Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an open-label, clustered group-randomised, crossover study.

BACKGROUND: Previously, we assessed selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) on survival and prevention of bacteraemia in patients in intensive-care units. In this analysis, we aimed to assess effectiveness of these interventions for prevention of respiratory tract colonisation and bacteraemia with highly resistant microorganisms acquired in intensive-care units. METHODS: We did an open-label, clustered group-randomised, crossover study in 13 intensive-care units in the Netherlands between May, 2004, and July, 2006. Participants admitted to intensive-care units with an expected duration of mechanical ventilation of more than 48 h or an expected stay of more than 72 h received SOD (topical tobramycin, colistin, and amphotericin B in the oropharynx), SDD (SOD antibiotics in the oropharynx and stomach plus 4 days' intravenous cefotaxime), or standard care. The computer-randomised order of study regimens was applied by an independent clinical pharmacist who was masked to intensive-care-unit identity. We calculated crude odds ratios (95% CI) for rates of bacteraemia or respiratory tract colonisation with highly resistant microorganisms in patients who stayed in intensive-care units for more than 3 days (ie, acquired infection). This trial is registered at http://isrctn.org, number ISRCTN35176830. FINDINGS: Data were available for 5927 (>99%) of 5939 patients, of whom 5463 (92%) were in intensive-care units for more than 3 days. 239 (13%) of 1837 patients in standard care acquired bacteraemia after 3 days, compared with 158 (9%) of 1758 in SOD (odds ratio 0·66, 95% CI 0·53-0·82), and 124 (7%) of 1868 in SDD (0·48, 0·38-0·60). Eight patients acquired bacteraemia with highly resistant microorganisms during SDD, compared with 18 patients (with 19 episodes) during standard care (0·41, 0·18-0·94; rate reduction [RR] 59%, absolute risk reduction [ARR] 0·6%) and 20 during SOD (0·37, 0·16-0·85; RR 63%, ARR 0·7%). Of the patients staying in intensive-care units for more than 3 days, we obtained endotracheal aspirate cultures for 881 (49%) patients receiving standard care, 886 (50%) receiving SOD, and 828 (44%) receiving SDD. 128 (15%) patients acquired respiratory tract colonisation with highly resistant microorganisms during standard care, compared with 74 (8%) during SDD (0·58, 0·43-0·78; RR 38%, ARR 5·5%) and 88 (10%) during SOD (0·65, 0·49-0·87; RR 32%, ARR 4·6%). Acquired respiratory tract colonisation with Gram-negative bacteria or cefotaxime-resistant and colistin-resistant pathogens was lowest during SDD. INTERPRETATION: Widespread use of SDD and SOD in intensive-care units with low levels of antibiotic resistance is justified. FUNDING: None.

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.

A bundle approach to reduce the incidence of external ventricular and lumbar drain-related infections.

OBJECT: An important complication of external CSF drainage is bacterial meningitis or ventriculitis, resulting in increased morbidity, mortality, and health care costs. In 2003, a high rate (37%) of probable drain-related infections was identified at the authors' hospital. A multidisciplinary working group was installed to reduce this incidence to < 10% within 1.5 years. METHODS: An intervention strategy based on 5 pillars (increased awareness, focused standard operating procedures, a diagnostic and therapeutic algorithm, timely administration of prophylaxis, and improvement of the drainage system) was designed and implemented from 2004 to 2006. During this period all patients with external CSF drainage were prospectively monitored. RESULTS: Between 2004 and 2006, there were 467 patients in whom 579 drains (external ventricular and external lumbar) had been placed. The overall incidence of drain-related infections was 16.2% in 2004, 8.9% in 2005, and 11.3% in 2006. For external lumbar drains the number of infections per 100 drain days was 2.4 in 2004, 0.6 in 2005, and 0.8 in 2006. For external ventricular drains these rates were 1.7, 1.0, and 1.2, respectively. Meanwhile, the causative noncutaneous microorganisms, indicative for systemic-contamination during manipulation, decreased. By retrospective analysis, the proportion of patients with a probable drain-related infection decreased from 37% in 2003 to 9% in 2005 and 2006. CONCLUSIONS: The authors' multidisciplinary approach in which different preventive measures were combined was associated with a significant reduction in the incidence of drain-related secondary meningitis, and thus provides an important improvement of patient safety.

Decontamination of the digestive tract and oropharynx: hospital acquired infections after discharge from the intensive care unit.

OBJECTIVE: To determine the incidence rates of hospital acquired infections (HAI) during the first 14 days after ICU discharge after treatment during ICU-stay with Selective Decontamination of the Digestive tract (SDD), Selective Oropharyngeal Decontamination (SOD) or Standard Care (SC). DESIGN: Prospective observational study. SETTING: ICUs in two tertiary care hospitals. PATIENTS: Patients discharged from the ICU to the ward. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Post-ICU incidences of HAI per 1,000 days at risk were 11.2, 12.9 and 8.3 for patients that had received SDD (n = 296), SOD (n = 286) or SC (n = 289) respectively in ICU, yielding relative risks, as compared to SC, of 1.49 (CI(95) 0.9-2.47) for SOD and 1.44 (CI(95) 0.87-2.39) for SDD. Incidences of surgical site infections (per 100 surgical procedures) were 4 after SC and 11.8 and 8 after SOD and SDD (p = 0.04). Among patients that succumbed in the hospital after ICU-stay (n = 58) eight (14%) had developed HAI after ICU discharge; 3 of 21 after SDD, 3 of 15 after SOD and 2 of 22 after SC. CONCLUSIONS: Incidences of HAI in general wards tended to be higher in patients that had received either SDD or SOD during ICU-stay, but it seems unlikely that these infections have an effect on hospital mortality rates.

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.

Failure to control an outbreak of qnrA1-positive multidrug-resistant Enterobacter cloacae infection despite adequate implementation of recommended infection control measures.

A large outbreak with an aminoglycoside-resistant Enterobacter cloacae (AREC) clone occurred at the University Medical Center Utrecht beginning in 2001 and continued up through the time that this study was completed. This clone (genotype I) contains a conjugative R plasmid carrying the qnrA1, bla(CTX-M-9), and aadB genes, encoding resistance to quinolones, extended-spectrum beta-lactamases, and aminoglycosides, respectively. The aim of this study was to determine whether this clone was more transmissible than other AREC strains. Therefore, the dissemination of this genotype and of other E. cloacae strains was studied. In addition, infection control measures taken were evaluated. Pulsed-field gel electrophoresis analysis divided the 191 AREC strains into 42 different genotypes, of which 5 (12%) involved at least three patients. Aside from this outbreak (133 patients), only two other small outbreaks occurred, showing that the infection control measures were successful for all strains but one. Among 324 aminoglycoside-susceptible E. cloacae strains, 34/166 (20%) genotypes were identified from at least three patients, but only 4 involved small outbreaks. The outbreak strain was also detected in 11 of 15 other Dutch hospitals and caused outbreaks in at least 4. Evaluation of infection control measures showed that the outbreak strain disseminated throughout the hospital despite adequate implementation of internationally accepted guidelines on the control of multidrug-resistant Enterobacteriaceae (MRE). In conclusion, some MRE strains are better able to spread than others, and these strains may not be controlled by the current infection control guidelines. Strategies to identify such strains in an early phase and adapted guidelines for such "superbugs" are needed to prevent these clones from becoming endemic.

Extensive hospital-wide spread of a multidrug-resistant enterobacter cloacae clone, with late detection due to a variable antibiogram and frequent patient transfer.

A hospital-wide increase in the number of patients with aminoglycoside-resistant Enterobacter cloacae (AREC) isolated from clinical cultures was detected in December 2002 using a classical surveillance system (CSS). CSS refers to a strategy based on the recognition of an increased incidence of a species with a particular antibiogram at certain wards in a limited period. Since clonal spread was suspected, hospital records were reviewed for E. cloacae culture-positive patients. Based upon genotyping of 139 clinical E. cloacae isolates from 80 patients, it was concluded that 53 patients had had clinical cultures with a single AREC clone since April 2001. Determinants for unnoticed spread were investigated retrospectively, as was the possibility that a computer-assisted surveillance method would have detected this outbreak at an earlier stage. Determinants associated with late detection of clonal spread were the following: (i) the absence of a hospital-wide increase in incidence of E. cloacae cases for 1.5 years, (ii) the long time interval between cases, (iii) the hospital-wide occurrence of new cases, due to a high number of patient transfers between wards, (iv) the large variety of clinical sites, and (v) the high variability of antibiograms (n = 33). Retrospective application of a recently described computer-assisted surveillance method as well as an "in-house"-developed algorithm resulted in earlier detection of the outbreak of 6 and 12 months, respectively. These findings suggest that computerized tools for surveillance may recognize resistance trends that are too complex to be detected by manual review and indicate the need for prospective evaluation of such algorithms.

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.

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.

Surveillance for hospital-acquired infections on surgical wards in a Dutch university hospital.

OBJECTIVES: To determine incidence rates of hospital-acquired infections and to develop preventive measures to reduce the risk of hospital-acquired infections. METHODS: Prospective surveillance for hospital-acquired infections was performed during a 5-year period in the wards housing general and vascular, thoracic, orthopedic, and general gynecologic and gynecologic-oncologic surgery of the University Medical Center Utrecht, the Netherlands. Data were collected from patients with and without infections, using criteria of the Centers for Disease Control and Prevention. RESULTS: The infection control team recorded 648 hospital-acquired infections affecting 550 (14%) of 3,845 patients. The incidence density was 17.8 per 1,000 patient-days. Patients with hospital-acquired infections were hospitalized for 19.8 days versus 7.7 days for patients without hospital-acquired infections. Prolongation of stay among patients with hospital-acquired infections may have resulted in 664 fewer admissions due to unavailable beds. Different specialties were associated with different infection rates at different sites, requiring a tailor-made approach. Interventions were recommended for respiratory tract infections in the thoracic surgery ward and for surgical-site infections in the orthopedic and gynecologic surgery wards. CONCLUSIONS: Surveillance in four surgical wards showed that each had its own prominent infection, risk factors, and indications for specific recommendations. Because prospective surveillance requires extensive resources, we considered a modified approach based on a half-yearly point-prevalence survey of hospital-acquired infections in all wards of our hospital. Such surveillance can be extended with procedure-specific prospective surveillance when indicated.

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.