The reluctance to use organs from donors who have died from severe infections is based on the potential transmission of an infectious agent to the recipient and on the uncertainty about allograft ...function in the setting of severe donor sepsis.
From 1999 to 2007, donor hospital records were reviewed which focused on microbiology cultures and sensitivity results; type and duration of antimicrobial therapy; hemodynamic data, results of echocardiogram, and imaging studies. Preliminary positive and negative results from pre-harvest blood, respiratory, urine, and cerebrospinal fluid cultures were verified with the procurement agency. The harvesting surgeon performed gross inspection of donor valvular structures.
Nine donor hearts were transplanted from patients who expired from community onset infections with severe septic shock, meningitis, and/or pneumonia caused by Streptococcus pneumoniae (n = 4), Streptococcus milleri (n = 2), Neisseria meningitidis (n = 2), and unidentified gram- positive cocci (n = 1). Four donors had probable infection-induced intracranial hemorrhage, and all donors were vasopressor-dependent before organ procurement. No evidence of donor-transmitted infection, sepsis, or rejection was observed, and long-term function remained excellent; allograft dysfunction in three patients resolved after transplant. Our series of nine donors represents approximately 1.3% of successfully transplanted cardiac allografts during the respective period of review.
Patients succumbing to severe infections (meningitis, pneumonia, and septic shock) should not be arbitrarily excluded for possible heart donation. Assessing the suitability of donors with severe infections requires flawless communication between the donor and transplant facility, including a comprehensive evaluation of donor infection and pathogen(s), severity of sepsis, adequacy of antimicrobial treatment, and the degree of sepsis-induced myocardial dysfunction.
Many physicians in the United States and other nonendemic countries lack familiarity with New World cutaneous leishmaniasis (CL) and fail to include it in their differential diagnosis when seeing ...patients with suggestive lesions and recent high-risk travel. Moreover, even when the diagnosis of New World CL is considered and confirmed, physicians in the United States still face obstacles in obtaining appropriate treatment. In this report, we present 3 cases of New World CL that were either initially misdiagnosed or faced significant delays in therapy. We also discuss the optimal approach by which to confirm New World CL and to collaborate with professional colleagues at the Centers for Disease Control and Prevention in treating individual patients. In particular, when pentavalent antimonial treatment is needed for treatment, physicians must obtain appropriate diagnostic studies, communicate with experts at the Centers for Disease Control and Prevention, complete necessary paperwork, and obtain approval from their local institutional review board to administer it.
Ceftazidime-avibactam is the first antimicrobial approved by the U.S. FDA for the treatment of carbapenem-resistant Enterobacteriaceae. Avibactam, a non-β-lactam β-lactamase inhibitor, inactivates ...class A serine carbapenemases, including Klebsiella pneumoniae carbapenemase (KPC). We report a KPC-producing K. pneumoniae isolate resistant to ceftazidime-avibactam (MIC, 32/4 μg/ml) from a patient with no prior treatment with ceftazidime-avibactam.
Antibiotic selective pressure may result in changes to antimicrobial susceptibility throughout the course of infection, especially for organisms that harbour chromosomally encoded AmpC β-lactamases, ...notably Enterobacter spp., in which hyperexpression of ampC may be induced following treatment with cephalosporins. In this study, we document a case of bacteraemia caused by a blaSME-1-harbouring Serratia marcescens that subsequently developed resistance to expanded-spectrum cephalosporins, piperacillin/tazobactam and fluoroquinolones, over the course of several months of treatment with piperacillin/tazobactam and ciprofloxacin.
Susceptibility testing and WGS were performed on three S. marcescens isolates from the patient. β-Lactamase activity in the presence or absence of induction by imipenem was measured by nitrocefin hydrolysis assays. Expression of ampC and blaSME-1 under the same conditions was determined by real-time PCR.
WGS demonstrated accumulation of missense and nonsense mutations in ampD associated with stable derepression of AmpC. Gene expression and β-lactamase activity of both AmpC and SME-1 were inducible in the initial susceptible isolate, but were constitutively high in the resistant isolate, in which total β-lactamase activity was increased by 128-fold.
Although development of such in vitro resistance due to selective pressure imposed by antibiotics is reportedly low in S. marcescens, our findings highlight the need to evaluate isolates on a regular basis during long-term antibiotic therapy.
There is no evidence that currently recommended vaccines overload or weaken the infant immune system. Infants have an enormous capacity to respond safely and effectively to multiple vaccines. The ...schedule for the administration of childhood vaccines is tailored to the unique developmental pattern of the infant immune system. Childhood vaccines provide immediate protection from common childhood illness and establish the foundation for lifelong immunity that develops with subsequent vaccination or infection. Widespread vaccination of infants and children represents a public health triumph of the 20th century. This fact must be reinforced continually by health care workers and parent education to help maintain progress in the 21st century.
Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International ...Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics.
Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post‐lung transplantation. Lung allograft airway colonization by Aspergillus species is common ...among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post‐lung transplantation. We reviewed all lung transplant recipients transplanted in our center between January 2000 and June 2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87–520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post‐lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS.
Aspergillus colonization of the lung allograft is associated with an increased risk of bronchiolitis obliterans syndrome. See Editorial by Garantziotis and Palmer on page 1705–1706.
Artemisinin derivatives are the key active ingredients in Artemisinin combination therapies (ACTs), the most effective therapies available for treatment of malaria. Because the raw material is ...extracted from plants with long growing seasons, artemisinin is often in short supply, and fermentation would be an attractive alternative production method to supplement the plant source. Previous work showed that high levels of amorpha-4,11-diene, an artemisinin precursor, can be made in Escherichia coli using a heterologous mevalonate pathway derived from yeast (Saccharomyces cerevisiae), though the reconstructed mevalonate pathway was limited at a particular enzymatic step.
By combining improvements in the heterologous mevalonate pathway with a superior fermentation process, commercially relevant titers were achieved in fed-batch fermentations. Yeast genes for HMG-CoA synthase and HMG-CoA reductase (the second and third enzymes in the pathway) were replaced with equivalent genes from Staphylococcus aureus, more than doubling production. Amorpha-4,11-diene titers were further increased by optimizing nitrogen delivery in the fermentation process. Successful cultivation of the improved strain under carbon and nitrogen restriction consistently yielded 90 g/L dry cell weight and an average titer of 27.4 g/L amorpha-4,11-diene.
Production of >25 g/L amorpha-4,11-diene by fermentation followed by chemical conversion to artemisinin may allow for development of a process to provide an alternative source of artemisinin to be incorporated into ACTs.
Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly ...understood. Based on the association of TGF-β with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single-center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF-β and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF-β and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76–5.38) for the most severe form of PGD. TGF-β and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF-β and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF-β biology.
PDF
