Population Pharmacokinetics of High-Dose Tigecycline in Patients with Sepsis or Septic Shock.

Tigecycline is a glycylcycline often used in critically ill patients as the antibiotic of last resort. The pharmacokinetics (PK) of tigecycline in intensive care unit (ICU) patients can be affected by severe pathophysiological changes so that standard dosing might not be adequate. The aim of this study was to describe population PK of high-dose tigecycline in patients with sepsis or septic shock and evaluate the relationship between individual PK parameters and patient covariates. The study population consisted of 37 adult ICU patients receiving a 200-mg loading dose of tigecycline followed by multiple doses of 100 mg every 12 h. Blood samples were collected at 0.5, 2, 4, 8, and 12 h after dose administration. A two-compartment model with interindividual (IIV) and interoccasion (IOV) variability in PK parameters was used to describe the concentration-time course of tigecycline. The estimated values of mean population PK parameters were 22.1 liters/h and 69.4 liters/h for elimination and intercompartmental clearance, respectively, and 162 liters and 87.9 liters for volume of the central and peripheral compartment, respectively. The IIV and IOV in clearance were less than 20%. The estimated values of distribution volumes were different from previously published values, which might be due to pathophysiological changes in ICU patients. No systematic relationship between individual PK parameters and patient covariates was found. The developed model does not show evidence that individual tigecycline dosing adjustment based on patient covariates is necessary to obtain the same target concentration in patients with sepsis or septic shock. Dosing adjustments should be based on the pathogens, their susceptibility, and PK targets.

Early diagnosis and treatment of invasive aspergillosis as a main determinant of outcome - review of literature according to the presented case report.

Although. Aspergillus spp infection is not the major cause of morbidity in Intensive Care Units (ICUs), mortality among patients treated for it is tremendous. Moreover, invasive aspergillosis (IA) is an independent risk factor of hospital costs and length of stay. The prevalence of this disease is inversely correlated with the immunocompetence of individuals; for instance, the incidence of IA among patients with leukemia is estimated as high as 12.7%. Although there is a significant improvement in the antifungal armamentarium, the appropriate treatment is still being given too late, mostly because of late diagnosis. As well as the diagnosis, the criteria for recognition of IA constitute a challenge. OBJECTIVE: The aim of this review, based on a case report, is to introduce the problem of poor diagnosis and treatment of IA, especially in the critical care settings. The presented scenario is an example which assists in showing the evidence-based medicine (EBM) approach to the treatment of fungal infections. Furthermore, to demonstrate the appropriate approach to diagnosis and treatment of invasive aspergillosis, the guidelines of The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) are presented. CONCLUSIONS: According to presented literature, Galactomannan assay enables early diagnosis and remains a specific and sensitive tool to diagnose Asppergillosis, both in serum and BAL fluid. The guidelines recommend voriconazole as a first line treatment in IA. Failure to detect and implement proper antifungal treatment may lead to fatal consequences, as in the presented case.

The effect of pre-emptive analgesia on the level of postoperative pain in women undergoing surgery for breast neoplasm.

AIM OF THE STUDY: Dynamic development of research on pain has resulted in the formulation of the concept of pre-emptive analgesia, which involves administration of analgesics before the first pain-producing stimulus appears. It is meant to prevent increased sensitivity to pain in the postoperative period. The aim of this study was to assess the possibilities of modifying the intensity of postoperative pain evaluated with the visual analogue scale (VAS) in patients after surgical treatment for breast neoplasm offered by pre-emptive analgesia. MATERIAL AND METHODS: The intensity of postoperative pain was measured immediately after the surgery as well as 6, 12, 18, and 24 hours later in 100 women who had undergone surgery for breast tumour. The correlation between experienced pain and the type of analgesic administered pre-emptively, including metamizole, tramadol, ketoprofen, and placebo was examined. The effect of other correlates such as the extensiveness of surgery, systolic and diastolic blood pressure, and heart rate on the level of experienced pain as well as the usefulness of physiological parameters for its assessment were also analysed. RESULTS: The conducted study demonstrated the effectiveness of tramadol (p = 0.004) and ketoprofen (p = 0.039) administered half an hour before the beginning of surgery, but there was no similar effect in the case of metamizole (p = 1.0). A positive correlation was observed between the level of experienced pain and blood pressure values (p < 0.001). Heart rate does not seem to be significantly linked with the intensity of experienced pain (p = 0.157).

Successful treatment of anti-NMDA receptor encephalitis with a prompt ovarian tumour removal and prolonged course of plasmapheresis: A case report.

Anti-N-methyl-d-aspartate-receptor (NMDAR) encephalitis is an uncommon autoimmune disorder with a wide spectrum of neuropsychiatric symptoms. There is a great requirement to emphasize the importance of a multidisciplinary team approach in the process of diagnosis and treatment of the potentially fatal condition, including psychiatrists, neurologists, gynaecologists and intensivists. Physicians must be aware that psychiatric and neurological disorders, which are typical features for NMDAR encephalitis in young women with ovarian tumours, may progress into status epilepticus and respiratory insufficiency. This disease can only be successfully treated with prompt surgical intervention and an early implementation of a wide array of immunosuppressive therapies. Optimal timing of initiation of therapeutic plasma exchange, as well as duration of treatment necessary to achieve desirable outcomes in patients with NMDAR remains unknown. The present case report aims to raise awareness about the importance of early implementation of this potentially life-saving therapy and continuing the treatment courses until full subsidence of symptoms.