Elena Beam

Cytomegalovirus in Solid Organ Transplantation: Epidemiology, Prevention, and Treatment

Cytomegalovirus (CMV) is one of the most important pathogens that infect solid organ transplant recipients. CMV is associated with increased morbidity and mortality in this population as a result of its numerous direct and indirect effects. Prevention strategies consist of preemptive therapy and antiviral prophylaxis, and the choice of which preventive approach to implement should be guided by advantages and drawbacks related to the population being managed. There are differences in the approaches to the laboratory diagnosis and treatment of CMV infection and disease depending on assay availability, clinical presentation, disease severity, and specific transplant populations. In this article, the authors aim to summarize recent publications and updates in the epidemiology, diagnosis, prevention, and treatment of CMV infection in solid organ transplant recipients during the past year, including a brief review of future directions in the field.

Impact of urinary tract infection on allograft function after kidney transplantation

Urinary tract infection (UTI) is the most common infectious complication after kidney transplantation. We aim to determine its impact on allograft function as indicated by several measures such as iothalamate glomerular filtration rate (iGFR), estimated glomerular filtration rate (eGFR), and creatinine value.

Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis.

BACKGROUND Urinary tract infections (UTI), the most common infectious complications after kidney transplantation, are associated with poor allograft survival. Identifying its predisposing factors is therefore remarkably important in order to optimize prevention strategies. MATERIAL AND METHODS A retrospective study was performed in a cohort of patients who received kidney transplantation between June 2007 and June 2009. Factors associated with development of UTI were assessed. RESULTS The population consisted of 301 patients, with majority receiving allograft from living donors (85%). A total of 101 patients (34%) developed at least one episode of UTI, and 25% of the episodes occurred during the first year after transplantation. Risk factors associated with increased risk of UTI were female gender, recurrent UTI prior to transplant, and presence of urological abnormalities. Trimethoprim-sulfamethoxazole (TMP-SMZ) use was associated with a lower risk of UTI, including a lower risk of recurrent UTI. CONCLUSIONS In this cohort of predominantly living donor kidney transplant recipients, we report a high incidence of UTI, despite our practice of early ureteral and Foley catheter removal. Female gender and prior recurrent UTI or urological abnormalities were predisposing factors, while TMP-SMZ use had a protective role. These clinical relevant findings should guide clinicians in optimizing prevention strategies against UTI in kidney transplant recipients.

Cytomegalovirus infection in liver transplant recipients: Updates on clinical management

Cytomegalovirus (CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years, and clinical guidelines have been recently updated. Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currently-recruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries. Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir (AIC246) and brincidofovir (CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.

Mycobacterium arupense Flexor Tenosynovitis: Case Report and Review of Antimicrobial Susceptibility Profiles for 40 Clinical Isolates

ABSTRACT We describe a case of chronic tenosynovitis in the hand of a 58-year-old cattle farmer. Surgical biopsy specimens grew Mycobacterium arupense. The patient responded to surgery and antimicrobial therapy based on in vitro susceptibility testing. The antimicrobial susceptibility profiles of the isolate from this patient and 39 additional clinical isolates are presented.

A survey of infection prevention and control practices among hematopoietic stem cell transplant centers

This survey of the American Society of Transplantation Infectious Disease Community of Practice demonstrates variations in clinical practices among hematopoietic stem cell transplant centers on selected infection prevention and control practices. Our findings highlight a need and emphasize an opportunity to optimize patient care through standardization of practices in this vulnerable population.

Development of high-grade daptomycin resistance in Corynebacterium striatum while on therapy

We report a case of a 62-year-old male with ischemic cardiomyopathy complicated by cardiogenic shock who underwent placement of a left-ventricular assist device (LVAD; HeartMate II) in July 2013 as destination therapy. This was complicated by a sternal infection with Candida albicans and Staphylococcus epidermidis in October 2013, which was managed conservatively with chronic suppression with fluconazole and minocycline. In December 2016, he presented with a febrile illness without localizing signs and was diagnosed with a Corynebacterium striatum bloodstream infection, which cleared within 24 h of vancomycin initiation. Computed tomography (CT) of the chest, abdomen, and pelvis noted a tiny amount of retrosternal fluid adjacent to the LVAD cannula. Transesophageal echocardiography (TEE) was not suggestive of endocarditis. Susceptibility testing revealed resistance to ciprofloxacin (MIC of 2 g/ml), clindamycin (MIC of 2 g/ml), ceftriaxone (MIC of 2 g/ml), and trimethoprim-sulfamethoxazole (MICs of 2/38 g/ml). The isolate was susceptible to meropenem (MIC of 0.25 g/ml), vancomycin (MIC of 1 g/ml), linezolid (MIC of 2 g/ml), and doxycycline (MIC of 4 g/ml) and intermediately susceptible to penicillin (MIC of 1 g/ml). Daptomycin susceptibility testing was performed by the concentration gradient diffusion method Etest on Mueller-Hinton agar containing 5% sheep blood and revealed a MIC of 0.12 g/ml. He was switched to intravenous daptomycin (6 mg/kg/day) for outpatient therapy for 7 weeks with plans for chronic suppression. About 6 weeks into therapy, the patient was readmitted with recurrence of fevers and chills. Blood cultures grew a C. striatum strain that had developed high-grade daptomycin resistance (MIC of 256 g/ml) but retained susceptibility to vancomycin (MIC of 1 g/ml). His intravenous line was removed, a tip culture was negative, and TEE and CT results were unchanged. He was switched to intravenous vancomycin, and his blood cultures cleared within 24 h. He is currently undergoing 6 weeks of vancomycin therapy without a relapse of bacteremia. An increase in the number of clinically significant infections due to Corynebacterium sp. is reported as more complex patients are managed with immunosuppression and long-term prosthetic devices. Daptomycin inhibits bacterial replication by multiple mechanisms, including membrane targeting and interruption of cell wall synthesis, resulting in disruption of the bacterial cell wall and leakage of cellular components and cell death. Data are limited regarding the development of high-grade daptomycin resistance during therapy. We performed a literature search and identified three similar cases of patients with LVAD-associated infections with C. striatum that developed high-grade daptomycin resistance during therapy, resulting in relapsed infection (1, 2). The genetic basis of daptomycin resistance in Corynebacterium sp. is not fully understood. It is proposed that a large bacterial burden with large prosthetic devices and/or prolonged exposure to daptomycin may be causative factors. In other Grampositive pathogens, such as Staphylococcus aureus and Enterococcus sp., mutations Accepted manuscript posted online 8 May 2017 Citation Ajmal S, Saleh OA, Beam E. 2017. Development of high-grade daptomycin resistance in a patient being treated for Corynebacterium striatum infection. Antimicrob Agents Chemother 61:e00705-17. https://doi .org/10.1128/AAC.00705-17. Copyright

Cytomegalovirus (CMV) DNA Quantification in Bronchoalveolar Lavage Fluid of Immunocompromised Patients with CMV Pneumonia

Cytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA‐approved PCR assay (Cobas® AmpliPrep/Cobas TaqMan® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsy‐proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/106 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients.

Unrecognized pre-transplant disseminated Coxiella burnetti infection diagnosed in a post-transplant heart-kidney recipient

To the best of our knowledge, we report the first case of pre‐transplant unrecognized disseminated Coxiella burnetii infection, unmasked in the post‐transplant period leading to both heart and kidney allograft dysfunction. A 59 year old man with a history of simultaneous heart‐kidney transplantation due to end stage heart failure from severe aortic regurgitation (AR) and cryoglobulinemic immune complex mediated concentric necrotizing glomerulonephritis (GN), presents with a history of intermittent fevers and fatigue. Prior to transplantation he was treated for multiple episodes of culture negative endocarditis requiring bio‐prosthetic valve replacement. Evaluation of fever included a transesophageal echocardiogram (TEE) that revealed a large hyperechoic mass on the anterior mitral leaflet with perforation, severe mitral regurgitation and moderate AR. Blood cultures were negative at that time. Owing to development of allograft mitral and aortic valve insufficiency, he underwent allograft bio‐prosthetic mitral valve (MV) replacement and aortic valvuloplasty 2 years following his transplantation. Pathologic examination of the allograft mitral valve demonstrated fibrinopurulent exudate with degenerating bacterial organisms, consistent with vegetation and myxoid degenerative changes. Due to a high suspicion for native heart C. burnetii prosthetic valve endocarditis prior to transplantation, we re‐evaluated the native explanted heart histopathology, as well as the explanted allograft MV. Cardiac allograft and native MV were positive for C. burnetii by real‐time PCR. C. burnetii serology was consistent with persistent infection as well.

A survey of infection prevention and control practices among solid organ transplantation centers

HIGHLIGHTSInfection prevention and control strategies vary among transplantation centers.Standard hand hygiene is most often used in solid organ transplantation centers.Infection prevention practices differ among the solid organ populations. &NA; There are no standard guidelines for infection prevention and control practices among solid organ transplantation centers. To characterize the differences in infection prevention and control strategies, an electronic survey was performed in 2015 among members of American Society of Transplantation Infectious Diseases Community of Practice. These results highlight notable practice differences.