Laboratory Diagnosis of Mycobacterial Infections: New Tools and Lessons Learned

Even in the 21st century, tuberculosis continues to be a problem. Although the number of cases continues gradually to decrease in the United States, cases get more difficult to treat, specifically those that are multiple-drug resistant. Infection of one-third of the world's population ensures that tuberculosis will not disappear in the near future. In light of this, it will be useful to know the goals for the health care system and how these goals may be accomplished. Laboratory testing in the mycobacteriology field is experiencing more changes today than ever before. Determining what assays will be most useful to the clinician is a challenge, and acceptance of the new technology by the medical community an even greater one. Clinicians must use the best available resources to determine the most appropriate care for their patients and work together with the laboratory to ensure that the communication channels are open. This review focuses on current state-of-the-art resources useful for accurate and rapid laboratory diagnosis of mycobacterial infection

The impact of changes in Clinical Microbiology Laboratory location and ownership on the practice of Infectious Diseases

The number of onsite clinical microbiology laboratories in hospitals is decreasing, likely related to the business model for laboratory consolidation and labor shortages, and this impacts a variety of clinical practices including banking isolates for clinical or epidemiologic purposes. To determine the impact of these trends, infectious disease (ID) physicians were surveyed regarding their perceptions of offsite services. Clinical microbiology practices for retention of clinical isolates for future use were also determined. Surveys were sent to members of the Infectious Diseases Society of America\u27s (IDSA) Emerging Infections Network (EIN). The EIN is a sentinel network of ID physicians who care for adult and/or pediatric patients in North America and who are members of IDSA. The response rate was 763 (45%) of 1,680 potential respondents. Five hundred forty (81%) respondents reported interacting with the clinical microbiology laboratory. Eighty-six percent of respondents thought an onsite laboratory very important for timely diagnostic reporting and ongoing communication with the clinical microbiologist. Thirty-five percent practiced in institutions where the core microbiology laboratory has been moved offsite, and an additional 7% (N=38) reported that movement of core laboratory functions offsite was being considered. The respondents reported that only 24% of laboratories banked all isolates with the majority saving isolates for less than 30 days. Based on these results, the trend towards centralized core laboratories negatively impacts the practice of ID physicians, potentially delays effective implementation of prompt and targeted care for patients with serious infections, and similarly adversely impacts infection control epidemiologic investigations

Discrete Routh Reduction

This paper develops the theory of abelian Routh reduction for discrete mechanical systems and applies it to the variational integration of mechanical systems with abelian symmetry. The reduction of variational Runge-Kutta discretizations is considered, as well as the extent to which symmetry reduction and discretization commute. These reduced methods allow the direct simulation of dynamical features such as relative equilibria and relative periodic orbits that can be obscured or difficult to identify in the unreduced dynamics. The methods are demonstrated for the dynamics of an Earth orbiting satellite with a non-spherical $J_2$ correction, as well as the double spherical pendulum. The $J_2$ problem is interesting because in the unreduced picture, geometric phases inherent in the model and those due to numerical discretization can be hard to distinguish, but this issue does not appear in the reduced algorithm, where one can directly observe interesting dynamical structures in the reduced phase space (the cotangent bundle of shape space), in which the geometric phases have been removed. The main feature of the double spherical pendulum example is that it has a nontrivial magnetic term in its reduced symplectic form. Our method is still efficient as it can directly handle the essential non-canonical nature of the symplectic structure. In contrast, a traditional symplectic method for canonical systems could require repeated coordinate changes if one is evoking Darboux' theorem to transform the symplectic structure into canonical form, thereby incurring additional computational cost. Our method allows one to design reduced symplectic integrators in a natural way, despite the noncanonical nature of the symplectic structure.Comment: 24 pages, 7 figures, numerous minor improvements, references added, fixed typo

Variational and Geometric Structures of Discrete Dirac Mechanics

In this paper, we develop the theoretical foundations of discrete Dirac mechanics, that is, discrete mechanics of degenerate Lagrangian/Hamiltonian systems with constraints. We first construct discrete analogues of Tulczyjew's triple and induced Dirac structures by considering the geometry of symplectic maps and their associated generating functions. We demonstrate that this framework provides a means of deriving discrete Lagrange-Dirac and nonholonomic Hamiltonian systems. In particular, this yields nonholonomic Lagrangian and Hamiltonian integrators. We also introduce discrete Lagrange-d'Alembert-Pontryagin and Hamilton-d'Alembert variational principles, which provide an alternative derivation of the same set of integration algorithms. The paper provides a unified treatment of discrete Lagrangian and Hamiltonian mechanics in the more general setting of discrete Dirac mechanics, as well as a generalization of symplectic and Poisson integrators to the broader category of Dirac integrators.Comment: 26 pages; published online in Foundations of Computational Mathematics (2011

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)a

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients

Detection of Bloodstream Infections in Adults: How Many Blood Cultures Are Needed?▿

Although several reports have shown that two to three 20-ml blood cultures are adequate for the detection of bacteremia and fungemia in adults, a recent study (F. R. Cockerill et al., Clin. Infect. Dis. 38:1724-1730, 2004) found that two blood cultures detected only 80% of bloodstream infections and that three blood cultures detected 96% of episodes. We reviewed data at two university hospitals to determine whether the recent observations by Cockerill et al. are applicable more widely. We assessed all blood cultures obtained from adult inpatients from 1 January 2004 through 31 December 2005 at Robert Wood Johnson University Hospital and Duke University Medical Center. All instances in which ≥3 blood cultures per patient were obtained during a 24-h period were included. The medical records of patients who met the inclusion criteria were reviewed retrospectively to determine the clinical significance of the positive blood culture (true infection versus contamination). Data were analyzed to determine the cumulative sensitivity of blood cultures obtained sequentially during the 24-h time period. Of 629 unimicrobial episodes with ≥3 blood cultures obtained during the 24-h period, 460 (73.1%) were detected with the first blood culture, 564 (89.7%) were detected with the first two blood cultures, 618 (98.2%) were detected with the first three blood cultures, and 628 (99.8%) were detected with the first four blood cultures. Of 351 unimicrobial episodes with ≥4 blood cultures obtained during the 24-h period, 257 (73.2%) were detected with the first blood culture, 308 (93.9%) were detected with the first two blood cultures, 340 (96.9%) were detected with the first three blood cultures, and 350 (99.7%) were detected with the first four blood cultures. Among unimicrobial episodes, Staphylococcus aureus was more likely to be detected with the first blood culture (approximately 90% detected with the first blood culture). There were 58 polymicrobial episodes in which ≥3 blood cultures were obtained. Forty-seven (81.0%) were detected with the first blood culture, 54 (93.1%) were detected with the first two blood cultures, and 58 (100%) were detected with the first three blood cultures. The results of this study indicate that two blood cultures in a 24-h period will detect approximately 90% of bloodstream infections in adults. To achieve a detection rate of >99%, as many as four blood cultures may be needed. The previously held axiom that virtually all bloodstream infections can be detected with two to three blood cultures may no longer be valid but may also depend on the definition of the “first” blood culture obtained (see Materials and Methods and Discussion in the text)

Multilaboratory Validation of Rapid Spot Tests for Identification of Escherichia coli

To validate the accuracy of rapid tests for identification of Escherichia coli, five laboratories sequentially collected 1,064 fresh, clinically significant strains with core criteria of indole-positive, oxidase-negative, nonspreading organisms on sheep blood agar plates (BAP), having typical gram-negative rod plate morphology, defined as good growth on gram-negative rod-selective media. An algorithm using beta-hemolysis on BAP, lactose reaction on eosin-methylene blue or MacConkey agar, l-pyrrolidonyl-β-naphthylamide (PYR), and 4-methylumbelliferyl-β-d-glucuronide (MUG) was evaluated. Identifications using the algorithm were compared to those obtained using commercial kit system identifications. One thousand strains were E. coli and 64 were not E. coli by kit identifications, which were supplemented with conventional biochemical testing of low probability profiles. Of the 1,064 isolates meeting the core criteria, 294 were beta-hemolytic and did not require further testing to be identified as E. coli. None of the 64 non-E. coli strains were hemolytic, although other indole-positive, lactose-negative species were found to be hemolytic when further strains were examined in a follow-up study. Of the remaining strains, 628 were identified as E. coli by a lactose-positive and PYR-negative reaction. For nonhemolytic, lactose-negative E. coli, PYR was not helpful, but a positive MUG reaction identified 65 of 78 isolates as E. coli. The remaining 13 E. coli strains required kit identifications. This scheme for E. coli identification misidentified three non-E. coli strains as E. coli, for an error rate of 0.3%. A total of 13 kit identifications, 657 PYR tests, and 113 MUG tests were needed to identify 1,000 E. coli strains with the algorithm. The use of this rapid system saves laboratory resources, provides timely identifications, and yields rare misidentifications