Summary Klebsiella pneumoniae is the most clinically relevant species of this genus, known to cause both community-acquired and nosocomial infections worldwide. In the past two decades, a distinct ...hypervirulent strain of K pneumoniae , characterised by its hypermucoviscous phenotype, has emerged as a clinically significant pathogen responsible for highly invasive infections. We present a case of osteomyelitis due to hypervirulent K pneumoniae reported in the USA. Genomic testing of the K pneumoniae isolate was performed due to the striking clinical presentation of the infection as well as the hypermucoid nature of the isolates, raising the suspicion for possible infection with the hypervirulent strain. Whole-genome sequencing and additional PCR testing demonstrated the isolate to be a K1 serotype, sequence type 23 strain expressing rmpA and rmpA2 . Given the multiple reports of this pathogen causing invasive infections, clinicians should be aware of the possible presentation of metastatic and severe infection, including osteomyelitis, due to the hypervirulent strain of K pneumoniae not typical of classic K pneumoniae variants. In this Grand Round, we review the clinical features of hypervirulent K pneumoniae and its link to invasive infections, and discuss the need for improved awareness and identification of the pathogen.
Identification of bloodstream infections is among the most critical tasks performed by the clinical microbiology laboratory. While the criteria for achieving an adequate blood culture specimen in ...adults have been well described, there is much more ambiguity in pediatric populations. This minireview focuses on the available pediatric literature pertaining to the collection of an optimal blood culture specimen, including timing, volume, and bottle selection, as well as rapid diagnostic approaches and their role in the management of pediatric bloodstream infections.
Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal ...homeostasis is unknown. Here, we show that Aim2−/− mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2−/− mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2−/− mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2−/− mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.
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•AIM2 senses intestinal microbial DNA and activates the inflammasome•The AIM2 inflammasome protects mice from experimental colitis•The AIM2 inflammasome controls the growth of commensal Escherichia coli•The inflammasome triggers antimicrobial peptide production by epithelial cells
AIM2 is a cytosolic DNA sensor. Hu et al. demonstrate that intestinal microbial DNA activates the AIM2 inflammasome. AIM2 activation leads to the production of IL-1β and IL-18, which participate in the regulation of intestinal microbiota such as Escherichia coli via induction of the antimicrobial peptides in intestinal epithelial cells.
Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the ...dextran sulfate sodium (DSS) and azoxymethane + DSS models. Mice lacking the inflammasome adaptor protein PYCARD (ASC) and caspase-1 demonstrate increased disease outcome, morbidity, histopathology, and polyp formation. The increased tumor burden is correlated with attenuated levels of IL-1beta and IL-18 at the tumor site. To decipher the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) component that is involved in colitis and CAC, we assessed Nlrp3 and Nlrc4 deficient mice. Nlrp3(-/-) mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3(-/-) mice than in Pycard(-/-) or Casp1(-/-) animals. No significant differences were observed in disease progression or outcome in Nlrc4(-/-) mice compared with similarly treated wild-type animals. Bone marrow reconstitution experiments show that Nlrp3 gene expression and function in hematopoietic cells, rather than intestinal epithelial cells or stromal cells, is responsible for protection against increased tumorigenesis. These data suggest that the inflammasome functions as an attenuator of colitis and CAC.
Rapid diagnostic tests are needed to improve patient care and to combat the problem of antimicrobial resistance. The Accelerate Pheno system (Accelerate Diagnostics, Tucson, AZ) is a new diagnostic ...device that can provide rapid bacterial identification and antimicrobial susceptibility test (AST) results directly from a positive blood culture. The device was compared to the standard of care at two academic medical centers. There were 298 blood cultures included in the study, and the Accelerate Pheno system provided a definitive identification result in 218 instances (73.2%). The Accelerate Pheno system provided a definitive and correct result for 173 runs (58.1%). The Accelerate Pheno system demonstrated an overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 94.7%, 98.9%, 83.7%, and 99.7%, respectively. An AST result was available for analysis in 146 instances. The overall category agreement was 94.1% with 12 very major errors, 5 major errors, and 55 minor errors. After a discrepancy analysis, there were 5 very major errors and 4 major errors. The Accelerate Pheno system provided an identification result in 1.4 h and an AST result in 6.6 h; the identification and AST results were 41.5 h and 48.4 h faster than those with the standard of care, respectively. This study demonstrated that the Accelerate Pheno system is able to provide fast and accurate organism identification and AST data. A limitation is the frequency with which cultures required the use of alternative identification and AST methods.
The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3), its adaptor protein ...PYCARD (ASC), and caspase-1 during infection with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture induced IL-1beta secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3(-/-), Casp-1(-/-), and WT mice showed no differences in pulmonary IL-1beta production, bacterial burden, or long-term survival. In contrast, a significant role was observed for Pycard in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of Pycard(-/-) mice. Decreased survival of Pycard(-/-) animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The advent of new diagnostics assays for Group A Streptococcus, influenza, and respiratory syncytial virus now provide rapid results with increased sensitivity and specificity. Molecular testing is ...no longer confined to the walls of the laboratory, but moving to the patient in the form of point-of-care tests. In addition, multiplex syndromic panels are allowing broad testing of pathogens associated with a single clinical presentation. This article focuses specifically on rapid diagnostic tests for pathogens most affecting children. Rapid and accurate pathogen detection in children may result in decreased time to optimal antimicrobial treatment and improved patient outcomes.
The Anelloviridae family consists of non-enveloped, circular, single-stranded DNA viruses. Three genera of anellovirus are known to infect humans, named TTV, TTMDV, and TTMV. Although anelloviruses ...were initially thought to cause non-A-G viral hepatitis, continued research has shown no definitive associations between anellovirus and human disease to date. Using high-throughput sequencing, we investigated the association between anelloviruses and fever in pediatric patients 2-36 months of age. We determined that although anelloviruses were present in a large number of specimens from both febrile and afebrile patients, they were more prevalent in the plasma and nasopharyngeal (NP) specimens of febrile patients compared to afebrile controls. Using PCR to detect each of the three species of anellovirus that infect humans, we found that anellovirus species TTV and TTMDV were more prevalent in the plasma and NP specimens of febrile patients compared to afebrile controls. This was not the case for species TTMV which was found in similar percentages of febrile and afebrile patient specimens. Analysis of patient age showed that the percentage of plasma and NP specimens containing anellovirus increased with age until patients were 19-24 months of age, after which the percentage of anellovirus positive patient specimens dropped. This trend was striking for TTV and TTMDV and very modest for TTMV in both plasma and NP specimens. Finally, as the temperature of febrile patients increased, so too did the frequency of TTV and TTMDV detection. Again, TTMV was equally present in both febrile and afebrile patient specimens. Taken together these data indicate that the human anellovirus species TTV and TTMDV are associated with fever in children, while the highly related human anellovirus TTMV has no association with fever.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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