Attributable mortality of vancomycin resistance in ampicillin-resistant Enterococcus faecium bacteremia in Denmark and the Netherlands: A matched cohort study.

OBJECTIVE: To study whether replacement of nosocomial ampicillin-resistant Enterococcus faecium (ARE) clones by vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineages, increases mortality in patients with E. faecium bacteremia, and to evaluate whether any such increase is mediated by a delay in appropriate antibiotic therapy. DESIGN: Retrospective, matched-cohort study. SETTING: The study included 20 Dutch and Danish hospitals from 2009 to 2014. PATIENTS: Within the study period, 63 patients with VRE bacteremia (36 Dutch and 27 Danish) were identified and subsequently matched to 234 patients with ARE bacteremia (130 Dutch and 104 Danish) for hospital, ward, length of hospital stay prior to bacteremia, and age. For all patients, 30-day mortality after bacteremia onset was assessed. METHODS: The risk ratio (RR) reflecting the impact of vancomycin resistance on 30-day mortality was estimated using Cox regression with further analytic control for confounding factors. RESULTS: The 30-day mortality rates were 27% and 38% for ARE in the Netherlands and Denmark, respectively, and the 30-day mortality rates were 33% and 48% for VRE in these respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval, 1.06-2.25). Although appropriate antibiotic therapy was initiated later for VRE than for ARE bacteremia, further analysis did not reveal mediation of the increased mortality risk. CONCLUSIONS: Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.

From a case-control survey to a diagnostic viral gastroenteritis panel for testing of general practitioners' patients.

OBJECTIVE: To evaluate the pathogenicity of a broad range of 11 possible gastroenteritis viruses, by means of statistical relationships with cases vs. controls, or Ct-values, in order to establish the most appropriate diagnostic panel for our general practitioner (GP) patients in the Netherlands (2010-2012). METHODS: Archived stool samples from 1340 cases and 1100 controls were retested using internally controlled multiplex real-time PCRs for putative pathogenic gastroenteritis viruses: adenovirus, astrovirus, bocavirus, enterovirus, norovirus GI and GII, human parechovirus, rotavirus, salivirus, sapovirus, and torovirus. RESULTS: The prevalence of any virus in symptomatic cases and asymptomatic controls was 16.6% (223/1340) and 10.2% (112/1100), respectively. Prevalence of astrovirus (adjusted odds ratio (aOR) 10.37; 95% confidence interval (CI) 1.34-80.06) and norovirus GII (aOR 3.10; CI 1.62-5.92) was significantly higher in cases versus controls. Rotavirus was encountered only in cases. We did not find torovirus and there was no statistically significant relationship with cases for salivirus (aOR 1,67; (CI) 0.43-6.54)), adenovirus non-group F (aOR 1.20; CI 0.75-1.91), bocavirus (aOR 0.85; CI 0.05-13.64), enterovirus (aOR 0.83; CI 0.50-1.37), human parechovirus (aOR 1.61; CI 0.54-4.77) and sapovirus (aOR 1.15; CI 0.67-1.98). Though adenovirus group F (aOR 6.37; CI 0.80-50.92) and norovirus GI (aOR 2.22, CI: 0.79-6.23) are known enteropathogenic viruses and were more prevalent in cases than in controls, this did not reach significance in this study. The Ct value did not discriminate between carriage and disease in PCR-positive subjects. CONCLUSIONS: In our population, diagnostic gastroenteritis tests should screen for adenovirus group F, astrovirus, noroviruses GI and GII, and rotavirus. Case-control studies as ours are lacking and should also be carried out in populations from other epidemiological backgrounds.

Bacterial agents in vulvovaginitis and vaginal discharge: a 10-year retrospective study in the Netherlands.

Vulvovaginitis is a common problem in the GP's practice. Causes are bacterial vaginosis (BV), Candida infection and sexually transmitted infections (STIs). Only if empirical treatment fails, a vaginal swab is sent in for culture and BV detection. However, without culture essential, bacterial pathogens may escape diagnosis. Many molecular BV assays have recently appeared on the marketplace, all quite differing in price and targets. However, for years, the Nugent score has been the gold standard for BV detection. We analysed retrospectively 10 years of microbiology results of vulvovaginal swabs, focusing on less frequently reported bacterial pathogens, and assessed the characteristics of BV diagnostics. Vulvovaginal swabs sent in between 2010 and 2020 from > 11,000 GP patients with vulvovaginitis associated symptoms, but negative STI tests, were analysed. First cultures and repeat cultures after at least 6 months were included in four age groups: < 12, 12-17, 18-51 and > 51 years. Candida species and BV were most frequently found, with the highest prevalence in premenopausal women. Haemophilus influenzae, beta-haemolytic streptococci, Streptococcus pneumoniae and Staphylococcus aureus were isolated in 5.6% of all cultures, with the highest percentages in children and postmenopausal women. If empirical treatment of vulvovaginitis fails, bacterial culture should be performed to detect all potentially pathogenic microorganisms to obtain a higher rate of successful diagnosis and treatment, avoiding unnecessary antimicrobial use and costs. For BV detection, molecular testing may seem attractive, but Nugent scoring still remains the low-cost gold standard. We recommend incorporating the above in the appropriate guidelines.

Distribution and relevance of Dientamoeba fragilis and Blastocystis species in gastroenteritis: results from a case-control study.

The actual role of Dientamoeba fragilis and Blastocystis in patients with gastrointestinal symptoms is still under debate. A multicenter case-control study was performed in The Netherlands to elucidate the clinical relevance of molecular diagnostics results in gastroenteritis (GE). Samples from this case-control study were used to perform a detailed analysis on the presence of D. fragilis and Blastocystis in relation to gastrointestinal symptoms. In the present study, a real-time PCR for Blastocystis was performed on 1374 case samples and 1026 control samples from the multicenter gastroenteritis case-control study previously tested for D. fragilis. Prevalence of both micro-organisms was highest in children under 20 years of age and lowest in the oldest age group. A significantly lower overall detection of D. fragilis and Blastocystis was found in cases (both 25.8%) as compared to controls (37.6% and 40.0%, respectively). The difference for D. fragilis was statistically significant for subjects above 20 years of age. For Blastocystis, the difference was statistically significant in all age groups, except in children less than 5 years of age. A negative relation between D. fragilis-positive cases and diarrhea was found in this study population. More GE symptoms were reported in cases without D. fragilis or Blastocystis. In the present study, prevalence of both D. fragilis and Blastocystis is lower in cases with gastroenteritic symptoms than in controls. Besides, in cases with D. fragilis or Blastocystis, no association is shown between any of the GE symptoms. Interestingly, this suggests that the presence of these protozoans may be considered characteristic of a healthy intestinal microbiome.

Contact precautions in single-bed or multiple-bed rooms for patients with extended-spectrum ß-lactamase-producing Enterobacteriaceae in Dutch hospitals: a cluster-randomised, crossover, non-inferiority study.

BACKGROUND: Use of single-bed rooms for control of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is under debate; the added value when applying contact precautions has not been shown. We aimed to assess whether an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae. METHODS: We did a cluster-randomised, crossover, non-inferiority study on medical and surgical wards of 16 Dutch hospitals. During two consecutive study periods, either contact precautions in a single-bed room or contact precautions in a multiple-bed room were applied as the preferred isolation strategy for patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample (index patients). Eligible index patients were aged 18 years or older, had no strict indication for barrier precautions in a single-bed room, had a culture result reported within 7 days of culture and before discharge, and had no wardmate known to be colonised or infected with an ESBL-producing Enterobacteriaceae isolate of the same bacterial species with a similar antibiogram. Hospitals were randomly assigned in a 1:1 ratio by computer to one of two sequences of isolation strategies, stratified by university or non-university hospital. Allocation was masked for laboratory technicians who assessed the outcomes but not for patients, treating doctors, and infection-control practitioners enrolling index patients. The primary outcome was transmission of ESBL-producing Enterobacteriaceae to wardmates, which was defined as rectal carriage of an ESBL-producing Enterobacteriaceae isolate that was clonally related to the index patient's isolate in at least one wardmate. The primary analysis was done in the per-protocol population, which included patients who were adherent to the assigned room type. A 10% non-inferiority margin for the risk difference was used to assess non-inferiority. This study is registered with Nederlands Trialregister, NTR2799. FINDINGS: 16 hospitals were randomised, eight to each sequence of isolation strategies. All hospitals randomised to the sequence single-bed room then multiple-bed room and five of eight hospitals randomised to the sequence multiple-bed room then single-bed room completed both study periods and were analysed. From April 24, 2011, to Feb 27, 2014, 1652 index patients and 12 875 wardmates were assessed for eligibility. Of those, 693 index patients and 9527 wardmates were enrolled and 463 index patients and 7093 wardmates were included in the per-protocol population. Transmission of ESBL-producing Enterobacteriaceae to at least one wardmate was identified for 11 (4%) of 275 index patients during the single-bed room strategy period and for 14 (7%) of 188 index patients during the multiple-bed room strategy period (crude risk difference 3·4%, 90% CI -0·3 to 7·1). INTERPRETATION: For patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample, an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae. Non-inferiority of the multiple-bed room strategy might change the current single-bed room preference for isolation of patients with ESBL-producing Enterobacteriaceae and, thus, broaden infection-control options for ESBL-producing Enterobacteriaceae in daily clinical practice. FUNDING: Netherlands Organisation for Health Research and Development.

Room Sharing in Hospitalized Children With Bronchiolitis and the Occurrence of Hospital-Acquired Infections: A Prospective Cohort Study.

OBJECTIVES: To determine the prevalence and severity of hospital-acquired infections (HAIs) in children hospitalized for bronchiolitis when patients share a room, irrespective of the causative virus. METHODS: A prospective cohort study during 4 winter seasons (2012-2016) was conducted in a Dutch general pediatric ward including otherwise healthy children <2 years of age hospitalized for bronchiolitis. Patients shared a 1-to-4-bed hospital room irrespective of virological diagnosis. The main outcome measures were HAIs assessed through multiplex polymerase chain reaction and disease severity. RESULTS: HAIs occurred in 28 of 218 included patients (12.8%), most frequently with rhinovirus (17 of 28; 60.7%). In 3 (10.7%) of 28 HAIs, the same virus was identified in roommates. Only 1 patient became cross-infected with respiratory syncytial virus, although this patient never shared a room with a patient infected with respiratory syncytial virus. HAI was not associated with more severe disease. The median length of hospitalization was 3.5 days (interquartile range [IQR] 1-6) compared with 3 days (IQR 2-6; P = .86); the number of PICU admissions was 0% versus 5.3% (P = .21); the median days of oxygen supplementation was 2.5 (IQR 1-4) versus 2 (IQR 1-4; P = .58); the median days of tube feeding was 2 (IQR 0-5) versus 2 (interquartile range: 0-5; P = .77); and the readmission rate was 0% versus 5.8% (P = .19) in patients with and without HAI, respectively. CONCLUSIONS: HAIs among patients with bronchiolitis are common but not associated with more severe disease. Room sharing with appropriate hygiene does not play a relevant role in the transmission of viruses between patients with bronchiolitis, regardless of the viruses involved. On the basis of these findings, we suggest that room sharing of patients with bronchiolitis is safe.

Efficacy of Pre-Operative Antimicrobial Prophylaxis in Patients Undergoing Pancreatoduodenectomy: A Multi-Center Retrospective Analysis.

BACKGROUND: The most common complications after pancreaticoduodenectomy (PD) are infectious, despite the standard use of cefazolin and metronidazole prophylaxis. Pre-operative biliary drainage (PBD) is a well-known risk factor for infectious complications. The objective was to identify the pathogens in intra-operative bile cultures in patients undergoing PD-with and without PBD-to determine the optimal antimicrobial prophylaxis regimen. PATIENTS AND METHODS: Patients who underwent PD between 2009 and 2016 were identified retrospectively in three major teaching hospitals in The Netherlands. Organisms isolated from intra-operative bile cultures were studied. If pathogen coverage by standard prophylaxis was incomplete, the most appropriate alternative regimen was determined. RESULTS: Of this large cohort of 352 patients, 56% underwent PBD and 44% did not. Positive bile cultures were found in 87.9% in the PBD group, compared with 31.8% in the non-PBD group. The micro-organisms isolated most commonly were Enterococcus, Streptococcus, and Klebsiella species. Cefazolin and metronidazole were appropriate in only 71% of patients. Adding gentamicin would provide complete coverage in 99% of PBD and 100% of non-PBD patients. CONCLUSIONS: Our data confirm that PBD prior to PD leads to microbial colonization and antibiotic resistance. To potentially prevent infectious complications, gentamicin may be added to the standard antimicrobial prophylaxis.

Epidemiology of Extended-Spectrum ß-Lactamase-Producing E. coli and Vancomycin-Resistant Enterococci in the Northern Dutch-German Cross-Border Region.

Objectives: To reveal the prevalence and epidemiology of extended-spectrum ß-lactamase (ESBL)- and/or plasmid AmpC (pAmpC)- and carbapenemase (CP) producing Enterobacteriaceae and vancomycin-resistant enterococci (VRE) across the Northern Dutch-German border region. Methods: A point-prevalence study on ESBL/pAmpC/CP producing Enterobacteriaceae and VRE was carried out in hospitalized patients in the Northern Netherlands (n = 445, 2012-2013) and Germany (n = 242, 2012). Healthy individuals from the Dutch community (n = 400, 2010-2012) were also screened. In addition, a genome-wide gene-by-gene approach was applied to study the epidemiology of ESBL-Escherichia coli and VRE. Results: A total of 34 isolates from 27 patients (6.1%) admitted to Dutch hospitals were ESBL/pAmpC positive and 29 ESBL-E. coli, three pAmpC-E. coli, one ESBL-Enterobacter cloacae, and one pAmpC-Proteus mirabilis were found. In the German hospital, 18 isolates (16 E. coli and 2 Klebsiella pneumoniae) from 17 patients (7.7%) were ESBL positive. In isolates from the hospitalized patients CTX-M-15 was the most frequently detected ESBL-gene. In the Dutch community, 11 individuals (2.75%) were ESBL/pAmpC positive: 10 ESBL-E. coli (CTX-M-1 being the most prevalent gene) and one pAmpC E. coli. Six Dutch (1.3%) and four German (3.9%) hospitalized patients were colonized with VRE. Genetic relatedness by core genome multi-locus sequence typing (cgMLST) was found between two ESBL-E. coli isolates from Dutch and German cross-border hospitals and between VRE isolates from different hospitals within the same region. Conclusion: The prevalence of ESBL/pAmpC-Enterobacteriaceae was similar in hospitalized patients across the Dutch-German border region, whereas VRE prevalence was slightly higher on the German side. The overall prevalence of the studied pathogens was lower in the community than in hospitals in the Northern Netherlands. Cross-border transmission of ESBL-E. coli and VRE seems unlikely based on cgMLST analysis, however continuous monitoring is necessary to control their spread and stay informed about their epidemiology.

Infectious Complications after Major Abdominal Cancer Surgery: In Search of Improvable Risk Factors.

BACKGROUND: Major resections for esophageal, gastric, hepatic, pancreatic, and colorectal cancer continue to be associated with a high peri-operative morbidity of up to 30%-40%. To a large extent, this morbidity is caused by infectious complications that add up to a considerable burden to patients and hospital costs. The objective of this large retrospective cross-sectional study was to determine independent patient and operation-related risk factors for infectious complications after major abdominal cancer operations to elucidate how infection rates can be reduced and improve health-care quality. PATIENTS AND METHODS: In 1,389 cancer patients who underwent a major resection procedure between 2009 and 2013, infectious complications and their independent determinants were analyzed by multivariable logistic regression (p < 0.05). RESULTS: Male gender was a risk factor for infections in general, whereas patients ≥65 y (odds ratio [OR] 1.75; p = 0.008), urinary tract infection (OR 0.51; p = 0.004), American Society of Anesthesiologists score (OR 1.55; p = 0.004), overall (OR 1.70; p = 0.037), vascular (OR 1.59; p = 0.020), and neurologic comorbidity (OR 2.22; p = 0.001) were associated significantly with pneumonia. Intra-abdominal drainage (OR 1.41; p = 0.024) and a duration of surgery of ≥180 min (OR 1.85; p = 0.001) were risk factors for surgical site infections. Total parenteral nutrition was significantly associated with intravascular catheter-induced infections (OR 18.09; p < 0.001) and sepsis (OR 6.69; p < 0.001). CONCLUSIONS: In this study, several independent risk factors for infectious complications in major abdominal cancer operations were identified, providing opportunities for further reducing peri-operative infections. General awareness and focus on preventing infectious complications may have a significant impact on health-care outcomes and costs.

Co-infections in children hospitalised for bronchiolitis: role of roomsharing.

BACKGROUND: Bronchiolitis is a major cause for hospitalisation in young children during the winter season, with respiratory syncytial virus (RSV) as the main causative virus. Apart from standard hygiene measures, cohorting of RSV-infected patients separately from RSV-negative patients is frequently applied to prevent cross-infection, although evidence to support this practice is lacking. The objective is to evaluate the risk of room sharing between RSV-positive and RSV-negative patients. METHODS: We performed a prospective observational cohort study in children < 2 years hospitalised with acute bronchiolitis. During the first day of admission, patients shared one room, pending results of virological diagnosis (PCR). When diagnostic results were available, RSV-positive and RSV-negative patients were separated. Standard hygienic measures (gowns, gloves, masks, hand washing) were used in all patients. RESULTS: We included 48 patients (83% RSV-positive). Co-infection was found in nine patients at admission, and two during hospitalisation (23%). The two patients with acquired co-infection had been nursed in a single room during the entire admission. None of 37 patients sharing a room with other bronchiolitis patients (20 with patients with a different virus) were co-infected during admission. Disease severity in co-infection was not worse than in mono-infection. CONCLUSION: One in five patients with bronchiolitis was co-infected, but co-infection acquired during admission was rare and was not associated with more severe disease. Room sharing between RSV-positive and RSV-negative patients (on the first day of admission) did not influence the risk of co-infection, suggesting that cohorting of RSV-infected patients separate from non-RSV-infected patients may not be indicated.

Respiratory disease and Trichomonas vaginalis in premature newborn twins.

In premature newborn twins with respiratory disease, Trichomonas vaginalis infection was diagnosed by chance findings in respiratory samples and was confirmed by polymerase chain reaction of urine and vaginal samples from the boy and girl, respectively. Trichomonas vaginalis should be considered as a possible cause of respiratory disease in newborns and modern molecular detection techniques can help in the diagnosis.

[Should all dermatologists still be considered 'dermato-venereologists' in the year 2013?]. / Dermatoloog anno 2013 nog altijd dermato-venereoloog?

This commentary primarily focuses on the appropriateness of the predicate 'venereologist' for dermatologists in the Netherlands. If the quantity of care delivered were to be the most important factor needed for the qualification 'venereologist', the answer to the title question would undoubtedly be 'no' because more than 70% of sexually transmitted disease (STD) care is delivered in primary care centres. After the reorganisation of STD care in the Netherlands in 2006, 8 coordinating municipal STD centres were allocated for the primary care of pre-defined risk groups. By utilizing multidisciplinary guidelines, the Dutch Society of Dermatologists and Venereologists plays an important coordinating and supervisory role in current primary and in-hospital STD care.

[A man with neutropenic fever]. / Een man met neutropene koorts.

A 43-year-old patient with recurrent acute myeloid leukemia (AML) was treated with high-dose cytarabine. After two weeks of neutropenic fever, multiple cutaneous nodules appeared. Histopathological examination of a skin biopsy showed a mycosis and Fusarium solani was cultured. Despite antimycotic therapy, the patient died due to complications of his AML treatment.

Does electronic clinical microbiology results reporting influence medical decision making: a pre- and post-interview study of medical specialists.

BACKGROUND: Clinicians view the accuracy of test results and the turnaround time as the two most important service aspects of the clinical microbiology laboratory. Because of the time needed for the culturing of infectious agents, final hardcopy culture results will often be available too late to have a significant impact on early antimicrobial therapy decisions, vital in infectious disease management. The clinical microbiologist therefore reports to the clinician clinically relevant preliminary results at any moment during the diagnostic process, mostly by telephone. Telephone reporting is error prone, however. Electronic reporting of culture results instead of reporting on paper may shorten the turnaround time and may ensure correct communication of results. The purpose of this study was to assess the impact of the implementation of electronic reporting of final microbiology results on medical decision making. METHODS: In a pre- and post-interview study using a semi-structured design we asked medical specialists in our hospital about their use and appreciation of clinical microbiology results reporting before and after the implementation of an electronic reporting system. RESULTS: Electronic reporting was highly appreciated by all interviewed clinicians. Major advantages were reduction of hardcopy handling and the possibility to review results in relation to other patient data. Use and meaning of microbiology reports differ significantly between medical specialties. Most clinicians need preliminary results for therapy decisions quickly. Therefore, after the implementation of electronic reporting, telephone consultation between clinician and microbiologist remained the key means of communication. CONCLUSIONS: Overall, electronic reporting increased the workflow efficiency of the medical specialists, but did not have an impact on their decision-making.

Evaluation and implementation of a chromogenic agar medium for salmonella detection in stool in routine laboratory diagnostics.

We evaluated which chromogenic agar medium for Salmonella detection in stool would be most sensitive and specific in our culture protocol. The use of BBL CHROMagar Salmonella chromogenic medium combined with xylose-lysine-deoxycholate agar yielded a sensitivity of 100% and also reduced workload and costs.

Identification and susceptibility testing of Enterobacteriaceae and Pseudomonas aeruginosa by direct inoculation from positive BACTEC blood culture bottles into Vitek 2.

Inoculation of an automated system for rapid identification (ID) and antimicrobial susceptibility testing (AST) directly from positive blood culture bottles will reduce the turnaround time of laboratory diagnosis of septicemic patients, which benefits clinical outcome and decreases patient costs. Direct test results, however, must always be confirmed by testing a pure overnight culture, which is the "gold standard." We studied the accuracy of direct testing versus repeat testing in order to investigate the possibility of refraining from repeat testing. We also assessed the clinical risk of reporting results based on direct testing only. We inoculated Vitek 2 (bioMérieux) directly from 410 positive BACTEC 9240 (BD) blood culture bottles containing gram-negative rods and studied the ID and AST results. In a comparison of direct inoculation with the standard method, a total of 344 isolates of Enterobacteriaceae and Pseudomonas aeruginosa were tested, and 93.0% were correctly identified. Of the 39 (10.2%) samples that contained bacilli not identifiable by Vitek 2, only 1 gave a conclusive, correct result. The overall MIC agreement among 312 isolates was 99.2%, with 0.8% very major and 0.02% major error rates. Of only three (polymicrobial) samples, the direct susceptibility pattern would be reported to the clinician as too sensitive. Vitek 2 results obtained from direct inoculation of blood culture bottles containing gram-negative bacilli are safe enough for immediate reporting, provided that ID and AST are consistent. Repeat testing is not necessary, unless Gram stain or overnight subculture results raise doubt about the purity of the culture.