| 1. |
- Sansone, Martina, et al.
(författare)
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Extensive Hospital In-Ward Clustering Revealed By Molecular Characterization of Influenza A Virus Infection.
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:9
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Tidskriftsartikel (refereegranskat)abstract
- Nosocomial transmission of influenza A virus (InfA) infection is not fully recognized. The aim of this study was to describe the characteristics of hospitalized patients with InfA infections during an entire season and to investigate in-ward transmission at a large, acute-care hospital.During the 2016-17 season, all hospitalized patients≥18 years old with laboratory-verified (real-time polymerase chain reaction) InfA were identified. Cases were characterized according to age; sex; comorbidity; antiviral therapy; viral load, expressed as cycle threshold values; length of hospital stay; 30-day mortality; and whether the InfA infection met criteria for a health care-associated influenza A infection (HCAI). Respiratory samples positive for InfA that were collected at the same wards within 7 days were chosen for whole-genome sequencing (WGS) and a phylogenetic analysis was performed to detect clustering. For reference, concurrent InfA strains from patients with community-acquired infection were included.We identified a total of 435 InfA cases, of which 114 (26%) met the HCAI criteria. The overall 30-day mortality rate was higher among patients with HCAI (9.6% vs 4.6% among non-HCAI patients), although the difference was not statistically significant in a multivariable analysis, where age was the only independent risk factor for death (P<.05). We identified 8 closely related clusters (involving≥3 cases) and another 10 pairs of strains, supporting in-ward transmission.We found that the in-ward transmission of InfA occurs frequently and that HCAI may have severe outcomes. WGS may be used for outbreak investigations, as well as for evaluations of the effects of preventive measures.
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| 2. |
- Kamerlin, Shina C. L., 1981-, et al.
(författare)
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Managing Coronavirus Disease 2019 Spread With Voluntary Public Health Measures : Sweden as a Case Study for Pandemic Control
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:12, s. 3174-3181
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe coronavirus disease 19 (COVID-19) pandemic has spread globally, causing extensive illness and mortality. In advance of effective antiviral therapies, countries have applied different public health strategies to control spread and manage healthcare need. Sweden has taken a unique approach of not implementing strict closures, instead urging personal responsibility. We analyze the results of this and other potential strategies for pandemic control in Sweden.MethodsWe implemented individual-based modeling of COVID-19 spread in Sweden using population, employment, and household data. Epidemiological parameters for COVID-19 were validated on a limited date range; where substantial uncertainties remained, multiple parameters were tested. The effects of different public health strategies were tested over a 160-day period, analyzed for their effects on intensive care unit (ICU) demand and death rate, and compared with Swedish data for April 2020.ResultsSwedish mortality rates are intermediate between rates for European countries that quickly imposed stringent public health controls and those for countries that acted later. Models most closely reproducing reported mortality data suggest that large portions of the population voluntarily self-isolate. Swedish ICU use rates remained lower than predicted, but a large fraction of deaths occurred in non-ICU patients. This suggests that patient prognosis was considered in ICU admission, reducing healthcare load at a cost of decreased survival in patients not admitted.ConclusionsThe Swedish COVID-19 strategy has thus far yielded a striking result: mild mandates overlaid with voluntary measures can achieve results highly similar to late-onset stringent mandates. However, this policy causes more healthcare demand and more deaths than early stringent control and depends on continued public will.
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| 3. |
- Svensson, Elin M., 1985-, et al.
(författare)
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Model-based meta-analysis of rifampicin exposure and mortality in Indonesian tuberculous meningitis trials
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:8, s. 1817-1823
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIntensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.MethodsAn individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750–1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.ResultsPharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%–6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3–2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival.ConclusionsHigher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.
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| 4. |
- Alsved, Malin, et al.
(författare)
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Sources of Airborne Norovirus in Hospital Outbreaks
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 70:10, s. 2023-2028
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Noroviruses are the major cause of viral gastroenteritis. Disease transmission is difficult to prevent and outbreaks in healthcare facilities commonly occur. Contact with infected persons and contaminated environments are believed to be the main routes of transmission. However, noroviruses have recently been found in aerosols and airborne transmission has been suggested. The aim of our study was to investigate associations between symptoms of gastroenteritis and presence of airborne norovirus, and to investigate the size of norovirus carrying particles.METHODS: Air sampling was repeatedly performed close to 26 patients with norovirus infections. Samples were analysed for norovirus RNA by RT-qPCR. The times since the patients' last episodes of vomiting and diarrhoea were recorded. Size separating aerosol particle collection was also performed in ward corridors.RESULTS: Norovirus RNA was found in 21 (24%) of 86 air samples from 10 different patients. Only air samples during outbreaks, or before a succeeding outbreak, tested positive for norovirus RNA. Airborne norovirus RNA was also strongly associated with a shorter time period since the last vomiting episode (odds ratio 8.1, p=0.04 within 3 hours since the last vomiting episode). The concentration of airborne norovirus ranged from 5-215 copies/m3, and detectable amounts of norovirus RNA were found in particles <0.95 µm and >4.51 µm.CONCLUSIONS: The results suggest that recent vomiting is the major source of airborne norovirus and imply a connection between airborne norovirus and outbreaks. The presence of norovirus RNA in submicrometre particles indicates that airborne transmission can be an important transmission route.
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| 5. |
- Dickstein, Yaakov, et al.
(författare)
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Acinetobacter Infections : Reply to Wilson et al
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:5, s. 1358-1359
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Dickstein, Yaakov, et al.
(författare)
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Colistin Resistance Development Following Colistin-Meropenem Combination Therapy Versus Colistin Monotherapy in Patients With Infections Caused by Carbapenem-Resistant Organisms
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:10, s. 2599-2607
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We evaluated whether carbapenem-colistin combination therapy given to patients with infections due to carbapenem-resistant Gram-negative organisms reduces the emergence of colistin resistance compared to colistin monotherapy.METHODS: This is a pre-planned analysis of a secondary outcome from a randomized controlled trial comparing colistin monotherapy with colistin-meropenem combination for the treatment of severe infections caused by carbapenem-resistant, colistin-susceptible Gram-negative bacteria. We evaluated rectal swabs taken on day 7 from enrollment or later for the presence of new colistin-resistant (ColR) isolates. We evaluated the emergence of any ColR isolate and the emergence of ColR Enterobacteriaceae (ColR-E).RESULTS: Data were available for 214 patients for the primary analysis; emergent ColR organisms were detected in 22 (10.3%). No difference was observed between patients randomized to treatment with colistin monotherapy (10/106, 9.4%) vs. patients randomized to colistin-meropenem combination therapy (12/108, 11.1%), p=0.669. ColR-E organisms were detected in 18/249 (7.2%) patients available for analysis. No difference was observed between the two treatment arms (colistin monotherapy 6/128 [4.7%] vs. combination therapy 12/121 [9.9%], p=0.111). Enterobacteriaceae as the index isolate was found to be associated with development of ColR-E (HR 3.875 95% CI 1.475-10.184, p=0.006).CONCLUSIONS: Carbapenem-colistin combination therapy did not reduce the incidence of colistin resistance emergence in patients with infections due to carbapenem-resistant organisms. Further studies are necessary to elucidate the development of colistin resistance and methods for its prevention.
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| 7. |
- Hansson, Karin, et al.
(författare)
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Tick-borne encephalitis (TBE) vaccine failures : A ten-year retrospective study supporting the rationale for adding an extra priming dose in individuals from the age of 50 years
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 70:2, s. 245-251
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Southern Sweden is endemic for tick borne encephalitis (TBE), with Stockholm County as one of the high-risk areas. The aim of this study was to describe cases of vaccine failures, and to optimize future vaccination recommendations.METHODS: Patients with TBE were identified in the notification database at the Department of Communicable Disease Control and Prevention in the county of Stockholm during 2006-2015. Vaccine failure was defined as TBE despite adherence to the recommended vaccination schedule with at least two doses. Clinical data were extracted from medical records.RESULTS: A total of 1004 TBE cases were identified, 53 (5%) were defined as vaccine failures. In this latter group the median age was 62 years (6-83). Forty-three (81%) patients were over 50 years of age and two were children. Approximately half of the patients had comorbidities with diseases affecting the immune system accounting for 26% of all cases.Vaccine failures following the third or fourth vaccine dose accounted for 36 (68%) of the patients. Severe and moderate TBE disease affected 81% of the cases.CONCLUSION: To our knowledge, this is the largest documented cohort of TBE-vaccine failures. Vaccine failure after five TBE-vaccine doses is rare. Our data provides rationale for adding an extra priming dose to the age group 50 years and older.
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| 8. |
- LaCourse, S. M., et al.
(författare)
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Importance of inclusion of pregnant and breastfeeding women in COVID-19 therapeutic trials
- 2020
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 71:15, s. 879-881
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Tidskriftsartikel (refereegranskat)abstract
- Investigators are employing unprecedented innovation in the design of clinical trials to rapidly and rigorously assess potentially promising therapies for COVID-19; this is in stark contrast to the continued near universal regressive practice of exclusion of pregnant and breastfeeding women from these trials. The few trials which allow their inclusion focus on post-exposure prophylaxis or outpatient treatment of milder disease, limiting the options available to pregnant women with severe COVID-19 to compassionate use of remdesivir, or off-label drug use of hydroxychloroquine or other therapies. These restrictions were put in place despite experience with these drugs in pregnant women. In this Viewpoint, we call attention to the need and urgency to engage pregnant women in COVID-19 treatment trials now in order to develop data-driven recommendations regarding the risks and benefits of therapies in this unique but not uncommon population. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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| 9. |
- Lenk, E. J., et al.
(författare)
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A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa-coendemic Areas : Cost Analysis of a Pilot in the Soa Health District, Cameroon
- 2020
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Ingår i: Clinical Infectious Diseases. - : NLM (Medline). - 1058-4838 .- 1537-6591. ; 70:8, s. 1628-1635
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. METHODS: Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. RESULTS: The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9-$3.6), US$5.2 ($4.5-$8.3), and US$5.4 ($4.6-$8.6), respectively. CONCLUSIONS: TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.
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| 10. |
- Susanto, Budi Octasari, et al.
(författare)
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Rifampicin can be given as flat-dosing instead of weight-band dosing
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:12, s. 3055-3060
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The weight-band dosing in tuberculosis treatment regimen has been implemented in clinical practice for decades. Patients will receive different number of fixed dose combination (FDC) tablets according to their weight-band. However, some analysis have shown that weight was not the best covariate to explain variability of rifampicin exposure. Furthermore, the rationale for using weight-band dosing instead of flat-dosing becomes questionable. Therefore, this study aimed to compare the average and the variability of rifampicin exposure after weight-band dosing and flat-dosing.METHODS: Rifampicin exposure were simulated using previously published population pharmacokinetics model at dose 10-40 mg/kg for weight-band dosing and dose 600-2400 mg for flat-dosing. The median AUC0-24h after day 7 and 14 were compared as well as the variability of each dose group between weight-band and flat-dosing.RESULTS: The difference of median AUC0-24h of all dose groups between flat-dosing and weight-band dosing were considered low (< 20%) except for the lowest dose. At the dose of 10 mg/kg (600 mg for flat-dosing), flat-dosing resulted in higher median AUC0-24h compared to the weight-band dosing. A marginal decrease in between-patient variability was predicted for weight-band dosing compared to flat-dosing.CONCLUSIONS: Weight-band dosing yields a small and non-clinically relevant decrease in variability of AUC0-24h.
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