Cefuroxime is a semi-synthetic antibiotic used to manage and prevent bacterial infections. It belongs to the cephalosporin class, characterized by their ability to kill bacteria through a shared structural feature. The medication is available as an intravenous or intramuscular injection for serious infections, and as an orally active form, cefuroxime axetil, for outpatient treatment. Its broad effectiveness makes it a frequent choice for treating common community-acquired illnesses.
Chemical Classification and Structure
Cefuroxime is classified as a second-generation cephalosporin, distinguished by enhanced activity against Gram-negative bacteria compared to first-generation counterparts. Like all cephalosporins, its molecular core is a four-membered beta-lactam ring fused to a six-membered dihydrothiazine ring. This nucleus is responsible for the drug’s antibacterial function.
The specific chemical modifications attached to this core structure define cefuroxime. A defining feature is the presence of a syn-oxime group at the C-7 position. This side chain modification is instrumental in shielding the nearby beta-lactam ring from enzymatic breakdown. This stability significantly increases the drug’s resistance against many common bacterial beta-lactamase enzymes.
Mechanism of Action
The bactericidal action of cefuroxime disrupts the construction of the bacterial cell wall. The drug acts by mimicking the natural substrate of bacterial enzymes known as Penicillin-Binding Proteins (PBPs). These PBPs are transpeptidases that perform the final step in cell wall synthesis: the cross-linking of peptidoglycan strands.
Cefuroxime irreversibly binds to the active site of these PBPs, particularly PBP3, forming a stable covalent bond with a serine residue. This binding neutralizes the enzyme’s function, preventing the formation of peptide cross-links in the peptidoglycan layer. Without this cross-linking, the cell wall becomes structurally unsound. The weakened wall cannot withstand the high internal osmotic pressure, leading to cell lysis and the death of the organism.
Antimicrobial Spectrum
Cefuroxime exhibits a broad spectrum of activity, encompassing many Gram-positive cocci and Gram-negative bacilli. Its second-generation status means it maintains efficacy against Gram-positive organisms such as Streptococcus pneumoniae and Streptococcus pyogenes. It is also active against penicillinase-producing strains of Staphylococcus aureus, but it is not effective against Methicillin-Resistant Staphylococcus aureus (MRSA) strains.
The drug provides improved coverage against Gram-negative bacteria compared to first-generation cephalosporins. Key susceptible Gram-negative pathogens include Haemophilus influenzae (including beta-lactamase producing strains) and many Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae. Cefuroxime is frequently used to treat infections such as:
- Community-acquired pneumonia
- Acute bacterial otitis media
- Skin and soft tissue infections
- Complicated urinary tract infections
- Early Lyme disease caused by Borrelia burgdorferi
However, the drug does not provide reliable coverage against Pseudomonas aeruginosa or most Enterococcus species.
Mechanisms of Bacterial Resistance
The most common resistance mechanism involves the synthesis of beta-lactamase enzymes, which hydrolyze the bond within the antibiotic’s beta-lactam ring. This hydrolysis opens the ring structure, rendering the molecule inactive and unable to bind to the PBPs. Although the syn-oxime group provides stability against certain older beta-lactamases, the increasing prevalence of modern Extended-Spectrum Beta-Lactamases (ESBLs) can still cause drug inactivation.
Alteration of the drug’s target site is another strategy for bacterial resistance. This involves mutations in the genes that code for the Penicillin-Binding Proteins, resulting in modified PBP structures. These altered PBPs have a reduced binding affinity for cefuroxime and other beta-lactam antibiotics. Even when the drug is present, the modified PBPs can continue to perform the cell wall cross-linking function, allowing the bacterium to survive.
Gram-negative organisms employ additional mechanisms that contribute to resistance by reducing the drug’s access to its target. These bacteria can modify the size or number of porin channels in their outer membrane, limiting the amount of cefuroxime that can enter the cell. Furthermore, some bacteria utilize efflux pumps, which pump the antibiotic out of the bacterial cell.