Introduction Because of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety. Materials and methods This review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy. Conclusions and discussion Amphotericin B is eliminated unchanged via urine and faeces. Flucytosine and fluconazole display low protein binding and are eliminated by the kidney. Itraconazole, voriconazole, posaconazole and isavuconazole are metabolised in the liver. Azoles are substrates and inhibitors of cytochrome P450 (CYP) isoenzymes and are therefore involved in numerous drug–drug interactions. Anidulafungin is spontaneously degraded in the plasma. Caspofungin and micafungin undergo enzymatic metabolism in the liver, which is independent of CYP. Although several drug–drug interactions occur during caspofungin and micafungin treatment, echinocandins display a lower potential for drug–drug interactions. Flucytosine and azoles penetrate into most of relevant tissues. Amphotericin B accumulates in the liver and in the spleen. Its concentrations in lung and kidney are intermediate and relatively low myocardium and brain. Tissue distribution of echinocandins is similar to that of amphotericin. Combination antifungal therapy is established for cryptococcosis but controversial in other IFIs such as invasive aspergillosis and mucormycosis.

Base excess (BE) and lactate concentration may predict mortality in critically ill patients. However, the predictive values of alactic BE (aBE; the sum of BE and lactate), or a combination of BE and lactate are unknown. The study aimed to investigate whether BE, lactate, and aBE measured on admission to ICU may predict the 28-day mortality for patients undergoing any form of shock. In 143 consecutive adults, arterial BE, lactate, and aBE were measured upon ICU admission. Receiver Operating Curve (ROC) characteristics and Cox proportional hazard regression models (adjusted to age, gender, forms of shock, and presence of severe renal failure) were then used to investigate any association between these parameters and 28-day mortality. aBE < −3.63 mmol/L was found to be associated with a hazard ratio of 3.19 (HR; 95% confidence interval (CI): 1.62–6.27) for mortality. Risk of death was higher for BE < −9.5 mmol/L (HR: 4.22; 95% CI: 2.21–8.05), particularly at lactate concentrations > 4.5 mmol/L (HR: 4.62; 95% CI: 2.56–8.33). A 15.71% mortality rate was found for the combined condition of BE > cut-off and lactate < cut-off. When BE was below but lactate above their respective cut-offs, the mortality rate increased to 78.91%. The Cox regression model demonstrated that the predictive values of BE and lactate were mutually independent and additive. The 28-day mortality in shock patients admitted to ICU can be predicted by aBE, but BE and lactate deliver greater prognostic value, particularly when combined. The clinical value of our findings deserves further prospective evaluation.

Patients with sepsis admitted to the intensive care unit often present with acid-base disorders. As the traditional interpretation might be clinically misleading, an alternative approach described by Stewart may allow one to quantify the individual components of acid-base abnormalities and provide an insight into their pathogenesis. The aim of our study was to compare the traditional and Stewart approaches in the analysis of acid-base disturbance. We analyzed arterial blood gases (ABG) taken from 43 ICU septic patients from admission to discharge categorising them according to SBE values. The traditional concept analysis was compared with the physicochemical approach using the Stewart equations. 990 ABGs were analysed. In the SBE < -2 mEq L⁻¹ group, hyperlactatemia was observed in 34.7% ABG, hypoalbuminemia in 100% and SIG acidosis in 42% ABG. Moreover, a Cl/Na ratio > 0.75 was present in 96.9% ABG. In the normal range SBE group, elevated lactates were present in 21.3% ABG, SIG acidosis in 14.9%, elevated Cl/Na ratio in 98.4% and hypoalbuminemia in all 324 ABG. In the metabolic alkalosis group (SBE > +2 mEq L⁻¹), hyperlactatemia was observed in 18.4% ABG, SIG acidosis in 5% ABG, Cl/Na ratio> 0.75 in 88.8%, while 99.1% samples revealed hypoalbuminemia. The use of the Stewart model may improve our understanding of the underlying pathophysiological mechanism and the true etiology of the derangements of acid-base disorders. Indeed, it proves that patients may suffer from mixed arterial blood gas disorders hidden under normal values of SBE and pH.

African trypanosomiasis is a parasitic infection sporadically imported to Europe by tourists or immigrants returning from endemic areas. We present the first and an unusual case of East African trypanosomiasis imported to Poland by a patient returning from a tourist trip to Uganda and Rwanda, which was successfully treated with pentamidine.

Dexmedetomidine (DEX) is a fairly new alfa₂-agonist which has been increasingly used in recent years for analgosedation, mostly because it offers a unique ability of providing both moderate level of sedation and analgesia without respiratory depression. Despite of many papers published, there are still only a few concerning the PK of the drug given as long-term infusion in ICU patients. The aim of this work was to characterize the population pharmacokinetics of dexmedetomidine and to investigate the potential benefits of individualization of drug dosing based on patient characteristics in the heterogeneous group of medical and surgical patients staying in intensive care unit. This study was performed in the group of 17 males and 10 females patients with a median age of 59.5 years and median body weight of 75 kg. Blood samples for dexmedetomidine assay were collected from arterial catheter, during and after discontinuation of a standard infusion, that ranged from 24 to 102 h. The following covariates were examined to influence dexmedetomidine PK: age, sex, body weight, patients’ health status described by Sequential Organ Failure Assessment Score (SOFA), inotropes usage, and infusion duration. The dexmedetomidine PK was best described by a two-compartment model. The typical values of PK parameters were estimated as 27 L for the volume of the central compartment, 87.6 L for the volume of the peripheral compartment, 38.5 L/h (9.2 mL/min/kg for a 70 kg patient) for systemic clearance and 46.4 L/h for the distribution clearance. Those values are consistent with literature findings. We were unable to show any significant relationship between collected covariates and dexmedetomidine PK. This study does not provide sufficient evidence to support the individualization of dexmedetomidine dosing based on age, sex, body weight, SOFA, and infusion duration.