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BackgroundCarbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms.MethodsTo overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years.ResultsOur CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment.ConclusionsCollectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage of Klebsiella pneumoniae There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniae carbapenemases) beta-lactamases encoded by blaKPC2, blaKPC3, and blaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401 element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.

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.

During the past decade, there has been an emergence of carbapenem-resistant Enterobacteriaceae that produce carbapenemases, enzymes that efficiently hydrolyze carbapenems, as well as most β-lactam drugs (1). The most common [...]

The case of a 24-year-old woman with abdominal pain and shock is discussed to arrive at a better understanding of intestinal bacillus anthracis infection with sepsis. The different treatment methodologies and management regime for the same are highlighted.

A case study of a 58-year old woman with fever and neck pain is discussed to better understand the causes and symptoms of spinal epidural abscess. The diagnosis and treatment suggested were also discussed.

Human infections caused by Bartonella species was studied and presented. A case study of a 43-year old woman having a fever after traveling in Peru for 3 weeks is presented

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. [ABSTRACT FROM AUTHOR]

* Context.--Case reports have described detection of candidemia by examination of peripheral blood smears. It is unclear whether this method has wider applicability for early detection of fungemia. Objective.--To determine [...]

Techniques for diagnosing Helicobacter pylori infection are classifiable as invasive or noninvasive. Invasive diagnostic methods require a gastric biopsy obtained via esophagogastroduodenal endoscopy and include histologic examination, microbiologic culture, or [...], * Objective.--To evaluate simultaneous diagnosis of infection and molecular resistance testing of Helicobacter pylori. Methods.--Gastric biopsies were obtained from 26 rapid urease-positive and 51 rapid urease-negative test kits used to diagnose H pylori infection. Following glass bead-assisted DNA isolation, amplification of H pylori 16S ribosomal DNA (rDNA), glmM, and 23S rDNA target genes was performed. Results.--Helicobacter pylori DNA was successfully amplified from 100% (26/26) of urease-positive and 3.9% (2/ 51) of urease-negative gastric biopsies. Subsequent restriction enzyme-mediated digestion of 23S rDNA amplification products revealed that 17% (4/24) of urease-positive and H pylori DNA-positive biopsy specimens contained point mutations (A2142G or A2143G) associated with clarithromycin resistance. Helicobacter pylori DNA from gastric biopsies was successfully amplified 8 weeks following rapid urease testing. Conclusion.--Helicobacter pylori genotyping may be used to detect macrolide-resistant H pylori in individuals prior to initiation of therapy or in patients refractory to anti-H pylori therapy. Two urease-negative specimens yielded Helicobacter DNA distinct from that of H pylori and indicated the need for further investigations of Helicobacter species present in the human stomach. (Arch Pathol Lab Med. 2001;125:493-497)