Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections.

Early initiation of antimicrobial therapy targeting resistant bacterial pathogens causing sepsis and bloodstream infections (BSIs) is critical for a successful outcome. The T2Resistance Panel (T2R) detects the following resistance genes within organisms that commonly cause BSIs directly from patient blood samples: blaKPC, blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, blaOXA, vanA, vanB, and mecA/mecC. We conducted a prospective study in two major medical centers for the detection of circulating resistance genes by T2R in patients with BSIs. T2R reports were compared to antimicrobial susceptibility testing (AST), phenotypic identification, and standard molecular detection assays. Among 59 enrolled patients, 25 resistance genes were identified: blaKPC (n = 10), blaNDM/bla/IMP/blaVIM (n = 5), blaCTXM-14/15 (n = 4), blaAmpC (n = 2), and mecA/mecC (n = 4). Median time-to-positive-T2R in both hospitals was 4.4 hours [interquartile range (IQR): 3.65-4.97 hours] in comparison to that for positive blood cultures with final reporting of AST of 58.34 h (IQR: 45.51-111.2 hours; P < 0.0001). The sensitivity of T2R to detect the following genes in comparison to AST was 100% for blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, mecA/mecC and 87.5% for blaKPC. When monitored for the impact of significant antimicrobial changes, there were 32 events of discontinuation of unnecessary antibiotics and 17 events of escalation of antibiotics, including initiation of ceftazidime/avibactam in six patients in response to positive T2R results for blaKPC. In summary, T2R markers were highly sensitive for the detection of drug resistance genes in patients with bacterial BSIs, when compared with standard molecular resistance detection systems and phenotypic identification assays while significantly reducing by approximately 90% the time to detection of resistance compared to standard methodology and impacting clinical decisions for antimicrobial therapy. IMPORTANCE: This is the first reported study to our knowledge to identify key bacterial resistance genes directly from the bloodstream within 3 to 5 hours in patients with bloodstream infections and sepsis. The study further demonstrated a direct effect in modifying initial empirical antibacterial therapy in response to T2R signal to treat resistant bacteria causing bloodstream infections and sepsis.

Post-Traumatic Stress Disorder and Burnout in Healthcare Professionals During the SARS-CoV-2 Pandemic: a Cross-Sectional Study.

INTRODUCTION: Healthcare professionals who are directly involved in the diagnosis, treatment, and general care of patients with SARS-CoV-2 are at risk of developing adverse psychological reactions. A cross-sectional study of healthcare professionals aimed to determine the impact of the SARS-CoV-2 pandemic on the mental health of healthcare professionals in two of the largest referral hospitals in Athens, Greece. METHODS: The study was conducted in the two largest SARS-CoV-2 referral hospitals in Athens, Greece. An assessment and the interrelationship of post-traumatic stress disorder, using the Impact of Event Scale-Revised [IES-R]) and burnout, using the Maslach Burnout Inventory [MBI]) was carried out. RESULTS: A total of 162 subjects were enrolled in the study. Fifty-six (35%) had an IES-R score > 33, suggesting post-traumatic stress disorder. Forty-nine (30%) had an MBI score > 27. Seventy-five (46%) had a personal accomplishment score of < 33 and 46 (28%) had a depersonalization score >10. Stepwise backward logistic regression revealed that the only independent variable that was retained regarding the presence of post-traumatic stress disorder was the emotional exhaustion score of the MBI (at a cut-off of 24 in this scale, the 95% CI of the odds ratio for the presence of post-traumatic stress disorder was 1.077-1.173). CONCLUSIONS: In this sample of first-line Greek healthcare professionals against SARS-CoV-2, most of them were proven to be quite resilient to this challenge. One-third of them had post-traumatic stress disorder, which depended on their degree of emotional exhaustion. Healthcare professionals, as represented by this study, performed their duties without feeling helpless and developing adverse psychological reactions.

Hospital Resources May Be an Important Aspect of Mortality Rate among Critically Ill Patients with COVID-19: The Paradigm of Greece.

For critically ill patients with coronavirus disease 2019 (COVID-19) who require intensive care unit (ICU) admission, extremely high mortality rates (even 97%) have been reported. We hypothesized that overburdened hospital resources by the extent of the pandemic rather than the disease per se might play an important role on unfavorable prognosis. We sought to determine the outcome of such patients admitted to the general ICUs of a hospital with sufficient resources. We performed a prospective observational study of adult patients with COVID-19 consecutively admitted to COVID-designated ICUs at Evangelismos Hospital, Athens, Greece. Among 50 patients, ICU and hospital mortality was 32% (16/50). Median PaO2/FiO2 was 121 mmHg (interquartile range (IQR), 86-171 mmHg) and most patients had moderate or severe acute respiratory distress syndrome (ARDS). Hospital resources may be an important aspect of mortality rates, since severely ill COVID-19 patients with moderate and severe ARDS may have understandable mortality, provided that they are admitted to general ICUs without limitations on hospital resources.

Lactate Kinetics Reflect Organ Dysfunction and Are Associated with Adverse Outcomes in Intensive Care Unit Patients with COVID-19 Pneumonia: Preliminary Results from a GREEK Single-Centre Study.

Coronavirus disease-19 (COVID-19) continues to be a health threat worldwide. Increased blood lactate is common in intensive care unit (ICU) patients; however, its association with outcomes in ICU COVID-19 patients remains currently unexplored. In this retrospective, observational study we assessed whether lactate is associated with outcomes in COVID-19 patients. Blood lactate was measured on ICU admission and thereafter daily up to day 14 in 45 patients with confirmed COVID-19 pneumonia. Acute physiology and chronic health evaluation (APACHE II) was calculated on ICU admission, and sequential organ failure assessment (SOFA) score was assessed on admission and every second day. The cohort was divided into survivors and non-survivors based on 28-day ICU mortality (24.4%). Cox regression analysis revealed that maximum lactate on admission was independently related to 28-day ICU mortality with time in the presence of APACHE II (RR = 2.45, p = 0.008). Lactate's area under the curve for detecting 28-day ICU mortality was 0.77 (p = 0.008). Mixed model analysis showed that mean daily lactate levels were higher in non-survivors (p < 0.0001); the model applied on SOFA scores showed a similar time pattern. Thus, initial blood lactate was an independent outcome predictor in COVID-19 ICU patients. The time course of lactate mirrors organ dysfunction and is associated with poor clinical outcomes.

Emergence of a pandrug-resistant VIM-1-producing Providencia stuartii clonal strain causing an outbreak in a Greek intensive care unit.

Here we describe an outbreak caused by a pandrug-resistant Providencia stuartii strain involving 15 critically ill patients in a Greek intensive care unit (ICU) during September-November 2011. All isolates harboured the blaVIM-1 gene and a class 1 integron structure of 1913 bp as well as blaSHV-5 and blaTEM-1. Pulsed-field gel electrophoresis (PFGE) demonstrated that isolates from all 15 patients belonged to a single P. stuartii clonal type. As all of the infected patients were hospitalised during overlapping time periods, horizontal intra-ICU transmission was considered as the main route for the dissemination of the outbreak strain. The outbreak ended following reinforcement of infection control measures, including implementation of additional barrier precautions for infected patients.

Cytomegalovirus reactivation in a general, nonimmunosuppressed intensive care unit population: incidence, risk factors, associations with organ dysfunction, and inflammatory biomarkers.

PURPOSE: Cytomegalovirus (CMV) reactivation, a significant cause of morbidity and mortality in immunosuppression, may affect "immunocompetent" seropositive critically ill patients. The aim of this prospective, observational study was to define the incidence, risk factors, and the association with morbidity and mortality of CMV reactivation in a general population of critically ill immunocompetent patients. We also studied the relationship between reactivation and patients' inflammatory response, as expressed by cytokine levels and stress up-regulation by salivary cortisol. METHODS: This study included mechanically ventilated CMV-seropositive patients. A quantitative real-time polymerase chain reaction (PCR) was performed for CMV plasma DNAemia determination, upon intensive care unit (ICU) admission and weekly thereafter until day 28. Cytomegalovirus reactivation was defined as CMV plasma DNAemia greater than or equal to 500 copies/mL. Upon ICU admission, interferon γ, interleukin (IL) 10, IL-17A, IL-2, IL-6, and tumor necrosis factor α were quantified in plasma, and morning saliva was obtained to measure cortisol. Disease severity was assessed by Acute Physiology and Chronic Health Evaluation II score, whereas the degree of organ dysfunction was quantified by Sequential Organ Failure Assessment score. Mortality, duration of mechanical ventilation, and ICU length of stay were recorded. RESULTS: During the study period, 80 (51 men) patients with a median age of 63 years fulfilled the inclusion criteria. Reactivation of CMV occurred in 11 patients (13.75%). Median day of reactivation was day 7 post ICU admission. Total number of red blood cell units transfused (odds ratio [OR], 1.50; confidence interval [CI], 1.06-2.13; P = .02) and C-reactive protein levels upon ICU admission (OR, 1.01; CI, 1.00-1.02; P = .02) were independently associated with CMV reactivation. High IL-10 was marginally related to reactivation (P = .06). Sequential Organ Failure Assessment scores were higher in the group with CMV reactivation compared with patients without reactivation during the entire 28-day observation period (P < .006). Salivary cortisol, mortality, length of ICU stay, and duration of mechanical ventilation were similar in the 2 groups. CONCLUSIONS: Cytomegalovirus reactivation occurred in 13.75% of critically ill, immunocompetent patients. The degree of inflammation and the total number of transfused red blood cells units constituted risk factors. Cytomegalovirus reactivation was associated with more severe of organ dysfunction, but not with a worse clinical outcome.

Longitudinal assessment of adrenal function in the early and prolonged phases of critical illness in septic patients: relations to cytokine levels and outcome.

CONTEXT: Adrenal dysfunction remains a controversial issue in critical care. The long-stay intensive care unit (ICU) population may be at increased risk of adrenal insufficiency. OBJECTIVE: We aimed to determine whether adrenal dysfunction develops during the course of sepsis. DESIGN: This is a prospective observational longitudinal study. SETTING: The study was conducted in the ICU of a secondary/tertiary care hospital. PATIENTS: We studied 51 consecutive mechanically ventilated patients with sepsis. INTERVENTION: We measured cortisol, ACTH, cortisol-binding globulin, cytokines, and cortisol 30 minutes after 1 µg ACTH(1-24), upon sepsis diagnosis and every 3 to 4 days, until Day 30 or until recovery or death. MAIN OUTCOME MEASURES: We looked for changes in baseline and stimulated cortisol levels and its relationship to ACTH levels, sepsis severity or survival. RESULTS: Baseline and stimulated cortisol levels did not vary significantly. Septic patients with shock had higher baseline (20 ± 6 vs 17 ± 5 µg/dL, P = .03) and stimulated cortisol levels (26 ± 5 vs 23 ± 6 µg/dL, P = .04), compared with those without shock. On Day 1, ACTH levels could not predict cortisol levels (R(2) = 0.06, P = .08). ACTH levels increased significantly after Day 10 and, at this time point, they related to cortisol levels (R(2) = 0.35, P < .001). Development of septic shock, or resolution from it, was not associated with changes in baseline, stimulated cortisol levels, or the cortisol increment. There was much inpatient variability in the diagnosis of adrenal dysfunction at different time points. CONCLUSIONS: Total cortisol levels relate both to the severity and outcome of sepsis and remain fairly unchanged during the course of illness. Initially, cortisol levels are largely ACTH independent, whereas ACTH increases and correlates with cortisol levels later on. Adrenal dysfunction does not seem to be a major problem during the prolonged phase of sepsis. Although not significant, the variation in cortisol levels may be such that classification of patients varies, questioning the utility of arbitrary cut-offs to define adrenal dysfunction in septic patients.

Prediction of the renal replacement therapy requirement in mechanically ventilated critically ill patients by combining biomarkers for glomerular filtration and tubular damage.

PURPOSE: Mechanically ventilated critically ill patients with high severity score indices need a very cautious therapeutic approach. Considering that inappropriate decisions on renal replacement therapy (RRT) initiation may promote unwanted adverse effects, we evaluated whether a panel of novel and traditional renal markers is superior to conventional renal marker in predicting RRT requirements in this group of patients. METHODS: This was a prospective observational study, performed at the two distinct multidisciplinary intensive care units (ICUs) of a 1000-bed tertiary hospital. Of 310 consecutive patients, 106 patients fulfilled the inclusion criteria of the study. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum creatinine (sCr) and serum cystatin C (sCysC) were determined on ICU admission. The predictive performance of all markers for first RRT was tested and compared based on the area under the receiver operating characteristic (ROC) curves. Time-dependent ROC curves were used to assess the earlier time point where the markers presented their maximum area under the curve (AUC). RESULTS: All studied biomarkers and acute physiology and chronic health evaluation (APACHE) II score, were significant independent predictors of RRT (uNGAL-AUC=0.73, sCysC-AUC=0.76, sCr-AUC=0.78, APACHE-AUC=0.73, P<0.0001). sCysC and sCr showed early maximum predictive ability within 10 days of ICU admission, while uNGAL and APACHE II score within 11 days of ICU admission. sCr combined with normalized (n)NGAL and sCysC combined with either nNGAL or uNGAL established best predictors for the RRT initiation (AUC-ROC=0.8). Distinguishing patients without acute kidney injury (AKI) on ICU entry, the combination of sCysC and APACHE II score proved best (AUC-ROC=0.78). CONCLUSIONS: Specific markers of kidney dysfunction and of kidney damage can be successfully combined to increase the prognostic capability for RRT initiation. The presence of AKI affects diagnostic performance. Without an established AKI on ICU admission, future RRT requirement was better predicted by the combination of illness severity with a marker of glomerular filtration rate. With AKI on ICU admission a combination of the marker of glomerular filtration rate with one of tubular injury proved best.

Combination of renal biomarkers predicts acute kidney injury in critically ill adults.

OBJECTIVE: Most studies so far have focused on the performance of individual biomarkers to detect early acute kidney injury (AKI) in the adult intensive care unit (ICU) patients; however, they have not determined the predictive ability of their combinations. The aim of this study was to compare the predictive abilities of plasma neutrophil gelatinase-associated lipocalin (pNGAL), urine neutrophil gelatinase-associated lipocalin (uNGAL), plasma cystatin C (pCysC), serum creatinine (sCr), and their combinations in detecting AKI in an adult general ICU population. METHODS: A total of 100 consecutive ICU patients were included in the analysis. AKI was defined according to RIFLE criteria. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: AKI occurred in 36% of patients 7 days post-admission. All three novel biomarkers as well as sCr had moderate predictive abilities for AKI occurrence. The most efficient combinations (pNGAL + sCr and pNGAL + uNGAL + sCr) were selected to participate in the subsequent analyses. Both combinations, when added to a reference clinical model, increased its AUC significantly (0.858, p = 0.04). Their NRI (0.78, p = 0.0002) was equal to that of pNGAL, but higher than that of the other three biomarkers, whereas their IDI was higher than that of any individual biomarker (0.23, p = 0.0001). Both combinations had better specificities, positive likelihood ratios, and positive predictive values than those of any individual biomarker. CONCLUSION: The biomarker combinations had better predictive characteristics compared with those of each biomarker alone.

Thyroid function during critical illness.

The metabolic support of the critically ill patient is a relatively new target of active research and little is as yet known about the effects of critical illness on metabolism. The nonthyroidal illness syndrome, also known as the low T3 syndrome or euthyroid sick syndrome, describes a condition characterized by abnormal thyroid function tests encountered in patients with acute or chronic systemic illnesses. The laboratory parameters of this syndrome include low serum levels of triiodothyronine (T3) and high levels of reverse T3, with normal or low levels of thyroxine (T4) and normal or low levels of thyroid-stimulating hormone (TSH). This condition may affect 60 to 70% of critically ill patients. The changes in serum thyroid hormone levels in the critically ill patient seem to result from alterations in the peripheral metabolism of the thyroid hormones, in TSH regulation, in the binding of thyroid hormone to transport-protein and in receptor binding and intracellular uptake. Medications also have a very important role in these alterations. Hormonal changes can be seen within the first hours of critical illness and, interestingly, these changes correlate with final outcome. Data on the beneficial effect of thyroid hormone treatment on outcome in critically ill patients are so far controversial. Thyroid function generally returns to normal as the acute illness resolves.

Epidemiology, risk factors for and outcome of candidaemia among non-neutropenic patients in a Greek intensive care unit.

To determine the epidemiology, risk factors for and outcome of candidaemia in critically ill patients, a matched case-control study was performed in a 25-bed intensive care unit (ICU) from August 2004 to January 2006. Candidaemia occurred in 33 patients; each patient was matched to four controls according to admission illness severity, diagnostic category and length of ICU stay. Candida non-albicans species predominated (67.7%). The presence of acute respiratory distress syndrome (ARDS) was the only independent risk factor for candidaemia development (OR, 2.93; 95% CI 1.09-7.81, P = 0.032). Mortality was 60.6% among patients with candidaemia and 22% among controls (P < 0.001). The presence of candidaemia (OR, 9.37; 95% CI 3.48-25.26, P < 0.001) and the illness severity on admission (acute physiologic and chronic health evaluation II score, OR, 1.17; 95% CI 1.12-1.24, P < 0.001) were independently associated with mortality. Among candidaemic patients, risk factors for mortality were the severity of organ dysfunction (sequential organ failure assessment score, OR, 1.57; 95% CI 1.00-2.46, P = 0.05) and a low serum albumin level (OR, 0.74; 95% CI 0.59-0.94, P = 0.012) both of them occurred on candidaemia onset. We conclude that in critically ill patients matched for illness severity and length of ICU stay, the only independent risk factor for candidaemia was the presence of ARDS. Mortality was independently associated with acquisition of candidaemia and with the illness severity at candidaemia onset.

Complications involving gall bladder and biliary tract in cardiovascular surgery.

BACKGROUND/AIMS: This study aimed to ascertain the frequency of biliary complications following cardiac surgery, to determine preoperative risk factors and to identify the significance of prompt diagnosis and institution of therapy. METHODOLOGY: All patients who underwent open-heart surgery (4588 patients) during a period of 3 years were examined prospectively for complications involving gall bladder and biliary tract. Patients with preoperative hepatic dysfunction or biliary disorders were excluded from this study. RESULTS: Biliary complications occurred in 14 patients. Gangrene of gallbladder (n=5) and acute acalculous cholecystitis (n = 5) were the most common complications followed by distension of the common bile duct (n = 2), cholelithiasis (n = 1) and empyema (n = 1). The majority of complications presented within the 3rd postoperative week. Chole cystectomy was performed in 5 patients and percutaneous drainage of the gallbladder in 7. Mortality rate was 43%. Biliary complications correlated with advanced age, the male sex, combined surgical procedures, preoperative low cardiac output syndrome, prolonged bypass and aortic cross-clump time, mechanical ventilation, the usage of Intra-Aortic Balloon Pumping, multiple transfusions and the administration of inotrops. CONCLUSIONS: Biliary complications after cardiac surgery are uncommon but life threatening and may result from hypoperfusion. Clinical features are often subtle, and a high index of suspicion is necessary for an early diagnosis and appropriate treatment.

Pseudomonas aeruginosa susceptible only to colistin in intensive care unit patients.

BACKGROUND: Gram-negative bacilli, including multi-drug-resistant (MDR) Pseudomonas aeruginosa, are responsible for severe intensive care unit (ICU)-acquired infections, mainly pneumonia and bacteremia. The aim of this study was to determine the incidence of MDR strains of Pseudomonas in patients undergoing cardiac surgery, to elucidate the effectiveness of treating these patients with colistin, and to assess the safety of the drug. METHODS: A prospective study was conducted among 1,452 patients who underwent surgery for a variety of cardiac lesions over a one-year period, and who spent a portion of the recovery period in the surgical ICU. Their case histories were analyzed to identify infectious complications. Diagnosis of infection was based on clinical data, and the pathogen was tested with respect to its susceptibility to colistin (polymyxin E). The clinical response to the antibiotic was evaluated. RESULTS: Over the 12-month period, among 115 infected patients, 15 were affected by strains of P. aeruginosa. In 10 patients, this pathogen proved resistant to all potentially active antibiotics except colistin. All of the affected patients were being ventilated mechanically, and eight of them presented with ventilator-associated pneumonia (VAP), whereas one patient suffered a deep incisional surgical site infection and bacteremia and the remaining patient had a superficial infection of a lower-extremity vein graft donor site. The MDR pathogen was introduced to the hospital by three patients transferred from three institutions. All patients were treated with intravenous colistin. In cases of VAP, aerosolized colistin was added. Deterioration of renal function occurred in three patients (30%), all of whom had a history of renal insufficiency. Cure or clinical improvement was observed in seven patients (70%), whereas four patients, including one who improved initially, developed sepsis and died with multiple organ dysfunction syndrome (mortality rate 40%). CONCLUSIONS: The increasing prevalence of MDR P. aeruginosa in ICU patients has rekindled interest in polymyxins, which had been abandoned because of toxic side effects. Colistin retained significant in vitro activity against this virulent organism, had an acceptable safety profile, and should be considered as a treatment option in critically ill patients with infection caused by MDR gram-negative bacilli. Aerosolized colistin may merit further consideration as a therapeutic intervention for patients with refractory pulmonary infections.

Methicillin-resistant Staphylococcus aureus preventing strategy in cardiac surgery.

OBJECTIVES: The aim of this survey was to elucidate the efficacy of methicillin-resistant Staphylococcus aureus (MRSA) preventing strategy in our institution by investigating the incidence and evaluating the morbidity and mortality associated with this multi-resistant virulent organism. METHODS: A prospective observational cohort among patients submitted to cardiovascular surgical procedures was conducted from 1 January 1997 to 31 December 2005. Preventing strategy included active screening programs by nasal swabs for all patients admitted from other hospitals or being at risk for developing infectious complications. Carriers or infected patients remained isolated and were treated promptly. Furthermore, all newly employed health care workers were screened for MRSA and carriers were treated with mupirocin until the eradication of the pathogen. RESULTS: Throughout the 9-year study period 826 infectious complications were registered among 15,270 cardiac surgical patients. Total infection rate was 5.4%. MRSA was identified in 86 patients; 56 patients proved carriers and 30 infected. The MRSA associated infection rate was 0.2%. During this period of time mean ICU stay was 1.7 days and ICU mortality rate was 2.9%. MRSA infected patients presented a mean ICU stay of 46.5 days and a mortality rate of 30%. In ten patients, MRSA was detected in tracheal secretions, in four patients in swabs taken from donor site infection and in four patients from superficial sternal surgical wound. In ten patients the pathogen was isolated from cultures of the surgical site drainage and the diagnosis of post-sternotomy mediastinitis was confirmed. The remaining two patients were defined as having severe sepsis; MRSA was documented in central venous catheter tips and blood cultures. CONCLUSIONS: The prompt determination, isolation and appropriate treatment of MRSA patients admitted from other institutions combined with the detection and elimination of carriers among new health care workers and patients at high risk of developing infectious complications prevented further spread of the pathogen.

Preventing strategy of multidrug-resistant Acinetobacter baumanii susceptible only to colistin in cardiac surgical intensive care units.

OBJECTIVE: The study aimed to determine the incidence and mortality of multidrug-resistant Acinetobacter baumannii in cardiac surgery, to elucidate the effectiveness of colistin treatment and to identify if the additional measures to the recommended procedures were able to control the dissemination of the pathogen. METHODS: A prospective observational cohort was conducted among cardiac surgical patients from 1 September 2005 to 31 December 2006. We reviewed the prophylactic measures of the surgical intensive care unit and implemented a two scale multiple program. Scale I included classical infection control measures, while Scale II referred to the geographic isolation of multidrug-resistant Acinetobacter baumannii patients and environmental intense surveillance. RESULTS: Among 151 out of 1935 infected patients 20 were colonized and infected by strains of multidrug-resistant A. baumannii susceptible only to colistin. Seventeen patients presented respiratory tract infection, one patient suffered deep surgical site infection and two patients catheter related infection. Transmission of the pathogen occurred via two patients transferred from two other institutions. They were all treated with colistin. Cure or clinical improvement was observed only in four patients (20%). Scale I measures were implemented for the whole 16-month period while scale II for two separate periods of 3 weeks. Environmental specimens (n>350) proved negative. CONCLUSIONS: The increasing prevalence of multidrug-resistant A. baumannii in surgical intensive care unit patients creates demand on strict screening and contact precautions. Following this infection control strategy we were able to achieve intermittent eradication of the pathogen during a 16-month period with continuous function of the intensive care unit. Despite the significant in vitro activity of colistin against multidrug-resistant Acinetobacter baumannii the results were discouraging.

Thyroid function changes and cytokine alterations following major surgery.

To establish whether cytokine release is implicated in thyroid hormone changes during surgical stress we studied 36 adult patients (20 men; mean age +/- SD: 68.5 +/- 10.5 years) undergoing elective major abdominal operations. We measured tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8 and IL-10 and thyrotropin (TSH), free thyroxine (FT(4)) and triiodothyronine (T(3)) before scheduled non-emergency surgery, immediately postoperatively, on the 1st postoperative day (post-1) and on the 2nd postoperative day (post-2). TNF-alpha, IL-6 and IL-8 peaked on day post-1 whereas IL-10 peaked immediately postoperatively. Fourteen of 36 patients had low T(3) levels after surgery, indicating non-thyroidal illness (NTI). Significant negative correlations were noted among TNF-alpha, IL-6 and IL-8 against T(3) and FT(4). Cytokines are responsible, at least in part, for NTI following major operations.

Tumour necrosis factor-alpha (TNFalpha) and interleukin-10 are crucial mediators in post-operative systemic inflammatory response and determine the occurrence of complications after major abdominal surgery.

BACKGROUND: The course of serum cytokine levels in patients with postoperative systemic inflammatory response syndrome (SIRS) after major abdominal surgery remains currently unclear. METHODS: Blood was sampled pre- and post-operatively and on days 1 and 2 in 40 patients undergoing major abdominal surgery. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin (IL) -6, IL-8, and IL-10 were measured by the LINCOplex assay; those of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by an enzyme immunoassay. RESULTS: Compared to their pre-operative values, sTREM-1 was elevated on day 2; TNFalpha on day 1; IL-6 and IL-10 post-operatively and on days 1 and 2; and IL-8 post-operatively and on day 1. The duration of operation correlated with TNFalpha and IL-10 at all sampling times, and with IL-6 post-operatively. There were no differences in cytokine concentrations between patients who exhibited post-operative complications and those who did not. IL-10/TNFalpha below 30 was found in all patients with complications (100%) and in 20 patients without complications (64.5%, p: 0.043). CONCLUSIONS: SIRS following major surgery is characterised by complex alterations in cytokine concentrations. The balance between TNFalpha and IL-10 seems to determine the occurrence of post-operative complications.