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Carbapenems are considered to be among the last line antibiotics against extended-spectrum β-lactamase producing Enterobacterales. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been frequently reported and its spread in Europe is indisputable and poses an enormous threat to hospitalized patients which is of growing concern. This review aims to record prevalence of CRKP in the Balkan region and to review the current knowledge about this life-threatening pathogen. In this review, we summarize data about clinical isolates of carbapenem-resistant K. pneumoniae from Greece, Croatia, Romania, Bulgaria, Serbia, Slovenia, Montenegro, Bosnia-Herzegovina and Albania from published reports between 2000 and 2023. Among Balkan countries, Greece and Romania are the ones with the most reports about CRKP. Since 2007, KPCs are the dominant carbapenemases in both countries. KPC-2 and NDM-1-producing K. pneumoniae strains have been identified as the most frequent CRKP in Croatia, Bulgaria, Serbia, and Slovenia. OXA-48 enzyme has been identified in most Balkan countries. In addition, since 2018, CRKP sequence type 11 (ST11) seems to have replaced ST258 in Balkan Peninsula, while ST15 continues to thrive throughout the years. Not only efficacy of colistin against CRKP has decreased dramatically during the last ten years but colistin resistance mechanism is based on alterations of chromosomal mgrB gene, rather than the already known mcr genes.Moreover, ceftazidime-avibactam-resistant CRKP were detected mostly in Greece. Emergence of CRKP poses a severe threat to the Balkan countries. Due to the narrow therapeutic window, it is essential to prevent the spread of multiresistant K. pneumoniae strains.

In this study, the performance of two commonly used routine antimicrobial susceptibility testing methods, the automated VITEK(®)2 system and Etest (bioMérieux, Marcy-l'Étoile, France), was compared with the standard broth microdilution (BMD) method on 87 multidrug- and carbapenem-resistant Acinetobacter baumannii clinical isolates. Clinical and Laboratory Standards Institute (CLSI) 2015 breakpoints (susceptible, ≤4 mg/L; intermediate, 8 mg/L; and resistant, ≥16 mg/L) were used. Minocycline showed excellent activity, with 94.3% of isolates susceptible by BMD (VITEK(®)2, 73.6%; Etest, 63.2%). The MIC50/90 values (minimum inhibitory concentrations required to inhibit 50% and 90% of the isolates, respectively) were as follows: BMD, 1/4 mg/L; VITEK(®)2, ≤1/8 mg/L; and Etest, 4/16 mg/L. Etest produced 14.9% major/20.7% minor errors and VITEK(®)2 produced 3.4% major/17.2% minor errors. These data indicate that VITEK(®)2 may be more reliable than Etest for routine susceptibility testing of minocycline for A. baumannii isolates. As both VITEK(®)2 and Etest produced higher minocycline MICs compared with the reference method, BMD may be needed to validate the categorisation of carbapenem-resistant A. baumannii by these assays as minocycline non-susceptible., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Glucose metabolism of children with drug-resistant epilepsy, controlled by antiepileptic drugs epilepsy, and first-time nonfebrile seizures was studied through the performance of an oral glucose tolerance test and through insulin, C-peptide, and glycosylated hemoglobin measurements. In the refractory epilepsy group, there were more abnormal oral glucose tolerance test results (62.07%) in comparison to the controlled epilepsy group (25%) and the group of first-time seizures (21.21%). There was a significant difference between the group of refractory epilepsy and every other group concerning the abnormality of the oral glucose tolerance test (P < .05). The mean values of insulin, HbA 1c , and C-peptide levels were normal for all groups. The results of the present study suggest that there is a distinction of refractory epilepsies from the drug-controlled ones and the first-induced seizures relating to their metabolic profile, regardless of the type of seizures.

Introduction: Concentrations of B-type natriuretic peptide (BNP) are recognised as a reliable marker of ventricular dysfunction in adults. In this study, plasma levels of BNP were determined in children with congenital heart disease (CHD) involving a left-to-right shunt, and were correlated with the shunt volume., Methods: Seventy-six children (38 boys/38 girls, mean age 22.4 months) with CHD (Group A: 31 with atrial septal defect [ASD], 23 with ventricular septal defect [VSD], 8 with ASD and VSD, 14 with patent ductus arteriosus [PDA]) and 34 healthy children (group B) were studied. BNP was measured by chemiluminescent microparticle immunoassay in all children. The amount of shunt (the ratio of pulmonary blood flow/systemic blood flow: Qp/Qs) was measured using Doppler velocimetry and two-dimensional echocardiography. A haemodynamically significant left-to-right shunt was defined as Qp/Qs>1.5. Correlations were evaluated between all patient groups and healthy subjects and BNP was compared with echocardiographic data reflecting right and left ventricle volume overload., Results: Thirty-four children of group A had Qp/Qs>1.5 (group A1) and 42 Qp/Qs<1.5 (group A2). BNP levels were higher in group A1 than group A2 (p=0.015), while there were no significant differences in BNP between group A2 and group B (p=0.79). BNP 24.4 pg/ml was determined as the cut-off point to identify patients with Qp/Qs>1.5. BNP values were similar among patients with ASD and VSD, but they were significantly higher in patients with PDA. BNP was positively correlated with Qp/Qs (r=0.59, p<0.001), and with the pulmonary artery velocity (r=0.27) and gradient (r=0.49), while there was a negative correlation with ejection fraction (r=-0.14). BNP levels were significantly higher in 10 infants with clinical signs of heart failure (p=0.025)., Conclusion: These results, which are consistent with previous reports, suggest a possible role of BNP as an early diagnostic marker of the significance of shunt in children with CHD.

A pilot prospective follow-up study of the role of the branched chain amino acids as additional therapy to the ketogenic diet was carried out in 17 children, aged between 2 and 7 years, with refractory epilepsy. All of these patients were on the ketogenic diet; none of them was seizure free, while only 13 had more or less benefited from the diet. The addition of branched chain amino acids induced a 100% seizure reduction in 3 patients, while a 50% to 90% reduction was noticed in 5. Moreover, in all of the patients, no reduction in ketosis was recorded despite the change in the fat-to-protein ratio from 4:1 to 2.5:1. Although our data are preliminary, we suggest that branched chain amino acids may increase the effectiveness of the ketogenic diet and the diet could be more easily tolerated by the patients because of the change in the ratio of fat to protein.