Infected foot ulcers in male and female diabetic patients: a clinico-bioinformative study
<p>Abstract</p> <p>Background</p> <p>The study aimed at (i) characterizing the mode of transmission of <it>bla</it><sub>CTX-M </sub>and <it>bla</it><sub>TEM-1 </sub>among extended-spectrum-β-lactamase (ESBL)-producing <...
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| Format: | Book |
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BMC,
2010-01-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Background</p> <p>The study aimed at (i) characterizing the mode of transmission of <it>bla</it><sub>CTX-M </sub>and <it>bla</it><sub>TEM-1 </sub>among extended-spectrum-β-lactamase (ESBL)-producing <it>Escherichia coli </it>strains isolated from infected diabetic foot ulcers, and (ii) identifying the risk factors for "sex-associated multidrug resistant Gram-negative bacterial (MDRGNB)-infection status" of the ulcers.</p> <p>Methods</p> <p>Seventy-seven diabetic patients having clinically infected foot ulcers were studied in a consecutive series. The <it>E. coli </it>strains isolated from the ulcers were screened for <it>bla</it><sub>CTX-M</sub>, <it>bla</it><sub>TEM-1</sub>, <it>armA</it>, <it>rmtA </it>and <it>rmtB </it>during the 2-year study-period. PCR amplified <it>bla</it><sub>CTX-M </sub>genes were cloned and sequenced. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was used for the analysis of genetic relatedness of the ESBL-producers. Risk factors for "sex-associated MDRGNB-infection status" of ulcers were assessed. Modeling was performed using Swiss-Model-Server and verified by Procheck and verify3D programmes. Discovery Studio2.0 (Accelrys) was used to prepare Ramachandran plots. Z-scores were calculated using 'WHAT IF'-package. Docking of cefotaxime with modeled CTX-M-15 enzyme was performed using Hex5.1.</p> <p>Results</p> <p>Among 51 <it>E. coli </it>isolates, 14 (27.5%) ESBL-producers were identified. Only 7 Class1 integrons, 2 <it>bla</it><sub>CTX-M-15</sub>, and 1 <it>bla</it><sub>TEM-1 </sub>were detected. Ceftazidime and cefotaxime resistance markers were present on the plasmidic DNA of both the <it>bla</it><sub>CTX-M-15 </sub>positive strains and were transmissible through conjugation. The residues Asn132, Glu166, Pro167, Val172, Lys234 and Thr235 of CTX-M-15 were found to make important contacts with cefotaxime in the docked-complex. Multivariate analysis proved 'Glycemic control at discharge' as the single independent risk factor.</p> <p>Conclusions</p> <p>Male diabetic patients with MDRGNB-infected foot ulcers have poor glycemic control and hence they might have higher mortality rates compared to their female counterparts. Plasmid-mediated conjugal transfer, albeit at a low frequency might be the possible mechanism of transfer of <it>bla</it><sub>CTX-M-15 </sub>resistance marker in the present setting. Since the docking results proved that the amino acid residues Asn132, Glu166, Pro167, Val172, Lys234 and Thr235 of CTX-M-15 (enzyme) make important contacts with cefotaxime (drug) in the 'enzyme-drug complex', researchers are expected to duly utilize this information for designing more potent and versatile CTX-M-inhibitors.</p> |
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| Item Description: | 10.1186/1476-0711-9-2 1476-0711 |