Inflammatory Response in COVID-19 Depending on the Severity of the Disease and the Vaccination Status.

The aim of this study was to analyze the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and procalcitonin in COVID-19 patients with different forms of the disease. We performed a prospective cohort study on 137 COVID-19 consecutive patients, divided into four groups according to the severity of the disease as follows: 30 patients in the mild form group, 49 in the moderate form group, 28 in the severe form group, and 30 in the critical form group. The tested parameters were correlated with COVID-19 severity. Significant differences were registered between the form of COVID-19 depending on the vaccination status, between LDH concentrations depending on the virus variant, and in IL-6, CRP, and ferritin concentrations and vaccination status depending on the gender. ROC analysis revealed that D-dimer best predicted COVID-19 severe forms and LDH predicted the virus variant. Our findings confirmed the interdependence relationships observed between inflammation markers in relation to the clinical severity of COVID-19, with all the tested biomarkers increasing in severe and critical COVID-19. IL-6, CRP, ferritin, LDH, and D-dimer were increased in all COVID-19 forms. These inflammatory markers were lower in Omicron-infected patients. The unvaccinated patients developed more severe forms compared to the vaccinated ones, and a higher proportion of them needed hospitalization. D-dimer could predict a severe form of COVID-19, while LDH could predict the virus variant.

"Primum, non nocere": The Epidemiology of Toxigenic Clostridioides difficile Strains in the Antibiotic Era-Insights from a Prospective Study at a Regional Infectious Diseases Hospital in Eastern Europe.

Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the severity of the disease. Our study aims to elucidate the significance of toxigenic Clostridioides difficile (CD) strains in the clinical and therapeutic aspects of managing patients diagnosed with CDI. We conducted a single-center prospective study, including patients with CDI from north-eastern Romania. We subsequently conducted molecular biology testing to ascertain the prevalence of the presumptive 027/NAP1/BI strain within aforementioned geographic region. The patients were systematically compared and assessed both clinically and biologically, employing standardized and comparative methodologies. The study enrolled fifty patients with CDI admitted between January 2020 and June 2020. Among the investigated patients, 43 (86%) exhibited infection with toxigenic CD strains positive for toxin B genes (tcdB), binary toxin genes (cdtA and cdtB), and deletion 117 in regulatory genes (tcdC), while the remaining 7 (14%) tested negative for binary toxin genes (cdtA and cdtB) and deletion 117 in tcdC. The presence of the presumptive 027/NAP1/BI strains was linked to a higher recurrence rate (35.56%, p = 0.025), cardiovascular comorbidities (65.1% vs. 14.2%, p = 0.016), and vancomycin treatment (55.8% vs. 14.3%, p = 0.049). The findings of our investigation revealed an elevated incidence of colitis attributed to presumptive 027/NAP1/BI. Despite the prevalence of the presumptive 027 strain and its associated heightened inflammation among the patients studied, no significant differences were observed regarding the clinical course or mortality outcomes.

Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action.

Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative.

Overcoming Drug Resistance in a Clinical C. albicans Strain Using Photoactivated Curcumin as an Adjuvant.

The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical Candida albicans strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of C. albicans in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.

Antibiotic resistance of non-fermenting Gram-negative bacilli isolated at a large Infectious Diseases Hospital in North-Eastern Romania, during an 11-year period.

INTRODUCTION: Increased antibiotic resistance of non-fermenting Gram-negative bacilli (NFGNB) associated with increased morbidity and mortality makes the infections they produce a major public health problem. This study aims to assess the evolution of antibiotic susceptibility and the level of NFGNB antibiotic resistance. METHODS: We carried out a retrospective study on 994 NFGNB strains which had been isolated in the Clinical Laboratory of the "Sf. Parascheva" Clinical Hospital of Infectious Diseases, Iasi, during a period of 11 years (2008-2018). RESULTS: Of the 994 NFGNB analyzed, 322 were Acinetobacter spp. and 672 Pseudomonas aeruginosa. Also, 882 NFGNB were isolated from non-sterile sites, in which there was a higher burden of P. aeruginosa strains (n=617). Acinetobacter spp. presented over 70% resistance to the majority of antibiotics. Three pandrug-resistant P. aeruginosa strains were identified. The rate of colistin resistance was 2.91% for P. aeruginosa and 3.33% for Acinetobacter spp. A comparative analysis of the antibiotic susceptibility of strains isolated from non-sterile sites versus sterile sites revealed statistically significant differences only for Acinetobacter spp. The percentage of resistant strains was significantly higher in tracheobronchial aspirate compared to sputum. CONCLUSIONS: The results show that Acinetobacter spp. is substantially more resistant to antibiotics compared to P. aeruginosa and that the use of medical devices can favor the occurrence of infections with multidrug-resistant strains.

The importance of histopathologic aspects in the diagnosis of dissecting cellulitis of the scalp.

Dissecting cellulitis of the scalp or dissecting folliculitis also known as "perifoliculitis capitis abscedens et suffodiens" (PCAS), is a rare, severe and distinct dermatological disease. It most probably occurs because of follicular occlusion via hyperkeratosis, having the same mechanism of acnea conglobata and hidradenitis suppurativa. These dermatoses may be associated or may have an isolated evolution. PCAS is one of the primitive cicatricial alopecia of neutrophilic type (with pustules). What is characteristic for the histopathologic picture of the disease is the deep inflammatory infiltrate, placed at the reticular derm or hypoderm level. The initial perifolliculitis evolves towards forming profound abscesses and the destruction of polysebaceous follicles because of granuloma, usually lymphoplasmocitary and with gigantic cells. Here is the case of a 24-year-old male with records of acne conglobata and cicatricial alopecia of the scalp, with relapsed inflammatory nodular lesions on the surface of the alopecic plaques and follicular pustules on their margin. The patient had followed before hospitalizing a systemic treatment with antibiotics (azithromycin, tetracycline, ciprofloxacin, in therapeutic schemes that the patient cannot mention, but anyway of short time) and after that a treatment with retinoids (isotretinoin, 20-30 mg/day, in two successive therapies of one month each). The evolution of the disease under these treatments was with outbreaks and short times of remission of the acne lesions and nodular lesions of the scalp. The clinical diagnosis of PCAS is difficult, especially in the initial stage of the disease, as it was the case of the patient presented here. We underline the importance of a correct history of the disease, of the complete clinical exams and the need of paraclinical investigations (histopathologic exam from the lesional biopsy - microscopy and immunohistochemistry) in order to come with a positive diagnosis of PCAS and a differential one.

THE PATIENT-DOCTOR-PSYCHOLOGIST TRIANGLE IN A CASE Of SEVERE IMUNOSUPRESSION IN THE HIV INFECTION.

In the last two years the Romanian adult population infected with the human immunodeficiency virus (HIV) has increased due to sexual transmission, both heterosexual and homosexual. The case presented is that of a 33 year-old man, admitted to the Infectious Diseases Hospital in Iasi with acute respiratory failure and a confirmation of Kaposi's sarcoma. Tests later proved positive for HIV, the patient being included in the stage AIDS C3 (acute immunodeficiency syndrome). The respiratory failure was suspected to be caused by Pneumocystis carinii and cotrimoxazol therapy, oxygen therapy and anti-retroviral therapy were established. He was also referred to the oncology hospital for treatment of Kaposi's sarcoma. The patient's adherence to therapy was influenced by a strong doctor-patient relationship, as well as by psychological counseling and support. Creating a functional doctor-patient-psychologist team is key throughout the HIV-positive patient's existence, for supporting long term adherence to therapy and acceptance of the diagnosis. This case highlights the need for a strong psychosocial compartment in every medical center that deals with HIV-infected individuals.

Pyoderma vegetans developed on chronic leg ulcer.

Pyoderma vegetans is a rare disorder that more commonly affects middle-aged persons, with a male predilection. It is characterized by vegetating lesions that coalescence into a plaque with eroded surface, covered by purulent discharge and crusts. The etiology of this disease is not known with certainty, but it is often associated with bacterial infections in immunocompromised patients. We report the case of a 73-year-old men who presented to the Iasi Dermatology Clinic with a large, irregular, relatively well-defined dermohypodermic ulcer, with infiltrated sclerosing borders, accompanied by pain, with the floor covered in the Northern part by a proliferative, vegetative bleeding area, and the rest by a yellowish secretion and cellular debris, located on the left leg. Bacteriological examination of ulcer secretion identified Pseudomonas aeruginosa. Anatomopathological examination confirmed the development of Pyoderma vegetans on chronic leg ulcer. Under specific treatment for chronic leg ulcer and eradication of infectious focus the outcome was favorable both in terms of trophic ulcer scar- ring and Pyoderma vegetans healing.

Demodex: commensal or pathogen?

UNLABELLED: Demodex mites are considered commensals of human pilosebaceous units. Their role in skin disease is controversial. The aim of our study was to investigate the Demodex infection in patients with characteristic skin lesions and to correlate the level of infestation with epidemiological and clinical features. MATERIAL AND METHODS: we have studied 120 symptomatic patients, diagnosed between January 2012 and December 2012; the detection of mites was realized by microscopic examination of potassium hydroxide preparations from biological samples taken by scraping and squeezing method. RESULTS: The total prevalence rate of infection in our study group was 40.83%. We did not find statistical significant correlation with gender or age or with the type of lesions. CONCLUSIONS: Prevalence of Demodex infestation in facial dermatitis is high and its detection must be taken into consideration in routine diagnostic of facial suggestive lesions.

Emergence of a new group CTX-M enzyme in Romania and risk factors for extended spectrum beta-lactamase producing E. coli infections.

Antibiotic resistance rates in E. coli are rapidly rising, with worrisome aspects especially regarding community--acquired resistance to third- and fourth-generation cephalosporins and fluoroquinolones. The objectives of this prospective cohort study was to determine the resistance profile of E. coli for two categories of patients (< 49 years and > or = 50 years), risk factors for ESBL positivity and to investigate the molecular epidemiology of ESBL type CTX-M enzymes. A total of 885 strains of E. coli were isolated in the Infectious Diseases Hospital laboratory between June 2008 and June 2011 and E. coli resistance due to ESBL production was noted in 17% of cases. We found that previous therapy with cephalosporins, hospitalization and urinary catheter were risk factors for ESBL positivity. We noted significant differences concerning resistance rate between patients under 49 years and aged more than 50 years for ciprofloxacin (19% and 38%, respectively, p = 0,0001), for gentamicin (15% and 23%, p = 0,008), ceftazidime (15% and 24%, p = 0,001) and ESBL positivity (14% and 20%, p = 0.009). This study highlights the predominance of CTX-M producing strains (92.5% of ESBLs-positive E. coli harboured bla CTX-M genes); CTX-M-15 producing isolates were the most common, accounting for 96% of isolates. Only 4% were belonging to CTX-M group-9, an emerging ESBL group which is newly described in Romania.

[Metallo-beta-lactamase-mediated resistance among carbapenem-resistant Pseudomonas aeruginosa clinical isolates]. / Rezistenta prin metalo-beta-lactamaze la izolate clinice de Pseudomonas aeruginosa rezistente la carbapeneme.

UNLABELLED: The aim of our study was to evaluate the antimicrobial susceptibility profile and the presence of metallo-beta-lactamases (MBLs) among carbapenem-resistant Pseudomonas aeruginosa clinical isolates. MATERIAL AND METHODS: A total of 84 P. aeruginosa clinical isolates collected between January 2007- February 2011 from four university hospitals in Iasi (North-East region of Romania) were randomly selected. Antimicrobial susceptibility testing was performed according to CLSI 2010 (Clinical and Laboratory Standards Institute) guidelines. The isolates were tested for MBLs using EPI (EDTA-phenanthroline-imipenem) phenotypic test and polymerase chain reaction (PCR) for bla(VIM) and bla(IMP). RESULTS: Fifty-eight carbapenem resistant strains were identified, from which 24 (41,3%) were positive for VIM-type MBLs. No IMP - type MBL was detected. All MBL-producing isolates displayed a MDR (multidrug resistant) phenotype, two of them were XDR (extensively drug-resistant). Colistin remained the most effective antibiotic. CONCLUSIONS: The high proportion of MBL producing P. aeruginosa clinical isolates urges the need for a better use of antibiotics and for efficient infection control measures to prevent dissemination of MBL producers. This is the first report of VIM-like enzymes in P. aeruginosa isolates from the Iasi area.

[Clinico-epidemiological features and antimicrobial resistance pattern in gonococcal infection]. / Aspecte clinico-epidemiologice si particularitati ale sensibilitatii la antibiotice în infectia gonococica.

AIM: To analyze clinical and epidemiological features in patients with gonococcal infection attended Dermato-Venerology Clinic in Iasi and regional dermato-venerology offices and to evaluate gonococcal antimicrobial resistance pattern. METHODS: The study was carried out on 129 patients clinically diagnosed and bacteriologically confirmed with gonococcal infection who were subsequently submitted to a questionnaire. We studied their demographic characteristics (sex, age, nationality, marital status), clinical features (site of infection, symptoms, concurrent STI, previous history of gonorrhoea) and behavioral aspects (education, number and type of sexual partners, safe sexual practices). RESULTS: We found in our patients a strong association of gonorrhoea with young male individual, poor educational level and with clinical symptoms of urethritis. The level of antimicrobial resistance is higher than in other European countries. CONCLUSIONS: The poor health-seeking behavior, symptoms not specific enough, resistance pattern, lack of accessible and sensitive diagnostic methods lead to undiagnosed and probably mistreated gonorrhoea.

[Clinical and microbiological study regarding surface antibacterial properties of bioactive dental materials]. / Studiu clinico-microbiologic privind proprietatile antibacteriene ale unor materiale de restaurare cu caracter bioactiv.

UNLABELLED: In the new era of dentistry the coronal restoration materials must possess "bio-active" features represented by fluor ions release, chemical adhesion and antibacterial agents. AIM: Our study aims to determine the surface antibacterial properties of glassionomer cements and compomers. MATERIALS AND METHOD: The study group included 64 patients with high cariogenic risk with 80 teeth with acute and chronic dental caries affecting proximal and occlusal dental surfaces. The teeth with cariogenic lesions were restored with zinc-oxide-eugenol (n=20), glassionomer cement GC Fuji Triage (n=20), glassionomer cement modified with resins Fuji II LC (n=20), compomer Dyract (n=20). DENTOCULT SM test (Orion Diagnostica, Finland) was used for bacterial analyses. The samples from bacterial biofilm were collected from the restorated dental surfaces (study group) and intact enamel surfaces (control group). The recorded data were processed using non-parametrical statistical tests. RESULTS: The lowest mean value of bacterial indices was recorded for glassionomer cement Fuji Triage (0.4), and Fuji II LC (1.2), material with highest surface antibacterial properties. The highest value (1.5) was recorded for compomer Dyract. The Kruskal-Wallis test proves the significant statistical differences between the three bioactive materials. CONCLUSION: The materials with bioactive features have the ability to inhibate the growth of Streptococcus mutans in bacterial biofilm to the surfaces of coronal restoration.

[Antimicrobial resistance in Neisseria gonorrheae in North-East Romania]. / Rezistenta la antibiotice a Neisseria gonorrhoeae in zona Moldovei.

OBJECTIVES: The emergence of gonococcal isolates with reduced susceptibility or resistance to antimicrobial agents is a significant concern in the whole world. This study is performed to evaluate evolution of antimicrobial resistance patterns of N. gonorrhoeae isolates from north-east Romania. METHODS: We studied antimicrobial resistance in 81 strains of N. gonorrhoeae isolated from Sexually Transmitted Diseases Clinic in Iasi. The antimicrobial agents tested were Penicillin, Tetracycline, Ciprofloxacin, Cefixime, Ceftriaxone and Spectinomycin. RESULTS AND CONCLUSIONS: As we expected, resistance to Penicillin, Tetracycline and Ciprofloxacin is high and can't no longer be recommended for the treatment of gonorrhea in our area; Ceftriaxone, Cefixime and Spectinomycin should be considered the antimicrobial of choice. We isolated a strain with modified sensitivity to Cefixime, a fact that we should be worry about.