Modern approaches to antibacterial therapy in purulent and necrotic complications of diabetes

Abstract

Background. The incidence of purulent and necrotic complications (PNC) in patients with diabetes mellitus (DM) is 3 times higher than in people without diabetes, and the duration of treatment is 2 times longer. The reasons for this include loss of sensitivity, which increases the risk of injury; autonomic neuropathy with the formation of skin cracks, which increase the likelihood of infection; motor neuropathy with the development of keratoses and deformities; disorders of the circulation (in both main arteries and in microcirculation).
 Objective. To describe modern approaches to antibacterial therapy (ABT) in PNC of DM.
 Materials and methods. Analysis of literature data on this topic; own research. The study involved 149 patients with diabetic foot who underwent 198 surgeries. 75 patients were admitted with diabetes decompensation. Main group patients (n=45) were prescribed a balanced infusion (Gekodez, Xylate, Gluxyl) and ABT (Leflocin 750, Linelid, Brakson (all medication produced by “Yuria-Pharm”) according to the indications), and the control group patients (n=30) ere prescribed standard infusion therapy and ABT.
 Results and discussion. In diabetes, purulent infection leads to decompensation of carbohydrate metabolism, and the latter, in turn, worsens the course of purulent infections. 1 ml of pus inactivates 12-15 U of insulin (endogenous or exogenous). The main types of PNC in patients with diabetes include purulent and inflammatory diseases of the skin and adipose tissue, mastitis, parotitis, arthritis, pleurisy, peritonitis, paraproctitis, diabetic foot syndrome (DFS). DFS is a specific symptom complex of foot lesions in diabetes. Its pathogenesis is based on the diabetic micro- and macroangiopathy, peripheral neuropathy of the lower extremities, and osteoarthropathy. There are 3 clinical forms of DFS: neuropathic and infected, ischemic and gangrenous, and mixed. Each hour 55 amputations of the lower extremities are performed globally due to DFS. The main treatment for patients with stage III-V DFS is surgery, which should be supplemented with ABT. The initial empirical ABT should affect the full range of potential pathogens. A combination of several antibiotics with a synergistic effect is used; correction is performed in 72 hours after receiving the results of microbiological examination. For infections that do not threaten limb amputation, fluoroquinolones, lincosamides, cephalosporins of the first generation are prescribed. In case of infections that threaten limb amputation, it is advisable to prescribe fluoroquinolones in combination with lincosamides, ampicillin/sulbactam, cephalosporins of the second generation; with the addition of metronidazole. For life-threatening infections, tienams, vancomycin + aztreonam + metronidazole, clindamycin + ampicillin/sulbactam are prescribed. In addition to the antibacterial power of the drug, its ability to penetrate into the infection focus has a great impact. It was shown that when 750 mg of levofloxacin was administered 120-150 min before necrectomy, its concentration along the cut-off line exceeded the minimum inhibitory concentration for 90 % of bacteria. The advantages of fluoroquinolones also include a high degree of bactericidal activity, a wide range of antimicrobial action, and a long half-life. After fluoroquinolones intake, a kind of “sugar crisis” can occur with changes in blood glucose levels. Its mechanism is still unclear. 80 % of all cases of impaired glucose homeostasis on the background of fluoroquinolones occur with the use of gatifloxacin. Leflocin (“Yuria-Pharm”) is a third-generation fluoroquinolone that has the least effect on carbohydrate metabolism among all drugs in its class. At a dose of 750 mg Leflocin can be used once a day. Staphylococcus aureus is the leading pathogen in DFS. The prevalence of its methicillin-resistant strains is increasing and currently is about 15-30 %. Linezolid (Linelid, “Yuria-Pharm”) – a synthetic antibiotic used to treat severe infectious processes caused by gram-positive bacteria resistant to other AB – is the drug of choice in case of detection of such strains. Linezolid provides effective concentrations in the inflammatory focus in DFS. If the DFS infection is caused by gram-negative bacteria, it is advisable to prescribe tobramycin (Brakson, “Yuria-Pharm”) – a natural aminoglycoside of the third generation for parenteral and local treatment. According to the results of our own study, combined infusion therapy and ABT was accompanied by significantly fewer cases of loss of consciousness than standard treatment (4.2 % vs. 10.8 %; p=0.025), acute renal failure (4.72 % vs. 10 %; p=0.031), the average score of pain on a visual-analog scale (3.12 vs. 4.25 points; p=0.042), the duration of inpatient treatment after surgery (25.8 vs. 36.1 days; p=0.029).
 Conclusions. 1. Modern ABT in patients with DM and PNC should be comprehensive and affect the main links in the pathogenesis. 2. The choice of antibiotic should be made taking into account the degree of penetration of the drug into the focus of the pathological process and the sensitivity of microorganisms. 3. In case of PNC of DFS it is reasonable to use Leflocin (gram-positive flora), Linelid (methicillin-resistant staphylococcus), Brakson (gram-negative flora).