21 (100%) in HIV-positive patients (CD4: median, 10 cells/mL; range, 3-300 cells/mL). Delayed or missed diagnoses were seen in 3 cases of BAL GMS-negative PJP. Re-examination of BAL GMS slides showed rare P jiroveci cysts in 1 case. CONCLUSIONS.­: BAL GMS has poor sensitivity for PJP in HIV-negative immunocompromised patients. Using BAL GMS as a sole method for PJP may result in missed or delayed diagnoses in this population.

Heart or lung transplant outcomes in HIV-infected recipients.

BACKGROUND: Limited published data exist on outcomes related to heart and/or lung transplantation in human immunodeficiency virus (HIV)-infected individuals. METHODS: We conducted a multicenter retrospective study of heart and lung transplantation in HIV-infected patients and describe key transplant- and HIV-related outcomes. RESULTS: We identified 29 HIV-infected thoracic transplant recipients (21 heart, 7 lung, and 1 heart and/or lung) across 14 transplant centers from 2000 through 2016. Compared with an International Society for Heart and Lung Transplantation registry cohort, we demonstrated similar 1-, 3-, and 5-year patient and allograft survivals for each organ type with a median follow up of 1,064 (range, 184-3,745) days for heart and 1,540 (range, 116-3,206) days for lung recipients. At 1 year, significant rejection rates were high (62%) for heart transplant recipients (HTRs). Risk factors for rejection were inconclusive, likely because of small numbers, but may be related to cautious early immunosuppression and infrequent use of induction therapy. Pulmonary bacterial infections were high (86%) for lung transplant recipients (LTRs). Median CD4 counts changed from baseline to 1 year from 399 to 411 cells/µl for HTRs and 638 to 280 cells/µl for LTRs. Acquired immunodeficiency syndrome-related events, including infections and malignancies, were rare. Rates of severe renal dysfunction suggest a need to modify nephrotoxic anti-retrovirals and/or immunosuppressants. CONCLUSIONS: HIV-infected HTRs and LTRs have similar survival rates to their HIV-uninfected counterparts. Although optimal immunosuppression is not defined, it should be at least as aggressive as that for HIV-uninfected recipients. Such data may help pave the way for the use of hearts and lungs from HIV-infected donors in HIV-infected recipients through HIV Organ Policy Equity Act protocols.

Management of Mycobacterium Other than Tuberculosis in Solid Organ Transplantation.

Mycobacteria other than tuberculosis are important pathogens to consider in solid organ transplant recipients. Delay in recognition and treatment may incur significant morbidity and mortality. Management of mycobacteria other than tuberculosis requires a knowledge of treatment specific for each species and drug-drug interactions between antimicrobial and immunosuppressive drugs. Therapy in solid organ transplant can be prolonged and may require a reduction in immunosuppression to improve outcomes.

Diagnosing Ring-Enhancing Lesions in the Brain of a Patient With AIDS Without Brain Biopsy: A Case of Central Nervous System Histoplasmoma.

We report a case of a Puerto Rican male with advanced AIDS who presented with multiple falls and pancytopenia. Magnetic resonance imaging (MRI) of the brain, as initial workup, revealed 2 ring-enhancing brain lesions. Initial cerebrospinal fluid analysis revealed minimal cells, mildly elevated protein, and no organism seen on gram stain. Due to prohibitive thrombocytopenia, brain biopsy was deferred. He had neither clinical nor radiographic improvement despite empiric therapy for both toxoplasmosis and bacterial abscesses. Indicated by pancytopenia, bone marrow (BM) aspiration was performed. Culture of BM aspirate grew Histoplasma capsulatum. Urine histoplasma antigen was markedly elevated. He was treated with liposomal amphotericin B (LamB) for progressive disseminated histoplasmosis with probable central nervous system involvement. Cerebrospinal fluid histoplasma antigen obtained after 2 months of LamB was detected. After prolonged course of LamB, he took itraconazole. Brain MRI at 7-month follow-up revealed significant improvement from baseline study.

Emerging role of Actinomyces meyeri in brain abscesses: A case report and literature review.

We describe a case of a 29-year-old man from Pakistan who presented with progressive neurologic symptoms over 1 week and was found to have a right parietal cerebral abscess. Neurosurgical drainage cultures showed growth of Actinomyces meyeri, Streptococcus intermedius, and Parvimonas micra. An abscessed molar was identified as the likely port of entry and was extracted. The patient was treated with metronidazole, vancomycin, and doxycycline because of prior anaphylaxis to penicillin. At 6-month follow-up, repeat magnetic resonance imaging showed no signs of residual abscess. Culture-independent identification techniques (e.g., ribosomal sequencing) increasingly identify Actinomyces meyeri as a causative agent and significant pathogen in spontaneous brain abscesses. As understanding about Actinomyces meyeri's prevalence and pathogenesis improves, questions arise about optimal treatment strategy, which we discuss based on a literature review.

Integrase strand transferase inhibitors: the preferred antiretroviral regimen in HIV-positive renal transplantation.

In the era of antiretroviral therapy, people living with HIV/AIDS live longer and are subject to co-morbidities that affect the general population, such as chronic kidney disease. An increasing number of people living with HIV/AIDS with end-stage renal disease are candidates for renal transplantation. Prior experience demonstrated that HIV-positive renal transplant recipients had acceptable survival but graft survival was decreased and rejection rates were increased, possibly due to suboptimal management of immunosuppressive medications in the face of drug interactions with antiretroviral therapy, particularly protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Integrase strand transferase inhibitors are advantageous since they avoid drug-drug interactions with immunosuppressive drugs such as calcineurin inhibitors. We report clinical outcomes of 12 HIV-positive patients who underwent 13 kidney transplantations at our institution between 2000 and 2015. Cumulative survival was 75%, one-year and three-year survival were 100% and 63%. Integrase strand transferase inhibitor-based regimens were used in nine patients, of which eight survived. In patients on integrase strand transferase inhibitor, there was 100% graft survival and two had allograft rejection. In contrast, graft failure occurred in three patients on non-integrase strand transferase inhibitor-based regimens. Based on our study findings and on previously published data, we conclude that integrase strand transferase inhibitor-based therapy, preferably instituted prior to transplantation, is the preferred antiretroviral regimen in HIV-positive renal transplantation.

Graft loss among renal-transplant recipients with early reduction of immunosuppression for BK viremia.

AIM: To review the incidence of graft loss and acute rejection among renal transplant recipients with early reduction of immunosuppression for BK viremia. METHODS: We performed a retrospective analysis of consecutive de-novo kidney-only transplants from January 2009 to December 2012 to evaluate the incidence of Polyoma-virus associated nephropathy (PyVAN). Recipient plasma was screened for BKV DNA via quantitative polymerase chain reaction (PCR) at months 1, 3, 6, 9 and 12 post-transplant and on worsening graft function. Immunosuppression was reduced at ≥ 3-log copies/mL. Those with viremia of ≥ 4-log copies/mL (presumptive PyVAN) underwent renal transplant biopsy. Presumptive PyVAN (PP) and definitive PyVAN (DP; biopsy-proven) were treated by immunosuppression reduction (IR) only. RESULTS: Among 319 kidney transplant recipients, the median age was 53 years (range 19-83), 65.8% were male, and 58.9% were white. Biopsy-proven acute rejection was found in 18.5% within 0-168 wk. Death-censored graft loss occurred in 5.3% (n = 17) and graft loss attributable to PyVAN was 0.6% (n = 2). Forty-seven patients were diagnosed with PP (14.7%) and 18 (5.6%) with DP. Graft loss among participants with PyVAN (8.5%) and those without (4.8%) was not significantly different. Deceased donor kidney transplantation (OR = 2.3, 95%CI = 1.1-4.6) and AR (OR = 2.3, 95%CI = 1.2-4.7) were associated with PyVAN in the multivariate analysis. BK viremia between 3 and 4-log copies/mL occurred in 27 patients, all of whom underwent IR. Of these, 16 (59%) never developed PyVAN while 11 (41%) developed PyVAN (4 DP, 7 PP) within a range of 11-39 wk. CONCLUSION: Instituting an early reduction of immunosuppression, in the absence of adjunctive antivirals, is effective at preventing PyVAN and may be associated with a lower incidence of graft-loss without a reciprocal increase in the incidence of acute rejection.

Disseminated Histoplasmosis with Skin Lesions and Osteomyelitis in a Patient from the Philippines.

Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is a disease of protean manifestations and of global distribution. Although increasingly reported in Asia, there are few reports from the Philippines. Here, we describe a case of microbiologically diagnosed histoplasmosis, probably acquired from the Philippines, in a returning traveler who presented with a right foot wound and papular rash. The final diagnosis was disseminated histoplasmosis with cutaneous and bone involvement, both unusual manifestations of the disease.

Therapeutic Challenges of Hepatic Mucormycosis in Hematologic Malignancy: A Case Report and Review of the Literature.

BACKGROUND The clinical presentation of mucormycosis can vary widely based on various host factors. Among malignancy- and bone marrow transplant-associated infections, the lungs are the most common site of infection. Involvement of the gastrointestinal tract is less frequently encountered. The clinical presentation is often nonspecific, and cultures typically yield no growth, making the diagnosis challenging. CASE REPORT We present a case of isolated hepatic mucormycosis in the setting of neutropenic fever and abdominal pain following induction chemotherapy for the treatment of acute myeloid leukemia. The patient was treated with combination antifungal therapy with amphotericin and posaconazole without surgical resection, given the presence of multiple liver lesions. After a prolonged course of dual antifungal therapy, the size of her liver lesions improved. Unfortunately, her lymphoproliferative disorder proved fatal, following approximately 13 months of antifungal therapy. CONCLUSIONS Among patients with mucormycosis, mortality remains high, especially in the setting of gastrointestinal involvement. Although surgical resection along with dual antifungal therapy can improve outcomes, the high mortality rate necessitates further investigation into improved diagnostic and treatment strategies including optimal antifungal therapy.

Outcomes among older adult liver transplantation recipients in the model of end stage liver disease (MELD) era.

BACKGROUND: Since 2002, the Model of End Stage Liver Disease (MELD) score has been the basis of the liver transplant (LT) allocation system. Among older adult LT recipients, short-term outcomes in the MELD era were comparable to the pre-MELD era, but long-term outcomes remain unclear. MATERIAL AND METHODS: This is a retrospective cohort study using the UNOS data on patients age ≥ 50 years who underwent primary LT from February 27, 2002 until October 31, 2011. RESULTS: A total of 35,686 recipients met inclusion criteria. The cohort was divided into 5-year interval age groups. Five-year over-all survival rates for ages 50-54, 55-59, 60-64, 65-69, and 70+ were 72.2%, 71.6%, 69.5%, 65.0%, and 57.5%, respectively. Five-year graft survival rates after adjusting for death as competing risk for ages 50-54, 55-59,60-64, 65-69 and 70+ were 85.8%, 87.3%, 89.6%, 89.1% and 88.9%, respectively. By Cox proportional hazard modeling, age ≥ 60, increasing MELD, donor age ≥ 60, hepatitis C, hepatocellular carcinoma (HCC), dialysis and impaired pre-transplant functional status (FS) were associated with increased 5-year mortality. Using Fine and Gray sub-proportional hazard modeling adjusted for death as competing risk, 5-year graft failure was associated with donor age ≥ 60, increasing MELD, hepatitis C, HCC, and impaired pre-transplant FS. CONCLUSIONS: Among older LT recipients in the MELD era, long-term graft survival after adjusting for death as competing risk was improved with increasing age, while over-all survival was worse. Donor age, hepatitis C, and pre-transplant FS represent potentially modifiable risk factors that could influence long-term graft and patient survival.

Staphylococcus aureus bacteremia in solid organ transplant recipients: evidence for improved survival when compared with nontransplant patients.

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.