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Background: Azithromycin (AZI) is recommended with ceftriaxone (CRO) for treatment of uncomplicated gonococcal urethritis and cervicitis in the United States, and an AZI-susceptibility breakpoint is needed. Neither the Food and Drug Administration (FDA) nor the Clinical and Laboratory Standards Institute (CLSI) has set interpretive breakpoints for AZI susceptibility. As a result, AZI antimicrobial susceptibility testing (AST) cannot be interpreted using recognized standards. This has contributed to increasingly unavailable clinical laboratory AST, although gonorrhea is on the rise with >550 000 US gonorrhea cases reported to the Centers for Disease Control and Prevention in 2017, the highest number of cases since 1991., Methods: This article summarizes the rationale data reviewed by the CLSI in June 2018., Results: The CLSI decided to set a susceptible-only interpretive breakpoint at the minimum inhibitory concentration of ≤1 µg/mL. This is also the epidemiological cutoff value (ECV) (ie, the end of the wild-type susceptibility distribution). This breakpoint presumes that AZI (1-g single dose) is used in an approved regimen that includes an additional antimicrobial agent (ie, CRO 250 mg, intramuscular single dose)., Conclusions: Having a breakpoint can improve patient care and surveillance and allow future development and FDA regulatory approval of modernized AST to guide treatment. The breakpoint coincides with a European Committee on AST decision to remove previously established, differing AZI breakpoints and use the ECV as guidance for testing. The CLSI breakpoint is now the recognized standard that defines AZI susceptibility for gonococcal infections., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: The conventional 2-tiered serologic testing protocol for Lyme disease (LD), an enzyme immunoassay (EIA) followed by immunoglobulin M and immunoglobulin G Western blots, performs well in late-stage LD but is insensitive in patients with erythema migrans (EM), the most common manifestation of the illness. Western blots are also complex, difficult to interpret, and relatively expensive. In an effort to improve test performance and simplify testing in early LD, we evaluated several modified 2-tiered testing (MTTT) protocols, which use 2 assays designed as first-tier tests sequentially, without the need of Western blots., Methods: The MTTT protocols included (1) a whole-cell sonicate (WCS) EIA followed by a C6 EIA; (2) a WCS EIA followed by a VlsE chemiluminescence immunoassay (CLIA); and (3) a variable major protein-like sequence, expressed (VlsE) CLIA followed by a C6 EIA. Sensitivity was determined using serum from 55 patients with erythema migrans; specificity was determined using serum from 50 patients with other illnesses and 1227 healthy subjects., Results: Sensitivity of the various MTTT protocols in patients with acute erythema migrans ranged from 36% (95% confidence interval [CI], 25%-50%) to 54% (95% CI, 42%-67%), compared with 25% (95% CI, 16%-38%) using the conventional protocol (P = .003-0.3). Among control subjects, the 3 MTTT protocols were similarly specific (99.3%-99.5%) compared with conventional 2-tiered testing (99.5% specificity; P = .6-1.0)., Conclusions: Although there were minor differences in sensitivity and specificity among MTTT protocols, each provides comparable or greater sensitivity in acute EM, and similar specificity compared with conventional 2-tiered testing, obviating the need for Western blots., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Objectives: The scope of activities performed by clinical laboratory directors is sometimes unfamiliar to other physicians or hospital administrators. Consequently, hospital leadership may undervalue the role and assume that many director level activities could be delegated to a professional manager. In this study, we sought to define the activities of academic laboratory directors, and to determine which activities require doctorate level medical or scientific expertise., Methods: We performed an audit of laboratory director activities at a large academic medical center by reviewing electronic calendars and other available records from the preceding 12 consecutive months. For episodic activities, the directors estimated the average number of hours devoted over the 1-year period., Results: On average, directors worked 54.9 hours per week and performed at least some service work 47.7 weeks per year. Administrative duties accounted for the greatest proportion of effort (47.1%), followed by clinical activities (33.1%) and academic activities (19.8%). Among administrative duties, those that required doctorate level medical or scientific expertise comprised 60.3% of the total administrative effort, whereas the remaining 39.7% (18.7% of total activity) could be performed by a professional manager.., Conclusions: Although the activities of clinical laboratory directors have been described elsewhere, this is the first study detailing the effort allocated to these various activities in quantitative terms. The study demonstrated that less than 20% of an academic laboratory director's effort involves administrative activities that could potentially be performed by a professional manager lacking doctorate level medical or scientific expertise., (Copyright© by the American Society for Clinical Pathology.)

Background: Carbapenems are recommended for treatment of Enterobacter infections with AmpC phenotypes. Although isolates are typically susceptible to cefepime in vitro, there are few data supporting its clinical efficacy., Methods: We reviewed all cases of Enterobacter species bacteremia at 2 academic hospitals from 2005 to 2011. Outcomes of interest were (1) persistent bacteremia ≥1 calendar day and (2) in-hospital mortality. We fit logistic regression models, adjusting for clinical risk factors and Pitt bacteremia score and performed propensity score analyses to compare the efficacy of cefepime and carbapenems., Results: Three hundred sixty-eight patients experienced Enterobacter species bacteremia and received at least 1 antimicrobial agent, of whom 52 (14%) died during hospitalization. Median age was 59 years; 19% were neutropenic, and 22% were in an intensive care unit on the day of bacteremia. Twenty-nine (11%) patients had persistent bacteremia for ≥1 day after antibacterial initiation. None of the 36 patients who received single-agent cefepime (0%) had persistent bacteremia, as opposed to 4 of 16 (25%) of those who received single-agent carbapenem (P < .01). In multivariable models, there was no association between carbapenem use and persistent bacteremia (adjusted odds ratio [aOR], 1.52; 95% CI, .58-3.98; P = .39), and a nonsignificant lower odds ratio with cefepime use (aOR, 0.52; 95% CI, .19-1.40; P = .19). In-hospital mortality was similar for use of cefepime and carbapenems in adjusted regression models and propensity-score matched analyses., Conclusions: Cefepime has a similar efficacy as carbapenems for the treatment of Enterobacter species bacteremia. Its use should be further explored as a carbapenem-sparing agent in this clinical scenario.

In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.

Background: Physicians in the United States sometimes need to evaluate a patient for suspected Lyme borreliosis (LB) who may have acquired the infection in Europe. Using serum samples from European LB patients, we compared the performance of European and US serodiagnostic tests, including newer-generation assays containing Vmp-like sequence, expressed or its C6 peptide., Methods: The sensitivity of each assay was determined using 64 serum samples from LB patients with early or late disease manifestations who acquired the infection in Europe. Specificity was measured using 100 sera from healthy subjects from a nonendemic area., Results: For the detection of European-acquired infection, conventional 2-tiered testing (enzyme-linked immunosorbent assay [ELISA] followed by immunoblotting) using US assays had an overall sensitivity and specificity of 52% and 100%, compared with 81% (P = .0007) and 99% (P = 1.00) using analogous European tests. The sensitivity of a US C6 ELISA used as a stand-alone test (88% overall) was statistically comparable to that of conventional 2-tiered testing using European tests (P = .47) and was 100% specific. Similarly, an alternative 2-tiered algorithm using a standard US ELISA followed by a C6 ELISA was comparably sensitive (84% overall) compared with conventional 2-tiered testing using European assays (P = .82), and specificity remained 100%., Conclusions: European assays outperformed analogous US assays in a conventional 2-tiered testing algorithm. However, a C6 ELISA used as a stand-alone test or in the second tier of a 2-tiered algorithm performed comparably to conventional 2-tiered testing using European assays, and can be used for evaluation of any patient, regardless of travel history.

Widespread resistance in Enterobacteriaceae and Pseudomonas aeruginosa to cephalosporin and monobactam antibiotics due to extended-spectrum β-lactamases (ESBLs) has resulted in the need for reassessment of the interpretative criteria (breakpoints) established for these agents more than 2 decades ago. Following extensive evaluation, the Clinical and Laboratory Standards Institute recently adopted and published new breakpoints for these agents for use in clinical laboratories and provided updated recommendations for use of the ESBL screening test. This paper summarizes the background and supportive rationale for new interpretative criteria for cephalosporins and aztreonam for testing Enterobacteriaceae.

Background: Lyme disease (LD) antibody testing currently involves a 2-tiered algorithm with a whole-cell sonicate (WCS) enzyme immunoassay (EIA), followed by IgM/IgG Western immunoblots. A single EIA using the C6 peptide of the Borrelia burgdorferi variable-major protein-like sequence expressed lipoprotein provides similar or better sensitivity but less specificity, compared with standard 2-tiered testing. Here, we investigated an alternative 2-tiered strategy, in which the first step remained a WCS EIA, but immunoblotting was replaced by a C6 EIA., Methods: We determined the sensitivity of the 3 testing strategies with use of 91 serum samples from research study patients with LD and 78 serum samples from patients with LD whose samples were submitted to our hospital's clinical laboratory. Specificity was measured using 54 patients with other illnesses and 1246 healthy subjects from areas where the infection is endemic and nonendemic., Results: The 2-EIA algorithm in early LD had similar sensitivity as C6 testing alone, and both strategies had better sensitivity than did standard 2-tiered testing (61% and 64%, respectively, vs 48%; P = .03 and P = .008). For late disease, all 3 strategies had 100% sensitivity. The specificity of the 2-EIA algorithm was equal to that of standard 2-tiered testing, and both 2-tiered strategies were more specific than C6 testing alone (for both, 99.5% vs 98.4%; P = .01). The positive predictive value of the 2-EIA algorithm was 70%, compared with 66% for standard 2-tiered testing and 43% for the C6 EIA alone., Conclusions: The 2-EIA strategy matched the individual strengths of the C6 EIA and Western blotting, without the drawbacks. The 2 EIAs provided sensitivity comparable to that of the C6 EIA but maintained the specificity of standard 2-tiered testing.

Background: Standard 2-tiered immunoglobulin G (IgG) testing has performed well in late Lyme disease (LD), but IgM testing early in the illness has been problematic. IgG VlsE antibody testing, by itself, improves early sensitivity, but may lower specificity. We studied whether elements of the 2 approaches could be combined to produce a second-tier IgG blot that performs well throughout the infection., Methods: Separate serum sets from LD patients and control subjects were tested independently at 2 medical centers using whole-cell enzyme immunoassays and IgM and IgG immunoblots, with recombinant VlsE added to the IgG blots. The results from both centers were combined, and a new second-tier IgG algorithm was developed., Results: With standard 2-tiered IgM and IgG testing, 31% of patients with active erythema migrans (stage 1), 63% of those with acute neuroborreliosis or carditis (stage 2), and 100% of those with arthritis or late neurologic involvement (stage 3) had positive results. Using new IgG criteria, in which only the VlsE band was scored as a second-tier test among patients with early LD (stage 1 or 2) and 5 of 11 IgG bands were required in those with stage 3 LD, 34% of patients with stage 1, 96% of those with stage 2, and 100% of those with stage 3 infection had positive responses. Both new and standard testing achieved 100% specificity., Conclusions: Compared with standard IgM and IgG testing, the new IgG algorithm (with VlsE band) eliminates the need for IgM testing; it provides comparable or better sensitivity, and it maintains high specificity.

An important task of the clinical microbiology laboratory is the performance of antimicrobial susceptibility testing of significant bacterial isolates. The goals of testing are to detect possible drug resistance in common pathogens and to assure susceptibility to drugs of choice for particular infections. The most widely used testing methods include broth microdilution or rapid automated instrument methods that use commercially marketed materials and devices. Manual methods that provide flexibility and possible cost savings include the disk diffusion and gradient diffusion methods. Each method has strengths and weaknesses, including organisms that may be accurately tested by the method. Some methods provide quantitative results (eg, minimum inhibitory concentration), and all provide qualitative assessments using the categories susceptible, intermediate, or resistant. In general, current testing methods provide accurate detection of common antimicrobial resistance mechanisms. However, newer or emerging mechanisms of resistance require constant vigilance regarding the ability of each test method to accurately detect resistance.

Background: Examination of multiple stool specimens per patient to rule out parasitic infection continues to be recommended in the literature. Attractive alternatives have been proposed, such as examination of a single specimen, but data to support their use have been inconclusive., Methods: We reviewed the results of comprehensive stool ova and parasite examinations performed during a 1-year period to determine the incremental value of examining >1 specimen. Next, we implemented rejection criteria, allowing analysis of only a single specimen in most cases, and studied the impact of the change by reviewing data from a subsequent year., Results: Prior to implementation of rejection criteria, 91% of parasites were detected in the first specimen submitted, although many clinical evaluations (72%) involved the submission of only 1 stool specimen. When at least 3 specimens were submitted, the sensitivity of examining the first in the series was 72%. Even the latter sensitivity provides negative predictive values of approximately 98%, approximately 97%, approximately 95%, or approximately 93% when the prevalence of parasites among those tested is 5%, 10%, 15%, or 20%, respectively. Examination of additional specimens after examination of the first specimen that yielded a positive finding revealed previously undetected parasites in only 10% of cases. After the application of rejection criteria, the parasite detection rate did not change significantly., Conclusions: Comprehensive examination of a single stool specimen is sufficient for most patients, when the prevalence of infection among the tested population is up to 20%. Rational use of the stool ova and parasite examination relies on communication between clinician and laboratory, and retention of deferred specimens in case examination of additional specimens is clinically warranted.

Linezolid is an important therapeutic option for treatment of infections caused by glycopeptide- and beta-lactam-resistant gram-positive organisms. Linezolid resistance is caused by mutations within the domain V region of the 23S ribosomal RNA (rRNA) gene, which is present in multiple copies in most bacteria. Among clinical Staphylococcus aureus isolates, there has been only 1 reported case of linezolid resistance. In the present study, this isolate was further characterized by determination of the number of mutant 23S rRNA copies, assessment of the stability of the resistant phenotype, and comparison of its growth characteristics with those of linezolid-susceptible S. aureus. All 5 copies of the 23S rRNA gene contained a G2576U mutation in the domain V region. After serial passage on antibiotic-free medium, the isolate maintained resistance to high concentrations of linezolid. Compared with 2 linezolid-susceptible S. aureus isolates, the linezolid-resistant S. aureus isolate demonstrated no significant differences in in vitro growth characteristics.