cefotaxime and Diabetic-Foot

The aims of this study were: (i) To investigate the activity of recombinant AMPs HNP-1 and hBD-1 in combination with cefotaxime against Staphylococcus aureus strains (MSSA and MRSA) in vitro using checkerboard method; (ii) To investigate the activity of HNP-1 and hBD-1 encapsulated in silicon nanoparticles (niosomes) in the treatment of MRSA-infected wound in rats. For this S. aureus strains (MSSA and MRSA) were isolated from patients with diabetic foot infection. Cefotaxime, recombinant HNP-1 and hBD-1 (in all possible combinations with each other) were used for testing by the checkerboard method. Two niosomal topical gels with HNP-1/hBD-1 were prepared to treat MRSA-infected wounds in rats. Gels were administered once a day, the control group-without treatment. Wound healing rate was calculated on the 4th, 9th and 16th days of the experiment and compared using one-way ANOVA with Bonferroni correction. MIC of HNP-1 for MSSA and MRSA was the same-1 mg/L. MIC of hBD-1 for MSSA and MRSA was also the same-0.5 mg/L. Topical gels with niosomal HNP-1 (or hBD-1) showed a significantly faster wound healing in comparison with the control. The data obtained open up prospects for use of AMPs encapsulated in silica nanoparticles for the development of new antibiotics.

Topics: Administration, Topical; alpha-Defensins; Animals; Anti-Bacterial Agents; beta-Defensins; Cefotaxime; Diabetic Foot; Drug Therapy, Combination; Gels; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Nanoparticles; Rats; Rats, Wistar; Silicon Dioxide; Staphylococcal Infections; Staphylococcus aureus; Wound Healing

The study aimed at (i) characterizing the mode of transmission of bla(CTX-M) and bla(TEM-1) among extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli 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.. Seventy-seven diabetic patients having clinically infected foot ulcers were studied in a consecutive series. The E. coli strains isolated from the ulcers were screened for bla(CTX-M), bla(TEM-1), armA, rmtA and rmtB during the 2-year study-period. PCR amplified bla(CTX-M) 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.. Among 51 E. coli isolates, 14 (27.5%) ESBL-producers were identified. Only 7 Class1 integrons, 2 bla(CTX-M-15), and 1 bla(TEM-1) were detected. Ceftazidime and cefotaxime resistance markers were present on the plasmidic DNA of both the bla(CTX-M-15) 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.. 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 bla(CTX-M-15) 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.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Blood Glucose; Cefotaxime; Ceftazidime; Conjugation, Genetic; Diabetic Foot; Escherichia coli; Escherichia coli Infections; Female; Humans; India; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Risk Factors