Andrea Lassnigg

Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?

Objective:Traditional cutoff values of serum creatinine considered to define postoperative acute renal failure have been challenged recently. In a previous investigation we demonstrated that minimal changes in serum creatinine concentration were associated with a substantial decrease in survival after cardiac surgery. In this investigation, we assessed the impact of minimal absolute increases in serum creatinine in a second institution, and we analyzed whether relative changes, as in the RIFLE classification and, partially, in Acute Kidney Injury Network (AKIN) classification, confer a different prognostic potential. Design:Prospective analysis. Setting:University hospital. Patients:All consecutive patients undergoing cardiac surgery in the University Hospital of Zurich (Center USZ) over a 46-month period. Interventions:Patients were prospectively documented. We analyzed maximal changes in serum creatinine in the first 48 hrs postoperatively (&Dgr;Crea) regarding death within 30 days. Results were compared with those of the University Hospital Vienna (Center AKH). Moreover, the prognostic potential of &Dgr;Crea within 48 hrs vs. serum creatinine elements according to RIFLE and AKIN classifications was assessed. Measurements and Main Results:A total of 3,123 patients were evaluated from USZ. The majority of patients had decreased postoperative serum creatinine values (negative &Dgr;Crea) and the lowest mortality (1.8%). Minimal increases, [0, 0.5) mg·dL−1, were associated with a more than doubled mortality in both centers (5%/6%). Mortality, according to RIFLE and AKIN classifications for both populations combined, was as follows: 7,023 (3.6%), 160 (29%), 43 (19%), and 15 (33%) for RIFLE Normal, Risk, Injury, and Failure; 6,644 (2.8), 463 (16.4), 3 (66.7), and 131 (1.8) for AKIN stage 0, 1, 2, and 3. Conclusions:Measuring repeat serum creatinine concentrations within 48 hrs and determining &Dgr;Crea were the most effective discrimination method to find patients at risk for adverse postoperative outcome after cardiac surgery, better than application of this sole criterion to the RIFLE (least discriminatory) or the AKIN classification.

Antifungal susceptibility of Candida albicans in biofilms

Candida albicans are the most common fungi associated with biofilm‐related infections. Biofilms are defined as microbial communities encased in a matrix of extracellular polymeric substances. The most important feature of biofilm growth is the high resistance to antimicrobial agents that can be up to 1000‐fold greater than that of planktonic cells. This review discusses the factors affecting antifungal resistance as well as activity of mono‐ and combination therapy of different antifungal classes and antifungal activity in vitro and in vivo against C. albicans biofilms.

In vitro activity of antifungal combinations against Candida albicans biofilms.

OBJECTIVES The aim of the present study was to evaluate the in vitro activity and synergism of the combinations of amphotericin B/caspofungin and amphotericin B/posaconazole against Candida albicans, grown either as planktonic cells or in biofilms. METHODS Ten C. albicans bloodstream isolates used in this study were collected from intensive care patients admitted to the Vienna University Hospital between 2006 and 2007. Chequerboard tests were employed to determine the efficacy of the antifungal combinations amphotericin B/caspofungin and amphotericin B/posaconazole against both planktonic cells and biofilms. C. albicans biofilms were prepared using the static microtitre plate model. The activity of antifungal combination therapy was determined by visual reading for planktonic cells and using the XTT assay for biofilms. RESULTS For Candida biofilms the median MIC was 4 mg/L for amphotericin B and caspofungin, and >256 mg/L for posaconazole. The combination amphotericin B/posaconazole yielded synergism [fractional inhibitory concentration index (FICI) <0.26], whereas amphotericin B/caspofungin yielded indifferent interaction only (FICI 0.75-1.25) against all isolates when grown in biofilms. Under planktonic conditions, synergism was demonstrable for the combination amphotericin B/caspofungin against 4 of the 10 isolates, whereas the combination of caspofungin/posaconazole was indifferent against all tested isolates. CONCLUSIONS We showed that MICs for planktonic and biofilm forms of C. albicans were much lower when treated with an antifungal combination than when treated with single agents. The combination of amphotericin B/posaconazole yielded synergism against Candida biofilms, whereas amphotericin B/caspofungin yielded indifferent interaction.

Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery

BACKGROUND Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. METHODS We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringers lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. RESULTS The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (P<0.0001). Both colloids affected clot formation and clot strength and caused slight increases in serum creatinine. CONCLUSIONS Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.

Invasive fungal infections and (1,3)-β-d-glucan serum concentrations in long-term intensive care patients

OBJECTIVE Invasive fungal infections are associated with high morbidity and increased mortality. This study was performed to assess the epidemiology of fungal infections and to determine (1,3)-beta-D-glucan serum concentrations in patients admitted to intensive care units (ICUs). PATIENTS AND METHODS Overall 197 patients were admitted to nine medical and surgical intensive care units (ICUs) at a 2200-bed university hospital during a 3-month period. Retrospectively, the patients were split into three groups: group A comprised 24 patients with proven invasive fungal infections admitted for a median of 40 days. Group B comprised 58 patients who were admitted to the ICU for 30 days but without fungal infection. One hundred and fifteen post-operative patients served as controls (group C). The levels of (1,3)-beta-D-glucan were monitored in all patients twice weekly during their ICU admittance. RESULTS Average (1,3)-beta-D-glucan concentrations were significantly higher in the patients with fungal infections compared to group B and group C (median 44 vs. 22 and 12.9 pg/ml, respectively; p<0.001). For a serum (1,3)-beta-D-glucan level of 40 pg/ml, the sensitivity, the specificity, the positive predictive value, the negative predictive value, the area under the curve of the receiver operating characteristics (AUC ROC) curve, the likelihood ratio (LR)+ and LR- were 52.2, 75.9, 46.2, 80, 0.7, 2.16, and 0.63, respectively, on day 7. Patients in group A had bacterial infections significantly more often than patients in group B (p=0.003). The hospitalization before ICU admittance for group A was significantly longer than for groups B and C (median 19 (group A) vs. 6 (group B) vs. 10 (group C) days; p<0.05). CONCLUSIONS Longer hospitalization and multiple bacterial infections were found to be the main risk factors for invasive fungal infections. Long-term ICU patients have elevated (1,3)-beta-D-glucan levels, not only due to invasive fungal infections, but also due to the serious underlying diseases and conditions, inter-current complications, and intensive care measures. Yet, persistently high serum levels of (1,3)-beta-D-glucan in ICU patients may be indicative of invasive fungal infections and warrant additional diagnostic efforts.

Antifungal activity of amphotericin B, caspofungin and posaconazole on Candida albicans biofilms in intermediate and mature development phases

The aim of this study was to examine the antifungal activity of amphotericin B, caspofungin and posaconazole on Candida albicans biofilms in the intermediate and mature development phases. Candida albicans biofilms, previously grown for either 24, 48 or 72 h in 96‐well microtitre plates, were treated for 48 h with amphotericin B, caspofungin or posaconazole in increasing concentrations according to the respective minimal inhibitory concentration (MIC) determined for planktonic cells (1–128 × MIC). The biofilms were quantified using the mean optical density (OD) determined by XTT assay. Antifungal activities were expressed as percentage of reduction in OD of drug‐treated biofilms compared to untreated biofilms. To test the fungicidal activity of antifungal agents, the unfixed biofilms were scraped off and seeded to Sabouraud agar. Caspofungin and amphotericin B showed higher activity against C. albicans biofilm grown for 24 h and 72 h (≥50% reduction of OD) than biofilms grown for 48 h, whereas posaconazole showed similar, but reduced activity against all phases of C. albicans biofilm (≤50% reduction of OD). Caspofungin at 1–4 × MIC achieved the greatest decrease in the biofilm OD grown for 24, 48 and 72 h, whereas amphotericin B showed dose‐dependent activity. However, all tested antifungals failed to reach fungicidal activity in all biofilm development phases.

Effects of Vancomycin, Daptomycin, Fosfomycin, Tigecycline, and Ceftriaxone on Staphylococcus epidermidis Biofilms

Infection of medical implanted material is associated with considerable morbidity and costs. In the following work, we investigated the effects of vancomycin, daptomycin, fosfomycin, tigecycline, and ceftriaxone on biofilms formed by Staphylococcus epidermidis isolates causative for implant infection and catheter‐associated bacteremia. Biofilms were studied using the static microtiter plate model and incubated with the antibiotics increasing the concentration from 1× to 128× the minimal inhibitory concentration (MIC) of the respective isolate tested. To quantify the reduction of the biomass, the optical density ratio (ODr) of stained biofilms and the number of growing bacteria were determined. Incubation of the staphylococcal biofilms with the antibiotics decreased the biofilm ODr (at baseline = 1) for ceftriaxone (0.83 ± 0.48) but minimally only for fosfomycin (0.96 ± 0.64), daptomycin (1.05 ± 0.59), tigecycline (1.18 ± 0.66), and vancomycin (0.98 ± 0.44) at exceedingly high concentrations of 128 × MIC. The significant reduction of the bacterial growth was not achieved for all antibiotics, not even at the highest concentrations tested. Using higher doses of the antibiotics may be of some value in the treatment of biofilm‐associated infections, although effects are seen only at clinically unachievable doses. However, to eradicate the staphylococcal biofilm, additional measures like debridement and/or removal of the implant are needed.

Effects of Azithromycin in Combination with Vancomycin, Daptomycin, Fosfomycin, Tigecycline, and Ceftriaxone on Staphylococcus epidermidis Biofilms

ABSTRACT Staphylococcal biofilms on surgical implants are the underlying cause of a lack of response to antimicrobial treatment. We investigated the effects of vancomycin (VAN), daptomycin (DAP), fosfomycin (FOS), tigecycline (TGC), and ceftriaxone (CRX), alone and in combination with azithromycin (AZI), on established biofilms of Staphylococcus epidermidis. Biofilms were studied using the static microtiter plate model with established S. epidermidis biofilms, with an initial inoculum of 106/ml in 96-well polystyrene flat-bottom microtiter plates. Biofilms were inoculated with VAN, DAP, FOS, TGC, or CRX at two concentrations, alone or in combination with AZI (2, 512, or 1,024 mg/liter). To assess the reduction in biomass, the optical density ratio (ODr), calculated as (optical density [OD] of the treated biofilm)/(OD of the untreated biofilm, taken as 1), was used. For antibacterial efficacy, the viable bacterial count was used. Reductions in the biofilm ODr were observed for VAN (15 and 40 mg/liter) and FOS (200 mg/liter) only (ODr [mean ± standard deviation] for VAN at 15 and 40 mg/liter, 0.77 ± 0.32 and 0.8 ± 0.35, respectively; ODr for FOS at 200 mg/liter, 0.78 ± 0.26; P < 0.05), but not for DAP (2 and 5 mg/liter), TGC (0.2 and 2 mg/liter), or CRX (600 and 2,400 mg/liter). The addition of AZI had no further effect on the ODr, but a significant reduction of bacterial growth was achieved with high doses of AZI plus TGC or AZI plus CRX (a 3-log count reduction for AZI at 1,024 mg/liter plus CRX at 600 mg/liter and for AZI at 512 or 1,024 mg/liter plus CRX at 2,400 mg/liter; a 2-log count reduction for AZI at 512 or 1,024 mg/liter plus TGC at 2 mg/liter [P < 0.05]). No significant reduction in bacterial growth was observed for FOS (50 and 200 mg/liter), DAP (2 and 5 mg/liter), or TGC (0.2 mg/liter) in combination with AZI. None of the antibiotics at either concentration reduced the bacterial count of the biofilms when used alone. Thus, the use of a combination of AZI plus TGC, FOS, or CRX at high concentrations has little effect on biofilm density but significantly reduces bacterial growth.

A Randomized, Double-Blind Comparison of Licorice Versus Sugar-Water Gargle for Prevention of Postoperative Sore Throat and Postextubation Coughing

BACKGROUND:One small study suggests that gargling with licorice before induction of anesthesia reduces the risk of postoperative sore throat. Double-lumen tubes are large and thus especially likely to provoke sore throats. We therefore tested the hypothesis that preoperative gargling with licorice solution prevents postoperative sore throat and postextubation coughing in patients intubated with double-lumen tubes. METHODS:We enrolled 236 patients having elective thoracic surgery who required intubation with a double-lumen endotracheal tube. Patients were randomly assigned to gargle 5 minutes before induction of anesthesia for 1 minute with: (1) Extractum Liquiritiae Fluidum (licorice 0.5 g); or (2) Sirupus Simplex (sugar 5 g); each diluted in 30 mL water. Sore throat and postextubation coughing were evaluated 30 minutes, 90 minutes, and 4 hours after arrival in the postanesthesia care unit, and the first postoperative morning using an 11-point Likert scale by an investigator blinded to treatment. RESULTS:The incidence of postoperative sore throat was significantly reduced in patients who gargled with licorice rather than sugar-water: 19% and 36% at 30 minutes, 10% and 35% at 1.5 hours, and 21% and 45% at 4 hours, respectively. The corresponding estimated treatment effects (relative risks) were 0.54 (95% CI, 0.30–0.99, licorice versus sugar-water; P = 0.005), 0.31 (0.14–0.68) (P < 0.001), and 0.48 (0.28–0.83) (P < 0.001). CONCLUSION:Licorice gargling halved the incidence of sore throat. Preinduction gargling with licorice appears to be a simple way to prevent a common and bothersome complication.

Acute hyponatremia after cardioplegia by histidine-tryptophane-ketoglutarate – a retrospective study

BackgroundHyponatremia is the most common electrolyte disorder in hospitalized patients and is known to be associated with increased mortality. The administration of antegrade single-shot, up to two liters, histidine-tryptophane-ketoglutarate (HTK) solution for adequate electromechanical cardiac arrest and myocardial preservation during minimally invasive aortic valve replacement (MIAVR) is a standard procedure. We aimed to determine the impact of HTK infusion on electrolyte and acid–base balance.MethodsIn this retrospective analysis we reviewed data on patient characteristics, type of surgery, arterial blood gas analysis during surgery and intra-/postoperative laboratory results of patients receiving surgery for MIAVR at a large tertiary care university hospital.ResultsA total of 25 patients were included in the study. All patients were normonatremic at start of surgery. All patients developed hyponatremia after administration of HTK solution with a significant drop of serum sodium of 15 mmol/L (p < 0.01). Measured osmolality did not change during all times of surgery compared to start of surgery (p = 0.28 – p = 0.79), indicating isotonic hyponatremia. After administration of HTK solution pH fell significantly due to development of metabolic acidosis.ConclusionsAcute hyponatremia during cardioplegia with HTK solution is isotonic and should probably not be corrected without presence of hypotonicity as confirmed by measurement of serum osmolality.