Antibiotics: Classification, Spectrum of Activity and Safety

Vocabulary practice flashcards covering antibiotic classifications, mechanisms of action, chemical scaffolds, spectra of activity, pharmacokinetic kill characteristics, and major safety profiles from the lecture by Enoch Omonge.

Bactericidal Antibiotics

Antibacterial agents that kill bacteria and reduce bacterial load; they are particularly appropriate for patients with poor immunity. Examples include penicillins, aminoglycosides, cephalosporins, vancomycin, and ciprofloxacin.

Bacteriostatic Antibiotics

Antibacterial agents that inhibit the growth and reproduction of bacteria, requiring an intact host immune system to eliminate the infection. Examples include sulfonamides, tetracyclines, chloramphenicol, and erythromycin.

Concentration-Dependent Killing ($C_{\max}/\text{MIC}$)

A bacterial kill pattern where antimicrobial efficacy increases as the peak drug concentration relative to the minimum inhibitory concentration ($C_{\max}/\text{MIC}$) increases, characteristic of aminoglycosides.

Time-Dependent Killing ($T > \text{MIC}$)

A bacterial kill pattern where efficacy depends on the duration of time that serum drug concentrations remain above the minimum inhibitory concentration ($T > \text{MIC}$), characteristic of $\beta$-lactams.

AUC/MIC-Dependent Killing

A pharmacodynamic kill characteristic where efficacy correlates with the ratio of the total area under the concentration-time curve to the minimum inhibitory concentration ($\text{AUC}/\text{MIC}$), characteristic of fluoroquinolones.

Bacterial Kill Characteristics Graph

A pharmacodynamic plot illustrating the three major bactericidal profiles: concentration-dependent killing ($C_{\max}/\text{MIC}$), AUC-dependent killing ($\text{AUC}/\text{MIC}$), and time-dependent killing ($T > \text{MIC}$) relative to minimum inhibitory concentration ($\text{MIC}$).

$\beta$-Lactam Ring

A four-membered cyclic amide ring in which the nitrogen atom is attached to the beta carbon relative to the carbonyl group; it forms the core antibacterial scaffold of penicillins, cephalosporins, carbapenems, and monobactams.

Peptidoglycan Layer

A bacterial cell wall carbohydrate composed of alternating units of N-acetylmuramic acid (NAM/NAMA) and N-acetylglucosamine (NAG/NAGA), cross-linked from an L-Lys residue to the terminal D-Ala-D-Ala link on an adjacent NAM unit.

Gram-Negative Bacilli (GNB) Resistance Mechanisms

Mechanisms used by Gram-negative bacteria to evade antibiotic activity, including porin loss or mutation, enzymatic hydrolysis by $\beta$-lactamases, target modification, antibiotic enzymatic modification, and overexpression of efflux pumps.

Narrow-Spectrum Penicillins

Penicillin derivatives with targeted activity, primarily against Gram-positive organisms, including Benzylpenicillin (Penicillin G), Phenoxymethylpenicillin (Pen V), and Flucloxacillin.

Broad-Spectrum Penicillins

Penicillin agents with expanded activity covering both Gram-positive and Gram-negative organisms, including Ampicillin, Amoxicillin/Co-amoxiclav, and Piperacillin with Tazobactam (Tazocin).

First-Generation Cephalosporins

Cephalosporin agents such as Cefalexin (Cephalexin), Cefazolin, and Cephalothin that provide strong activity against methicillin-sensitive Staphylococcus aureus (MSSA), Streptococci, and many Enterobacteriaceae.

Second-Generation Cephalosporins

Cephalosporins including Cefuroxime, Cefotetan, and Cefoxitin that exhibit enhanced stability against Gram-negative bacteria but reduced activity against Staphylococcus aureus compared to first-generation agents.

Third-Generation Cephalosporins

Cephalosporins such as Ceftriaxone, Cefotaxime, and Cefoperazone that possess broader activity against Gram-negative pathogens.

Fourth-Generation Cephalosporins

Cephalosporin antibiotics, exemplified by Cefepime, that have enhanced resistance to degradation by chromosomal $\beta$-lactamases.

$\beta$-Lactamase Inhibitors

Molecules such as Clavulanic acid, Tazobactam, and Avibactam that bind and inactivate bacterial $\beta$-lactamase enzymes, preventing hydrolysis of co-administered $\beta$-lactam antibiotics.

Carbapenems

A class of broad-spectrum $\beta$-lactam antibiotics that includes Meropenem, Imipenem, Doripenem, and Ertapenem, characterized by high resistance stability and broad clinical potency.

Macrolides Mechanism of Action

Inhibition of bacterial protein synthesis by binding to the 50S ribosomal subunit; agents include Erythromycin, Clarithromycin, Azithromycin, and Telithromycin.

Macrolides Spectrum and Elimination

Antibiotics that undergo entirely hepatic elimination, display activity against Gram-positive aerobes, upper airway anaerobes, and atypical bacteria, but have no activity against Enterobacteriaceae.

Erythromycin Estolate Adverse Effects

Specific toxicities associated with the estolate formulation of Erythromycin, prominently including cholestatic hepatitis and ototoxicity when administered in high doses.

Aminoglycosides Mechanism of Action

Bactericidal inhibition of protein synthesis through irreversible binding to the bacterial 30S ribosomal subunit; naturally occurring members include Streptomycin, Neomycin, Kanamycin, Tobramycin, and Gentamicin.

Semisynthetic Aminoglycosides

Chemically modified aminoglycosides developed to counter resistance, including Amikacin (derived from Kanamycin) and Netilmicin (derived from Sisomicin).

Aminoglycoside Nephrotoxicity

Direct proximal tubular damage caused by aminoglycosides that is reversible if recognized early; risk factors include elevated trough serum concentrations, prolonged therapy, underlying renal impairment, and concomitant nephrotoxins.

Aminoglycoside Ototoxicity

Irreversible damage to the 8th cranial nerve causing vestibular impairment (dizziness, vertigo, ataxia) and auditory impairment (tinnitus, decreased hearing).

Therapeutic Drug Monitoring (TDM) in Aminoglycosides

Serum drug concentration surveillance utilized to avoid toxicity from elevated levels, requiring dose reduction when $\text{eGFR} < 70\,\text{ml/min}$ and caution in dehydration or concurrent nephrotoxic drug use.

Quinolones Mechanism of Action

Inhibition of bacterial nucleic acid synthesis by targeting DNA gyrase, exerting bactericidal effects against a wide variety of Gram-positive, Gram-negative, and atypical bacteria.

Quinolone Adverse Drug Reactions (ADRs)

Major safety concerns associated with quinolones, including high-dose neurotoxicity, risk of tendon rupture with prolonged use, high risk for Clostridioides difficile infection, and contraindication in children and pregnancy.

Tetracyclines Mechanism of Action

Bacteriostatic inhibition of bacterial protein synthesis achieved by reversibly binding to the 30S ribosomal subunit, thereby preventing polypeptide chain elongation.

Tetracyclines Spectrum of Activity

A broad spectrum encompassing Gram-positive aerobic cocci and rods (Staphylococci, Streptococci), Gram-negative aerobic bacteria, and atypical organisms (Mycoplasmas, Chlamydiae, Rickettsiae, and protozoa).

Glycopeptides

Large-molecule cell wall synthesis inhibitors (Vancomycin and Teicoplanin) active only against Gram-positive bacteria; typically second-line agents except as first-line therapy for MRSA and Clostridioides difficile infections.

Metronidazole

A bactericidal antibiotic, amoebicide, and anti-protozoal agent active against Trichomonas vaginalis that inhibits bacterial DNA synthesis and is strictly limited to anaerobic infections.

Metronidazole Adverse Effects

Characteristic side effects including a metallic taste in the mouth, a disulfiram-like Antabuse reaction with alcohol, and neurotoxicity (peripheral neuropathy, seizures, and ataxia) following prolonged use.