Resistance In Respiratory Infections Research Articles

Based on molecular docking and real-time PCR technology, the two-component system Bae SR was investigated on the mechanism of drug resistance in CRAB.

This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain reaction (PCR). The two-component system Bae SR of Acinetobacter baumannii was subjected to molecular docking with imipenem, meropenem, and levofloxacin. Antibacterial assays and fluorescence quantitative PCR were used to explore protein-ligand interactions and molecular biological resistance mechanisms related to CRAB. The analysis of the two-component system in A. baumannii revealed that imipenem exhibited the highest docking energy in Bae S at - 5.81kcal/mol, while the docking energy for meropenem was - 4.92kcal/mol. For Bae R, imipenem had a maximum docking energy of - 4.28kcal/mol, compared with - 4.60kcal/mol for meropenem. The highest binding energies for Bae S-levofloxacin and Bae R-levofloxacin were - 3.60 and - 3.65kcal/mol, respectively. All imipenem-resistant strains had minimum inhibitory concentration (MIC) values of 16µg/mL, whereas levofloxacin-resistant strains had MIC values of 8µg/mL. The time-sterilization curve showed a significant decrease in bacterial colony numbers at 2h under the action of 8µg/mL imipenem, indicating antibacterial effects. In contrast, levofloxacin did not exhibit any antibacterial activity. Fluorescence quantitative PCR results revealed significantly increased relative expression levels of bae S and bae R genes in the CRAB group, which were 2 and 1.5 times higher than those in the CSAB group, respectively, with statistically significant differences. Molecular docking in this study found that the combination of Bae SR and carbapenem antibiotics (imipenem, meropenem) exhibited stronger affinity and stability compared with levofloxacin. Moreover, the overexpression of the two-component system genes in carbapenem-resistant A. baumannii enhanced its resistance to carbapenem, providing theoretical and practical insights into carbapenem resistance in respiratory tract infections caused by A. baumannii.

Non-Digestible Oligosaccharides: A Novel Treatment for Respiratory Infections?

Emerging antimicrobial resistance in respiratory infections requires novel intervention strategies. Non-digestible oligosaccharides (NDOs) are a diverse group of carbohydrates with broad protective effects. In addition to promoting the colonization of beneficial gut microbiota and maintaining the intestinal homeostasis, NDOs act as decoy receptors, effectively blocking the attachment of pathogens on host cells. NDOs also function as a bacteriostatic agent, inhibiting the growth of specific pathogenic bacteria. Based on this fact, NDOs potentiate the actions of antimicrobial drugs. Therefore, there is an increasing interest in characterizing the anti-infective properties of NDOs. This focused review provides insights into the mechanisms by which representative NDOs may suppress respiratory infections by targeting pathogens and host cells. We summarized the most interesting mechanisms of NDOs, including maintenance of gut microbiota homeostasis, interference with TLR-mediated signaling, anti-oxidative effects and bacterial toxin neutralization, bacteriostatic and bactericidal effects, and anti-adhesion or anti-invasive properties. A detailed understanding of anti-infective mechanisms of NDOs against respiratory pathogens may contribute to the development of add-on therapy or alternatives to antimicrobials.

Diphenhydramine and levofloxacin combination therapy against antimicrobial resistance in respiratory tract infections.

Background: Antibiotics are in use since decades to treat various infections caused by Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Diphenhydramine, an H1 receptor blocker possesses a weak antibiotic action but when combined with other antibiotics may potentiate their antibacterial activity. Materials & methods: This study investigated in vitro antibacterial activity of diphenhydramine when used alone and in combination with levofloxacin against methicillin-resistant S. aureusand P. aeruginosa. Results: The combined antibacterial effect of the drugs against bacteria showed a fractional inhibitory concentration index of ≤0.5, in other words, synergism. No cytotoxicity was observed as percentage cell viability was >50%. Conclusion: The combination of diphenhydramine and levofloxacin exerted antibacterial activity, and was not found to be cytotoxic when given in combination against P. aeruginosa and S. aureus.

Etiological Trends and Patterns of Antimicrobial Resistance in Respiratory Infections.

Background:Respiratory infections are one of the commonest causes of morbidity and mortality related to infectious diseases worldwide. The emergence of antimicrobial resistance is a major global health problem which is well established in developing countries. Good clinical suspicion and correct laboratory identification of respiratory infection causing organisms followed by the appropriate management are needed to compact both community-acquired and nosocomial infection respiratory infections.Objectives:A retrospective study was carried out to elucidate the etiology of respiratory infections in Sudan, as well as to guide the physician to the best antimicrobial alternatives used in the treatment of respiratory infection.Method:Respiratory isolates that have been morphologically identified and biologically characterized were subjected to antibiotic susceptibility testing.Results:A total of 1481 respiratory specimens were examined, recovering 377 organisms from 350 culture positive samples [225(59.7%) sputum, 94(24.9%) broncho-alveolar lavage (BAL), 58(15.4%) Pleural fluid], the commonest organisms were Klebsiella ssp. (25.20%) and mycobacterium tuberculosis (25.20%), followed by Staphylococcus aureus(19.89%) and Pseudomonas aeruginosa(8.49%). High rate of resistance of bacterial isolates was observed to Co-trimoxazole (BA), Ampicillin sulbactam (AS), Cefotaxime (CF) and Tetracycline (TE), being 80%, 72.3%, 68.8% and 66.9% respectively; on the other hand, very low resistance rate was found to Amikacin (AK) and Levofloxacin (LE), being 4.6% and 8.5%, respectively.Conclusion:Guided prescription of antimicrobial agents must be implemented and controlled to limit further spread of antimicrobial resistance.

What is new in otitis media?

The “wait and see” approach in acute otitis media (AOM), consisting of postponing the antibiotic administration for a few days, has been advocated mainly to counteract the increased bacterial resistance in respiratory infections. This approach is not justified in children less than 2 years of age and this for several reasons. First, AOM is an acute inflammation of the middle ear caused in about 70% of cases by bacteria. Redness and bulging of the tympanic membrane are characteristic findings in bacterial AOM. Second, AOM is associated with long-term dysfunction of the inflamed eustachian tube (ET), particularly in children less than 2 years of age. In this age group, the small calibre of the ET together with its horizontal direction result in impaired clearance, ventilation and protection of the middle ear. Third, recent prospective studies have shown poor long-term prognosis of AOM in children below 2 years with at least 50% of recurrences and persisting otitis media with effusion (OME) in about 35% 6 months after AOM. Viruses elicit AOM in about 30% of children. A prolonged course of AOM has been observed when bacterial and viral infections are combined because viral infection is also associated with ET dysfunction in young children. Bacterial and viral testing of the nasopharyngeal aspirate is an excellent tool both for initial treatment and recurrence of AOM. Antibiotic treatment of AOM is mandatory in children less than 2 years of age to decrease inflammation in the middle ear but also of the ET particularly during the first episode. The best choice is amoxicillin because of its superior penetration in the middle ear. Streptococci pneumoniae with intermediary bacterial resistance to penicillin are particularly associated with recurrent AOM. Therefore the dosage of amoxicillin should be 90 mg/kg per day in three doses. In recurrent AOM with β-lactamase-producing bacilli, amoxicillin should be associated with clavulanic acid at a dose of 6.4 mg/kg per day. The duration of the treatment is not established yet but 10 days is reasonable for a first episode of AOM. OME may be a precursor initiating AOM but also a complication thereof. OME needs a watchful waiting approach. When associated with deafness for 2–3 months in children over 2 years of age, an antibiotic should be given according to the results of the bacterial resistance in the nasopharyngeal aspirate. The high rate of complications of tympanostomy tube insertion outweighs the beneficial effect on hearing loss. The poor results of this procedure are due to the absence of effects on ET dysfunction. Pneumococcal vaccination has little beneficial effects on recurrent AOM and its use in infants needs further studies. Treatment with amoxicillin is indicated in all children younger than 2 years with a first episode of AOM presenting with redness and bulging of the tympanic membrane. Combined amoxicillin and clavulanic acid should be given in patients with β-lactamase-producing bacteria. The duration of treatment is estimated to be at least 10 days depending on the findings by pneumo-otoscopy and tympanometry. Bacterial and viral testing of the nasopharyngeal aspirate is highly recommended particularly in children in day care centres as well as for regular follow-up. The high recurrence rate is due to the long-lasting dysfunction of the eustachian tube and the immune immaturity of children less than 2 years of age.

Clinical impact of antibiotic resistance in respiratory tract infections

Streptococcus pneumoniae is the most common causative pathogen of community-acquired respiratory tract infections. In vitro evidence indicates that S. pneumoniae is increasingly resistant to commonly prescribed antimicrobial agents including the macrolides. The clinical relevance of resistance, however, has not been clearly established. This article reviews the risk factors influencing selection of resistant pneumococci, discusses endpoints used to assess the impact of resistance on clinical outcome, and proposes strategies to minimise the impact of resistance. Evidence demonstrating treatment failures due to macrolide-resistant S. pneumoniae is also reviewed. Increasing rates of resistance among S. pneumoniae present numerous clinical challenges, and require carefully selected treatment strategies to preserve antibacterial efficacy. Antibiotics with a low propensity for stimulating resistance should be chosen wherever possible.

Quinolones making moves in respiratory tract infections

The new third-generation quinolones may be the solution to the problem of increasing bacterial resistance in respiratory tract infections (RTIs). These agents, which include sparfloxacin, grepafloxacin and levofloxacin, appear to be at least as effective as the most recent macrolides in the treatment of RTIs, according to presentations at the 20th International Congress on Chemotherapy [Sydney, Australia; July 1997].