Evaluating the incidence of ampC-ß-lactamase genes, biofilm formation, and antibiotic resistance among hypervirulent and classical Klebsiella pneumoniae strains.

AIM: Both immunocompetent and healthy individuals can become life-threateningly ill when exposed to the hypervirulent (hvKp) strains of Klebsiella pneumoniae (Kp). The main objectives of this study were to evaluate the presence of ampC-lactamase genes, biofilm formation, and antibiotic resistance in clinical strains of hvKp and cKp (classical K. pneumoniae). MATERIALS AND METHODS: Kp strains were collected from patients referred to Shahidzadeh Hospital in Behbahan City, Khuzestan Province, Iran. Several techniques were used to identify hvKp. The hypermucoviscosity phenotype was determined using the string test. Isolates that developed dark colonies on tellurite agar were assumed to be hvKp strains. If any of the iucA, iutA, or peg-344 genes were detected, the isolates were classified as hvKp. Phenotypic and genotypic detection of AmpC ß-lactamases of hvKp strains was performed by the combined disk method and polymerase chain reaction, respectively. In addition, crystal violet staining was used to determine the biofilm formation of these isolates. RESULTS: For this study, 76 non-duplicative isolates of Kp were collected. Overall, 22 (28.94%) strains had positive string test results, and 31 (40.78%) isolates were grown in tellurite-containing medium. The genes iucA and iutA or peg-344 were found in 23.68% of all Kp strains and in 50% of tellurite-resistant isolates, respectively. The most effective antibiotics against hvKp isolates were tetracycline (85.52%) and chloramphenicol (63.15%). Using the cefoxitin disc diffusion method, we observed that 56.57% (43/76) of the strains were AmpC producer. A total of 30.26% (n = 23/76) of the isolates tested positive for at least one ampC gene, including blaDHA (52.63%, n = 40), blaCIT (40.78%, n = 31), blaACC (19.76%, n = 15), blaMOX (25%, n = 19), and blaFOX (43.42%, n = 33). Biofilm formation analysis revealed that most hvKp isolates were weak (n = 6, 40%) and moderate (n = 5, 33.33%) biofilm producers. CONCLUSION: Healthcare practitioners should consider the possibility of the existence and acquisition of hvKp everywhere. The exact mechanisms of bacterial acquisition are also unknown, and it is unclear whether the occurrence of infections is related to healthcare or not. Thus, there are still many questions about hvKp that need to be investigated.

Detection of qacΔE Efflux Pump Gene among the Clinical Isolates of Escherichia coli and its Correlation with Resistance to Disinfectants.

BACKGROUND: Disinfectants and antiseptics inhibit the dissemination of pathogenic organisms in hospitals but often cause disinfectant-resistant microorganisms, an important factor for nosocomial infection. This study aimed to evaluate the correlation between qacΔE efflux pump gene and its resistance to disinfectants among Escherichia coli clinical isolates. METHODS: A total of 97 E. coli isolates were isolated from patients with urinary tract infections. The minimum inhibition concentration (MIC) value of chlorhexidine and benzalkonium chloride was determined using broth microdilution method. Effect of efflux pumps was assessed by MIC test in the presence of phenylalanine-arginine ß-naphthylamide (PAßN), and then the qacΔE efflux pump gene was detected using polymerase chain reaction (PCR). RESULT: Of the isolates, 85.6% and 61.9% were resistant to chlorhexidine and benzalkonium chloride, respectively. Following the treatment of isolates with the efflux pump's inhibitor, PAßN, the MIC value of chlorhexidine and benzalkonium chloride decreased in 75.2% and 57.7% of the isolates, respectively. A significant correlation was found between PAßN treatment and the change in the resistant strains to susceptible strains (p = 0.021). The qacΔE gene was detected in 84.5% (n = 82) of the isolates, and the presence of the gene amongst disinfectant-resistant strains was also significant (p < 0.001). CONCLUSIONS: It is suggested to conduct other studies on other efflux pumps, as well as to periodically monitor the resistance to disinfectants. Substances inhibiting efflux pumps and neutral compounds are effective in the reduction of resistance to disinfectants. New disinfectants and drugs should be designed.

Evaluation of the effect of Saccharomyces cerevisiae on the expression of enterotoxin genes in Escherichia coli O157: H7 (EHEC) and Escherichia coli H10407 (ETEC).

Enterotoxigenic (ETEC) and enterohemorrhagic Escherichia coli (EHEC) are the most important intestinal pathogens. Probiotics play an effective role in reducing the expression of virulence factor genes in intestinal pathogenic bacteria. The aim of the present study is to investigate the effect of probiotic Saccharomyces cerevisiae S3 on the expression of enterotoxin genes in both ETEC and EHEC. Supernatant and lysate of S. cerevisiae S3 are prepared. Subminimal inhibitory concentrations (sub-MIC) of supernatant and lysate are individually exerted to O157: H7 and H10407. The genes' expression of enterotoxins (elt, est, stx1, and stx2) are then determined using real-time PCR technique. The results showed, the yeast supernatant could decrease the expression of the elt gene in ETEC and that of stx1 in EHEC. Of note, in other cases, stx1 and est genes' expression increased. The lysate had no inhibitory effect on the expressions of elt, est, and stx2 genes, but it increased the expression of genes in both ETEC and EHEC. Lysate extract only decreased the expression of stx1 in O157: H7. Our study shows some interesting results regarding the effectiveness of the compounds produced by S. cerevisiae S3 in the expressions of toxin genes in both ETEC and EHEC. We recommend more similar studies be performed in this regard.

An overview on inactivated and live-attenuated SARS-CoV-2 vaccines.

After about 2 years since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first infections were detected in Wuhan city of China in December 2019, which was followed by a worldwide pandemic with a record of 5.41 million deaths. Due to urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19), attempts for producing efficient vaccines are inexhaustibly continuing. According to a report by the World Health Organization (WHO) on COVID-19 vaccine tracker and landscape, there are 149 vaccine candidates all over the world. Inactivated SARS-CoV-2 vaccines as a conventional vaccine platform consist of whole virus particles grown in cell culture and inactivated by chemicals. Because of benefits such as antigenic similarity to real virion inducing humoral and cellular immune responses and ease for transport and storage, these vaccines, including the vaccines produced by Bharat Biotech, Sinopharm, and Sinovac, are in use at large scales. In this study, we have a review on inactivated SARS-CoV-2 vaccines that are passing their phase 3 and 4 clinical trials, population which was included in the trials, vaccine producers, the efficiency, adverse effects, and components of vaccines, and other vaccine features.

Clinical manifestations, treatment options, and comorbidities in COVID-19 relapse patients: A systematic review.

INTRODUCTION: Interest revolving around coronavirus disease 2019 (COVID-19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), PCR redetection, and COVID-19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID-19 relapse patients. MATERIALS AND METHODS: For this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT-PCR. RESULTS: Fifty-four studies included 207 cases of COVID-19 reinfection. Children were less likely to have COVID-19 relapse. However, the most patients were in the age group of 20-40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS-CoV-2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID-19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died. CONCLUSION: We found the potency of COVID-19 recurrence as an outstanding issue. This feature should be regarded in the COVID-19 management. Furthermore, the first and second COVID-19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.

Clinical symptoms, diagnosis, treatment, and outcome of COVID-19-associated encephalitis: A systematic review of case reports and case series.

INTRODUCTION: Since COVID-19 outbreak, various studies mentioned the occurrence of neurological disorders. Of these, encephalitis is known as a critical neurological complication in COVID-19 patients. Numerous case reports and case series have found encephalitis in relation to COVID-19, which have not been systematically reviewed. This study aims to evaluate the clinical symptoms, diagnosis, treatment, and outcome of COVID-19-associated encephalitis. METHODS: We used the Pubmed/Medline, Embase, and Web of Science databases to search for reports on COVID-19-associated encephalitis from January 1, 2019, to March 7, 2021. The irrelevant studies were excluded based on screening and further evaluation. Then, the information relating diagnosis, treatment, clinical manifestations, comorbidities, and outcome was extracted and evaluated. RESULTS: From 4455 initial studies, 45 articles met our criteria and were selected for further evaluation. Included publications reported an overall number of 53 COVID-19-related encephalitis cases. MRI showed hyperintensity of brain regions including white matter (44.68%), temporal lobe (17.02%), and thalamus (12.76%). Also, brain CT scan revealed the hypodensity of the white matter (17.14%) and cerebral hemorrhages/hemorrhagic foci (11.42%) as the most frequent findings. The IV methylprednisolone/oral prednisone (36.11%), IV immunoglobulin (27.77%), and acyclovir (16.66%) were more preferred for COVID-19 patients with encephalitis. From the 46 patients, 13 (28.26%) patients were died in the hospital. CONCLUSION: In this systematic review, characteristics of COVID-19-associated encephalitis including clinical symptoms, diagnosis, treatment, and outcome were described. COVID-19-associated encephalitis can accompany with other neurological symptoms and involve different brain. Although majority of encephalitis condition are reversible, but it can lead to life-threatening status. Therefore, further investigation of COVID-19-associated encephalitis is required.

Secondary Klebsiella pneumoniae infection in patients with COVID-19: A systematic review.

This study aims to investigate the development of secondary bacterial infection and risk factors associated with it in critical COVID-19 patients, and to identify the most common pathogen groups in them. All the cohort studies were retrieved from Scopus, Google Scholar, Web of Science, and MEDLINE from the inception of COVID-19 to 2022 for the following keywords: 'Klebsiella" AND "COVID-19". The most common comorbidities among the patients with COVID-19 were respiratory disease (33.62%), obesity (28.99%), and heart disease or cardiovascular disease (16.31%). We report 42.91% rate of Klebsiella spp co-infection in ICU admission patients, mostly related to K. pneumonia (26.81%), K. aerogenes (9.4%), and K. oxytoca (6.7%). The overall incidence of bacterial infection in hospitalized COVID-19 patients is estimated at 15.5% and in 32.5% of cases of co-infection patients deceased. The threat of carbapenem-resistant K. pneumoniae infections in patients with COVID-19 is imminent, therefore rational antibiotic therapy based on antibiotic sensitivity test should be implemented.

Clinical efficacy of probiotics in prevention of infectious diseases among hospitalized patients in ICU and non-ICU wards in clinical randomized trials: A systematic review.

Background and Aims: The present study aimed to review probiotics' clinical efficacy in preventing infectious diseases among hospitalized patients in ICU and non-ICU wards. Methods: A search of Medline, EMBASE, The Cochrane Library, Science Direct, Open Grey, and Google Scholar was conducted for eligible publications from 2002 to 2020 following the requirements outlined in the PRISMA guideline. The search strategy was based on the combination of the following terms: "probiotics," "prebiotics," "synbiotics," and "cross-infection." The logical operators "AND" (or the equivalent operator for the databases) and "OR" (e.g., probiotics OR prebiotics OR synbiotics) were used. Results: The results indicated that the probiotic consumption caused a significant reduction in antibiotic-associated diarrhea (AAD) and Clostridioides difficile infection (CDI) in 2/8 randomized clinical trials (RCTs) investigating AAD/CDI. Also, 5/12 clinical trials highlighted the considerable effects of probiotics on the reduction or prevention of ventilator associated pneumoniae (VAP), so the mean prevalence of VAP was lower in the probiotic group than in the placebo group. The total rate of nosocomial infections among preterm infants was nonsignificantly higher in the probiotic group compared to the control group. Conclusion: This systematic review shows that the administration of probiotics has moderate preventive or mitigating effects on the occurrence of VAP in ICU patients, CDI, AAD, and nosocomial infections among children. Consequently, applying antibiotics along with the proper probiotic species can be advantageous.

Brucellosis control methods with an emphasis on vaccination: a systematic review.

INTRODUCTION: Brucellosis is considered as one of the main zoonotic infections and a major public health concern worldwide. The aim of the present study was to evaluate various strategies for controlling brucellosis with an especial emphasis on efficacy of vaccination. AREAS COVERED: International databanks (Web of Science, PubMed, Embase) were searched for potentially relevant studies published from 1 January 2011 to 25 March 2021 using the following keywords: 'Brucella,' 'Brucella abortus,' 'Brucella melitensis,' 'Brucella canis,' 'Brucella suis,' 'brucellosis,' 'Bang disease,' 'undulant fever,' 'Malta fever,' 'vaccination,' 'vaccine,' and 'immunization.' The literature search was restricted to original articles published in English. EXPERT OPINION: Various methods are employed to prevent and control brucellosis, such as removing sick animals by slaughtering, separating sick animals from the herd, and vaccination. Preventing, controlling, and eradicating brucellosis requires a lot of financial support, perseverance, and time. In order to conduct a detailed study, it is recommended that more studies be conducted in developing countries and different parts of the world.

Evaluation of immune responses to Brucella vaccines in mouse models: A systematic review.

Introduction: Despite the accessibility of several live attenuated vaccines for animals, currently, there is no licensed vaccine for brucellosis in human populations. Available and confirmed animal vaccines may be harmful and considered inappropriate for humans. Thus, human vaccines for brucellosis are required. We aimed to evaluate the effects of Brucella vaccines on mouse models and discuss the potential mechanisms of these vaccines for the design of the appropriate human vaccines. Materials and methods: A systematic search was carried out in Web of Science, Embase, and PubMed/Medline databases. The following MeSH terms were applied: brucellosis, vaccine, Brucella, and vaccination. The original manuscripts describing the Brucella vaccines on mouse models were included. The review articles, editorials, correspondences, case reports, case series, duplicate publications, and articles with insufficient data were excluded. Results: Of the 163 full texts that were screened, 17 articles reached to inclusion criteria. Combining the results of these trials revealed a reduction in bacterial load and colonization rate of Brucella in the spleen, an increase in inflammatory markers, especially IFN-γ and IL-4, and the highest levels of antibody classes in vaccinated animals compared to animals challenged with various virulent strains of Brucella. The majority of studies found that different anti-Brucella vaccines induced a significant protective effect in animals challenged with Brucella strains. Additionally, mice were given the highest level of Brucella vaccine protection and significant clearance of Brucella strains when the immunization was delivered via the IP (intraperitoneal) or IP-IN (intranasal) routes. Conclusion: Brucella is responsible for half-million new cases globally annually, and the lack of a proper human vaccine poses the risk of brucellosis. A variety of vaccines are used to prevent brucellosis. Subunit vaccines and recombinant human vaccines have higher safety and protective properties. Although vaccination helps brucellosis control, it does not eradicate the disease. Thus, we recommend the following strategies. (a) establishment of a registration system; (b) close monitoring of slaughterhouses, markets, and herds; (c) training veterinarians; (d) legal protection of the consequences of non-compliance with preventive measures.

Clinical Manifestations, Imaging Procedures and Laboratory Parameters among Hospitalized Patients with COVID-19 in Ilam Province, Western Iran.

Background: COVID-19 is the last global threat which WHO confirmed it as a pandemic on March 11, 2020. In the Middle East, Iran was the first country where the SARS-Cov-2 was detected. The epidemiological and economic challenges of Iran make this country a particularly relevant subject of study. In the current study, we aimed to evaluate the clinical, radiological and laboratory findings in hospitalized COVID-19 confirmed cases in Ilam province, western of Iran. Methods: Overall, 2204 hospitalized RT-PCR confirmed patients with COVID-19 were considered in this study. Electronic medical records, including clinical symptoms, radiological images, laboratory findings, and the comorbidities of patients with COVID-19 were collected and analyzed. In addition, the medication regimens used in these patients were evaluated. The patients were classified in discharged and died groups according to their outcomes. Then, clinical, radiological and laboratory findings as well as treatment regimens and underlying diseases were compared in these two groups. Results: Among the patients, 1209 (54.85%) were male and 995 (45.14%) were female. Pneumonia, dyspnea and cough, were the most common clinical data in both discharged and died groups. Among the comorbidities, COPD, and cancer were significantly more common in the dead patients than in the living. The results of laboratory tests showed that blood creatinine, BUN, ESR, Na+, WBC, and neutrophil count have increased in deceased group compared to the survivors. However, the lymphocyte count decreased in deceased patients. The evaluation of radiographs demonstrated that there were significant correlations between bilateral pneumonia, ground glass opacity, bilateral patchy shadowing, and pleural effusion with death. Conclusion: The current investigation indicated the special profile of COVID-19 in west of Iran. Discharged and dead patients with COVID-19 had distinct clinical, radiological and laboratory features, which were separated by principal component analysis. Identifying these characteristics of the disease would translate into the implementation of practical measures to improve results.

Prevalence, diagnosis, and manifestations of brucellosis: A systematic review and meta-analysis.

Objectives: Brucellosis is one of the most prevalent zoonotic diseases common between humans and animals. Despite eradication efforts, the burden of the disease is well-known in endemic countries and in countries where brucellosis has not been an important health issue until recently. The aim of this study was to evaluate the prevalence, diagnosis, and manifestations of brucellosis. Methods: In this study, PubMed, Web of Science, Scopus, Embase, and Google scholar databases were systematically searched to find studies published from 2011 to 2021. The search was conducted using text words and Medical Subject Headings (MeSH) Terms on the prevalence of brucellosis. Stata software 14.0 was used for all analyses. Results: Based on the results, the pooled prevalence of brucellosis was 15.27% (95% CI: 9.68-21.86; heterogeneity I 2 index: 97.43; p < 0.001) for man and 15.33% (95% CI: 7.19-25.75; heterogeneity I 2 index: 98.19; p < 0.001) for woman. Age (coefficient: 0.240; p = 0.480), gender (coefficient: -0.017; p = 0.800), and publication year (coefficient: 0.114; p = 0.861) showed no significant effect on heterogeneity among studies. Egger's test indicated a significant publication bias for the prevalence of brucellosis (coefficient 3.894; p < 0.001). Moreover, the trim-and-fill method exhibited that the adjusted prevalence of brucellosis (18.30%, 95% CI: 14.10-22.52) was not significantly different from the original prevalence of brucellosis. Conclusion: The pooled estimate for brucellosis prevalence was estimated as 15.53%. To better understand the epidemiology of brucellosis globally, more extensive studies are needed to be conducted throughout the world, especially in developing and low-income countries.

Molecular typing and antibiotic resistance patterns among clinical isolates of Acinetobacter baumannii recovered from burn patients in Tehran, Iran.

Acinetobacter baumannii (A. baumannii) is now considered a highly resistant pathogen to various types of antibiotics. Therefore, tracking the source of its prevalence and continuous control is crucial. This study aimed to determine antibiotic resistance and perform various molecular typing methods on clinical isolates of A. baumannii isolated from hospitalized burn patients in Shahid Motahari Burn Hospital, Tehran, Iran. Hospital isolates were confirmed by phenotypic and molecular methods. Then the sensitivity to different antibiotics was determined using the minimum inhibitory concentration (MIC) method. In order to perform molecular typing, three-locus dual assay multiplex polymerase chain reaction (PCR), multiple-locus variable-number tandem repeat analysis (MLVA), and multilocus sequence typing (MLST) methods were used. Among the 60 isolates collected, the frequencies of multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates were 90 and 10%, respectively. The most effective antibiotics were colistin with 100% and tigecycline with 83.33% sensitivity. Isolates were 100% resistant to piperacillin/tazobactam and cephalosporins, and 68.3% were resistant to carbapenem. The results of multiplex PCR showed five groups that international clone I (IC I) and IC II were the most common. The MLVA method identified 34 MLVA types (MTs), 5 clusters, and 25 singletons. Multilocus sequence typing results for tigecycline-resistant isolates showed seven different sequence types (STs). Increasing antibiotic resistance in A. baumannii isolates requires careful management to control and prevent the occurrence of the pre-antibiotic era. The results of this study confirm that the population structure of A. baumannii isolates has a high diversity. More extensive studies are needed in Iran to better understand the epidemiology of A. baumannii.

Clinical Characteristics, Diagnosis, Treatment, and Mortality Rate of TB/COVID-19 Coinfectetd Patients: A Systematic Review.

Introduction: Novel coronavirus (COVID-19) and tuberculosis (TB) are the newest and one of the oldest global threats, respectively. In the COVID-19 era, due to the health system's focus on the COVID-19 epidemic, the national TB control program received less attention, leading to a worsening of the global TB epidemic. In this study, we will review the characteristics of TB patients coinfected with COVID-19. Material and Methods: Using Scopus, PubMed/Medline, Embase, and Web of Science databases, a systematic search was performed. Case reports and case series on TB/COVID-19 coinfection published from January 1, 2019 to February 24, 2021 were collected. There were no limitations regarding publication language. Results: Eleven case series and 20 case reports were identified from 18 countries, with the majority them being from India (N = 6) and China (N = 4). Overall, 146 patients (114 men and 32 women) coinfected with TB and COVID-19 enrolled. Smoking (15.1%), diabetes (14.4%), and hypertension (8.9%) were the most frequent comorbidities among these patients. The COVID-19 patients with TB mainly suffered fever (78.8%), cough (63.7%), and respiratory distress (22.6%). Hydroxychloroquine (64.0%) and lopinavir/ritonavir (39.5%) were the most common treatments for them. The mortality rate was 13.0% and the rate of discharged patients was 87.0%. Conclusion: Global prevalence of COVID-19-related deaths is 6.6%. Our results showed that 13.0% of patients with TB/COVID-19 died. Thus, this study indicated that coinfection of TB and COVID-19 can increase the mortality. The respiratory symptoms of TB and COVID-19 are very similar, and this causes them to be misdiagnosed. In addition, TB is sometimes diagnosed later than COVID-19 and the severity of the disease worsens, especially in patients with underlying conditions. Therefore, patients with TB should be screened regularly in the COVID-19 era to prevent the spread of the TB/COVID-19 coinfection.