Increasing Spectrum in Antimicrobial Resistance of Shigella Isolates in Bangladesh: Resistance to Azithromycin and Ceftriaxone and Decreased Susceptibility to Ciprofloxacin

Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p<0.01) and nalidixic acid (from 19% to 51%, p<0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to ≥3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p<0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] ≥32 μg/mL) and had 10-fold higher MIC90 (0.25 μg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 μg/mL) and nalidixic acid (MIC 128 μg/mL) and low to ceftriaxone (MIC 0.023 μg/mL). Conjugative R-plasmids-encoded extended-spectrum ß-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution

Increasing Spectrum in Antimicrobial Resistance of Shigella Isolates in Bangladesh: Resistance to Azithromycin and Ceftriaxone and Decreased Susceptibility to Ciprofloxacin

Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and com\uadpared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p&lt;0.01) and nalidixic acid (from 19% to 51%, p&lt;0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/ce\uadfixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to 653 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p&lt;0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] 6532 \u3bcg/mL) and had 10-fold higher MIC90 (0.25 \u3bcg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 \u3bcg/mL) and nalidixic acid (MIC 128 \u3bcg/mL) and low to ceftriaxone (MIC 0.023 \u3bcg/mL). Conjugative R-plasmids-encoded extended-spectrum \u3b2-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution

ニューモリシン ワ ハイエン キュウキン カンセン ニ オケル インターロイキン 1アルファ オヨビ カスパーゼ 1 イソンテキ サイトカイン ノ サンセイ オウトウ ニ ジュウヨウナ ヤクワリ オ ハタス : カスパーゼ 1 カッセイカ ニ オケル ニューモリシン シンキ キノウ ノ ドウテイ

京都大学0048新制・課程博士博士(医学)甲第13713号医博第3228号新制||医||967(附属図書館)UT51-2008-C630京都大学大学院医学研究科病理系専攻(主査)教授 長田 重一, 教授 西渕 光昭, 教授 一山 智学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Critical Involvement of Pneumolysin in Production of Interleukin-1α and Caspase-1-Dependent Cytokines in Infection with Streptococcus pneumoniae In Vitro: a Novel Function of Pneumolysin in Caspase-1 Activation▿

Pneumolysin is a pore-forming cytolysin known as a major virulence determinant of Streptococcus pneumoniae. This protein toxin has also been shown to activate the Toll-like receptor 4 (TLR4) signaling pathway. In this study, a mutant S. pneumoniae strain deficient in pneumolysin (Δply) and a recombinant pneumolysin protein (rPLY) were constructed. Upon infection of macrophages in vitro, the ability to induce the production of interleukin-1α (IL-1α), IL-1β, and IL-18 was severely impaired in the Δply mutant, whereas there was no marked difference in the induction of tumor necrosis factor alpha (TNF-α) and IL-12p40 between the wild type and the Δply mutant of S. pneumoniae. When macrophages were stimulated with rPLY, the production of IL-1α, IL-1β, and IL-18 was strongly induced in a TLR4-dependent manner, whereas lipopolysaccharide, a canonical TLR4 agonist, hardly induced these cytokines. In contrast, lipopolysaccharide was more potent than rPLY in inducing the production of TNF-α, IL-6, and IL-12p40, the cytokines requiring no caspase activation. Activation of caspase-1 was observed in macrophages stimulated with rPLY but not in those stimulated with lipopolysaccharide, and the level of activation was higher in macrophages infected with wild-type S. pneumoniae than in those infected with the Δply mutant. These results clearly indicate that pneumolysin plays a key role in the host response to S. pneumoniae, particularly in the induction of caspase-1-dependent cytokines

Extended-spectrum β-lactamase-mediated third-generation cephalosporin resistance in Shigella isolates in Bangladesh

This article does not have an abstract

<i>In vivo</i> cure of pEl1573-colonized mice.

<p><i>In vivo</i> cure of pEl1573-colonized mice.</p

Plasmid interference for curing antibiotic resistance plasmids <i>in vivo</i>

<div><p>Antibiotic resistance increases the likelihood of death from infection by common pathogens such as <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> in developed and developing countries alike. Most important modern antibiotic resistance genes spread between such species on self-transmissible (conjugative) plasmids. These plasmids are traditionally grouped on the basis of replicon incompatibility (Inc), which prevents coexistence of related plasmids in the same cell. These plasmids also use post-segregational killing (‘addiction’) systems, which poison any bacterial cells that lose the addictive plasmid, to guarantee their own survival. This study demonstrates that plasmid incompatibilities and addiction systems can be exploited to achieve the safe and complete eradication of antibiotic resistance from bacteria <i>in vitro</i> and in the mouse gut. Conjugative ‘interference plasmids’ were constructed by specifically deleting toxin and antibiotic resistance genes from target plasmids. These interference plasmids efficiently cured the corresponding antibiotic resistant target plasmid from different <i>Enterobacteriaceae in vitro</i> and restored antibiotic susceptibility <i>in vivo</i> to all bacterial populations into which plasmid-mediated resistance had spread. This approach might allow eradication of emergent or established populations of resistance plasmids in individuals at risk of severe sepsis, enabling subsequent use of less toxic and/or more effective antibiotics than would otherwise be possible, if sepsis develops. The generalisability of this approach and its potential applications in bioremediation of animal and environmental microbiomes should now be systematically explored.</p></div