Antibiotic Stewardship
Antibiotic stewardship is the clinical method for using antibiotics so that the patient receives effective treatment while avoidable antimicrobial harm is reduced. It is not a slogan about using fewer antibiotics. It is the disciplined sequence:
diagnose the syndrome -> assess severity -> sample correctly -> start the right empirical therapy when needed -> optimise dose and source control -> review evidence -> narrow, stop or complete
O&G is a high-stakes stewardship environment. A septic pregnant or puerperal patient must not wait while clinicians debate resistance. At the same time, caesarean prophylaxis, miscarriage care, urinary symptoms, vaginal discharge, pelvic pain, surgical complications and preterm membrane rupture can generate repeated antibiotic exposure. Good stewardship holds both truths: early adequate therapy saves lives in sepsis; unnecessary or prolonged therapy drives toxicity, microbiome injury and resistance.
This chapter teaches the pharmacological method, beginning from the cell biology of how antibiotics work and ending with the prescribing discipline that flows from it. Detailed clinical regimens belong in the linked Intermediate and Final chapters and in current local guidance.
The First Principle: Selective Toxicity
Before any stewardship rule makes sense, understand what an antibiotic actually is. An antibiotic is a drug that damages a bacterium more than it damages the patient. That gap is called selective toxicity, and the whole of antibacterial pharmacology is the search for biochemical structures or pathways the bacterium has and the human host does not. Where such a unique target exists, the drug can be given in doses lethal to bacteria but tolerable to us. Where bacterial and human biochemistry overlap closely, selective toxicity is poor and the drug is more toxic to the patient.
This single idea explains the entire map of antibiotic classes, their spectra, and their side-effect profiles. It is the foundation everything else in this chapter rests on.
A bacterium is a prokaryotic cell. Compared with our own eukaryotic cells it differs in ways the drug exploits:
| Bacterial feature | Why it matters as a drug target | Human cell equivalent |
|---|---|---|
| Peptidoglycan cell wall | A mesh polymer unique to bacteria; gives the cell its shape and resists osmotic bursting | Humans have no cell wall, so wall-active drugs spare us |
| 70S ribosome | Bacterial protein-synthesis machinery is structurally distinct | Human cells use the larger 80S ribosome |
| Folate synthesised from scratch | Bacteria must build folate; humans take it in from the diet | Human cells import preformed folate |
| Bacterial DNA-handling enzymes | DNA gyrase and bacterial RNA polymerase differ from ours | Human enzymes have different structure and affinity |
Where the major classes strike
Antibiotic classes are organised by which of these unique targets they attack. You do not need every agent for Primary, but you should be able to place each mechanism on the cell and predict its consequences.
| Target | Class examples | Mechanism in one line | Stewardship consequence |
|---|---|---|---|
| Cell-wall synthesis | Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams); glycopeptides (vancomycin) | Beta-lactams bind the transpeptidases (penicillin-binding proteins) that cross-link peptidoglycan; glycopeptides block incorporation of new wall units | Excellent selective toxicity; allergy and resistance via enzyme destruction dominate the risk |
| Protein synthesis (70S ribosome) | Macrolides, lincosamides (clindamycin), tetracyclines, aminoglycosides, chloramphenicol | Bind bacterial ribosomal subunits and halt translation | Useful where the wall is not a target; aminoglycoside renal and auditory toxicity needs exposure control |
| Nucleic acid handling | Fluoroquinolones; rifamycins (rifampicin) | Quinolones inhibit DNA gyrase/topoisomerase, preventing supercoiling; rifampicin inhibits bacterial RNA polymerase | Broad and ecologically disruptive; reserve for defined indications |
| Folate pathway | Sulphonamides, trimethoprim | Act at sequential steps of folate synthesis the bacterium cannot bypass | Synergy when combined; relevant in pregnancy because folate metabolism is shared |
| Anaerobic DNA damage | Nitroimidazoles (metronidazole) | Only the reduced form is active, and it is generated only at the very low oxygen tension inside anaerobes | Naturally anaerobe-selective; central to pelvic and polymicrobial cover |
Two features fall straight out of this map. Mycoplasma species have no cell wall and chlamydiae lack peptidoglycan, so both are intrinsically resistant to beta-lactams; they must be hit at the ribosome (for example with a macrolide or tetracycline) or elsewhere. That is not acquired resistance to overcome with a higher dose — it is a structural fact, and it explains why a wall-active drug will never clear a Mycoplasma genitalium or Chlamydia trachomatis infection no matter how "strong" it sounds.
Bacteriostatic versus bactericidal
A second basic distinction shapes interpretation. A bactericidal drug kills the organism; a bacteriostatic drug arrests its growth and leaves clearance to host defences. The clinical relevance for stewardship is that a bacteriostatic agent depends on a competent immune system and on culture being taken before the drug arrests the organisms — a stalled but living bacterium may still be present and may not grow on a sample taken after dosing. In severe infection, and in the immunocompromised, the killing-versus-stalling distinction is part of why empirical choice and timing matter.
How Resistance Arises
If selective toxicity is how antibiotics win, resistance is how bacteria escape, and stewardship exists largely because resistance is selected by the very act of prescribing. A bacterium becomes resistant by one of four general mechanisms — each the mirror image of a step the drug relies on:
| Resistance mechanism | What the bacterium does | Worked example |
|---|---|---|
| Reduced entry | Changes its outer membrane so the drug cannot get in | Gram-negative outer membrane excludes vancomycin |
| Active efflux | Pumps the drug back out faster than it accumulates | Tetracycline efflux pumps |
| Drug-destroying enzymes | Produces enzymes that chemically inactivate the drug | Beta-lactamases cleave the beta-lactam ring; aminoglycoside-modifying enzymes |
| Target alteration | Modifies, masks or duplicates the binding site so the drug cannot act | Altered DNA gyrase (quinolone resistance); altered RNA polymerase (rifampicin resistance); altered penicillin-binding proteins in methicillin-resistant Staphylococcus aureus |
The Gram-negative outer membrane and the periplasmic space deserve a moment, because they explain much of obstetric and gynaecological resistance. Gram-negative bacteria carry an extra outer lipopolysaccharide membrane that both keeps some drugs out and houses beta-lactamases in the periplasmic space, where they destroy beta-lactams before the drug reaches its target. This is why Gram-negative cover is harder to guarantee empirically and why escalating broad-spectrum pressure breeds the most clinically threatening organisms.