Will regulatory and financial considerations dampen innovation in the clinical microbiology laboratory?

Over a million prosthetic joints are placed in patients in the United States annually. Of those that fail, 25% will be due to infection, with an estimated cost approaching 1 billion dollars. Despite the clinical and economic importance of these infections, the techniques for their detection are relatively insensitive. An innovative method for detecting these infections by using blood culture bottles (BCB) to culture specimens of periprosthetic tissue (PPT) was described in a recent article [T. N. Peel, et al., mBio 7(1):e01776-15, 2016, doi:10.1128/mBio.01776-15]. There are two potential stumbling blocks to the widespread implementation of this innovation. First, the FDA judges such an application of BCB as an “off-label use” and as such, a laboratorydeveloped test (LDT). LDTs are coming under greater scrutiny by the FDA and may require extensive, costly validation studies in laboratories that adopt this methodology. Second, the Center for Medicare and Medicaid Services has established a Hospital Acquired Condition Reduction Act under which institutions performing in the lowest quartile forfeit 1% of their Medicare reimbursement. Hospital-acquired infections are an important component of this quality metric. Although prosthetic joint infection (PJI) rates are not currently a hospital quality metric, given their cost and increasing frequency, it is reasonable to expect that they may become one. Will those with financial oversight allow an innovative technique that will require an expensive validation and may put the institution at risk for loss of CMS reimbursement

Referral letters to the emergency department: is the medication list accurate?

Medication errors are common when patients transfer across healthcare boundaries. This study was designed to investigate the quality of information on medicines provided by general practitioners (GPs) on emergency department (ED) referral letters. A convenience sample of referral letters to the ED of a teaching hospital was reviewed. The medication list and/or patient\u27s drug allergy status were noted. Medicines reconciliation including patient (or carer) interview was conducted to determine the patient\u27s actual home medication list. This was compared with the GP list and any discrepancies were identified and addressed. A total of 92 referral letters were included in the analysis of which 60 were computer-generated and 32 were hand-written. GPs provided dose and frequency of administration information in 47 (51%) of the letters sampled i.e. 44 (71%) computer-generated versus 3 (10%) hand-written; p \u3c 0.001. In addition, the patient was taking their medicines exactly as per the GP list in 20 (22%) of cases. The patient\u27s drug allergy status was documented in 13 (14%) of the letters

Ex vivo expansion of megakaryocyte precursors from umbilical cord blood CD34+ cells in a closed liquid culture system

AbstractUmbilical cord blood (UCB) provides a rich source of stem cells for transplantation after myeloablative therapy. One major disadvantage of UCB transplantation is delayed platelet engraftment. We propose to hasten platelet engraftment by expanding the number of megakaryocyte (MK) precursors (CD34/CD41 cells) through cytokine stimulation within a closed, pre-clinical liquid culture system. Clinical engraftment data suggest a 5- to 10-fold increase in MK precursors in a UCB unit can accelerate platelet engraftment, so this was our goal. Thirteen UCB samples from full-term births were Ficoll-separated and frozen for subsequent use. On thawing, the mononuclear cell population was positively selected for CD34+ expression. The cells were cultured in gas-permeable Teflon-coated bags in serum-free medium containing the following cytokines: recombinant human interleukin-3, recombinant human Flt3 ligand, recombinant human stem cell factor, and recombinant human thrombopoietin. MK lineage cell expansion was assessed using mononuclear cell count and flow cytometry (CD34/41, CD41, CD34/61, and CD61 expression) on days 7, 11, and 14. Optimal expansion of CD34/41 and CD41 cells was observed at day 11, with a median 6-fold and 33-fold increase in the starting cell doses, respectively. CD34/61 and CD61 cell expansion at day 11 was 7-fold and 14-fold, respectively. MK precursors can be successfully expanded from CD34+ UCB cells in a closed liquid culture system using interleukin-3, recombinant human Flt3 ligand, recombinant human stem cell factor, and recombinant human thrombopoietin to a level that should have a clinical impact in the transplantation setting. Our ex vivo expansion technique needs to be further optimized before it can be used in a pilot UCB transplantation trial. © 2003 American Society for Blood and Marrow TransplantationBiology of Blood and Marrow Transplantation 9:151-156 (2003

DVT Presentations to an Emergency Department: A Study of Guideline Based Care and Decision Making.

Pre-test probability scoring and blood tests for deep venous thrombosis (DVT) assessment are sensitive, but not specific leading to increased demands on radiology services. Three hundred and eighty-five patients presenting to an Emergency Department (ED), with suspected DVT, were studied to explore our actual work-up of patients with possible DVT relating to risk stratification, further investigation and follow up. Of the 205 patients with an initially negative scan, 36 (17.6%) were brought for review to the ED Consultant clinic. Thirty-four (16.6%) patients underwent repeat compression ultrasound with 5 (2.4%) demonstrating a DVT on the second scan. Repeat compression ultrasound scans were performed on 34 (16.6%) patients with an initially negative scan, with essentially the same diagnostic yield as other larger studies where 100% of such patients had repeat scanning. Where there is ongoing concern, repeat above-knee compression ultrasound within one week will pick up a small number of deep venous thromboses

Evaluation of RGM Medium for Isolation of Nontuberculous Mycobacteria from Respiratory Samples from Patients with Cystic Fibrosis in the United States

ABSTRACT A novel selective agar (RGM medium) has been advocated for the isolation of rapidly growing mycobacteria from the sputa of cystic fibrosis (CF) patients. The aim of this study was to compare RGM medium to Burkholderia cepacia selective agar (BCSA) and a standard acid-fast bacillus (AFB) culture method for the isolation of nontuberculous mycobacteria (NTM) from patients with CF. The applicability of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for the identification of NTM isolated on RGM medium was also assessed. Respiratory samples ( n = 869) were collected from 487 CF patients and inoculated directly onto RGM medium and BCSA. Cultures were incubated at 30°C and examined for up to 28 days. A subset of 212 samples (from 172 patients) was also cultured by using a mycobacterial growth indicator tube (MGIT) and on Lowenstein-Jensen medium following dual decontamination. By using a combination of all methods, 98 mycobacteria were isolated from 869 samples (11.3%). The sensitivity of RGM medium (96.9%) was significantly higher than that of BCSA (35.7%) for the isolation of mycobacteria ( P < 0.0001). The sensitivity of RGM medium was also superior to that of standard AFB culture for the isolation of mycobacteria (92.2% versus 47.1%; P < 0.0001). MALDI-TOF MS was effective for the identification of mycobacteria in RGM medium. RGM medium offers a simple and highly effective tool for the isolation of NTM from patients with CF. Extended incubation of RGM medium for 28 days facilitates the isolation of slow-growing species, including members of the Mycobacterium avium complex (MAVC)

Capnocytophaga ochracea Septicemia

A case report describing Capnocytophaga ochracea (Bacteroides ochraceus) septicemia in a 21-year-old male patient receiving chemotherapy for acute lymphocytic leukemia is presented. The unusual features of this organism are discussed together with a review of the literature

Point-Counterpoint: Should Interferon Gamma Release Assays Become the Standard Method for Screening Patients for Mycobacterium tuberculosis Infections in the United States?

The Centers for Disease Control and Prevention recently published updated guidelines for the use of interferon gamma release assays (IGRAs) to detect Mycobacterium tuberculosis. This document gives a balanced analysis of the strengths and weaknesses of IGRAs. To date, these assays have not been widely adopted in the United States by clinical laboratories. We have asked two experts, Thomas Alexander of Summa Health Care, who has adopted an IGRA for M. tuberculosis detection in his laboratory, and Melissa Miller of UNC Hospitals, who has evaluated one but has not chosen to adopt it, to explain how each reached this decision based on their experience with the test and the data that have been published concerning IGRA

Comparison of Matrix-Assisted Laser Desorption Ionization–Time of Flight (MALDI-TOF) Mass Spectrometry Platforms for the Identification of Gram-Negative Rods from Patients with Cystic Fibrosis

We evaluated the performance of the Bruker Biotyper and the bioMérieux Vitek MS with both the SARAMIS v4.09 and Knowledge Base v2.0 databases for the identification of 203 non-glucose-fermenting Gram-negative rods that had previously been identified by 16S rRNA gene sequencing. Including those that underwent repeat testing, 96.6%, 90.1%, and 93.6% of isolates, respectively, had identifications that agreed with the previous identification

Burkholderia gladioli: Five year experience in a cystic fibrosis and lung transplantation center

Background: The impact of infection with Burkholderia gladioli in cystic fibrosis, other chronic airway diseases and immunosuppressed patients is unknown. Methods: A six-year retrospective review of all patients with B. gladioli infection was performed in a tertiary referral center with cystic fibrosis and lung transplantation programs. In addition, a targeted survey of all 251 lung transplant recipients was performed. Available B. gladioli isolates were analyzed via pulsed field gel electrophoresis. Results: Thirty-five patients were culture positive for B. gladioli, including 33 CF patients. No bacteremia was identified. Isolates were available in 18 patients and all were genetically distinct. Two-thirds of these isolates were susceptible to usual anti-pseudomonal antibiotics. After acquisition, only 40% of CF patients were chronically infected (≥2 positive cultures separated by at least 6 months). Chronic infection was associated with resistance to ≥2 antibiotic groups on initial culture and failure of eradication after antibiotic therapy. The impact of acquisition of B. gladioli infection in chronic infection was variable. Three CF patients with chronic infection underwent lung transplantation. One post-transplant patient developed a B. gladioli mediastinal abscess, which was treated successfully. Conclusions: The majority of patients' culture positive for B. gladioli at our center have CF. B. gladioli infection is often transient and is compatible with satisfactory post-lung transplantation outcomes

Burkholderia gladioli: Five year experience in a cystic fibrosis and lung transplantation center

Background: The impact of infection with Burkholderia gladioli in cystic fibrosis, other chronic airway diseases and immunosuppressed patients is unknown. Methods: A six-year retrospective review of all patients with B. gladioli infection was performed in a tertiary referral center with cystic fibrosis and lung transplantation programs. In addition, a targeted survey of all 251 lung transplant recipients was performed. Available B. gladioli isolates were analyzed via pulsed field gel electrophoresis. Results: Thirty-five patients were culture positive for B. gladioli, including 33 CF patients. No bacteremia was identified. Isolates were available in 18 patients and all were genetically distinct. Two-thirds of these isolates were susceptible to usual anti-pseudomonal antibiotics. After acquisition, only 40% of CF patients were chronically infected (≥2 positive cultures separated by at least 6 months). Chronic infection was associated with resistance to ≥2 antibiotic groups on initial culture and failure of eradication after antibiotic therapy. The impact of acquisition of B. gladioli infection in chronic infection was variable. Three CF patients with chronic infection underwent lung transplantation. One post-transplant patient developed a B. gladioli mediastinal abscess, which was treated successfully. Conclusions: The majority of patients' culture positive for B. gladioli at our center have CF. B. gladioli infection is often transient and is compatible with satisfactory post-lung transplantation outcomes