Bacterial bloodstream infection in critically ill patients with COVID-19: a retrospective cohort study.

Background: Intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19), have a high risk of developing bloodstream infections (BSIs). However, the characteristics of and risk factors for BSIs in these patients remain unclear. Objective: We aimed to identify prevalent causative pathogens of BSI and related factors in critically ill patients with COVID-19. Design: This was a single-center, retrospective cohort study. Methods: We analyzed the clinical characteristics and outcomes of 201 ICU patients with COVID-19. Logistic regression analysis was conducted to identify factors associated with BSI occurrence. Furthermore, we identified the primary causative pathogens of BSIs. The study outcomes were death or ICU discharge. Results: Among the 201 included patients, 43 (21.4%) patients developed BSI. The mortality rate was non-significantly higher in the BSI group than in the BSI group (65.1% versus 58.9%, p = 0.487). There were significant between-group differences in the obesity prevalence and sex distribution, but not corticosteroid usage. BSI occurrence was significantly associated with duration of mechanical ventilation (MV), presence of ventilator-associated pneumonia, use of neuromuscular blocking agents, length of stay in ICU (ICU LOS), high body mass index (BMI), and male sex. The main causative pathogens were Klebsiella pneumoniae, Acinetobacter baumannii, and Enterococcus faecalis. Multi-drug-resistant pathogens were found in 87% of cases. Regardless of the origin, the common risk factors for BSI were ICU LOS and MV duration. All BSIs were acquired within the hospital setting, with ≈60% of the cases being primary BSIs. A small proportion of the BSI cases were catheter-related (four cases, 6.2%). Ventilator-associated pneumonia and urinary tract infections were present in 25% and 9.4% of the BSI cases, respectively. On average, the first positive blood culture appeared ≈11.4 (±9.7) days after ICU admission. Conclusion: Elucidating the risk factors for and common pathogens of BSI can inform prompt management and prevention of BSIs.

Plasmid Mediated mcr-1.1 Colistin-Resistance in Clinical Extraintestinal Escherichia coli Strains Isolated in Poland.

Objectives: The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a "last-resort" antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne mcr colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal Escherichia coli strains. Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical E. coli strains. Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene. Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an "epidemic" plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.

Abdominoplasty Skin-Based Dressing for Deep Wound Treatment-Evaluation of Different Methods of Preparation on Therapeutic Potential.

The management of hard-to-heal wounds is a significant clinical challenge. Acellular dermal matrices (ADMs) have been successfully introduced to enhance the healing process. Here, we aimed to develop protocol for the preparation of novel ADMs from abdominoplasty skin. We used three different decellularization protocols for skin processing, namely, 1M NaCl and sodium dodecyl sulfate (SDS, in ADM1); 2M NaCl and sodium dodecyl sulfate (SDS, in ADM1); and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We assessed the effectiveness of decellularization and ADM's structure by using histochemical and immunochemical staining. In addition, we evaluated the therapeutic potential of novel ADMs in a murine model of wound healing. Furthermore, targeted transcriptomic profiling of genes associated with wound healing was performed. First, we found that all three proposed methods of decellularization effectively removed cellular components from abdominoplasty skin. We showed, however, significant differences in the presence of class I human leukocyte antigen (HLA class I ABC), Talin 1/2, and chondroitin sulfate proteoglycan (NG2). In addition, we found that protocols, when utilized differentially, influenced the preservation of types I, III, IV, and VII collagens. Finally, we showed that abdominoplasty skin-derived ADMs might serve as an effective and safe option for deep wound treatment. More importantly, our novel dressing (ADM1) improves the kinetics of wound closure and scar maturation in the proliferative and remodeling phases of wound healing. In conclusion, we developed a protocol for abdominoplasty skin decellularization suitable for the preparation of biological dressings. We showed that different decellularization methods affect the purity, structure, and therapeutic properties of ADMs.

Skin Substitute Preparation Method Induces Immunomodulatory Changes in Co-Incubated Cells through Collagen Modification.

Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin. Here we propose a novel strategy for ADM preparation from human abdominoplasty-derived skin. Skin was processed using three different methods of decellularization involving the use of ionic detergent (sodium dodecyl sulfate; SDS, in hADM 1), non-ionic detergent (Triton X-100 in hADM 2), and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We next evaluated the immunogenicity and immunomodulatory properties of this novel hADM by using an in vitro model of peripheral blood mononuclear cell culture, flow cytometry, and cytokine assays. We found that similarly sourced but differentially processed hADMs possess distinct immunogenicity. hADM 1 showed no immunogenic effects as evidenced by low T cell proliferation and no significant change in cytokine profile. In contrast, hADMs 2 and 3 showed relatively higher immunogenicity. Moreover, our novel hADMs exerted no effect on T cell composition after three-day of coincubation. However, we observed significant changes in the composition of monocytes, indicating their maturation toward a phenotype possessing anti-inflammatory and pro-angiogenic properties. Taken together, we showed here that abdominoplasty skin is suitable for hADM manufacturing. More importantly, the use of SDS-based protocols for the purposes of dermal matrix decellularization allows for the preparation of non-immunogenic scaffolds with high therapeutic potential. Despite these encouraging results, further studies are needed to evaluate the beneficial effects of our hADM 1 on deep and hard-healing wounds.

Optimization of Novel Human Acellular Dermal Dressing Sterilization for Routine Use in Clinical Practice.

Gamma rays and electrons with kinetic energy up to 10 MeV are routinely used to sterilize biomaterials. To date, the effects of irradiation upon human acellular dermal matrices (hADMs) remain to be fully elucidated. The optimal irradiation dosage remains a critical parameter affecting the final product structure and, by extension, its therapeutic potential. ADM slides were prepared by various digestion methods. The influence of various doses of radiation sterilization using a high-energy electron beam on the structure of collagen, the formation of free radicals and immune responses to non-irradiated (native) and irradiated hADM was investigated. The study of the structure changes was carried out using the following methods: immunohistology, immunoblotting, and electron paramagnetic resonance (EPR) spectroscopy. It was shown that radiation sterilization did not change the architecture and three-dimensional structure of hADM; however, it significantly influenced the degradation of collagen fibers and induced the production of free radicals in a dose-dependent manner. More importantly, the observed effects did not disrupt the therapeutic potential of the new transplants. Therefore, radiation sterilization at a dose of 35kGy can ensure high sterility of the dressing while maintaining its therapeutic potential.

Expression of MexAB-OprM efflux pump system and susceptibility to antibiotics of different Pseudomonas aeruginosa clones isolated from patients hospitalized in two intensive care units at University Hospital in Bialystok (northeastern Poland) between January 2002 and December 2009.

We investigated the genetic similarities and expression of the MexAB-OprM efflux pump system in different clones of multiresistant Pseudomonas aeruginosa strains collected from 2002 to 2009 at two intensive care units (ICU). Regulatory and structural genes mexB, mexR, and mexA were found in 99%, 98%, and 94% of tested strains, respectively. The presence of class 1 integron was found in 90% of the strains, while class 2 integron in only one strain (Psa506). Class 3 integron was not found in any of the tested strains. Among the eleven clones identified, only two clones, I and D, exhibited higher levels of mexB gene expression than the other clones. Clone I had the highest expression (FC = 10.36, p < 0.05). The results of our study indicated a high level of MexAB-OprM pump expression in groups of strains isolated in the years 2008-2009 (FC = 12.92, p < 0.03) and 2002-2006 (FC = 5.14, p < 0.03). There were no statistically significant differences in resistance to all tested antibiotics among the various clones. The high level of antimicrobial resistance may have been due to the coexistence of different resistance mechanisms among the studied P. aeruginosa strains. However, this does not exclude the contribution of the MexAB-OprM pump, particularly in resistance to meropenem and ciprofloxacin.

Assessment of serum IGF-1 and adipokines related to metabolic dysfunction in HIV-infected adults.

PURPOSE: HIV/HAART associated metabolic syndrome (HAMS) seems to result from direct influence of HIV, adverse effects of combined antiretroviral therapy (cART) and individual genetic predisposition. This study aimed to assess the influence of HIV infection and cART on serum concentration of insulin-like growth factor-1 (IGF-1) and adipokines related to metabolic abnormalities. METHODS: Seventy-two HIV infected patients including 48 HIV/HCV coinfected were enrolled in this study. Insulin resistance was evaluated by Homeostatic Model Assessment (HOMA) indexes. Serum concentrations of IGF-1, adiponectin, chemerin and visfatin were measured by ELISA. RESULTS: Significant correlation between serum IGF-1 level and CD4 lymphocytes count was demonstrated and the lowest values were observed in subjects with CD4<200 cells/µL. Serum concentration of IGF-1 was significantly higher in patients treated with protease inhibitors based regimen compared to non-nucleoside reverse transcriptase inhibitors and healthy subjects. A significant negative correlation between serum concentration of adiponectin and waist-hip ratio as an indicator of central obesity, was found. There were significant positive correlations between serum concentration of chemerin and HOMA1-IR and serum IGF-1 concentration. Serum chemerin was increased in patients with insulin resistance vs. those with preserved insulin sensitivity. CONCLUSIONS: According to these results HAMS is associated with insulin resistance and imbalance of adipokines serum concentration, therefore identification of pathways related to HAMS development might be helpful in management of the syndrome. Serum IGF-1 largely depends on level of immunodeficiency in HIV-infection and may provide a link between immune dysfunction and development of HIV-associated lipodystrophy, AIDS wasting syndrome, diabetes and/or cardiovascular diseases in HIV-infected patients.

Distribution of AdeABC efflux system genes in genotypically diverse strains of clinical Acinetobacter baumannii.

Acinetobacter baumannii has emerged as a highly problematic hospital-associated pathogen. Different mechanisms contribute to the formation of multidrug resistance in A. baumannii, including the AdeABC efflux system. Distribution of the structural and regulatory genes encoding the AdeABC efflux system among genetically diverse clinical A. baumannii strains was achieved by using PCR and pulsed-field gel electrophoresis techniques. The distribution of adeABRS genes is extremely high among our A. baumannii strains, except the adeC gene. We have observed a large proportion of strains presenting multidrug-resistance phenotype for several years. The efflux pump could be an important mechanism in these strains in resistance to antibiotics.

Occurrence of the aacA4 gene among multidrug resistant strains of Pseudomonas aeruginosa isolated from bronchial secretions obtained from the Intensive Therapy Unit at University Hospital in Bialystok, Poland.

The aim of this study was to investigate the prevalence of the aacA4 gene in a population of multidrug resistant strains of P. aeruginosa isolated from bronchial secretions obtained from the Intensive Therapy Unit (ITU). Twelve MDR isolates were tested for antibiotic susceptibility and the presence of the aacA4 gene. In this study, 58.3% of the strains contained (6')-Ib' aminoglycoside acetyltransferase gene. All of the studied strains (aacA4-positive and aacA4-negative) were susceptible only to colistine (100%). Among other antibiotics, the lowest resistance rates were those shown against ceftazidime (14.3% to 20%) and imipenem (28.6% to 40%). Our studies frequently revealed the presence of the aacA4 gene as a factor responsible for resistance; it is probable that other mechanisms of resistance to aminoglycoside antibiotics also occurred.

Susceptibility, phenotypes of resistance, and extended-spectrum ß-lactamases in Acinetobacter baumannii strains.

Acinetobacter baumannii plays an increasing role in the pathogenesis of infections in humans. The bacilli are frequently isolated from patients treated in intensive care units. A growing resistance to antibiotics is leading to the emergence of strains that are multidrug-resistant and resistant to all available agents. The objective of this study was to assess susceptibility to antibiotics and to determine the presence and current level of the extended-spectrum ß-lactamases (ESBLs) and attempt to isolate the Acinetobacter baumannii strain carrying the blaPER gene. A total of 51 strains of A. baumannii identified by phenotypic features were examined. That the strains belonged to the species was confirmed by the presence of the blaOXA-51-like; gene. A broth microdilution method was used for antibacterial susceptibility testing. The occurrence of ESBLs was determined using phenotypic double-disk synergy tests. The PCR technique was used to confirm the presence of the blaPER-1; gene encoding ESBL. The most active antibiotics were meropenem, cefepime and ampicillin/sulbactam, with susceptibility shown by 76.5%, 60.8% and 56.9% of the strains, respectively. The strains exhibited the highest resistance (> 75%) to piperacillin, tetracycline, ciprofloxacin and cefotaxime. Phenotypic tests revealed ESBL mechanism of resistance in approximately 20% of Acinetobacter baumannii isolates. However, the PCR technique did not confirm the presence of the blaPER-1; gene in any of the Acinetobacter baumannii strains examined in our hospital. Acinetobacter baumannii strains demonstrate considerable resistance to many groups of antibiotics. Our findings indicate the involvement of enzymes belonging to families other than PER ß-lactamase in resistance to ß-lactams in A. baumannii.

[Acute prosthetic valve thrombosis in a patient with neoplastic disease--difficulties with anticoagulation therapy]. / Ostra zakrzepica na sztucznej zastawce mitralnej u kobiety z choroba nowotworowa. Trudnosci leczenia przeciwzakrzepowego.

A case of a 50-year-old woman with prosthetic mitral valve complicated by severe thrombosis as an effect of incorrect anticoagulation treatment during rectal cancer biopsy, is presented. During echocardiographic evaluation a dysfunction prosthetic mitral valve with extremely high maximal mitral gradient (50.2 mmHg) was found. The patient was qualified for surgical intervention and mechanical prosthetic mitral valve was replaced by a biological one. This report underlines the difficulties in the anticoagulation therapy in patients with prosthetic heart valves.

[Thrombolysis during cardiopulmonary resuscitation--own clinical observations--case report]. / Zastosowanie leków fibrynolitycznych podczas resuscytacji oddechowo-krazeniowej--doswiadczenia wlasne--opis przypadku.

Thrombolytic therapy is contraindicated in the course of cardiopulmonary resuscitation (CPR). If the primary cause of cardiac arrest is myocardial infarction or massive pulmonary embolism, fibrynolysis may be life-saving. We present a case report of a woman admitted to the Intensive Care Unit with cardiac arrest with symptoms suggesting myocardial infarction or pulmonary embolism. After unsuccessful conservative CPR a single dose of 500000 IU streptase was administered. Heart action returned 10 minutes later, nevertheless the patient needed mechanical ventilation and circulatory system stabilization therapy (catecholamines) in doses dependent on haemodynamic parameters. During hospitalization she regained consciousness. She presented no neurological defects and after 5 days was discharged to the Cardiology Department. Electrocardiography and echocardiography done after successful resuscitation was specific to infero-lateral myocardial infarction. Although safety and efficacy of thrombolytic therapy at resuscitation was extensively studied, this procedure is still controversial. Till now, there is no data concerning thrombolytic treatment in such clinical situations, which are based on clinical trials, and such treatment is introduced in dramatic situations, as a last, lifesaving option.

[Staphylococcal infections as an important problem in intensive therapy--own clinical observations]. / Zakazenia gronkowcowe jako istotny problem w intensywnej terapii - doswiadczenia wlasne.

The microbiological monitoring in the Intensive Care Units, in the last few years, revealed a significant increase of infections caused by Gram+ bacteria. Authors of multi-center studies focus upon the problems related to the treatment of the infections caused by the methicilline-resistant staphylococci (MRS) as well as to its spreading. The Staphylococcal infections were 26.6 % of all bacterial infections in the Intensive Care Unit of the Department of Anesthesiology and Intensive Care of the Medical Academy in Bialystok, during one year observation. MRS rods counted 21.4% among all pathogens isolated from the specimens collected from the patients, undergoing the treatment in the ICU, and were responsible for 83.6% of all Staphylococcal infections. The analysis revealed the significant percentage MRS rods resistant to commonly used empirical antibiotic therapy. Our experience shows that vancomycin or linezolid should be used, as an empirical antibiotic therapy, in suspected MRS-caused severe infections along with the simultaneous monitoring of changes in G+ bacteria drug resistance and strict infection-control regime.

[Problems of perioperative period in patients with Steinert's myotonic dystrophy operated due to cataract]. / problemy okresu okolooperacyjnego u chorych na dystrofie miotoniczna steinerta, operowanych z powodu zacmy.

Steinert's myotonic dystrophy is a genetically conditioned systemic disease with symptoms related to circulatory, respiratory, muscular, endocrine and mental disturbances. Most if not all of these patients develop lens opacification as a presenting symptom and need to undergo cataract surgery. Nevertheless, selection of a type of anaesthesia can arise to a problem in these patients because local anaesthesia can be insufficient whereas general endotracheal anaesthesia is known, to potentially provoke serious postoperative complications. In this contribution we discuss problems we faced during cataract surgery in three siblings affected by Steinert's myotonic dystrophy. Two of them were operated on in local anaesthesia and developed intraoperative problems related to sudden increase of intraocular pressure, bleeding and vitreous efflux. After receiving a thorough examination the youngest of the three was operated on under short acting general intravenous anaesthesia (propofol and/or benzodiazepines, piperidine derived opioids, non-polarizing paralytics). We conclude that short acting general intravenous anaesthesia can help in avoiding both, local ocular complications during surgery and problems in the postoperative period.

[Assessment of the release of thyroid hormones in septic shock--prognostic significance]. / Ocena wydzielania hormonów tarczycy we wstrzasie septycznym--znaczenie prognostyczne.

UNLABELLED: Septic shock is the reason of human body organs dysfunctions including the hormonal system. There are abnormal thyroid hormones releasing as well. It is also noticed that sepsis caused serious disturbances in pituitary-thyroid axis functions. This is called euthyroid sick syndrom - (ESS). THE AIM: To qualify the prognostic value of thyroid hormones serum levels changes in patients with septic shock. MATERIAL AND METHODS: 20 patients with septic shock were included into study. Septic shock was diagnosed according to AACP/SCCM criteria. The study group was divided into two subgroups: survivors (n = 10) and nonsurvivors (n = 10). 20 healthy volunteers were the control group. Blood for analysis was taken at the moment of septic shock recognition and on the 1st, 2nd, 5th and 10th day of the observation between 8 a.m. and 9 a.m. We studied thyrotropin (TSH), free triiodothyronine fraction (fT3) and free thyroxin fraction (fT4) serum levels, APACHE II and APACHE III score, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). RESULTS: During our study we noticed significant decrease of fT3 and TSH serum levels (respectively 2.36 +/- 0.79 pg/ml and 0.76 +/- 1.12mU/I) according to the control group (respectively 3.28 +/- 0.61 pg/ml and 0.95 +/- 0.46mU/l). Nonsurvivors had significantly lower TSH serum level (0.37 +/- 0.62 mU/I) in comparison to survivors (1.27 +/- 1.45 mU/I) in spite of very similar fT3 serum level (respectively 2.45 +/- 0.87 pg/ml and 2.22 +/- 0.66 pg/ml). It could mean that there were disturbances in the pituitary-thyroid axis function in patients who did not survive. Our study did not show any correlations between thyroid hormones serum levels and APACHE II score, APACHE III score, ALI or ARDS. CONCLUSIONS: This study show that low TSH serum level could be a significant prognostic factor of death in patient with septic shock especially with low fT3 serum level. The results also suggest that ESS could be a consequence of pituitary TSH releasing disturbances.

[Serum levels of luteinizing hormone, testosterone and prolactin in patients with septic shock]. / Stezenie hormonu luteinizujacego, testosteronu i prolaktyny u chorych we wstrzasie septycznym.

Many studies show important disturbances in hormonal balance in patients with severe sepsis. There are a lot of factors, which are involved in this process but the role of sex steroid hormones is unknown; especially, the role of testosterone, which is one of the anabolic hormones and a immune function modulator. We hope that sex steroid hormone mechanisms of action recognition in septic shock may help in treatment of such patients. The aim of this study was to evaluate changes in sex hormone concentrations in septic patients and their prognostic significance. We studied serum level of luteinizing hormone (LH), testosterone (T) and prolactin (PRL) in 20 patients with septic shock and in healthy male volunteers (n = 20). Septic patients were divided into two groups: survivors (group I, n = 10) and nonsurvivors (group II, n = 10). We noticed significant decrease of testosterone and LH serum levels in septic group vs the controls and correlation between T and LH serum levels and survival. Acute lung injury was associated with higher PRL serum level and was independent from the LH and T serum level. We also noticed incorrect pituitary down-regulation of testosterone secretion. Our study showed that sex steroid hormones can be good prognostic factors of survival and complications of septic shock.

[The efficacy of intraventricularly administered vancomycin in the case of central nervous system infection caused by enterococcus faecalis]. / Skutecznosc wankomycyny stosowanej dokomorowo w zakazeniu osrodkowego ukladu nerwowego wywolanego przez Enterococcus faecalis.

The case of 40 years old man with subarachnoid hemorrhage with intraventricular bleeding and with consecutive cerebro-meningitis is presented. The bacterial pathogen was Enterococcus faecalis sensitive only to glycopeptide antibiotics. The standard therapy with intravenously administered Vancomycin and Teicoplanin was not effective. Because of the worsening of patient's clinical status and clinical symptoms of sepsis the intraventricular Vancomycin (20 mg/day) was introduced. At the second day of the therapy the gradual patient's recovery was observed. The symptoms typical for meningitis diminished as well as cerebro-spinal fluid (CSF) parameters normalized. There was no bacterial growth in the blood serum and in CSF. As we can observe the intraventricular administration of Vancomycin is efficient method of cerebro-meningitis treatment. In our opinion the blood-brain barrier, even pathologically changed by infection, do not allow antibiotics to penetrate CSF, even in the maximal intravenous doses. In the cases of cerebro-meningitis caused by bacteria sensitive only to glycopeptide antibiotics, the intraventricular administration of the drug might be an alternative way of therapy especially when the doses of intravenous antibiotics need to be reduced.