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- Baltekin, Özden, et al.
(author)
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Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging
- 2017
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:34, s. 9170-9175
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Journal article (peer-reviewed)abstract
- The emergence and spread of antibiotic-resistant bacteria are aggravated by incorrect prescription and use of antibiotics. A core problem is that there is no sufficiently fast diagnostic test to guide correct antibiotic prescription at the point of care. Here, we investigate if it is possible to develop a point-of-care susceptibility test for urinary tract infection, a disease that 100 million women suffer from annually and that exhibits widespread antibiotic resistance. We capture bacterial cells directly from samples with low bacterial counts (10(4) cfu/mL) using a custom-designed microfluidic chip and monitor their individual growth rates using microscopy. By averaging the growth rate response to an antibiotic over many individual cells, we can push the detection time to the biological response time of the bacteria. We find that it is possible to detect changes in growth rate in response to each of nine antibiotics that are used to treat urinary tract infections in minutes. In a test of 49 clinical uropathogenic Escherichia coli (UPEC) isolates, all were correctly classified as susceptible or resistant to ciprofloxacin in less than 10 min. The total time for antibiotic susceptibility testing, from loading of sample to diagnostic readout, is less than 30 min, which allows the development of a point-of-care test that can guide correct treatment of urinary tract infection.
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| 2. |
- Carlsson, Markus, et al.
(author)
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Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
- 2009
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
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Journal article (peer-reviewed)abstract
- Objective:To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Design:Prospective parallel-grouped placebo-controlled randomized interventional experimental study.Setting:University research unit.Subjects: Healthy pigs.Interventions:The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.Measurements and Main Results:During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Conclusions:Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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| 3. |
- Fraenkel, Carl-Johan, et al.
(author)
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The First Swedish Outbreak with VIM-2-Producing Pseudomonas aeruginosa, Occurring between 2006 and 2007, Was Probably Due to Contaminated Hospital Sinks
- 2023
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In: Microorganisms. - : MDPI. - 2076-2607. ; 11:4
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Journal article (peer-reviewed)abstract
- Multidrug-resistant Pseudomonas aeruginosa is an increasing clinical problem worldwide. The aim of this study was to describe the first outbreak of a Verona integron-borne metallo-ss-lactamase (VIM)-2-producing P. aeruginosa strain in Sweden and its expansion in the region. A cluster of multidrug-resistant P. aeruginosa appeared at two neighbouring hospitals in 2006. The isolates were characterized by PCR, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing. Patient charts, laboratory records, and hygiene routines were reviewed, and patients, staff, and the environment were screened. The investigation revealed a clonal outbreak of a VIM-2-producing P. aeruginosa strain belonging to the high-risk clonal complex 111, susceptible only to gentamicin and colistin. No direct contact between patients could be established, but most of them had stayed in certain rooms/wards weeks to months apart. Cultures from two sinks yielded growth of the same strain. The outbreak ended when control measures against the sinks were taken, but new cases occurred in a tertiary care hospital in the region. In conclusion, when facing prolonged outbreaks with this bacterium, sinks and other water sources in the hospital environment should be considered. By implementing proactive control measures to limit the bacterial load in sinks, the waterborne transmission of P. aeruginosa may be reduced.
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| 7. |
- Goscinski, Gunilla, et al.
(author)
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Propensity to release endotoxin after two repeated doses of cefuroxime in an in vitro kinetic model : Higher release after the second dose
- 2007
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In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 60:2, s. 328-333
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Journal article (peer-reviewed)abstract
- Objectives: To study endotoxin release from two strains of Escherichia coli after exposure to two repeated doses of cefuroxime in an in vitro kinetic model. Methods: Cefuroxime in concentrations simulating human pharmacokinetics was added to the bacterial solution with a repeated dose after 12 h. In another experiment, tobramycin was given concomitantly with the second dose of cefuroxime. Samples for viable counts and endotoxin analyses were drawn before the addition of antibiotics and at 2 and 4 h after each dose. Results: The propensity to release endotoxin, expressed as log10 endotoxin release (EU)/log10 killed bacteria, was higher after the second than after the first dose, 0.80 ± 0.04 and 0.65 ± 0.01, respectively, in the ATCC strain and 0.80 ± 0.04 and 0.65 ± 0.02, respectively, in the clinical strain (P < 0.001). Endotoxin was released earlier after the second dose (P < 0.001). Addition of tobramycin at the second dose reduced the endotoxin release in comparison with that of cefuroxime alone (P < 0.001). Conclusions: The propensity to liberate endotoxin is higher after the second dose of cefuroxime than after the first, resulting in a higher release of endotoxin than expected from bacterial count. The release after the second dose can be reduced by the addition of tobramycin.
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| 8. |
- Goscinski, Gunilla, et al.
(author)
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Release of SpeA from Streptococcus pyogenes after exposure to penicillin : dependency on dose and inhibition by clindamycin
- 2006
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:11-12, s. 983-987
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Journal article (peer-reviewed)abstract
- The amount and time course of SpeA release from group A streptococci (GAS) was studied at different starting inoculae after exposure to different doses of penicillin, clindamycin or a combination of the 2. The release was related to the bacterial concentration and killing rate. A clinical GAS strain was exposed to benzylpenicillin, 2 and 1000 × MIC, clindamycin, 2 and 32 × MIC, or combinations of the 2. Samples for viable counts and SpeA analyses were drawn before and after the addition of antibiotics and at 3, 6 and 24 h. The SpeA release was higher at low than at high concentrations of penicillin and the combination (both, p < 0.05). The addition of clindamycin to penicillin reduced SpeA production at both concentrations (p < 0.01). Most SpeA was released before 3 h, and for penicillin and the combination, the amount correlated to the number of killed bacteria during this period (r = 0.50; p < 0.05). A positive correlation was found between the inoculum size and the SpeA concentration at time zero (r = 0.54; p < 0.05). The SpeA concentration was dependent on the initial number of bacteria, the class of antibiotic, the dose of penicillin and the killing rate.
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| 10. |
- Granström, Brith, et al.
(author)
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Return to work after oropharyngeal cancer treatment-Highlighting a growing working-age population
- 2020
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In: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 42:8, s. 1893-1901
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Journal article (peer-reviewed)abstract
- Background To describe the frequency of patients returning to work after treatment for oropharyngeal cancer and to identify predictors and physical barriers that might interfere with the return to work process. Methods Cross-sectional study including 295 patients. Data were collected regarding work/sick leave situation at 1 month before diagnosis and 15 months after diagnosis. The situation before diagnosis was retrospectively recalled by the patients. Two subscales and two single items from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 were used. Data were analyzed with multivariate logistic regression. Results Fifteen months after diagnosis, 212 patients (72%) were working. To be working 15 months after diagnosis was associated with working before diagnosis. Swallowing difficulties, problems talking on the telephone, and physical appearance were negatively associated with returning to work. Conclusions The large number of individuals returning to work is encouraging for patients diagnosed with oropharyngeal cancer.
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