| 1. |
- Isaksson, Jenny, et al.
(författare)
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Comparison of species identification of endocarditis associated viridans streptococci using rnpB genotyping and 2 MALDI-TOF systems
- 2015
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Ingår i: Diagnostic Microbiology and Infectious Disease. - : Elsevier BV. - 0732-8893 .- 1879-0070. ; 81:4, s. 240-245
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus spp. are important causes of infective endocarditis but challenging in species identification. This study compared identification based on sequence determination of the rnpB gene with 2 systems of matrix-assisted laser desorption ionization-time of flight mass spectrometry, MALDI Biotyper (Bruker) and VITEK MS IVD (bioMerieux). Blood culture isolates of viridans streptococci from 63 patients with infective endocarditis were tested. The 3 methods showed full agreement for all 36 isolates identified in the Anginosus, Bovis, and Mutans groups or identified as Streptococcus cristatus, Streptococcus gordonii, or Streptococcus sanguinis. None of the methods could reliably identify the 23 isolates to the species level when designated as Streptococcus mitis, Streptococcus oralis, or Streptococcus tigurinus. In 7 isolates classified to the Mitis group, the rnpB sequences deviated strikingly from all reference sequences, and additional analysis of sodA and groEL genes indicated the occurrence of yet unidentified Streptococcus spp. (C) 2015 Elsevier Inc. All rights reserved.
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| 2. |
- Kurland, Siri, et al.
(författare)
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A 10-year retrospective study of infective endocarditis at a University Hospital with special regard to the timing of surgical evaluation in S. viridans endocarditis
- 1999
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Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548 .- 1651-1980. ; 31:1, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- A total of 154 episodes of infective endocarditis (IE) in 149 patients were studied retrospectively with special regard to the major aetiological groups and the surgical evaluation. There were 136 episodes of native valve endocarditis (NVE) (88%) and 18 episodes of prosthetic valve endocarditis (PVE) (12%). Three major groups of NVE crystallized: Streptococcus viridans in 37 (27%), Staphylococcus aureus in 39 (29%) and culture negative IE in 28 (21%) episodes. In these groups surgery during the active phase was required in 41, 28 and 18%, respectively. At the operation myocardial abscess was found in as many as 7/15 cases with S. viridans, but in only in 3/11 cases with S. aureus and 1/5 cases with culture negative IE. The mean duration of preoperative antibiotic treatment was 34 d. This long period of unsuccessful pharmacotherapy, preceded by a mean of 47 d from start of symptoms to admission to hospital, has probably resulted in the high frequency of myocardial abscess in S. viridans NVE. Surgical evaluation should be considered when fever persists beyond 10 d of adequate treatment, even in the absence of clinically apparent complications. Among the PVE episodes, 11/18 were managed with pharmacological treatment alone. Uncomplicated PVE may thus often be successfully treated with antibiotics alone.
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| 6. |
- Kurland, Siri, et al.
(författare)
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Human plasma protein levels alter the in vitro antifungal activity of caspofungin : An explanation to the effect in critically ill?
- 2022
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Ingår i: Mycoses. - : John Wiley & Sons. - 0933-7407 .- 1439-0507. ; 65:1, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUCtot/MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated.ObjectivesFungal killing activity of caspofungin in vitro was investigated under varying levels of human plasma protein.MethodsTime-kill studies were performed with clinically relevant caspofungin concentrations of 1-9 mg/L on four blood isolates of C. glabrata, three susceptible and one strain with reduced susceptibility, in human plasma and plasma diluted to 50% and 25% using Ringer's acetate.ResultsEnhanced fungal killing of the three susceptible strains was observed in plasma with lower protein content (p < .001). AUCtot/MIC required for a 1 log10 CFU/ml kill at 24 h in 50% and 25% plasma was reduced with 36 + 12 and 80 + 9%, respectively. The maximum effect was seen at total caspofungin concentrations of 4–9 × MIC. For the strain with reduced susceptibility, growth was significantly decreased at lower protein levels.ConclusionsReduced human plasma protein levels increase the antifungal activity of caspofungin in vitro, most likely by increasing the free concentration. Low plasma protein levels in critically ill patients with candidemia might explain a better response to caspofungin than expected from generally accepted target attainment and should be taken into consideration when assessing TDM based on total plasma concentrations.
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| 7. |
- Kurland, Siri
(författare)
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Invasive Candida infections : Treatment of the critically ill and patients with infective endocarditis
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Invasive Candida infections have a major impact on morbidity and mortality in critically ill patients. Prompt initiation of effective antifungal therapy and source control are cornerstones in management. The echinocandin caspofungin is first-line treatment in invasive Candida infections and dosage is based on the Child-Pugh liver scoring system, developed for patients with chronic liver disease. Pathophysiological changes in the critically ill, e.g. hypoalbuminemia, may affect antifungal pharmacokinetics (PK) and drug exposure, calling into question if dosage regimens are adequate for this group. Candida infective endocarditis (CIE) is a rare but serious form of deep-seated Candida infection, burdened with high mortality rates. The standard of care has been antifungal therapy combined with cardiac valve surgery. The overall aim of this thesis was to study aspects of invasive Candida infections in relation to caspofungin pharmacokinetics and pharmacodynamics (PK/PD) and the management of patients with CIE.In a prospective study of critically ill patients, we investigated the prevalence of hepatic impairment, the effect of Child-Pugh score on caspofungin PK and whether caspofungin PK/PD targets were achieved. The prevalence of patients with pathological liver function tests was high, but the Child-Pugh score did not significantly impact caspofungin PK. The PK/PD target was reached, but with small margins. No dose reduction is warranted in critically ill patients with hepatic impairment, in the absence of chronic liver disease.The impact of plasma protein levels on the antifungal activity of caspofungin at clinically relevant concentrations was studied in time-kill experiments. Reduced plasma protein levels in vitro increased caspofungin’s fungicidal effect on Candida glabrata. In a retrospective observational study, we compared the effect of echinocandins, mainly caspofungin, on the outcome in patients with CIE with those of other antifungal regimens. We found no significant differences in outcome between regimens. Further investigation of the CIE cohort showed that Candida parapsilosis was overrepresented in CIE compared with candidemia, indicating a higher propensity to cause CIE. In the overall CIE cohort, surgery did not improve outcome. Therefore, the recommendation of surgery in all patients with CIE may be questioned. Long-term suppressive antifungal therapy reduced the number of relapses.
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| 8. |
- Kurland, Siri, et al.
(författare)
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Pharmacokinetics of Caspofungin in Critically Ill Patients in Relation to Liver Dysfunction : Differential Impact of Plasma Albumin and Bilirubin Levels
- 2019
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 63:6
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Tidskriftsartikel (refereegranskat)abstract
- Caspofungin has a liver-dependent metabolism. Reduction of the dose is recommended based on Child-Pugh (C-P) score. In critically ill patients, drug pharmacokinetics (PK) may be altered. The aim of this study was to investigate the prevalence of abnormal liver function tests, increased C-P scores, their effects on caspofungin PK, and whether pharmacokinetic-pharmacodynamic (PK/PD) targets were attained in patients with suspected candidiasis. Intensive care unit patients receiving caspofungin were prospectively included. PK parameters were determined on days 2, 5, and 10, and their correlations to the individual liver function tests and the C-P score were analyzed. Forty-six patients were included with C-P class A (n = 5), B (n = 40), and C (n = 1). On day 5 (steady state), the median and interquartile range for area under the curve from 0 to 24 h (AUC(0-24)), clearance (CL), and central volume of distribution (V-1) were 57.8 (51.6 to 69.8) mg.h/liter, 0.88 (0.78 to 1.04) liters/h, and 11.9 (9.6 to 13.1) liters, respectively. The C-P score did not correlate with AUC(0-24) (r = 0.03; P = 0.84), CL (r = -0.07; P = 0.68), or V-1 (r = 0.19; P = 0.26), but there was a bilirubin-driven negative correlation with the elimination rate constant (r = -0.46; P = 0.004). Hypoalbuminemia correlated with low AUC(0-24) (r = 0.45; P = 0.005) and was associated with higher clearance (r = -0.31; P = 0.062) and somewhat higher V-1 (r = -0.15; P = 0.37), resulting in a negative correlation with the elimination rate constant (r = -0.34; P = 0.042). For Candida strains with minimal inhibitory concentrations of >= 0.064 mu g/ml, PK/PD targets were not attained in all patients. The caspofungin dose should not be reduced in critically ill patients in the absence of cirrhosis, and we advise against the use of the C-P score in patients with trauma- or sepsis-induced liver injury.
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| 10. |
- Ostrowska, Bozena, et al.
(författare)
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Device infections related to cardiac resynchronization therapy in clinical practice-An analysis of its prevalence, risk factors and routine surveillance at a single center university hospital.
- 2021
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Ingår i: Clinical Cardiology. - : John Wiley & Sons. - 0160-9289 .- 1932-8737. ; 44:6, s. 739-747
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The implantation rates of cardiac implantable electronic devices have steadily increased, accompanied by a steeper rise of device related infections (DRI).HYPOTHESIS: The prevalence of DRI for cardiac resynchronization therapy (CRT) is higher in clinical practice than reported previously, even at a university hospital, and likely higher than reported to the national device registry.METHODS: Electronic medical records of consecutive patients undergoing a CRT procedure between January 2016 and December 2017 were analyzed. Clinical history, procedure related variables and complications were reviewed by specialists in cardiology and infectious diseases.RESULTS: A total of 171 patients, mean aged 74 years, 138 males (80.7%) were included. Twelve DRI occurred in 10 patients during mean 2.5 years follow-up, giving a prevalence of 7% (incidence of 29/1000 person-years). Reoperation, pocket haematoma, ≥3 procedures, previous device infection and indwelling central venous line were the strongest predictive factors according to univariate analysis. Out of 63/171 (36.8%) major complications, 31(49.2%) were lead-related. There were 49/171 (28.7%) reoperations and 15/171 (8.8%) minor complications. The number major complications and DRI reported to the national device registry were 7/171 (4.1%) and 2/171 (0.6%), respectively, reflecting a 5-fold underreporting.CONCLUSIONS: The high rate of CRT device infections is in sharp contrast to those reported by others and to the national device registry. Although a center specific explanation cannot be excluded, the high rates highlight a major issue with registries, reinforcing the need for better surveillance and automatic reporting of device related complications.
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