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- Damgaard, Tobias, et al.
(författare)
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Estimated glomerular filtration rate as a tool for early identification of patients with insufficient exposure to beta-lactam antibiotics in intensive care units
- 2024
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Ingår i: Infectious Diseases. - : Taylor & Francis Group. - 2374-4235 .- 2374-4243.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Only about 50% of intensive care unit (ICU) patients reach a free trough concentration above MIC (100% fT > MIC) of beta-lactam antibiotics. Although dose adjustments based on therapeutic drug monitoring (TDM) could be beneficial, TDM is not widely available. We investigated serum creatinine-based estimated GFR (eGFR) as a rapid screening tool to identify ICU patients at risk of insufficient exposure. Method: Ninety-three adult patients admitted to four ICUs in southeast Sweden treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Beta-lactam trough concentrations were measured. The concentration target was set to 100% fT > MICECOFF (2, 4, and 16 mg/L based on calculated free levels for meropenem, cefotaxime, and piperacillin, respectively). eGFR was primarily determined via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and compared to three other eGFR equations. Data was analysed using logistic regression and receiver operative characteristic (ROC) curves. Results: With intermittent standard dosing, insufficient exposure was common in patients with a relative eGFR >= 48mL/min/1.73m(2) [85%, (45/53)], particularly when treated with cefotaxime [96%, (24/25)]. This eGFR cut-off had a sensitivity of 92% and specificity of 82% (AUC 0.871, p < 0.001) in identifying insufficient exposure. In contrast, patients with eGFR <48mL/min/1.73m(2) had high target attainment [90%, (36/40)] with a wide variability in drug exposure. There was no difference between the four eGFR equations (AUC 0.866-0.872, cut-offs 44-51 ml/min/1.73m(2)). Conclusion: Serum creatinine-based eGFR is a simple and widely available surrogate marker with potential for early identification of ICU patients at risk of insufficient exposure to piperacillin, meropenem, and cefotaxime.
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- Hammarström, Helena, et al.
(författare)
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Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies
- 2023
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Ingår i: Clinical Infectious Diseases. - : University of Chicago Press. - 1058-4838 .- 1537-6591. ; 76:3, s. e1252-e1260
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies have reported that reduced dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP) but data is lacking for patients with hematologic malignancies.METHODS: This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at six Swedish University Hospitals. Treatment with 7.5-15 mg TMP/kg/day (reduced dose) was compared with >15-20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (ΔPaO2/FiO2) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30.RESULTS: Out of a total of 113 included patients, 80 patients received reduced dose, and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, neither before nor after controlling for potential confounders in an adjusted regression model (-13,6 mmHg [95% CI -56,7-29,5] and -9,4 mmHg, [95% CI -50.5-31.7], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups, 18% vs. 21% and 14% vs. 15%, respectively. Among patients with mild to moderate pneumonia, defined as PaO2/FiO2>200 mmHg, all 44 patients receiving reduced dose were alive at day 30.CONCLUSION: In this cohort of 113 patients with hematologic malignancies, reduced dose TMP-SMX was effective and safe for treating mild to moderate PJP.
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- Holmbom, Martin, 1984-, et al.
(författare)
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Fluoroquinolone-resistant Escherichia coli among the rectal flora is the predominant risk factor for severe infection after transrectal ultrasound-guided prostate biopsy : a prospective observational study
- 2023
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden. - 2168-1805 .- 2168-1813. ; 58, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infection of the prostate gland following biopsy, usually with Escherichia coli, is a common complication, despite the use of antimicrobial prophylaxis. A fluoroquinolone (FQ) is commonly prescribed as prophylaxis. Worryingly, the rate of fluoroquinolone-resistant (FQ-R) E. coli species has been shown to be increasing. OBJECTIVE: This study aimed to identify risk factors associated with infection after transrectal ultrasound-guided prostate biopsy (TRUS-Bx). METHODS: This was a prospective study on patients undergoing TRUS-Bx in southeast Sweden. Prebiopsy rectal and urine cultures were obtained, and antimicrobial susceptibility and risk-group stratification were determined. Multivariate analyses were performed to identify independent risk factors for post-biopsy urinary tract infection (UTI) and FQ-R E. coli in the rectal flora. RESULTS: In all, 283 patients were included, of whom 18 (6.4%) developed post-TRUS-Bx UTIs. Of these, 10 (3.5%) had an UTI without systemic inflammatory response syndrome (SIRS) and 8 (2.8%) had a UTI with SIRS. Being in the medium- or high-risk groups of infectious complications was not an independent risk factor for UTI with SIRS after TRUS-Bx, but low-level FQ-resistance (minimum inhibitory concentration (MIC): 0.125-0.25 mg/L) or FQ-resistance (MIC > 0.5 mg/L) among E. coli in the faecal flora was. Risk for SIRS increased in parallel with increasing degrees of FQ-resistance. Significant risk factor for harbouring FQ-R E.coli was travelling outside Europe within the previous 12 months. CONCLUSION: The predominant risk factor for UTI with SIRS after TRUS-Bx was FQ-R E. coli among the faecal flora. The difficulty in identifying this type of risk factor demonstrates a need for studies on the development of a general approach either with rectal swab culture for targeted prophylaxis, or prior rectal preparation with a bactericidal agent such as povidone-iodine before TRUS-Bx to reduce the risk of FQ-R E. coli-related infection.
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- Krifors, Anders, et al.
(författare)
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Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden : a prospective multicentre cohort study
- 2024
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 56:2, s. 110-115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden.METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and β-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions.RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, β-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01).CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care.TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.
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- Woksepp, Hanna, et al.
(författare)
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Simultaneous Measurement of 11 Antibiotics for use in the Intensive Care Unit by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry
- 2022
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Ingår i: Therapeutic Drug Monitoring. - Philadelphia, PA, United States : Lippincott Williams & Wilkins. - 0163-4356 .- 1536-3694. ; 44:2, s. 308-318
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies indicate that a high proportion of patients in the intensive care unit (ICU) fail to attain adequate antibiotic levels. Thus, there is a need to monitor the antibiotic concentration to ensure effective treatment. Herein, the authors aimed to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification of antimicrobials to assess individualized therapeutic drug monitoring (TDM).METHODS: A UHPLC-MS/MS method with 11 antibiotics (ciprofloxacin, moxifloxacin, benzylpenicillin, levofloxacin, linezolid, rifampicin, meropenem, cloxacillin, cefotaxime, clindamycin, and piperacillin) was developed. Chromatographic separation was performed using a Kinetex biphenyl reversed-phase column, with gradient elution using 0.1% formic acid (FA) and methanol with 0.1% FA. Sample preparation was performed using methanol protein precipitation. The total run time was 5 min.RESULTS: For all analytes, the inter-assay inaccuracies for calibrators were ≤5%. The inter-day inaccuracies for the quality controls (QCs) were ≤5% for all analytes. The inter-assay precision for calibration standards ranged between 1.42% and 6.11%. The inter-assay imprecision for QCs of all antibiotics and concentrations ranged between 3.60% and 16.1%. Inter-assay inaccuracy and imprecision for the QCs and calibration standards were ≤15% for all drugs, except benzylpenicillin.CONCLUSION: A rapid UHPLC-MS/MS method was developed for the simultaneous quantification of 11 different antibiotics. Minimal sample preparation was required to ensure a rapid turnaround time. The method was applied to clinical samples collected from four ICUs.
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