Successful ceftazidime‐avibactam treatment of post‐surgery Burkholderia multivorans genomovar II bacteremia and brain abscesses in a young lung transplanted woman with cystic fibrosis

Burkholderia cepacia complex (Bcc) includes several phenotypically similar but genotypically distinct gram‐negative bacteria (GNB) that can colonize the respiratory tract of Cystic Fibrosis (CF) patients. Pathogens are difficult to treat due to intrinsic resistance to multiple antibiotics and are associated to a more rapid decline in lung function and to increased mortality, particularly after lung transplantation. For all these reasons, chronic infection by Burkholderia (B) cenocepacia is presently considered a relative or absolute contraindication in almost all lung transplant centres. We report the case of a young adult CF patient chronically colonized by B multivorans genomovar II, with diabetes and end‐stage renal disease treated with renal replacement therapy: a few months after lung transplantation, she developed post‐surgery B multivorans bacteremia and multiple brain abscesses. This severe infection did not improve despite multiple standard antibiotic regimen. The introduction of ceftazidime‐avibactam, a new β‐lactam/ β‐lactamase inhibitor combination resulted in clinical recovery and in radiological and biochemical improvement.     

Disseminated Burkholderia gladioli infection in a lung transplant recipient with underlying hypocomplementemic urticarial vasculitis

G.R. Thompson III, B.L. Wickes, M.L. Herrera, T.C. Haman, J.S. Lewis II, J.H. Jorgensen. Disseminated Burkholderia gladioli infection in a lung transplant recipient with underlying hypocomplementemic urticarial vasculitis.
Transpl Infect Dis 2011: 13: 641–645. All rights reserved Abstract: Burkholderia gladioli is difficult to definitively identify within the laboratory using phenotypic testing alone. We describe a case of recurrent B. gladioli infection in a lung transplant recipient with underlying hypocomplementemic urticarial vasculitis syndrome, discuss the difficulties encountered with laboratory identification, provide a review of the methodology required for definitive identification, and discuss potential pathophysiologic mechanisms in this patient responsible for the difficulty in treatment.     

Antibiotic failure in a renal transplant patient with Rhodococcus equi infection: an indication for surgical lobectomy

Rhodococcus equi is an animal pathogen that causes infrequent but challenging infections in immunocompromised individuals, few of which have been described in solid organ transplant recipients. Common clinical presentations include indolent cough, fever, and dyspnea, with necrotizing pneumonia and cavitation. We report a case of a dense right upper lung pneumonia with resultant R. equi bacteremia in a renal transplant recipient. Our patient initially responded to antibiotic treatment with resolution of bacteremia and clinical recovery, followed by interval progression in her right upper lobe consolidation on follow‐up computed tomography scans. She underwent lobectomy for definitive therapy with resolution of symptoms. Lobectomy can be utilized in isolated infection after antibiotic failure with excellent clinical outcomes.     

Bordetella holmesii bacteremia in a renal transplant recipient: emergence of a new pathogen

Bordetella holmesii is a gram‐negative rod that was initially identified in 1995. It causes bacteremia, pneumonia, and endocarditis mostly in patients with anatomical or functional asplenia. We report here, to the best of our knowledge, the first case of B. holmesii bacteremia in a renal transplant recipient following rituximab therapy for recurrence of membranoproliferative glomerulonephritis.     

Sofosbuvir and ledipasvir improve patient‐reported outcomes in patients co‐infected with hepatitis C and human immunodeficiency virus

A fixed‐dose combination of ledipasvir and sofosbuvir (LDV/SOF) has been approved for treatment of HCV patients. We assessed the effect of LDV/SOF on patient‐reported outcomes (PROs) in HIV–HCV‐co‐infected patients. Patient‐reported outcomes data from HIV–HCV‐co‐infected patients who were treated with LDV/SOF for 12 weeks were collected as a part of a clinical trial (ION‐4). Historical controls were HIV–HCV‐co‐infected patients treated with SOF and ribavirin (RBV) in PHOTON‐1. We included 335 HIV–HCV‐co‐infected patients (SVR‐12 in HCV genotype 1 was 96%) who received LDV/SOF, while 223 patients (SVR‐12 in HCV genotype 1 was 76.3%) received SOF/RBV. During treatment, patients receiving LDV/SOF showed improvement in all of their PRO scores (+6.0% in activity/energy of CLDQ‐HCV, +5.0% in fatigue score of FACIT‐F, +6.8% in physical component of SF‐36; all P < 0.0001) while those receiving SOF+RBV showed moderate decline in some of their PRO scores (?4.8% in physical functioning of SF‐36, ?4.4% in fatigue score of FACIT‐F, both P < 0.001). Patients who achieved sustained virologic response with LDV/SOF also showed improvement of PROs (average +5.1%) while those treated with SOF/RBV showed less or no improvement (average +1.4%). In a multivariate analysis, in addition to depression and fatigue, receiving SOF+RBV (vs LDV/SOF) was independently associated with more PRO impairment during treatment (beta ?6.1 to ?12.1%, P < 0.001). Hence, HIV–HCV patients treated with LDV/SOF show significant improvement of their health‐related quality of life and other patient‐reported outcomes during treatment and after treatment cessation.     

Bordetella bronchiseptica bloodstream infection in a renal transplant patient

Bordetella bronchiseptica is a gram‐negative coccobacillus that infects animals, but rarely affects humans. B. bronchiseptica has been reported to cause disease in immunocompromised hosts. We present a case of a 61‐year‐old man with a renal transplant who developed B. bronchiseptica bacteremia likely as a result of close contact between dogs and his skin cancer biopsy sites. The patient was successfully treated with 2 weeks of oral levofloxacin. This case alerts physicians to B. bronchiseptica as a cause of bacteremia in solid organ transplant patients with exposure to animals.     

Early diagnosis of Ehrlichia ewingii infection in a lung transplant recipient by peripheral blood smear

Ehrlichiosis in lung transplant (LT) recipients is associated with severe outcomes. Ehrlichia ewingii is a less frequent cause of symptomatic ehrlichiosis, characterized by cytoplasmic inclusions (morulae) within circulating neutrophils. We report a case of E. ewingii infection in an LT recipient diagnosed promptly by blood smear exam and confirmed with molecular studies.     

Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients

Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density (BMD) in patients with haemophilia with or without co‐infections. Seventy‐eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each (HIV‐HCV co‐infected, HCV mono‐infected and uninfected). The BMD was measured by dual energy X‐ray absorptiometry (DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F‐BMD reduction in all the three groups, whereas L‐BMD was significantly lower in co‐infected patients (P < 0.05). The clinical score was higher in co‐infected (P < 0.002) and mono‐infected (P < 0.006). The radiological score was higher in mono‐infected than in the other two groups (P < 0.001). Overall 25‐hydroxyvitamin D (25‐OH Vit D) was reduced (87%). Bone‐specific alkaline phosphatase (b‐ALP) and telopeptide were increased in co‐infected (P < 0.001 and P < 0.01) and mono‐infected (P < 0.001 and P < 0.02). The result of the homogeneous F‐BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L‐BMD in co‐infected and the increase of b‐ALP and telopeptide in co‐infected and mono‐infected groups suggest faster bone metabolism in case of infections.     

Successful lung transplantation for chronic Mycobacterium abscessus infection in advanced cystic fibrosis,a case series

Pulmonary Mycobacterium abscessus infection in cystic fibrosis (CF) patients is difficult to treat and considered a contra‐indication for lung transplantation in most centers. We present four CF patients with chronic pulmonary M abscessus infection, in whom lung transplantation was performed. Through intensive treatment before transplantation, we achieved control of the infection in all but one patient. After a mean of 16 months of follow up, 3 patients are doing well, without evidence of local or disseminated recurrence. One patient died early post‐transplant due to an unrelated cause. These findings support the possibility of lung transplantation with favorable outcome in CF patients with M abscessus infection.     

Outcomes of transplantation using organs from a donor infected with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae

Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC‐producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC‐producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC‐producing K. pneumoniae. All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.     

HCV RNA decline in chronic HCV genotype 2 and 3 during standard of care treatment according to IL28B polymorphism

The IL28 gene is highly associated with sustained viral response (SVR) in patients infected with genotype 1 after standard of care (SOC) treatment with peg‐IFN and ribavirin. It is also associated with a steeper first phase HCV RNA decline during treatment. In genotype 2 and 3 infections, these correlations are less obvious. We studied the IL28B association to rapid viral response (RVR), SVR, first and second phase HCV RNA decline during treatment in 100 HCV mono‐infected and 13 HCV/HIV co‐infected patients. We found a significantly higher mean baseline HCV RNA level in IL28B SNP CC than non‐CC mono‐infected patients, 6.99 vs 6.30 log₁₀ IU/mL (P = 0.02), and a significantly larger median 1st phase decline in patients with CC than non‐CC genotype, 2.03 vs 1.37 log₁₀ IU/mL, respectively. The overall SVR rate in HCV mono‐infected patients was 87% vs 77% in HCV/HIV co‐infected patients, with no correlation to IL28B SNP. In mono‐infected patients with RVR, the SVR rate was high and independent of IL28B genotype. In mono‐infected patients who failed to achieve RVR who had IL28B CC and non‐CC genotype, 64% and 67% achieved SVR, respectively. In genotype 2 and 3 infected patients, the 1st phase HCV RNA decline was steeper in patients with IL28B CC vs non‐CC genotype during SOC treatment. This did not translate into a higher frequency of RVR or SVR. Hence, the clinical relevance of pretreatment analysis of IL28B polymorphisms in genotype 2 and 3 infected patients can be questioned in patients with expected high SVR rate.     

Bacteremia due to Campylobacter in renal transplantation: a case report and review of literature

Campylobacter species are the leading cause of acute bacterial diarrhea in industrialized countries. However, bacteremia is detected in <1% of patients with Campylobacter enteritis and is most likely to occur in patients who are immunocompromised or of older age. To our knowledge, only 2 cases of Campylobacter jejuni bacteremia have been reported in renal transplant recipients (RTRs). We present a case of an RTR with C. jejuni bacteremia presenting as self‐limiting diarrhea followed by fever and cellulitis. The patient was successfully treated with a 2‐week course of imipenem and developed no other complications. We review all cases of Campylobacter bacteremia in RTRs, and discuss clinical presentation and treatment of this potentially fatal disease.     

Role of IFN‐λs,IFN‐λs related genes and the DEPDC5 gene in Hepatitis B virus‐related liver disease

Recent studies have associated genetic variation near the interleukin 28B (IL28B/IFN‐λ3) gene with natural clearance of the hepatitis C virus (HCV) infection, and a common variant in the DEP domain containing 5 (DEPDC5) locus on chromosome 22 has been shown to affect susceptibility to hepatocellular carcinoma (HCC) in Japanese individuals with chronic HCV infection. This study was conducted to determine whether polymorphisms near or in interferon‐lambda (IFN‐λs) genes and their receptor genes such as interleukin 28 receptor, alpha (IL28RA) and interleukin 10 receptor, beta (IL10RB) as well as p21_activated kinases 4 (PAK4) and iron/zinc purple acid phosphatase‐like protein (PAPL), which are locate upstream of IFN‐λs, and lastly the DEPDC5 gene are associated with hepatitis B virus‐related liver disease in Han Chinese. The study subjects included 507 normal healthy controls, 350 individuals with natural clearance of HBV and 792 HBV‐infected patients. The patients were categorized into 157 inactive carriers (Case I), 216 active carriers (Case II), 111 cirrhotics (Case III) and 308 HCC patients (Case IV) subgroups. Seven single nucleotide polymorphisms (SNPs) were genotyped using the Matrix‐assisted Laser Desorption/Ionisation mass spectrometric (MALDI‐TOF MS) SNP genotyping assay. Rs423058 upstream of PAPL, rs2834167 in IL10RB and rs1012068 in DEPDC5 were associated with chronic HBV status, HBV natural clearance and the presence of HCC (P = 0.0004–0.024), respectively. PAPL, IL10RB and DEPDC5 polymorphisms have an impact on progression of HBV‐related liver disease. However, IFN‐λs genes as a tool to differentiate between different clinical courses of HBV infection were not useful in the Han Chinese population.     

A cluster of scedosporiosis in lung transplant candidates and recipients: The Zurich experience and review of the literature

Scedosporium species are fungal pathogens increasingly recognized in cystic fibrosis (CF). They can cause multiresistant, life‐threatening infections that are of particular concern in CF patients undergoing lung transplantation, as optimal treatment remains unclear. Here, we describe our Zurich experience of CF patients with Scedosporium infection. Disseminated infection occurred in one patient after transplantation and was successfully treated. We propose a step‐by‐step approach to treat candidates with colonization, and discuss our cases in the context of the current literature.     

Disseminated Hormographiella aspergillata infection with involvement of the lung,brain, and small intestine following allogeneic hematopoietic stem cell transplantation: case report and literature review

Disseminated infection by Hormographiella aspergillata is extremely rare and small intestine involvement has not been reported previously. A 51‐year‐old man with myelodysplastic syndrome developed pneumonia after cord blood cell transplantation. Fungal growth from the biopsied lung was identified as H. aspergillata by morphology and the gene analysis. Although antifungal agents including voriconazole and liposomal amphotericin B were administered, he died of disseminated H. aspergillata infection. We review the literature and discuss the treatment and prognosis.     

Evolution of glomerular filtration rate in HIV‐infected,HIV–HBV‐coinfected and HBV‐infected patients receiving tenofovir disoproxil fumarate

We aimed to compare the evolution of estimated glomerular filtration rate (eGFR) in HIV‐, HIV–HBV‐ and HBV‐infected patients treated with tenofovir disoproxil fumarate (TDF). Three groups of patients receiving TDF > 12 months were recruited: 194 HIV‐infected patients, 85 HIV–HBV‐coinfected patients and 50 HBV‐infected patients. eGFR was estimated using the Modification of the Diet in Renal Disease (MDRD) equation. Multivariate regression models were constructed to estimate factors associated with eGFR decrease from baseline. A total of 329 patients were studied. Median follow‐up was 2.7 years. Median eGFR decrease was ?4.9 (?16.6 to +7.2) mL/min/1.73 m². After multivariate stepwise regression analysis, age (P = 0.0002), non‐African origin (P < 0.0001), baseline eGFR (P < 0.0001) and TDF duration (P = 0.02) were associated with eGFR decrease in the whole population, while hypertension, diabetes and type of infection were not. Age (P < 0.0001), non‐African origin (P = 0.0004), baseline eGFR (P < 0.0001) and TDF duration (P = 0.007) remained associated with eGFR decline in HIV and HIV–HBV‐infected patients, while other variables including HIV risk factor, CDC stage, CD4 and HIV‐RNA levels were not. Age (P = 0.03), non‐African origin (P = 0.004), baseline eGFR (P < 0.0001) and baseline HBV–DNA > 2000 IU/mL (P = 0.04) were associated with eGFR decline in HBV and HIV–HBV‐infected patients, while other variables including HBV risk factor and fibrosis stage were not. Estimated glomerular filtration rate decline under TDF therapy appears mainly associated with older age, non‐African origin, higher baseline eGFR and longer TDF administration but not with the type of viral infection. Regular follow‐up of renal function, especially tubular function is recommended during TDF therapy.     

Burkholderia gladioli – a predictor of poor outcome in cystic fibrosis patients who receive lung transplants? A case of locally invasive rhinosinusitis and persistent bacteremia in a 36-year-old lung transplant recipient with cystic fibrosis

There have been very few reports describing postlung transplant outcomes in patients’ infected/colonized with Burkholderia gladioli pretransplant. A case involving a lung transplant recipient with cystic fibrosis who ultimately died as a result of severe rhinosinusitis due to B gladioli infection in the context of postlung transplant immunosuppression is reported.     

Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV‐coinfected patients

Accelerated intrahepatic hepatitis C virus (HCV) pathogenesis is likely the result of dysregulation within both the innate and adaptive immune compartments, but the exact contribution of peripheral blood and liver lymphocyte subsets remains unclear. Prolonged activation and expansion of immunoregulatory cells have been thought to play a role. We determined immune cell subset frequency in contemporaneous liver and peripheral blood samples from chronic HCV‐infected and HIV/HCV‐coinfected individuals. Peripheral blood mononuclear cells (PBMC) and biopsy‐derived liver‐infiltrating lymphocytes from 26 HIV/HCV‐coinfected, 10 chronic HCV‐infected and 10 HIV‐infected individuals were assessed for various subsets of T and B lymphocytes, dendritic cell, natural killer (NK) cell and NK T‐cell frequency by flow cytometry. CD8⁺ T cells expressing the exhaustion marker PD‐1 were increased in HCV‐infected individuals compared with uninfected individuals (P = 0.02), and HIV coinfection enhanced this effect (P = 0.005). In the liver, regulatory CD4⁺CD25⁺Foxp3⁺ T cells, as well as CD4⁺CD25⁺PD1⁺ T cells, were more frequent in HIV/HCV‐coinfected than in HCV‐monoinfected samples (P < 0.001). HCV was associated with increased regulatory T cells, PD‐1⁺ T cells and decreased memory B cells, regardless of HIV infection (P ≤ 0.005 for all). Low CD8⁺ expression was observed only in PD‐1⁺CD8⁺ T cells from HCV‐infected individuals and healthy controls (P = 0.002) and was associated with enhanced expansion of exhausted CD8⁺ T cells when exposed in vitro to PHA or CMV peptides. In conclusion, in HIV/HCV coinfection, ongoing HCV replication is associated with increased regulatory and exhausted T cells in the periphery and liver that may impact control of HCV. Simultaneous characterization of liver and peripheral blood highlights the disproportionate intrahepatic compartmentalization of immunoregulatory T cells, which may contribute to establishment of chronicity and hepatic fibrogenesis in HIV coinfection.     

Successful heart transplantation in patients with active Staphylococcus bloodstream infection and suspected mechanical circulatory support device infection

Background

An active bloodstream infection (BSI) is typically considered a contraindication to heart transplantation (HT). However, in some patients with Staphylococcus bacteremia and mechanical circulatory support device infection, positive blood cultures may persist until removal of the infected device, and eradicating the infection prior to HT may not be possible. We report the outcomes of six patients with active Staphylococcus BSI at the time of HT.

Methods

All cases of HT performed at The Mount Sinai Hospital from 2009 through 2015 were reviewed. All patients with a mechanical circulatory support device and an active Staphylococcus BSI at the time of HT were included.

Results

Six patients with active Staphylococcus bacteremia and suspected mechanical circulatory support device infection underwent HT. All patients were bacteremic with Staphylococcus species at the time of HT. All were managed with antimicrobial therapy, radical debridement at the time of HT, and limited use of immunosuppression, and all survived until hospital discharge with no evidence of relapsed Staphylococcus infection.

Conclusion

These results suggest that some carefully selected patients with active Staphylococcus bacteremia and suspected mechanical circulatory support device infection may safely undergo HT, and that HT may effectively eliminate the underlying infection.     

Pseudozyma and other non‐Candida opportunistic yeast bloodstream infections in a large stem cell transplant center

Non‐Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non‐Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non‐Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin‐resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.