Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia.

OBJECTIVES: The role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk. METHODS: An observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture. RESULTS: Among 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p < 0.0001). Propensity score-weighted Cox proportional hazards models revealed that obtaining FUBCs was associated with reductions in all-cause (hazard ratio (HR) 0.629; 95% confidence interval (CI), 0.511-0.772; p < 0.0001) and attributable mortality (HR 0.628; 95% CI, 0.480-0.820; p 0.0007). Positive FUBCs were associated with increased all-cause mortality (49/228, 21%, vs. 110/885, 11%; p 0.0005) and attributable mortality (27/228, 12%, vs. 61/885, 7%; p 0.01) relative to negative FUBCs. Propensity score-weighted Cox proportional hazards models revealed that positive FUBCs were associated with increased all-cause (HR 2.099; 95% CI, 1.567-2.811; p < 0.0001) and attributable mortality (HR 1.800; 95% CI, 1.245-2.603; p 0.002). In a calibration analysis, a scoring system accurately identified patients at high risk of positive FUBCs. CONCLUSIONS: Rates of positive FUBCs were high and identified patients at increased risk for mortality. Clinical variables can identify patients at high risk for positive FUBCs. FUBCs should be considered in the management of GNB.

Successful Diagnosis of Intestinal Mycobacterium avium Complex Infection in a Kidney Transplant Recipient Using Nasogastric Aspirate Culture: A Case Report.

Intestinal Mycobacterium avium complex (MAC) infections are rare and can be challenging to diagnose. We describe a case of intestinal MAC infection in a kidney transplant recipient with 5 months of unexplained weight loss and abdominal pain who developed intestinal obstruction. Esophagoduodenoscopy with biopsies was performed but was nondiagnostic. Intestinal MAC was diagnosed via nasogastric aspirate culture results. The patient's symptoms rapidly improved after initiation of appropriate treatment, but he later died of aspiration pneumonia and candidemia.

Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections.

Patients infected or colonized with carbapenem-resistant Klebsiella pneumoniae (CRKp) are often chronically and acutely ill, which results in substantial mortality unrelated to infection. Therefore, estimating excess mortality due to CRKp infections is challenging. The Consortium on Resistance against Carbapenems in K. pneumoniae (CRACKLE) is a prospective multicenter study. Here, patients in CRACKLE were evaluated at the time of their first CRKp bloodstream infection (BSI), pneumonia or urinary tract infection (UTI). A control cohort of patients with CRKp urinary colonization without CRKp infection was constructed. Excess hospital mortality was defined as mortality in cases after subtracting mortality in controls. In addition, the adjusted hazard ratios (aHR) for time-to-hospital-mortality at 30 days associated with infection compared with colonization were calculated in Cox proportional hazard models. In the study period, 260 patients with CRKp infections were included in the BSI (90 patients), pneumonia (49 patients) and UTI (121 patients) groups, who were compared with 223 controls. All-cause hospital mortality in controls was 12%. Excess hospital mortality was 27% in both patients with BSI and those with pneumonia. Excess hospital mortality was not observed in patients with UTI. In multivariable analyses, BSI and pneumonia compared with controls were associated with aHR of 2.59 (95% CI 1.52-4.50, p <0.001) and 3.44 (95% CI 1.80-6.48, p <0.001), respectively. In conclusion, in patients with CRKp infection, pneumonia is associated with the highest excess hospital mortality. Patients with BSI have slightly lower excess hospital mortality rates, whereas excess hospital mortality was not observed in hospitalized patients with UTI.

Tigecycline therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria leads to tigecycline resistance.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasing global threat. Here, we describe the prevalence and impact of tigecycline use in a cohort of patients with CRKP bacteriuria nested within a multicentre, prospective study. In the 21-month study period, 260 unique patients were included. Tigecycline was given to 80 (31%) patients. The use of tigecycline during the index hospitalization was significantly associated with the subsequent development of tigecycline resistance in the same patient (OR, 6.13; 95% CI, 1.15-48.65; p 0.03). In conclusion, the use of tigecycline with CRKP bacteriuria is common, and is associated with the subsequent development of tigecycline resistance.

KIR and HLA interactions are associated with control of primary CMV infection in solid organ transplant recipients.

Cytomegalovirus (CMV) infection remains a major source of morbidity and mortality in solid organ transplant recipients. Killer immunoglobulin-like receptors(KIR) are genetically polymorphic natural killer(NK) cell receptors important in antiviral responses. A retrospective, single-center cohort study was performed to study the interaction of KIR genotype and primary control of CMV infection after transplantation.Time to first CMV viremia was determined for a cohort of 531 CMV serology donor positive/recipient negative solid organ transplant recipients. Of the KIR genes,KIR2DL3 and KIR2DS2 were most strongly associated with time to CMV viremia in random survival forest analysis. As KIR2DL3 and KIR2DS2 both interact with HLA-C1, these interactions were evaluated. Seventy six recipients were found to be positive for both KIR2DL3 and KIR2DS2 and expressed only HLA-C1 antigens in both recipient and donor. These patients had a substantially reduced hazard of CMV viremia in the first year after solid organ transplantation (hazard ratio 0.44, 95% CI 0.27­0.72, p=0.0012). In KIR2DL3+/KIR2DS2+/HLA-C1/1 recipients who received an organ from a non-C1/1 donor, this protective effect was not observed. These results improve our understanding of human NK cell function in primary CMV infection after transplant.

[Development of the multidisciplinary guideline on 'work and severe mental illness']. / Ontwikkeling van de multidisciplinaire richtlijn 'Werk en ernstige psychische aandoeningen'

BACKGROUND: In the Netherlands only a comparatively low percentage (18-19%) of persons with severe mental illness (SMI) are in paid employment. The problem consists not only of finding a job but also of holding it down. AIM: To develop guidelines that will ensure that patients with SMI have the best possible access to paid employment and that the drop-out rate for this group is as low as possible. METHOD: We reviewed the literature systematically and reviewed the results revealed by focus groups and case studies. RESULTS: There is strong evidence that the integrated approach 'Individual Placement and Support' is effective in keeping people in employment. There are indications that self-management strategies and programmes and assessment instruments are also effective in this regard. CONCLUSION: The guidelines recommend that persons with SMI should be given continuing support so they can remain in paid employment. More research is needed into how effective self-management programmes and assessment instruments can be in keeping this group of persons in employment. Collaborations between various sectors also needs to be further investigated.

Effect of the influenza A (H1N1) live attenuated intranasal vaccine on nitric oxide (FE(NO)) and other volatiles in exhaled breath.

For the 2009 influenza A (H1N1) pandemic, vaccination and infection control were the main modes of prevention. A live attenuated H1N1 vaccine mimics natural infection and works by evoking a host immune response, but currently there are no easy methods to measure such a response. To determine if an immune response could be measured in exhaled breath, exhaled nitric oxide (FE(NO)) and other exhaled breath volatiles using selected ion flow tube mass spectrometry (SIFT-MS) were measured before and daily for seven days after administering the H1N1 2009 monovalent live intranasal vaccine (FluMist®, MedImmune LLC) in nine healthy healthcare workers (age 35 ± 7 years; five females). On day 3 after H1N1 FluMist® administration there were increases in FE(NO) (MEAN±SEM: day 0 15 ± 3 ppb, day 3 19 ± 3 ppb; p < 0.001) and breath isoprene (MEAN±SEM: day 0 59 ± 15 ppb, day 3 99 ± 17 ppb; p = 0.02). MS analysis identified the greatest number of changes in exhaled breath on day 3 with 137 product ion masses that changed from baseline. The exhaled breath changes on day 3 after H1N1 vaccination may reflect the underlying host immune response. However, further work to elucidate the sources of the exhaled breath changes is necessary.

Recommended curriculum for subspecialty training in transplant infectious disease on behalf of the American Society of Transplantation Infectious Diseases Community of Practice Educational Initiatives Working Group.

The American Society of Transplantation Infectious Diseases (ID) Community of Practice has established an education workgroup to identify core components of a curriculum for training specialists in transplant ID. Clinical, laboratory, and research training form the triad of components on which an additional year of ID training, dedicated to the care of solid organ and hematopoietic stem cell transplant recipients, should be based. The recommended training environment would have access to adequate numbers of transplant patients, along with qualified faculty committed to teaching specialized fellows in this area. The learning objectives for both inpatient and outpatient clinical training are presented. The laboratory component requires trainees to attain expertize in utilizing and interpreting cutting-edge diagnostics used in transplant medicine. The research component may involve basic science, and translational or clinical research individualized to the trainee. Finally, suggestions for evaluation of both the fellows and the training program are provided.

Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area.

BACKGROUND: Many clinical scenarios have been encountered by patients who developed histoplasmosis after receiving a solid organ transplant at a large transplant center in an endemic area. METHODS: Cases of posttransplantation histoplasmosis were identified by use of multiple methods, including reviews of microbiology test results, transplant databases, and billing codes. Data were obtained retrospectively. Descriptive statistics were used. RESULTS: During the 1997-2007 study period, 3436 patients received a solid organ transplant, and 38 patients were identified as having posttransplantation histoplasmosis. Of these 38 patients, 9 were excluded from our study because the diagnosis was solely clinical. Of the remaining 29 patients, 14 had posttransplantation histoplasmosis (incidence, 1 case per 1000 person-years); 14 showed histologic evidence of histoplasmosis in the recipient or donor tissue, which was encountered unexpectedly at the time of transplantation; and 1 had histoplasmosis before receiving the transplant. Of the 14 patients who developed histoplasmosis after transplantation, 5 were heart transplant recipients, 3 were lung transplant recipients, 3 were kidney transplant recipients, 1 was a liver transplant recipient, 1 was a pancreas transplant recipient, and 1 was a kidney-pancreas transplant recipient. The median time from transplantation to diagnosis was 17 months (interquartile range, 8.1-46 months), and the median time from onset of symptoms to diagnosis 3 weeks (interquartile range, 1.9-6.5 weeks). All recipients had disseminated disease. The most common treatment was amphotericin B and itraconazole. All were cured, or still on treatment, but symptom-free. Of the 14 patients who had an explanted organ or donor tissue that showed histologic evidence of histoplasmosis, 13 (93%) were lung transplant recipients, and 1 (7%) was a liver transplant recipient. None of these patients developed active histoplasmosis, but all received prophylactic treatment. Finally, 1 patient had histoplasmosis before transplantation; he was treated with itraconazole 3 months before and after transplantation, and he did well. CONCLUSIONS: In conclusion, posttransplantation histoplasmosis is rare (1 case per 1000 transplant-person-years; 95% confidence interval, 0.6-1.7), even in endemic areas. Prognosis is good but requires protracted therapy. Patients with latent infection did not develop posttransplantation histoplasmosis when prophylaxis was used.

Seizures in the critically ill: the role of imipenem.

PURPOSE: To determine the risk of seizures in critically ill patients receiving the antibiotic imipenem, a broad-spectrum antibiotic that has been associated with seizures. Reports generally have not considered other contributing factors such as dose, seizure history, and morbidity index of the underlying illness necessitating the antibiotic. METHODS: Charts of all patients in a 450-bed municipal hospital who received imipenem in a 6-month period, as determined by pharmacy records, were reviewed for dosage and duration of imipenem use, occurrence of seizures. and mortality outcome. Attention was paid to demographic features; pattern of seizure occurrence during, before, and after imipenem use; renal function; and correction for dosage based on size. RESULTS: Seventy-five charts were reviewed. Sixty-three patients had no seizures during the hospitalization, four had seizures while receiving imipenem, and eight had seizures during the hospitalization but before or after imipenem use. The incidence of seizures was 4/1,000 patient-days on, and 3.9/1,000 patient-days off imipenem (not significant). The risk of seizure in both groups was considerably higher in those patients with a history of seizures before hospitalization. The presence of other factors that could contribute to increased concentration of imipenem in the brain, such as renal failure or acute stroke, did not contribute to seizure incidence. Metabolic derangement, anoxia, and phenytoin discontinuation did contribute to seizure incidence. CONCLUSIONS: Seizure incidence is increased in all critically ill patients (16% of patients studied), but with no added risk during the period patients received imipenem. Determining the proper dose based on a patient's body mass, correction of dose in the presence of renal failure, and avoidance of excess of 2 g/day of imipenem removes any added risk for seizures from imipenem. Despite experimental data to suggest action of imipenem on the glutamate/N-methyl-d-aspartate receptor, or interference with binding to the gamma-aminobutyric acid receptor, and early clinical studies that warned against its use because of seizure risk, we found that careful use of this antibiotic is safe.