Prevalence and molecular characterization of colistin resistance in Pseudomonas aeruginosa isolates: insights from a study in Ardabil hospitals.

BACKGROUND: Pseudomonas aeruginosa is a common cause of nosocomial infections. However, the emergence of multidrug-resistant strains has complicated the treatment of P. aeruginosa infections. While polymyxins have been the mainstay for treatment, there is a global increase in resistance to these antibiotics. Therefore, our study aimed to determine the prevalence and molecular details of colistin resistance in P. aeruginosa clinical isolates collected between June 2019 and May 2023, as well as the genetic linkage of colistin-resistant P. aeruginosa isolates. RESULTS: The resistance rate to colistin was 9% (n = 18) among P. aeruginosa isolates. All 18 colistin-resistant isolates were biofilm producers and carried genes associated with biofilm formation. Furthermore, the presence of genes encoding efflux pumps, TCSs, and outer membrane porin was observed in all colistin-resistant P. aeruginosa strains, while the mcr-1 gene was not detected. Amino acid substitutions were identified only in the PmrB protein of multidrug- and colistin-resistant strains. The expression levels of mexA, mexC, mexE, mexY, phoP, and pmrA genes in the 18 colistin-resistant P. aeruginosa strains were as follows: 88.8%, 94.4%, 11.1%, 83.3%, 83.3%, and 38.8%, respectively. Additionally, down-regulation of the oprD gene was observed in 44.4% of colistin-resistant P. aeruginosa strains. CONCLUSION: This study reports the emergence of colistin resistance with various mechanisms among P. aeruginosa strains in Ardabil hospitals. We recommend avoiding unnecessary use of colistin to prevent potential future increases in colistin resistance.

Prevalence and mechanisms of ciprofloxacin resistance in Escherichia coli isolated from hospitalized patients, healthy carriers, and wastewaters in Iran.

BACKGROUND: This study was aimed to evaluate the prevalence and molecular characteristics of ciprofloxacin resistance among 346 Escherichia coli isolates collected from clinical specimens (n = 82), healthy children (n = 176), municipal wastewater (n = 34), hospital wastewater (n = 33), poultry slaughterhouse wastewater (n = 12) and livestock (n = 9) slaughterhouse wastewater in Iran. METHODS: Ciprofloxacin minimum inhibitory concentration (MIC) was determined by agar dilution assay. Phylogroups and plasmid-mediated quinolone resistance (PMQR) genes were identified using PCR. Mutations in gyrA, gyrB, parC, and parE genes and amino acid alterations were screened through sequencing assay. The effect of efflux pump inhibitor (PAßN) on ciprofloxacin MICs in ciprofloxacin-resistant isolates was investigated using the microdilution method. RESULTS: In total, 28.03% of E. coli isolates were phenotypically resistant to ciprofloxacin. Based on sources of isolation, 64.63%, 51.51%, 33.33%, 14.70%, 10.22% and 8.33% of isolates from clinical specimens, hospital wastewater, livestock wastewater, municipal wastewater, healthy children and poultry wastewater were ciprofloxacin-resistant, respectively. Eighty-one point eighty-one percent (Ser-83 → Leu + Asp-87 → Asn; 78.78% and Ser-83 → Leu only; 3.03% (of ciprofloxacin-resistant E. coli isolates showed missense mutation in GyrA subunit of DNA gyrase, while no amino-acid substitution was noted in the GyrB subunit. DNA sequence analyses of the ParC and ParE subunits of topoisomerase IV exhibited amino-acid changes in 30.30% (Ser-80 → Ile + Glu-84 → Val; 18.18%, Ser-80 → Ile only; 9.10% and Glu-84 → Val only; 3.03%0 (and 15.38% (Ser-458 → Ala) of ciprofloxacin-resistant E. coli isolates, respectively. The PMQR genes, aac(6')-Ib-cr, qnrS, qnrB, oqxA, oqxB, and qepA were detected in 43.29%, 74.22%, 9.27%, 14.43%, 30.92% and 1.03% of ciprofloxacin-resistant isolates, respectively. No isolate was found to be positive for qnrA and qnrD genes. In isolates harboring the OqxA/B efflux pump, the MIC of ciprofloxacin was reduced twofold in the presence of PAßN, as an efflux pump inhibitor. The phylogroups B2 (48.45%) and A (20.65%) were the most predominant groups identified in ciprofloxacin-resistant isolates. CONCLUSIONS: This study proved the high incidence of ciprofloxacin-resistant E. coli isolates in both clinical and non-clinical settings in Iran. Chromosomal gene mutations and PMQR genes were identified in ciprofloxacin resistance among E. coli population.

Antibiotic resistance and virulence potentials of E. faecalis and E. faecium in hospital wastewater: a case study in Ardabil, Iran.

Hospital wastewater can contaminate the environment with antibiotic-resistant and virulent bacteria. We analyzed wastewater samples from four hospitals in Ardabil province, Iran for Enterococcus faecium and Enterococcus faecalis using culture and molecular methods. We also performed antimicrobial susceptibility testing and polymerase chain reaction testing for resistance and virulence genes. Out of 141 enterococci isolates, 68.8% were E. faecium and 23.4% were E. faecalis. Ciprofloxacin and rifampicin showed the highest level of resistance against E. faecalis and E. faecium isolates at 65%. High-level gentamicin resistance (HLGR), high-level streptomycin resistance (HLSR), ampicillin, and vancomycin resistance were observed in 25, 5, 10, and 5.15% of E. faecium, and 15, 6, 15, and 3.03% of E. faecalis isolates, respectively. The ant(6')-Ia and ant(3')-Ia genes that were responsible for streptomycin resistance were observed in HLSR isolates and aph(3')-IIIa and aac(6') Ie-aph(2″)-Ia genes accounting for gentamicin resistance were detected in HLGR isolates. vanA was the predominant gene detected in vancomycin-resistant isolates. The majority of isolates were positive for gelE, asa1, esp, cylA, and hyl virulence genes. We found that drug-resistant and virulent E. faecalis and E. faecium isolates were prevalent in hospital wastewater. Proper treatment strategies are required to prevent their dissemination into the environment.

Association of carbapenem and multidrug resistance with the expression of efflux pump-encoding genes in Pseudomonas aeruginosa clinical isolates.

Efflux pumps play an important role in the emergence of antibiotic-resistant Pseudomonas aeruginosa strains. The present study aimed to assess the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps in carbapenem-resistant and multidrug-resistant (MDR) P. aeruginosa strains isolated from clinical specimens between June 2019 and January 2022 in Ardabil city. The presence of efflux pump-encoding genes, i.e. mexA, mexC, mexE, and mexY, was assessed using the polymerase chain reaction (PCR) technique in 48 carbapenem-resistant and MDR P. aeruginosa strains. Real-time reverse transcription PCR was employed to evaluate the expression levels of mexA, mexC, mexE, and mexY genes. All 48 carbapenem-resistant and MDR P. aeruginosa strains harbored efflux pump-encoding genes including mexA, mexC, mexE, and mexY according to the PCR results. Overexpression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps was detected in 75% (n = 36), 83.3% (n = 40), 10.4% (n = 5) and 41.6% (n = 20) of the clinical isolates of P. aeruginosa, respectively. This study revealed that the presence and overexpression of efflux pumps are associated with the emergence of carbapenem-resistant and MDR P. aeruginosa strains. Therefore, research on efflux pump inhibitors of P. aeruginosa will be a worthwhile endeavor to increase the clinical efficiency of available antibiotics and prevent ensuing treatment failure.

Imipenem resistance associated with amino acid alterations of the OprD porin in Pseudomonas aeruginosa clinical isolates.

Globally, the spread of carbapenem-resistant strains has limited treatment options for multidrug-resistant (MDR) Pseudomonas aeruginosa infections. This study aimed to determine the role of point mutations as well as the expression level of the oprD gene in the emergence of imipenem-resistant P. aeruginosa strains isolated from patients referred to Ardabil hospitals. A total of 48 imipenem-resistant clinical isolates of P. aeruginosa collected between June 2019 and January 2022 were used in this study. Detection of the oprD gene and its amino acid alterations was performed using the polymerase chain reaction (PCR) and DNA sequencing techniques. The expression level of the oprD gene in imipenem-resistant strains was determined using the real-time quantitative reverse transcription PCR (RT-PCR) method. All imipenem-resistant P. aeruginosa strains were positive for the oprD gene based on the PCR results, and also five selected isolates indicated one or more amino acid alterations. Detected amino acid alterations in the OprD porin were Ala210Ile, Gln202Glu, Ala189Val, Ala186Pro, Leu170Phe, Leu127Val, Thr115Lys, and Ser103Thr. Based on the RT-PCR results, the oprD gene was downregulated in 79.1% of imipenem-resistant P. aeruginosa strains. However, 20.9% of strains showed overexpression of the oprD gene. Probably, resistance to imipenem in these strains is associated with the presence of carbapenemases, AmpC cephalosporinase, or efflux pumps. Owing to the high prevalence of imipenem-resistant P. aeruginosa strains due to various resistance mechanisms in Ardabil hospitals, the implementation of surveillance programs to reduce the spread of these resistant microorganisms along with rational selection and prescription of antibiotics is recommended.

Prevalence of resistance genes to biocides in antibiotic-resistant Pseudomonas aeruginosa clinical isolates.

BACKGROUND: Biocides are frequently used as preservative, disinfectant and sterilizer against many microorganisms in hospitals, industry and home. However, the reduced susceptibility rate of Pseudomonas aeruginosa (P. aeruginosa) strains to biocides is increasing. The aim of this study was to evaluate the antimicrobial activity of four frequently used biocides against P. aeruginosa and to determine the prevalence of genes involved in biocide resistance. METHODS: A total of 76 clinical isolates of P. aeruginosa strains were used in the present study. The minimum inhibitory concentrations (MICs) of four biocides, i.e. chlorhexidine digluconate, benzalkonium chloride, triclosan and formaldehyde, against P. aeruginosa strains were determined using agar dilution method. In addition, the prevalence of biocide resistance genes was determined using the polymerase chain reaction (PCR) method. RESULTS: In the present study, the highest MIC90 and MIC95 (epidemiological cut-off) values were observed for benzalkonium chloride (1024 µg/mL), followed by formaldehyde (512 µg/mL), triclosan (512 µg/mL) and chlorhexidine digluconate (64 µg/mL). Furthermore, the prevalence of qacEΔ1, qacE, qacG, fabV, cepA and fabI genes were 73.7% (n = 56), 26.3% (n = 20), 11.8% (n = 9), 84.2% (n = 64), 81.5% (n = 62) and 0% (n = 0), respectively. A significant association was observed between the presence of biocide resistance genes and MICs (p < 0.05). Furthermore, there was no significant association between the presence of biocide resistance genes and antibiotic resistance (p > 0.05), except for levofloxacin and norfloxacin antibiotics and qacE and qacG genes (p < 0.05). CONCLUSION: Our results revealed that chlorhexidine digluconate is the most effective biocide against P. aeruginosa isolates in Ardabil hospitals. However, we recommend continuous monitoring of the antimicrobial activity of biocides and the prevalence of biocide-associated resistance genes for a better prevention of microorganism dissemination and infection control in hospitals.

Immunogenicity of HspX/EsxS fusion protein of Mycobacterium tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants after subcutaneous administration in animal model.

BACKGROUND: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is one of the most common and dangerous infectious diseases in the world. Despite vaccination with BCG, it is still considered as a major health problem. Therefore, design and production of an effective novel vaccine against TB is necessary. Our aim was to evaluate immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX, PLUSCOM nano-adjuvants and MPLA through the subcutaneous route in mice model. METHODS: HspX/EsxS fused protein of M. tuberculosis was cloned, expressed and purified in the prokaryotic system. ISCOMATRIX and PLUSCOM nano-adjuvants were prepared by film hydration method. Subcutaneous immunization of BALB/c mice was performed by different formulations. IFN-γ, IL-4, IL-17 and TGF-ß cytokines levels as well as serum IgG1, IgG2a. RESULTS: Our results showed that subcutaneous administration of mice with HspX/EsxS along with three adjuvants, ISCOMATRIX, PLUSCOM and MPLA increased immunogenicity of multi-stage fusion protein of M. tuberculosis. Additionally, HspX/EsxS protein + ISCOMATRIX or + PLUSCOM nano-adjuvants induced stronger Th1, IgG2a and IgG1 immune responses compared to MPLA adjuvant. Totally, HspX/EsxS/ISCOMATRIX/MPLA, HspX/EsxS/PLUSCOM/MPLA and two BCG booster groups could significantly induce higher Th1 and IgG2a immune responses. CONCLUSION: With regard to ability of ISCOMATRIX, PLUSCOM and MPLA adjuvants to increase immunogenicity of HspX/EsxS protein through induction of IFN-γ and IgG2a immune responses, it seems that these adjuvants and especially ISCOMATRIX and PLUSCOM, could also improve BCG efficacy as a BCG booster.

Potential of Cationic Liposomes as Adjuvants/Delivery Systems for Tuberculosis Subunit Vaccines.

The weakness of the BCG vaccine and its highly variable protective efficacy in controlling tuberculosis (TB) in different age groups as well as in different geographic areas has led to intense efforts towards the development and design of novel vaccines. Currently, there are several strategies to develop novel TB vaccines. Each strategy has its advantages and disadvantages. However, the most important of these strategies is the development of subunit vaccines. In recent years, the use of cationic liposome-based vaccines has been considered due to their capacity to elicit strong humoral and cellular immune responses against TB infections. In this review, we aim to evaluate the potential for cationic liposomes to be used as adjuvants/delivery systems for eliciting immune responses against TB subunit vaccines. The present review shows that cationic liposomes have extensive applications either as adjuvants or delivery systems, to promote immune responses against Mycobacterium tuberculosis (Mtb) subunit vaccines. To overcome several limitations of these particles, they were used in combination with other immunostimulatory factors such as TDB, MPL, TDM, and Poly I:C. Cationic liposomes can provide long-term storage of subunit TB vaccines at the injection site, confer strong electrostatic interactions with APCs, potentiate both humoral and cellular (CD4 and CD8) immune responses, and induce a strong memory response by the immune system. Therefore, cationic liposomes can increase the potential of different TB subunit vaccines by serving as adjuvants/delivery systems. These properties suggest the use of cationic liposomes to produce an efficient vaccine against TB infections.

A systematic review and meta-analysis on the prevalence of antibiotic-resistant Listeria species in food, animal and human specimens in Iran.

The aim of this study was to determine the antimicrobial resistance characteristics of Listeria species isolated from foods and food processing environments, animal and human specimens in Iran. A systematic review of the papers published in Persian and English languages up to 20th May 2019 and indexed in the Scientific Information Database, PubMed, Scopus and Google Scholar databases using related keywords was conducted. Eligible articles were selected based on the predefined inclusion and exclusion criteria, followed by data extraction and meta-analysis using random-effects or fixed-effects models. A total of 27 articles were found reporting antibiotic resistance patterns of different Listeria species using disk diffusion method. Among Listeria species, Listeria monocytogenes resistance to commonly used antibiotics i.e. penicillin, ampicillin and gentamicin was as follows: 34.5%, 26.4%, 8.9% in isolates from foods and food processing environments, 47.1%, 29.5%, 9.2% in isolates from animal specimens and 56.8%, 29.5%, 32.4% in human strains, respectively. A high prevalence of L. monocytogenes strains resistant to penicillin, ampicillin and gentamicin was observed in Iran. Our findings suggested that trimethoprim/sulfamethoxazole, vancomycin and ciprofloxacin can be used as alternatives in the treatment of human listeriosis in Iran due to their low resistance rates.

PCSK9 and infection: A potentially useful or dangerous association?

Elevated plasma low-density lipoprotein-cholesterol (LDL-C) concentration is the most important risk factor for atherosclerotic cardiovascular diseases (CVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a ubiquitously expressed serine proteinase which plays a key role in cholesterol metabolism, but has been found to be implicated in some other lipid-independent physiological processes. In this review, the role of PCSK9 was evaluated not only concerning lipid metabolism but also hepatitis C virus (HCV) infection, bacterial infections/sepsis, and septic shock. Collected data from clinical trials revealed that treatment with PCSK9 inhibitors has beneficial effects in lowering LDL-C via inhibition of LDL-receptors (LDL-R), an antiviral effect on HCV infection via down-regulating the surface expression of LDL-R and CD81 on hepatic cells, and a positive association with increased inflammatory responses, as well as with septic shock by down-regulation of hepatocyte LDL-R. On the other hand, PCSK9 inhibition by therapeutic fully humanized antibodies has positive effects in reducing elevated LDL-C. However, their safety and tolerability is an important issue which has to be taken into consideration.

A novel antigen of Mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity.

BACKGROUND: Due to initiation of Mycobacterium tuberculosis infection via the mucosal tissue of the respiratory tract, intranasal administration of new tuberculosis vaccines is highly regarded to enhance mucosal immunity. Our outline was evaluation of mucosal and systemic immune responses in BALB/c mice after nasal delivery of HspX/EsxS fused antigen of Mycobacterium tuberculosis along with MPLA adjuvant entrapped in PLGA:DDA hybrid nanoparticles. METHODS: In this study, the double emulsion solvent evaporation method (w/o/w) was used to prepare different nanoparticle formulations containing HspX/EsxS protein and MPLA. Three weeks after the last nasal immunization of BALB/c mice, IgA antibody levels in nasal lavage and IFN-γ, IL-4, IL-17 and TGF-ß cytokines in supernatant of cultured splenocytes and also serum IgG1 and IgG2a titers were evaluated using ELISA method. RESULTS: Our results indicated that nasal vaccination with PLGA:DDA nanoparticles loaded with HspX/EsxS protein±MPLA, both with and without a prime dose of BCG could provide efficient Th1, Th17, IgA, IgG1 and IgG2a immune responses. CONCLUSION: These findings demonstrate that both PLGA:DDA hybrid nanoparticles as carrier/adjuvant and MPLA as adjuvant, could efficiently induce mucosal and systemic immune responses against HspX/EsxS antigen, alone or as a booster for BCG.

Are chitosan natural polymers suitable as adjuvant/delivery system for anti-tuberculosis vaccines?

Today, the effectiveness of the only approved tuberculosis (TB) vaccine, bacillus Calmette-Guerin (BCG), has encountered several serious problem in the control of TB infections including variable protection in adolescents and adults, the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) as well as HIV/AIDS co-infection. Various studies have shown that chitosan, a natural polymer, can serve as a potent carrier for the delivery of various hydrophilic molecules such as peptide, protein and drug agents due to some of its excellent characteristics including low toxicity, biodegradable and biocompatible properties and stability. Currently, these polysaccharide polymers have gained more attention as candidates for the adjuvant/delivery of anti-TB vaccines due to better cellular uptake, muco-adhesive characteristics, prolonged control release, persistent stimulation of the immune system, more efficient uptake by antigen processing cells (APCs), adjuvant/immunopotentiator function, and preventing antigen degradation in-vivo. The present study showed that the new generation of TB vaccine candidates when used in combination with chitosan and its derivatives as adjuvant or delivery system, could potently induce both protective and cell-mediated (CD4 and CD8) immune responses in animal models. In addition, they could also enhance protection against Mtb infection in TB-challenged mice and act as booster-vaccines to improve BCG-primed immunity and excellent prime-vaccines. The results of this study showed that parenteral and non-parenteral immunization of chitosan-based TB vaccines can induce appropriate immune responses; however, we suggest that based on some advantages of chitosan polymers and mucosal delivery route, non-parenteral immunization may be a better administration route for chitosan-based TB vaccines.

Prevalence of bacterial vaginosis in pregnant and non-pregnant Iranian women: a systematic review and meta-analysis.

PURPOSE: Bacterial vaginosis (BV) is a vaginal disorder which occurs either symptomatic or asymptomatic because of an imbalance between H2O2-producing Lactobacillus and Gardnerella vaginalis in the vagina. This systematic review and meta-analysis is the first to determine the prevalence of BV in pregnant and non-pregnant women in Iran. METHODS: We used national (SID, Irandoc, Iranmedex and Magiran) and international (PubMed, Scopus, Google Scholar and ISI web of knowledge) electronic databases to systematically search and collect available studies using related keywords (up to 1 December 2017). Inclusion and exclusion criteria were defined to select eligible studies. RESULTS: The overall prevalence of BV among Iranian women was 18.9% (95% CI 14-25). Gardnerella vaginalis was the most prevalent isolated bacteria. The prevalence of BV in non-pregnant women was 28% (95% CI 15.1-45.9) which was higher compared with pregnant women who had a prevalence of 16.5% (95% CI 12.5-21.6). CONCLUSION: The present review revealed a high prevalence of BV in non-pregnant women. Given that BV is associated with a series of reproductive complications such as infertility, taking preventive measures such as awareness of patients as well as monitoring and controlling of syndrome are essential.

Bacterial Co-infections in HIV/AIDS-positive Subjects: A Systematic Review and Meta-analysis.

BACKGROUND: Bacterial infections are the most common complications in people with HIV/AIDS. There has been no previous report on the prevalence of bacterial co-infections in Iranian HIV/AIDS-positive subjects. AIM: To evaluate the frequency of bacterial infections in hospitalized HIV/AIDS-infected patients in Iran. MATERIALS AND METHODS: Based on PRISMA guidelines, a computerized search in related data banks using relevant keywords was performed in both Persian and English languages for articles that were published until March 10, 2017. A total of 1118 original articles were systematically reviewed to identify eligible studies on the prevalence of bacterial co-infections in HIV/AIDS-infected patients from Iran. After screening for inclusion and exclusion criteria, we extracted data from 28 eligible articles for the meta-analysis. RESULTS: The overall bacterial infection rate among Iranian HIV/AIDS-positive individuals was estimated to be 48.6%. Gastrointestinal disorders (59.5%) were the most frequent bacterial infections in this group of patients followed by bacterial lymphadenopathy (38.9%), TB infection (38.2%), bacterial pneumonia (31.2%), brucellosis (26.3%), skin infections (13.3%) and sexually transmitted infections (9.7%). The prevalence of other bacterial infections including endocarditis, sepsis and Staphylococcus aureus (S. aureus) were 10%, 9.1%, and 6.9%, respectively. CONCLUSION: The prevalence of a wide spectrum of bacterial co-infections, especially endemic infections, in Iranian HIV/AIDS-infected patients, is alarming and calls for urgent need to improve the currently applied diagnostic and preventive methods. In addition, timely treatment of these infections is pivotal to decrease the morbidity and mortality rates in HIV/AIDS-infected patients.

Enhancement of the immunogenicity of a Mycobacterium tuberculosis fusion protein using ISCOMATRIX and PLUSCOM nano-adjuvants as prophylactic vaccine after nasal administration in mice.

Objectives: Tuberculosis (TB), a contagious disease caused by Mycobacterium tuberculosis (M. tuberculosis), remains a health problem worldwide and this infection has the highest mortality rate among bacterial infections. Current studies suggest that intranasal administration of new TB vaccines could enhance the immunogenicity of M. tuberculosis antigens. Hence, we aim to evaluate the protective efficacy and immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA through intranasal administration in a mice model. Materials and Methods: In the present study, the recombinant fusion protein was expressed in Escherichia coli and purified and used to prepare different nanoparticle formulations in combination with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA. Mice were intranasally vaccinated with each formulation three times at an interval of 2 weeks. Three weeks after the final vaccination, IFN-γ, IL-4. IL-17, and TGF-ß concentrations in the supernatant of cultured splenocytes of vaccinated mice as well as serum titers of IgG1 and IgG2a and sIgA titers in nasal lavage were determined. Results: According to obtained results, intranasally vaccinated mice with formulations containing ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA could effectively induce IFN-γ and sIgA responses. Moreover, both HspX/EsxS/ISCOMATRIX/MPLA and HspX/EsxS/PLUSCOM/MPLA and their BCG booster formulation could strongly stimulate the immune system and enhance the immunogenicity of M. tuberculosis antigens. Conclusion: The results demonstrate the potential of HspX/EsxS-fused protein in combination with ISCOMATRIX, PLUSCOM, and MPLA after nasal administration in enhancing the immune response against M. tuberculosis antigens. Both nanoparticles were good adjuvants in order to promote the immunogenicity of TB-fused antigens. So, nasal immunization with these formulations, could induce immune responses and be considered a new TB vaccine or a BCG booster.

Resistance pattern of Helicobacter pylori strains to clarithromycin, metronidazole, and amoxicillin in Isfahan, Iran.

BACKGROUND: Helicobacter pylori (H. pylori) resistance to antibiotics has become a global problem and is an important factor in determining the outcome of treatment of infected patients. The purpose of this study was to determine the H. pylori resistance to clarithromycin, metronidazole, and amoxicillin in gastrointestinal disorders patients. MATERIALS AND METHODS: In this study, a total of 260 gastric antrum biopsy specimens were collected from patients with gastrointestinal disorders who referred to Endoscopy Section of the Isfahan Hospitals. The E-test and Modified Disk Diffusion Method (MDDM) were used to verify the prevalence of antibiotic resistance in 78 H. pylori isolates to the clarithromycin, metronidazole, and amoxicillin. RESULTS: H. pylori resistance to clarithromycin, metronidazole, and amoxicillin were 15.3, 55.1, and 6.4%, respectively. In this study, we had one multidrug resistance (MDR) isolates from patient with gastritis and peptic ulcer disease. CONCLUSION: Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. According to the results obtained in this study, H. pylori resistance to clarithromycin and metronidazole was relatively high. MDR strains are emerging and will have an effect on the combination therapy.

Macrolide-Lincosamide Resistance and Virulence Genes in Staphylococcus aureus Isolated from Clinical Specimens in Ardabil, Iran.

Background & Objective: Staphylococcus aureus causes various hospital- and community-acquired infections. This study aimed to investigate the phenotypic and genotypic characteristics of erythromycin and inducible clindamycin resistance, virulence gene profiles, and spa types of S. aureus isolates collected from patients in Ardabil Province, Iran. Methods: A total of 118 clinical S. aureus isolates, including 50 (42.4%) methicillin-resistant S. aureus (MRSA) and 68 (57.6%) methicillin-susceptible S. aureus (MSSA) strains, were investigated. Resistance patterns were determined by the disk diffusion method and minimum inhibitory concentration (MIC) test. Inducible macrolide-lincosamide-streptogramin B (iMLSB) resistance was detected using D-test method. The polymerase chain reaction (PCR) was used to identify the virulence and resistance-encoding genes. Additionally, the spa types of the isolates were determined using the PCR, followed by sequencing. Results: In total, 49.1% (58/118) and 44% (52/118) of the isolates were resistant to erythromycin and clindamycin, respectively. Overall, 13.5% (16/118) of the isolates showed the iMLSB resistance phenotype. The ermC gene (72.4% [42]) was the most frequent erythromycin resistance-encoding gene, followed by ermA (60.3% [35]), ermB (60.3% [35]), ermTR (51.7% [30]), and msrA (15.5% [9]) genes among erythromycin-resistant isolates. The virulence genes hla, hld, sea, LukS PV, tst, seb, sed, eta, sec, and etb were detected in 93.2%, 74.5%, 70.3%, 32.2%, 29.6%, 17%, 8.5%, 8.5%, 5.9%, and 4.2% of the isolates, respectively. Ten different spa types were identified for 58 erythromycin-resistant S. aureus strains, of which t030 and t078 types were the most common types. Conclusion: A high frequency of macrolide- and lincosamide-resistant S. aureus isolates with different genetic backgrounds of resistance and virulence may be found in patients in Ardabil Province, Iran.

Prevalence of ESBL-Producing Enterobacter Species Resistant to Carbapenems in Iran: A Systematic Review and Meta-Analysis.

Background: Carbapenems are the last-line therapy for multidrug-resistant (MDR) infections caused by Enterobacterales, including those caused by Enterobacter species. However, the recent emergence of carbapenem-resistant (CR) and extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae pathogens, which are resistant to nearly all antibiotics, has raised concerns among international healthcare organizations. Hence, because there is no comprehensive data in Iran, the current study aimed to evaluate the prevalence of antibiotic resistance among Enterobacter species, especially CR and ESBL-producing strains, in Iran. Methods: The literature search was performed up to June 21, 2021, in national and international databases using MeSH-extracted keywords, i.e., Enterobacter, antibiotic resistance, carbapenem, ESBL, and Iran. Study selection was done based on the predefined inclusion and exclusion criteria, and data analysis was carried out using the Comprehensive Meta-Analysis (CMA) software. Results: The pooled prevalence of Enterobacter species resistant to various antibiotics is as follows: imipenem 16.6%, meropenem 16.2%, aztreonam 40.9%, ciprofloxacin 35.3%, norfloxacin 31%, levofloxacin 48%, gentamicin 42.1%, amikacin 30.3%, tobramycin 37.2%, tetracycline 50.1%, chloramphenicol 25.7%, trimethoprim/sulfamethoxazole 52%, nalidixic acid 49.1%, nitrofurantoin 43%, ceftriaxone 49.3%, cefixime 52.4%, cefotaxime 52.7%, ceftazidime 47.9%, cefepime 43.6%, and ceftizoxime 45.5%. The prevalence rates of MDR and ESBL-producing Enterobacter species in Iran were 63.1% and 32.8%, respectively. Conclusion: In accordance with the warning of international organizations, our results revealed a high prevalence of ESBL-producing Enterobacter species in Iran, which is probably associated with the high prevalence of Enterobacter species resistant to most of the assessed antibiotics, especially MDR strains. However, the resistance rate to carbapenems was relatively low, and these drugs can still be considered as drugs of choice for the treatment of Enterobacter infections in Iran. Nevertheless, continuous monitoring of drug resistance along with antibiotic therapy based on the local data and evaluation of the therapeutic efficacy of new antibiotics or combination therapeutic strategies, such as ceftazidime/avibactam, meropenem/vaborbactam, plazomicin, and eravacycline, is recommended.

Is Penicillin-Nonsusceptible Streptococcus pneumoniae a Significant Challenge to Healthcare System? A Systematic Review and Meta-Analysis.

BACKGROUND: In recent years, antibiotic-resistant pathogens including penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) have posed serious threats against human health. The aim of this meta-analysis was to investigate the prevalence of Streptococcus pneumoniae drug resistance particularly the incidence of PNSP strains in Iran. METHODS: A systematic search was done in national and international electronic databases using Persian and English keywords. Up until May 20, 2020, a total of 58 publications were detected as eligible articles based on the inclusion and exclusion criteria, and then the selected studies were enrolled for data extraction and meta-analysis according to the PRISMA guidelines. RESULTS: A high rate of PNSP (46.9%) and multidrug-resistant (MDR) S. pneumoniae (45.3%) in our isolates were evident. Furthermore, total frequency resistance to other drugs in S. pneumoniae was as follows: erythromycin 41.1%, azithromycin 53.2%, tetracycline 39.9%, levofloxacin 1.7%, rifampin 1.2%, clindamycin 31.7%, vancomycin 1.7%, trimethoprim/sulfamethoxazole 63.9%, chloramphenicol 20%, ceftriaxone 10.9%, amoxicillin 30.5%, ciprofloxacin 8.3%, imipenem 6.1%, linezolid 0%, and cefotaxime 8.3%. CONCLUSION: Although the overall prevalence of cephalosporin- and carbapenem-resistant Streptococcus pneumoniae was low, penicillin-resistant strains, especially PNSP, could become a significant challenge to the healthcare system in Iran. Hence, the prescription of penicillin as the first-choice antibiotic in the treatment of S. pneumoniae infections should be avoided.

An updated systematic review and meta-analysis on Mycobacterium tuberculosis antibiotic resistance in Iran (2013-2020).

This updated systematic review and meta-analysis follows two aims: 1) to assess Mycobacterium tuberculosis (M. tuberculosis) antibiotic resistance in Iran from 2013 to 2020 and, 2) to assess the trend of resistance from 1999 to 2020. Several national and international databases were systematically searched through MeSH extracted keywords to identify 41 published studies addressing drug-resistant M. tuberculosis in Iran. Meta-analysis was done based on the PRISMA protocols using Comprehensive Meta-Analysis software. The average prevalence of resistance to first- and second-line anti-TB drugs, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in new and previously treated tuberculosis (TB) cases in Iran during 2013-2020 were as follows: isoniazid 6.9%, rifampin 7.9%, ethambutol 5.7%, pyrazinamide 20.4%, para-aminosalicylic acid 4.6%, capreomycin 1.7%, cycloserine 1.8%, ethionamide 11.3%, ofloxacin 1.5%, kanamycin 3.8%, amikacin 2.2%, MDR-TB 6.3% and XDR-TB 0.9%. Based on the presented data, M. tuberculosis resistance to first- and second-line anti-TB drugs, as well as MDR-TB, was low during 2013-2020 in Iran. Furthermore, there was a declining trend in TB drug resistance from 1999 to 2020. Hence, to maintain the current decreasing trend and to control and eliminate TB infection in Iran, continuous monitoring of resistance patterns is recommended.