Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins.

Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum ß-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S Typhi observed here adds urgency to the need for typhoid prevention measures.

Silicon tube frontalis suspension in simple congenital blepharoptosis.

BACKGROUND: Ptosis is an abnormally low position of the upper eyelid. Congenital ptosis should be corrected in early years of childhood. The aim of this study was to assess the efficacy and complications of frontalis suspension using silicon tube for simple congenital blepharoptosis with poor levator function. METHODS: A prospective study was performed on 33 children who underwent frontalis suspension using silicon tube from Jan 2008 to Jun 2011 with a minimum of 6 month follow-up. Functional success was defined when 3 criteria were met: (a) satisfactory lid height defined as margin-to-reflex distance > or = 3.5 mm with minimal frontalis action (brow up); (b) satisfactory lid symmetry (< or = 2 mm asymmetry in margin-to-reflex distance) between two lids; and (c) satisfactory cosmesis, i.e., normal lid contours. RESULTS: The mean follow-up duration was 9 months (range 6.5-27 months). The functional success rate was 91.4% (32/35 eyes). Three eyes had complications. In one eye (2.8%), recurrence of ptosis due to slippage of knot was seen, one eye developed infection of tract, and one with bilateral ptosis developed abnormal tenting of one of the lid. CONCLUSION: In simple congenital ptosis with poor levator function, frontalis suspension using silicon tube has good efficacy and an excellent safety profile. The results of frontalis suspension using silicon tube are comparable to fascia lata and superior to other non-autogenous materials.