Molecular Mechanisms of Drug Resistance and Epidemiology of Multidrug-Resistant Variants of Neisseria gonorrhoeae.

The paper presents various issues related to the increasing drug resistance of Neisseria gonorrhoeae and the occurrence and spread of multidrug-resistant clones. One of the most important is the incidence and evolution of resistance mechanisms of N. gonorrhoeae to beta-lactam antibiotics. Chromosomal resistance to penicillins and oxyimino-cephalosporins and plasmid resistance to penicillins are discussed. Chromosomal resistance is associated with the presence of mutations in the PBP2 protein, containing mosaic variants and nonmosaic amino acid substitutions in the transpeptidase domain, and their correlation with mutations in the mtrR gene and its promoter regions (the MtrCDE membrane pump repressor) and in several other genes, which together determine reduced sensitivity or resistance to ceftriaxone and cefixime. Plasmid resistance to penicillins results from the production of beta-lactamases. There are different types of beta-lactamases as well as penicillinase plasmids. In addition to resistance to beta-lactam antibiotics, the paper covers the mechanisms and occurrence of resistance to macrolides (azithromycin), fluoroquinolones and some other antibiotics. Moreover, the most important epidemiological types of multidrug-resistant N. gonorrhoeae, prevalent in specific years and regions, are discussed. Epidemiological types are defined as sequence types, clonal complexes and genogroups obtained by various typing systems such as NG-STAR, NG-MAST and MLST. New perspectives on the treatment of N. gonorrhoeae infections are also presented, including new drugs active against multidrug-resistant strains.

Molecular Mechanisms of Drug Resistance in Staphylococcus aureus.

This paper discusses the mechanisms of S. aureus drug resistance including: (1) introduction. (2) resistance to beta-lactam antibiotics, with particular emphasis on the mec genes found in the Staphylococcaceae family, the structure and occurrence of SCCmec cassettes, as well as differences in the presence of some virulence genes and its expression in major epidemiological types and clones of HA-MRSA, CA-MRSA, and LA-MRSA strains. Other mechanisms of resistance to beta-lactam antibiotics will also be discussed, such as mutations in the gdpP gene, BORSA or MODSA phenotypes, as well as resistance to ceftobiprole and ceftaroline. (3) Resistance to glycopeptides (VRSA, VISA, hVISA strains, vancomycin tolerance). (4) Resistance to oxazolidinones (mutational and enzymatic resistance to linezolid). (5) Resistance to MLS-B (macrolides, lincosamides, ketolides, and streptogramin B). (6) Aminoglycosides and spectinomicin, including resistance genes, their regulation and localization (plasmids, transposons, class I integrons, SCCmec), and types and spectrum of enzymes that inactivate aminoglycosides. (7). Fluoroquinolones (8) Tetracyclines, including the mechanisms of active protection of the drug target site and active efflux of the drug from the bacterial cell. (9) Mupirocin. (10) Fusidic acid. (11) Daptomycin. (12) Resistance to other antibiotics and chemioterapeutics (e.g., streptogramins A, quinupristin/dalfopristin, chloramphenicol, rifampicin, fosfomycin, trimethoprim) (13) Molecular epidemiology of MRSA.

The impact of lifestyle upon the probability of late bacterial infection after soft-tissue filler augmentation.

Purpose: Little is known about the influence of lifestyle-related factors upon the risk of late bacterial infection (LBI) emerging at the site of soft-tissue filler augmentation. The aim of this study was to analyze the impact of some such factors on the risk of LBI by comparing their respective prevalence between two groups of previously healthy women: a group in which infection occurred at a site of cross-linked hyaluronic acid (HA) augmentation and a second group which did not have such an infection. Patients and methods: The infection group featured 25 women who developed LBI at a site of cross-linked HA augmentation; the control group featured 92 women who did not experience complications during a 24-month period of observation after the same procedure. Data was analyzed statistically using Chi-square tests and logistic regression. Results: The two groups did not differ significantly in terms of age. However, the frequency of antibiotic therapy, household pet ownership, occupation, hormone replacement therapy or contraception use, and attendance at a swimming pool, sauna, or gym attendance were found to vary with statistical significance, P<0.05. Conclusions: Women in the control group practiced a more active lifestyle. Antibiotic therapy in the year preceding cross-linked HA augmentation was a factor which rendered a patient predisposed towards the development of LBI. Pet ownership was more prominent among women who did not suffer LBI than within the group in which soft tissue filler-related complications had occurred.

Treatment of late bacterial infections resulting from soft-tissue filler injections.

PURPOSE: Late bacterial infections (LBIs) after esthetic facial augmentation using hyaluronic acid (HA) fillers are relatively rare yet severe complications that are difficult to treat. No adequate treatment standards have hitherto been formulated. We have bridged this gap by formulating a treatment scheme based on the principles of treating foreign-body implantation-related infections and treating bacterial growth in the form of biofilm. The objective of this study was to evaluate the efficacy of a comprehensive scheme for treating LBI complications after facial augmentation using cross-linked HA fillers. METHODS: A total of 22 patients with LBI symptoms at a site of cross-linked HA injection underwent treatment and observation. The comprehensive treatment scheme formulated by Marusza and Netsvyetayeva (M&N scheme) comprised draining the lesion, dissolution of cross-linked HA with hyaluronidase, broad-spectrum antibiotic combination therapy, and use of probiotics. While 17 patients underwent the M&N scheme, the remaining five were treated with other schemes. Statistical analysis of the data was performed using Mann-Whitney U and χ2 nonparametric tests with SAS 9.4 software. RESULTS: All 17 patients who underwent the M&N scheme experienced resolution of symptoms, with no recurrence of infection at the HA-injection sites. CONCLUSION: To treat LBI at a site of cross-linked HA administration, the principles applicable to infections resulting from implantation of a foreign body must be followed. The treatment period should be sufficiently long for complete resolution of symptoms. The efficacy of treatment is considered proven if 2 months have elapsed without recurrence since the symptoms resolved. The M&N scheme is recommended for use as the first therapeutic option for treating LBI related to soft-tissue fillers.

Skin bacterial flora as a potential risk factor predisposing to late bacterial infection after cross-linked hyaluronic acid gel augmentation.

INTRODUCTION: Cross-linked hyaluronic acid (HA) gel is widely used in esthetic medicine. Late bacterial infection (LBI) is a rare, but severe complication after HA augmentation. The aim of this study was to determine whether patients who underwent the HA injection procedure and developed LBI had qualitatively different bacterial flora on the skin compared to patients who underwent the procedure without any complications. METHODS: The study group comprised 10 previously healthy women with recently diagnosed, untreated LBI after HA augmentation. The control group comprised 17 healthy women who had a similar amount of HA injected with no complications. To assess the difference between the two groups, their skin flora was cultured from nasal swabs, both before and after antibiotic treatment in the study group. RESULTS: A significant increase in the incidence of Staphylococcus epidermidis was detected in the control group (P=0.000) compared to the study group. The study group showed a significantly higher incidence of Staphylococcus aureus (P=0.005), Klebsiella pneumoniae (P=0.006), Klebsiella oxytoca (P=0.048), and Staphylococcus haemolyticus (P=0.048) compared to the control group. CONCLUSION: The bacterial flora on the skin differed in patients with LBI from the control group. The control group's bacterial skin flora was dominated by S. epidermidis. Patients with LBI had a bacterial skin flora dominated by potentially pathogenic bacteria.

Staphylococcus aureus nasal carriage in Ukraine: antibacterial resistance and virulence factor encoding genes.

BACKGROUND: The number of studies regarding the incidence of multidrug resistant strains and distribution of genes encoding virulence factors, which have colonized the post-Soviet states, is considerably limited. The aim of the study was (1) to assess the Staphylococcus (S.) aureus nasal carriage rate, including Methicillin Resistant S. aureus (MRSA) strains in adult Ukrainian population, (2) to determine antibiotic resistant pattern and (3) the occurrence of Panton Valentine Leukocidine (PVL)-, Fibronectin-Binding Protein A (FnBPA)- and Exfoliative Toxin (ET)-encoding genes. METHODS: Nasal samples for S. aureus culture were obtained from 245 adults. The susceptibility pattern for several classes of antibiotics was determined by disk diffusion method according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The virulence factor encoding genes, mecA, lukS-lukF, eta, etb, etd, fnbA, were detected by Polymerase Chain Reaction (PCR). RESULTS: The S. aureus nasal carriage rate was 40%. The prevalence of nasal MRSA carriage in adults was 3.7%. LukS-lukF genes were detected in over 58% of the strains. ET-encoding genes were detected in over 39% of the strains and the most prevalent was etd. The fnbA gene was detected in over 59% of the strains. All MRSA isolates tested were positive for the mecA gene. LukS-lukF genes and the etd gene were commonly co-present in MRSA, while lukS-lukF genes and the fnbA gene were commonly co-present in Methicillin Sensitive S. aureus (MSSA) isolates. No significant difference was detected between the occurrence of lukS-lukF genes (P > 0.05) and the etd gene (P > 0.05) when comparing MRSA and MSSA. The occurrence of the fnbA gene was significantly more frequent in MSSA strains (P < 0.05). CONCLUSIONS: In Ukraine, S. aureus is a common cause of infection. The prevalence of S. aureus nasal carriage in our cohort of patients from Ukraine was 40.4%. We found that 9.1% of the strains were classified as MRSA and all MRSA isolates tested positive for the mecA gene. We also observed a high prevalence of PVL- and ET- encoding genes among S. aureus nasal carriage strains. A systematic surveillance system can help prevent transmission and spread of drug resistant toxin producing S. aureus strains.

Probable biofilm formation in the cheek as a complication of soft tissue filler resulting from improper endodontic treatment of tooth 16.

Injectable filling agents offer the promise of a better appearance without surgery and, among them, hyaluronic acid is the most commonly used. Although complications are rare, it is necessary to know the possible side effects and complications in order to be prepared for their management. That is why many researchers have been focusing on the interactions between hyaluronic acid and pathogens, inflammatory mediators, the immune system, and markers of oxidative stress to achieve efficient drug delivery, given that hyaluronic acid has widening applications in the field of nanomedicine. Here we report the case of a 37-year-old female patient who returned to our clinic with an abscess in her left cheek 3 months after a deep injection of 1 mL of stabilized hyaluronic acid in both cheeks. Steroid and antibiotic therapy was initiated without success, and abscess drainage was performed. Extraction of tooth 16 was performed 11 days after insertion of drains into the abscess. Laboratory blood tests showed acute inflammation of presumed bacterial etiology. Microbiological examination of pus was negative. Bacterial cultures were found in the extracted tooth. After antibiotic therapy, a complete reversal of the pathological process was observed. The present report highlights the need to assess periodontal problems prior to any aesthetic facial treatment. Analyses of further case reports and clinical studies are necessary to understand the potential role of hyaluronic acid in the formation of biofilm, and how to avoid this complication, thereby increasing the safety of hyaluronic acid-based procedures.