Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial.

IMPORTANCE: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE: To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS: Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES: Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS: In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE: Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION: trialregister.nlIdentifier: NTR1780.

Reduction of biofilm formation with trisodium citrate in haemodialysis catheters: a randomized controlled trial.

BACKGROUND: Formation of an intraluminal microbial biofilm is noted to play a significant role in the development of catheter-related infections (CRIs). Recently, it has been demonstrated that trisodium citrate (TSC) has superior antimicrobial effects over heparin for catheter locking. In this randomized controlled trial, we compared the influence of catheter locking with heparin and TSC on the in vivo intraluminal biofilm formation in haemodialysis catheters. METHODS: Six patients were studied from the time of catheter insertion for haemodialysis treatment. They were randomly assigned to TSC 30% or heparin 5000 U/ml for catheter locking for the duration of 1 month. After elective guidewire exchange of the catheter, the locking solution was also changed. After removal, catheters were dissected in three segments and examined by standardized scanning electron microscopy (SEM) to assess quantitative biofilm formation. Furthermore, standardized cultures of all segments were performed to identify any microorganisms. RESULTS: In catheters filled with TSC, the average coverage by biofilm was 16% versus 63% in the heparin group (P < 0.001). A total of eight subsegments were associated with local catheter infection in the patients who were randomized to heparin locking versus three subsegments who were assigned to TSC (P < 0.05). CONCLUSIONS: Our study demonstrates that using TSC 30% for catheter locking reduces the formation of microbial biofilm in haemodialysis catheters and culture-positive colonization. It is likely that this is the explanation for the observed prevention of CRIs by TSC locking.

[Dengue infection with fatal ending]. / Dengue-infectie met fatale afloop.

A 54-year-old man was admitted with fever following a trip to St. Maarten in the Dutch Antilles, from where he had returned 6 days earlier. One year prior to this he had been treated on an Intensive Care Unit for a severe influenza A infection. Physical examination revealed remarkably cold extremities, furthermore there was metabolic acidosis, extreme haemoconcentration, prolongation of prothrombin time and activated partial thromboplastin time. His clinical condition deteriorated rapidly and he died the day after admission. Neither IgG nor IgM antibodies against dengue were found, but PCR on dengue virus RNA was positive. Over past decades there has been a strong increase in the number of dengue virus infections in travellers returning from Southeast Asia, Central and South America, the Caribbean and Africa. Whilst in general a primary dengue virus infection does not result in severe disease, this case illustrates the potentially fatal consequences of dengue in travellers.

Nosocomial transmission of highly resistant microorganisms on a spinal cord rehabilitation ward.

BACKGROUND/OBJECTIVE: To study the mechanism of nosocomial transmission of highly resistant microorganisms (HRMOs). DESIGN: A prospective observational study. SETTING: A spinal cord ward of a rehabilitation center. PARTICIPANTS: Patients admitted to the spinal cord rehabilitation ward. OUTCOME MEASURES: HRMOs present in urine and feces. HRMOs, Enterobacteriaceae: (1) that produced an extended-spectrum beta-lactamase (ESBL), (2) that were resistant to carbapenems, (3) that fluoroquinolones and aminoglycosides (for Escherichia coli and Klebsiella species), or other Enterobacteriaceae species that were resistant to 2 of 3 of the following types of antibiotics (fluoroquinolones, aminoglycosides, cotrimoxazole). METHODS: Bacterial growth, identification and sensitivity were tested in urine cultures of 46 patients and faeces cultures of 15 patients. Data were collected on demographic characteristics, underlying diseases, reason and date of admission, room number, method of catheterization (suprapubic, clean intermittent catheterization or indwelling Foley catheter) and antibiotic use. RESULTS: Nine different HRMOs (7 E. coli, 1 Enterobacter cloacae, and 1 Citrobacter koseri) were isolated in urine samples from 15 patients. E. coli resistant to gentamicin, tetracycline, amoxicillin, cotrimoxazole, and ciprofloxacin were isolated from 8 patients during the study (cluster 1). One strain of multiresistant E coli found before the start of the study was not found during the study period (cluster 2). E coli strains producing an ESBL and resistant to tetracycline, cotrimoxazole, and ciprofloxacin were isolated from urine samples of 3 patients (cluster 3). Ciprofloxacin-resistant E. coli were present in feces of 3 patients (2 in cluster 1). Catheterization was found to be significantly more prevalent in patients with HRMOs. Most of the patients in cluster 1 were treated with antibiotics before the first isolation of the strain. CONCLUSIONS: HRMOs from urine samples were strongly correlated with the use of catheterization. A close correlation was found between prior use of antibiotics and colonization of the urinary tract on the level of the individual patient, which has been rarely described in the literature.

Effectiveness and cost-effectiveness of a pharmacy-based screening programme for Chlamydia trachomatis in a high-risk health centre population in Amsterdam using mailed home-collected urine samples.

In order to increase case-detection of Chlamydia trachomatis (CT) in a multicultural, low-income and high-CT-prevalence neighbourhood, a novel approach was piloted in collaboration with the pharmacy of the health centre. During a two-year period, women aged 15-29 years who collected their contraceptives at the pharmacy were offered CT-test materials. Home-collected urine could be mailed to the laboratory and the general practitioner received the results. Nine percent of respondents were CT-positive (14% among 15-24 year-olds). There was a strong association with Surinamese/Antillean background. Uptake of the programme was low (27%). Net cost per pelvic inflammatory disease prevented ranged from cost-saving up to 3872 Euros in a low complication rate/high testing cost scenario. Faced with higher risk, but low participation rates, active case-detection of CT-infections in 'high-prevalence-areas' needs a concerted approach by different providers and community organizations, both in secondary and primary prevention. Pharmacists can contribute if proper liaison is made with primary care providers and/or public health services for (partner-)treatment, counselling and comprehensive sexual health care.

Hepatitis A virus immunity and seroconversion among contacts of acute hepatitis A patients in Amsterdam, 1996-2000: an evaluation of current prevention policy.

OBJECTIVES: We evaluated the hepatitis A virus (HAV) control policy (hygienic precautions and passive immunization with immune globulin) for "household contacts" (defined as all people who lived in the same house and who shared the same toilet with the patient, people who took care of an HAV-infected child, and sexual partners of the patient) of acute hepatitis A patients between 1996 and 2000. METHODS: We examined the characteristics and the serological outcomes of household contacts. All susceptible contacts were invited for retesting 6 weeks after they received immune globulin. RESULTS: Of 1242 contacts of 569 HAV patients, more than 50% (n = 672) were found to be HAV immune. Among the remaining contacts, 161 (28.2%) had a concurrent infection, and 86 of these individuals were symptomatic. The remaining 409 susceptible contacts received immune globulin, with 186 (45%) returning for retesting 6 weeks later (64 [34%] were infected, but only 12 had symptoms). CONCLUSIONS: Immune globulin does not protect all household contacts from HAV infection; however, it attenuates symptoms and effectively reduces further HAV transmission.

Much gained by integrating contact tracing and vaccination in the hepatitis B antenatal screening program in Amsterdam, 1992-1999.

BACKGROUND/AIMS: Hepatitis B control in Europe concentrates on antenatal screening to reduce vertical transmission. To reduce horizontal transmission and the pool of infectious individuals, the Municipal Health Service of Amsterdam integrated tracing and immunising of contacts in the antenatal screening program. METHODS: An eight year (1992-1999) descriptive study of this public health program, where contacts are tested for serological markers of previous infection, and vaccination is offered to susceptible contacts. Chronically infected contacts are counselled and referred for treatment if justified. RESULTS: For 738 newly identified women testing positive for the hepatitis B surface antigen, 1219 contacts were reported; 1100 (90.4%) contacts participated, 476 (43%) had serological markers of previous infection, of whom 119 (25%) were infectious. Of 603 eligible contacts, 568 (94%) completed the vaccination series. Country of origin was an independent predictor of contact participation and compliance with completion of the vaccination series. Postvaccination titres for antibodies against the surface antigen were below 10 IU/L in 4.5% of contacts under 30, in 12.2% of those over 30. CONCLUSIONS: Tracing and immunising susceptible contacts of women screened as HBsAg-positive, should be an integral component of any country's HBV control program.

Patterns of resistance associated with integrons, the extended-spectrum beta-lactamase SHV-5 gene, and a multidrug efflux pump of Klebsiella pneumoniae causing a nosocomial outbreak.

Multiresistant Klebsiella pneumoniae caused a nosocomial outbreak. Resistance patterns of the presumed outbreak isolates varied among and within patients. In order to control the outbreak, screening for extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae was commenced. A number of susceptible K. pneumoniae strains were stored to serve as controls in genetic strain typing. Typing by pulsed-field gel electrophoresis proved the clonality of the strains in the recognized outbreak patients. Typing of the control strains by pulsed-field gel electrophoresis showed that at least one patient had been missed by the ESBL screening procedure. Further genetic typing confirmed the presence of the SHV-5 ESBL gene in all but one of the outbreak strains. Variable presence of integrons that carried the aminoglycoside resistance genes aadB and aadA2 was found. A gyrA mutation in codon 83 was present in all outbreak strains tested, despite considerable differences in ciprofloxacin MICs. The MICs of ciprofloxacin and the chemically unrelated drug cefoxitin were correlated (r = 0.86, P < 0.01) and were compatible with the overexpression of an efflux pump in a subset of the outbreak strains. We conclude that outbreak strains that express an ESBL gene only at a low level may pass unnoticed in a screening procedure, when the laboratory is unaware of variable ESBL expression. In this particular outbreak, screening for strains for which ciprofloxacin MICs were > or =0.25 micro g/ml would in retrospect have been the most sensitive method for detection of the K. pneumoniae outbreak strain.

Nasopharyngeal carriage of potential bacterial pathogens related to day care attendance, with special reference to the molecular epidemiology of Haemophilus influenzae.

Nasopharyngeal carriage of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis was studied in 259 children attending day care centers (DCC) in Amsterdam, The Netherlands, and in 276 control children. The DCC children were sampled a second time after 4 weeks. Carriage rates for DCC children and controls were 58 and 37% for S. pneumoniae, 37 and 11% for H. influenzae, and 80 and 48% for M. catarrhalis, respectively. No increased antibiotic resistance rates were found in strains isolated from DCC children. All H. influenzae isolates were typed by random amplified polymorphic DNA (RAPD) analysis. Evidence for frequent transmission of H. influenzae strains within DCC was found. In the control group only two isolates (4%) displayed identical RAPD types versus 38% of strains from DCC children. Colonization with H. influenzae appeared to be short-lived in these children; more than half of the children harboring H. influenzae in the first sample were negative in the second sample, whereas most children still positive in the second sample had a different genotype than in the first sample. Of the newly acquired strains in the second sample, 40% were identical to a strain that had been found in a child in the same DCC in the first sample. DCC are to be considered epidemiological niches with a high potential for the spread of pathogenic microorganisms.