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1.
Heliyon ; 10(4): e26193, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404880

RESUMO

Despite the widespread use of the Bacillus Calmette-Guérin (BCG) vaccine, Mycobacterium tuberculosis (MTB) continues to be a global burden. Vaccination has been proposed to prevent and treat tuberculosis (TB) infection, and several of them are in different phases of clinical trials. Though vaccine production is in progress but requires more attention. There are several TB vaccines in the trial phase, most of which are based on a combination of proteins/adjuvants or recombinant viral vectors used for selected MTB antigens. In this review, we attempted to discuss different types of TB vaccines based on the vaccine composition, the immune responses generated, and their clinical trial phases. Furthermore, we have briefly overviewed the effective delivery systems used for the TB vaccine and their effectiveness in different vaccines.

2.
Curr Microbiol ; 80(12): 382, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37864769

RESUMO

Urinary tract infection is the most common infection in almost half of the renal transplant patients. The development of UTI in these patients may progress to bacteremia, acute T cell-mediated rejection, impaired allograft function, or allograft loss, along with the increased risk of hospitalization and death. Among various pathogens implicated, Uropathogenic E. coli (UPEC), especially sequence type 131 (ST131), is the most virulent and multidrug-resistant pathogen. High antimicrobial resistance to most ß-lactam antibiotics, mediated by extended spectrum ß-lactamases (ESBLs) produced by UPEC, is a challenge in the clinical management of UTIs in kidney transplant recipients. Indeed, multidrug resistance to ß-lactam antibiotics is a direct consequence of ESBL production. Resistance to other antibiotics such as aminoglycosides, fluoroquinolones, and trimethoprim-sulphamethoxazole has also been reported in ESBLs-producing UPEC, which reduces the therapeutic options, rising healthcare-associated costs and subsequently leads to renal failure or even graft loss. In this review, we aimed to discuss the post-transplant risk factors of UTI, UPEC virulence factors (VF), and the related factors including quorum sensing, and stress resistance genes. Furthermore, we searched for the current treatment strategies and some of the alternate approaches proposed as therapeutic options that may affirm the treatment of ESBL-producing UPEC.


Assuntos
Infecções por Escherichia coli , Transplante de Rim , Infecções Urinárias , Escherichia coli Uropatogênica , Humanos , Escherichia coli Uropatogênica/genética , Infecções por Escherichia coli/tratamento farmacológico , beta-Lactamases/genética , Transplante de Rim/efeitos adversos , Aptidão , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Urinárias/tratamento farmacológico , beta-Lactamas
3.
Arch Microbiol ; 205(6): 226, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37156886

RESUMO

Uropathogenic Escherichia coli (UPEC) are the strains diverted from the intestinal status and account mainly for uropathogenicity. This pathotype has gained specifications in structure and virulence to turn into a competent uropathogenic organism. Biofilm formation and antibiotic resistance play an important role in the organism's persistence in the urinary tract. Increased consumption of carbapenem prescribed for multidrug-resistant (MDR) and Extended-spectrum-beta lactamase (ESBL)-producing UPECs, has added to the expansion of resistance. The World Health Organization (WHO) and Centre for Disease Control (CDC) placed the Carbapenem-resistant Enterobacteriaceae (CRE) on their treatment priority lists. Understanding both patterns of pathogenicity, and multiple drug resistance may provide guidance for the rational use of anti-bacterial agents in the clinic. Developing an effective vaccine, adherence-inhibiting compounds, cranberry juice, and probiotics are non-antibiotical approaches proposed for the treatment of drug-resistant UTIs. We aimed to review the distinguishing characteristics, current therapeutic options and promising non-antibiotical approaches against ESBL-producing and CRE UPECs.


Assuntos
Infecções por Escherichia coli , Infecções Urinárias , Escherichia coli Uropatogênica , Humanos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , beta-Lactamases
4.
Can J Infect Dis Med Microbiol ; 2022: 6086979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452942

RESUMO

Carbapenemase-resistant Klebsiella pneumoniae (CRKP) is a genuine burden for physicians and researchers. We aimed at carbapenemase resistance and its relation with capsular serotyping in K. pneumoniae and studied some clinical determinants, which may influence the clinical infections. Initially, 61 K. pneumoniae isolates obtained from various clinical specimens were confirmed at the molecular level and then antimicrobial susceptibility test was performed followed by capsular serotyping performed by multiplex PCR. All isolates were subjected to the detection of carbapenemase genes including bla KPC, bla NDM-1, bla OXA-48, bla VIM, and bla IMP. Clinical and demographic data of all patients were reviewed including age, gender, underlying diseases, and the treatment obtained. Multidrug-resistance was a predominant feature in 77% K. pneumoniae strains. Presence of extended-spectrum beta-lactamase was detected phenotypically in 59% K. pneumoniae strains. Carbapenem resistance was noticed phenotypically in 24.6% isolates. bla OXA-48 and bla NDM-1 were the most frequent carbapenemase genes. bla NDM-1 positive isolates correlated with gentamicin, amikacin, imipenem, and meropenem resistance (p < 0.05). The nosocomial isolates mostly harbored bla OXA-48 gene (p < 0.02). Amongst all the K. pneumoniae isolates, 59% isolates could be typed and serotype K54 had the highest prevalence followed by K20 and K5. Correlation between the carbapenemase genes, serotype and type of infection showed that bla OXA-48 positive strains had a significant association with K20 serotype and urinary tract infections (p=0.2) while, K20 serotype and bla KPC positive strains were significantly associated with wound infections (K20, p=0.3 and bla KPC, and p=0.4). Mucoid phenotype was not found related to presence of specific carbapenemase genes or serotypes except serotype K20 (p < 0.001). Patients with monotherapy had treatment failure in comparison to the combination therapy for bla KPC-associated infections. In conclusion, the present investigation exhibited the significant association between K20 serotype with bla OXA-48. The predominance of K54 reveals the possibility of endemicity in our hospital setting. K. pneumoniae isolated from wound specimens significantly harbors K20 serotype and bla KPC gene. Comprehensive clinical information and the distribution of antibiotic resistance genes, and serotypes may play important roles in the treatment process.

5.
Can J Infect Dis Med Microbiol ; 2022: 9916255, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36345550

RESUMO

Different clones of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are dominating geographically. One of the significant, hypervirulent, CA-MRSA and a significant health concern clones is USA3000, found worldwide regionally with varying frequencies. The clone harbors several mobile genetic elements (MGEs) including, arginine catabolic mobile element (ACME) and copper and mercury resistance genes (COMER), accomplished by horizontal gene transfer from S. epidermidis. Evidence suggests that ACME and COMER have a more prominent role in enhancing biofilm capacity and ultimately persistent infections. This review highlights the comprehensive view on ACME and COMER structure, their distribution, and the mechanism of action along with pathogenetic features of USA3000 encompassing their role in biofilm formation, adhesion, quorum sensing, resistance to antibiotics, chemotaxis, and nutrient uptake. We also provided an insight into the role of ACME and COMER genes in the survival of bacterium. Our results shed light on the emergence of two independent clones possessing ACME (North American) and COMER (South American) elements which later disseminated to other regions. ACME and COMER both are adjacent to staphylococcal cassette chromosome mec type IV (SCCmec IV). The acquisition of mecA, followed by COMER or ACME has been shown as a significant factor in the rise and fall of MRSA strains and their complex ability to adapt to hostile environments. The presence of ACME increases fitness, thereby allowing bacteria to colonize the skin and mucous membrane while COMER contributes to genetic stability by knocking over the copper-mediated killing in macrophages. Evidence suggests that ACME and COMER have a more prominent role in enhancing biofilm capacity and ultimately persistent infections. Interestingly, ACME strains have been shown to possess the ability to counteract skin acidity, thereby allowing increased skin colonization. A profound understanding of MGEs in S. aureus plays an important role in the prevention of epidemic clones.

6.
J Biomater Appl ; 37(1): 40-47, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35430919

RESUMO

This study attempted to explore the immunogenicity of chitosan nanoparticles containing fusion protein (Hspx-PPE44-EsxV; HPE) and resiquimod adjuvant (HPERC) in BALB/c mice. HPE was initially expressed in E. coli BL21 cells. HPE and resiquimod adjuvant were then encapsulated in chitosan nanoparticles (HPERC). One group of mice were subcutaneously vaccinated on days 0, 14, and 28 with HPERC, and the other group was primed with bacilli Calmette-Guérin (BCG) on day 0 and then boosted with HPERC on days 14 and 28. Two weeks after the last injection, IFN-γ, IL-4, and IL-17 in spleen cell culture supernatants, and IgG2a and IgG1 titers in sera were measured. HPERC size was 130.84 ± 12.08 nm (n = 5). Zeta potential of HPERC was 29 ± 4 mv. The highest IFN-γ concentration was detected in BCG-primed mice that were boosted with HPERC. In addition, IL-17 production was significantly increased in all groups compared with that of control, except in those that received nanoparticle (NP), adjuvant (ADJ), NP/ADJ, and fusion protein (Hspx-PPE44-EsxV) (HPE). Comparison of IFN-γ and IL-4 concentration determined that Th1 was activated in BCG-primed and HPERC-boosted group in comparison to the other groups. No significant difference in concentration of IL-4 was observed between groups receiving HPERC and BCG-primed and HPERC-boosted group in comparison to group BCG. Concentrations of IgG2a and IgG1 also increased compared to the control group and the rate of IgG2a was higher compared to IgG1. Chitosan containing HPERC vaccine could induce a high level of specific cytokines in mice. The group of mice which first received BCG and then HPERC as booster vaccine could produce significant amounts of IFN-γ, IL-17, and IgG2a.


Assuntos
Quitosana , Mycobacterium tuberculosis , Nanopartículas , Tuberculose , Adjuvantes Imunológicos , Animais , Antígenos de Bactérias , Vacina BCG , Proteínas de Bactérias , Escherichia coli/genética , Imidazóis , Imunoglobulina G , Interleucina-17 , Interleucina-4 , Camundongos , Tuberculose/prevenção & controle
8.
J Med Microbiol ; 70(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34623232

RESUMO

Alteration in the composition of the gut microbiota can lead to a number of chronic clinical diseases. Akkermansia muciniphila is an anaerobic bacteria constituting 3-5% of the gut microbial community in healthy adults. This bacterium is responsible for degenerating mucin in the gut; its scarcity leads to diverse clinical disorders. In this review, we focus on the role of A. muciniphila in diabetes, obesity and atherosclerosis, as well as the use of this bacterium as a next-generation probiotic. In regard to obesity and diabetes, human and animal trials have shown that A. muciniphila controls the essential regulatory system of glucose and energy metabolism. However, the underlying mechanisms by which A. muciniphila alleviates the complications of obesity, diabetes and atherosclerosis are unclear. At the same time, its abundance suggests improved metabolic disorders, such as metabolic endotoxemia, adiposity insulin resistance and glucose tolerance. The role of A. muciniphila is implicated in declining aortic lesions and atherosclerosis. Well-characterized virulence factors, antigens and cell wall extracts of A. muciniphila may act as effector molecules in these diseases. These molecules may provide novel mechanisms and strategies by which this bacterium could be used as a probiotic for the treatment of obesity, diabetes and atherosclerosis.


Assuntos
Aterosclerose/microbiologia , Diabetes Mellitus/microbiologia , Obesidade/microbiologia , Probióticos , Akkermansia/fisiologia , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Metabolismo Energético , Microbioma Gastrointestinal , Humanos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Probióticos/uso terapêutico
9.
Iran J Microbiol ; 13(3): 282-293, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34540166

RESUMO

BACKGROUND AND OBJECTIVES: Carbapenem treatment for Acinetobacter baumannii infections presently faces threats owing to the production of several types of carbapenemase enzymes, prevalence of which varies among different countries. We explored the current trend of antibiotic resistance in A. baumannii clinical isolates from North West Iran, sought the mechanism of carbapenem resistance and addressed the sequence type groups in carbapenem resistant A. baumannii (CRAB). MATERIALS AND METHODS: A. baumannii (n=112) isolates were recovered from various clinical specimens of patients admitted in internal, surgery, burn, infectious diseases and various ICUs wards. Genetically confirmed A. baumannii isolates were screened for carbapenem resistance by the Kirby-Bauer and E-test and the presence of bla MBL, bla OXA-like, ISAba1 genes by PCR. Sequence groups were identified by multiplex PCR. RESULTS: Multidrug-resistance (MDR) was a characteristic feature of all A. baumannii isolates. Frequency of oxacillinase genes in combination including bla OXA-51-like/bla OXA-23-like, bla OXA-51-like/blaOXA-24/40-likeand bla OXA-51-like/bla OXA-23-like/bla OXA-24/40-like was 82.1%, 36.6% and 25.8% respectively. Blending of oxacillinase and MBL genes was evident in eight bla OXA-23-like positive and 7 bla OXA-24-like positive isolates thereby depicting synchronous etiology of carbapenem resistance. Amongst CRAB isolates, 97.3% contained ISAba1 element and 50.9% belonged to the European clone II. CONCLUSION: Synchronicity among bla OXA-like with bla MBL and ISAba1 gene was a hallmark of this investigation. Though origin or route of transmission was not elucidated in this study but co-existence among OXA and MBL producing genes is a therapeutic concern demanding strict surveillance strategies and control programs to halt the dissemination of these isolates in the hospital setting.

10.
Folia Med (Plovdiv) ; 63(5): 726-737, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-35851208

RESUMO

INTRODUCTION: Acinetobacter baumannii infections are a growing public-health concern. The bacterium's potentiality to acquire resistance to a number of commonly used antibiotics has turned it into a formidable pathogen. AIMS: Molecular characterization of extensive drug resistant (XDR) typing of A. baumannii clinical isolates by polymerase chain reaction. MATERIALS AND METHODS: Thirty XDR A. baumannii were investigated for the presence of genes encoding carbapenemase resistance, biofilm capacity, autoinducer synthase, virulence and surface motility by polymerase chain reaction (PCR). Later, the isolates were typed by plasmid-based replicon (Rep) (PBRT) and trilocus sequence typing. RESULTS: All 30 XDR A. baumannii strains displayed genes related to surface motility, autoinducer synthase, virulence determinant, biofilm related genes except PER, and bap, the frequency of which was 83.3% and 76.6%, respectively. Analysis of rep genes showed highest frequency of rep6 and rep2 genes, with frequency of 75% and 65%, respectively. All XDR A. baumannii strains belonged to SG I (European clone II) group. CONCLUSIONS: Our results show the extraordinary plasticity of XDR A. baumannii and suggest that the strains have gained endemicity in our hospital, which could be a great concern in the near future.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos
11.
J Chemother ; 33(3): 137-155, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33243098

RESUMO

Acinetobacter baumannii, notorious for causing nosocomial infections especially in patients admitted to intensive care unit (ICU) and burn units, is best at displaying resistance to all existing antibiotic classes. Consequences of high potential for antibiotic resistance has resulted in extensive drug or even pan drug resistant A. baumannii. Carbapenems, mainly imipenem and meropenem, the last resort for the treatment of A. baumannii infections have fallen short due to the emergence of carbapenem resistant A. baumannii (CRAB). Though enzymatic degradation by production of class D ß-lactamases (Oxacillinases) and class B ß-lactamases (Metallo ß-lactamases) is the core mechanism of carbapenem resistance in A. baumannii; however over-expression of efflux pumps such as resistance-nodulation cell division (RND) family and variant form of porin proteins such as CarO have been implicated for CRAB inception. Transduction and outer membrane vesicles-mediated transfer play a role in carbapenemase determinants spread. Colistin, considered as the most promising antibacterial agent, nevertheless faces adverse effects flaws. Cefiderocol, eravacycline, new ß-lactam antibiotics, non-ß-lactam-ß-lactamase inhibitors, polymyxin B-derived molecules and bacteriophages are some other new treatment options streamlined.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/fisiologia , beta-Lactamases/farmacologia , Bacteriófagos/metabolismo , Cefalosporinas , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Polimixina B/farmacologia , Tetraciclinas/farmacologia , beta-Lactamas/farmacologia , Cefiderocol
12.
Infect Drug Resist ; 13: 1971-1980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606843

RESUMO

OBJECTIVE: Klebsiella pneumoniae, one of the clinical superbugs, causes diverse infections because of its variable capsular antigens. This study focused on K. pneumoniae and aimed to assess any correlation between capsular serotype, capsule-associated virulence genes, and evaluate its resistance to conventional antibiotics in order to gain insight into any regional differences. MATERIALS AND METHODS: A total of 61 K. pneumoniae collected from various clinical specimens were confirmed genotypically. Clinical and demographic data for all patients were reviewed. All isolates were subjected to antimicrobial susceptibility tests. Capsular serotyping and capsule-associated virulence genes were studied using the molecular method. RESULTS: All typeable isolates were typed into K5, K20, and K54 serotypes, and among them, K54 was observed to be predominant. The most common capsule-associated virulence genes comprised uge (93.4%), ycfM (91.8%), and wabG (88.5%), while wcaG (29.5%) and rmpA (21.3%) were noted at much lower prevalence rates. The gene wcaG was significantly associated with K54 positive isolates (p = 0.001), while rmpA was associated with K20 positive isolates (p = 0.01). CONCLUSION: Serotype K54 had a high frequency in isolates collected from patients with pulmonary diseases, while serotype K20 was associated with burn patients. Carbapenems and levofloxacin were the best therapeutic options for the treatment of infections with serotypes K20 and K54.

13.
Iran J Microbiol ; 12(2): 98-106, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32494343

RESUMO

BACKGROUND AND OBJECTIVES: Trend analysis reveals that Klebsiella pneumoniae has witnessed a steep enhancement in the antibiotic resistance and virulence over the last few decades. The present investigation aimed at a comprehensive approach investigating antibiotic susceptibility including, extended spectrum beta-lactamase (ESBL) and AmpC ß-lactamase (AmpC) resistance and the prevalence of virulence genes among the K. pneumoniae isolates. MATERIALS AND METHODS: Sixty-one K. pneumoniae isolates were obtained from various clinical infections. Antimicrobial susceptibility was performed by disk diffusion method. The Mast® D68C test detected the presence of ESBLs and AmpCs phenotypically, and later presence of ESBL and AmpC genes was observed by polymerase chain reaction (PCR). Multiplex-PCR was performed to investigate various virulence genes. RESULTS: Amongst 61 K. pneumoniae isolates, 59% were observed as ESBL and 14.7% as AmpC producers. All ESBL producers were positive for bla CTX-M-15 , while bla CTX-M-14 was observed in 54.1% isolates. The frequency of AmpC genes was as follows: bla CMY-2 (60.7%) and bla DHA-1 (34.4%). The most frequent virulence genes were those encoding enterobactin and lipopolysaccharide. Presence of mrkD was associated with bla DHA-1 gene, while bla CMY-2 significantly (p≤0.05) correlated with the presence of iutA and rmpA virulence genes. bla DHA-1 positive isolates had urine as a significant source, while bla CMY-2 positive isolates were mainly collected from wound exudates (p≤0.05). CONCLUSION: Our results highlight that ESBL and AmpC production along with a plethora of virulence trait on K. pneumoniae should be adequately considered to assess its pathogenesis and antibiotic resistance.

15.
Microb Drug Resist ; 25(6): 951-958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30817229

RESUMO

Uropathogenic Escherichia coli (UPEC) is a well-known pathogen that has perturbed the medical scenario because of its resistance to diverse therapeutic drugs and its ability to form a biofilm. Different O-serogroups are the prevalent cause of urinary tract infections (UTIs) along with their ability to form a biofilm. The present research aimed to assess antibiotic susceptibility, biofilm formation, and serotyping of UPEC isolates in conjunction with the demographic data. Antibiotic susceptibility was determined using the Kirby-Bauer method and biofilm formation was assessed phenotypically and at the molecular level. Serotyping was performed by multiplex PCR. A significant proportion of the total of 120 UPECs was isolated from women (p < 0.05). Most isolates were resistant to cefotaxime, ceftazidime, and tetracycline, but maintained their sensitivity to imipenem. O25, O15, O8, and O75 were the most commonly detected serogroups. Moreover, O25, O15, and O8 were the highest biofilm-producing serogroups among the UPEC isolates. Serogroups O75 and O21 were significantly associated with diabetic patients and subjects with renal disease, respectively (p < 0.05). Overall, our results show that UTI incidence in women should be a subject of concern. The high prevalence of the O25 serogroup associated with a specific antibiotic profile and a high percentage of biofilm formation suggests a close relation between serogroups and characteristic features of UPEC isolates.


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Sorogrupo , Sorotipagem/métodos , Adulto Jovem
17.
J Infect Chemother ; 23(2): 74-79, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27889248

RESUMO

Therapeutic resistance towards most of the current treatment regime by Acinetobacter baumannii has reduced the prescribing antibiotic pattern and option is being re-shifted towards more toxic agents including aminoglycosides. The present investigation aimed at to study various mechanisms towards aminoglycoside non-susceptibility in clinical isolates of A. baumannii. The bacteria were subjected to genetic basis assessment for the presence of aminoglycoside modifying enzymes (AME), 16S rRNA methylase encoding genes and relative expression of AdeABC and AbeM efflux pumps in relation to their susceptibility to five aminoglycosides. When isolates were subjected to typing by repetitive extragenic palindromic (REP) PCR, isolates could be separated into thirteen definite clones. The majority of isolates (94%) were positive for AME encoding genes. Possession of ant(2')-Ia correlated with non-susceptibility towards gentamicin, amikacin, kanamycin, tobramycin; while, presence of aph(3')-VIa attributed to resistance towards amikacin, kanamycin; possession of aac(3')-Ia allied with non-susceptibility to amikacin, tobramycin and presence of aac(3')IIa correlated with kanamycin non-susceptibility. Presence of armA was detected in 34.4%, 34.2%, 29.2%, 40.3%, and 64.2% of isolates showing non-susceptibility to gentamicin, amikacin, kanamycin, tobramycin and netilmicin, respectively. No isolates were found to carry rmtB or rmtC. Amikacin non-susceptibility in comparison to other aminoglycosides correlated with over production of adeB. Overall, the results represented a definitive correlation between presence of AME encoding genes as well as armA and resistance of A. baumannii towards aminoglycosides. On the other hand, the up-regulation of AdeABC and AbeM systems was found to have only the partial role in development of aminoglycoside resistance.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Aminoglicosídeos/farmacologia , Farmacorresistência Bacteriana/genética , tRNA Metiltransferases/genética , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/isolamento & purificação , Amicacina/farmacologia , Distribuição de Qui-Quadrado , Gentamicinas/farmacologia , Humanos , Irã (Geográfico) , Canamicina/farmacologia , Netilmicina/farmacologia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Tobramicina/farmacologia , tRNA Metiltransferases/isolamento & purificação
18.
Adv Pharm Bull ; 6(3): 367-375, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27766220

RESUMO

Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied. In vitro effect of 5-azacytidine on MCF-7 cell line studied by MTT assay, DAPI staining, Rhodamine B relative uptake, and also Real time RT-PCR was performed for studying difference effect of free and encapsulated drug on expression of RARß2 gene. Results: The formulation F5 with 55.84±0.46 % of entrapment efficiency shows zero order kinetic of drug release and selected for in vitro studies; the cytotoxicity of free drug and encapsulated drug in 48 h of incubation have significant difference. DAPI staining shows morphology of apoptotic nucleus in both free and encapsulated drug, Rhodamine B labeled SLNs show time dependency and accumulation of SLNs in cytoplasm. Real time qRT-PCR doesn't show any significant difference (p>0.05) in expression of RARß2 gene in both cells treated with free or encapsulated drug. Conclusion: The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine.

19.
Microb Drug Resist ; 22(5): 347-53, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26779992

RESUMO

We evaluated aminoglycoside resistance in 87 Acinetobacter baumannii strains isolated from four hospitals located in the North West region of Iran and typed them in sequence groups (SGs) using trilocus sequence-based scheme to compare their clonal relationships with international clones. Resistance toward aminoglycosides was assayed by minimum inhibitory concentration (MIC) and presence of aminoglycoside-modifying enzymes (AMEs), and ArmA-encoding genes were evaluated in different SGs. The majority of isolates belonged to SG1 (39%), SG2 (33.3%), and SG3 (12.6%), whereas the remaining ones were assigned to six novel variants of SGs. MIC determination revealed netilmicin as the most and kanamycin as the least active aminoglycosides against all groups. Among the varied SGs, isolates of SG2 showed more susceptibility toward all tested aminoglycosides. APH(3'')-VIa-encoding gene was predominant in SG1 (47%), SG2 (62%), and SG6-9 (100%). However, AAC(3')-Ia (100%) and ANT(2')-Ia (90.9%) were the dominant AMEs in SG3. There was significant association between harboring of aminoglycoside resistance genes and specific aminoglycosides: gene encoded by APH(3')-VIa was allied to resistance against amikacin and kanamycin, whereas ANT(2')-Ia was related to the resistance toward gentamicin and tobramycin in SG2. In SG1, tobramycin resistance was correlated with harboring of AAC(6')-Ib. Screening of armA demonstrated the presence of this gene in SG1 (58.8%), SG2 (10.3%), as well as SG3 (9%). Our results revealed definite correlation between the phenotypes and genotypes of aminoglycoside resistance in different clonal lineages of A. baumannii.


Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Metiltransferases/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/classificação , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Amicacina/farmacologia , Células Clonais , Expressão Gênica , Frequência do Gene , Genótipo , Gentamicinas/farmacologia , Hospitais , Humanos , Irã (Geográfico)/epidemiologia , Canamicina/farmacologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Netilmicina/farmacologia , Fenótipo , Filogenia , Tobramicina/farmacologia
20.
Adv Pharm Bull ; 5(3): 335-42, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26504755

RESUMO

PURPOSE: The study aimed at assessing any association between quinolone resistance, MDR and ESBL production and their relation with the presence of integrons in Esherichia coli and Klebsiella pneumoniae. METHODS: E.coli and K.pneumoniae isolated from various clinical infections were fully identified and analyzed for being quinolone resistant. These isolates were further tested for ESBL production, multi drug resistance and carriage of integrons. RESULTS: In total, 135 isolates were confirmed as quinolone resistant. K.pneumoniae was observed as potent ESBL producer in comparison to E.coli. Ciprofloxacin resistance in both organisms was related significantly with the presence of integron class 1, co-presence of class 1 and 2 as well as to the presence of ESBL production (p< 0.001). However, nalidixic acid resistance was related significantly (p< 0.01) with only integron class 1 and to the presence of ESBL production. Class 1 and 2 integrons were found in 73.5% of MDR isolates with 13.2% of them possessing both intI1 and intI2 genes. CONCLUSION: Prevalence of quinolone resistance together with ESBL production and MDR in E.coli and K.pneumoniae has contributed to the emergence of antibacterial resistance burden. The higher integron prevalence in our isolates advocates the potentiality of these isolates as a source for dissemination of resistance determinants.

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