COMPARISON OF TWO DIFFERENT METHODS FOR TIGECYCLINE SUSCEPTIBILITY TESTING IN ACINETOBACTER BAUMANNII.

- Tigecycline susceptibility testing (TST) presents a tremendous challenge for clinical microbiologists. Previous studies have shown that the Epsilometer test (E-test) and Vitek 2 automated system significantly overestimate the minimum inhibitory concentrations for tigecycline resistance compared to the broth microdilution method (BMM). This leads to very major errors or false susceptibility (i.e. the isolate is called susceptible when it is actually resistant). The aim of this study was to compare E-test against BMM for TST in carbapenem-resistant and carbapenem-susceptible Acinetobacter (A.) baumannii and to analyze changes in tigecycline susceptibility between two time periods (2009-2012 and 2013-2014), with BMM as the gold standard. Using the EUCAST criteria, the rate of resistance to tigecycline for the OXA-23 MBL-positive, OXA-23 MBL-negative and carbapenemase-negative strains for BMM was 54.5% (6/11), 29.4% (5/17) and 2.7% (1/37), respectively; the OXA-24/40 and OXA-58 producing organisms did not exhibit any resistance. With E-test, all OXA-23 MBL-positive organisms (11/11), 23.5% (4/17) of OXA-23 MBL-negative, and 4.1% of OXA-24/40 (3/74) strains displayed tigecycline resistance; there were no resistant strains among the OXA-58 and carbapenemase-negative isolates. Resistance emerged in the bacterial isolates from 2013 to 2014. Although tigecycline does not display cross-resistance, the highest rates of resistant A. baumannii isolates were observed among those producing VIM MBL, regardless of the testing method. These findings suggest that the commercial E-test does not provide reliable results for TST of A. baumannii. Further confirmation with the dilution method should be recommended, particularly in cases of serious infections.

[Importance of standardized stepwise screening in patients with resistant hypertension]. / Vaznost sistemskog probira u algoritmu dijagnostike rezistentne hipertenzije.

Resistant hypertension (RH) is a condition that confers a high cardiovascular risk to the patient due to both persistent blood pressure elevation and the high prevalence of comorbidities and organ damage. Hypertension is defined as resistant (RH) to treatment when a therapeutic strategy that includes appropriate lifestyle measures plus a diuretic and two other antihypertensive drugs belonging to different classes at adequate doses fails to lower blood pressure (BP) values to < 140 and 90 mm Hg, respectively. Prior to diagnosing a patient as having RH, it is important to document adherence and exclude white-coat hypertension, inaccurate measurement of BP, and secondary causes. Ambulatory BP monitoring (ABPM) has become an important tool in the diagnosis and follow-up of hypertensive patient, and it is even more important in the evaluation of those with resistant RH. Among patients with RH, it is very important to select patients with standardized stepwise screening: ABPM of resistant hypertensives has a circadian profile with a high proportion of nondipping. The possible reasons for the absence of dipping are sleep disturbance, obstructive sleep apnea, obesity, high salt intake in salt-sensitive subjects, orthostatic hypotension, autonomic dysfunction, chronic kidney disease, diabetic neuropathy, and old age. It seems reasonable to routinely use ABPM in the initial evaluation of all resistant hypertensive patients. In a significant number of these patients, ABPM will also be an essential tool in follow-up, especially regarding the possible effects of all therapeutic maneuvers that are devoted to bringing BP into the target ranges. The potential success of other therapeutic options such as renal denervation depends on the ability to select patients most likely to benefit.

[Resistant hypertension and reasons for excluding patients from treatment with renal denervation]. / Rezistentna hipertenzija i razlozi iskljucivanja za postupak renalne denervacije.

Increased activation of the sympathetic nervous system is identified as an important factor in the development and progression of hypertension. In this context, a catheter-based approach has been developed to disrupt the renal sympathetic nerves, i.e. renal denervation. Among patients with resistant hypertension, it is very important to select patients using standardized stepwise screening. The potential success of renal denervation depends on the ability to select patients most likely to benefit. A multidisciplinary meeting in necessary. In this work, we describe the potential reasons for excluding patients from treatment with renal denervation.

Importance of urinary NGAL, serum creatinine standardization and estimated glomerular filtration rate in resistant hypertension.

In patients with resistant hypertension (RH) we investigated the importance of urinary neutrophil gelatinase-associated lipocalin (uNGAL- a chemiluminescent microparticle immunoassay (CMIA) method became using (Abbott Diagnostics) for the measurement of NGAL in urine samples) and incidence of chronic kidney disease using the Modification of Diet in Renal Disease Study (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in estimating glomerular filtration rate (eGFR) based on standardised serum creatinine method traceable to isotope dilution mass spectrometry (IDMS) method. It would have been difficult to predict that levels of these biomarker would perform better organ damage than traditional measurements of kidney function such as standardised serum creatinine, MDRD, or CKD-EPI equations in special population such as RH. Serum creatinine concentrations were measured in 50 patients (24M:26F from RH Registar in Clinical Hospital Merkur) by the kinetic Jaffe method. There were no significant differences between the GFR values derived by MDRD and CKD-EPI equations in the group of patients with RH. 62% of patients have eGFR > 60 mL/minl/1.73 m2, while a 38% of patients have eGFR < 60 mL/min/1.73 m2. The measurement of NGAL in urine samples of 40 patients with RH showed no difference and seems to be of no use in further determination of renal impairement. Higher value of uNGAL in some resistant hypertension patients could have link in the repair stage after AKI and would reveal pathways that could link AKI and CKD.

Causative agents of bloodstream infections in two Croatian hospitals and their resistance mechanisms.

Blood samples were collected alongside with routine blood cultures (BC) from patients with suspected sepsis, to evaluate the prevalence of different causative agents in patients with bacteraemia. Among 667 blood samples, there were 122 positive BC (18%). Haemoglobin content, platelet number, and systolic blood pressure values were significantly lower in patients with positive BC, whereas serum lactate levels, CRP, creatinine and urea content were significantly higher in patients with positive BC. The rate of multidrug (MDR) or extensively drug resistant (XDR) bacteria was 24% (n = 29): Klebsiella pneumoniae (9), Pseudomonas aeruginosa (9), Acinetobacter baumannii (4), Escherichia coli (1), vancomycin resistant Enterococcus spp (VRE) (3), and methicillin-resistant Staphylococcus aureus MRSA (3). The dominant resistance mechanisms were the production of extended-spectrum ß-lactamases, OXA-48 carbapenemase, and colistin resistance in K. pneumoniae, VIM metallo-ß-lactamases in P. aeruginosa and OXA-23-like oxacillinases in A. baumannii. The study revealed high rate of MDR strains among positive BCs in Zagreb, Croatia.

[The effects of trimetazidine on QT-interval prolongation in patients with chronic kidney disease stage III-IV (predialysis CRD)]. / Ucinak trimetazidina na produljeni QT interval u bolesnika s kronicnom bubreznom bolesti III.-IV. stupnja (predijalizna kronicna bubrezna bolest).

Prolonged QT interval is a predictor of cardiovascular mortality. It indicates delayed repolarization of ventricular myocardium and is considered a precursor of malignant cardiac arrhythmias and sudden cardiac death. Increased cardiovascular risk (CVR) in the presence of prolonged QT interval, corrected by heart rate (QTc), is attributed to ventricular electrical instability. Patients with chronic renal disease (CRD) usually die from sudden cardiac death before reaching the final stage, final chronic kidney disease (CRD stage V). We investigated whether patients with CRD stage III-V have prolonged QT interval, what are the possible causes of this extension, and whether in this patient population trimetazidine application may affect the reduction in QT prolongation. Our study showed one quarter of predialysis patients, mostly asymptomatic, to have QT prolongation, thus being at a higher risk of CV events. Introducing trimetazidine along with standard therapy can reduce the incidence of sudden cardiac death, and calculation of the QTc index would be a useful and economical method of screening and monitoring high risk patients.

[Underestimated frequency of resistant hypertension in predialysis nondiabetic patients]. / Ucestalost rezistentne hipertenzije u hipertenzivnih nedijabetickih kronicnih bubreznih bolesnika (I.-IV. stadij) je podcijenjena.

The real prevalence of resistant hypertension (RH) is unknown. Studies suggest that it affects 10%-15% of patients treated for hypertension by primary care physicians. RH is defined as blood pressure (BP) remaining above the goal despite the use of optimal doses of 3 or more medicines of different classes (including a diuretic). It means BP >140/90 mm Hg for the general population and >130/80 mm Hg for patients with diabetes or kidney disease. Prior to diagnosing a patient as having RH, it is important to document medication compliance and exclude white-coat hypertension, inaccurate BP measurement, and secondary causes. The role of aldosterone in RH has gained increasing recognition. There is strong evidence for the use of spironolactone as a highly effective antihypertensive agent. Aldosterone plays a significant role in RH pathogenesis, primarily due to its vasoconstrictive effects and the possibility of altering vascular compliance. In RH, there is a high prevalence of cardiac and extra-cardiac target organ damage. It is known that BP control in chronic kidney disease is the key factor for reducing cardiovascular risk and renal disease progression. The objective of the study was to evaluate the prevalence of RH in predialysis nondiabetic (CKD stage I-IV) patients.

[Secondary (AA) amyloidosis in Crohn's disease]. / Sekundarna (AA) amiloidoza u bolesnika s Crohnovom bolescu.

Amyloidosis is a clinical entity that results from deposition of an extracellular protein material that causes disruption in normal architecture and impairs function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but serious complication that occurs in the context of cancer, chronic inflammation and chronic infectious diseases, including inflammatory bowel disease, mainly long-standing Crohn's disease. Renal failure is the most common clinical presentation of AA, ranging from nephrotic syndrome and impaired renal function to renal failure, with a potential for high morbidity. The incidence of the association of secondary amyloidosis in patients with Crohn's disease has been reported to be 0.5%-8%. We present a case of a 39-year-old male patient diagnosed with Crohn's disease at age 21 and submitted to right hemicolectomy because of ileus 17 years before. Thereafter, he was treated with corticosteroids for 15 years and with azathioprine for a short period; in the last three years he was on therapy with mesalazine alone. He was hospitalized due to worsening clinical condition and re-evaluation of the underlying disease. Physical examination revealed marked peripheral edema in both lower extremities. Endoscopic and radiographic examinations confirmed the underlying disease activity. Laboratory tests showed an increase of inflammatory reactants, anemia, hypocalcemia, and severe hypoalbuminemia and hypoproteinemia. He had proteinuria over 24 g/L and creatinine clearance of 66 mL/min, falling within second grade of chronic kidney disease. Renal biopsy was performed for evaluation of renal insufficiency with nephrotic range proteinuria. Congo red staining showed the presence of characteristic amyloid deposition; deposits immunoreacted with the antibody against amyloid A protein, confirming the diagnosis of secondary amyloidosis. The patient was suggested active induction treatment with corticosteroids and azathioprine to achieve remission of Crohn's disease, thereafter treatment with infliximab, but he did not consent with this therapy at that time. Studies with infliximab have demonstrated a decrease in SAA circulating levels and proteinuria, as well as stabilization of renal function. Amyloidosis is frequently described as a major cause of death in patients with Crohn's disease, with long-term mortality between 40% and 60%. Various therapeutic attempts such as azathioprine, colchicine, dimethyl sulfoxide, infliximab, and elemental diets have been tried but there is no definite treatment for secondary amyloidosis in Crohn's disease. Kidney transplantation may offer the best prospects for patients with Crohn's disease who develop amyloidosis and end-stage renal failure.

[Hyperhaemolytic siyndrome in patient without haemoglobinopathies]. / Sindrom hiperhemolize u bolesnice bez hemoglobinopatije.

Hyperhemolysis syndrome usually occurs in patients with sickle cell disease and possibly thalassemia who receive multiple transfusions. There are only few clinical reports on patients without hemoglobinopathies as in this report. Our patient was diagnosed with hyperhemolytic reaction and was infused with IVIG and methylprednisolone for several days. Signs of tissue hypoxia developed along with increased cardiac enzymes, hepatocellular and cerebrovascular injury, and finally death. On autopsy, there was no evidence for hemolytic uremic syndrome or thrombotic thrombocytopenic purpura.

[Acute plastic bronchitis--case report]. / Akutni odljevni bronhitis--prikaz bolesnika.

Plastic bronchitis is a rare disorder characterized by formation and sometimes dramatic expectoration of bronchial casts. It may occur at any age, but most published cases refer to pediatric population. We report a case of an 81-year-old man hospitalized at intensive care unit, who presented with the appearance of plastic bronchitis type I. He had profuse expectoration of several pieces, a few cm long and up to 1 cm wide, of wormlike reddish-brownish "tissue". Histologically, it was a slimy purulent secretion with abundant fibrin and blood and with cytopathic effect of herpes virus. The pathogenesis of plastic bronchitis is not clear.

[Erythroblasts in the peripheral blood of adult patient as an adverse prognostic sign--a case report]. / Eritroblasti u perifernoj krvi odraslog bolesnika kao nepovoljan prognosticki predznak--prikaz bolesnika.

Red blood cells (RBC) normally lose their nuclei before appearing in peripheral blood. After having undergone differentiation in bone marrow, blood cells must cross the blood-marrow barrier to enter the bloodstream. Erythroblasts, or nucleated red blood cells (NRBC), do not distort easily, so they cannot escape this barrier. Therefore, with the exception of the neonatal period, the presence of NRBCs in peripheral blood is always a pathologic finding. NRBCs may be found in the course of severe diseases and are associated with poor prognosis and higher mortality. The underlying pathophysiology of NRBCs in peripheral blood is not fully understood. It is hypothesized that their appearance could be provoked by either increased erythropoiesis or bone marrow micro-architectural damage mostly caused by inflammation and/or decreased tissue oxygenation. In addition, it is known that the mortality is higher in NRBC-positive patients as compared with NRBC-negative patients. Hereby we present a patient admitted to the hospital with the symptoms of cardiac failure and decompensated liver cirrhosis. The patient was already known to have liver cirrhosis of ethylic etiology, cardiac decompensation caused by hypertensive heart disease with permanent atrial fibrillation, chronic obstructive pulmonary disease, diabetes mellitus type 2, and cholelithiasis. During hospital stay, the patient developed acute pancreatitis and, soon after that, a stroke with left hemiparesis followed by cardiopulmonary arrest. Then he was transferred to the intensive care unit. Despite appropriate therapy, intensive care treatment and cardiopulmonary support, the patient's general state worsened, he developed multiple organ failure and died on day 10 of intensive care unit stay. Three days earlier, NRBCs were detected in peripheral blood and their concentration increased during the next two days before death. NRBCs are known to appear 1-3 weeks before death, but their appearance does not seem to be related to one particular cause of death. Still, detection of NRBCs is an independent risk of poor outcome, where the mortality increases with the increasing NRBC concentration. Detection of NRBCs in blood is a relatively early phenomenon prior to death, so screening for NRBCs may aid in the early identification of patients at high risk, and in making duly decision for NRBC-positive patients to obtain ongoing intensive care treatment.

[Pleural mesothelioma--case report]. / Mezoteliom pleure--prikaz bolesnika.

Pleural mesothelioma is a rare neoplasm with the incidence of 1-2 per million people. The incidence is higher in male population (10-30/million), whereas the incidence in female population is 2 per million. It occurs predominantly at older age (65+ years). The most common clinical manifestation of pleural mesothelioma is pleural effusion with dyspnea, which makes it a diagnostic problem since many cardiac diseases can have the same presentation. We report a case of pleural mesothelioma in an 80-year-old woman that presented with dyspnea and pleural effusion, which was at first considered as a sign of heart failure. Clinical presentation also included metabolic disorders and deep vein thrombosis, and the patient's epidemiologic history was negative, so diagnostic procedures including pleurocentesis were directed towards detection of the possible malignant disease. Cytologic analysis followed by biopsy pointed to the diagnosis of pleural mesothelioma. Persistent pleural effusions that do not coincide with cardiac disease, especially if accompanied by metabolic disorders and paraneoplastic syndromes, require additional diagnostic workup to identify the etiology of pleural effusion.

Relationship between polymorphonuclear leukocyte count in bronchoalveolar lavage fluid and bacterial content in Gram's stain and bacterial content in final microbiological report.

Eighty samples of bronchoalveolar lavage fluid (BALF) were obtained from the total of 48 patients (22 females and 26 males) and analyzed. Eighteen of those patients were organ transplant recipients. The relationship between polymorphonuclear leukocyte (PMN) count in direct sample and semi quantitative Gram-positive and Gram-negative bacterial content were analyzed in BALF samples. PMN count in direct sample and Gram-positive and Gram-negative bacterial content of the final microbiological report was compared as well. On the total number of samples PMN count in direct samples of BALF was statistically significant regarding the presence of Gram-positive bacteria in the same sample; it was nearly significant regarding the presence of Gram-negative bacteria; and it was statistically significant for the total bacterial content. If BALF samples are divided into those obtained from organ-transplant and those obtained from non-organ-transplant patients, positive, statistically significant relationship is found in the organ-transplant group, more specifically for the relationship between PMNs and total bacterial content. When PMN count in direct microbiological sample was compared with the results of the final microbiological report, statistically significant relationship was found neither with respect to all BALF samples, nor after dividing them into "organ-transplant" and "non-organ-transplant" group. We did not find differences caused by gender.

Life threatening complications after unsuccessful attempt of the guidewire dilating forceps tracheostomy in multi-trauma patient with cervical spine injury.

Percutaneous tracheostomy (PCT) is a safe method under proper patient selection, increased technical experience and bronchoscopy- or ultrasound-guided procedure. Trauma patients with cervical spine fractures and spinal cord injury are at a high risk for respiratory failure and require a definitive airway followed by prolonged mechanical ventilation. We would like to present multiple, life- threatening complications after unsuccessful attempt of the guidewire dilating forceps tracheostomy (GWDF) in one trauma patient with a cervical spine injury. With this case report we would like to lay emphasis on the importance of continuously bronchoscopy- or ultrasound-guided PTC in trauma patients, especially with cervical spine injury, as the need to respect the steep-learning curve in its performance.

[Rare complications of Salmonella enteritidis infection]. / Rijetke komplikacije infekcije salmonelom enteritidis.

We report 64-year old patient who was admitted in ICU with left side ileofemoral thrombosis and splenic abscess during Salmonella enteritidis infection.

The optimal pediatric induction dose of propofol in combination with reduced-dose rocuronium and alfentanil for day-case tonsillectomy in children.

OBJECTIVE: Tonsillectomy in children may be performed on a day-case basis. To achieve quality anesthesia and successful, fast recovery with minimal morbidity without the use of volatile anesthetic, the choice of drug combination has to be centered on one rapid- and short-acting hypnotic, opioid and non-depolarizing muscle relaxant. The aim of our study was to determine the optimal pediatric induction dose of propofol that by means of alfentanil and reduced-dose rocuronium allows the highest percentage of excellent intubating conditions. METHODS: One hundred and eleven children were randomized in three equal groups and included in prospective, double blind study. Anesthesia was induced with 2.0 (Group A), 2.5 (Group B) or 3.0 mg kg(-1) (Group C) of propofol proceeded by alfentanil (0.02 mg kg(-1)). Muscle relaxation was achieved with reduced-dose rocuronium (1.5x ED(95)) (0.45 mg kg(-1)). The intubating conditions were assessed using the four-point scoring system based on the difficulty of laryngoscopy, presence of vocal cord movement and the intensity of coughing. Neuromuscular transmission was monitored by means of acceleromyography with supramaximal train-of-four stimulation of the ulnar nerve by the frequency of 1Hz. RESULTS: Adequate intubating conditions were achieved in high percentages in all study groups (A = 94%, B = 95%, C = 98%) (P = 0.352). Significant higher differences of excellent and good intubating conditions, attributed to quality of laryngoscopy, movement of the vocal cords and intensity of coughing were observed in Group C (excellent = 94%, good = 4%) (B = excellent 80%, good = 18% and A = excellent 47%, good = 47%) (P = 0.0001). MAP decrease of 12% from the baseline occurred immediately only after 3.0 mg kg(-1) induction dose of propofol (80+/-7 mm Hg; A = 92 +/- 6, B = 88 +/- 9) (P = 0.005). CONCLUSIONS: Induction dose of 2.5 mg kg(-1) of propofol preceded by 0.02 mg kg(-1) of alfentanil in addition to reduced-dose rocuronium (0.45 mg kg(-1)) is the optimal pediatric induction dose of propofol for improving the most excellent intubating conditions without significant hemodynamic changes.

NATIVE VALVE ENDOCARDITIS CAUSED BY METHICILLIN-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS IN A PATIENT WITH ADVANCED LIVER CIRRHOSIS.

We present a case of a 50-year-old man with advanced liver cirrhosis and native valve infective endocarditis caused by methicillin-resistant Staphylococcus epidermidis. Bacterial infections are one of the most common complications of liver cirrhosis, but reports of infective endocarditis in patients with liver cirrhosis are relatively rare. Because of vulnerability of patients with advanced cirrhosis for developing infections, it is necessary to pay attention to the pathogens that are sometimes considered contamination and actively seek for the seat of infection, even in less expected areas (e.g., native heart valves without a history of heart disease).

CIRCADIAN RHYTHM OF BLOOD PRESSURE RESTORATION AND NEPHROTIC PROTEINURIA ALLEVIATION IN A PATIENT WITH CHRONIC KIDNEY DISEASE AFTER RENAL SYMPATHETIC DENERVATION.

Renal sympathetic denervation (RSD) could be an effective antihypertensive treatment of resistant hypertension that triggers additional positive effects on glucose metabolism and insulin sensitivity in type 2 diabetes mellitus. We report the effects of RSD in a patient with chronic kidney disease, type 2 diabetes mellitus and resistant hypertension, manifesting as blood pressure reduction with dipping pattern restoration, followed by nephrotic proteinuria alleviation. The non-dipping blood pressure pattern and proteinuria increase the risk of cardiovascular complications and accelerate kidney disease progression. Thus, further research documenting the frequency and investigating the mechanisms of these effects reported after RSD in chronic kidney disease patients with type 2 diabetes mellitus and resistant hypertension is necessary for the benefit of this high-risk patient population.

The right atrial thrombus: the sword of Damocles with real risk of massive pulmonary embolism.

Cases of 6 patients admitted at the intensive care unit for massive pulmonary embolism are reported. All patients presented with dyspnea, tachypnea, and tachycardia, and 4 were hypotensive and had syncope. Lung ventilation/ perfusion scans revealed perfusion defects in 4 patients. Transthoracic echocardiography (TTE) demonstrated acute cor pulmonale. It also revealed mobile right atrial thrombi in 5 patients, adherent thrombus in the right atrium in 1 patient and patent foramen ovale in 4 patients. Thrombolytic therapy was initiated in 4 patients, and 2 patients received heparin infusion only. Effects of thrombolysis were monitored using bedside TTE during the first 24 hours and in follow-up. The outcome of 4 patients who received thrombolytic therapy was good whereas other 2 patients, who received only heparin, died. Thrombotic mass disappeared 8 to 12 hours after initiation of therapy, and 10 weeks after discharge TTE showed normalized right ventricle dimensions and function in all 4 patients.