I now have comprehensive content from Katzung's 16th Edition. Let me compile the full, detailed answer on IV antibiotic mechanisms and coverage.
IV Antibiotics: Mechanism of Action and Coverage
Source: Katzung's Basic and Clinical Pharmacology, 16th Ed; Jawetz Medical Microbiology 28th Ed; Harrison's Principles of Internal Medicine 22E
1. BETA-LACTAMS
Mechanism of Action
Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) work by binding to penicillin-binding proteins (PBPs) - transpeptidase enzymes on the bacterial cell membrane. This inhibits the transpeptidation step of peptidoglycan cross-linking, halting cell wall synthesis. Without a complete cell wall, bacteria undergo osmotic lysis. They are bactericidal and require actively dividing bacteria for full effect.
Beta-lactams bind the transpeptidase at the PBP site, resulting in inhibition of transpeptidation, thus halting peptidoglycan synthesis. - Katzung 16th Ed
A. Penicillins (IV)
| Agent | Spectrum / Coverage |
|---|
| Penicillin G (IV) | Streptococci (Group A, B, viridans), Streptococcus pneumoniae (sensitive strains), Neisseria meningitidis, Treponema pallidum, Clostridium (not difficile), Actinomyces |
| Ampicillin (IV) | Extends to Enterococci, Listeria monocytogenes, H. influenzae (non-beta-lactamase), E. coli, Proteus mirabilis |
| Ampicillin-sulbactam (IV) | Above + beta-lactamase producing organisms, MSSA, Bacteroides |
| Piperacillin-tazobactam (IV) | Broadest: Pseudomonas aeruginosa, Enterobacterales, anaerobes, MSSA; NOT MRSA |
| Nafcillin / Oxacillin (IV) | MSSA primarily (anti-staphylococcal) |
B. Cephalosporins (IV)
| Generation | Agents | Coverage |
|---|
| 1st gen | Cefazolin | MSSA, streptococci, limited gram-negatives (E. coli, Klebsiella, Proteus). Surgical prophylaxis. |
| 2nd gen | Cefuroxime, Cefoxitin, Cefotetan | Expanded gram-negatives; Cefoxitin/Cefotetan also cover anaerobes (Bacteroides) |
| 3rd gen | Ceftriaxone, Cefotaxime, Ceftazidime | Broad gram-negative including H. influenzae, Neisseria, Enterobacterales, S. pneumoniae; Ceftazidime covers Pseudomonas |
| 4th gen | Cefepime | Extended gram-negative including Pseudomonas + better gram-positive (pneumococci, streptococci); stable to many beta-lactamases |
| 5th gen | Ceftaroline | MRSA + broad gram-negatives (NOT Pseudomonas) |
| Novel | Ceftolozane-tazobactam, Ceftazidime-avibactam | MDR and carbapenem-resistant Pseudomonas, ESBL/KPC-producing organisms |
C. Carbapenems (IV)
| Agent | Coverage |
|---|
| Imipenem-cilastatin | Broadest spectrum: most gram-negatives (including Pseudomonas), gram-positives, anaerobes. Resistant to most beta-lactamases but not carbapenemases (KPC, MBL). NOT: MRSA, VRE, C. difficile, Stenotrophomonas. Requires cilastatin to prevent renal dehydropeptidase degradation. |
| Meropenem | Similar to imipenem; slightly better gram-negative activity, not degraded by dehydropeptidase. Used for meningitis (better CNS penetration). |
| Ertapenem | NO Pseudomonas, NO Acinetobacter. Good for ESBL-producing Enterobacterales, community-acquired infections, once-daily dosing. |
| Meropenem-vaborbactam | Adds coverage against KPC-producing carbapenem-resistant Enterobacterales (CRE). |
The carbapenems are resistant to most beta-lactamases but not serine carbapenemases nor metallo-beta-lactamases. - Katzung 16th Ed
D. Monobactams (IV)
| Agent | Coverage |
|---|
| Aztreonam | Gram-negatives ONLY (including Pseudomonas). No gram-positive or anaerobic activity. Safe in penicillin allergy (no cross-reactivity except with ceftazidime). |
2. GLYCOPEPTIDES (IV)
Mechanism of Action
Vancomycin binds firmly to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide chains. This inhibits transglycosylase, preventing further elongation of peptidoglycan and ultimately inhibiting cell wall synthesis. It acts at a different step than beta-lactams (earlier - before transpeptidation), explaining why there is no cross-resistance. It is bactericidal against staphylococci and bacteriostatic against enterococci.
Vancomycin inhibits cell wall synthesis by binding firmly to the d-Ala-d-Ala terminus of nascent peptidoglycan pentapeptide - Katzung 16th Ed
| Agent | Coverage |
|---|
| Vancomycin (IV) | MRSA (drug of choice), MSSA, S. epidermidis, Streptococci, Enterococci (not VRE). For penicillin-allergic patients with serious gram-positive infections. C. difficile (oral form only for GI). |
| Teicoplanin (IV/IM) | Similar to vancomycin; MRSA, staphylococci, streptococci, enterococci. |
3. AMINOGLYCOSIDES (IV)
Mechanism of Action
Aminoglycosides have a two-step mechanism:
- They are taken up across the bacterial cell membrane via an energy-dependent process (requires aerobic respiration - hence inactive against anaerobes and in anaerobic/acidic environments).
- Inside, they bind to the 30S ribosomal subunit (specifically protein S12 in the case of streptomycin, multiple sites for newer aminoglycosides), causing misreading of mRNA codons - leading to incorporation of wrong amino acids and production of aberrant, non-functional proteins. These abnormal proteins insert into the cell membrane, increasing permeability and allowing more aminoglycoside entry - a self-amplifying process.
They are concentration-dependent bactericidal antibiotics.
The aminoglycoside blocks the normal activity of the "initiation complex" of peptide formation and binds to protein S12 on the 30S subunit - Jawetz Medical Microbiology 28th Ed
| Agent | Coverage |
|---|
| Gentamicin | Gram-negatives: Enterobacterales (E. coli, Klebsiella, Proteus, Serratia), Pseudomonas. Synergy with beta-lactams for gram-positives (Enterococcus, Staphylococcus, viridans streptococci in endocarditis). |
| Tobramycin | Similar to gentamicin; better Pseudomonas activity |
| Amikacin | Broadest: resistant to most inactivating enzymes; MDR gram-negatives, Mycobacteria (M. avium complex) |
| Streptomycin | Mycobacterium tuberculosis, plague (Y. pestis), tularemia, synergy in endocarditis |
Inactive against: Strict anaerobes, Streptococcus pneumoniae alone (need synergy).
4. FLUOROQUINOLONES (IV)
Mechanism of Action
Fluoroquinolones inhibit two bacterial enzymes critical for DNA replication and repair:
- DNA gyrase (topoisomerase II) - primary target in gram-negative bacteria. Introduces negative supercoils ahead of the replication fork.
- Topoisomerase IV - primary target in gram-positive bacteria. Required for decatenation (separation) of daughter chromosomes after replication.
By blocking these enzymes, fluoroquinolones cause ds-DNA strand breaks and are bactericidal. They are concentration-dependent killers.
| Agent | Coverage |
|---|
| Ciprofloxacin (IV) | Excellent gram-negatives: Pseudomonas, Enterobacterales, H. influenzae, Neisseria, Legionella. Moderate gram-positives. Atypicals (Chlamydia, Mycoplasma). NOT reliable for streptococci/pneumococci. |
| Levofloxacin (IV) | "Respiratory quinolone" - all of ciprofloxacin's gram-negative coverage PLUS excellent S. pneumoniae, atypicals (Legionella, Mycoplasma, Chlamydia), Mycobacteria. |
| Moxifloxacin (IV) | Best gram-positive and anaerobic coverage. Excellent for respiratory pathogens, atypicals, anaerobes (intra-abdominal). Less Pseudomonas activity than ciprofloxacin. |
5. LINCOSAMIDES & STREPTOGRAMINS (IV)
Mechanism of Action
Clindamycin and quinupristin-dalfopristin bind the 50S ribosomal subunit, inhibiting translocation of peptide chain during protein synthesis. They are generally bacteriostatic.
| Agent | Coverage |
|---|
| Clindamycin (IV) | MSSA, streptococci (Group A, B), anaerobes above the diaphragm (Bacteroides, Peptostreptococcus), Toxoplasma (with pyrimethamine), Pneumocystis (with primaquine). NOT gram-negatives. |
| Quinupristin-dalfopristin (Synercid) (IV) | VRE (E. faecium only, NOT faecalis), MRSA, resistant streptococci. Bactericidal combo (component A binds 50S, B stabilizes complex). |
6. OXAZOLIDINONES (IV)
Mechanism of Action
Linezolid binds to the 23S rRNA of the 50S ribosomal subunit, blocking formation of the 70S initiation complex - a unique mechanism not shared by any other antibiotic class. This prevents translation before it even begins.
| Agent | Coverage |
|---|
| Linezolid (IV/oral) | MRSA (DOC alongside vancomycin), VRE (both faecalis and faecium), drug-resistant pneumococci, streptococci. Used in MDR-TB. Bacteriostatic against most organisms but bactericidal against streptococci. |
7. LIPOPEPTIDES (IV)
Mechanism of Action
Daptomycin inserts its lipid tail into the bacterial cell membrane in a calcium-dependent manner, causing rapid depolarization of the membrane potential. This leads to loss of intracellular potassium, inhibition of DNA/RNA/protein synthesis, and rapid bactericidal death.
| Agent | Coverage |
|---|
| Daptomycin (IV) | Gram-positives ONLY: MRSA, VRE, penicillin-resistant S. pneumoniae, S. aureus endocarditis, complicated skin infections. Inactivated by pulmonary surfactant - NEVER use for pneumonia. |
8. CARBOXYPENICILLINS & TETRACYCLINES - IV
Tigecycline (IV - Glycylcycline)
Mechanism: Binds 30S ribosome (same class as tetracyclines) but overcomes major resistance mechanisms. Inhibits protein synthesis.
Coverage: Very broad - MRSA, VRE, ESBL-producing Enterobacterales, Acinetobacter, anaerobes, atypicals. NOT reliable against Pseudomonas or Proteus. Used for complicated intra-abdominal and skin infections.
9. POLYMYXINS (IV)
Mechanism of Action
Polymyxin B and colistin (polymyxin E) act as detergents - they are cationic cyclic polypeptides that bind to the anionic lipopolysaccharide (LPS) of gram-negative outer membranes, displacing calcium and magnesium ions that normally stabilize the membrane. This disrupts membrane integrity, leading to cell lysis.
| Agent | Coverage |
|---|
| Colistin / Polymyxin B (IV) | Last-resort agents for MDR gram-negatives ONLY: carbapenem-resistant Acinetobacter, Pseudomonas, KPC-producing Klebsiella. No gram-positive or anaerobic activity. Significant nephrotoxicity. |
Summary Table
| Class | MOA Target | Bactericidal? | Gram+ | Gram- | Anaerobes | Key IV Agents |
|---|
| Penicillins | PBP / transpeptidase (cell wall) | Yes | ++ | +/- | +/- | Pen G, Pip-Tazo, Ampicillin |
| Cephalosporins | PBP / transpeptidase | Yes | ++ | ++ | +/- | Cefazolin, Ceftriaxone, Cefepime |
| Carbapenems | PBP / transpeptidase | Yes | ++ | +++ | +++ | Imipenem, Meropenem, Ertapenem |
| Monobactams | PBP / transpeptidase | Yes | - | +++ | - | Aztreonam |
| Glycopeptides | D-Ala-D-Ala (cell wall) | Yes* | +++ | - | - | Vancomycin |
| Aminoglycosides | 30S ribosome | Yes | +/- | +++ | - | Gentamicin, Amikacin |
| Fluoroquinolones | DNA gyrase / Topo IV | Yes | ++ | +++ | +/- | Ciprofloxacin, Levofloxacin |
| Clindamycin | 50S ribosome | No | ++ | - | +++ | Clindamycin |
| Linezolid | 50S / 70S initiation | No* | +++ | - | - | Linezolid |
| Daptomycin | Cell membrane | Yes | +++ | - | - | Daptomycin |
| Tigecycline | 30S ribosome | No | ++ | ++ | ++ | Tigecycline |
| Polymyxins | Outer membrane (LPS) | Yes | - | +++ | - | Colistin, Polymyxin B |
Linezolid is bactericidal vs streptococci; Vancomycin bacteriostatic vs Enterococcus
Key clinical pearls:
- MRSA: Vancomycin (1st line), Daptomycin, Linezolid, Ceftaroline
- Pseudomonas: Pip-tazobactam, Ceftazidime, Cefepime, Imipenem/Meropenem, Ciprofloxacin, Aztreonam, Tobramycin - never Ertapenem
- VRE: Linezolid, Daptomycin, Quinupristin-dalfopristin (faecium only)
- CRE (carbapenem-resistant Enterobacterales): Ceftazidime-avibactam, Meropenem-vaborbactam, Colistin, Tigecycline
- Anaerobes: Metronidazole, Pip-tazobactam, Carbapenems, Moxifloxacin, Clindamycin