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We report on three patients with infective endocarditis, which differ greatly in clinical manifestations. Infective endocarditis (IE) is defined by, a mostly bacterial, infection of a native or prosthetic heart valve, the endocardial surface or a cardiac device. It is a rare condition, but it's incidence is increasing because of an increased incidence of elderly patients with chronic disease and cardiac devices. IE is heterogeneous in aetiology, clinical manifestations, and course. It can involve almost any organ system. The presentation often remains subtle and varies with nonspecific symptoms ranging from a mild infection to septic shock and multiorgan failure. IE remains a highly mortal disease, since the diagnosis is missed often. A thorough anamnesis and physical examination can be helpful. Blood cultures prior to antibiotics and echocardiography are key diagnostic steps if there's a clinical suspicion of IE.

Dentists and dental surgeons very frequently prescribe antibiotics to their patients. In a small percentage of cases, that is appropriate; however, patients can often also heal without antibiotic therapy. Microbiological analysis is only carried out in a very limited number of cases, and is complex and time-consuming. A small assortment of oral antibiotics is usually sufficient. Antibiotics are indicated when dental infection is accompanied by fever or indications of infection of a more systemic nature, such as trismus or lymphadenopathy. A patient with cellulitis of the head and neck area, with or without swallowing difficulties, should be treated with antibiotics in any case. In addition, antibiotics have a place in the treatment of periodontitis.

Scope: Antimicrobial stewardship teams are responsible for implementing antimicrobial stewardship programmes (ASP). However, in many countries, lack of funding challenges this obligation. A consensus procedure was performed to investigate which structural activities need to be performed by Dutch stewardship teams and how much time (and thus full-time equivalent (FTE) labor) is needed to perform these activities., Methods: In 2015, an electronic survey, based on a nonsystematic literature search and interviews with seven experienced stewardship teams, was sent to 21 stewardship teams that performed an ASP. This was followed by a semistructured face-to-face consensus meeting. Fourteen stewardship teams completed the survey (18% of Dutch acute-care hospitals), and 13 participated in the consensus meeting., Recommendations: The hours needed each year are dependent on hospital size and number of stewardship objectives monitored. If all activities are performed at a minimal base (one stewardship objective; minimal staffing standard), time investment was estimated to be 1393 to 2680 hours annually in the early phase, corresponding with 0.87 (300 beds) to 1.68 FTE (1200 beds), with a further increase to minimally 1.25 to 3.18 FTE in the following years with three stewardship objectives monitored (optimal staffing standards during the first few years of implementing an ASP). This consensus on required human resources provides a directive for structural financial support of stewardship teams in the Dutch context. Some stewardship activities (and related time investments) might be specific to the Dutch context and hospital setting. To develop standards for other settings, our methodology could be applied., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

According to the relevant literature, prosthetic joint infections caused by Listeria monocytogenes require two stage revision surgery or prosthesis removal for a successful outcome. We present the case of a patient who suffered such an infection after Total Knee Replacement surgery and was successfully treated with antibiotics, joint lavage, debridement and retention of the prosthesis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) is among the most accurate methods for Clostridium difficile infection (CDI) diagnosis. The obvious shortcoming of this approach is that multiple tests must be performed to establish a CDI diagnosis, which may delay treatment. Therefore, we sought to determine whether a preliminary diagnosis could be made on the basis of the quantitative results of the first test in algorithmic testing, which provide a measure of organism burden. To do so, we retrospectively analyzed two large collections of samples ( n = 2,669 and n = 1,718) that were submitted to the laboratories of two Dutch hospitals for CDI testing. Both hospitals apply a two-step testing algorithm in which a NAAT is followed by a toxin A/B EIA. Of all samples, 208 and 113 samples, respectively, tested positive by NAAT. Among these NAAT-positive samples, significantly lower mean quantification cycle ( C q ) values were found for patients whose stool eventually tested positive for toxin, compared with patients who tested negative for toxin (mean C q values of 24.4 versus 30.4 and 26.8 versus 32.2; P < 0.001 for both cohorts). Receiver operating characteristic curve analysis was performed to investigate the ability of C q values to predict toxin status and yielded areas under the curve of 0.826 and 0.854. Using the optimal C q cutoff values, prediction of the eventual toxin A/B EIA results was accurate for 78.9% and 80.5% of samples, respectively. In conclusion, C q values can serve as predictors of toxin status but, due to the suboptimal correlation between the two tests, additional toxin testing is still needed., (Copyright © 2018 American Society for Microbiology.)

Recent evidence shows that patients asymptomatically colonized with Clostridium difficile may contribute to the transmission of C. difficile in health care facilities. Additionally, these patients may have a higher risk of developing C. difficile infection. The aim of this study was to compare a commercially available PCR directed to both toxin A and B (artus C. difficile QS-RGQ kit CE; Qiagen), an enzyme-linked fluorescent assay to glutamate dehydrogenase (GDH ELFA) (Vidas, bioMérieux), and an in-house-developed PCR to tcdB, with (toxigenic) culture of C. difficile as the gold standard to detect asymptomatic colonization. Test performances were evaluated in a collection of 765 stool samples obtained from asymptomatic patients at admission to the hospital. The C. difficile prevalence in this collection was 5.1%, and 3.1% contained toxigenic C. difficile Compared to C. difficile culture, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the C. difficile GDH ELFA were 87.2%, 91.2%, 34.7%, and 99.3%, respectively. Compared with results of toxigenic culture, the sensitivity, specificity, PPV, and NPV of the commercially available PCR and the in-house PCR were 95.8%, 93.4%, 31.9%, 99.9%, and 87.5%, 98.8%, 70%, and 99.6%, respectively. We conclude that in a low-prevalence setting of asymptomatically colonized patients, both GDH ELFA and a nucleic acid amplification test can be applied as a first screening test, as they both display a high NPV. However, the low PPV of the tests hinders the use of these assays as stand-alone tests., (Copyright © 2017 American Society for Microbiology.)

Background: Antimicrobial stewardship is advocated to improve the quality of antimicrobial use. We did a systematic review and meta-analysis to assess whether antimicrobial stewardship objectives had any effects in hospitals and long-term care facilities on four predefined patients' outcomes: clinical outcomes, adverse events, costs, and bacterial resistance rates., Methods: We identified 14 stewardship objectives and did a separate systematic search for articles relating to each one in Embase, Ovid MEDLINE, and PubMed. Studies were included if they reported data on any of the four predefined outcomes in patients in whom the specific antimicrobial stewardship objective was assessed and compared the findings in patients in whom the objective was or was not met. We used a random-effects model to calculate relative risk reductions with relative risks and 95% CIs., Findings: We identified 145 unique studies with data on nine stewardship objectives. Overall, the quality of evidence was generally low and heterogeneity between studies was mostly moderate to high. For the objectives empirical therapy according to guidelines, de-escalation of therapy, switch from intravenous to oral treatment, therapeutic drug monitoring, use of a list of restricted antibiotics, and bedside consultation the overall evidence showed significant benefits for one or more of the four outcomes. Guideline-adherent empirical therapy was associated with a relative risk reduction for mortality of 35% (relative risk 0·65, 95% CI 0·54-0·80, p<0·0001) and for de-escalation of 56% (0·44, 0·30-0·66, p<0·0001). Evidence of effects was less clear for adjusting therapy according to renal function, discontinuing therapy based on lack of clinical or microbiological evidence of infection, and having a local antibiotic guide. We found no reports for the remaining five stewardship objectives or for long-term care facilities., Interpretation: Our findings of beneficial effects on outcomes with nine antimicrobial stewardship objectives suggest they can guide stewardship teams in their efforts to improve the quality of antibiotic use in hospitals., Funding: Dutch Working Party on Antibiotic Policy and Netherlands National Institute for Public Health and the Environment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A survey of diagnosis and treatment of invasive aspergillosis was conducted in eight University Medical Centers (UMCs) and eight non-academic teaching hospitals in the Netherlands. Against a background of emerging azole resistance in Aspergillus fumigatus routine resistance screening of clinical isolates was performed primarily in the UMCs. Azole resistance rates at the hospital level varied between 5% and 10%, although rates up to 30% were reported in high-risk wards. Voriconazole remained first choice for invasive aspergillosis in 13 out of 16 hospitals. In documented azole resistance 14 out of 16 centres treated patients with liposomal amphotericin B., (© 2015 Blackwell Verlag GmbH.)

Staphylococcus lugdunensis (SL) is a species belonging to the group of coagulase-negative staphylococci (CNS). It can cause severe infections such as endocarditis. Three cases of endocarditis caused by SL are presented. The first case describes a 71-year-old man with a fever and endogenous endophthalmitis. The second case describes delirium in an 87-year-old woman, thought to be due to pneumonia. The third case describes a 76-year-old man with an infection of unknown origin. In all cases, the first blood cultures drawn were positive for CNS and considered to be contaminated. However, all three patients were finally diagnosed as having severe endocarditis caused by SL. Two patients underwent valve replacement, one patient died due to ongoing sepsis. The first CNS-positive blood cultures drawn were wrongly denoted as being contaminated. Physicians should be aware of the pathogenic potential of SL and rule out contamination.

Fungal prosthetic joint infections are rare and difficult to treat. There is an ongoing discussion about the type and duration of antifungal treatment and the necessity of prosthesis removal. We report the first European case of an infected total knee arthroplasty with Coccidioides immitis. Treatment consisted of lifelong treatment with oral fluconazole at a dose of 400 mg/d, without total knee arthroplasty removal. After 6 months, the initial complaints of pain and swelling were completely resolved. This case report clearly states that a travel history and culturing for fungi are helpful in patients with persisting complaints after joint arthroplasty., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In order to perform a cost-effective search and destroy policy for methicillin-resistant Staphylococcus aureus (MRSA), a quick and reliable typing method is essential. In an area with a high level of animal-related MRSA ST398, pulsed field gel electrophoresis (PFGE) typing and spa-typing are not sufficient to discriminate between co-incidental findings and true transmission of MRSA. This study is the first to retrospectively show the performance of Raman spectroscopy in 16 well-documented outbreaks. We analysed 525 isolates, 286 MRSA ST398 and 239 from other PFGE clusters with Raman spectroscopy. When epidemiologically linked isolates from the outbreaks were analysed with PFGE as the reference standard, Raman spectroscopy correctly identified 97% of cases that were indistinguishable from the index case. With Raman cluster analysis, the most dominant distinction was between MRSA ST398 and other MRSA of human clonal lineages. Within MRSA ST398, 22 different Raman clusters were identified. Raman typing correctly identified an ST398 (spa type t567) outbreak in a hospital setting. No direct correlation was observed between Raman clusters and spa types. We conclude that Raman spectroscopy is a quick and reliable method of MRSA typing, which can be used in outbreak settings and it is comparable to PFGE, with the added advantage that PFGE non-typeable isolates can also be readily typed using the same sample preparation protocol., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

The purpose of this study was to evaluate the impact of the emergence of animal related methicillin resistant Staphylococcus aureus ST398 in an area with a high density of pig farms. A retrospective analysis was performed of all MRSA isolates in the laboratory database from 2002 till 2008 including typing results and clinical data from infection control archives and patient charts. The implementation of the screening of people in contact with pigs and veal calves for MRSA led to an increase in the average number of newly identified carriers from 16 per year between July 2002 and July 2006 to 148 between July 2006 and December 2008. This is a 925% increase of which 82% (108/132) was due to ST398. The majority (74%) came from targeted screening but 7% was due to unexpected findings. A wide range of infections with ST398 occurred in patients with and without contact with livestock varying from post-operative wound infections to sepsis and post-trauma osteomyelitis with an overrepresentation of spa type t567 among the clinical isolates. ST398 isolates were more often multi-resistant than isolates of other spa-types. The emergence of MRSA ST398 led to an increase in both MRSA carriers and MRSA infections.

At the Máxima Medisch Centrum in Veldhoven, The Netherlands, neonatal sepsis caused by invasive Streptococcus pneumoniae infection was diagnosed in 5 neonates between 1996 and 2004. This infection is relatively rare and its clinical features are variable, but often particularly severe and fulminant as was the case in 2 of the 5 children, one of whom died and the other was left with serious psychomotor retardation. The other 3 recovered fully. The child who died and one of the children who recovered are described in some detail. They were both prematurely born neonates, a girl and a boy, who presented almost immediately after birth with an early-onset sepsis caused by S. pneumoniae. In both cases neonatal cultures as well as maternal vaginal swabs were positive for S. pneumoniae growth. 2 different patients had other risk factors for peripartal infection. Neonatal pneumococcal infections are most likely transmitted trough the maternal vaginal tract. Maternal vaginal colonization is rare (0.11%), but associated with a high risk of transmission to the newborn. Asymptomatic neonatal colonization was not observed. In light of the likelihood of a high rate of transmission and subsequent infection, peripartal prophylactic antibiotic treatment is advised for all mothers with proven vaginal S. pneumoniae colonization. If this is not given or is not effective, then in contrast with the policy on patients with group B streptococcal colonization, prophylactic antibiotic treatment is advocated for all neonates born to colonized mothers. Amoxicillin is the preferred treatment. In areas of increasing macrolide resistance, erythromycin should only be advised in cases of penicillin allergy.

Comparative high-throughput amplified fragment length polymorphism (htAFLP) analysis was performed on a set of 25 complement-resistant and 23 complement-sensitive isolates of Moraxella catarrhalis in order to determine whether there were complement phenotype-specific markers within this species. The htAFLP analysis used 21 primer-pair combinations, generating 41 364 individual fragments and 2273 fragment length polymorphisms, with an average of 862 polymorphisms per isolate. Analysis of polymorphism data clearly indicated the presence of two phylogenetic lineages and 40 (2%) lineage-specific polymorphisms. However, despite the presence of 361 (16%) statistically significant complement phenotype-associated polymorphisms, no single marker was 100% complement phenotype-specific. Furthermore, no complement phenotype-specific marker was found within different phylogenetic lineages. These findings agree with previous results indicating that the complement resistance phenotype within M. catarrhalis is probably defined by multiple genes, although not all of these genes may be present within all M. catarrhalis isolates.

A hemolytic bystander assay was used to assess the functional serum mannose-binding lectin (MBL) activating capacity of five isolates of Moraxella catarrhalis obtained from children who suffered recurrent acute otitis media episodes. Results showed that this organism is only a poor activator of the lectin pathway of complement activation, with subsequent consequences for the etiology of otitis media by this organism.

A preliminary screening study of six Moraxella catarrhalis isolates from primary school children in the Netherlands identified a small 3.5 kb plasmid (pEMCJH03), containing four open reading frames, which encoded three mobilizing and one replicase protein. Insertion of a kanamycin containing transposon (yielding pEMCJH04) allowed selection and isolation of the plasmid in Escherichia coli. Natural transformation of pEMCJH04 into M. catarrhalis was successful for 25% (3/12) of non-isogenic isolates, with no link between (lack of) transformability and genetic lineage or (lack of) transformability and complement phenotype, though the transformation efficiency was found to be rather low at approximately 615CFU/microg (range=60-1040CFU/microg ). This is only the second publication detailing a plasmid isolated from this important respiratory pathogen, and the ability to clone and express foreign proteins in M. catarrhalis using pEMCJH04 could help in the development of a vaccine expression vector, as well as providing a useful tool for studying promoter activity and in complementation studies of gene knockout mutants.

Pulsed-field gel electrophoresis typing was performed on a retrospective set of 129 Moraxella catarrhalis isolates obtained over a 20 month period from 70 children admitted to, or presenting at, the Erasmus University Medical Center, Rotterdam, The Netherlands. The mean age of the children (at the end of the study) was 2.5 years, with a range of 6 months to 15 years. Fifty-one different M. catarrhalis types were isolated from the hospitalized children, with 31 % (22/70) being infected with two particularly prevalent M. catarrhalis types. These two prevalent types also exhibited different protein profiles. The majority (72%; 16/22) of the children infected with these two predominant types had spent at least 1 week on two paediatric intensive care wards. No exacerbation of existing disease or new disease was observed in children who experienced M. catarrhalis type changes.

Unlabelled: The role of Mycoplasma hominisas a causative agent for neonatal sepsis and meningitis is still unclear. Meningitis secondary to M. hominisis well-described in the literature; however, M. hominiscan also be isolated from cerebrospinal fluid (CSF) obtained from infants without signs of meningitis. We present a case of a full-term infant with meningo-encephalitis with seizures, epileptic activity on the EEG, inflammation of brain tissue on a CT scan, and cloudy CSF containing elevated cell counts, decreased glucose levels and elevated protein levels. M. hominiswas identified from the CSF by culture and by polymerase chain reaction (PCR) as the only possible causative agent. Furthermore, while empiric antibiotic and antiviral treatment for neonatal sepsis had failed, the meningo-encephalitis promptly responded upon antibiotic treatment with ciprofloxacin (20 mg/kg per day i.v.), to which M. hominisis susceptible., Conclusion: A meningo-encephalitis developed due to infection with M. hominisin a full-term infant, from which he recovered rapidly after start of treatment with ciprofloxacin.

Proteus mirabilis infection often leads to stone formation. We evaluated how bacterium-mucin adhesion, invasion, and intracellular crystal formation are related to antibiotic sensitivity and may cause frequent stone formation in enterocystoplasties. Five intestinal (Caco-2, HT29, HT29-18N2, HT29-FU, and HT29-MTX) and one ureter cell line (SV-HUC-1) were incubated in artificial urine with five Proteus mirabilis strains. Fluorescence-activated cell sorting (FACS), laser scanning microscopy, and electron microscopy evaluated cellular adhesion and/or invasion, pathologic changes to mitochondria, and P. mirabilis-mucin colocalization (MUC2 and MUC5AC). An MTT (thiazolyl blue tetrazolium bromide) assay and FACS analysis of caspase-3 evaluated the cellular response. Infected cells were incubated with antibiotics at dosages representing the expected urinary concentrations in a 10-year-old, 30-kg child to evaluate bacterial invasion and survival. All cell lines showed colocalization of P. mirabilis with human colonic mucin (i.e., MUC2) and human gastric mucin (i.e., MUC5AC). The correlation between membrane mucin expression and invasion was significant and opposite for SV-HUC-1 and HT29-MTX. Microscopically, invasion by P. mirabilis with intracellular crystal formation and mitochondrial damage was found. Double membranes surrounded bacteria in intestinal cells. Relative resistance to cotrimoxazole and augmentin was found in the presence of epithelial cells. Ciprofloxacin and gentamicin remained effective. Membrane mucin expression was correlated with relative antibiotic resistance. Cell invasion by P. mirabilis and mucin- and cell type-related distribution and response differences indicate bacterial tropism that affects crystal formation and mucosal presence. Bacterial invasion seems to have cell type-dependent mechanisms and prolong bacterial survival in antibiotic therapy, giving a new target for therapeutic optimalization of antibiotic treatment.

Objective: Our objective was to individualize tobramycin dosing regimens in neonates of various gestational ages with use of early therapeutic drug monitoring., Methods: This study was performed in neonatal patients with suspected septicemia in the first week of life. All patients received tobramycin, 4 mg/kg per dose, as a 30-minute intravenous infusion, with a gestational age-related initial interval of 48 hours (<32 weeks), 36 hours (32-36 weeks), and 24 hours (> or =37 weeks). The target serum peak and trough serum concentrations were 5 to 10 mg/L and 0.5 mg/L, respectively. Serum trough samples and 1- and 6-hour samples were taken after the first dose. Tobramycin concentrations were used to obtain gestational age-dependent population models with nonparametric expectation maximization software. To investigate the effect of timing of sampling in a second group of patients, serum trough samples and 3- and 8-hour samples were taken after the first dose of tobramycin was administered. Serum trough concentrations were predicted by use of linear pharmacokinetics in both groups and by use of the population models with bayesian feedback of 1 or 2 serum concentrations in the second group. These predicted concentrations were compared with actual serum trough concentrations. The predictive performance of the 1- to 6-hour and 3- to 8-hour models and the population models were compared with a gestational age-related model without therapeutic drug monitoring., Results: A total of 247 patients were analyzed: 206 with 1- to 6-hour serum samples and 41 with 3- to 8-hour serum samples. Peak serum concentrations were above 5 mg/L in 90.8% of cases, and trough serum concentrations were above 1 mg/L in 25.5% of cases. The 3- to 8-hour linear model had a bias of -0.31 mg/L and a precision of 0.48 mg/L, and it performed significantly better than the 1- to 6-hour model. The best nonparametric expectation maximization model had a bias of -0.11 mg/L and a precision of 0.45 mg/L. None of the models yielded a significant improvement of predictive performance over the model without therapeutic drug monitoring., Conclusions: Routine early therapeutic drug monitoring does not improve the model-based prediction of initial tobramycin dosing intervals in neonates in the first week of life.