INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování MeSH
- exsudáty a transsudáty metabolismus mikrobiologie MeSH
- infekce chirurgické rány * MeSH
- kardiochirurgické výkony * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- sternotomie * škodlivé účinky MeSH
- sternum chirurgie MeSH
- terapie ran pomocí řízeného podtlaku * metody MeSH
- vankomycin * aplikace a dávkování farmakokinetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- MeSH
- antibakteriální látky aplikace a dávkování farmakokinetika škodlivé účinky MeSH
- antifungální látky aplikace a dávkování farmakokinetika škodlivé účinky MeSH
- antivirové látky aplikace a dávkování farmakokinetika škodlivé účinky MeSH
- infekce dýchací soustavy * farmakoterapie MeSH
- lékové interakce MeSH
- lidé MeSH
- mikrobiota účinky léků MeSH
- monitorování léčiv MeSH
- monoklonální protilátky terapeutické užití MeSH
- nežádoucí účinky léčiv klasifikace patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Antibiotika jsou jednou z nejčastěji podávaných lékových skupin v intenzivní péči. Léčba kriticky nemocných s komunitními i nozokomiálními infekcemi má některá významná specifika oproti léčbě ambulantních pacientů či pacientů hospitalizovaných na standardních odděleních. Septické nemocné je nutno včasně léčit vhodně zvolenou empirickou antibiotickou léčbou v dostatečné dávce a v adekvátně zvolených dávkovacích intervalech. U těchto pacientů, na rozdíl od méně závažných stavů, nelze se začátkem antibiotické terapie vyčkávat. Farmakokinetika je u kriticky nemocných velmi často změněná, a navíc se dynamicky mění v průběhu onemocnění, proto je výhodné mít možnost monitorovat hladiny antibiotik v krvi a dle nich upravovat jejich dávkování. Zvolená terapie má být denně reevaluována a případně změněna na základě validních mikrobiologických výsledků. Vhodně provedená deeskalace je správným principem i u kriticky nemocných pacientů na jednotkách intenzivní péče. Článek se dotkne všech zmíněných aspektů a pokusí se nastínit zásady optimálně vedené antibiotické terapie v podmínkách intenzivní péče, podložené aktuálními znalostmi medicíny založené na důkazech.
Antibiotics are one of the most frequently administered groups of drugs in intensive care. The treatment of critically ill patients with community and nosocomial infections has some significant specifics compared to the treatment of outpatients or patients hospitalized in wards. Septic patients must be treated in a timely manner with an appropriately chosen empiric antibiotic treatment in a sufficient dose and at adequately selected dosing intervals. Compared to less serious conditions, these patients cannot wait to start antibiotic therapy. Pharmacokinetics is very often changed in critically ill patients, and it also changes dynamically during the course of the disease, so it is advantageous to be able to monitor the levels of antibiotics in the blood and adjust their dosage accordingly. The chosen therapy should be reevaluated daily and possibly adjusted based on valid microbiological results. Appropriately chosen de-escalation is the right principle even for critically ill patients in intensive care units. The article will touch on all the mentioned aspects and try to outline the principles of optimally guided antibiotic therapy in intensive care settings, supported by the current knowledge of evidence-based medicine.
- MeSH
- antibakteriální látky * farmakokinetika terapeutické užití MeSH
- antibiotická politika metody organizace a řízení MeSH
- farmakokinetika MeSH
- jednotky intenzivní péče * MeSH
- lidé MeSH
- monitorování léčiv metody MeSH
- péče o pacienty v kritickém stavu metody MeSH
- rozvrh dávkování léků MeSH
- sepse farmakoterapie MeSH
- způsoby aplikace léků MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- abdominální katastrofa,
- MeSH
- antibakteriální látky * farmakokinetika klasifikace terapeutické užití MeSH
- antifungální látky klasifikace terapeutické užití MeSH
- břišní dutina patologie MeSH
- lidé MeSH
- nitrobřišní infekce * etiologie farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
AIMS/HYPOTHESIS: The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. METHODS: For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). RESULTS: Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 μgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 μgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). CONCLUSIONS: Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování terapeutické užití MeSH
- diabetická noha * farmakoterapie metabolismus MeSH
- intravenózní podání MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrocirkulace * účinky léků MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: The objective of this study was to develop a population pharmacokinetic model of meropenem in a heterogeneous population of patients with a serious bacterial infection in order to propose dosing optimisation leading to improved achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target. METHODS: A total of 174 meropenem serum levels obtained from 144 patients during therapeutic drug monitoring were analysed using a non-linear mixed-effects modelling approach and Monte Carlo simulation was then used to compare various dosing regimens in order to optimise PK/PD target attainment. RESULTS: The meropenem volume of distribution of the patient population was 54.95 L, while clearance started at 3.27 L/hour and increased by 0.91 L/hour with each 1 mL/s/1.73 m2 of estimated glomerular filtration rate. Meropenem clearance was also 0.31 L/hour higher in postoperative patients with central nervous system infection. Meropenem administration by continuous infusion showed a significantly higher probability of attaining the PK/PD target than a standard 30 min infusion (95.3% vs 49.5%). CONCLUSIONS: A daily meropenem dose of 3 g, 6 g and 10.5 g administered by continuous infusion was shown to be accurate for patients with moderate to severe renal impairment, normal renal function to mild renal impairment and augmented renal clearance, respectively.
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování MeSH
- bakteriální infekce * farmakoterapie MeSH
- biologické modely * MeSH
- dospělí MeSH
- intravenózní infuze MeSH
- lidé středního věku MeSH
- lidé MeSH
- meropenem * farmakokinetika aplikace a dávkování MeSH
- metoda Monte Carlo MeSH
- monitorování léčiv metody MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: The objective of this study was to evaluate off-label high-dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug-resistant (XDR) Pseudomonas aeruginosa infections and then to compare the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target after standard and off-label high-dose regimens using population model-based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off-label high-dose ceftazidime treatment. METHODS: In patients treated with off-label high-dose ceftazidime (3 g every 6 h), blood samples were collected and ceftazidime serum levels measured using LC-MS/MS. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were then used to compare standard and high-dose regimens for PK/PD target attainment. RESULTS: A total of 14 cancer patients with serious infection suspected of XDR P. aeruginosa aetiology were eligible for PK analysis. XDR P. aeruginosa was confirmed in 10 patients as the causative pathogen. Population ceftazidime volume of distribution was 13.23 L, while clearance started at the baseline of 1.48 L/h and increased by 0.0076 L/h with each 1 mL/min/1.73 m2 of eGFR. High-dose regimen showed significantly higher probability of target attainment (i.e., 86% vs. 56% at MIC of 32 mg/L). This was translated into a very low mortality rate of 20%. Only one case of reversible neurological impairment was observed. CONCLUSION: We proved the superiority of the ceftazidime off-label high-dose regimen in PK/PD target attainment with very low occurrence of adverse effects. The off-label high-dose regimen should be used to optimize treatment of XDR P. aeruginosa infections.
- MeSH
- antibakteriální látky škodlivé účinky farmakokinetika MeSH
- ceftazidim škodlivé účinky farmakokinetika MeSH
- chromatografie kapalinová MeSH
- lidé MeSH
- metoda Monte Carlo MeSH
- mikrobiální testy citlivosti MeSH
- nádory * komplikace farmakoterapie MeSH
- off-label použití léčivého přípravku MeSH
- pseudomonádové infekce * farmakoterapie MeSH
- Pseudomonas aeruginosa MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Colistin is a lipopeptide antibiotic administered as an inactive prodrug-colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity, dependent on plasma concentrations. The number of patients with infections caused by multidrug-resistant Gram-negative bacteria sensitive only to colistin and the number of patients requiring extracorporeal membrane oxygenation (ECMO) support for severe respiratory failure increased significantly in association with COVID-19-induced infections. ECMO can generally affect the pharmacokinetics of drugs by creating a new compartment. METHODS AND ANALYSIS: The COL-ECMO2022 study is a prospective, non-randomised, single-centre, phase IV pharmacokinetic clinical trial designed to assess the influence of ECMO on the pharmacokinetics of colistin and CMS. Up to 30 patients treated with colistin will be included in the study and assigned to one of two arms, depending on the presence/absence of ECMO. All study participants will receive standard CMS dose intravenously. The plasma concentrations of colistin and CMS taken at defined intervals will be assessed by high-performance liquid chromatography-mass spectrometry. Patients will participate in the clinical trial for a maximum of three monitored dosing intervals. A population pharmacokinetic model will be developed to assess the influence of ECMO on pharmacokinetics. A difference greater than 25% is considered clinically significant. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of St. Anne's University Hospital Brno (Number 10ML/2022-AM). Related manuscripts will be submitted to peer-review journals. TRIAL REGISTRATION NUMBERS: EudraCT Number 2022-000291-19; NCT05542446.
- MeSH
- antibakteriální látky farmakokinetika MeSH
- COVID-19 * MeSH
- kolistin terapeutické užití MeSH
- kritický stav terapie MeSH
- lidé MeSH
- mimotělní membránová oxygenace * MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
