Fatal respiratory infection due to ST308 VIM-1-producing Pseudomonas aeruginosa in a lung transplant recipient: case report and review of the literature.

BACKGROUND: Data regarding the prevalence of metallo-ß-lactamases (MBLs) among Pseudomonas aeruginosa isolates in cystic fibrosis patients are scarce. Furthermore, there is limited knowledge on the effect of MBL production on patient outcomes. Here we describe a fatal respiratory infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient and the results of the subsequent epidemiological investigation. CASE PRESENTATION: P. aeruginosa isolates collected in the index patient and among patients temporally or spatially linked with the index patient were analyzed in terms of antibiotic susceptibility profile and MBL production. Whole-genome sequencing and phylogenetic reconstruction were also performed for all P. aeruginosa isolates producing VIM-type MBLs. A VIM-producing P. aeruginosa strain was identified in a lung biopsy of a lung transplant recipient with cystic fibrosis. The strain was VIM-1-producer and belonged to the ST308. Despite aggressive treatment, the transplant patient succumbed to the pulmonary infection due to the ST308 strain. A VIM-producing P. aeruginosa strain was also collected from the respiratory samples of a different cystic fibrosis patient attending the same cystic fibrosis center. This isolate harbored the blaVIM-2 gene and belonged to the clone ST175. This patient did not experience an adverse outcome. CONCLUSIONS: This is the first description of a fatal infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient. The circulation of P. aeruginosa isolates harboring MBLs pose a substantial risk to the cystic fibrosis population due to the limited therapeutic options available and their spreading potential.

Donor-derived tuberculosis (TB): isoniazid-resistant TB transmitted from a lung transplant donor with inadequately treated latent infection.

Donor-derived tuberculosis (TB) is an increasingly recognized complication of solid organ transplantation. We report a case of isoniazid-resistant pulmonary TB in a lung transplant recipient. The patient acquired the infection from the lung donor who was previously empirically treated with isoniazid for latent TB. The case highlights the caveat that, while adequate treatment of latent TB with isoniazid is presumed, meticulous screening of donors is required.

National Healthcare Delivery Systems Influence Lung Transplant Outcomes for Cystic Fibrosis.

Successful lung transplantation (LTx) depends on multiple components of healthcare delivery and performance. Therefore, we conducted an international registry analysis to compare post-LTx outcomes for cystic fibrosis (CF) patients using the UNOS registry in the United States and the National Health Service (NHS) Transplant Registry in the United Kingdom. Patients with CF who underwent lung or heart-lung transplantation in the United States or United Kingdom between January 1, 2000 and December 31, 2011 were included. The primary outcome was all-cause mortality. Kaplan-Meier analysis and Cox proportional hazards regression evaluated the effect of healthcare system and insurance on mortality after LTx. 2,307 US LTx recipients and 451 individuals in the United Kingdom were included. 894 (38.8%) US LTx recipients had publically funded Medicare/Medicaid insurance. US private insurance and UK patients had improved median predicted survival compared with US Medicare/Medicaid recipients (p < 0.001). In multivariable Cox regression, US Medicare/Medicaid insurance was associated with worse survival after LTx (US private: HR0.78,0.68-0.90,p = 0.001 and UK: HR0.63,0.41-0.97, p = 0.03). This study in CF patients is the largest comparison of LTx in two unique health systems. Both the United States and United Kingdom have similar early survival outcomes, suggesting important dissemination of best practices internationally. However, the performance of US public insurance is significantly worse and may put patients at risk.

Practical guidelines: lung transplantation in patients with cystic fibrosis.

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.

Effects of nutritional status and dietetic interventions on survival in Cystic Fibrosis patients before and after lung transplantation.

BACKGROUND: This study retrospectively investigated nutritional status, dietetic intervention and intake in Cystic Fibrosis (CF) patients before and after lung transplantation (LTX). METHODS: Body Mass Index (BMI), Fat Free Mass Index (FFMI) and nutritional intake were retrieved from 75 out-patients aged 15-53 years. Patients were seen every 3-4 months during the waiting list time (range 0-81 months) and up to 116 months after LTX. Survival was measured in months. RESULTS: The median BMI at baseline was 19.2 kg/m(2) (range: 15.3 to 28.4 kg/m(2)) with 29 patients (39%) below ≤18.5 kg/m(2). FFMI (measured in 65 patients) had a median of 15.2 kg/m(2) (range: 11.1 to 22.4 kg/m(2)) with 39 patients (60%) ≤16.7 kg/m(2) (men) or ≤14.6 kg/m(2) (women). Median energy intake was 2800 kcal, 239 kcal higher than the estimated energy requirement. However, 8 patients consumed ≥500 kcal less than recommended. Protein intake was 104 (range 60-187) g or 1.9 g/kg per day. Despite dietetic intervention with oral nutritional supplements (ONS) (36 patients), tube feeding (12 patients), or both (13 patients), BMI and FFMI hardly improved pre-LTX. LTX was performed in 51 patients (68%); 10 patients died during follow-up, median survival time was 41 months. A BMI ≤18.5 kg/m(2) was more prevalent in patients who died before LTX (6/9) or who died after LTX (4/10) than in patients who were still alive on the waiting list (5/15) or who survived LTX (14/41). Results for FFMI were comparable. From 6-12 months post-LTX, BMI and FFMI markedly improved, especially in underweight patients. CONCLUSION: A BMI ≤18.5 kg/m(2) and an FFMI ≤16.7 kg/m(2) (men) or ≤14.6 kg/m(2) (women) appears to impair survival in LTX candidates with CF. Patients maintained a low body weight before LTX. After LTX weight gain is achieved.

Lung transplantation in cystic fibrosis normalizes essential fatty acid profiles.

BACKGROUND: Cystic fibrosis (CF) can be a devastating disease. Disorders in essential fatty acid state are increasingly reported and various supplementation trials have been performed in an attempt to improve outcomes. However, the mechanisms leading to these disturbances remain elusive. We wanted to investigate the role of the diseased CF lung on fatty acid profiles. METHODS: We compared fatty acid profiles in patients with CF after lung transplantation (n=11) to age-matched healthy controls and homozygous F508del patients (n=22 each). RESULTS: Compared to healthy controls, in patients with CF, there are decreased levels of docosahexaenoic, linoleic and arachidonic acid and increased levels of mead acid. In patients that underwent a lung transplantation, levels of docosahexaenoic, linoleic and arachidonic acid were normal. Mead acid did not decrease significantly. CONCLUSIONS: The diseased CFTR deficient lung is a major determinant in the disturbed fatty acid profile in CF.

Acute irreversible oxalate nephropathy in a lung transplant recipient treated successfully with a renal transplant.

We report a 29 year old male cystic fibrosis patient with end stage lung disease and normal renal function who underwent a sequential double lung transplant. Medical history included: an ileal resection and pancreatic exocrine dysfunction. The postoperative period was complicated with haemorrhage and repeat surgery, requiring multiple blood transfusions and extensive antibiotic cover. Pancreatic supplements were interrupted. Acute renal failure attributed to haemodynamically-mediated acute tubular necrosis was managed expectantly. He remained dialysis dependent 8 weeks post surgery and was maintained on triple immunosuppression with tacrolimus, mycophenolate and prednisolone. A DTPA study was consistent with ATN. Renal biopsy revealed features consistent with tubular injury due to acute oxalate nephropathy (AON). Further biochemical characterization excluded primary hyperoxaluria but confirmed increased 24 hour urinary oxalate. He was maintained on enhanced frequency HDF and subsequently received an uncomplicated live related renal transplant 10 months post lung transplant with only additional basiliximab. Calcium carbonate was continued to manage post transplant hyperoxaluria and an early renal biopsy excluded recurrent oxalate injury. Enteric hyperoxaluria due to malabsorption in patients with CF especially with ileal resection, in addition to loss of gut Oxalobacter formigenes due to prolonged antimicrobials, increases the risk of AON. Increased awareness of this condition and screening prior to lung transplant is recommended.

Increased serum vitamin A and E levels after lung transplantation.

BACKGROUND: Adult cystic fibrosis (CF) patients experience significant increases in serum vitamin A and E levels after lung transplantation. It is unclear whether this finding is specific to the CF population or inherent to the lung transplantation process. METHODS: The objectives of this study were to assess pre- and postlung transplantation serum vitamin A and E levels in subjects with end-stage lung disease secondary to all causes. The study population consisted of adults who received a lung transplant at the Toronto Lung Transplant Program between 2004 and 2009. The mean change in serum vitamin A and E levels pre- and postlung transplant was evaluated using a paired t test, while differences in vitamin A and E levels between CF and non-CF subjects were determined using a Student's t test. RESULTS: Thirty-two CF and 21 non-CF subjects who underwent lung transplantation were included in the study. Mean serum vitamin A and vitamin E levels increased significantly after transplant, from 1.2 to 3.5 µmol/L (P<0.0001) and from 21.9 to 33.2 µmol/L (P<0.0001), respectively. The proportion of individuals with serum levels above the upper limit of normal increased from 7.6% to 88.7% (P<0.0001) and from 11.3% to 24.5% (P=0.02) for vitamin A and vitamin E, respectively. The dosage of vitamin supplementation did not increase after transplant. CONCLUSIONS: Significant increases in serum vitamin A and E levels were seen in both CF and non-CF subjects after lung transplantation. Further research is needed to understand the cause and clinical implications of these findings.

Reestablishment of hope as an intervention for a patient with cystic fibrosis awaiting lung transplantation.

Patients with cystic fibrosis (CF) experience a progressive deterioration in health leading to a shortened life expectancy with concomitant psychologic challenges that also may require intervention. Approaches to address psychologic dysfunction include insight-oriented therapy, cognitive-behavioral therapy, biofeedback, hypnosis, massage, music therapy, relaxation, and family therapy. Patients who learn to use coping strategies are more likely to adhere to treatment, which helps improve both their physical and psychologic well-being. Unique stressors arise for patients awaiting lung transplant as a result of their advanced state of disease along with their fear of death before donor lungs become available. This case report demonstrates some of the psychologic struggles faced by a 10-year-old with CF as he awaited lung transplantation, which led to a loss of hope and his request for withdrawal of care. Encouraging of the patient to express how his life might be improved yielded changes in his management that restored his hopefulness, and allowed him to survive long enough to undergo successful lung transplantation. Thus, reestablishment of hope might be studied as an additional intervention to help improve the well-being of patients who are seriously ill.

Diminishing role of contrast enema in simple meconium ileus.

PURPOSE: Contrast enema is the initial study of choice for simple meconium ileus to confirm diagnosis and to relieve obstruction. Despite favorable historically published results, our clinical impression suggests decreased effectiveness of the contrast enema resulting in more surgical interventions in contemporary practice. METHODS: A retrospective multiinstitutional review for a 12-year period was conducted for neonates diagnosed with meconium ileus by contrast enema. The neonates were divided into 2 groups-historic group (HG = before 2002) and contemporary group (CG = after 2002). T test was used for comparison of continuous variables and chi(2) for categorical data. RESULTS: Thirty-seven total patients were identified (21 females and 16 males). Obstruction was relieved in 8 neonates (22% overall success rate). Average enema attempt per patient was decreased in the CG group compared to HG (1.4 vs 1.9). The success rate in the CG group was 5.5% (1/18) compared to 39% (7/18) in HG. CONCLUSIONS: In this review, success of contrast enema for relief of meconium ileus has significantly decreased over time. These findings may be because of reluctance to repeat enemas, change in radiologist experience, or use of contrast agent. As a result, higher rates of operative intervention are now observed. In stable patients, surgeons should recommend repeat enemas before exploration.

Successful recovery after disseminated infection due to mycobacterium abscessus in a lung transplant patient: subcutaneous nodule as first manifestation--a case report.

Mycobacterium abscessus infection following lung transplantation (LT) has been described in a few cases. It is characterized by a variable initial location and subsequent course in this special risk group of patients, particularly those with cystic fibrosis (CF). Herein we have presented the case of a patient subjected to LT due to CF, who 1 year after transplantation developed a subcutaneous nodule produced by M abscessus, with subsequent hematogenous spread as well as bronchial and bone marrow involvement. Antecedents prior to LT included Staphylococcus aureus colonization and sputum positivity for Aspergillus fumigatus and Scedosporium apioespermum. Treatment with ciprofloxacin and linezolid was started on the basis of the antibiogram findings. The latter antibiotic was replaced by clarithromycin for 6 months. Two years later, the patient remains asymptomatic with respiratory function parameters in the normal range. The infected patient described herein was our only case with sepsis and multisystemic spread. The important mortality among such cases reported in the literature makes early diagnosis and treatment essential.

Increased vitamin A and E levels in adult cystic fibrosis patients after lung transplantation.

Most patients with cystic fibrosis (CF) and pancreatic insufficiency require supplementation with fat-soluble vitamins to maintain normal serum levels. Even with supplementation, toxicity is rare. We evaluated serum vitamin A and E levels in 23 adult patients with CF who underwent double lung transplantation. Twenty-one of the subjects were pancreatic insufficient. Fifteen subjects had serum vitamin levels before and after transplant. The median time posttransplantation for these subjects was 9 months. Mean serum vitamin A and E levels were significantly higher posttransplantation (P<0.0001, P<0.001, respectively). Eight subjects who only had posttransplant vitamin levels also had abnormally high vitamin A levels. Although the etiology of this novel finding is unclear, possibilities include altered absorption, drug interactions, impaired retinol metabolism, or increased hepatic synthesis of retinol binding protein.

A disciplined approach to spiritual care giving for adults living with cystic fibrosis.

Adults living with cystic fibrosis are less likely than other pulmonary patients to describe themselves as religious, to attend worship services regularly, to use god language, to describe their spiritual life, and in general, to give any obvious, outward indications of their spiritual strength, concerns, and depth. And yet, they have consistently demonstrated in chaplain-patient encounters an awareness of the function and importance of their spirituality in relation to life choices, coping with illness, facing mortality, and expressing life meaning, beliefs, and values. A disciplined approach by chaplains is a key component to engaging these patients so that each person's unique spiritual story unfolds. Results from The Discipline demonstrate how adults with cystic fibrosis are different in their expression and approach to spirituality from other pulmonary patients.

Newer therapies for cystic fibrosis.

Cystic fibrosis (CF) is a chronic, progressive, genetic disease caused by flawed ion transport across epithelial membranes due to a genetic mutation. Most therapeutic efforts are centred on the main clinical manifestations of the disease: progressive destructive airway disease and pancreatic insufficiency. Most individuals with CF succumb to lung disease. The present-day therapeutic armamentarium includes agents that have been used for many decades, some of which have experienced transformations in their formulation or mode of administration thanks to the introduction of new manufacturing technologies. The development of new therapies involves new conceptual approaches, based on recent understanding of the disease. These therapies await proof of concept or clinical experimentation before being accepted as useful means to arrest the progression of the disease. In this article we will review therapeutic agents introduced into the clinical arsenal in the last 20 years, as well as experimental therapies under active investigation.

Antibiotic susceptibility of multiply resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis, including candidates for transplantation.

Chronic lung disease caused by antibiotic-resistant Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is difficult to treat, especially in those who are lung transplantation candidates. Analysis of antibiotic susceptibility and synergy studies of 1,296 isolates revealed that 172 (13.3%) were multiply resistant (i.e., resistant to two or more classes of anti-Pseudomonas agents). beta-Lactam agents (including imipenem and aztreonam) or aminoglycosides inhibited only 11% of the multiply resistant strains, while ciprofloxacin inhibited 34%. High concentrations of tobramycin and gentamicin (200 micrograms/mL), achievable by aerosol administration, inhibited 95% of isolates and overwhelmed permeability-resistance mechanisms. Antimicrobial pairs tested in checkerboard dilutions of clinically achievable drug concentrations inhibited 75% of the multiply resistant strains. On average, three additive and 2.4 synergistic pairs of antimicrobial agents had activity per strain. Transplantation candidates were older than nontransplantation candidates (P = .034), and isolates from transplantation candidates were less likely to be inhibited by antibiotic combinations (P < .001). Administration of aerosolized aminoglycosides and synergy testing of antimicrobial combinations may represent viable therapeutic options for patients with CF.

Infectious complications of lung transplantation. Impact of cystic fibrosis.

It has been suggested that the presence of airway pathogens prior to lung transplantation (LT) in patients with cystic fibrosis (CF) may place these patients at a higher risk for infectious complications after LT. There is particular concern regarding patients colonized with multiresistant Pseudomonas, including P. cepacia, and fungi, including Aspergillus. We report our experience with LT for patients with CF and compare the results with those of patients with LT for other indications. Between January 1990 and March 1993, we performed LT for 27 patients with CF and 32 without CF. Nearly all (89%) of the patients with CF were colonized with P. aeruginosa; many were cultured with P. cepacia (19%) and Aspergillus (63%). The non-CF group rarely had organisms identified pre-LT. No patients with CF underwent pre-LT sinus drainage or received pre-LT treatment for Aspergillus. All of the patients received perioperative antibiotics and a standard regimen of immunosuppression and prophylactic antibiotics. The incidence of infectious complications was the same in the two groups; however, there was an association between obliterative bronchiolitis and pulmonary infections. One of the patients with CF with P. cepacia died as a result of this organism. None of the patients with CF required treatment for Aspergillus post-transplant. We conclude that patients with CF, despite the presence of airway pathogens, are at no greater risk of infectious complications after LT than are other patients.