Risk factors for the acquisition of OXA-48-producing Enterobacteriaceae in a hospital outbreak setting: a matched case-control study.

OBJECTIVES: In the context of a large outbreak of OXA-48-producing Enterobacteriaceae (OXA-E) in a Dutch hospital we determined risk factors for acquisition of OXA-E. PATIENTS AND METHODS: A matched case-control study was performed in which cases (culture positive for OXA-E) were matched 1:3 to controls (culture negative for OXA-E) based on hospital ward, index date (±1 week) and time exposed in the hospital (best match). Stratified analyses were performed for patients with OXA-E producing and not producing ESBL. Potential risk factors included age, gender, surgery and ICU admission within 30 days preceding the index date, presence of comorbidities and in-hospital antibiotic treatment within 30 days preceding the index date. Data analysis was performed using multivariable conditional logistic regression with Firth correction. RESULTS: In total, 73 cases were matched to 211 controls. In the multivariable conditional logistic regression model, male gender (OR 2.63, 95% CI 1.25-5.53), age (per year increase, OR 1.03, 95% CI 1.00-1.05) and use of fluoroquinolones within 30 days preceding the index date (OR 2.98, 95% CI 1.06-8.41) were risk factors for acquisition of OXA-E. In the stratified multivariable conditional logistic regression model, quinolone use was a risk factor for the acquisition of ESBL-producing OXA-E and surgery was a risk factor for the acquisition of non-ESBL-producing OXA-E. CONCLUSIONS: During a large, hospital-wide OXA-E outbreak, male gender, age and previous use of fluoroquinolones were risk factors for acquisition of OXA-E. These findings may help in optimizing screening and isolation strategies in future OXA-E outbreaks.

Raman spectroscopy-based identification of nosocomial outbreaks of the clonal bacterium Escherichia coli.

DNA-based techniques are frequently used to confirm the relatedness of putative outbreak isolates. These techniques often lack the discriminatory power when analyzing closely related microbes such as E. coli. Here the value of Raman spectroscopy as a typing tool for E. coli in a clinical setting was retrospectively evaluated.

Successful control of a hospital-wide outbreak of OXA-48 producing Enterobacteriaceae in the Netherlands, 2009 to 2011.

On 31 May 2011, after notification of Klebsiella pneumoniae (KP)(OXA-48;CTX-M-15) in two patients, nosocomial transmission was suspected in a Dutch hospital. Hospital-wide infection control measures and an outbreak investigation were initiated. A total of 72,147 patients were categorised into groups based on risk of OXA-48 colonisation or infection, and 7,527 were screened for Enterobacteriaceae(OXA-48) by polymerase chain reaction (PCR). Stored KP isolates (n=408) were retrospectively tested for OXA-48 and CTX-M-1 group extended-spectrum beta-lactamases (ESBL). 285 KP isolates from retrospective and prospective patient screening were genotyped by amplified fragment length polymorphism (AFLP). 41 isolates harbouring different Enterobacteriaceae species were analysed by plasmid multilocus sequence typing (pMLST). No nosocomial transmission of Enterobacteriaceae(OXA-48) was detected after 18 July 2011. Enterobacteriaceae(OXA-48) were found in 118 patients (KP (n=99), Escherichia coli (n=56), ≥1 Enterobacteriaceae(OXA-48) species (n=52)), of whom 21 had clinical infections. 39/41 (95%) of OXA-48 containing plasmids were identical in pMLST. Minimum inhibitory concentrations (MICs) of KP(OXA-48) and E. coli(OXA-48) for imipenem and meropenem ranged from ≤1 to ≥16 mg/L, and 153/157 (97%) had MIC >0.25 mg/L for ertapenem. AFLP identified a cluster of 203 genetically linked isolates (62 KP(OXA-48;CTX-M15); 107 KP(CTX-M-15); 34 KP(OXA-48)). The 'oldest' KP(CTX-M-15) and KP(OXA-48) clonal types originated from February 2009 and September 2010, respectively. The last presumed outbreak-related KP(OXA-48) was detected in April 2012. Uncontrolled transmission of KP(CTX-M-15) evolved into a nosocomial outbreak of KP(OXA-48;CTX-M15) with large phenotypical heterogeneity. Although the outbreak was successfully controlled, the contribution of individual containment measures and of the hospital relocating into a new building just before outbreak notification was impossible to quantify.

Universal risk assessment upon hospital admission for screening of carriage with multidrug-resistant micro-organisms in a Dutch tertiary care centre.

BACKGROUND: In Dutch hospitals a six-point questionnaire is currently mandatory for risk assessment to identify carriers of multidrug-resistant organisms (MDROs) at the time of hospitalization. Presence of one or more risk factors is followed by pre-emptive isolation and microbiological culturing. AIM: To evaluate the yield of the universal risk assessment in identifying MDRO carriers upon hospitalization. METHODS: A cross-sectional study was performed using routine healthcare data in a Dutch tertiary hospital between January 1st, 2015 and August 1st, 2019. MDRO risk assessment upon hospitalization included assessment of: known MDRO carriage, previous hospitalization in another Dutch hospital during an outbreak or a foreign hospital, living in an asylum centre, exposure to livestock farming, and household membership of a meticillin-resistant Staphylococcus aureus carrier. FINDINGS: In total, 144,051 admissions of 84,485 unique patients were included; 4480 (3.1%) admissions had a positive MDRO risk assessment. In 1516 (34%) admissions microbiological screening was performed, of which 341 (23%) yielded MDRO. Eighty-one patients were categorized as new MDRO carriers, as identified through MDRO risk assessment, reflecting 0.06% (95% confidence interval: 0.04-0.07) of all admissions and 1.8% (1.4-2.2) of those with positive risk assessment. As a result, the number of 'MDRO risk assessments needed to perform' and individual 'MDRO questions needed to ask' to detect one new MDRO carrier upon hospitalization were 1778 and 10,420, respectively. CONCLUSION: The yield of the current strategy of MDRO risk assessment upon hospitalization is limited and it needs thorough reconsideration.

[Methicillin-resistant Staphylococcus aureus of livestock origin in Dutch hospitals: high-risk patients need only to be investigated if admitted to hospital]. / Meticillineresistente Staphylococcus aureus afkomstig uit de veestapel in Nederlandse ziekenhuizen: risicopatiënten alleen controleren bij eventuele ziekenhuisopname.

OBJECTIVE: To determine the incidence and prevalence of carriage of methicillin-resistent Staphylococcus aureus (MRSA) in patients and hospital personnel, and to examine the consequences of the revised Dutch MRSA guideline with respect to patients who have frequent contact with pigs or calves (in the course of their work). DESIGN: Retrospective and prospective observational study using questionnaires. METHOD: Since July 2006 patients who have contact with living pigs or calves have been regarded as a high-risk group for MRSA carriage, after it was established that this occupational group had an increased chance of carriage of the so-called non-typable MRSA (NT-MRSA). An inventory was made of incidence and prevalence of MRSA carriage in patients and hospital personnel, and of the consequences of the new MRSA policy, for the period July-December 2006. RESULTS: Information was obtained from 58 Dutch hospitals. On January 1 2007, 37 (64%) hospitals had changed their MRSA policy; 22% of the hospitals it was applied in accordance with the MRSA guideline. The new guideline resulted in an increase of MRSA screenings by 15% and of detected MRSA carriers by 44%. 73% of all MRSA screenings took place in the out-patients department. In regions with high pig-density the incidence of NT-MRSA was 12% in patients with risk factors for carriage. In 49% of the hospitals one or more NT-MRSA carriers were detected (range 1-19 carriers). Possible transmission of NT-MRSA in hospital was shown in 3 of 1,007 (0.3%) hospital personnel, but in none of the 183 fellow-patients, examined. In the same period transmission of typable MRSA was demonstrated in 41 of 2,019 (2.0%) patients and 33 of 5,190 (0.6%) of hospital personnel examined. Prevalence of NT-MRSA carriage in 6,197 screened hospital personnel was 0.05% (n = 3). CONCLUSION: The revised Dutch MRSA guideline lead to an increase in the number of MRSA screenings by 15%, particularly in the out-patients department, and to an increase in the number of detected MRSA carriers by 44%. During 306 months of observation no patient-to-patient transmission ofNT-MRSA was demonstrated.

[Optimisation of the antibiotic policy in the Netherlands. XII. The SWAB guideline for antimicrobial eradication of MRSA in carriers]. / Optimaliseren van het antibioticabeleid in Nederland. XII. SWAB-richtlijn voor de behandeling van MRSA-dragerschap.

The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotics Policy) has developed evidence-based guidelines for the antimicrobial treatment of methicillin-resistant Staphylococcus aureus (MRSA) carriers for the eradication of MRSA. A distinction was made between uncomplicated and complicated carriage depending on the presence or absence of an active MRSA infection, skin lesions, foreign body material, mupirocin resistance and/or extranasal carriage. The indication for treatment is determined by the consequences of carriage for the carrier and his/her environment, the adverse events of treatment, and the likelihood of a successful treatment. The first choice of treatment in uncomplicated carriers is a combination of mupirocin nasal ointment and disinfectant soap for 5 days, along with hygiene advice. If treatment fails, sources in the vicinity of the patient must be sought. Complicated carriers receive a combination of 2 oral antibiotics, in addition to mupirocin nasal ointment and disinfectant soap, for at least 7 days.

Prevalence of hospital-acquired infections during successive surveillance surveys conducted at a university hospital in the Netherlands.

OBJECTIVE: To monitor hospital-wide trends in the prevalence of hospital-acquired infections (HAIs) in order to identify areas where the risk of infection is increasing. METHODS: Successive surveillance surveys were conducted twice yearly, from November 2001 until May 2004, to determine the prevalence of HAIs at 2 Dutch hospitals, using Centers for Disease Control and Prevention criteria. RESULTS: In all, 340 HAIs were observed in 295 (11.1%) of 2,661 patients surveyed. The overall prevalence per survey varied from 10.2% to 15.6%, with no significant differences between successive surveys. In the surgical department, the prevalence of HAIs increased from 10.8 cases per 100 surgeries in November 2001 to 20.4 cases per 100 surgeries in May 2002. Further analysis revealed a high prevalence of surgical site infection among patients who had an orthopedic procedure performed. In the neurology-neurosurgery department, the prevalence increased from 13.0 cases per 100 patients in May 2002 to 26.6 cases per 100 patients in May 2003 and involved several types of infection. Further analysis retrieved exceptionally high incidences of infections associated with cerebrospinal fluid drainage. Specific infection control interventions were developed and implemented in both departments. The total cost of the surveys was estimated to be euro9,100 per year. CONCLUSION: Successive performance of surveillance surveys is a simple and cheap method to monitor the prevalence of infection throughout the hospital and appeared instrumental in identifying 2 departments with increased infection rates.

Ecological replacement of Enterococcus faecalis by multiresistant clonal complex 17 Enterococcus faecium.

The proportion of enterococcal infections caused by ampicillin-resistant Enterococcus faecium (AREfm) in a European hospital increased from 2% in 1994 to 32% in 2005, with prevalence rates of AREfm endemicity of up to 35% in at least six hospital wards. Diabetes mellitus, three or more admissions in the preceding year, and use of beta-lactams and fluoroquinolones, were all associated with AREfm colonisation. Of 217 AREfm isolates that were genotyped, 97% belonged to clonal complex 17 (CC17). This ecological change mimics events preceding the emergence of vancomycin-resistant E. faecium (VREF) in the USA and may presage the emergence of CC17 VREF in European hospitals.

Hospital infection control in the Netherlands.

In this paper, the organization of infection control in Dutch hospitals will be described generally. Local organization of infection control departments can of course differ due to special needs, special expertise or interests of the members of a department.

Genotyping and preemptive isolation to control an outbreak of vancomycin-resistant Enterococcus faecium.

BACKGROUND: Control of vancomycin-resistant Enterococcus faecium (VRE) in European hospitals is hampered because of widespread asymptomatic carriage of VRE by healthy Europeans. In 2000, our hospital (The University Medical Center Utrecht, Utrecht, The Netherlands) was confronted with a large outbreak of VRE. INTERVENTION: On the basis of genotyping (by pulsed-field gel electrophoresis), epidemic and nonepidemic VRE strains were distinguished, and infection-control measures were exclusively targeted toward epidemic VRE. The outbreak was retrospectively divided into 3 periods of different infection-control measures. Compliance with use of alcohol-based hand rubs was enforced during all periods. Period I involved active surveillance, isolation of carriers, and cohorting (duration, 4 months); preemptive isolation of high-risk patients for VRE colonization was added in period II (7 months); and cohorting and preemptive isolation were abandoned in period III (18 months). METHODS: When the outbreak was identified, 27 patients in 6 wards were colonized; 93% were colonized with an epidemic VRE strain. Detection rates of nonepidemic VRE were 3.5%, 3.0%, and 2.9% among 683, 810, and 977 screened patients in periods I, II, and III, respectively, comparable to a prevalence of 2% (95% confidence interval [CI], 1%-3.5%) among 600 nonhospitalized persons. The relative risks of detecting epidemic VRE in periods II and III, compared with period I, were 0.67 (95% CI, 0.41-1.10) for period II and 0.02 (95% CI, 0.002-0.6) for period III. Infection-control measures were withheld for patients colonized with nonepidemic VRE (76 [54%] of 140 patients with a test result positive for VRE). Use of alcohol-based hand rubs increased by 31%-275% in outbreak wards. CONCLUSION: Genotyping-targeted infection control, isolation of VRE carriers, enhancement of hand-hygiene compliance, and preemptive isolation successfully controlled nosocomial spread of epidemic VRE infection.

Trends in fungaemia and antifungal susceptibility in the Netherlands.

We retrospectively evaluated fungaemia over the period 1996 to 2001 in five university hospitals. Over 350,000 blood cultures were collected during more than 7 million days of hospitalisation. The average rate of fungaemia over the six-year period was 0.82 per 10,000 patient days (range 0.65 to 1.21 per 10,000 patient days). The proportion of bloodstream infections caused by Candida albicans remained stable throughout the study period with a mean of 53% (range 48 to 62%). This is a change from trends described in previous studies, including a survey performed in the Netherlands. This study shows a new, stable rate of fungaemia and no further signs of increasing rate of infections due to non-albicans Candida species. Susceptibility to all tested antifungal agents remained stable throughout the study period.

[The Dutch MRSA policy should be retained]. / Het Nederlandse MRSA-beleid is succesvol.

The Dutch methicillin-resistant Staphylococcus aureus (MRSA) 'search and destroy' policy is effective. MRSA should be banned from hospitals: MRSA infections are associated with increased mortality and costs. In addition, widespread use of vancomycin for treating MRSA infections encourages the spread and development of vancomycin-resistant micro-organisms.

[Endocarditis due to meticillin-resistant Staphylococcus aureus originating from pigs]. / Endocarditis door meticillineresistente Staphylococcus aureus afkomstig van varkens.

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.

Dual effects of soluble CD14 on LPS priming of neutrophils.

To evaluate the effect of soluble CD14 (sCD14) on human neutrophil response to lipopolysaccharide (LPS), we developed an LPS-priming assay that measures the chemiluminescence response to N-formyl-methionyl-leucyl-phenylalanine stimulation. Priming by 1 ng/mL rough LPS occurred in the presence of either serum or recombinant LPS-binding protein (LBP) only. Priming was completely CD14-dependent because preincubation of the neutrophils with an anti-CD14 monoclonal antibody prevented priming. We hypothesize that sCD14 enhances LPS response in neutrophils, but this response is not as effective as LPS response via membrane CD14 (mCD14). In our experiments sCD14 is present in an excess compared with mCD14. Priming of neutrophils occurs with low LBP, supposedly via sCD14-LPS complexes. With high LBP, addition of sCD14 inhibited LPS-priming of neutrophils. In that case, LPS may be transported to sCD14, preventing a more effective response via mCD14. In this study we demonstrate that the effect of sCD14 on neutrophil response to LPS is a delicate balance between activation and inhibition depending on concentration of serum or LBP.

Quantitative evaluation of photopic ERG waveforms.

Quantitative, computer-based ways of representing photopic ERG waveforms are investigated and related to over-all retinal condition in a group of normal subjects and a group of patients with diagnosed retinitis pigmentosa. Sinusoidal stimulation and a Fourier series response representation have been selected. This combination provides a few parameters which facilitate waveform comparison, and it naturally lends itself to generalization if more detailed features of ERG recordings are to be included. On the basis of this type of waveform characterization, the over-all photopic retinal condition of any individual eye can be represented by a single number or by its location in various cluster diagrams and its distance from the normal cluster. As exemplified by the results herein described, such an automated approach can be particularly useful in screening large populations for retinal degenerations or in quantitatively following the progression of retinal degeneration over long periods of time.

A pilot study on infection control in 10 randomly selected European hospitals: results of a questionnaire survey.

We describe and compare the organization of infection control and some infection control practices in 10 hospitals in seven different European countries. Great differences were observed. By evaluating infection control and hygiene practices in different European centers, areas of prime importance for the development of a European infection control standard may be defined.

Outbreak of a susceptible strain of Acinetobacter species 13 (sensu Tjernberg and Ursing) in an adult neurosurgical intensive care unit.

Between December 1999 and June 2000, an outbreak caused by Acinetobacter emerged on the neurosurgical intensive care unit of our hospital. It was shown using automated ribotyping using Eco RI and pulsed-field gel electrophoresis that the outbreak was caused by spread of a single strain, which was identified by ribotyping and amplified ribosomal DNA restriction analysis as Acinetobacter DNA group 13TU (sensu Tjernberg and Ursing). The outbreak strain, which showed no antibiotic resistance, was identified in 23 patients, five of whom developed an infection. The organism was also isolated from various environmental sites. Cross-transmission among patients continued despite contact isolation of colonized patients and reinforcement of basic disinfection procedures. Eventually, after implementation of additional stringent measures such as cohorting of positive patients and daily disinfection of the floor, the outbreak was brought under control. This study demonstrates that apart from Acinetobacter baumanii, Acinetobacter 13TU strains, even when they are fully susceptible, may cause outbreaks that are difficult to control. Correct identification to the species level of Acinetobacter by genotypic methods is necessary to get insight in the importance of the different Acinetobacter genomic species in hospital epidemiology.

[Methicillin-resistant Staphylococcus aureus in medical and paramedical personnel returned from work in a foreign hospital]. / Meticillineresistente Staphylococcus aureus bij medisch en paramedisch personeel terug van werkbezoek aan een buitenlands ziekenhuis.

The cultures of two patients of the Surgical Intensive Care Unit (IC) of the Medical Centre of Utrecht University were found positive for methicillin-resistant Staphylococcus aureus (MRSA). A male nurse turned out to be the source, 4 months after his return from working in an English hospital. Cultures were, by mistake, not taken directly on arrival from abroad. Pulsed-field gel electrophoresis proved MRSA strains from both source and the 2 patients to be identical to a strain which was epidemic in Great Britain but had never occurred in the Netherlands. The IC has meanwhile been closed; at source investigation, 14 other patients and six staff members were found MRSA-positive. The policy in the hospital is to screen health care workers for MRSA carriership on return from an hospital abroad. The success of the policy depends strongly on the cooperation of health care workers in this matter.

[Epidemic of methicillin-resistant Staphylococcus aureus due to the transfer of 2 Dutch burn patients from a hospital outside of the Netherlands; who suffers the consequences?]. / Epidemie van meticillineresistente Staphylococcus aureus door overname uit een buitenlands ziekenhuis van 2 Nederlandse brandwondpatiënten; wie draagt de gevolgen?

Two burns patients who were transferred to the Central Military Hospital Utrecht from a foreign hospital, were found to be colonised with MRSA. During their 5-week hospitalisation, 21 healthcare workers and one patient became colonised with the same MRSA strain, despite isolation precautions. The department was closed for 29 days; 96 admissions were cancelled and 1411 screening cultures for MRSA were performed. Colonised healthcare workers were temporarily unable to work and additional costs were incurred for disposables and cleaning procedures. The resultant bill for this outbreak was approximately [symbol: see text] 122,500. MRSA outbreaks occur in hospitals with some degree of regularity, but the strong dispersal during this epidemic was exceptional. The transfer of possible MRSA-colonised patients from hospitals outside of the Netherlands sometimes faces opposition due to the considerable demands it makes on a hospital's personnel, organisation and finances. If this were to be compensated, then the currently successful Dutch MRSA policy could be coupled with a willingness to accept patients from hospitals outside of the Netherlands.