Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study.

INTRODUCTION: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.

Meropenem pharmacokinetic/pharmacodynamic target attainment and clinical response in ICU patients: A prospective observational study.

BACKGROUND: Several studies report lack of meropenem pharmacokinetic/pharmacodynamic (PK/PD) target attainment (TA) and risk of therapeutic failure with intermittent bolus infusions in intensive care unit (ICU) patients. The aim of this study was to describe meropenem TA in an ICU population and the clinical response in the first 72 h after therapy initiation. METHODS: A prospective observational study of ICU patients ≥18 years was conducted from 2014 to 2017. Patients with normal renal clearance (NRC) and augmented renal clearance (ARC) and patients on continuous renal replacement therapy (CRRT) were included. Meropenem was administered as intermittent bolus infusions, mainly at a dose of 1 g q6h. Peak, mid, and trough levels were sampled at 24, 48, and 72 h after therapy initiation. TA was defined as 100% T > 4× MIC or trough concentration above 4× MIC. Meropenem PK was estimated using traditional calculation methods and population pharmacokinetic modeling (P-metrics®). Clinical response was evaluated by change in C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA) score, leukocyte count, and defervescence. RESULTS: Eighty-seven patients were included, with a median Simplified Acute Physiology (SAPS) II score 37 and 90 days mortality rate of 32%. Median TA was 100% for all groups except for the ARC group with 45.5%. Median CRP fell from 175 (interquartile range [IQR], 88-257) to 70 (IQR, 30-114) (p < .001) in the total population. A reduction in SOFA score was observed only in the non-CRRT groups (p < .001). CONCLUSION: Intermittent meropenem bolus infusion q6h gives satisfactory TA in an ICU population with variable renal function and CRRT modality, except for ARC patients. No consistent relationship between TA and clinical endpoints were observed.

Guideline for management of septic arthritis in native joints (SANJO).

This clinical guideline is intended for use by orthopedic surgeons and physicians who care for patients with possible or documented septic arthritis of a native joint (SANJO). It includes evidence and opinion-based recommendations for the diagnosis and management of patients with SANJO.

Multiorgan inflammatory syndrome associated with SARS-CoV-2 in a child. / Multiorgan inflammatorisk syndrom assosiert med sars-CoV-2 hos et barn.

This case report describes a child with heart failure and incipient multiorgan failure following infection with SARS-CoV-2. This is not COVID-19, but a delayed immune response known as multiorgan inflammatory syndrome. We have treated a number of children with this condition, and similar cases have been reported internationally. Patients can quickly become seriously ill, with high fever, gastrointestinal symptoms and cardiogenic shock.

Correction: Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting.

[This corrects the article DOI: 10.1371/journal.pone.0187618.].

Transfer of a bla CTX-M-1-carrying plasmid between different Escherichia coli strains within the human gut explored by whole genome sequencing analyses.

Horizontal transfer of antibiotic resistance determinants contributes to dissemination of antibiotic resistance. Such transfer of resistance genes within the human gut has been documented in some in vivo studies. The present study investigated seven bla CTX-M-1-carrying Escherichia coli isolates from three consecutive faecal samples collected from one cystic fibrosis patient in a nine-months period, by analysing whole genome sequencing data. The analyses showed that the seven E. coli isolates represented three genetically diverse strains. All isolates contained bla CTX-M-1-carrying Incl1 plasmids that shared a common 101 kb backbone differing by only four SNPs. The plasmids harboured by the three different E. coli strains varied within limited regions suggestive of recombination events, according to the phylogenetic topology of the genomes of the isolates harbouring them. The findings strongly suggest that horizontal transfer of a bla CTX-M-1-carrying plasmid had occurred within the patient´s gut. The study illustrates the within-host diversity of faecally carried resistant E. coli isolates and highlights the value of collecting multiple bacterial colonies from longitudinally collected samples to assess faecal carriage of resistant enterobacteria. The clustering of the plasmids with the corresponding E. coli strains carrying them indicates that the plasmids appear to have adapted to their respective E. coli hosts.

Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting.

We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the observed phenotypic resistance in all 28 multidrug-resistant E. coli isolates examined.

A novel Direct MIC-gradient Strip Method to screen for antibiotic-resistant faecal Enterobacteriaceae.

A novel method to detect resistant faecal Enterobacteriaceae was developed by applying MIC-gradient strips directly onto agar plates inoculated with faeces. The method provided the susceptibility pattern (MICs) of the dominant bacterial population directly on the plates and also detected smaller resistant subpopulations with a sensitivity of 1/10(5).

Multilocus sequence typing of serial Candida albicans isolates from children with cancer, children with cystic fibrosis and healthy controls.

Candida albicans is a fungal pathogen, but also a commensal in many individuals. Since detailed molecular studies of children carrying C. albicans are lacking, we longitudinally investigated fecal and tonsillopharyngeal samples from 10 children undergoing treatment for cancer, six children treated for cystic fibrosis (CF), and seven healthy children during the time period of 1999-2008. Multilocus sequence typing (MLST) was performed on 62 C. albicans isolates. Only three of the 23 children (13%) were colonized with genetically unrelated strains in the longitudinal follow-up. We identified 32 different diploid sequence types (DSTs), but only one (409) was shared by two siblings. Most often, the fecal strain types were identical or closely related to the tonsillopharyngeal reservoirs. We found no closely related strain types in children who were hospitalized in the same ward or in children attending the same day care center. There was no sign of resistance to fluconazole, caspofungin, amphotericin B or flucytosine over time. This study shows that both children with cancer or CF, and healthy children usually harbor the same C. albicans strain over time. We did not find indications of clonal spread between children in the same environments, except in a pair of siblings.

[Bacterial resistance against antibiotics]. / Bakteriell resistens mot antibiotika.

BACKGROUND: Antibiotic resistance has progressed over many decades and is increasingly problematic. This paper gives a short summary of antibiotic resistance and its biology. MATERIAL AND METHODS: The authors have worked in this field for many years. References to major overviews and important work are given, but no systematic literature search has been done. RESULTS: Development of resistance is driven by positive selection of resistant clones of bacteria. There are multiple, often interlinked molecular mechanisms behind this resistance, and they all lead to a less effective interaction between antibiotics and their target. INTERPRETATION: Many observations of antibiotic resistance phenomena and their development over the last decades indicate that the problem is substantial, persisting and increasing. It will probably have an important impact on many medical disciplines in the future. Work to counteract this development is needed in every medical field in order to halt and hopefully counteract resistance development as strongly as we can.

[Coagulase-negative staphylococci--biofilm and antibiotic resistance]. / Biofilm og antibiotikaresistens hos koagulasenegative stafylokokker.

BACKGROUND: Coagulase-negative staphylococci (CoNS) may cause serious infections in immunocompromized patients. CoNS often display multiresistance to antibiotics, and biofilm production is the central virulence factor. Our aim was to investigate these factors in CoNS that colonize children with an increased risk of CoNS infections. MATERIAL AND METHOD: We collected CoNS isolates from intravasal catheters (n = 19) and the skin (n = 47) from 30 hospitalized neonates, and CoNS skin isolates from 20 children with cancer before (n = 20) and after (n = 18) six months of cancer treatment. We analyzed antibiotic resistance and biofilm production with phenotypic methods. We used PCR to detect genes that encode antibiotic resistance and biofilm formation. RESULTS: 11 of 19 (58 %) catheter isolates and 14 of 47 (30 %) skin isolates (p = 0.04) produced biofilm. We found an increasing prevalence of oxacillin resistance (20 % versus 67 %, p = 0.004) and gentamicin resistance (15 % versus 67 %, p = 0.003) after six months of cancer treatment. Biofilm positive CoNS isolates displayed higher levels of antibiotic resistance than biofilm-negative isolates. INTERPRETATION: Our results indicate that sick neonates and children hospitalized with cancer are colonized with pathogenic CoNS strains demonstrating virulence- and antibiotic-resistance patterns that are different from those found in CoNS in healthy people who are not hospitalized.

Febrile neutropenia in children with cancer: a retrospective Norwegian multicentre study of clinical and microbiological outcome.

Our objective was to describe clinical and laboratory characteristics, treatment and outcome among Norwegian children with cancer suffering from chemotherapy-induced febrile neutropenia (FN). We retrospectively reviewed data on paediatric FN episodes in 7 Norwegian hospitals during a 2.5-y period. A total of 236 episodes of FN occurred in 95 children. Acute lymphoblastic leukaemia was the most common diagnosis (49 patients). Blood cultures yielded growth in 39 episodes (17%). Primary empirical antibiotic regimens could be assigned to 2 main groups: 1) benzylpenicillin or ampicillin and an aminoglycoside (58%) or 2) a regimen based on third-generation cephalosporins (42%). There were no statistically significant differences in outcome between the 2 regimens in terms of need to change initial antibiotic treatment, d of fever or maximum C-reactive protein values. One infection-related death (fungal septicaemia) occurred during the study period. We conclude that incidence of septicaemia and clinical outcome is similar to recent international trials on paediatric FN, but antibiotic treatment in Norway differs from international guidelines. However, patients in our study were successfully and safely treated, irrespective of the primary empirical antibiotic regimen.