Trends in Non-Tuberculous Mycobacterial Lung Disease and Treatment Outcomes in a Low-Tuberculosis Prevalence Setting: A Retrospective Analysis.

BACKGROUND: Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. METHODS: A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021. RESULTS: Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was M. avium complex (MAC), followed by M. malmoense and M. abscessus. In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response. CONCLUSION: A favourable response to treatment was seen in 74% of patients with a high relapse rate.

Necrotising soft tissue infections. / Nekrotiserende bløtdelsinfeksjoner.

Necrotising soft tissue infections can affect the skin, subcutaneous tissue, superficial fascia, deep fascia and musculature. The infections are severe, they spread quickly and can result in extensive tissue loss. Although rare, morbidity and mortality rates are high. Early clinical identification is crucial for the outcome, and rapid infection control through surgery and targeted antibiotic treatment is needed to save lives. Few prospective clinical trials have been conducted for the treatment of this type of infection. Specific challenges include rapid identification of the condition and the uncertain efficacy of the various treatment options. In this clinical review article, we describe clinical characteristics, diagnostics and treatment.

Streptococcus dysgalactiae Bloodstream Infections, Norway, 1999-2021.

Streptococcus dysgalactiae increasingly is recognized as a pathogen of concern for human health. However, longitudinal surveillance data describing temporal trends of S. dysgalactiae are scarce. We retrospectively identified all ß-hemolytic streptococcal bloodstream infections reported in Bergen, in western Norway, during 1999-2021. To explore S. dysgalactiae disease burden in a broader context, we mapped the incidence of all microbial species causing bloodstream infections during 2012-2021. We found S. dysgalactiae incidence rates substantially increased during the study period; by 2021, S. dysgalactiae was the fifth most common pathogen causing bloodstream infections in our region. We noted genotypic shifts and found that the rising trend was related in part to the introduction and expansion of the stG62647 emm-type. S. dysgalactiae is among the most common causes of bloodstream infections in western Norway, and increased surveillance and unambiguous species identification are needed to monitor the disease burden attributable to this pathogen.

Escherichia marmotae-a Human Pathogen Easily Misidentified as Escherichia coli.

We hereby present the first descriptions of human-invasive infections caused by Escherichia marmotae, a recently described species that encompasses the former "Escherichia cryptic clade V." We describe four cases, one acute sepsis of unknown origin, one postoperative sepsis after cholecystectomy, one spondylodiscitis, and one upper urinary tract infection. Cases were identified through unsystematic queries in a single clinical lab over 6 months. Through genome sequencing of the causative strains combined with available genomes from elsewhere, we demonstrate Es. marmotae to be a likely ubiquitous species containing genotypic virulence traits associated with Escherichia pathogenicity. The invasive isolates were scattered among isolates from a range of nonhuman sources in the phylogenetic analyses, thus indicating inherent virulence in multiple lineages. Pan genome analyses indicate that Es. marmotae has a large accessory genome and is likely to obtain ecologically advantageous traits, such as genes encoding antimicrobial resistance. Reliable identification might be possible by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), but relevant spectra are missing in commercial databases. It can be identified through 16S rRNA gene sequencing. Escherichia marmotae could represent a relatively common human pathogen, and improved diagnostics will provide a better understanding of its clinical importance. IMPORTANCE Escherichia coli is the most common pathogen found in blood cultures and urine and among the most important pathogenic species in the realm of human health. The notion that some of these isolates are not Es. coli but rather another species within the same genus may have implications for what Es. coli constitutes. We only recently have obtained methods to separate the two species, which means that possible differences in important clinical aspects, such as antimicrobial resistance rates, virulence, and phylogenetic structure, may exist. We believe that Es. marmotae as a common pathogen is new merely because we have not looked or bothered to distinguish between the thousands of invasive Escherichia passing through microbiological laboratories each day.

Consistent Biofilm Formation by Streptococcus pyogenes emm 1 Isolated From Patients With Necrotizing Soft Tissue Infections.

OBJECTIVES: Biofilm formation has been demonstrated in muscle and soft tissue samples from patients with necrotizing soft tissue infection (NSTI) caused by Streptococcus pyogenes, but the clinical importance of this observation is not clear. Although M-protein has been shown to be important for in vitro biofilm formation in S. pyogenes, the evidence for an association between emm type and biofilm forming capacity is conflicting. Here we characterize the biofilm forming capacity in a collection of S. pyogenes isolates causing NSTI, and relate this to emm type of the isolates and clinical characteristics of the patients. METHODS: Bacterial isolates and clinical data were obtained from NSTI patients enrolled in a multicenter prospective observational study. Biofilm forming capacity was determined using a microtiter plate assay. RESULTS: Among 57 cases, the three most frequently encountered emm types were emm1 (n = 22), emm3 (n = 13), and emm28 (n = 7). The distribution of biofilm forming capacity in emm1 was qualitatively (narrow-ranged normal distribution) and quantitatively (21/22 isolates in the intermediate range) different from other emm types (wide ranged, multimodal distribution with 5/35 isolates in the same range as emm1). There were no significant associations between biofilm forming capacity and clinical characteristics of the patients. CONCLUSIONS: The biofilm forming capacity of emm1 isolates was uniform and differed significantly from other emm types. The impact of biofilm formation in NSTI caused by S. pyogenes on clinical outcomes remains uncertain.

Carbapenem-Resistant Enterobacteriaceae-Implications for Treating Acute Leukemias, a Subgroup of Hematological Malignancies.

Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae presence (e.g., Klebsiella pneumonia and Escherichia coli) is a frequent cause of bloodstream infections in AL patients. Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging health problem worldwide; however, the incidence of CRE varies greatly between different regions. Carbapenem resistance in Enterobacteriaceae is caused by different mechanisms, and CRE may display various resistance profiles. Bacterial co-expression of genes conferring resistance to both broad-spectrum ß-lactam antibiotics (including carbapenems) and other classes of antibiotics may give rise to multidrug-resistant organisms (MDROs). The spread of CRE represents a major treatment challenge for clinicians due to lack of randomized clinical trials (RCTs), a limited number of antibiotics available, and the side-effects associated with them. Most research concerning CRE infections in AL patients are limited to case reports and retrospective reviews. Current research recommends treatment with older antibiotics, such as polymyxins, fosfomycin, older aminoglycosides, and in some cases carbapenems. To prevent the spread of resistant microbes, it is of pivotal interest to implement antibiotic stewardship to reduce broad-spectrum antibiotic treatment, but without giving too narrow a treatment to neutropenic infected patients.

A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+ T cell responses.

TRIAL REGISTRATION: ClinicalTrials.gov ClinicalTrials.gov, Project ID: NCT02870751.

Stratification by interferon-γ release assay level predicts risk of incident TB.

INTRODUCTION: Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. METHODS: In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. RESULTS: The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). CONCLUSIONS: Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

Zoonotic necrotizing myositis caused by Streptococcus equi subsp. zooepidemicus in a farmer.

BACKGROUND: Streptococcus equi subsp. zooepidemicus is a beta-hemolytic group C streptococcus mainly causing infections in domesticated animals. Here we describe the first case of zoonotic necrotizing myositis caused by this bacterium. CASE PRESENTATION: The patient was a 73-year-old, previously healthy farmer with two asymptomatic Shetland ponies in his stable. After close contact with the ponies while feeding them, he rapidly developed erythema of his left thigh and sepsis with multiple organ failure. The clinical course was severe and complicated, requiring repetitive surgical excision of necrotic muscle, treatment with vasopressors, mechanical ventilation and continuous venovenous hemofiltration, along with adjunctive hyperbaric oxygen therapy. The patient was discharged from hospital at day 30, without obvious sequelae. The streptococcal isolate was identified as Streptococcus equi by MALDI-ToF MS, and was later assigned subspecies identification as S. equi subsp. zooepidemicus. Multilocus sequence typing identified the strain as a novel sequence type (ST 364), closely related to types previously identified in horses and cattle. A focused proteomic analysis revealed that the ST 364 expressed putative virulence factors similar to that of Streptococcus pyogenes, including homologues of the M protein, streptodornases, interleukin 8-protease and proteins involved in the biosynthesis of streptolysin S. CONCLUSION: This case illustrates the zoonotic potential of S. equi subsp. zooepidemicus and the importance of early clinical recognition, rapid and radical surgical therapy, appropriate antibiotics and adequate supportive measures when necrotizing soft tissue infection is suspected. The expression of Streptococcus pyogenes-like putative virulence determinants in ST 364 might partially explain the fulminant clinical picture.

Extended spectrum cephalosporin resistance among clinical isolates of Enterobacteriaceae in West Norway during 2006-2013; a prospective surveillance study.

Routine surveillance of resistance to broad-spectrum cephalosporins in Enterobacteriaceae and phenotypic identification of underlying mechanisms using a simple strategy was commenced in 2006 at our laboratory, serving West Norway. This report focuses on the results until 2013. The classical plasmid-mediated extended spectrum beta-lactamase (ESBLA ) among clinically relevant Escherichia coli isolates showed an increase from 0.6% to 4.3% during the surveillance period, while prevalence for other mechanisms remained stable, below 0.7%. ESBLA in Klebsiella pneumoniae had similar prevalence in 2006 (0.6%) and 2013 (4.4%), but in between it peaked to 3.9% in 2008 and to 9.3% in 2011. Within the other species, the numbers of clinically relevant isolates and isolates-producing ESBLA were much lower. An increasing resistance due to hyperproduction of AmpC enzymes was seen in Enterobacter and Citrobacter, with prevalence increasing from 18% and 12.2% in 2006 to 27.5% and 26.1% in 2013, respectively. Hyperproduction of KOXY enzyme in Klebsiella oxytoca remained below 9.5% and did not show an increasing trend. The overall increase in the proportions of isolates-producing ESBLA in E. coli/K. pneumoniae and hyperproduction of AmpC in Enterobacter/Citrobacter necessitates measures to hinder the spread of resistant bacteria and vigilant antibiotic stewardship.

Experimental infection of healthy volunteers with enterotoxigenic Escherichia coli wild-type strain TW10598 in a hospital ward.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea in resource-limited regions. It is also an important cause of diarrhea in travellers to these areas.To evaluate the protective efficacy of new ETEC vaccines that are under development, there is a need to increase the capacity to undertake Phase IIB (human challenge) clinical trials and to develop suitable challenge models. METHODS: An in-hospital study was performed where fasting adult volunteers were experimentally infected with 1 × 106 to 1 × 109 colony forming units (CFUs) of the wild-type ETEC strain TW10598, which had been isolated from a child with diarrhea in West Africa in 1997. We recorded symptoms and physical signs and measured serum immune response to the TW10598 bacterium. RESULTS: We included 30 volunteers with mean age 22.8 (range 19.8, 27.4) years. The most common symptoms were diarrhea (77%), abdominal pain (67%), nausea (63%), and abdominal cramping (53%). Seven subjects (23%) experienced fever, none were hypotensive. Most of the volunteers responded with a substantial rise in the level of serum IgA antibodies against the challenge strain. CONCLUSIONS: We established the capacity and methods for safely undertaking challenge studies to measure the efficacy of ETEC vaccine candidates in a hospital ward. Strain TW10598 elicited both clinical symptoms and an immune response across the doses given.

The decline of the impetigo epidemic caused by the epidemic European fusidic acid-resistant impetigo clone: an 11.5-year population-based incidence study from a community in Western Norway.

BACKGROUND: From around the year 2000, Northern Europe experienced a rise in impetigo caused by Staphylococcus aureus resistant to fusidic acid. A single clone of S. aureus was found to be the bacterial pathogen involved in the impetigo outbreak in Norway, Sweden, the UK and Ireland, termed 'the epidemic European fusidic acid-resistant impetigo clone' (EEFIC). We have followed the incidence of impetigo during the years 2001-2012 based on all patients in general practice in the island community of Austevoll, Western Norway. We previously reported a marked decline of impetigo incidence in Austevoll, from 0.0260 cases per person-year in 2002 to 0.0038 in 2009. This article explores indications of an end to the impetigo epidemic caused by the EEFIC clone. METHODS: All four general practitioners (GPs) in the community (mean population = 4400) were asked to diagnose impetigo in a uniform way and to take bacterial specimens from all impetigo cases. Phenotypic characteristics of specimen bacteria were determined for the whole period and molecular analyses were performed on isolates in the period 2008-2012. RESULTS: We observed a further decline in incidence of impetigo in Austevoll in the study period. The proportion of fusidic acid-resistant S. aureus isolates decreased during the period 2002-2012, with a mean of 80% in the epidemic years of 2002-2004, 55% in 2005-2009, and 6% in 2010-2012. In total, 44 S. aureus isolates from impetigo were subject to molecular analyses in the period 2008-2012, and 11 were found to be related to the EEFIC. All EEFIC isolates were found in 2008-2009, with no new isolates in 2010-2012. CONCLUSION: There is an apparent end to the impetigo epidemic related to the EEFIC in this population in Western Norway.

Impetigo in a population over 8.5 years: incidence, fusidic acid resistance and molecular characteristics.

OBJECTIVES: From around year 2000, impetigo caused by fusidic acid-resistant Staphylococcus aureus was observed in countries of Northern Europe. The bacteria were found to represent a clone, the epidemic European fusidic acid-resistant impetigo clone (EEFIC). This study reports longitudinal data on the incidence and bacteriology of impetigo in a Norwegian island community during the years 2001-09. PATIENTS AND METHODS: All encounters with general practitioners regarding impetigo were registered. Bacterial swabs were taken in a high percentage of cases. Annual incidence was calculated. Phenotypic characteristics of the bacteria were determined for the whole period, and in 2008 and 2009 we also performed PFGE and spa typing. RESULTS: Outbreaks of impetigo were observed in 2002, 2003 and 2004, but since then the incidence decreased greatly. S. aureus was cultured from the impetigo site in the majority of cases. The proportion of S. aureus isolates resistant to fusidic acid decreased from 80% in 2002-04 to 45% in 2008-09. For 28 S. aureus isolates analysed by molecular methods in 2008-09, we found that nearly all cases of fusidic acid resistance were due to the presence of the EEFIC. CONCLUSIONS: S. aureus resistance to fusidic acid in relation to impetigo is now less frequent in this population than at the start of the century. At present, most S. aureus bacteria resistant to fusidic acid in impetigo belong to the EEFIC.

Emergence of clonally related Klebsiella pneumoniae isolates of sequence type 258 producing plasmid-mediated KPC carbapenemase in Norway and Sweden.

BACKGROUND: The class A carbapenemase KPC has disseminated rapidly worldwide, challenging the treatment of Gram-negative infections. This report describes the first KPC-producing Klebsiella pneumoniae isolates identified in Norway (n=6) and the second isolate from Sweden. METHODS: Antimicrobial susceptibility profiles were determined using Etest. PCR and sequencing were used to determine the bla(KPC) variant, the surrounding genetic structure and the presence of AmpC and extended-spectrum beta-lactamase genes. PFGE and multilocus sequence typing (MLST) were used for epidemiological comparisons. Localization of bla(KPC) was investigated by S1 nuclease digestion, followed by PFGE and Southern blot hybridization. RESULTS: All isolates expressed a multidrug-resistant phenotype with some variability in the carbapenem susceptibility profile. The Norwegian isolates carried bla(KPC-2), while the Swedish isolate carried bla(KPC-3). All isolates carried TEM-1, but were negative for bla(CTX-M) and bla(AmpC) genes. SHV-11 and SHV-12 were detected in the Norwegian isolates, while the Swedish isolate carried only SHV-11. Isolates from four patients were associated with import from Greece (n=3) and Israel. The other isolates were probably associated with local transmissions. PFGE and MLST showed that the isolates were clonally related, with three isolates displaying ST258, a single locus variant of ST11 previously associated with the clonal spread of CTX-M-15-producing K. pneumoniae in Hungary. In all isolates, bla(KPC) was located on plasmids as part of isoform a of Tn4401. CONCLUSIONS: The emergence of KPC-producing isolates of K. pneumoniae in Norway and Sweden is associated with multiple import events and probable local transmission of a successful multiresistant ST258 clone, closely related to the CTX-M-15-producing ST11 clone previously described in Hungary.

The interaction between military education and health: a survey among conscripts undergoing officer training in Norway.

An increasing number of soldiers are unable to finish their military training because of health problems. In the summer of 1999, 236 (96%) of 246 officer training school applicants in Harstad, Northern Norway, were enrolled in the survey. Those selected for military education estimated their physical condition better (p < 0.02), participated in athletic sport more frequently (p < 0.05), and smoked four times less (p < 0.001) than those who were dismissed. Thirty-nine percent of those accepted for further military education went to see the doctor during the 3-week introductory period compared with 20% among those who were dismissed (p < 0.002). The overall consultation rate in the introductory period was 52.5 per 100 cadet months. During the rest of the education, the consultation rate dropped significantly to 43.1 (p < 0.02). The magnitude of health-related problems during military education is a concern from a medical point of view and can, at least in part, be attributed to the level of physical activity of the military education.