Hetty E. M. Blok

A dutch approach to methicillin-resistant Staphylococcus aureus

C. van der Werken Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands Methicillin-resistant Staphylococcus aureus (MRSA), first reported in 1962, has now emerged as a major cause of nosocomial infections [1]. Strains of MRSA are efficient colonizers of the skin and mucous membranes and can cause outbreaks that are difficult to control [1–3]. In addition, they have demonstrated remarkable ability to become resistant to other antibiotics. Numerous MRSA strains are now resistant to many antibiotics, including erythromycin, tetracycline, gentamicin and the fluoroquinolones [1, 2, 4]. In centers with high incidence rates of MRSA, however, the only therapeutic option for patients with MRSA infections is treatment with vancomycin or teicoplanin. It is therefore alarming that vancomycin intermediatesusceptible MRSA strains (VISA) are being isolated with increasing frequency [5]. VISA strains have also been reported from several centers in the USA. A recent editorial describing this phenomenon was titled “Vancomycin resistant Staphylococcus aureus: apocalypse now?” [6].

Ecological effects of selective decontamination on resistant gram-negative bacterial colonization.

RATIONALE Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) eradicate gram-negative bacteria (GNB) from the intestinal and respiratory tract in intensive care unit (ICU) patients, but their effect on antibiotic resistance remains controversial. OBJECTIVES We quantified the effects of SDD and SOD on bacterial ecology in 13 ICUs that participated in a study, in which SDD, SOD, or standard care was used during consecutive periods of 6 months (de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, et al. N Engl J Med 2009;360:20-31). METHODS Point prevalence surveys of rectal and respiratory samples were performed once monthly in all ICU patients (receiving or not receiving SOD/SDD). Effects of SDD on rectal, and of SDD/SOD on respiratory tract, carriage of GNB were determined by comparing results from consecutive point prevalence surveys during intervention (6 mo for SDD and 12 mo for SDD/SOD) with consecutive point prevalence data in the pre- and postintervention periods. MEASUREMENTS AND MAIN RESULTS During SDD, average proportions of patients with intestinal colonization with GNB resistant to either ceftazidime, tobramycin, or ciprofloxacin were 5, 7, and 7%, and increased to 15, 13, and 13% postintervention (P < 0.05). During SDD/SOD resistance levels in the respiratory tract were not more than 6% for all three antibiotics but increased gradually (for ceftazidime; P < 0.05 for trend) during intervention and to levels of 10% or more for all three antibiotics postintervention (P < 0.05). CONCLUSIONS SOD and SDD have marked effects on the bacterial ecology in an ICU, with rising ceftazidime resistance prevalence rates in the respiratory tract during intervention and a considerable rebound effect of ceftazidime resistance in the intestinal tract after discontinuation of SDD.

Evidence of Extensive Interspecies Transfer of Integron-Mediated Antimicrobial Resistance Genes among Multidrug-Resistant Enterobacteriaceae in a Clinical Setting

Multidrug resistance in gram-negative bacteria appears to be primarily the result of the acquisition of resistance genes by horizontal transfer. To what extent horizontal transfer may be responsible for the emergence of multidrug resistance in a clinical setting, however, has rarely been investigated. Therefore, the integron contents of isolates collected during a nosocomial outbreak of genotypically unrelated multidrug-resistant Enterobacteriaceae were characterized. The integron was chosen as a marker of transfer because of its association with multiresistance. Some genotypically identical isolates harbored different integrons. Grouping patients carrying the same integron yielded 6 epidemiologically linked clusters, with each cluster representing a different integron. Several patients carried multiple species harboring the same integron. Conjugation experiments with these strains resulted in the transfer of complete resistance patterns at high frequencies (10(-2) to 10(-4)). These findings provide strong evidence that the horizontal transfer of resistance genes contributed largely to the emergence of multidrug-resistant Enterobacteriaceae in this clinical setting.

Presence of Integron-Associated Resistance in the Community Is Widespread and Contributes to Multidrug Resistance in the Hospital

ABSTRACT Integrons are strongly associated with the multidrug resistance seen in gram-negative bacilli in the hospital environment. No data, however, are available on their prevalence in the community. This study is the first to show that integrons are widespread in Enterobacteriaceae in the community and that integron-associated resistance genes in the community constitute a substantial reservoir for multidrug resistance in the hospital.

Role of healthcare workers in outbreaks of methicillin-resistant Staphylococcus aureus: a 10-year evaluation from a Dutch university hospital.

BACKGROUND AND OBJECTIVE The benefit of screening healthcare workers (HCWs) at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage and furloughing MRSA-positive HCWs to prevent spread to patients is controversial. We evaluated our MRSA program for HCWs between 1992 and 2002. SETTING A university medical center in The Netherlands, where methicillin resistance has been kept below 0.5% of all nosocomial S. aureus infections using active surveillance cultures and isolation of colonized patients. DESIGN HCWs caring for MRSA-positive patients or patients in foreign hospitals were screened for MRSA. MRSA-positive HCWs had additional cultures, temporary exclusion from patient-related work, assessment of risk factors for persisting carriage, decolonization therapy with mupirocin intranasally and chlorhexidine baths for skin and hair, and follow-up cultures. RESULTS Fifty-nine HCWs were colonized with MRSA. Seven of 840 screened employees contracted MRSA in foreign hospitals; 36 acquired MRSA after contact with MRSA-positive patients despite isolation precautions (attack rate per outbreak varied from less than 1% to 15%). Our hospital experienced 17 MRSA outbreaks, including 13 episodes in which HCWs were involved. HCWs were index cases of at least 4 outbreaks. In 8 outbreaks, HCWs acquired MRSA after caring for MRSA-positive patients despite isolation precautions. CONCLUSION Postexposure screening of HCWs allowed early detection of MRSA carriage and prevention of subsequent transmission to patients. Where the MRSA prevalence is higher, the role of HCWs may be greater. In such settings, an adapted version of our program could help prevent dissemination.

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.

High acquisition and environmental contamination rates of CC17 ampicillin-resistant Enterococcus faecium in a Dutch hospital

BACKGROUND Enterococcus faecium has rapidly emerged as a nosocomial pathogen worldwide, and the majority of these isolates belong to clonal complex-17 (CC17). In Europe, CC17 isolates are usually ampicillin-resistant, but most are still vancomycin-sensitive. We aimed to study ampicillin-resistant E. faecium (ARE) epidemiology in our hospital. METHODS In a 3 month study, 210 of 358 admissions (59%) to haematology and gastroenterology/nephrology were screened for rectal ARE colonization on admission (<48 h) and 148 of 210 (70%) also at discharge (<72 h). In a second (3 month) study, environmental swabs from eight predetermined sites were obtained from ARE-colonized haematology patients once weekly. All ARE isolates were genotyped by multiple-locus variable-number tandem repeat analysis (MLVA). RESULTS ARE admission prevalence was 10% and 16% and acquisition rates were 39% and 15% in haematology and gastroenterology/nephrology, respectively. Carriage on admission was associated with previous admission <1 year (OR 5.0, 95% CI 1.8-14.0) and acquisition with beta-lactam (OR 2.7, 95% CI 1.1-6.7) and quinolone use (OR 3.1, 95% CI 1.1-8.2). Five of the 57 (9%) colonized patients developed invasive ARE infections. Genotyping revealed 12 genotypes (all CC17) with two MLVA types responsible for 94% of acquisitions. In 18 of the 19 colonized patients, the environment was contaminated with ARE. Sites most often contaminated were the toilet seat (43%), over-bed table (34%) and television remote control (28%). CONCLUSIONS CC17 ARE epidemiology is characterized by high admission (10% to 16%), acquisition (15% to 39%) and environmental contamination (22%) rates, resulting from cross-transmission, readmission and antibiotic pressure. A multifaceted infection control approach will be needed to curtail further spread.

Methicillin-resistant Staphylococcus aureus carriage among patients after hospital discharge.

BACKGROUND AND OBJECTIVE At the University Medical Center Utrecht (UMCU), follow-up implies an inventory of risk factors and screening for MRSA colonization among all MRSA-positive patients for at least 6 months. If risk factors or positive cultures persist or re-emerge, longer follow-up is indicated and isolation at readmission. This study investigated how long MRSA-positive patients remained colonized after hospital discharge and which risk factors were important. Furthermore, the results of eradication therapy were evaluated. DESIGN All patients who were positive for MRSA at the UMCU between January 1991 and January 2001 were analyzed regarding carriage state, presence of risk factors for prolonged carriage of Staphylococcus aureus, and eradication treatment. RESULTS A total of 135 patients were included in the study. The median follow-up time was 1.2 years. Eighteen percent of the patients were dismissed from follow-up 1 year after discharge. Only 5 patients were dismissed after 6 months. Among patients with no risk factors, eradication treatment was effective for 95% within 1 year. Among patients with persistent risk factors, treatment was effective for 89% within 2 years. CONCLUSIONS Based on these findings, eradication therapy should be prescribed for all MRSA carriers, independent of the presence of risk factors. MRSA-positive patients should be evaluated for 6 months for the presence of risk factors and MRSA carriage. Screening for risk factors is important because intermittent MRSA carriage was found in a significant number of our patients. Patients with negative MRSA cultures and without risk factors for 12 months can be safely dismissed from follow-up.

Surveillance of nosocomial infections in geriatric patients

Prospective surveillance of hospital-acquired infections was undertaken in the geriatric ward of the University Hospital, Utrecht, the Netherlands. The medical records of 300 patients were studied for the presence of nosocomial infections using the criteria defined by the Centers for Disease Control (CDC), Atlanta, Georgia, USA. Data were collected from patients with and without infection, which allowed for the analysis of risk factors for nosocomial infection. In 100 out of 300 patients (33.3%), a total of 126 infections was diagnosed. The incidence of nosocomial infections was 16.9 per 1000 days of stay in the hospital. The mean length of stay of patients with infection was 39 days, while that of patients without infection was 17.8 days. Infections developed after an average stay of 13.3 days in the hospital. Patients with infections were 2.6 years older than patients without infections (P = 0.005). Dehydration was shown to be a major risk factor for infection (RR = 2.1, 95% CI: 1.4-3.2). Of the infections, 58.7% were urinary tract infections (UTIs, asymptomatic and symptomatic). The most important risk factor for an asymptomatic UTI was an indwelling urinary catheter (RR = 7.3, 95% CI: 3.1-17.1). The duration of use of the indwelling urinary catheter was of significant influence in the development of a UTI. Seventy percent of the patients with an asymptomatic UTI were treated with antibiotics. Infections of the gastrointestinal tract accounted for 19.8% of all nosocomial infections. The majority of these infections were due to an outbreak of Clostridium difficile. In conclusion, the length of stay may be prolonged by a nosocomial infection. In this study, the main risk factors for developing a nosocomial infection were age, dehydration and the presence of an urinary catheter. Our observations showed that age is a predisposing factor for nosocomial infection and that the risk increases with each year, even for geriatric patients.

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.