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Background: Susceptibility to respiratory infections increases with age. Diagnosing and treating tuberculosis in the elderly comes with the challenges of fewer specific symptoms and possibly more side effects of treatment. Much is unknown when it comes to tuberculosis in the elderly, especially in relation to inflammation, which may impact mortality. We, therefore, investigated a clinical cohort of elderly tuberculosis patients., Methods: Patients aged ≥65 years, admitted to our tuberculosis reference center between 2005 and 2021, were retrospectively included in our cohort. Sociodemographic data, clinical characteristics, laboratory results, including inflammatory markers at baseline (monocyte, neutrophil, lymphocyte count, and CRP levels), and treatment outcomes were collected. They were compared to the National Dutch TB Registry and analyzed using descriptive statistics. Survival analysis was performed using univariate Cox regression analysis and a log-rank test. Results were visualized in Kaplan-Meier curves., Results: 104 elderly tuberculosis patients, mostly European, with a mean age of 75 years, were included. None were HIV-infected. Miliary tuberculosis cases were overrepresented (14 %) compared to the National Dutch TB Registry (5 % in elderly, 2 % adults). Fever occurred in 77 % (57/74), and the duration of fever decreased with age. Innate immune markers, including monocyte/lymphocyte-ratio, moderately correlated with CRP. Overall mortality was 15 %, and highest (33 %) in patients with CRP levels >100 mg/mL., Conclusion: In elderly tuberculosis patients in a low-incidence setting, mortality rates are higher in comparison to younger patients. The overrepresentation of miliary tuberculosis may suggest waning immunity, with a subset of patients exhibiting strong inflammation associated with increased mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Conflicts of interest: none declared.

Background: Paradoxical inflammatory responses can occur during microbiologically successful antituberculous therapy. Optimal treatment is unknown, but corticosteroids are used most often. It is likely that interleukin-1 (IL-1) plays a central role in the development of these paradoxical responses, and if corticosteroids fail or are undesirable because of adverse effects, anti-IL-1 therapy may therefore be a rational choice., Methods: We present seven HIV-negative tuberculosis patients with paradoxical responses, two with exclusively pulmonary and five with extrapulmonary tuberculosis. All had received corticosteroids, with unsatisfactory effect. Patients were treated with the IL-1 receptor antagonist anakinra and monitored for reduction of fever and inflammatory markers, imaging evidence of stabilization or regression of lesions, and respiratory improvement., Findings: Six patients had anemia and four patients had lymphopenia at the start of the antituberculosis treatment. Fever was present in six patients at the moment of paradoxical response. Anakinra resulted in the decrease of fever within days, followed by resolution of symptoms and radiological improvement in five patients. Anakinra induced neutropenia, necessitating its cessation in two patients, who recovered quickly afterward., Conclusion: Anakinra can be considered in HIV-negative tuberculosis patients with paradoxical responses when steroids fail or are undesired. Given its favorable safety profile and reversible side effects, it is conceivable that anakinra might also be used as first-line adjuvant treatment for paradoxical responses., Funding: A.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: A number of community-acquired MRSA (CA-MRSA) clonal lineages dominate worldwide. ST80 was dominant in Europe and has increasingly been described from the Middle East. Here we report the whole genome sequence of the first ST80 CA-MRSA from the USA., Methods: CA-MRSA isolate S0924 was obtained from a patient admitted to Cook County Hospital (Chicago, IL, USA) who came from Syria; the isolate belonged to spa type t044 and ST80. The whole genome sequence of S0924 was determined and compared with three previously published whole genome sequences of ST80 CA-MRSA from Europe and a newly sequenced ST80 CA-MRSA from the Netherlands (S1475)., Results: Based on spa typing, SCCmec type and virulence gene profile, this US ST80 isolate is indistinguishable from the European CA-MRSA ST80 clone. SNP analysis within the conserved core genome showed clear differences between the strains with up to 144 SNPs differing between S0924 and strain S1800, an ST80 MRSA from Greece. The gene content showed 21 regions of difference between the US and European isolates, although these were largely restricted to mobile genetic elements. Phylogenetic reconstruction indicated that the European strains were more closely related to each other than to the US strain. The SNP data suggest that a common ancestor existed around two decades ago, indicating that the US and European ST80 strains are clonally linked., Conclusions: These data combined with the country of origin of the patient suggest that ST80 S0924 was probably relatively recently introduced into the USA from Syria., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Methicillin resistance in Staphylococcus aureus and coagulase-negative staphylococci (CoNS) is caused by expression of the low-affinity penicillin-binding protein (PBP) 2a encoded by the mecA gene. This gene is carried on the staphylococcal cassette chromosome mec (SCCmec) of which several types and subtypes have been described. CoNS and S. aureus share SCCmec types and it has been suggested that CoNS are a potential reservoir of mecA for S. aureus. Evidence for this is mainly based on PCR typing of SCCmec or on sequence-based methods including only a limited number of strains. In this study, we determined the genetic relatedness of ccrB sequences contained in SCCmec elements of a spatio-temporally diverse and comprehensive collection of methicillin-resistant CoNS and S. aureus., Methods: Part of the ccrB genes of 367 methicillin-resistant CoNS and 94 methicillin-resistant S. aureus (MRSA) were sequenced and compared., Results: The data revealed that 92 of 94 (98%) MRSA isolates carried ccrB genes, involving different ccrB alleles, which were indistinguishable from ccrB genes of methicillin-resistant CoNS. In total, 273 of 367 (74%) CoNS shared ccrB gene sequences with MRSA., Conclusions: The high rate of identical ccrB sequences in a geographically, temporally and genotypically diverse set of S. aureus and CoNS isolates indicates frequent horizontal transfer of SCCmec between CoNS and S. aureus, which may have contributed to the emergence of MRSA.

Introduction: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA., Materials and Methods: Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements., Conclusion: The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone.

Background: Microarray-based Comparative Genomic Hybridisation (CGH) has been used to assess genetic variability between bacterial strains. Crucial for interpretation of microarray data is the availability of a reference to compare signal intensities to reliably determine presence or divergence each DNA fragment. However, the production of a good reference becomes unfeasible when microarrays are based on pan-genomes.When only a single strain is used as a reference for a multistrain array, the accessory gene pool will be partially represented by reference DNA, although these genes represent the genomic repertoire that can explain differences in virulence, pathogenicity or transmissibility between strains. The lack of a reference makes interpretation of the data for these genes difficult and, if the test signal is low, they are often deleted from the analysis. We aimed to develop novel methods to determine the presence or divergence of genes in a Staphylococcus aureus multistrain PCR product microarray-based CGH approach for which reference DNA was not available for some probes., Results: In this study we have developed 6 new methods to predict divergence and presence of all genes spotted on a multistrain Staphylococcus aureus DNA microarray, published previously, including those gene spots that lack reference signals. When considering specificity and PPV (i.e. the false-positive rate) as the most important criteria for evaluating these methods, the method that defined gene presence based on a signal at least twice as high as the background and higher than the reference signal (method 4) had the best test characteristics. For this method specificity was 100% and 82% for MRSA252 (compared to the GACK method) and all spots (compared to sequence data), respectively, and PPV were 100% and 76% for MRSA252 (compared to the GACK method) and all spots (compared to sequence data), respectively., Conclusion: A definition of gene presence based on signal at least twice as high as the background and higher than the reference signal (method 4) had the best test characteristics, allowing the analysis of 6-17% more of the genes not present in the reference strain. This method is recommended to analyse microarray data that partially lack a reference signal.

A 63-year-old woman with a kidney transplant was admitted with endocarditis caused by meticillin-resistant Staphylococcus aureus (MRSA). Once her antibiotic therapy had been adjusted to the sensitivity-pattern of the bacterial strain she recovered, without the need for surgical intervention. The isolated S. aureus was typed by multi-locus sequence typing as sequence type 398, a MRSA-strain that has recently been isolated from a high percentage of Dutch pigs. This is the first report of a life-threatening infection with this pig MRSA. This strain is genetically different from the globally dispersed nosocomial MRSA-strains, and also from the strains that have been epidemic for several years in the USA as the causative agent ofcommunity-acquired skin infections. The Dutch Working Group on Infection Prevention (WIP) has recently adjusted its guidelines to halt further spread of this strain, and advises that the population at risk (pig breeders, slaughterhouse personnel and veterinarians) be held in isolation when hospitalised until MRSA colonisation has been excluded. The patient described here, however, did not belong to this population at risk.