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Background: The aim was to determine whether salvage treatment with systemic antibiotics is a safe and effective strategy for Enterobacterales bloodstream infections (BSI) in pediatric oncology patients with a central venous catheter (CVC)., Methods: A retrospective study was performed on oncology and stem cell recipient patients with a CVC and blood culture with Enterobacterales , at the Princess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands. Analyses were performed for all BSI and for episodes meeting central line-associated bloodstream infection (CLABSI) criteria. The cumulative incidence of an event (ie, removal, intensive care admission or death) was estimated after blood culture collection for episodes primarily treated with antibiotics. The effect of prognostic factors on the hazard of the event of interest was assessed by estimating a Cox proportional hazard regression model., Results: In total, 95 CVC-related Enterobacterales BSIs in 82 patients were included; 12 (13%) BSIs required immediate CVC removal and for 83 (87%) BSIs CVC salvage was attempted. The cumulative incidence of events at 60 days was 53.0% [95% confidence interval (CI): 41.7-63.1] for BSIs (n = 83), and 64.4% (95% CI: 48.3-76.7) for CLABSIs (n = 45). The events occurred after a median of 6 (Q1-Q3: 2-15) and 6 (Q1-Q3: 2-20) days for BSIs and CLABSIs, respectively. Intensive care admission after salvage treatment was required in 16% of the BSIs and CLABSIs, resulting in death in 5% and 2% of cases, respectively. No significant association between risk factors and events was found., Conclusions: The cumulative incidence of an event at 60 days after salvage treatment for Enterobacterales CLABSIs and BSIs in pediatric oncology patients is high. Immediate CVC removal appears recommendable for this patient group., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies., Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors., Design, Setting, and Participants: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio., Exposure: Preoperative S aureus colonization., Main Outcomes and Measures: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models., Results: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs., Conclusions and Relevance: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa , with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa . Three methods are described: a clinical isolate infection model, utilising isolates obtained from patients with CF; an incomplete antibiotic clearance model, leading to bacterial bounce-back; and the establishment of chronic infection; and an adapted water bottle chronic infection model. These models circumvent the requirement for a surgical procedure and, importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.

Introduction. Haemophilus influenzae is a commensal of the respiratory tract that is frequently present in cystic fibrosis (CF) patients and may cause infection. Antibiotic resistance is well described for CF strains, and virulence factors have been proposed. Hypothesis/Gap. The genetic diversity of H. influenzae strains present in the lungs of persons with CF is largely unknown despite the fact that this organism is considered to be a pathogen in this condition. The aim was to establish the genetic diversity and susceptibility of H. influenzae strains from persons with CF, and to screen the whole genomes of these strains for the presence of antibiotic resistance determinants and proposed virulence factors. Methods. A total of 67 strains, recovered from respiratory samples from persons with CF from the UK ( n =1), Poland ( n =2), Spain ( n =24) and the Netherlands ( n =40), were subjected to whole-genome sequencing using Illumina technology and tested for antibiotic susceptibility. Forty-nine of these strains (one per different sequence type) were analysed for encoded virulence factors and resistance determinants. Results. The 67 strains represented 49 different sequence types. Susceptibility testing showed that all strains were susceptible to aztreonam, ciprofloxacin, imipenem and tetracycline. Susceptibility to ampicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, cefuroxime, cefixime, ceftriaxone, cefepime, meropenem, clarithromycin, co-trimoxazole and levofloxacin ranged from 70.2-98.5%. Only 6/49 strains (12.2%) harboured acquired resistance genes. Mutations associated with a ß-lactamase-negative ampicillin-resistant phenotype were present in four strains (8.2 %). The potential virulence factors, urease, haemoglobin- and haptoglobin-binding protein/carbamate kinase, and OmpP5 (OmpA), were encoded in more than half of the strains. The genes for HMW1, HMW2, H. influenzae adhesin, a IgA-specific serine endopeptidase autotransporter precursor, a TonB-dependent siderophore, an ABC-transporter ATP-binding protein, a methyltransferase, a BolA-family transcriptional regulator, glycosyltransferase Lic2B, a helix-turn-helix protein, an aspartate semialdehyde dehydrogenase and another glycosyltransferase were present in less than half of the strains. Conclusion. The H. influenzae strains showed limited levels of resistance, with the highest being against co-trimoxazole. Sequences encoding a carbamate kinase and a haemoglobin- and haemoglobin-haptoglobin-binding-like protein, a glycosyl transferase and an urease may aid the colonization of the CF lung. The adhesins and other identified putative virulence factors did not seem to be necessary for colonization.

Background: The potential pathogenic role of Stenotrophomonas maltophilia in lung disease and in particular in cystic fibrosis is unclear. To develop further understanding of the biology of this taxa, the taxonomic position, antibiotic resistance and virulence factors of S. maltophilia isolates from patients with chronic lung disease were studied., Results: A total of 111 isolates recovered between 2003 and 2016 from respiratory samples from patients in five different countries were included. Based on a cut-off of 95%, analysis of average nucleotide identity by BLAST (ANIb) showed that the 111 isolates identified as S. maltophilia by Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS) belonged to S. maltophilia (n = 65), S. pavanii (n = 6) and 13 putative novel species (n = 40), which each included 1-5 isolates; these groupings coincided with the results of the 16S rDNA analysis, and the L1 and L2 ß-lactamase Neighbor-Joining phylogeny. Chromosomally encoded aminoglycoside resistance was identified in all S. maltophilia and S. pavani isolates, while acquired antibiotic resistance genes were present in only a few isolates. Nevertheless, phenotypic resistance levels against commonly used antibiotics, determined by standard broth microbroth dilution, were high. Although putative virulence genes were present in all isolates, the percentage of positive isolates varied. The Xps II secretion system responsible for the secretion of the StmPr1-3 proteases was mainly limited to isolates identified as S. maltophilia based on ANIb, but no correlation with phenotypic expression of protease activity was found. The RPF two-component quorum sensing system involved in virulence and antibiotic resistance expression has two main variants with one variant lacking 190 amino acids in the sensing region., Conclusions: The putative novel Stenotrophomonas species recovered from patient samples and identified by MALDI-TOF/MS as S. maltophilia, differed from S. maltophilia in resistance and virulence genes, and therefore possibly in pathogenicity. Revision of the Stenotrophomonas taxonomy is needed in order to reliably identify strains within the genus and elucidate the role of the different species in disease., (© 2022. The Author(s).)

The role of Achromobacter species in lung disease remains unclear. The aim of this study was to characterize Achromobacter isolated from persons with cystic fibrosis and from other clinical samples. Whole genome sequences from 101 Achromobacter isolates were determined (81 from patients with cystic fibrosis and 20 from other patients) and analysed. Taxonomic analysis showed nine species including two putative novel species. Thirty-five novel sequence types were present. The most active agent was co-trimoxazole followed by imipenem, but Minimal Inhibitory Concentrations (MICs) were high. Acquired antibiotic resistance genes were rare. Their presence did not correlate with minimal inhibitory concentrations suggesting that other mechanisms are involved. Genes for proposed virulence factors were present in only some isolates. Two putative novel species were identified. The putative virulence properties of Achromobacter involved in infections are variable. Despite the high MICs, acquired resistance genes are uncommon., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Inhaled antibiotics are a common and valuable therapy for patients suffering from chronic lung infection, with this particularly well demonstrated for patients with cystic fibrosis. However, in vitro tests to predict patient response to inhaled antibiotic therapy are currently lacking. There are indications that antimicrobial susceptibility testing (AST) may have a role in guidance of therapy, but which tests would correlate best still needs to be researched in clinical studies or animal models. Applying the principles of European Committee on Antimicrobial Susceptibility Testing methodology, the analysis of relevant and reliable data correlating different AST tests to patients' outcomes may yield clinical breakpoints for susceptibility, but these data are currently unavailable. At present, we believe that it is unlikely that standard determination of minimum inhibitory concentration will prove the best predictor., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

To improve understanding of the role of Ralstonia in cystic fibrosis (CF), whole genomes of 18 strains from clinical samples were sequenced using Illumina technology. Sequences were analysed by core genome Multi-Locus Sequence Typing, Average Nucleotide Identity based on BLAST (ANIb), RAST annotation, and by ResFinder. Phylogenetic analysis was performed for the 16S rRNA gene, and the OXA-22 and OXA-60 ß-lactamase families. The minimal inhibitory concentrations (MICs) were determined using broth microdilution. ANIb data for the 18 isolates and 54 strains from GenBank, supported by phylogenetic analysis, showed that 8 groups of clusters (A-H), as well as subgroups that should be considered as species or subspecies. Groups A-C contain strains previously identified as Ralstonia solanacearum and Ralstonia pseudosolanacearum. We propose that group A is a novel species. Group B and C are Ralstonia syzygii, Ralstonia solanacearum, respectively. Group D is composed of Ralstonia mannitolilytica and Group E of Ralstonia pickettii. Group F and G should be considered novel species. Group H strains belong to R. insidiosa. OXA-22 and OXA-60 family ß-lactamases were encoded by all strains. Co-trimoxazole generally showed high activity with low MICs (≤1 mg/l) as did ciprofloxacin (≤0.12 mg/l). MICs against the other antibiotics were more variable, but generally high. RAST annotation revealed limited differences between the strains, and virulence factors were not identified. The taxonomy of the genus Ralstonia is in need of revision, but sequencing additional isolates is needed. Antibiotic resistance levels are high. Annotation did not identify potential virulence factors., (© 2021. The Author(s).)

Background: Sepsis is a major cause of morbidity and mortality worldwide. Early recognition and treatment of sepsis is associated with improved outcome. The emergency department (ED) is the department where patients with sepsis seek care. However, recognition of sepsis in the ED remains difficult. Different alert and triage systems, screening scores and intervention strategies have been developed to assist clinicians in early recognition of sepsis and to optimize management., Objectives: This narrative review describes currently applied interventions or interventions we can start using today, such as screening scores, (automated) triage systems, sepsis teams and clinical pathways in sepsis care; and it summarizes evidence for the effect of implementation of these interventions in the ED on patient management and outcomes., Sources: A systematic literature search was conducted in PubMed, resulting in 39 eligible studies., Content: The main sepsis interventions in the ED are (automated) triage systems, sepsis teams and clinical pathways, the most integrative being a clinical pathway. Implementation of any of these interventions in sepsis care will generally lead to increased protocol adherence. Presumably increased adherence to sepsis guidelines and bundles will lead to better patient outcomes, but the level of evidence to support this improvement is low, whereas implementation of interventions is often complex and costly. No studies comparing different interventions were identified. Two essential factors for success of interventions in the ED are obtaining the support from all professionals and providing ongoing education. The vulnerability of these interventions lies in the lack of accurate tools to identify sepsis; diagnosing sepsis ultimately still relies on clinical assessments. A lack of specificity or sepsis alerts may lead to alert fatigue and/or overtreatment., Implications: The severity and poor outcome of sepsis as well as the frequency of its presentation in EDs make a structured, protocol-based approach towards these patients essential, preferably as part of a clinical pathway., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Haemophilus parainfluenzae is considered part of the normal oropharyngeal flora but is known to occasionally cause infections. It is closely related to Haemophilus influenzae Here, we report the genome sequence of H. parainfluenzae COPD-014-E1 O, which was cultured from the sputum of a patient with chronic obstructive pulmonary disease., (Copyright © 2020 Fluit et al.)

Local prophylaxis with antibiotic-loaded bone cement is a successful method to prevent post-operative infections in patients receiving orthopaedic implants. No comparable method is available for uncemented implants. Therefore, a hydrogel consisting of hyaluronic and polylactic acids was evaluated in a rabbit model for delivery of antimicrobial agents to prevent post-operative infections. In a pilot study, the suitability of the in vivo model was assessed by testing the hydrogel as carrier material for antimicrobial agents.In the main study, the antimicrobial-agent-loaded hydrogel was evaluated for infection prophylaxis. Rabbits received a titanium rod intramedullary in the tibia after contamination with Staphylococcus aureus. The rods were coated with unloaded hydrogel (Gel), hydrogel loaded with 2 % (Van2) or 5 % vancomycin (Van5), bioactive glass (BAG) or N-acetyl-L-cysteine (NAC). To analyse the infection severity after 28 d, histopathological, bacteriological, micro-computed tomographic and haematological analyses were performed. In the pilot study, the Van5 group had less infection (0/6 infected) as compared to the Gel group (5/5, p = 0.000) and the in vivo model was deemed suitable. In the main study, in the Van2 and Van5 groups, the number of infected animals was lower [1/6 (p = 0.006) and 2/6 (p = 0.044) infected, respectively]. In contrast, BAG and NAC groups showed no infection reduction (5/6 both groups, p = 0.997). The hydrogel can be used as a local carrier of vancomycin for prophylaxis of implant-related infections.The present study showed promising results for local delivery of antibacterial agents by hydrogel to prevent implant-related infections.

The objective was to determine the in vitro antimicrobial susceptibility of Pseudomonas aeruginosa isolates cultured from cystic fibrosis (CF) patients and explore associations between strain sequence type and susceptibility. Fourteen antibiotics and antibiotic combinations, including the novel antibacterial peptide murepavadin, were tested for activity against 414 Pseudomonas aeruginosa isolates cultured from respiratory samples of CF patients. The complete genomes of the isolates were sequenced, and minimum spanning trees were constructed based on the sequence types (STs). Percentages of resistance according to CLSI 2019 breakpoints were as follows: cefepime, 14%; ceftazidime, 11%; ceftazidime-avibactam, 7%; ceftolozane-tazobactam, 3%; piperacillin-tazobactam, 12%; meropenem, 18%; imipenem, 32%; aztreonam, 23%; ciprofloxacin, 30%; gentamicin, 30%; tobramycin, 12%; amikacin, 18%; and colistin, 4%. Murepavadin MIC 50 and MIC 90 were 0.12 mg/liter and 2 mg/liter, respectively. There were no apparent clonal clusters associated with resistance, but higher MICs did appear to occur more often in STs with multiple isolates than in single ST isolates. In general, the CF isolates showed a wide genetic distribution. P. aeruginosa CF isolates exhibited the lowest resistance rates against ceftolozane-tazobactam, ceftazidime-avibactam, and colistin. Murepavadin demonstrated the highest activity on a per-weight basis and may therefore become a valuable addition to the currently available antibiotics for treatment of respiratory infection in people with CF., (Copyright © 2020 American Society for Microbiology.)

Objective: The Pseudomonas koreensis group bacteria are usually found in soil and are associated with plants. Currently they are poorly described. Here we report on the whole genome sequence of a bacterial isolate from a patient with bronchiectasis that was first identified as P. koreensis, and on its position in the P. koreensis group., Results: Strain 16-537536 was isolated from a patient with bronchiectasis from Spain and initially identified by MALDI-TOF as P. koreensis, a member of the Pseudomonas fluorescens complex. However, the average nucleotide identity analysis (ANIb) and whole genome alignments of the draft genome sequence of this strain showed it to be a member of the P. koreensis group of the P. fluorescens complex, but belonging to an undescribed species. In addition, based on ANIb analysis, the P. koreensis group contains several other unnamed species. Several genes for putative virulence factors were identified. The only antibiotic resistance gene present in strain 16-537536 was a class C β-lactamase. The correct identification of bacterial species from patients is of utmost importance in order to understand their pathogenesis and to track the potential spread of pathogens between patients. Whole genome sequence data should be included for the description of new species.

Aim: Genetic characterization of Pandoraea strains recovered from cystic fibrosis patients. Materials & methods: The whole-genome sequence of 12 Pandoraea strains was determined using Illumina technology. The position of the strains within the genus Pandoraea was analyzed using selected partial gene sequences, core genome multi-locus sequence typing and average nucleotide identity analysis. Furthermore, the sequences were annotated. Results: The results show that some strains previously identified as Pandoraea pnomenusa , Pandoraea sputorum , Pandoraea oxalativorans  and Pandoraea pulmonicola belong to novel species. The strains did not harbor acquired antibiotic resistance genes but encoded an OXA-type ß-lactamase. Conclusion: The taxonomy of the genus Pandoraea needs to be revised.

Median cystic fibrosis (CF) survival has increased dramatically over time due to several factors, including greater availability and use of antimicrobial therapies. During the progression of CF lung disease, however, the emergence of multidrug antimicrobial resistance can limit treatment effectiveness, threatening patient longevity. Current planktonic-based antimicrobial susceptibility testing lacks the ability to predict clinical response to antimicrobial treatment of chronic CF lung infections. There are numerous reasons for these limitations including bacterial phenotypic and genotypic diversity, polymicrobial interactions, and impaired antibiotic efficacy within the CF lung environment. The parallels to other chronic diseases such as non-CF bronchiectasis are discussed as well as research priorities for moving forward., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background Context: Surgical site infections (SSIs) are notorious complications in spinal surgery and cause substantial patient morbidity. Intraoperative decontamination of the wound with povidone-iodine irrigation or vancomycin powder has gained attention lately, but the efficacy of either intervention is unclear., Purpose: To determine the efficacy of intrawound povidone-iodine or vancomycin in reducing the incidence of deep- and superficial SSIs in instrumented spinal surgery., Study Design/setting: Retrospective cohort study., Patient Sample: A retrospective chart review was performed including all consecutive adult patients undergoing open, posterior, instrumented spinal surgery at any level between January 2012 and August 2017., Outcome Measures: The presence of SSI was evaluated according to the criteria published by the Centers for Disease Control and Prevention. The SSIs were divided into deep SSIs (below the muscular fascia) and superficial SSIs (above the muscular fascia)., Methods: A retrospective cohort without intrawound treatment was compared with two separate, consecutive intervention groups. One intrawound group received 1.3g/L povidone-iodine irrigation and the other received 1-2 grams of intrawound vancomycin powder at the end of surgery. Incidence of SSIs, as well as demographic, surgical and patient-related variables were registered and compared between groups. In patients with SSI, additional microbiological data were collected., Results: In total, 853 patients were included. In the control group (N=257), 25 (9.7%) patients developed a deep and 13 (5.1%) developed a superficial SSI. In the povidone-iodine group (N=217), 21 (9.7%) patients developed a deep and two (0.9%) developed a superficial SSI. Compared with the control group, there was no significant difference in the incidence of deep SSIs (risk ratio [RR]: 1.00, 95% CI 0.57-1.73), although the number of superficial SSIs was reduced significantly (RR 0.18, 95% CI 0.04-0.80). In the vancomycin group (N=379), 19 (5.0%) patients developed a deep and six (1.6%) developed a superficial SSI. Both deep (RR: 0.52, 95% CI 0.29-0.92) and superficial SSIs (RR: 0.31, 95% CI 0.12-0.81) were significantly reduced in the vancomycin group compared with the control group, even when correcting for several risk factors associated with SSIs in a multivariable logistic regression analysis. There were no significant differences in complications between the 3 groups. No gram-negative selection or vancomycin-resistance was seen in the vancomycin group., Conclusions: Intrawound application of vancomycin was associated with a significant reduction in both deep and superficial SSIs in instrumented spinal surgery. A 1.3g/L intrawound povidone-iodine solution did not show a reduction in deep SSIs, although a reduction of superficial SSIs was observed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Haemophilus haemolyticus is considered a commensal of the respiratory tract that can cause opportunistic infections. It is closely related to Haemophilus influenzae Here, we report the genome sequence of H. haemolyticus 16/010 O, which was isolated from sputum from a cystic fibrosis patient., (Copyright © 2019 Fluit et al.)

A 13-year old neutropenic boy succumbed to bacteremia and sepsis with a Pseudomonas aeruginosa strain that rapidly developed resistance to carbapenems during meropenem monotherapy. Whole genome sequencing of the susceptible and resistant blood culture isolates revealed the meropenem-resistant phenotype to be caused by truncation of the OprD gene, which added to a preexisting inactivated mexR gene.

Infection of the driveline or pump pocket is a common complication in patients with ventricular assist devices (VADs) and Staphylococcus aureus is the main pathogen causing such infections. Limited evidence is currently available to guide the choice of antibiotic therapy and the duration of treatment in these patients. Patients at the University Medical Center Utrecht who developed a VAD-related S. aureus infection between 2007 and 2016 were retrospectively assessed. Blood culture isolates were typed by whole genome sequencing to differentiate between relapses and reinfections, and to determine whether antibiotic therapy had led to acquisition of resistance mutations. Twenty-eight patients had S. aureus VAD infections. Ten of these patients also suffered S. aureus bacteremia. Discontinuation of antibiotic therapy was followed by relapse in 50% of the patients without prior S. aureus bacteremia and in 80% of patients with bacteremia. Oral cephalexin could ultimately suppress the infection for the duration of follow-up in 8/8 patients without S. aureus bacteremia and in 3/6 patients with S. aureus bacteremia. Clindamycin failed as suppressive therapy in 4/4 patients. Cephalexin appears an adequate choice for antibiotic suppression of VAD infections with methicillin-susceptible S. aureus. In patients without systemic symptoms, it may be justified to attempt to stop therapy after treatment of the acute infection, but antibiotic suppression until heart transplant seems indicated in patients with S. aureus bacteremia., (© 2018 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organ and Transplantation (ICAOT).)

Based on current research, there are no valid reasons to assume that influenza vaccination of people aged 60 and over without any other medical indications, in the context of the national programme of influenza prevention, leads to significant, relevant and cost-effective health benefits. In view of the pressure on health care budgets and the decreasing social willingness to vaccinate, it is of great and urgent importance that the actual effect of influenza vaccination is quantified in a double-blind placebo-controlled randomized trial (RCT) with relevant outcome measures, which does not suffer from the methodological shortcomings of the few previous studies. In order to demonstrate a 10% reduction in hospitalisation for respiratory infections, this RCT should include approximately 100,000 subjects and follow these participants for three years. We consider such a trial feasible in the Dutch situation.

Aims: To determine if type 2 diabetes mellitus (T2DM) is associated with the spectrum of uropathogens and antimicrobial resistance in urinary tract infections (UTI) in primary care., Methods: A cross-sectional study in female outpatients ≥30 years with positive urine cultures. T2DM patients were 1:1 matched to controls by age group and general practitioner (GP). GPs were sent questionnaires for additional data. Uropathogens and resistance patterns were compared between patients with and without T2DM. Multivariable regression analysis was performed to assess the independent association between T2DM and resistance to first line treatments, defined as resistance to nitrofurantoin, trimethoprim, fosfomycin, ciprofloxacin, amoxicillin/clavulanic acid and/or trimethoprim/sulfamethoxazole., Results: In 566 urine cultures, 680 uropathogens were found. Resistance to first line treatment antibiotics was present in 62.5% of patients. Frequencies and resistance rates of uropathogens did not differ between both groups of patients. Previous UTI and previous hospital admission were independent risk factors for resistance, but T2DM was not., Conclusions: In this study T2DM was not an independent risk factor for antimicrobial resistance in UTI in primary care. Previous UTI and hospitalisation are drivers of resistance and should be included in the decision to perform a urine culture to target first line UTI treatment., (Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

The objective of this study was to determine if specific species of microorganisms are associated with severe infection and amputation in patients with a diabetic foot infection and to evaluate the effectiveness of clindamycin and ciprofloxacin in this population. A retrospective cohort study was performed at the University Medical Center Utrecht, The Netherlands, for the period January 1st 2005 to January 1st 2010. Patients with ICD-9 codes 'diabetic foot' were selected from the hospital database. We evaluated the association of Staphylococcus aureus and Gram-negative species (GNS) with severity of infection, number of amputations, and healing rates. No significant association was found between the different microorganisms and infection severity. Coinfections of GNS and S. aureus were significantly associated with amputation compared to infections with only S. aureus [p = 0.016, odds ratio (OR) 4.9, confidence interval (CI) 1.4-16.9]. The empiric antibiotic regimen of clindamycin and ciprofloxacin covered only 85 % of S. aureus and 78 % of GNS diabetic foot infections. In mild diabetic foot infection in the studied population, where methicillin-sensitive S. aureus and streptococci are the most likely pathogens, a beta-lactam antibiotic such as flucloxacillin would likely be more effective than clindamycin. In moderate and severe infections, where GNS as a causative organism cannot be safely excluded, broad-spectrum antibiotic therapy may be more adequate.

Background: Pitted keratolysis (PK) is a common plantar skin manifestation in army personnel, farmers and athletes. Due to pain while walking and marching, the condition can cause reduced operational deployability (in case of army personnel)., Objective: We used a questionnaire to investigate currently used treatment options of PK and perceptions on perceived efficacy of these treatments among Royal Netherlands Armed Forces primary health care physicians., Methods: A cross-sectional anonymous postal questionnaire survey was conducted among all Royal Netherlands Armed Forces primary health care physicians. In addition to question about prescription behaviour on the treatment of PK by topical and oral therapies and given non-pharmacological treatment, several questions assessed perceived efficacy of these therapies., Results: Of the 164 eligible primary health care physicians, 51 (31.1%) completed the questionnaire. Half of physicians had seen less than five patients with PK in the preceding year. Two-thirds of physicians reported problems with operational deployability in less than 10% of army personnel with PK. PK was treated mostly with topical and non-pharmacological treatments. Oral therapy was seldom prescribed. For hyperhidrosis, aluminium chloride hexahydrate was used in most cases., Conclusion: PK and related reduced operational deployability were less often reported than expected in this study. Dutch physicians prefer combined topical antibiotic therapy with non-pharmacological treatments and perceive the efficacy of topical antibiotic therapy superior to non-pharmacological treatments. Preventive measures, topical antibiotic therapy and adequate treatment of hyperhidrosis are the mainstay methods in the management of patients with PK., (© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.)

In November 2011 51 Libyan war casualties were admitted to the Major Incident Hospital in Utrecht and from there were transferred to 26 other Dutch hospitals. Cultures and clinical data were collected to establish the prevalence of multidrug-resistant (MDR) bacteria in this patient group and to identify the associated risk factors. The prevalence of MDR bacteria was 59% (30/51 patients); extended spectrum β-lactamase-producing enterobacteriaceae were most common (26/51 patients: 51%). The major risk factor for carriage of MDR bacteria was the presence of open wounds at admission to the Major Incident Hospital., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Although Gram-negative micro-organisms are frequently associated with catheter-related bloodstream infections, the prognostic value and clinical implication of a positive catheter tip culture with Gram-negative micro-organisms without preceding bacteremia remains unclear. We determined the outcomes of patients with intravascular catheters colonized with these micro-organisms, without preceding positive blood cultures, and identified risk factors for the development of subsequent Gram-negative bacteremia. All patients with positive intravascular catheter tip cultures with Gram-negative micro-organisms at the University Medical Center, Utrecht, The Netherlands, between 2005 and 2009, were retrospectively studied. Patients with Gram-negative bacteremia within 48 h before catheter removal were excluded. The main outcome measure was bacteremia with Gram-negative micro-organisms. Other endpoints were length of the hospital stay, in-hospital mortality, secondary complications of Gram-negative bacteremia, and duration of intensive care admission. A total of 280 catheters from 248 patients were colonized with Gram-negative micro-organisms. Sixty-seven cases were excluded because of preceding positive blood cultures, leaving 213 catheter tips from 181 patients for analysis. In 40 (19%) cases, subsequent Gram-negative bacteremia developed. In multivariate analysis, arterial catheters were independently associated with subsequent Gram-negative bacteremia (odds ratio [OR] = 5.00, 95% confidence interval [CI]: 1.20-20.92), as was selective decontamination of the digestive tract (SDD) (OR = 2.47, 95% CI: 1.07-5.69). Gram-negative bacteremia in patients who received SDD was predominantly caused by cefotaxime (part of the SDD)-resistant organisms. Mortality was significantly higher in the group with subsequent Gram-negative bacteremia (35% versus 20%, OR = 2.12, 95% CI: 1.00-4.49). Patients with a catheter tip colonized with Gram-negative micro-organisms had a high chance of subsequent Gram-negative bacteremia from any cause. This may be clinically relevant, as starting antibiotic treatment pre-emptively in high-risk patients with Gram-negative micro-organisms cultured from arterial intravenous catheters may be beneficial.

Background: The impact of Candida-colonized catheter tips in patients without candidemia is unclear., Methods: A retrospective study of patients with tip cultures positive for Candida was conducted over an 8-year period, to determine the outcomes in patients with Candida cultured from an intravascular catheter tip in the absence of preceding Candida-positive blood cultures. The primary outcome measure was definite candidemia. Secondary outcomes included possible candidemia and in-hospital mortality. A possible candidemia was defined as clinical signs and symptoms of invasive candidiasis without explanation other than a candidemia, but with negative blood cultures., Results: Sixty-eight cultures from 64 patients were included in the study. Definite candidemia developed in three cases (4%) and possible candidemia developed in five cases (7%). In-hospital mortality was significantly increased in patients with definite or possible candidemia (63% vs. 22%, p=0.028). Risk factors for the development of definite or possible candidemia were catheter time in situ >8 days (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.1-32.9) and abdominal surgery (OR 6.0, 95% CI 1.1-32.4)., Conclusions: Intravascular catheter tip colonization in patients without preceding blood cultures with Candida is associated with candidemia in from 4% of patients (definite candidemia) up to 12% of patients (definite and possible candidemia combined). Considering the adverse prognosis associated with delayed treatment of candidemia, preemptive treatment based on catheter tip cultures might outweigh the disadvantages of costs and side effects of antifungal therapy., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Object: A frequent complication of CSF drains is secondary meningitis. This study was designed to assess the predictive value of a positive culture from a CSF drain tip for the development of secondary meningitis., Methods: The authors conducted a retrospective study of an 8-year period in which patients were treated in a tertiary care hospital in The Netherlands. Patients with positive cultures from CSF drain tips were identified from the microbiology database. Patient charts were reviewed to retrieve demographic, clinical, and laboratory data. Statistical analysis was performed using multivariate logistic regression to determine significant risk factors for the development of secondary meningitis., Results: A total of 139 patients with positive CSF-drain cultures were included; 72 patients (52%) suffered secondary meningitis at the time of CSF drain removal, or developed it consecutively. Development of secondary meningitis was associated with use of ventricular drains (OR 3.4 vs lumbar drains; 95% CI 1.7-6.8), with age less than 18 years (OR 4.7; 95% CI 1.3-17.3), and with colonization with Staphylococcus aureus (OR 3.1 vs other microorganisms; CI 1.2-8.5). Thirty-two patients (44% of total secondary meningitis) were diagnosed with secondary meningitis 24 hours or more after CSF drain removal; in 13 patients (18%) the diagnosis was made after 48 hours or more., Conclusions: Positive CSF-drain cultures are strongly associated with development of secondary meningitis. A positive CSF-drain culture may precede clinical symptoms and should therefore be communicated to the treating physician by the microbiological laboratory as soon as possible, and prophylactic antibiotic therapy should be considered.

A 68-year-old man who had undergone two penetrating keratoplasties of his left eye was admitted with early corneal graft failure. Culture of the anterior chamber fluid yielded Paracoccus yeei, a nonfermentative gram-negative bacillus which thus far had only been implicated in ocular disease by means of PCR and 16S rRNA gene sequencing directly on patient material.

Patients with Staphylococcus aureus colonization of an intravascular catheter but without demonstrated bacteremia within 24 h after intravascular catheter removal had a 24% (12 of 49 patients) chance of subsequent S. aureus bacteremia if they did not receive immediate antistaphylococcal antibiotics. Treatment within 24 h after intravascular catheter removal led to a 83% reduction in the incidence of subsequent bacteremia.

In this retrospective cohort study, patients who had Staphylococcus aureus bacteremia but who lacked signs and symptoms of urinary tract infection due to S. aureus and who did not have an indwelling urinary catheter had a likelihood of S. aureus bacteriuria of 2.5% (2 of 79 patients). Therefore, we strongly question the theory that S. aureus bacteremia causes S. aureus bacteriuria.

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.

A 57-year-old man requiring ventilation after gastric-tube reconstruction (due to oesophageal carcinoma) and a 16-year-old boy with thoracic trauma developed pneumonia caused by Pseudomonas aeruginosa and other pathogens. Their infections persisted during treatment with antibiotics. The antibiotic colistin was added and the clinical condition improved in both patients after 3-4 weeks. Eventually, they both were transferred to a rehabilitation clinic. The use of colistin was abandoned in the 1970s due to alleged nephro- and neurotoxicity. In recent observational studies, the drug appeared to cause fewer toxic side-effects than previously thought. Colistin is only registered for inhaled use for lung infections and for resistant pulmonary infections in patients with cystic fibrosis, but it may also be effective in the treatment of other patients with multidrug-resistant, Gram-negative bacteria.

The potential application of lantibiotics as food-preserving agents and more recently as antibiotics has strongly increased the interest in these antibacterial peptides. Here, we report the elucidation of the primary and three-dimensional structures of the novel lantibiotic epilancin 15X from Staphylococcus epidermidis using high-resolution nuclear magnetic resonance spectroscopy and tandem mass spectrometry. The molecule contains ten post-translationally modified amino acids, three lanthionine ring structures and a hydroxy-propionyl N-terminal moiety. The primary and tertiary structure and the distribution of positive charges are closely similar to the previously identified lantibiotic epilancin K7, most likely indicative of a common mode of action.

This study compared the metal Nebuchamber with the polycarbonate Volumatic spacer in vivo as well as in vitro. Seventeen asthmatic patients were evaluated in a crossover placebo-controlled double-blind study. Bronchodilation, heart rate and serum potassium levels were measured at baseline and 15 min after administration of salbutamol. Cumulative dose-response curves (200, 400, 800 and 1600 microg) were constructed. The Andersen Cascade Impactor was used to compare the aerodynamic particle size distribution. The FEV(1) measurements showed highly significant differences between placebo and the two active preparations (P<0.001), but not between the two active preparations (P=0.433). The serum potassium levels also showed highly significant differences between placebo and the two active preparations (P=0.009), but not between the two active preparations (P=0.532). Only 1600 microg salbutamol dose raised the heart rate significantly, but the difference between the two active preparations was not significant. The in vitro deposition study revealed no significant differences in the delivered dose or in the fine particle dose (P>0.05). In conclusion, there are no significant differences between the Volumatic and Nebuchamber either in vivo or in vitro.

Shigella genes expressed during infection likely contribute to adaptation and virulence in the host. Using differential display PCR (DDPCR), a cDNA fragment from Shigella flexneri serotype 5 that showed enhanced expression in a murine model was identified, cloned and sequenced. Enhanced expression was verified by RNA dot blot. The full-length gene was cloned using PCR and sequenced. The complete gene sequence was BLAST searched against GenBank, and exhibited strong homology to genes encoding Haemophilus influenzae D15 and Pasteurella multocida Oma87 protective outer membrane antigens. The S. flexneri gene putatively encodes a approximately 90-kDa protein and was termed oma90. The deduced amino acid sequence from oma90 was analyzed and compared to the D15/Oma87 antigens. Additionally, oma90 mapped to a cluster of orthologous groups, and probably contains an ancient conserved domain. The chromosomal organization of oma90 was similar to that for H. influenzae and P. multocida as well as for other known homologues. Northern blot revealed that the oma90 transcript encoded only oma90. This report represents the first description of a S. flexneri gene identified based on enhanced expression in the host. Furthermore, we report the first evidence demonstrating in vivo regulation of a member of the d15/oma87 gene family.