Investigating the antimicrobial activity, cytotoxicity, and action mechanism of acylated and amidated derivatives of AurH1 antifungal peptide.

BACKGROUND: The increasing growth of microbial resistance threatens the health of human societies. Therefore, the discovery and design of new antibiotics seem necessary. Today, antimicrobial peptides (AMPs) are receiving attention due to their unique properties. In our previous studies, exclusive antifungal effects of AurH1, which is a truncated and modified form of Aurein1.2, were synthesized. In this study, AurH1 antifungal peptide was synthesized into acylated (Ac-AurH1) and amidated (AurH1-NH2) derivatives, and their antifungal activity, cytotoxicity, anticancer activity, hemolytic effects were investigated. Finally, the time- of killing, the action mechanism of amidated and acylated peptides, and the effects of salts and human serum on their antimicrobial potency were determined. All the results obtained about these peptides were compared with the AurH1 without chemical modifications. RESULTS: The results showed that amidation at the C-terminal of AurH1 compared to acylation at the N-terminal of it can improve the antifungal properties and cytotoxicity of AurH1. The results showed that AurH1 amidation can maintain the antifungal activity of this peptide in the culture medium containing specific dilutions of human serum compared to the intact AurH1. Also, the amidation of the C-terminal of AurH1 could not affect the mechanism of action and its time -of killing. CONCLUSION: As a result, the amidation of the C-terminal of the AurH1 is a suitable strategy to improve its antifungal properties and cytotoxicity. This modification can enhance its properties for animal studies.

Klebsiella pneumoniae vaccine studies in animal models.

The treatment of Klebsiella pneumoniae is faced with challenges demanding the development of a vaccination strategy. However, no approved and globally available vaccine exists yet. This study aimed to systematically review all published data on K. pneumoniae vaccines in animal models. Without time restrictions, electronic databases were searched using appropriate keywords. The retrieved studies were screened and the data of those that matched our inclusion criteria were collected and analyzed. In total, 2027 records were retrieved; of which 35 studies were included for systematic review. The most frequently used animal model was BALB/c mice. Proteins, polysaccharides, and their combinations (conjugates) were the most common vaccine candidates used. The amount of antigen, the route used for immunization, and the challenge strategy was varying in the studies and were chosen based on several factors such as the animal model, the type of antigen, and the schedule of immunization. Almost all studies claimed that their vaccine was effective/protective, indicated by increasing survival rate, reducing organ bacterial load, and eliciting protective antibody and/or cytokine responses. Altogether, the information presented here will assist researchers to have a better look at the K. pneumoniae vaccine candidates and to take more effective steps in the future.

Prevention of mother-to-child transmission of HIV in Kermanshah, west of Iran from 2014 to 2021.

BACKGROUND: This study aimed to evaluate the implementation of the prevention of mother-to-child transmission (PMTCT) of the HIV-PMTCT program in Kermanshah, west of Iran, from 2014 to 2021. METHODS: The data of all HIV-infected mothers and their infants who were monitored by the Kermanshah behavioral diseases counseling center was extracted and recorded in a checklist. RESULTS: Out of 95 included infant, 45 (47.4%) were girls and 50 (52.6%) were boys. The mothers were mostly infected with HIV via their infected spouse. The pregnancies of 77 cases (82.1%) were in accordance with the national guideline. The average length of treatment for this group was 185 days. Of the 18 mothers who did not receive treatment, nine were diagnosed during childbirth and nine had no available information. All infants born from infected mothers underwent after-birth-antiretroviral prophylaxis, and all remained healthy. There was no statistically significant relationship between the birth weight and height of neonates with maternal age, maternal last viral load, disease stage, education, and maternal CD4 levels. Only a statistically significant relationship was observed between the duration of treatment and the infants' weight. CONCLUSION: The results suggest the feasibility and effectiveness of the PMTCT program for HIV-positive mothers in Kermanshah. It seems that if pregnant HIV-positive women are diagnosed early and covered by a good prevention program on time, the risk of HIV to their babies will be reduced, significantly.

Determination of antifungal activity and action mechanism of the modified Aurein 1.2 peptide derivatives.

BACKGROUND: With the emergence of drug-resistant fungi and the increased population prone to fungal infections, more effective antifungal drugs are needed. Aurein 1.2 is a potent antimicrobial peptide. Here, we designed a novel derivative of Aurein 1.2, called Aurein N3, which is a modified form of Aurein N2 (another Aurein 1.2 derivative), in which Lys 8 residue was replaced with Leu 13, and was also modified by creating two other mutations. METHODS: Aurein N3 was designed using several algorithms and docking studies. All peptides were synthesized and some of their bio-activity indices such as antifungal properties on 11 fungi, cytotoxicity, hemolysis, and time of the killing were investigated. Electron microscopy, lived/dead staining, and ergosterol binding assay were performed to study their mechanism of action. RESULTS: In comparison to Aurein 1.2 and N2, the docking studies showed that Aurein N3 has reduced binding energy toward ergosterol. The antifungal assessments showed that both Aurein N2 and N3 had strong activity against many fungi. Aurein N3 had lower cytotoxicity and higher binding capability to ergosterol. The hemolytic activity of Aurein N2 and N3 was less than parental Aurein 1.2. All peptides were able to attack the cell wall/membrane and enter the fungi cells. CONCLUSION: Here we introduced a novel derivative of Aurein 1.2 which has lower cytotoxicity, higher ergosterol-binding capability, and comparable antifungal activity compared to the original peptides. It can bind to ergosterol and can also attack the cell wall/membrane of fungi, although more studies are required to find its accurate mechanism of action.

First report of antifungal activity of CecropinA-Magenin2 (CE-MA) hybrid peptide and its truncated derivatives.

The use of natural antimicrobial peptides (AMPs) is limited. Modifications of peptides by in silico predictions and computational methods can lead to more accurate designs and reducing their high synthesis costs, instability, and cytotoxicity. In this study, the antifungal properties of CecropinA-Magenin2 (CE-MA) hybrid peptide and its truncated derivatives were evaluated. Eleven C-terminal-truncated derivatives were designed and three of them with 10, 8 and 6 residues namely CMt1, CMt2 and CMt3 were selected through an initial screening based on the prediction of antimicrobial and antifungal activities, toxicity and physicochemical properties. These derivatives and the parental CE-MA peptide were synthesized. Then, based on molecular docking studies, antimicrobial tests and cytotoxicity assays, CMt1 peptide was selected for further studies such as time of killing, combinatorial effects with other drugs and the mechanism of action. The results showed that CE-MA is a weak antifungal peptide but its truncated derivative, CMt1 showed a strong antifungal activity with less toxicity. The results of the ergosterol assay, confocal microscopy and FE-SEM studies indicated that invasion to cell wall and membrane components were the main antifungal mechanisms of CMt1 peptide. Altogether, here we introduce a new truncated peptide with a strong antifungal activity with less toxicity which can be a good candidate for further in vivo and clinical studies to be used as an antifungal drug.

Heterogeneity of humoral immune response to Leishmania tropica in an experimental model.

Humoral (antibody) response is an important part of immunity against pathogens. Despite the clear role of cell-mediated immune response in protection against leishmaniasis, the role of humoral responses is challenging. There is very limited data regarding humoral immune response against Leishmania tropica which is the causative agent of human cutaneous leishmaniasis in many parts of the world. Here, we have compared pathogenicity and antibody response against six Iranian Leishmania tropica isolates in BALB/c mice. A Leishmania major isolate was used for comparison. The parasites were injected into the mice followed by the evaluation of the lesion development, parasite load, and antibody responses (IgG1 and IgG2a). Our findings showed that some isolates caused the large lesions and high parasite load in the spleen and lymph node, while other isolates led to no lesion, no splenic parasitism, and low parasite load in the lymph node. The more pathogenic isolates induced higher antibody responses (IgG1 and IgG2a). Our results indicated that there is substantial heterogeneity among various Leishmania tropica isolates regarding the humoral immune response as well as the pathogenicity.

Leishmania tropica: suggestive evidences for the effect of infectious dose on pathogenicity and immunogenicity in an experimental model.

Leishmania (L.) tropica is a causative agent of cutaneous and occasionally visceral or viscerotropic leishmaniasis in humans. The dose of parasites influences the course and outcome of disease in some Leishmania species. The effect of parasite dose on L. tropica infection in an experimental model was studied in the current paper. High and low doses of L. tropica were used for ear infection of BALB/c mice and lesion development, parasite load, and cytokine responses were assessed. L. major infection was used for comparison. Pre-infected mice were challenged in the footpad by a fixed high dose of L. tropica, and immune response and protection level were evaluated. High dose L. tropica infection in comparison to low dose results in higher lesion diameters, higher load of parasite in draining lymph node, higher levels of interferon-γ and interleukin-10, dissemination of parasite to spleen, and induction of protection against further L. tropica challenge. Comparison of L. tropica with L. major showed that L. tropica results in lower lesion diameters, more potential for growth in lymph nodes at early phases of infection, parasite dissemination to spleen, lower levels of IL-10, and a permanent lower cytokine response against low parasite dose in comparison to high dose. Our findings suggest that for L. tropica infection, only the high dose results in visceralization of the parasite and protection against further challenge of L. tropica. Therefore, the parasite dose may be an important factor in pathogenesis and immunity in L. tropica infection.

Investigating the relationship between Epstein-Barr virus infection and gastric cancer: A systematic review and meta-analysis.

Background and Aims: Gastric cancer (GC) is a common cancer type worldwide, and various factors can be involved in its occurrence. One of these factors is Epstein-Barr virus (EBV) infection. In this regard, a systematic review and meta-analysis was conducted to achieve a better understanding of the EBV prevalence in GC samples. Methods: English databases were searched and studies that reported the prevalence and etiological factors of EBV related to GC from July 2007 to November 2022 were retrieved. The reported data were selected based on the inclusion and exclusion criteria. The pooled prevalence of EBV infection with 95% confidence intervals was calculated. Quality assessment, heterogeneity testing, and publication bias assessment were also performed. The literature search showed 953 studies, of which 87 studies met our inclusion criteria and were used for meta-analysis. Results: The pooled prevalence of EBV infection related to GC was estimated to be 9.5% (95% confidence interval [CI]: 8.2%-11%) in the general population. The prevalence of EBV infection related to GC by gender was 13.5% (95% CI: 11.1%-16.3%) in males and 7.6% (95% CI: 5.4%-10.6%) in females. No significant differences were observed in terms of geographical region. Out of the 87 studies included in the meta-analysis, the most common diagnostic test was in situ hybridization (58 cases). Conclusions: Altogether, the results indicated that EBV infection is one of the important factors in the development of GC. However, this does not necessarily mean that EBV infection directly causes GC since other factors may also be involved in the development of GC. Therefore, it is recommended to conduct extensive epidemiological studies on various aspects of the relationship between this virus and GC, which can provide valuable information for understanding the relationship between EBV and GC.

An In silico Study on B-cell Epitope Mapping of Acinetobacter baumannii Outer Membrane Protein K.

BACKGROUND: Acinetobacter baumannii is one of the main causes of nosocomial infections. No vaccine has yet been licensed for use in humans, and efforts are still ongoing. OBJECTIVE: In the present study, we have predicted the B-cell epitopes of A. baumannii's outer membrane protein K (OMPK) by using epitope prediction algorithms as possible vaccine candidates for future studies. METHODS: The linear B-cell epitopes were predicted by seven different prediction tools. The 3D structure of OMPK was modeled and used for discontinuous epitope prediction by ElliPro and DiscoTope 2.0 tools. The final linear epitopes and the discontinuous epitope segments were checked for potential allergenicity, toxicity, human similarity, and experimental records. The structure and physicochemical features of the final epitopic peptide were assessed by numerous bioinformatics tools. RESULTS: Many B-cell epitopes were detected that could be assessed for possible antigenicity and immunogenicity. Also, an epitopic 22-mer region (peptide) of OMPK was found that contained both linear and discontinuous B-cell epitopes. This epitopic peptide has been found to possess appropriate physicochemical and structural properties to be an A. baumannii vaccine candidate. CONCLUSION: Altogether, here, the high immunogenic B-cell epitopes of OMPK have been identified, and a high immunogenic 22-mer peptide as an A. baumannii vaccine candidate has been introduced. The in vitro/in vivo studies of this peptide are recommended to decide its real efficacy and efficiency.

Human vaccine candidates for infections caused by Klebsiella pneumoniae: A systematic review.

Background and Aims: There are many difficulties in treating Klebsiella pneumoniae, necessitating the creation of more preventative/therapeutic measures like vaccinations. However, after numerous attempts, there is still no authorized and widely accessible vaccine. The present study aimed to systematically review published studies on K. pneumoniae vaccines in human subjects/samples. Methods: To find published studies, several electronic databases, including Scopus, PubMed, Web of Science, ClinicalKey, ClinicalTrials.gov, and Cochrane Library were searched without time limitation using the appropriate keywords. Studies were scrutinized, and the information from those that met our inclusion criteria was gathered and analyzed. Results: In total, 691 studies were found, of which 14 articles were included for systematic review. Bacterial lysate containing K. pneumoniae was the most studied vaccine candidate. As the main indicator of human immune responses to K. pneumoniae, antibody responses were determined by most studies. The antigen amount, the route of immunization, and the immunization schedule were varying in the studies and were chosen based on several factors such as the disease model, the vaccine type, the vaccination setting (prophylactic or therapeutic), and so on. Conclusion: The majority of studies asserted that their vaccination was efficient and safe, which was demonstrated by a decrease in the rate of infections and the induction of protective antibody, cell-dependent, and/or cytokine responses. Altogether, the information provided here will help researchers examine the K. pneumoniae vaccine candidates more closely and take future actions that will be more consistently successful.

Comparison of the Effect of Two Therapeutic Interventions for the Treatment of Chronic Constipation in Children With Cerebral Palsy: A Randomized Clinical Trial.

Objectives. Constipation is one of the most common gastrointestinal symptoms in children with neurological disorders. This study was performed to compare the therapeutic effect of polyethylene glycol (PEG) plus domperidone with PEG plus placebo in the treatment of chronic constipation in children with cerebral palsy. Methods. In this a double-blind clinical trial study was done on the children with cerebral palsy who had chronic constipation and was referred to Mohammad Kermanshahi hospital of Kermanshah city in the west of Iran. The participants were randomly divided into 2 groups with 2 therapies of PEG combined with domperidone (case group, n = 21) and PEG with placebo (control group, n = 21). The information was extracted from patients based on the checklist before and after treatment and the response to treatment in the 2 groups were determined and compared. The data were analyzed by T-test or Mann-Whitney U test to compare quantitative variables and Chi-square and Fisher's exact tests for comparing qualitative variables. Results. In both case and control groups, all Rome IV criteria for a diagnosis of chronic constipation except incontinence were significantly reduced after treatment. However, the successful response rate in the case group (PEG + domperidone) was 90.5%, while this rate was 61.9% in the control group. Conclusion. Based on the results of the present study, it seems that PEG plus domperidone had a positive effect on the treatment of children with cerebral palsy and chronic constipation.

Comment on Islam et al. Helminth Parasites among Rodents in the Middle East Countries: A Systematic Review and Meta-Analysis. Animals 2020, 10, 2342.

I read with great interest the article by Islam et al. entitled "Helminth parasites among rodents in the Middle East countries: a systematic review and meta-analysis" published in Animals in December 2020 [...].

Phenotypic, genotypic, and metabolic resistance mechanisms of ESKAPE bacteria to chemical disinfectants: a systematic review and meta-analysis.

BACKGROUND: The presence of resistant ESKAPE pathogens to antimicrobials including chemical disinfectants (ChDs) is a serious threat to public health worldwide. In the present study, we systematically reviewed published reports on mechanisms beyond ChD resistance of ESKAPE bacteria. RESEARCH DESIGN AND METHODS: Several databases without date limitations were searched. Studies focused on the ChD resistance/tolerance mechanisms of ESKAPE bacteria were included. Meta-analysis was done to assess the frequency of tolerance and genes in ESKAPE clinical isolates. By screening of initial 6733 records, finally, 41 studies were included. RESULTS: The overall tolerance to at least one ChD was 48.6%. Pseudomonas aeruginosa and Acinetobacter baumannii were highly ChD-resistant. In several studies, phenotypic changes including changes in general morphology, pump function, cell surface, and membrane, as well as metabolic changes were observed after ChD addition. The resistance gene frequency was 70.2% for norfloxacin efflux pump genes, 40.6% for qac major facilitator superfamily genes, and 22.2% for qac small multidrug resistance genes. CONCLUSION: We systematically reviewed the effect of various mechanisms in the resistance process of ESKAPE bacteria to ChDs. However, except for the impact of genes, the numbers of studies investigating other mechanisms were very limited, demanding carrying out more studies in this field.

Epitope mapping of Acinetobacter baumannii outer membrane protein W (OmpW) and laboratory study of an OmpW-derivative peptide.

Outer membrane protein W (OmpW) is a less-known A. baumannii antigen with potential immunogenic properties. The epitopes of this protein are not well-identified yet. Therefore, in the present study, B- and T-cell epitopes of A. baumannii OmpW were found using comprehensive in silico and partially in vitro studies. The T-cell (both class-I and class-II) and B-cell (both linear and conformational) epitopes were predicted and screened through many bioinformatics approaches including the prediction of IFN-γ production, immunogenicity, toxicity, allergenicity, human similarity, and clustering. A single 15-mer epitopic peptide containing a linear B-cell and both classes of T-cell epitopes were found and used for further assays. For in vitro assays, patient- and healthy control-derived peripheral blood mononuclear cells were stimulated with the 15-mer peptide, Phytohemagglutinin, or medium alone, and cell proliferation and IFN-γ production assays were performed. The bioinformatics studies led to mapping OmpW epitopes and introducing a 15-mer peptide. In vitro assays to some extent showed its potency in cell proliferation but not in IFN-γ induction, although the responses were not very expressive and faced some questions/limitations. In general, in the current study, we mapped the most immunogenic epitopes of OmpW that may be used for future studies and also assayed one of these epitopes in vitro, which was shown to have an immunogenicity potential. However, the induced immune responses were not strong which suggests that the present peptide needs a series of biotechnological manipulations to be used as a potential vaccine candidate. More studies in this field are recommended.

Two peptides derivate from Acinetobacter baumannii outer membrane protein K as vaccine candidates: a comprehensive in silico study.

BACKGROUND: The lack of appropriate vaccines is an obstacle to the effective management of A. baumannii infections. Peptide vaccines offer an attractive and promising preventive strategy against A. baumannii. OBJECTIVE: In this study, we identified specific T cell epitopes of A. baumannii outer membrane protein K (OMPK) using comprehensive bioinformatics and detailed molecular docking analysis. METHODS: Both class-I and class-II T cell epitopes of A. baumannii OMPK were predicted by three tools namely IEDB, SYFPEITHI, and ProPred. The predicted epitopes were shortlisted based on several analyses including prediction scoring, clustering, exclusion of human similarity, considering immunogenicity and cytokine production, and removal of toxic and/or allergen epitopes. The epitopic peptides with high prediction scores and appropriate properties containing both class-I and class-II T cell epitopes were selected. Two of these class I/II epitopic peptides were chosen for molecular docking studies and assessing their physicochemical properties as vaccine candidates. RESULTS: The results showed many T-cell epitopes of OMPK that could be evaluated for possible immunogenicity. Two of these epitopes (containing both class-I and II epitopes) had high prediction scores, were predicted by several tools, attached to several HLAs, and had the best docking score. They had different physicochemical properties and were conserved among Acinetobacter species. DISCUSSION: We identified the A. baumannii OMPK high immunogenic class-I and class-II T cell epitopes and introduced two promising high immunogenic peptides as vaccine candidates. It is recommended to perform in vitro/in vivo investigation of these peptides to determine their true efficacy and efficiency.

Co-infection of COVID-19 and parasitic diseases: A systematic review.

Co-infection of COVID-19 with other diseases increases the challenges related to its treatment management. COVID-19 co-infection with parasites is studied with low frequency. Here, we systematically reviewed the cases of parasitic disease co-infection with COVID-19. All articles on COVID-19 co-infected with parasites (protozoa, helminths, and ectoparasites), were screened through defined inclusion/exclusion criteria. Of 2190 records, 35 studies remained for data extraction. The majority of studies were about COVID-19 co-infected with malaria, followed by strongyloidiasis, amoebiasis, chagas, filariasis, giardiasis, leishmaniasis, lophomoniasis, myiasis, and toxoplasmosis. No or low manifestation differences were reported between the co-infected cases and naïve COVID-19 or naïve parasitic disease. Although there was a relatively low number of reports on parasitic diseases-COVID-19 co-infection, COVID-19 and some parasitic diseases have overlapping symptoms and also COVID-19 conditions and treatment regimens may cause some parasites re-emergence, relapse, or re-activation. Therefore, more attention should be paid to the on-time diagnosis of COVID-19 and the co-infected parasites.

Finding epitopes of Klebsiella pneumoniae outer membrane protein-K17 (OMPK17) and introducing a 25-mer peptide of it as a vaccine candidate.

No approved vaccine exists for Klebsiella pneumoniae yet. Outer membrane protein-K17 (OMPK17) is involved in K. pneumoniae pathogenesis. No information has been found about OMPK17 dominant epitopes in the literature. Therefore, this study aimed to predict both T cell and B cell epitopes of K. pneumoniae OMPK17 via immunoinformatics approaches. Both T cell (class-I and II) and B cell (linear and discontinuous) epitopes of OMPK17 were predicted. Several screening analyses were performed including clustering, immunogenicity, human similarity, toxicity, allergenicity, conservancy, docking, and structural/physicochemical suitability. The results showed that some regions of OMPK17 have more potential as epitopes. The most possible epitopes were found via several analyses including the selection of higher-scoring epitopes, the epitopes predicted with more tools, more immunogenic epitopes, the epitopes capable of producing interferon-gamma, the epitopes with more dissimilarity to human peptides, and non-toxic and non-allergenic epitopes. By comparing the best T cell and B cell epitopes, we reached a 25-mer peptide containing both T cell (class-I and class-II) and B cell (linear) epitopes and comprising appropriate physicochemical characteristics that are required for K. pneumoniae vaccine development. The in vitro/in vivo study of this peptide is recommended to clarify its actual efficiency and efficacy. Supplementary information: The online version contains supplementary material available at 10.1007/s11756-023-01371-0.

A new multi-epitope vaccine candidate based on S and M proteins is effective in inducing humoral and cellular immune responses against SARS-CoV-2 variants: an in silico design approach.

Available COVID-19 vaccines are primarily based on SARS-CoV-2 spike protein (S). Due to the emergence of new SARS-CoV-2 variants, other virus proteins with more conservancy, such as Membrane (M) protein, are desired for vaccine development. The reverse vaccinology approach was employed to design a multi-epitope SARS-CoV-2 vaccine candidate based on S and M proteins. Cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), linear B-lymphocyte (LBL) and conformational B-lymphocyte (CBL) of S and M proteins were predicted and screened to choose the best epitopes. A multi-epitope vaccine candidate was constructed using selected CTL, HTL and LBL epitopes. The efficiency of the construct in binding to some immune receptors and an RBD-potent neutralizing monoclonal antibody (bebtelovimab) was predicted, and its immunogenicity was simulated. Finally, in silico cloning of the constructed gene was performed. The potency of our construct as a SARS-CoV-2 vaccine was validated using several bioinformatics tools. The simulation results showed that the construct can induce both cellular and humoral immune responses by producing appropriate cytokines, and it can even create an excellent immune memory response. Furthermore, the designed construct interacts with innate immune receptors such as TLR2 and TLR4 and the terminal variable domain of bebtelovimab with high affinity. We developed a multi-epitope construct based on the S and M proteins of the SARS-CoV-2 virus with high immunogenicity potential using the most up-to-date immunoinformatics and computational biology approaches. The actual efficiency of this multi-epitope vaccine should be further evaluated via in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

High burden of MDR, XDR, PDR, and MBL producing Gram negative bacteria causing infections in Kermanshah health centers during 2019-2020.

Background and Objectives: Microorganisms producing Metallo-Beta-Lactamase (MBL) are a threat and cause of concern as they have become one of the most feared resistance mechanisms. This study was designed to explore the prevalence of MBL production in clinical isolates of Gram negative bacteria using phenotypic MBL detection. Materials and Methods: A total of 248 isolates were collected from various clinical samples and were evaluated for carbapenem resistance and MBL production. All strains were screened for MBL production using Double Disk Confirmatory Test (DDCT). Results: The results of screening for MBL production using phenotypic disk diffusion method showed that in the 85 isolates were carbapenemase positive; including, 10 (16.1%) Klebsiella pneumoniae, 9 (14.5%) Escherichia coli, 58 (93.6%) Acinetobacter baumannii, and 8 (12.9%) Pseudomonas aeruginosa isolates. Also, 83 (97.6) Carbapenemase-producing isolates were resistant to at least four classes of antimicrobials (MDR). Conclusion: A. baumannii was the most common carbapenem resistant bacterium in medical centers in Kermanshah. Significant multiple drug resistance (MDR) incidence was observed compared to different classes of antibiotics.

Prevalence of Mycobacterium tuberculosis mutations associated with isoniazid and rifampicin resistance: A systematic review and meta-analysis.

Tuberculosis (TB) is still one of the leading causes of worldwide death, especially following the emergence of strains resistant to isoniazid (INH) and rifampicin (RIF). This study aimed to systematically review published articles focusing on the prevalence of INH and/or RIF resistance-associated mutations of Mycobacterium tuberculosis isolates in recent years. Literature databases were searched using appropriate keywords. The data of the included studies were extracted and used for a random-effects model meta-analysis. Of the initial 1442 studies, 29 were finally eligible to be included in the review. The overall resistance to INH and RIF was about 17.2% and 7.3%, respectively. There was no difference between the frequency of INH and RIF resistance using different phenotypic or genotypic methods. The INH and/or RIF resistance was higher in Asia. The S315T mutation in KatG (23.7 %), C-15 T in InhA (10.7 %), and S531L in RpoB (13.5 %) were the most prevalent mutations. Altogether, the results showed that due to S531L in RpoB, S315T in KatG, and C-15 T in InhA mutations INH- and RIF-resistant M. tuberculosis isolates were widely distributed. Thus, it would be diagnostically and epidemiologically beneficial to track these gene mutations among resistant isolates.