Lyme disease: modern approaches to treatment and prevention (based on international recommendations of 2020)

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily in the United States and Europe. Given the great social and medical importance of this problem, an updated version of the clinical guidelines for the prevention, diagnosis and treatment of PD was published in November 2020 by a committee of experts of the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN) and the American College of Rheumatology (ACR). This article discusses the main issues of the use of antibacterial drugs in LD. The most commonly used medications are doxycycline, amoxicillin, cefuroxime axetil, and ceftriaxone. Patients with erythema migrans receive appropriate antibiotics for 7–14 days, depending on the medication used. In case of other clinical manifestations of LD, the duration of treatment is extended to 14–28 days. Antibiotic prophylaxis is carried out using a single oral dose of 200 mg doxycycline for adults and 4.4 mg/kg (with a maximum of 200 mg) for children. This treatment scheme is highly efficient, easy to administer, and has a relatively low risk of adverse events.

Lyme disease: Modern approaches to prevention, diagnosis and treatment

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily the United States and Europe. In endemic areas, early LD is a common disease that requires high medical vigilance. Considering the extreme relevance of this problem for public health, in November 2020, the committee of experts of three American scientific societies published an updated version of the clinical guidelines for the prevention, diagnosis and treatment of LD, the main provisions of which are presented in this article. It is emphasized that in the absence of vaccines, the risk of LD and other diseases transmitted by ticks can be reduced by using personal protective equipment and repellents. Antibiotic prophylaxis is carried out by a single oral administration of doxycycline. In the laboratory diagnosis of LD, the determination of antibodies to B. burgdorfery in the blood serum is a first-line study. At the second stage, serum samples are examined using an immunoblot for IgM and IgG. The basis of treatment of LD is rational antibiotic therapy. The choice of an antibiotic depends on a number of factors, including the presence of extracutaneous manifestations of LD (neuroborreliosis, carditis, arthritis). The most commonly used are doxycycline, amoxicillin, cefuroxime-axetil and ceftriaxone.

Antibiotic resistance in predominantly occurring gram-negative bacterial community from treated sewage Jaipur to assess the need for going beyond coliform standards

Antibiotic resistance surveillance is an objective of global action plan on antimicrobial resistance endorsed by the World Health Organization. The current study reports the identification of frequently occurring Gram-negative bacterial community (GNBC) previously isolated from municipal treated wastewater and their antibiotic resistance profiles. Further, the genes responsible for extended-spectrum beta lactamases (ESBL) activity were identified in ESBL-positive organisms. The isolates were characterized using biochemical assays and identification was confirmed by VITEK®2 automated system. Antibiotic susceptibility testing against seven different classes of antibiotics was also performed on the same system using AST-N280 cards. The most dominant isolates identified were Acinetobacter baumannii, Morganella morganii, Kluyvera intermedia, Stenotrophomonas maltophilia, Escherichia coli, Aeromonas hydrophila/caviae, Klebsiella pneumoniae, Enterobacter cloacae and Citrobacter freundii. The isolates were observed to be significantly resistant against the antibiotics amoxicillin-clavulanic acid, cefuroxime, cefuroxime axetil and colistin. Two of the isolates, E. cloacae sp. dissolvens and S. maltophilia, were found to be positive for ESBL activity encoded by blaCTX-M gene. The possible intrusion of hospital wastewater in domestic sewage is also discussed. This study may help assess the risk of wastewater reuse by detecting dominant bacteria as a step towards the development of new microbiological standards.

Enzyme Models—From Catalysis to Prodrugs

Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.

The effect of generic market entry on antibiotic prescriptions in the United States

When patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)—aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin—and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed.

Molecular Structure of Cefuroxime Axetil Complexes with α-, β-, γ-, and 2-Hydroxypropyl-β-Cyclodextrins: Molecular Simulations and Raman Spectroscopic and Imaging Studies

The formation of cefuroxime axetil+cyclodextrin (CA+CD) complexes increases the aqueous solubility of CA, improves its physico-chemical properties, and facilitates a biomembrane-mediated drug delivery process. In CD-based tablet formulations, it is crucial to investigate the molecular details of complexes in final pharmaceutical preparation. In this study, Raman spectroscopy and mapping were applied for the detection and identification of chemical groups involved in α-, β-, γ-, and 2-hydroxypropyl-β-CD (2-HP- β-CD)+CA complexation process. The experimental studies have been complemented by molecular dynamics-based investigations, providing additional molecular details of CA+CD interactions. It has been demonstrated that CA forms the guest–host type inclusion complexes with all studied CDs; however, the nature of the interactions is slightly different. It seems that both α- and β-CD interact with furanyl and methoxy moieties of CA, γ-CD forms a more diverse pattern of interactions with CA, which are not observed in other CDs, whereas 2HP-β-CD binds CA with the contribution of hydrogen bonding. Apart from supporting this interpretation of the experimental data, molecular dynamics simulations allowed for ordering the CA+CD binding affinities. The obtained results proved that the molecular details of the host–guest complexation can be successfully predicted from the combination of Raman spectroscopy and molecular modeling.