Antibiotics: Understanding their Classifications

Bacteriostatic Antibiotics

Bactericidal agents function by directly eliminating bacteria. They do this by disrupting the formation of bacterial cell walls, interfering with enzyme activity, or halting protein synthesis—mechanisms that ultimately cause bacterial cell death. In contrast, bacteriostatic antibiotics work by suppressing bacterial growth and reproduction. They achieve this by blocking essential functions such as protein creation or DNA replication. These agents don’t kill bacteria outright but instead allow the body’s immune system time to clear the infection. However, the distinction between bactericidal and bacteriostatic is not always clear-cut. Some bacteriostatic antibiotics can become bactericidal at higher doses, and certain bactericidal antibiotics may only inhibit growth under specific conditions. Therefore, the choice of antibiotic should consider factors such as the Minimum Bactericidal Concentration (MBC)—the lowest concentration required to kill 99.99% of bacteria—and the Minimum Inhibitory Concentration (MIC)—the lowest amount that prevents visible growth. Typically, bactericidal antibiotics are preferred in cases of severe infection or when the patient’s immune response is compromised, while bacteriostatic antibiotics are often used for milder infections, where controlling growth is sufficient for recovery.¹ ⁸ ⁹

Bactericidal Antibiotics Targeting Cell Wall Synthesis

These antibiotics kill bacteria by preventing them from building or maintaining their protective outer cell walls, leading to structural failure and cell death. They can be divided into beta-lactam and non-lactam categories. Beta-lactam antibiotics contain a beta-lactam ring that binds to and disables the enzymes needed for constructing the bacterial cell wall. This group includes penicillins, cephalosporins, carbapenems, and monobactams. Non-lactam antibiotics, while lacking the beta-lactam ring, still disrupt cell wall construction through other mechanisms and include glycopeptides, lipoglycopeptides, lipopeptides, polypeptides, and phosphonates.¹ ⁸ ⁹

Beta-Lactam Antibiotics

Penicillins, discovered in 1929 and used clinically by 1943, were the first naturally derived antibiotics. They block cell wall formation by binding to penicillin-binding proteins. These drugs mainly target gram-positive organisms and some gram-negative cocci, treating conditions like syphilis, clostridial infections, and endocarditis. Broader-spectrum penicillins, such as amoxicillin and ampicillin, also cover some gram-negative bacilli. Penicillinase-resistant forms are used against resistant Staphylococcus aureus, and extended-spectrum types are effective against Pseudomonas aeruginosa. Penicillins are often paired with beta-lactamase inhibitors like clavulanate or sulbactam to overcome resistance. Though generally safe in pregnancy and breastfeeding, risks should be evaluated on a case-by-case basis.¹ ¹⁰

Cephalosporins, introduced in 1964, are broad-spectrum agents that vary in activity across their five generations. First-generation drugs treat gram-positive cocci and are used for skin infections. Later generations have increasing gram-negative coverage and are used for more severe infections, with fifth-generation cephalosporins like ceftaroline offering activity against MRSA. Cephalosporins are typically considered safe during pregnancy but may affect infant gut flora during breastfeeding.¹ ¹¹

Monobactams, such as aztreonam, were developed in 1981. They are active only against aerobic gram-negative organisms, including Pseudomonas aeruginosa, and are particularly useful for patients allergic to penicillins. They are not effective against anaerobes or gram-positive bacteria. While usually safe during breastfeeding, dosing adjustments are needed for renal impairment, and risks during pregnancy must be weighed carefully.¹ ¹²

Carbapenems, including ertapenem, imipenem, and meropenem, were discovered in the 1970s and introduced clinically in the 1980s. These powerful broad-spectrum agents disrupt bacterial cell wall synthesis and are effective against difficult infections, including resistant gram-negative bacteria. Often given with other antibiotics like aminoglycosides, some, such as imipenem, require co-administration with cilastatin or relebactam to improve efficacy. Due to structural similarity to penicillins, they may provoke allergic reactions. These drugs are effective for serious infections such as sepsis and pneumonia. While generally considered low-risk during pregnancy and breastfeeding, close monitoring is recommended.¹ ¹³ ¹⁴

Non-Beta-Lactam Antibiotics

Vancomycin, a glycopeptide, is primarily used intravenously due to poor GI absorption. It binds to the D-Ala-D-Ala portion of the bacterial cell wall and is effective against gram-positive organisms, including resistant Staphylococcus aureus. It is also used orally for Clostridioides difficile infections. Due to uncertain risks during pregnancy and breastfeeding, its use is limited to when benefits outweigh risks.¹ ¹⁵

Lipoglycopeptides like dalbavancin, oritavancin, teicoplanin, and telavancin interfere with both cell wall synthesis and membrane integrity. Their long half-lives support single-dose regimens. They are active against resistant strains such as vancomycin-resistant enterococci. Though promising, animal studies raise fetal concerns, and data on breastfeeding are limited. Caution is advised during pregnancy.¹ ¹⁶

Daptomycin, the only approved lipopeptide, works by depolarizing bacterial membranes, leading to rapid bacterial death. It is particularly useful for treating infections by MRSA and VRE. It is not effective for pneumonia due to poor lung penetration. While animal studies show no fetal harm, limited human data require careful consideration in pregnancy.¹ ¹⁷

Polypeptides, including colistin and polymyxin B, damage bacterial membranes by increasing permeability. Mostly used topically, IV forms are reserved for drug-resistant infections like ventilator-associated pneumonia. Due to potential toxicity, they are used when safer alternatives are not available. Clinical studies on their combination therapies are limited.¹ ¹⁸

Phosphonates, such as fosfomycin, inhibit bacterial wall synthesis through MurA enzyme inhibition. They are active against many resistant organisms and commonly used for urinary tract infections. Oral forms are used for uncomplicated infections, while IV versions handle more serious multidrug-resistant cases. Generally safe during pregnancy, their impact during breastfeeding is not well defined.¹ ¹⁹

Bactericidal Antibiotics Targeting Enzymes or Protein Synthesis

These antibiotics interfere with vital cellular processes like DNA replication or protein synthesis, resulting in bacterial death. Included in this group are fluoroquinolones, mupirocin, sulfonamides, azoles, nitrofurans, and ansamycins.¹ ⁸ ⁹

Fluoroquinolones, first used clinically in 1962, inhibit DNA replication by targeting DNA gyrase and topoisomerase IV. Examples include ciprofloxacin, levofloxacin, and moxifloxacin. They are active against both gram-positive and gram-negative organisms, but concerns over systemic toxicity and increasing resistance have limited their use.¹ ²⁰

Mupirocin, a topical antibiotic introduced in 1985, inhibits isoleucyl-tRNA synthetase, halting bacterial protein production. It is used to treat superficial skin infections and nasal Staphylococcus aureus colonization. Resistance may develop with prolonged use.¹ ²¹

Metronidazole, an azole antibiotic, damages bacterial DNA after cell penetration. It is effective against anaerobes and protozoa, making it a first-line agent for infections like bacterial vaginosis. It distributes well in body fluids and crosses the blood-brain barrier.¹ ²²

Nitrofurantoin, part of the nitrofuran class, also disrupts bacterial DNA. It targets uropathogens such as E. coli and is used for uncomplicated urinary infections. Though safe during most of pregnancy, it is avoided at term and during early breastfeeding due to risk of neonatal hemolysis.¹ ²³

Ansamycins, including rifampin, rifabutin, and rifapentine, block RNA synthesis by inhibiting DNA-dependent RNA polymerase. Rifampin is widely used for tuberculosis, while rifabutin is preferred in HIV patients for its lower risk of drug interactions. Rifapentine is used for latent TB. These drugs penetrate well into tissues and abscesses.¹ ²⁴

Bacteriostatic Antibiotics

Bacteriostatic antibiotics inhibit bacterial growth by targeting DNA synthesis, protein production, or metabolic pathways. They allow the immune system to eliminate the infection and may act as bactericidal agents at high concentrations. This category includes sulfonamides, aminoglycosides, tetracyclines, macrolides, streptogramins, lincosamides, oxazolidinones, amphenicols, and pleuromutilins.¹ ⁸ ⁹

Sulfonamides inhibit folate synthesis by blocking the conversion of p-aminobenzoic acid to dihydropteroate, a step vital for bacterial DNA production. Available in oral, topical, and ophthalmic forms, sulfonamides are used for urinary tract infections, burns, and inflammatory bowel disease.¹ ²⁵

Aminoglycosides, such as gentamicin, bind to the 30S ribosomal subunit, blocking protein synthesis. Given by injection, they are effective against gram-negative infections but have limited use against anaerobes.¹ ²⁶

Tetracyclines, like doxycycline and minocycline, inhibit protein synthesis by attaching to the 30S ribosome. They treat infections like Lyme disease, malaria, and rickettsial diseases, but resistance limits their use.¹ ²⁷

Macrolides, including erythromycin and azithromycin, bind to the 50S ribosomal subunit, halting protein production. They are effective against respiratory pathogens and often used when penicillins are contraindicated.¹ ²⁸

Streptogramins, such as quinupristin-dalfopristin, are IV antibiotics targeting resistant bacteria like VRE and MRSA. They disrupt protein synthesis and are used for severe infections when other options fail.²⁹ ³⁰

Lincosamides, particularly clindamycin, inhibit protein synthesis and are used against anaerobic infections and resistant strains like CA-MRSA. Topical versions treat acne, while oral or IV forms manage systemic infections.¹ ²⁹ ³¹

Oxazolidinones, such as linezolid and tedizolid, are synthetic agents effective against resistant pathogens like MRSA and VRE. They are reserved for infections unresponsive to other treatments.³²

Amphenicols, like chloramphenicol, bind to the 50S ribosomal subunit to block protein synthesis. Once widely used, chloramphenicol is now limited to specific infections due to its risk of bone marrow toxicity.³³