Marcel Hochreiter

Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial.

IntroductionThe development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients.MethodsAll patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to <1 ng/ml or the PCT value was >1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days.ResultsA total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome.ConclusionsMonitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine.AnnotationResults were previously published in German in Anaesthesist 2008; 57: 571–577 (PMID: 18463831).Trial registrationISRCTN10288268

Pretransplant model for end stage liver disease score predicts posttransplant incidence of fungal infections after liver transplantation.

Liver transplant recipients are at a significant risk for invasive fungal infections (IFI). This retrospective study evaluated the impact of the pretransplant model for end stage liver disease (MELD) on the incidence of posttransplant IFI in a single centre. From 2004 to 2008, 385 liver transplantations were included, from which 210 transplantations were conducted allocated by Child Turcotte Pugh and 175 were allocated by MELD score. Both groups differed regarding the age of transplant recipients (50.1 ± 10.7 vs. 52.5 ± 9.9, P = 0.036), pretransplant MELD score (16.43 ± 8.33 vs. 18.29 ± 9.05), rate of re‐transplantations, duration of surgery, demand in blood transfusions and rates of renal impairments. In the MELD era, higher incidences of IFI (pre‐MELD 11.9%, MELD 24.0%, P < 0.05) and Candida infections (9% vs. 18.9%, P < 0.05) were observed. There was no difference in the incidence of probable or possible aspergillosis. Mortality, length of stay in intensive care or hospital, and duration of mechanical ventilation did not differ between the pre‐MELD and MELD era. Regardless the date of transplantation, patients with fungi‐positive samples showed higher mortality rates than patients without. MELD score was analysed as independent predictors for posttransplant IFI. Higher MELD scores predispose to a more problematic postoperative course and are associated with an increase in fungal infections.

Prognostic impact of lymph node involvement and the extent of lymphadenectomy (LAD) in adenocarcinoma of the esophagogastric junction (AEG)

BackgroundThe prognostic importance of lymph node (LN) involvement for patients with adenocarcinoma of the esophagogastric junction (AEG) is well-known. In the latest edition of the UICC staging system, the number of metastatic LNs was taken into account, while the extent of lymphadenectomy (LAD) remains unaddressed. Removal of at least six LNs is recommended, but there is no defined minimum number as to classify as (y)pN0. We examined the prognostic value of the number of positive LNs, number of LNs removed, and LN ratio (LNR) in order to determine the influence of an adequate LAD on overall survival (OS).MethodsWe analyzed data of 316 patients with AEG treated in our institution (2001–2011) regarding clinicopathological data, treatment, morbidity, mortality, and long-term prognosis. Univariate and multivariate analysis was performed using Cox regression to evaluate the prognostic impact of(y)pN category, number of LNs removed and LNR.ResultsOS decreased with higher count of positive LNs (p < 0.001) and higher LNR (p < 0.001). Whether >6, >15, or >30 LNs were removed did not influence OS, neither in the entire study population nor within individual (y)pT or (y)pN categories. Multivariate analysis revealed LNR (p < 0.001) besides M category (p = 0.015) and tracheotomy during the postoperative course (p = 0.005) as independent predictors of OS.ConclusionThe classification according to the number of involved LNs in the latest edition of the UICC staging system improves prognostication in patients with AEG. The importance of an adequate LAD is shown by the high prognostic relevance of the LNR rather than the absolute number of LNs removed.

Antibiotikatherapie bei operativen Intensivpatienten

The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p<0.001) without unfavorable effects on clinical outcome.

How much European prescribing physicians know about invasive fungal infections management

BackgroundThe use of systemic antifungal agents has increased in most tertiary care centers. However, antifungal stewardship has deserved very little attention. Our objective was to assess the knowledge of European prescribing physicians as a first step of an international program of antifungal stewardship.MethodsStaff physicians and residents of 4 European countries were invited to complete a 20-point questionnaire that was based on current guidelines of invasive candidiasis and invasive aspergillosis.Results121 physicians (44.6% staff, 55.4% residents) from Spain 53.7%, Italy 17.4%, Denmark 16.5% and Germany 12.4% completed the survey. Hospital departments involved were: medical 51.2%, ICUs 43%, surgical 3.3% and pharmaceutical 2.5%. The mean score of adequate responses (± SD) was 5.8 ± 1.7 points, with statistically significant differences between study site and type of physicians. Regarding candidiasis, 69% of the physicians clearly distinguished colonization from infection and the local rate of fluconazole resistance was known by 24%. The accepted indications of antifungal prophylaxis were known by 38%. Regarding aspergillosis, 52% of responders could differentiate colonization from infection and 42% knew the diagnostic value of galactomannan. Radiological features of invasive aspergillosis were well recognized by 58% of physicians and 57% of them were aware of the antifungal considered as first line treatment. However, only 37% knew the recommended length of therapy.ConclusionsThis simple, easily completed questionnaire enabled us to identify some weakness in the knowledge of invasive fungal infection management among European physicians. This survey could serve as a guide to design a future tailored European training program.

Acid–base balance during muscular exercise: response to Dr. Böning and Dr. Maassen

We appreciate the interest of Böning and Maassen in our article on exercise and acid–base homeostasis previously published in this journal (Lühker et al. 2017). In their comment, the authors postulate that the Henderson–Hasselbalch approach is more appropriate than Stewart’s approach to acid–base balance and pH regulation. The long-lasting controversy about the superiority of the one compared to the other approach has yielded a bulk of literature and pro-con debates including distinguished researchers and clinicians. Currently, there is no clear evidence which of the ‘modern’ approaches, the Stewart approach or the bicarbonate-centred Henderson–Hasselbalch approach, is the most suitable under all circumstances. One criticism regarding the Henderson–Hasselbalch approach is that it depends solely on bicarbonate (HCO3), carbon dioxide (CO2), and the respective dissociation constant. The Stewart approach considers this relationship as important contributor to acid–base balance but expands this description to a total of six physicochemical equations. As addressed by Böning and Maassen, the Henderson–Hasselbalch equation is derived from a chemical equation. We agree that this equation sufficiently describes acid–base changes under a variety of clinical and experimental circumstances. However, the validity of an equation depends on the given situation, and for many acid–base phenomena, the Stewart approach appears to provide deeper insights than the bicarbonate-centred approaches (Story 2004). Our study (Lühker et al. 2017) suggests that exercise during normoxia and hypoxia is one of these phenomena. One major ingredient of the human body is water. Therefore, virtually, all processes take place in an aqueous solution and the dissociation of water is a central element of Stewart’s approach. Water is the almost infinite source of hydrogen ions, whose concentrations define the actual acid–base condition. Böning and Maassen postulate that changes of strong ions cannot be causative for changes in acid–base balance during exercise but rather mirror them in one compartment, while the opposite may happen in the neighbouring one. During exercise, there are, in fact, multiple and simultaneously occurring chemical, physical, and physiological reactions of which ion shifts are an essential part. The assumption that these ion shifts only mirror changes in acid–base homeostasis without affecting other ongoing processes is probably too simplistic. Because both strong and weak ions, as well as CO2, affect the dissociation of water, a change in any of these variables ultimately leads to a change in hydrogen ions and hydroxyl ions (Lindinger and Heigenhauser 2008). The ion movements during exercise follow the laws of mass conservation, mass action, and electroneutrality in an aqueous milieu. Because different compartments are separated by membranes with different permeability coefficients for anions and cations, changes in the strong ion difference (SID) in one compartment are inevitably linked to opposite changes in the adjacent compartment. Böning and Maassen raised the interesting question whether there are also other acids than lactic acid contributing to the exercise-induced acidosis. Indeed, our own results Communicated by Editors-in-Chief Westerterp/Westerblad.

Antibiotikatherapie bei operativen Intensivpatienten@@@Antibiotic treatment of surgical intensive care patients: Prokalzitonin zur Steuerung der Therapiedauer@@@Procalcitonin to guide duration of therapy

The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p<0.001) without unfavorable effects on clinical outcome.