Cephalosporins represent a significant class of antibiotics closely related to penicillins, both structurally and functionally. Unlike penicillins, most cephalosporins are produced synthetically, with alterations in their chemical structure influencing their antibacterial activity and pharmacokinetic properties. This class of antibiotics shares a common β-lactam ring structure with penicillins, which is crucial for their bactericidal activity.
Cephalosporins are classified into five generations based on their antibacterial spectrum, bacterial susceptibility patterns, and resistance to β-lactamases. The first-generation cephalosporins act as substitutes for penicillin G and are effective against Gram-positive organisms such as Staphylococcus aureus (including methicillin-sensitive strains) and some Gram-negative bacteria like Proteus mirabilis and Escherichia coli. However, they are less effective against penicillin-resistant Streptococcus pneumoniae.
Second-generation cephalosporins :have increased activity against Gram-negative bacteria, including Haemophilus influenzae, Klebsiella species, Proteus species, and Escherichia coli. Additionally, cephamycins such as cefoxitin and cefotetan provide coverage against anaerobic bacteria, making them valuable for treating infections involving mixed flora.
Third-generation cephalosporins :are important in treating infections caused by Gram-negative bacilli, especially those producing β-lactamases. They exhibit less activity against methicillin-sensitive Staphylococcus aureus (MSSA) but have broad-spectrum activity against Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae. However, their use is associated with collateral damage, including the induction of antimicrobial resistance and the development of Clostridium difficile infection.
Fourth-generation cephalosporins:, such as cefepime, have an expanded spectrum of activity, including coverage against Gram-positive organisms like Streptococcus pneumoniae and some Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Cefepime is particularly valuable in the treatment of serious infections, including hospital-acquired pneumonia and complicated urinary tract infections.
Advanced generation
Ceftaroline, an advanced-generation cephalosporin, is the first β-lactam antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA). It is indicated for the treatment of skin and skin infections and community-acquired typepneumonia. However, ceftaroline’s coverage does not extend to certain pathogens such as Pseudomonas aeruginosa and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae.
Resistance
Resistance to cephalosporins primarily occurs through the hydrolysis of the β-lactam ring by β-lactamases or reduced affinity for penicillin-binding proteins (PBPs). This resistance poses a significant challenge in the treatment of bacterial infections, necessitating the development of new antibiotics and antimicrobial stewardship programs to preserve the effectiveness of existing therapies.
Pharmacokinetics:
In terms of pharmacokinetics, most cephalosporins are administered intravenously or intramuscularly due to their poor oral absorption. They distribute well into various body fluids, including cerebrospinal fluid, making them effective in treating central nervous system infections. Renal elimination is the primary route for most cephalosporins, necessitating dose adjustments in patients with renal dysfunction to prevent accumulation and toxicity.
Adverse reaction:
While cephalosporins are generally well-tolerated, allergic reactions, including anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, can occur. Individuals with a history of severe allergic reactions to penicillins should avoid cephalosporins or use them with caution due to the potential for cross-reactivity. Current data suggest that cross-reactivity between penicillins and cephalosporins is relatively low, primarily determined by similarities in side-chain structures rather than the β-lactam.
Conclusion:
Cephalosporin’s are essential antibiotics, offering a broad spectrum of activity against various bacterial infections. Classified into five generations, they have evolved to address bacterial resistance mechanisms. While generally well-tolerated, allergic reactions remain a concern, particularly in patients with penicillin allergies. Despite this, cephalosporins are valuable treatment options, with advanced generations like ceftaroline providing coverage against multidrug-resistant pathogens such as MRSA. However, the emergence of resistance highlights the need for judicious use and ongoing research to preserve their effectiveness in combating infectious diseases.
