Association between colorectal cancer, the frequency of Bacteroides fragilis, and the level of mismatch repair genes expression in the biopsy samples of Iranian patients.

BACKGROUND: Deficient DNA mismatch repair (MMR) can cause microsatellite instability (MSI) and is more common in colorectal cancer (CRC) patients. Understanding the carcinogenic mechanism of bacteria and their impact on cancer cells is crucial. Bacteroides fragilis (B. fragilis) has been identified as a potential promoter of tumorigenesis through the alteration of signaling pathways. This study aims to assess the expression levels of msh2, msh6, mlh1, and the relative frequency of B. fragilis in biopsy samples from CRC patients. MATERIALS AND METHODS: Based on the sequence of mlh1, msh2, and msh6 genes, B. fragilis specific 16srRNA and bacterial universal 16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: Significant increases in the expression levels of mlh1, msh2, and msh6 genes were observed in the cancer group. Additionally, the expression of these MMR genes showed a significant elevation in samples positive for B. fragilis presence. The relative frequency of B. fragilis in the cancer group demonstrated a significant rise compared to the control group. CONCLUSION: The findings suggest a potential correlation between the abundance of B. fragilis and alterations in the expression of MMR genes. Since these genes can play a role in modifying colon cancer, investigating microbial characteristics and gene expression changes in CRC could offer a viable solution for CRC diagnosis.

Genetic diversity and biofilm formation of invasive and noninvasive Streptococcus agalactiae isolates: Emergence of hypervirulent CC19 strains in Tehran, Iran.

The prevalence of Streptococcus agalactiae infections in adult populations is increasing. The current study aimed to characterize the genetic features of S. agalactiae strains responsible for different infections. A cross-sectional study was performed on 65 S. agalactiae strains (30 invasive and 35 noninvasive) isolated from non-pregnant women. All S. agalactiae isolates were confirmed by atr and dltS PCR assays. Antibiotic susceptibility patterns were determined using the disk diffusion method. Biofilm production was investigated by microtiter plate assay. PCR was done to detect resistance determinants. Isolates were characterized using the multilocus sequence typing (MLST) method. cMLSB, iMLSB, and M phenotypes accounted for 47.7%, 30.8%, and 6.2%, respectively. MDR was detected in 15.4% of noninvasive and 44.6% of invasive isolates. MtP assay indicated that 80% of isolates were biofilm producers. Biofilm formation was common among noninvasive compared with invasive strains (94.3% versus 66.7%). tet (M) (46.2%) and erm (B) (69.2%) were the most prevalent tetracycline and macrolide-resistance genes. The most prevalent serotype was type III (50.8%), followed by Ia (18.4%), II (15.4%), V (12.3%), and IV (3.1%). The frequency of serotype III among biofilm producer strains (81.8%) was found to be significantly higher than that of non-producer isolates (18.2%) (P < 0.05). S. agalactiae was resolved within four clonal complexes, including CC19 (46.2%; in both invasive and noninvasive), followed by CC23 (30.8%; only noninvasive isolates), CC1 (15.4%; only noninvasive isolates) and CC17 (7.6%; only invasive isolates). The main sequence types (STs) found were ST19 (27.7%), ST17 (7.7%), ST27 (6.2%), and ST28 (4.6%) linked with invasive infections and ST23 (18.4%), ST933 (12.3%), ST644 (9.2%), ST19 (7.7%), ST1 (6.2%) found in noninvasive infections. The high prevalence of CC19 and CC23 clones among S. agalactiae strains reflects the emergence of these lineages as successful clones in Iran.

The Relationship between the Biofilm Genes and Antibiotic Resistance in Stenotrophomonas maltophilia.

Objectives: Today, Stenotrophomonas maltophilia (S. maltophilia) is a major opportunistic pathogen among hospitalized or immunocompromised patients. Antibiotic-resistant clinical isolates are increasing in several parts of the world. Various antibiotic-resistance and biofilm-forming genes are identified in this bacterium. Its capacity to form biofilms is an important virulence factor that may impact antibiotic-resistance patterns. In the current study, we evaluated the biofilm-formation capacity, antibiotic-resistance profile, and prevalence of biofilm-forming genes as well as antibiotic resistance genes among S. maltophilia isolates. Materials and Methods: In this cross-sectional study, 94 clinical S. maltophilia isolates were recovered from four tertiary-care hospitals in Iran between 2021 and 2022. The presence of the selected antibiotic-resistance genes and biofilm-forming genes was examined by polymerase chain reaction (PCR). The ability of biofilm formation was examined by microtiter plate assay. The Kirby-Bauer disc diffusion method was used to evaluate the trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and minocycline resistance. Results: S. maltophilia is mainly isolated from bloodstream infections. Notably, 98.93% of isolates were biofilm producers, of which 19.35%, 60.22%, and 20.43% produced strong, moderate, and weak biofilm, respectively. The frequency of biofilm genes was 100%, 97.88%, 96.80%, and 75.53% for spgM, rmlA, smf-1, and rpfF, respectively. Isolates with the genotype of smf-1+/rmlA+/spgM+/rpfF+ were mostly strong biofilm producers. Among the antibiotic-resistance genes, the Smqnr, L1, and sul1 had the highest prevalence (76.59%, 72.34%, and 64.89), respectively. Antimicrobial susceptibility evaluation showed 1.06%, 3.19%, and 6.3% resistance to minocycline, TMP-SMX, and levofloxacin. Conclusion: The results of the current study demonstrated that S. maltophilia isolates differ in biofilm-forming ability. Moreover, smf-1, rmlA, and spgM genes were presented in all strong biofilm producers. Although the overall resistance rate to the evaluated antibiotics was high, there was no statistically significant relation between antibiotic resistance and the type of biofilm.

COVID-19 and coronary artery disease; A systematic review and meta-analysis.

Background and aim: Patients with underlying cardiovascular disorders such as coronary artery disease (CAD) are more prone to severe forms and multiple complications of COVID-19. The present systematic review and meta-analysis aimed to investigate the impact of CAD on patients with COVID-19. Methods: Main electronic databases, including Medline (via PubMed), EMBASE, and Web of Science, were carefully searched and reviewed for original research articles published between 2019 and 2021. One hundred nine studies that address CAD in patients with COVID-19 were selected and analyzed. Results: Following search and screening processes, 109 relevant publications were selected for analysis. The meta-analysis of prevalence studies indicated that the frequency of CAD among patients with COVID-19 was reported in 10 countries with an overall frequency of 12.4% [(95% CI) 11.1-13.8] among 20079 COVID-19 patients. According to case reports/case series studies, 50.9% of COVID-19 patients suffered from CAD. Fever was the most common symptom in these patients (47%); 36.5% also had hypertension. Conclusion: The results obtained during the present study show that the simultaneous presence of COVID-19 and CAD, especially in men and elderly patients, can increase the risks and complications of both diseases. Therefore, careful examination of the condition of this group of patients for timely diagnosis and treatment is strongly recommended.

Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases.

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases. Video Abstract.

Association between colorectal cancer and expression levels of miR-21, miR-17-5P, miR-155 genes and the presence of Fusobacterium nucleatum in biopsy samples obtained from Iranian patients.

BACKGROUND: Colorectal cancer (CRC) is considered the second-deadliest and third-most common malignancy worldwide. Studying the carcinogenic mechanism of bacteria or their role in aggravating cancer can be precious. Fusobacterium nucleatum (F. nucleatum) is one of the important bacteria in the occurrence and spread of CRC. In this study, we investigated the expression levels of miR-21, miR-17-5P, miR-155, and the relative frequency of F. nucleatum in biopsy samples from patients with CRC. METHOD: DNA and RNA samples were extracted using a tissue extraction kit, and then cDNAs were synthesized using a related kit. Based on the sequence of miR-17-5P, miR-21, and miR-155 genes, F. nucleatum specific 16srRNA and bacterial universal16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: The expression level of miR-21, miR-17-5P, and miR-155 genes showed a significant increase in the cancer group. Also, the expression of the mentioned miRNAs was significantly raised in the positive samples for F. nucleatum presence. The relative frequency of F. nucleatum in the cancer group was significantly increased compared to the control group. CONCLUSION: Due to the changes in the expression of genes involved in causing CRC in the presence of F. nucleatum, it is possible to prompt identification and provide therapeutic solutions to cancer patients by studying their microbial profiles and the expression changes of different selected genes.

Prevalence and genetic characteristics of fusidic acid resistant Staphylococcus aureus clinical isolates: Emergence of t030 strains carrying fusB in Tehran, Iran.

The literature on fusidic acid resistant Staphylococcus aureus strains is scarce in Iran, although the emergence of these strains in health care settings is increasing. This descriptive cross-sectional study was conducted on 68 fusidic acid resistant S. aureus strains to learn about the molecular characteristics and antimicrobial resistance of strains isolated from hospitalized patients. In the present study, the prevalence of resistance to fusidic acid in S. aureus isolates was 15.1%. Fusidic acid resistance determinative factors (fusB, fusC and fusD) were identified by multiplex PCR assay. To detect the existence of fusA and fusE determinants and their mutation status, amplifications and sequencing were performed. Molecular characterization of fusidic acid resistant isolates was investigated by SCCmec and spa typing methods. All strains were MRSA and multi drug resistant. Two (2.9%) and 31 (45.6%) isolates were resistant to vancomycin and mupirocin respectively. The SCCmec type IV was highly prevalent representing 50% followed by types III (51.5%), and SCCmec types II (13.2%). fusB, was the most predominant acquired gene (66.2%) followed by fusC (19.1%), and fusA (14.7%). The mutations in fusA were present in 10 isolates with 5 (50%) having L461K mutation showing fusidic acid MIC values of ≥256 µg ml-1 followed by H457Y (40%), and H457Q (10%) showing fusidic acid MIC values of 128 and 64 µg ml-1 respectively. Isolates were allocated to ten particular t030 (22.1%), t037 (14.6%), t408 (11.8%), t064 (11.8%), t008 (10.3%), t002 (8.8%), t005 (5.9%), t790 (5.9%), t318 (4.4%), and t018 (4.4%) spa types. fusA positive isolates were assigned to particular spa types t002 (60%), and t005 (40%). There may be be a spreading of fusidic acid resistance among MRSA, creating worrying public concern. This research notes the importance of adequate data of local prevalence of FA-resistant MRSA in Iran for taking appropriate measures to treat, control and reduce the incidence of these isolates.

Global prevalence and distribution of antibiotic resistance among clinical isolates of Stenotrophomonas maltophilia: A systematic review and meta-analysis.

OBJECTIVES: Stenotrophomonas maltophilia (S. maltophilia), an opportunistic pathogen, causes infection in patients undergoing immunosuppressive therapy, mechanical ventilation, or catheters and in long-term hospitalized patients. Due to its extensive resistance to various antibiotics and chemotherapeutic agents, S. maltophilia is challenging to treat. Using case reports, case series, and prevalence studies, the current study provides a systematic review and meta-analysis of antibiotic resistance profiles across clinical isolates of S. maltophilia. METHODS: A systematic literature search was performed for original research articles published in Medline, Web of Science, and Embase databases from 2000 to 2022. Statistical analysis was performed using STATA 14 software to report antibiotic resistance of S. maltophilia clinical isolates worldwide. RESULTS: 223 studies (39 case reports/case series and 184 prevalence studies) were collected for analysis. A meta-analysis of prevalence studies demonstrated that the most antibiotic resistance worldwide was to levofloxacin, trimethoprim-sulfamethoxazole (TMP/SMX), and minocycline (14.4%, 9.2%, and 1.4%, respectively). Resistance to TMP/SMX (36.84%), levofloxacin (19.29%), and minocycline (1.75%) were the most prevalent antibiotic resistance types found in evaluated case reports/case series studies. The highest resistance rate to TMP/SMX was reported in Asia (19.29%), Europe (10.52%), and America (7.01%), respectively. CONCLUSION: Considering the high resistance to TMP/SMX, more attention should be paid to patients' drug regimens to prevent the emergence of multidrug-resistant S. maltophilia isolates.

COVID-19 and tuberculosis coinfection: An overview of case reports/case series and meta-analysis of prevalence studies.

Background and aim: Coronavirus disease 2019 (COVID-19) coinfection with other respiratory pathogens poses a serious concern that can complicate diagnosis, treatment, and prognosis. Since COVID-19 and tuberculosis are both severe respiratory infections, their symptoms may overlap and even increase mortality in case of coinfection. The current study aimed to investigate the coinfection of tuberculosis and COVID-19 worldwide through a systematic review and meta-analysis. Methods: A systematic literature search based on the Systematic Reviews and Meta-Analyses" (PRISMA) was performed on September 28, 2021, for original research articles published in PubMed, Web of Science, and Embase databases from December 2019 to September 2021 using relevant keywords. Data analysis was performed using Stata 14 software. Results: The final evaluation included 18 prevalence studies with 5843 patients with COVID-19 and 101 patients with COVID-19 and Mycobacterium tuberculosis (M. tuberculosis). The prevalence of tuberculosis infection was 1.1% in patients with confirmed COVID-19. This coinfection among patients with COVID-19 was 3.6% in Africa, 1.5% in Asia, and 1.1% in America. Eighteen case reports and 57 case series were also selected. Eighty-nine adults (67 men and 22 women) with a mean age of 45.14 years had concurrent infections with tuberculosis. The most common clinical manifestations were fever, cough, and weight loss. A total of 20.83% of evaluated patients died, whereas 65.62% recovered. Lopinavir/ritonavir was the most widely used antiviral drug for 10.41% of patients. Conclusion: COVID-19 has a low prevalence of tuberculosis coinfection, but it remains a critical issue, especially for high-risk individuals. The exact rate of simultaneous tuberculosis in COVID-19 patients could not be reported since we didn't have access to all data worldwide. Therefore, further studies in this field are strongly recommended.

Detection of multidrug-resistant Acinetobacter baumannii from burn patients and healthcare workers in Iran.

Multidrug-resistant (MDR) Acinetobacter baumannii is a serious global health threat. Burn patients are at high risk to acquire A. baumannii infections from endogenous sources. This study evaluated carbapenem resistance and clonal relatedness of A. baumannii isolated from burn patients and healthcare workers (HCWs).The study was performed in 100 non-duplicated A. baumannii isolates from nasal and hand samples of hospitalized burn patients and HCWs in two hospitals of Iran from June 2020 to August 2021. Antimicrobial susceptibility testing was performed and carbapenemase genes were detected by PCR. Clonal relatedness of A. baumannii isolates was determined by two single-locus sequence-based typing of blaOXA-51-like and ampC and by multilocus sequence typing (MLST).All A. baumannii isolates were found to be MDR while susceptible to colistin. The intI1, conserved segments of class 1 integron (intI1 CS), blaIMP, blaVIM, blaOXA-51-like, and blaOXA-23-like, genes were detected in 32.5%, 29.1%, 36%, 95.3%, 100%, 100%; and 14.3%, 14.3%, 21.4%, 92.9%, 100%, and 85.7% of isolates from patients and from healthcare workers, respectively. The blaOXA-58, and blaOXA-143 were not detected among the isolates. Using dual-locus blaOXA-51-like and ampC sequence-based typing (SBT), the isolates obtained from nasal samples of burn patients were grouped into 3 clusters including blaOXA-317, blaADC-88 (72.1%); blaOXA-64, ampC-25 (18.6%); and blaOXA-69, ampC-1 (9.3%). While only allele type blaOXA-317, blaADC-88 was determined among isolates from HCWs. MLST results showed A. baumannii ST136, ST25, and ST1 from burn patients. However, A. baumannii strains from HCWs belonged to ST136. Our findings indicate high prevalence of globally spreading of MDR A. baumannii ST136 carrying blaOXA-23-like from nasal and hand samples of burn patients and HCWs.

Emerging Challenges in Staphylococcus aureus Bloodstream Infections: Insights from Coagulase Typing, Toxin Genes, and Antibiotic Resistance Patterns.

Background: The incidence of complications and mortality associated with Staphylococcus aureus (S. aureus) bloodstream infections has been increasing significantly, particularly in developing countries where control strategies against this virulent pathogen and its resistance to antibacterial agents are insufficient. The aim of this study was to investigate coagulase typing, the prevalence of toxin genes, and the antibiotic resistance profile of S. aureus isolated from bloodstream infections. Methods: Antibiotic susceptibility of the isolates was determined by the disk diffusion method. The prevalence of toxin genes was determined using the polymerase chain reaction (PCR) method. Genetic variability of isolates was determined using multiplex PCR based on coagulase gene polymorphism. Results: Out of 120 strains, 55 (46%) were methicillin-resistant S. aureus (MRSA) and 65 (54%) were methicillin-sensitive S. aureus (MSSA). All isolates were susceptible to linezolid and teicoplanin but showed varying levels of resistance to other antibiotics. The highest resistance was observed for ampicillin (92.5%), gentamicin (69.2%), and amikacin (68.3%). Multidrug resistance was observed in all isolates. PCR analysis revealed a higher prevalence of toxin genes in MRSA (tst: 38%, pvl: 29.1%, eta: 10%, and etb: 4.1%) than that in MSSA. According to the coa typing, the most prevalent types were coa III (29.2%), coa II (26.7%), and coa VI (10%). Conclusion: The presence of genetic variability and widespread multidrug resistance in our hospitals emphasizes the circulation of various coa types. Therefore, it is crucial to implement antimicrobial stewardship and infection control measures to prevent and control the spread of these strains.

SARS-CoV-2 and HIV co-infection; clinical features, diagnosis, and treatment strategies: A systematic review and meta-analysis.

Background and aim: Coronavirus disease 2019 (COVID-19) in people living with human immunodeficiency virus (HIV) who has a compromised immune system can be associated with more significant risks for severe complications. To date, no comprehensive study has been performed to evaluate HIV in patients with COVID-19. In the present study, we assessed the status of patients co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV as a systematic review and meta-analysis. Methods: A systematic literature search strategy was conducted via reviewing original research articles published in Medline, Web of Science, and Embase databases in 2019 and 2020. Statistical analysis was performed using STATA software, version 14.0 (Stata Corporation, College Station, Texas, USA), to report the prevalence of HIV among patients with COVID-19. Case reports/case series were also evaluated as a systematic review. Results: Sixty-three studies (53 case reports/case series and ten prevalence studies) were included in our study. A meta-analysis of prevalence studies showed that HIV infection among patients with COVID-19 was reported in 6 countries (Uganda, China, Iran, USA, Italy, and Spain) with an overall frequency of 1.2% [(95% CI) 0.8-1.7] among 14,424 COVID-19 patients. According to the case reports and case series, 111 patients with HIV have been reported among 113 patients with COVID-19 from 19 countries. Most of the cases were in the USA, China, Italy, and Spain. Conclusion: The small number of SARS-CoV-2-HIV co-infected patients reported in the literature makes it difficult to draw precise conclusions. However, since people with HIV are more likely to develop more severe complications of COVID-19, targeted policies to address this raised risk in the current pandemic should be considered. Our findings highlight the importance of identifying underlying diseases, co-infections, co-morbidities, laboratory findings, and beneficial treatment strategies for HIV patients during the COVID-19 pandemic.

Investigation of drug regimens and treatment outcome in patients with Mycobacterium Simiae: a systematic review.

INTRODUCTION: Mycobacterium simiae (M.simiae), a non-tuberculous mycobacterium (NTM), rare causes infection including localized pulmonary to disseminated disease in immunocompromised patients. An optimal pharmacological management practice has not yet been defined for this infection. This study investigates drug regimens and treatment outcomes in patients with M. simiae to describe different drug regimen with the therapeutic response. AREAS COVERED: The three databases PubMed, Scopus, and Web of science were systematically searched from June 1994 to June 2021 to retrieve relevant articles. The inclusion criterion included studies, which reported treatment outcomes in patients with M. simiae infections. Treatment success was defined as the achievement of culture conversion, and the improvement of the symptoms and radiologic signs among the patients. EXPERT OPINION: Data of 223 patients were retrieved from 40 studies. Duration of the treatment regimens used in different studies ranged from 2 to 12 months. The most common treatment regimens administered for M. simiae infection were as follows: clarithromycin, rifampin, ethambutol, moxifloxacin, or ciprofloxacin and amikacin plus cotrimoxazole or pyrazinamide in some regimens. Macrolides, such as clarithromycin, combined with quinolones (such as moxifloxacin) and TMP/SMX, which are used in combination, had the most significant effect on eliminating the pulmonary signs of M. simiae.

Isolation and Chemical Characterization of an Alpha-Helical Peptide, Dendrocin-ZM1, Derived from Zataria multiflora Boiss with Potent Antibacterial Activity.

Today, resistance of microorganisms to antibiotics has become a major challenge. To overcome this problem, development of new drugs, besides research on their antibacterial activity, is essential. Among chemical components, antimicrobial peptides (AMPs) exhibit antibacterial activity and can be selected as suitable antimicrobial candidates. In this study, a novel antimicrobial peptide, called dendrocin-ZM1, with a molecular weight of ~3716.48 Da, was isolated from Zataria multiflora Boiss (ZM) and purified via precipitation with ammonium sulfate and reverse-phase HPLC chromatography; it was then sequenced via Edman degradation. The in silico method was used to examine the physicochemical properties of dendrocin-ZM1. In this study, four reference strains (gram-positive and gram-negative) and one clinical vancomycin-resistant Staphylococcus aureus strain were used to survey the antimicrobial activities. Moreover, to examine cytotoxicity and hemolytic activity, a HEK-293 cell line and human red blood cells (RBCs) were used, respectively. Evaluation of the physicochemical properties of dendrocin-ZM1, as an AMP, indicated a net charge of + 7 and a hydrophobicity percentage of 54%. This peptide had an amphipathic alpha-helical conformation. It exhibited broad-spectrum antibacterial activities against the tested strains at minimum inhibitory concentrations (MICs) of 4-16 µg/mL. Besides, this peptide showed negligible hemolysis and cytotoxicity in the MIC range. It also exhibited heat stability at temperatures of 20 to 80 °C and was active in a broad pH range (from 6.0 to 10.0). Overall, the present results suggested dendrocin-ZM1 as a remarkable antimicrobial candidate.

Mupirocin-Resistant Staphylococcus aureus in Iran: A Biofilm Production and Genetic Characteristics.

The spread of mupirocin-resistant Staphylococcus aureus strains in hospitals and communities is a universal challenge. Limited data is available on the genetic features of high-level mupirocin resistant- (HLMUPR-) S. aureus isolates in Tehran. In the present research, we investigated 48 high-level mupirocin resistance S. aureus by antimicrobial activity, virulence analysis, biofilm formation, multilocus sequence typing (MLST), and staphylocoagulase (SC) typing. All the HLMUPR strains were positive for mupA gene. The frequency of multidrug resistance was 97.9%. Twenty-one (43.8%) were toxinogenic with 14 producing pvl (29.2%), 5 tst (10.4%), and two eta (4.2%). Among the HLMUPR isolates, biofilm production was detected in 45 (89.6%) isolates with complete dominance clfB, clfA genes, and a noticeably high frequency fnbA (95.8%), followed by fnbB (93.8%), eno and icaD (each 83.3%), sdrC (81.3%), ebps (79.2%), icaA (75%), sdrD (66.7%), fib (60.4%), sdrE (50%), cna (41.7%), and bap (4.2%). Coagulase typing distinguished isolates into four genotypic patterns including III (50%), II (27.1%), and type IVa (22.9%). A total of three clonal complexes (CCs) and 4 sequence types (STs) including CC/ST22 as the most prevalent (52.1%), CC8/ST239 (20.8%), CC/ST8 (16.7%), and CC/ST5 (10.4%) were identified in current work. According to our analysis, nonbiofilm producer isolates belonged to CC8/ST239 (6.3%) and CC/ST8 (4.2%). Fusidic acid-resistant isolates belonged to CC/ST45 (n = 3) and CC8/ST239 (n = 1). Observations highlighted the circulation of the CC/ST22 HLMUPR S. aureus strains with strong biofilm-production ability in our hospitals, indicating the possibility of transmission of this type between community and hospital.

Global prevalence and molecular epidemiology of mcr-mediated colistin resistance in Escherichia coli clinical isolates: a systematic review.

OBJECTIVES: The continuing rise in infections caused by multidrug-resistant (MDR) bacteria is one of the most serious public-health issues in society today. Colistin is a last-resort antimicrobial drug used to treat infections caused by MDR Gram-negative bacteria, therefore resistance to this antibiotic is extremely hazardous. The current study aimed to evaluate the global prevalence nd distribution of colistin resistance genes among human clinical isolates of Escherichia coli by systematic review. METHODS: PubMed, Embase and Web of Science databases were systematically searched. For further evaluation, all original English language articles that reported colistin resistance in E. coli clinical isolates published between 2000 and 2020 were examined. RESULTS: Of 4857 initial articles, after various stages of review and evaluation 190 related articles were selected for the systematic review. More than 79% of the publications selected in this research were published from 2014-2020. In Asia, Europe, America, Africa and Oceania, the prevalence of mobile colistin resistance (mcr)-harbouring colistin-resistant E. coli was 66.72%, 25.49%, 5.19%, 2.27% and 0.32 %, respectively. CONCLUSION: The recent widespread dissemination of E. coli strains harbouring mcr genes conferring colistin resistance, especially in Asia and Europe, is concerning and requires more attention.

Diagnostic Accuracy of Pyrazinamide Susceptibility Testing in Mycobacterium tuberculosis: A Systematic Review with Meta-Analysis.

Introduction: Pyrazinamide (PZA) susceptibility testing plays a critical role in determining the appropriate treatment regimens for multidrug-resistant tuberculosis. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of sequencing PZA susceptibility tests against culture-based susceptibility testing methods as the reference standard. Methods: We searched the MEDLINE/PubMed, Embase, and Web of Science databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (version 1.4, Cochrane Colloquium, Barcelona, Spain), STATA (version 14, Stata Corporation, College Station, TX), and RevMan (version 5.3, The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark) software. Results: A total of 72 articles, published between 2000 and 2019, comprising data for 8,701 isolates of Mycobacterium tuberculosis were included in the final analysis. The pooled sensitivity and specificity of the PZA sequencing test against all reference tests (the combination of BACTEC mycobacteria growth indicator tube 960 (MGIT 960), BACTEC 460, and proportion method) were 87% (95% CI: 85-88) and 94.7% (95% CI: 94-95). The positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve estimates were found to be 12.0 (95% CI: 9.0-16.0), 0.17 (95% CI: 0.13-0.21), 106 (95% CI: 71-158), and 96%, respectively. Deek's test result indicated a low likelihood for publication bias (p = 0.01). Conclusions: Our analysis indicated that PZA sequencing may be used in combination with conventional tests due to the advantage of the time to result and in scenarios where culture tests are not feasible. Further work to improve molecular tests would benefit from the availability of standardized reference standards and improvements to the methodology.

Emergence of CC8/ST239- SCCmec III/t421 tigecycline resistant and CC/ST22-SCCmec IV/t790 vancomycin resistant Staphylococcus aureus strains isolated from wound: A two-year multi-center study in Tehran, Iran.

Staphylococcus aureus as an opportunistic bacterial pathogen with intrinsic and acquired resistance to many antibiotics is a worldwide problem. The current study was undertaken to evaluate the resistance pattern, and determine the genetic types of multidrug-resistant S. aureus isolated from wound. This cross-sectional study was conducted over the period of two years (from December 2018 to November 2020) at the hospitals affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran. In present study, 75 multidrug-resistant S. aureus isolates collected from wound infections were investigated. Phenotypic resistance was assessed by Kirby-Bauer disk diffusion method. Conventional PCR was performed for the detection of virulence encoding genes. Genotyping of strains was performed based on coa gene polymorphism using multiplex-PCR assay. SCCmec typing, spa typing and MLST were also used to characterize the genotype of the mupirocin, tigecycline and vancomycin resistant multidrug-resistant S. aureus isolates. All 75 multidrug-resistant S. aureus isolates in the study were confirmed as MRSA. Coagulase typing distinguished isolates into five genotypic patterns including III (40%), I (24%), IVb (16%), V (10.7%) and type X (9.3%). Resistance to tigecycline was detected in 4% of MDR-MRSA isolates and all belonged to CC8/ST239- SCCmec III/t421 lineage. According to our analysis, one VRSA strain was identified that belonged to coa type V and CC/ST22-SCCmec IV/t790 lineage. Resistance to mupirocin was detected in 9.3% of strains. All 7 mupirocin resistant MDR-MRSA isolates exhibited resistance to mupirocin in high level. Of these, 4 isolates belonged to CC/ST8-SCCmec IV/t008 (57.1%), 2 isolates belonged to CC/ST8-SCCmec IV/t064 (28.6%) and one isolate to CC/ST22-SCCmec IV/t790 (14.3%). Altogether, current survey provides a snapshot of the characteristics of S. aureus strains isolated from patients. Our observations highlighted type III as predominant coa type among multidrug-resistant MDR strains indicating low heterogeneity of these isolates. Our study also indicates the importance of continuous monitoring of the genotypes of MDR-MRSA isolates to prevent nosocomial outbreaks and the spread of MDR isolates.

The Global Prevalence of Daptomycin, Tigecycline, and Linezolid-Resistant Enterococcus faecalis and Enterococcus faecium Strains From Human Clinical Samples: A Systematic Review and Meta-Analysis.

Background and Aim: The predominant species of the Enterococcus, Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) cause great variety of infections. Therefore, the expansion of antimicrobial resistance in the Enterococcus is one of the most important global concerns. This study was conducted to investigate the prevalence of resistance to linezolid, tigecycline, and daptomycin among enterococcal strains isolated from human clinical specimens worldwide. Methods: Several databases including Web of Science, EMBASE, and Medline (via PubMed), were carefully searched and reviewed for original research articles available in databases and published between 2000 and 2020. A total of 114 studies worldwide that address E. faecalis and E. faecium resistance to linezolid, tigecycline, and daptomycin were analyzed by STATA software. Results: The overall prevalence of antibiotic-resistant E. faecalis and E. faecium was reported to be 0.9 and 0.6%, respectively. E. faecalis and E. faecium were more resistant to the linezolid (2.2%) and daptomycin (9%), respectively. The prevalence of tigecyline-resistant E. facium (1%) strains was higher than E. faecalis strains (0.3%). Accordingly, the prevalence of linezolid-resistant E. faecalis was higher in Asia (2.8%), while linezolid-resistant E. faecium was higher in the America (3.4%). Regarding tigecycline-resistance, a higher prevalence of E. faecalis (0.4%) and E. faecium (3.9%) was reported in Europe. Conclusion: In conclusion, this meta-analysis shows that there is an emerging resistance in Enterococcus strains. Despite the rising resistance of enterococci to antibiotics, our results demonstrate that tigecycline, daptomycin, and linezolid can still be used for the treatment of enterococcal infections worldwide.