Multidrug-Resistant Bacteria in Surgical Intensive Care Units: Antibiotic Susceptibility and ß-Lactamase Characterization.

Multidrug-resistant (MDR) bacteria of the utmost importance are extended-spectrum ß-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). In this study, an evaluation of MDR bacteria in surgical intensive care units in a tertiary referral hospital was conducted. The study aimed to characterize ß-lactamases and other resistance traits of Gram-negative bacteria isolated in surgical intensive care units (ICUs). Disk diffusion and the broth dilution method were used for antibiotic susceptibility testing, whereas ESBL screening was performed through a double disk synergy test and an inhibitor-based test with clavulanic acid. A total of 119 MDR bacterial isolates were analysed. ESBL production was observed in half of the Proteus mirabilis, 90% of the Klebsiella pneumoniae and all of the Enterobacter cloacae and Escherichia coli isolates. OXA-48 carbapenemase, carried by the L plasmid, was detected in 34 K. pneumoniae and one E. coli and Enterobacter cloacae complex isolates, whereas NDM occurred sporadically and was identified in three K. pneumoniae isolates. OXA-48 positive isolates coharboured ESBLs belonging to the CTX-M family in all but one isolate. OXA-23 carbapenemase was confirmed in all A. baumannii isolates. The findings of this study provide valuable insight of resistance determinants of Enterobacterales and A. baumannii which will enhance surveillance and intervention strategies that are necessary to curb the ever-growing carbapenem resistance rates.

Evolution of Beta-Lactamases in Urinary Klebsiella pneumoniae Isolates from Croatia; from Extended-Spectrum Beta-Lactamases to Carbapenemases and Colistin Resistance.

K. pneumoniae isolates often harbor various antibiotic resistance determinants including extended-spectrum ß-lactamases (ESBLs), plasmid-mediated AmpC ß-lactamases (p-Amp-C) and carbapenemases. In this study we analyzed 65 K. pneumoniae isolates obtained from urinary tract infections in the outpatients setting, with regard to antibiotic susceptibility, ß-lactamase production, virulence traits and plasmid content.Antibiotic susceptibility was determined by broth microdilution method. PCR was applied to detect genes encoding ESBLs, p-Amp-C and carbapenemases and plasmid incompatibility groups. Phenotypic methods were applied to characterize virulence determinants. Increasing resistance trend was observed for amoxicillin/clavulanate, imipenem, meropenem and ciprofloxacin. The study showed that ESBLs belonging to the CTX-M family, conferring high level of resistance to expanded-spectrum cephalosporins (ESC) were the dominant resistance trait among early isolates (2013 to 2016) whereas OXA-48 carbapenemase, belonging to class D, emerged in significant numbers after 2017. OXA-48 producing organisms coharbored ESBLs. KPC-2 was dominant among isolates from Dubrovnik in the recent years. Colistin resistance was reported in three isolates. Inc L/M was the dominant plasmid in the later period, encoding OXA-48. Hyperviscosity was linked to KPC positivity and emerged in the later period. This report describes evolution of antibiotic resistance in K. pneumoniae from ESBLs to carbapenemases and colistin resistance. The study demonstrated the ability of K. pneumoniae to acquire various resistance determinants, over time. The striking diversity of the UTI isolates could result from introduction of the isolates from the hospitals, transfer of plasmids and multidirectional evolution.

THE EFFECT OF REGIONAL VS. GENERAL ANESTHESIA ON THE IMMUNE RESPONSE IN BREAST CANCER SURGERY: A NARRATIVE REVIEW OF THE LITERATURE.

For breast cancer patients, surgery remains the cornerstone in treatment. Perioperative and postoperative period is associated with impaired immune function that can have profound implications for cancer patients in terms of tumor recurrence and metastases. The three main factors include surgery and related neuroendocrine stress response, anesthetic drugs, including opioid analgesics and postoperative pain. The most investigated immune cells are natural killer (NK) cells that are affected by both anesthesia and surgery. It has been demonstrated that ketamine, thiopental, volatile anesthetics, fentanyl and morphine, but not propofol, remifentanil or tramadol reduce the number of circulating NK cells and depress their toxicity. The level of NK cells' cytotoxicity is inversely proportional to the stage and spread of cancer. Regional anesthesia and its potential beneficial effects on the perioperative immune response and long-term outcome after surgery has been investigated as an alternative to general anesthesia in patients undergoing breast cancer surgery. In this paper, we present a review of literature aimed to assess the impact of regional anesthesia techniques on the immune response in patients undergoing breast cancer surgery and how it compares to general anesthesia.

Gram-negative bacteria as causative agents of ventilator-associated pneumonia and their respective resistance mechanisms.

Ventilator-associated pneumonia (VAP) is a serious and common complication in patients admitted to intensive care unit (ICU) and contributes to mortality. Multidrug Gram-negative bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae are frequently associated with VAP in ICU. A prospective study was set up in three ICUs of the University Hospital Center Zagreb and one ICU in General Hospital Pula from September 2017 to March 2018. Antibiotic susceptibility was determined by broth microdilution method. Production of extended-spectrum ß-lactamases (ESBLs) was determined by double-disk synergy test and carbapenemases by Hodge and carbapenem inactivation method (CIM). The genes encoding ESBLs, carbapenemases of class A, B and D and qnr genes were determined by PCR. In total 97 Gram-negative bacteria isolates were analyzed. P. aeruginosa demonstrated high resistance rates for imipenem and meropenem with 74% and 68% of resistant strains, respectively. Moderate resistance rates were observed for ceftazidime andpiperacillin/tazobactam, ciprofloxacin and gentamicin (44%). All except three A. baumannii isolates, were resistant to carbapenems and to all other antibiotics apart from colistin and amikacin. Eight A. baumannii isolates were positive for blaOXA-23 and 12 for blaOXA-24 genes. Four K. pneumoniae and two E. cloacae strains were ESBL positive and harboured group 1 of CTX-M ß-lactamases. Three P. mirabilis strains were positive for plasmid-mediated ampC ß-lactamase of CMY family. Two carbapenem-resistant K. pneumoniae harboured OXA-48 and one carbapenem-resistant E. cloacae VIM-1. A high proportion of multidrug-resistant P. aeruginosa, K. pneumoniae and extensively resistant A. baumannii was reported. Acquired resistance mechanisms, mainly production of carbapenemases and ESBLs were dominant in A. baumannii and K. pneumoniae, respectively. Resistance of P. aeruginosa isolates was more likely due to upregulation of efflux pumps or porin loss. A marked diversity of ß-lactamases was identified in Enterobacteriaceae.

REGIONAL ANESTHESIA FOR NEUROSURGERY.

During neurosurgery procedures it is vital to assure optimal cerebral perfusion and oxygenation. Despite physiological autoregulation of brain perfusion, maintaining hemodynamic stability and good oxygenation during anesthesia is vital for success. General anesthesia with mechanical ventilation and current drugs provide excellent hemodynamic condition and it is the first choice for most neurosurgery procedures. However, sometimes it is very hard to avoid brief increase or decrease in blood pressure especially during period of intense pain, or without pain stimulation. This could be detrimental for patients presented with high intracranial pressure and brain edema. Modifying anesthesia depth or treatment with vasoactive drugs usually is needed to overcome such circumstances. On the other hand it is important to wake the patients quickly after anesthesia for neurological exam. That is why regional anesthesia of scalp and spine could show beneficial effects by decreasing pain stimuli and hemodynamic variability with sparing effect of anesthetics drugs. Also regional techniques provide excellent postoperative pain relief, especially after spinal surgery.

Consequence of Elevated Fibroblast Growth Factor 23 Levels in Acute Kidney Injury, Renal Recovery and Overall Survival in Intensive Care Unit Patients After Major Surgery.

The main goal of our study was to investigate the role of increased fibroblast growth factor 23 (FGF23) levels on renal recovery and overall survival. We conducted a prospective case-control cohort study, which included 121 adult cases who developed AKI after major surgical procedures. The subjects were followed-up until the last enrolled patient survived 180 days or until the time of death. Higher FGF23 levels positively correlated with serum creatinine levels (P < 0.05). Significantly higher number of patients without diuresis and with FGF23 ≤ 709 RU/mL survived when compared to patients without diuresis and with FGF23 ≥ 709 RU/mL (P < 0.001). FGF23 levels >709 RU/mL were a good predictive tool for overall mortality in a 6-month period (P < 0.05). This is the first study to analyze the impact of FGF23 values on short-term renal recovery and survival of patients with AKI after major surgery. The FGF23 increase related to AKI especially in more severe stages and in patients without diuresis is an independent risk factor for mortality.

Epidemic spread of OXA-48 beta-lactamase in Croatia.

PURPOSE: A dramatic increase in OXA-48 ß-lactamase was observed recently not only in large hospital centres, but also in smaller suburban hospital centres in geographic areas bordering Croatia. The aim of the study was to analyse the epidemiology, the mechanisms of antibiotic resistance and the routes of spread of OXA-48 carbapenemase in Croatia. METHODS: Carbapenemase and other ß-lactamase and fluoroquinolone resistance genes were detected by PCR and sequencing. Whole-genome sequencing (WGS) was performed on five representative isolates. The isolates were genotyped by PFGE. RESULTS: Forty-eight isolates positive for OXA-48, collected from seven hospital centres in Croatia from May 2016 to May 2017, were analysed (40 Klebsiella pneumoniae, 5 Enterobacter cloacae, 2 Escherichia coli and one Citrobacter freundii). Thirty-three isolates were ESBL positive and harboured group 1 CTX-M 1 ß-lactamases. In addition to the ß-lactam resistance genes detected by PCR (blaSHV-1, blaOXA-48 and blaOXA-1), WGS of five representative isolates revealed the presence of genes encoding aminoglycoside resistance, aadA2 and aph3-Ia, fluoroquinolone resistance determinants aac(6)Ib-c, oqxA and oqxB, the sulfonamide resistance gene sul1, and fosA (fosfomycin resistance). IncL plasmid was found in all isolates. Two K. pneumoniae isolates belonged to ST16, two E. cloacae to ST66 and E. coli to ST354. K. pneumoniae isolates were allocated to five clusters by PFGE which occured in different hospitals, indicating epidemic spread. CONCLUSIONS: The OXA-48-positive organisms found in this study showed wide variability in antibiotic susceptibility, ß-lactamase content and PFGE banding patterns. This study revealed a switch from the predominance of VIM-1 in 2012-2013 to that of OXA-48 in the 2015 to 2017.

Effect of Inhalational Anesthetics on Acute Kidney Injury

Acute kidney injury (AKI) is a serious complication associated with increased morbidity and mortality. Total incidence of AKI in hospitalized patients is 1%-5%. As many as 30% of these patients develop AKI in the perioperative period, which is associated with anesthesia and surgery. Despite scientific advances and improved surgery techniques, as well as treatment in intensive care units, no significant decrease in AKI incidence has been achieved. To change this outcome, it is important to identify patients at risk of AKI and prevent its occurrence. Correct selection of anesthetic drugs during general anesthesia, adjusted to the individual needs of patients, also influences the overall outcome of treatment. Nowadays, inhalational anesthetics are not considered nephrotoxic. The more so, inhalational anesthetics have a strong and direct protective effect on many organs through preconditioning and postconditioning. New studies have shown that sevoflurane diminishes ischemia/ reperfusion kidney injury and has an anti-inflammatory effect, thus having the potential to reduce the occurrence of AKI. Given the incidence of AKI in the perioperative period, as well as new findings about anesthetics, the issue of anesthetic selection during general anesthesia might be of crucial importance for the final outcome of treatment.

Vascular access for chronic hemodialysis in a patient with epidermolysis bullosa dystrophica Hallopeau-Siemens.

Epidermolysis bullosa is a rare genetic hereditary disease characterized with mechanobullous dermatosis. Except cutaneous, these patients have various extracutaneous manifestations and some types of epidermolysis bullosa comprise almost all organ systems. Because of prolonged life span, chronic renal insufficiency has become an important cause of morbidity and death in these patients. Establishment of functional vascular dialysis access is a great challenge for both the doctors and the patients. Multidisciplinary approach is essential. We present a case of successful establishment of dialysis access via Tesio catheter in a young woman suffering from epidermolysis bullosa dystrophica Hallopeau-Siemens and end-stage renal disease. Since then, the Tesio catheter inserted via the right internal jugular vein has been the functional mean of dialysis. The patient was given the opportunity to lead a quality and active life in spite of disabling disease. Several cases of successful dialysis access establishment with dialysis catheters via central veins have been reported. We report the successful establishment of long-term dialysis access via Tesio catheter and suggest this approach as ideal for these patients. This is the first report dealing with vascular access in this group of patients.

[Pathophysiology of delirium]. / Patofiziologija delirija.

Today's understanding of the pathophysiological mechanisms of delirium is still limited, but there are several promising hypotheses. It is believed that biomarkers sensitive to death of neurons or glial cells indicate delirium. Several neurotransmitters are considered to be involved in the state of delirium, with greatest emphasis on acetylcholine and dopamine acting in opposite ways; acetylcholine reduces, while dopamine increases neuron excitability. Other neurotransmitters that probably play a role in the pathogenesis of delirium are GABA, glutamate and monoamines. Sepsis leading to systemic inflammatory response syndrome often presents with delirium and perhaps is the most common causal factor for delirium in intensive care unit; sedatives and analgesics are also common iatrogenic risk factors. Patients receiving benzodiazepines are more likely to have postoperative delirium than those who do not. Postoperative cognitive changes are more common in older than in younger patients, and they can be categorized as postoperative delirium, postoperative cognitive dysfunction and dementia. The mechanisms responsible for postoperative cognitive changes are not fully understood, but it is certain that they are multifactorial. Risk factors may be associated with patient characteristics, type of surgery and type of anesthesia.

Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma.

BACKGROUND: Recent studies demonstrated that the expression pattern of bone morphogenetic protein-7 (BMP-7) is altered in different tumors. We determined expression of BMP-7 in human clear cell renal carcinoma (CCRC). METHODS: Samples from cancer and corresponding healthy tissue were obtained from 20 patients who underwent nephrectomy for CCRC. Expression of BMP-7 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression was analyzed by immunohistochemistry. RESULTS: RT-PCR showed strong down-regulation of BMP-7 mRNA in cancer tissue. Immunohistochemistry revealed expression of BMP-7 in normal renal tissue, with almost complete loss of BMP-7 expression in malignant cells of 6 patients (30%). After 3 years of follow-up, 5 out of 6 patients with high BMP-7 mRNA expression were alive and disease-free, compared with 9 out of 14 patients with low BMP-7 mRNA expression. CONCLUSIONS: BMP-7 mRNA and protein expression were down-regulated in CCRC. Further prospective studies are needed to characterize the role of BMP-7 in human CCRC.