Molecular basis of the efficacy of cefaclor against Haemophilus influenzae

M Picard1, F Malouin

  • 1Département de Microbiologie and Laboratorie, Centre Hospitalier de l'Université Laval, Québec, Canada.

Insights

Cefaclor effectively inhibits beta-lactamase-producing Haemophilus influenzae. Its superior resistance to beta-lactamase enzymes allows for higher concentrations in the periplasmic space, enhancing its antibacterial activity.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Beta-lactamase-producing bacteria, such as Haemophilus influenzae, pose a significant challenge in treating infections.
  • Understanding the mechanisms of antibiotic efficacy against resistant strains is crucial for effective treatment strategies.

Purpose of the Study:

  • To investigate the inhibitory activity and mechanism of cefaclor against a beta-lactamase-producing strain of Haemophilus influenzae.
  • To compare the efficacy of cefaclor with ampicillin in this resistant bacterial strain.

Main Methods:

  • Assessing the inhibitory activity of cefaclor against Haemophilus influenzae.
  • Calculating permeability coefficients for cefaclor and ampicillin.
  • Measuring periplasmic concentrations of both antibiotics.

Main Results:

  • Cefaclor demonstrated sustained inhibitory activity against the beta-lactamase-producing Haemophilus influenzae.
  • Despite ampicillin having a higher calculated permeability coefficient, cefaclor achieved a 5.7-fold higher periplasmic concentration.
  • Cefaclor exhibited greater resistance to beta-lactamase activity.

Conclusions:

  • Cefaclor's enhanced efficacy against beta-lactamase-producing Haemophilus influenzae is attributed to its superior beta-lactamase resistance.
  • Higher periplasmic concentrations of cefaclor facilitate adequate binding to essential penicillin-binding proteins, leading to effective bacterial inhibition.

Related Concept Videos

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence01:22

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Influenza01:27

Influenza

Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...