We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of (14)C-PhIP (2 microM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72+/-0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of (14)C-PhIP from maternal to fetal circulation (FM ratio 0.90+/-0.08 at 6 h, p
The ABCG2 c.421C>A single-nucleotide polymorphism (SNP) was determined in 660 healthy Finnish volunteers, of whom 32 participated in a pharmacokinetic crossover study involving the administration of 20 mg atorvastatin and rosuvastatin. The frequency of the c.421A variant allele was 9.5% (95% confidence interval 8.1-11.3%). Subjects with the c.421AA genotype (n = 4) had a 72% larger mean area under the plasma atorvastatin concentration-time curve from time 0 to infinity (AUC(0-infinity)) than individuals with the c.421CC genotype had (n = 16; P = 0.049). In participants with the c.421AA genotype, the rosuvastatin AUC(0-infinity) was 100% greater than in those with c.421CA (n = 12) and 144% greater than in those with the c.421CC genotype. Also, those with the c.421AA genotype showed peak plasma rosuvastatin concentrations 108% higher than those in the c.421CA genotype group and 131% higher than those in the c.421CC genotype group (P
BACKGROUND: Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among Helicobacter pylori isolates. MATERIALS AND METHODS: We analyzed H. pylori data from the Centers for Disease Control and Prevention (CDC)'s sentinel surveillance in Alaska from July 1999 to June 2003 to determine the proportion of culture-positive biopsies from Alaska Native persons undergoing routine upper-endoscopy, and the susceptibility of H. pylori isolates to metronidazole [minimum inhibitory concentration (MIC) of > 8 g metronidazole/mL), clarithromycin (MIC > or = 1), tetracycline (MIC > or = 2) and amoxicillin (MIC > or = 1)] using agar dilution. RESULTS: Nine-hundred sixty-four biopsy specimens were obtained from 687 participants; 352 (51%) patients tested culture positive. Mean age of both culture-positive and culture-negative patients was 51 years. Metronidazole resistance was demonstrated in isolates from 155 (44%) persons, clarithromycin resistance from 108 (31%) persons, amoxicillin resistance from 8 (2%) persons, and 0 for tetracycline resistance. Metronidazole and clarithromycin resistance varied by geographic region. Female patients were more likely than male subjects to show metronidazole resistance (p
Enterococci are common causative agents in a broad range of human infections. Although formerly considered to be of low virulence, in recent years they have emerged as important pathogens, particularly in the hospital environment. Enterococci are not only intrinsically resistant to several antibiotics, but are also characterised by a potent and unique ability to exchange genetic material. With the increasing prevalence of strains resistant to ampicillin, aminoglycosides and glycopeptides, serious therapeutic difficulties have become more common. Epidemiological aspects, the mechanisms of action, the detection of antibiotic resistance, and the situation of enterococci in Sweden are discussed in the article.
Escherichia coli was the most commonly isolated pathogen in the Canadian Ward Surveillance Study 2007-2009 (3789 isolates). Susceptibility to cefazolin (34.1%), trimethoprim-sulfamethoxazole (73.8%), ciprofloxacin (78.4%), and levofloxacin (78.8%) was lowest. Susceptibility was above 90% for meropenem (100%), tigecycline (99.9%), piperacillin-tazobactam (97.6%), nitrofurantoin (96.9%), ceftazidime (95.6%), amoxicillin-clavulanate (94.9%), ceftriaxone (94.1%), cefoxitin (92.3%), and gentamicin (90.8%). Over the study period, there was a significant reduction in susceptibility to amoxicillin-clavulanate and trimethoprim-sulfamethoxazole for urinary tract isolates. Inpatient status was associated with greater resistance to nearly all antimicrobials including greater multidrug resistance (MDR). Increasing age was associated with resistance to fluoroquinolones, ceftriaxone, piperacillin-tazobactam, and MDR. Female gender was associated with susceptibility to fluoroquinolones and nitrofurantoin. In conclusion, greater antimicrobial resistance and MDR in E. coli were observed in inpatients, males, and with increasing age. The deterioration of susceptibility to trimethoprim-sulfamethoxazole continues with the greatest reduction in urinary isolates. Significant regional differences in resistance rates were apparent.
BACKGROUND: Rising numbers of bullous impetigo caused by Staphylococcus aureus resistant to fucidic acid have been seen in Norway over the last few years. MATERIAL AND METHODS: We present a population-based cohort study of an epidemic in an island community in western Norway with approximately 4450 people. The district's doctors agreed upon guidelines for regimes of antibiotic treatment; taking specimens for bacteriological examination was made routine procedure. The patients included in the study were identified from all patient files from all consultations with all doctors in the district. Clinical, therapeutical and bacteriological variables were registered. A comparison with the present Norwegian guidelines developed by a conference of experts is made. RESULTS: 108 patients were diagnosed as having bullous impetigo (2.4% of the population). Bacteriological swabs were taken from 95 (88%) patients. Staphylococcus aureuswas the bacteriologic aetiology in 79 (83%) of these and were found to be resistant to fusidic acid in 67 (85%) isolates. DISCUSSION: Our findings support the hypothesis that the rising numbers of impetigo might be caused by a clone of Staphylococcus aureus that is resistant to fusidic acid.
To describe the investigation and management of an outbreak due to multiresistant Acinetobacter baumannii and to determine risk factors for acquisition of the organism.
A 14-bed regional burn unit in a Canadian tertiary-care teaching hospital.
Case-control study with multivariate analysis of potential risk factors using logistic regression analysis. Surveillance cultures were obtained from the hospital environment, from noninfected patients, and from healthcare providers.
A total of 31 (13%) of 247 patients with acute burn injuries acquired multiresistant A. baumannii between December 1998 and March 2000; 18 (58%) of the patients were infected. The organism was recovered from the hospital environment and the hands of healthcare providers. Significant risk factors for acquisition of multiresistant A. baumannii were receipt of blood products (odds ratio [OR], 10.8; 95% confidence interval [CI95], 3.4 to 34.4; P
To investigate an outbreak of multidrug-resistant Pseudomonas aeruginosa in an intensive care unit (ICU).
Epidemiologic investigation, environmental assessment, and ambidirectional cohort study.
A secondary-care university hospital with a 10-bed ICU.
All patients admitted to the ICU receiving ventilator treatment from December 1, 1999, to September 1, 2000.
An outbreak in an ICU with multidrug-resistant isolates of P aeruginosa belonging to one amplified fragment-length polymorphism (AFLP)-defined genetic cluster was identified, characterized, and cleared. Molecular typing of bacterial isolates with AFLP made it possible to identify the outbreak and make rational decisions during the outbreak period. The outbreak included 19 patients during the study period. Infection with bacterial isolates belonging to the AFLP cluster was associated with reduced survival (odds ratio, 5.26; 95% confidence interval, 1.14 to 24.26). Enhanced barrier and hygiene precautions, cohorting of patients, and altered antibiotic policy were not sufficient to eliminate the outbreak. At the end of the study period (in July), there was a change in the outbreak pattern from long (December to June) to short (July) incubation times before colonization and from primarily tracheal colonization (December to June) to primarily gastric or enteral July) colonization. In this period, the bacterium was also isolated from water taps.
Complete elimination of the outbreak was achieved after weekly pasteurization of the water taps of the ICU and use of sterile water as a solvent in the gastric tubes.
BACKGROUND: Food-borne salmonella infections have become a major problem in industrialized countries. The strain of Salmonella enterica serotype typhimurium known as definitive phage type 104 (DT104) is usually resistant to five drugs: ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline. An increasing proportion of DT104 isolates also have reduced susceptibility to fluoroquinolones. METHODS: The Danish salmonella surveillance program determines the phage types of all typhimurium strains from the food chain, and in the case of suspected outbreaks, five-drug-resistant strains are characterized by molecular methods. All patients infected with five-drug-resistant typhimurium are interviewed to obtain clinical and epidemiologic data. In 1998, an outbreak of salmonella occurred, in which the strain of typhimurium DT104 was new to Denmark. We investigated this outbreak and report here our findings. RESULTS: Until 1997, DT104 infections made up less than 1 percent of all human salmonella infections. The strain isolated from patients in the first community outbreak of DT104 in Denmark, in 1998 was resistant to nalidixic acid and had reduced susceptibility to fluoroquinolones. The outbreak included 25 culture-confirmed cases. Eleven patients were hospitalized, and two died. The molecular epidemiology and data from patients indicated that the primary source was a Danish swine herd. Furthermore, the investigation suggested reduced clinical effectiveness of treatment with fluoroquinolones. CONCLUSIONS: Our investigation of an outbreak of DT104 documented the spread of quinolone-resistant bacteria from food animals to humans; this spread was associated with infections that were difficult to treat. Because of the increase in quinolone resistance in salmonella, the use of fluoroquinolones in food animals should be restricted.
Comment In: N Engl J Med. 2000 Mar 2;342(9):66110702060