Dysbiosis in pregnant mice induced by transfer of human vaginal microbiota followed by reversal of pathological changes in the uterus and placenta via progesterone treatment.

OBJECTIVE: The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified. We aimed to show the immunomodulatory effect of progesterone on the inflammation of uterine tissue triggered by dysbiotic vaginal microbiota in a pregnant mouse model. METHODS: Healthy (n = 6) and dysbiotic (n = 7) vaginal microbiota samples isolated from pregnant women were transferred to control (n = 10) and dysbiotic (n = 14) pregnant mouse groups. The dysbiotic microbiota transferred group was treated with 1 mg progesterone (n = 7). Flow cytometry and immunohistochemistry analyses were used to evaluate inflammatory processes. Vaginal microbiota samples were analyzed by 16 S rRNA sequencing. RESULTS: Vaginal exposure to dysbiotic microbiota resulted in macrophage accumulation in the uterus and cellular damage in the placenta. Even though TNF and IL-6 elevations were not significant after dysbiotic microbiota transplantation, progesterone treatment decreased TNF and IL-6 expressions from 49.085 to 31.274% (p = 0.0313) and 29.279-21.216% (p = 0.0167), respectively. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed. CONCLUSION: Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Our results also guide the development of new strategies for preventing preterm birth.

The vaginal microbiome composition during pregnancy in a region compromising different ethnic origins.

BACKGROUND: The vaginal microbiota plays a significant role in pregnancy outcomes and newborn health. Indeed, the composition and diversity of the vaginal microbiota can vary among different ethnic groups. Our study aimed to investigate the composition of the vaginal microbiome throughout the three trimesters of pregnancy and to identify any potential variations or patterns in the Turkish population compromising mixed ethnicities. METHOD: We conducted a longitudinal study to characterize the vaginal microbiota of pregnant women. The study included a total of 25 participants, and the samples were collected at each trimester: 11-13 weeks, 20-24 weeks and 28-34 weeks gestation. RESULTS: Lactobacillus species were consistently found to be dominant in the vaginal microbiota throughout all trimesters of pregnancy. Among Lactobacillus species, L. crispatus had the highest abundance in all trimesters (40.6%, 40.8% and 44.4%, respectively). L. iners was the second most prevalent species (28.5%, 31% and 25.04, respectively). Our findings reveal that the dominant composition of the vaginal microbiota aligns with the CST-type I, commonly observed in the European population. CONCLUSIONS: This suggests that there are shared mechanisms influencing the microbial communities in the vagina, which are likely influenced by factors such as genetics, lifestyle, and cultural behaviors rather than ethnicity alone. The complex interplay of these factors contributes to the establishment and maintenance of the vaginal microbiota during pregnancy. Understanding the underlying mechanisms and their impact on vaginal health across diverse populations is essential for improving pregnancy outcomes. The study was approved by the Koc University Ethical Committee (no:2019.093.IRB2.030) and registered at the clinical trials.

Alterations in vaginal microbiota among pregnant women with COVID-19.

The maintenance of vaginal microbiota is an important factor to achieve optimum pregnancy outcomes. The study aims to describe the alterations in the composition of vaginal microbiota in pregnant women with coronavirus disease 2019 (COVID-19). This was a prospective case-control study. Vaginal swabs were collected from uninfected pregnant women (n = 28) and pregnant women with COVID-19 (n = 19) during the active phase of infection and within a month after recovering from infection. The vaginal microbiota on the swabs was examined by 16S rRNA gene sequencing. Shannon index indicates that alpha diversity is significantly higher in women with COVID-19 (p = 0.012). There was a significant decrease in Firmicutes (p = 0.014) with an increase in Bacteroidota (p = 0.018) phyla and a decrease in Lactobacillus (p = 0.007) genus in women with COVID-19 than those of uninfected pregnant women. The relative abundance of L. crispatus, L. iners, L. gasseri, and L. jensenii were lower in the COVID-19 group than in uninfected pregnant women. In subgroup analysis, the amount of Ureaplasma spp. was higher in women with moderate/severe than those of asymptomatic/mild disease (p = 0.036). The study revealed that vaginal dysbiosis with low abundance of Lactobacillus species occurred in pregnant women infected with severe acute respiratory syndrome coronavirus-2. These findings may lead to new studies to elucidate the risk of pregnancy adverse outcomes related to COVID-19.

Immunogenicity after two doses of inactivated virus vaccine in healthcare workers with and without previous COVID-19 infection: Prospective observational study.

Vaccines have been seen as the most important solution for ending the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the antibody levels after inactivated virus vaccination. We included 148 healthcare workers (74 with prior COVID-19 infection and 74 with not). They received two doses of inactivated virus vaccine (CoronaVac). Serum samples were prospectively collected three times (Days 0, 28, 56). We measured SARS-CoV-2 IgGsp antibodies quantitatively and neutralizing antibodies. After the first dose, antibody responses did not develop in 64.8% of the participants without prior COVID-19 infection. All participants had developed antibody responses after the second dose. We observed that IgGsp antibody titers elicited by a single vaccine dose in participants with prior COVID-19 infection were higher than after two doses of vaccine in participants without prior infection (geometric mean titer: 898 and 607 AU/ml). IgGsp antibodies, participants with prior COVID-19 infection had higher antibody levels as geometric mean titers at all time points (p < 0.001). We also found a positive correlation between IgGsp antibody titers and neutralizing capacity (rs = 0.697, p < 0.001). Although people without prior COVID-19 infection should complete their vaccination protocol, the adequacy of a single dose of vaccine is still in question for individuals with prior COVID-19. New methods are needed to measure the duration of protection of vaccines and their effectiveness against variants as the world is vaccinated. We believe quantitative IgGsp values may reflect the neutralization capacity of some vaccines.

Effect of BTN162b2 and CoronaVac boosters on humoral and cellular immunity of individuals previously fully vaccinated with CoronaVac against SARS-CoV-2: A longitudinal study.

BACKGROUND: It is essential to know about immune response levels after booster doses of the two different types of vaccines, mRNA, and the inactivated, currently used against COVID-19. For this purpose, we aimed to determine the effects of BNT162b2 (BNT) and CoronaVac (CV) boosters on the humoral and cellular immunity of individuals who had two doses of CV vaccination. METHODS: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul, Turkey. Individuals who had been previously immunized with two doses of CV and no history of COVID-19 were included. The baseline blood samples were collected 3-5 months after the second dose of CV. Follow-up blood samples were taken 1 and 3 months after administration of third doses of CV, or one dose of BNT boosters. Neutralizing antibody titers were measured by plaque reduction assay. The CD4+ T cell, CD8+ T cell, effector CD4+CD38+CD69+ T cell, and effector CD8+CD38+CD69+ T cell ratios were determined by flow cytometry. The intracellular IFN-γ and IL-2 responses were measured by ELISpot assay. RESULTS: We found a 3.38-fold increase in neutralizing antibody geometric mean titers (NA GMT, 78.69) 1 month after BNT booster and maintained at the third month (NA GMT, 80). Nevertheless, in the CV booster group, significantly lower NA GMT than BNT after 1 month and 3 months were observed (21.44 and 28.44, respectively) (p < .001). In the ELISpot assay, IL-2 levels after BNT were higher than baseline and CV booster (p < .001) while IFN-γ levels were significantly higher than baseline (p < .001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated predominantly in the third month of the BNT boosters. CONCLUSION: The neutralizing antibody levels after 3 months of the BNT booster were higher than the antibody levels after CV in fully vaccinated individuals. On the contrary, ratio of the effector T cells increased along with greater IFN-γ activation after BNT booster. By considering the waning immunity, we suggest a new booster dose with BNT for the countries that already had two doses of primary CV regimens.

A meta-analysis for the role of aminoglycosides and tigecyclines in combined regimens against colistin- and carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

We aimed to describe the effect of aminoglycosides and tigecycline to reduce the mortality in colistin- and carbapenem-resistant Klebsiella pneumoniae (ColR-CR-Kp) infections. We included the studies with defined outcomes after active or non-active antibiotic treatment of ColR-CR-Kp infections. The active treatment was defined as adequate antibiotic use for at least 3 days (72 h) after the diagnosis of ColR-CR-Kp infection by culture. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the checklist of PRISMA 2020 was applied. Crude and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated and pooled in the random effects model. Adding aminoglycosides to the existing treatment regimen reduced overall mortality significantly (OR 0.34, 95% CI 0.20-0.58). Overall mortality was 34% in patients treated with aminoglycoside-combined regimens and was 60% in patients treated with non-aminoglycoside regimens. Treatment with tigecycline is not found to reduce mortality (OR: 0.76, 95% CI: 0.47-1.23). Our results suggest that aminoglycoside addition to the existing regimen of colistin- and carbapenem-resistant Klebsiella pneumoniae infections reduces mortality significantly.

Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting.

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.

Rapid Molecular Detection of Gastrointestinal Pathogens and Its Role in Antimicrobial Stewardship.

We aimed to detect the etiological agents of acute diarrhea by a molecular gastrointestinal pathogen test (MGPT) and to assess the impact of MGPT on antimicrobial stewardship programs (ASP). This is a prospective observational study and was conducted between 1 January 2015 and 30 June 2017. We included consequent patients who had acute diarrhea. At the end of 2015, we implemented ASP in acute diarrhea cases and compared the outcomes in the pre-ASP and post-ASP periods. An FDA-cleared multiplexed gastrointestinal PCR panel system, the BioFire FilmArray (Idaho Technology, Salt Lake City, UT), which detects 20 pathogens in stool, was used. In 499 out of 699 patients (71%), at least one pathogen was detected. Among 314 adults with positive MGPT, 101 (32%) enteropathogenic Escherichia coli (EPEC), 71 (23%) enteroaggregative E. coli (EAEC), 68 (22%) enterotoxigenic E. coli (ETEC), 55 (18%) Shiga toxin-producing E. coli (STEC) (17%) Norovirus, 48 (15%) Campylobacter, 21 (7%) Salmonella, and 20 (6%) Clostridium difficile strains were detected. Among 185 children, 55 (30%) EPEC, 37 (20%) C. difficile, 32 (17%) Norovirus, 29 (16%) EAEC, 22 (12%) STEC, 21 (11%) ETEC, 21 (11%) Campylobacter, 20 (11%) Salmonella, and 16 (5%) Rotavirus strains were detected. Inappropriate antibiotic use decreased in the post-ASP period compared with the pre-ASP period among inpatients (42.9% and 25.8%, respectively; P = 0.023). Using MGPT in clinical practice significantly decreased the unnecessary use of antibiotics. Detection of high rates of C. difficile in children and Salmonella spp., as well as relatively high rates of Campylobacter spp., which were hard to isolate by routine stool culture, were remarkable.

Impact of the ST101 clone on fatality among patients with colistin-resistant Klebsiella pneumoniae infection.

Objectives: We describe the molecular characteristics of colistin resistance and its impact on patient mortality. Methods: A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR. Results: A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates. Conclusions: Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.

The rapid diagnosis of viral respiratory tract infections and its impact on antimicrobial stewardship programs.

We aimed to describe the potential benefit of new rapid molecular respiratory tests (MRT) in decreasing inappropriate antibiotic use among the inpatients presenting with influenza-like illness (ILI). We included patients from inpatient and outpatient departments who had ILI and performed MRT between 1 January 2015 and 31 December 2016 in a 265-bed private hospital in Istanbul. At the end of 2015, we implemented antimicrobial stewardship including systematic use of MRT. Then, we compared our observations between the year 2015 and the year 2016. We designed the study according to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) tool. A U.S. Food and Drug Administration (FDA)-cleared multiplexed polymerase chain reaction (PCR) system (BioFire FilmArray, Idaho Technology, Salt Lake City, UT) which detects 17 viruses and three bacteria was used for diagnosis. In total, 1317 patients were included; 630 (48%) were inpatients and 569 (43%) were older than 16 years of age. At least one virus was detected in 747 (57%) patients. Rhinovirus/enterovirus, influenza virus, and adenovirus were the most commonly detected. Among hospitalized patients, in children, a significant decrease in antibiotic use (44.5% in 2015 and 28.8% in 2016, p = 0.009) was observed, but in adults, the decrease was not statistically significant (72% in 2015 and 63% in 2016, p = 0.36). The duration of antibiotic use after the detection of virus was significantly decreased in both children and adults (p < 0.001 and p = 0.007, respectively). By using MRT, inappropriate antibiotic use and, also, duration of inappropriate antibiotic use after the detection of virus was significantly decreased. It is time to increase the awareness about the viral etiology in respiratory tract infections (RTIs) and implement MRT in clinical practice.

Cytokine response in crimean-congo hemorrhagic fever virus infection.

We described the predictive role of cytokines in fatality of Crimean Congo Hemorrhagic Fever Virus (CCHFV) infection by using daily clinical sera samples. Consequent serum samples of the selected patients in different severity groups and healthy controls were examined by using human cytokine 17-plex assay. We included 12 (23%) mild, 30 (58%) moderate, 10 (19%) severe patients, and 10 healthy volunteers. The mean age of the patients was 52 (sd 15), 52% were female. Forty-six patients (88%) received ribavirin. During disease course, the median levels of IL-6, IL-8, IL-10, IL-10/12, IFN-γ, MCP-1, and MIP-1b were found to be significantly higher among CCHF patients than the healthy controls. Within the first 5 days after onset of disease, among the fatal cases, the median levels of IL-6 and IL-8 were found to be significantly higher than the survived ones (Fig. 3), and MCP-1 was elevated among fatal cases, but statistical significance was not detected. In receiver operating characteristic (ROC) analysis, IL-8 (92%), IL-6 (92%), MCP-1 (79%) were found to be the most significant cytokines in predicting the fatality rates in the early period of the disease (5 days). IL-6 and IL-8 can predict the poor outcome, within the first 5 days of disease course. Elevated IL-6 and IL-8 levels within first 5 days could be used as prognostic markers.

Emerging Escherichia coli O25b/ST131 clone predicts treatment failure in urinary tract infections.

BACKGROUND: We described the clinical predictive role of emerging Escherichia coli O25b/sequence type 131 (ST131) in treatment failure of urinary tract infection. METHODS: In this prospective observational cohort study, the outpatients with acute cystitis with isolation of E. coli in their urine cultures were assessed. All the patients were followed up for clinical cure after 10 days of treatment. Detection of the E. coli O25:H4/ST131 clone was performed by multiplex polymerase chain reaction (PCR) for phylogroup typing and using PCR with primers for O25b rfb and allele 3 of the pabB gene. RESULTS: In a cohort of patients with diagnosis of acute urinary cystitis, 294 patients whose urine cultures were positive with a growth of >10(4) colony-forming units/mL of E. coli were included in the study. In empiric therapy, ciprofloxacin was the first choice of drug (27%), followed by phosphomycin (23%), trimethoprim-sulfamethoxazole (TMP-SMX) (9%), and cefuroxime (7%). The resistance rate was 39% against ciprofloxacin, 44% against TMP-SMX, and 25% against cefuroxime. Thirty-five of 294 (12%) isolates were typed under the O25/ST131 clone. The clinical cure rate was 85% after the treatment. In multivariate analysis, detection of the O25/ST131 clone (odds ratio [OR], 4; 95% confidence interval [CI], 1.51-10.93; P = .005) and diabetes mellitus (OR, 2.1; 95% CI, .99-4.79; P = .05) were found to be significant risk factors for the treatment failure. In another multivariate analysis performed among quinolone-resistant isolates, treatment failure was 3 times more common among the patients who were infected with ST131 E. coli (OR, 3; 95% CI, 1.27-7.4; P = .012). CONCLUSIONS: In urinary tract infections, the E. coli ST131 clone seems to be a consistent predictor of treatment failure.

Discrepancy between IDSA and ESGBOR in Lyme disease: Individual participant meta-analysis in Türkiye.

BACKGROUND: The evidence on the prevalence of Lyme borreliosis (LB) is limited, but there is a suspicion of overdiagnosis of LB in recent years. We reviewed the LB diagnosis and treatment-related data in Türkiye, based on the Infectious Diseases Society of America (IDSA) 2020 and European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis (ESGBOR) 2018 guidelines. By detecting the disagreements between these two, we outlined the areas to be improved for future guidelines. METHODS: We performed a literature search according to the PRISMA guidelines in PubMed, Ovid-Medline, Web of Science, Turkish Medline, Scopus, CINAHL, ULAKBIM TR Index, Google Scholar and Cochrane Library databases. We included the published cases in a database and evaluated according to IDSA and ESGBOR guidelines. We outlined the reasons for misdiagnoses and inappropriate uses of antibiotics. RESULTS: We included 42 relevant studies with 84 LB cases reported from Türkiye between 1990 and December 2022. Among 84 cases, the most common clinical findings were nervous system findings (n = 37, 44.0%), erythema migrans (n = 29, 34.5%) and ophthalmologic findings (n = 15, 17.9%). The IDSA 2020 and ESGBOR 2018 guidelines agreed on the diagnosis of 71 (84.5%) cases; there was an agreement that 31 cases (36.9%) were misdiagnosed and 40 cases (47.6%) were correctly diagnosed, and there was disagreement for 13 cases (15.5%). Serum immunoglobulin M (IgM), IgG measurements by ELISA and western blot were widely performed, and they were effective in definitive diagnosis merely when used according to guidelines. Inappropriate use of antibiotics was detected in 42 (50.0%) of cases which were classified in the following categories: incorrect LB diagnosis, inappropriate choice of antibiotic, inappropriate route of drug administration and prolonged antibiotic treatment. CONCLUSION: Overdiagnosis and non-adherence to guidelines is a common problem. The discordance between seroprevalence and clinical studies necessitates a consensus over the best clinical approach.

Selective antibacterial and antibiofilm activity of chlorinated hemicyanine against gram-positive bacteria.

Antibiotic-free therapies are highly needed due to the limited success of conventional approaches especially against biofilm related infections. In this direction, antimicrobial phototherapy, either in the form of antimicrobial photothermal therapy (aPTT) or antimicrobial photodynamic therapy (aPDT), have appeared to be highly promising candidates in recent years. These are local and promising approaches for antibiotic resistant bacterial infections and biofilms. Organic small photosensitizers (PSs) are extensively preferred in antimicrobial phototherapy applications as they offer a great opportunity to combine therapeutic action (aPTT, aPDT or both) with fluorescence imaging on a single molecule. In this study, the bactericidal effect of cationic chlorinated hemicyanine (Cl-Hem)-based type I PS, which can function as a dual aPDT/aPTT agent, was investigated on both planktonic cells and biofilms of different gram-positive (E. faecalis and S. epidermidis) and gram-negative bacteria (P. aeruginosa and K. pneumoniae) with and without 640 nm laser irradiation. Cl-Hem was shown to induce a selective phototheranostic activity against gram-positive bacteria (E. faecalis and S. epidermidis). Cl-Hem exhibited both dose and laser irradiation time dependent bactericidal effect on planktonic and biofilms of S. epidermidis. These results clearly showed that highly potent Cl-Hem can treat resistant microbial infections, while allowing fluorescence detection at the same time. High biofilm reduction observed with combined aPDT/aPTT action of Cl-Hem together with its non-cytotoxic nature points out that Cl-Hem is a promising PS for antibacterial and antibiofilm treatments.

Erythrocyte-Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects.

Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte-leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.

Surveillance of respiratory viruses by aerosol screening in indoor air as an early warning system for epidemics.

The development of effective methods for the surveillance of seasonal respiratory viruses is required for the timely management of outbreaks. We aimed to survey Influenza-A, Influenza-B, RSV-A, Rhinovirus and SARS-CoV-2 surveillance in a tertiary hospital and a campus over 5 months. The effectiveness of air screening as an early warning system for respiratory viruses was evaluated in correlation with respiratory tract panel test results. The overall viral positivity was higher on the campus than in the hospital (55.0% vs. 38.0%). Influenza A was the most prevalent pathogen in both locations. There were two influenza peaks (42nd and 49th weeks) in the hospital air, and a delayed peak was detected on campus in the 1st-week of January. Panel tests indicated a high rate of Influenza A in late December. RSV-A-positivity was higher on the campus than the hospital (21.6% vs. 7.4%). Moreover, we detected two RSV-A peaks in the campus air (48th and 51st weeks) but only one peak in the hospital and panel tests (week 49). Although rhinovirus was the most common pathogen in panel tests, rhinovirus positivity was low in air samples. The air screening for Influenza-B and SARS-Cov-2 revealed comparable positivity rates with panel tests. Air screening can be integrated into surveillance programs to support infection control programs for potential epidemics of respiratory virus infections except for rhinoviruses.

[Investigation of biofilm-associated antibiotic susceptibilities of methicillin-resistant staphylococci isolated from catheter-related nosocomial infections]. / Kateter ile iliskili hastane enfeksiyonlarindan izole edilen metisiline dirençli stafilokoklarda biyofilm ile iliskili antibiyotik duyarliliginin arastirilmasi

Risks for development of local and/or systemic infections are the most important complications of catheters that are widely used during hospitalization process. The aims of this study were to investigate and compare the antibiotic susceptibilities of methicillin-resistant staphylococci isolated from catheters, in planktonic and biofilm forms, and to evaluate the antimicrobial effects of antibiotics on those forms alone and in combinations. A total of 30 strains [15 methicillin-resistant Staphylococcus aureus (MRSA) and 15 methicillin-resistant coagulase-negative staphylococci (MR-CNS)] isolated from catheter cultures of patients hospitalized in different clinics and intensive care units in Baskent University Medical School Hospital between 2006-2009, were included in the study. The antibiotic sensitivities of MRSA and MR-CNS isolates were investigated in vitro in planktonic phase and on sessile cells after biofilm was formed. Vancomycin, ciprofloxacin, rifampicin, gentamicin, meropenem, tigecycline, linezolid, ceftazidime and cephazolin were used for antibiotic susceptibility testing. The sensitivity of planktonic cells to antibiotics was primarily investigated, so that minimal inhibitor concentration (MIC) and minimal bactericidal concentration (MBC) values were determined by broth microdilution method. Afterwards, each strain was transformed to sessile cell in a biofilm environment, and MIC and MBC values were also determined for sessile cells. Double and triple antibiotic combinations were prepared, the effectiveness of combinations were studied on both planktonic and biofilm cells with multiple-combination bactericidal testing (MCBT) method. The data set obtained from planktonic and biofilm cells for each antibiotic analyzed via two proportion z test. Statistically significant decreases were found in the sensitivities of sessile cells when compared to planktonic cells (p< 0.01). The tests performed with the use of double and triple antibiotic combinations also showed the susceptibility decrease between planktonic and biofilm forms to be significant in most of the combinations (p< 0.01). The comparison of double and triple antibiotic combinations against planktonic and sessile cells as determined by the inhibition of more than 90% of the strains, revealed no significant difference . Vancomycin and tigecycline were the most effective antibiotics for all isolates in planktonic and sessile cells. Combinations containing vancomycin and rifampicin showed the best activity both double and triple antibiotic combinations against biofilm. In conclusion, our data indicated that combination therapy, especially double combinations of antibiotics seem to be a rational approach for biofilm-related infections.

Does Emerging Carbapenem Resistance in Acinetobacter baumannii Increase the Case Fatality Rate? Systematic Review and Meta-Analysis.

BACKGROUND: In the era of rising carbapenem resistance, we aimed to investigate the change in mortality rate and positivity of carbapenemase genes in Acinetobacter baumannii. METHODS: Preferred Reporting Items for Systematic Review (PRISMA) guidelines were adopted in this systematic review. Our literature search included the Cochrane Library, Pubmed, Scopus, Web of Science, Medline, Tubitak TR Dizin, and Harman databases for studies dating back from 2003 to 2023 reporting bloodstream A. baumannii infections in Türkiye. A simple linear regression model was used to determine the association between resistance, mortality, and time. RESULTS: A total of 1717 studies were identified through a literature search, and 21 articles were selected based on the availability of the data regarding mortality and resistance rate (four articles) or the molecular epidemiology of carbapenem-resistant A. baumannii (17 articles) in Türkiye. From 2007 to 2018, the carbapenem resistance rate increased (p = 0.025). The OXA-23 and OXA-58 positivities were inversely correlated (p = 0.025). CONCLUSIONS: Despite the emergence of carbapenem resistance, mortality did not increase in parallel, which may be due to improved medical advancements or the fitness cost of bacteria upon prolonged antimicrobial exposure. Therefore, we suggest further global research with the foresight to assess clonal relatedness that might affect the carbapenem resistance rate.

Fimbria targeting superparamagnetic iron oxide nanoparticles enhance the antimicrobial and antibiofilm activity of ciprofloxacin against quinolone-resistant E. coli.

High quinolone resistance of Escherichia coli limits the therapy options for urinary tract infection (UTI). In response to the urgent need for efficient treatment of multidrug-resistant infections, we designed a fimbriae targeting superparamagnetic iron oxide nanoparticle (SPION) delivering ciprofloxacin to ciprofloxacin-resistant E. coli. Bovine serum albumin (BSA) conjugated poly(acrylic acid) (PAA) coated SPIONs (BSA@PAA@SPION) were developed for encapsulation of ciprofloxacin and the nanoparticles were tagged with 4-aminophenyl-α-D-mannopyrannoside (mannoside, Man) to target E. coli fimbriae. Ciprofloxacin-loaded mannoside tagged nanoparticles (Cip-Man-BSA@PAA@SPION) provided high antibacterial activity (97.1 and 97.5%, respectively) with a dose of 32 µg/mL ciprofloxacin against two ciprofloxacin-resistant E. coli isolates. Furthermore, a strong biofilm inhibition (86.9% and 98.5%, respectively) was achieved in the isolates at a dose 16 and 8 times lower than the minimum biofilm eradication concentration (MBEC) of ciprofloxacin. Weaker growth inhibition was observed with untargeted nanoparticles, Cip-BSA@PAA@SPIONs, confirming that targeting E. coli fimbria with mannoside-tagged nanoparticles increases the ciprofloxacin efficiency to treat ciprofloxacin-resistant E. coli. Enhanced killing activity against ciprofloxacin-resistant E. coli planktonic cells and strong growth inhibition of their biofilms suggest that Cip-Man-BSA@PAA@SPION system might be an alternative and/or complementary therapeutic option for the treatment of quinolone-resistant E. coli infections.

B Cell Subtypes in Individuals Received mRNA or Inactivated Vaccine Boosters After Fully Vaccinated with CoronaVac: A Longitudinal Study.

In this study, we aimed to investigate the changes in the B cell subpopulations after homologous or heterologous COVID-19 boosters. Blood samples were collected after baseline (3-5 months after two doses of CoronaVac), 1 and 3 months after BNT162b2 (n=28 and n=6), and CoronaVac (n=7 and n=4) boosters. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with B cell markers, the ratios of naïve (CD19+CD20+CD27-), memory (CD19+CD20+CD27+), memory B cells expressing IgG (CD19+CD20+CD27+IgG+), and effector memory B cells (CD19+CD20+CD27+CD38+) were identified with flow cytometry. Significantly higher expression of memory B cells was observed in one month with BNT162b2 (12.16% one month, 5.98% three months) and CoronaVac (14.18% one month, 9.00% three months) boosters. IgG expressing memory B cell expression was significantly higher with BNT162b2 than with CoronaVac booster in one month (22.70% and 13.95%, respectively). The ratio of effector B cells in the first month after CoronaVac booster (25.44%) was significantly higher than the BNT162b2 booster (9.90%, p =0.0263).