Antibiotics

TL;DR. Antibiotics exploit differences between bacterial and human cells, which is why they are so effective and so specific. They do nothing whatever against viruses, which cause most coughs, colds, sore throats, and sinus infections. Resistance is not a future problem: it already causes over a million deaths a year directly. The advice to "always finish the course" is being actively revised, because for many infections shorter courses work as well and generate less resistance, though you should still follow the specific instruction you were given rather than stopping when you feel better. Most reported penicillin allergy is not allergy, and that mislabelling causes measurable harm.

1. How they work

Antibiotics target structures or processes bacteria have and human cells do not.

Bactericidal versus bacteriostatic: some kill bacteria outright, others stop them multiplying and leave the immune system to finish. The distinction matters clinically mainly in severe infection and in immunocompromised patients.

Spectrum: narrow-spectrum drugs hit few species and cause less collateral damage; broad-spectrum drugs hit many, are used when the organism is unknown or the patient is very unwell, and do more damage to the microbiome and to resistance. Good practice is to start broad if someone is seriously ill and then narrow once the culture identifies the organism, which is why cultures are taken before starting.

2. A short history

Penicillin. Alexander Fleming noticed in 1928 that a contaminating Penicillium mould had cleared a zone of staphylococci on a culture plate. He published and largely moved on, unable to purify it. Howard Florey, Ernst Chain, and Norman Heatley at Oxford did the work that turned it into a drug, from 1938, and the first patient, a policeman named Albert Alexander, improved dramatically and then died when supplies ran out. Mass production was achieved in the US during the Second World War, from a strain found on a mouldy cantaloupe in Peoria, Illinois.

The scale of the change is hard to overstate. Before antibiotics, a scratch could kill, childbirth was dangerous, pneumonia killed roughly a third of those who got it, and surgery was constrained by infection. Antibiotics made modern surgery, chemotherapy, transplantation, and intensive care possible.

Fleming's Nobel lecture in 1945 warned about resistance, describing exactly how underdosing would select for resistant organisms. He was right within a decade.

3. Resistance

Bacteria acquire resistance by:

• Mutation and selection under antibiotic pressure.
• Horizontal gene transfer: plasmids carrying resistance genes passed between bacteria, including between species. This is why resistance spreads much faster than mutation alone would predict.

Mechanisms: enzymes that destroy the drug (beta-lactamases), altered targets so the drug does not bind (MRSA), efflux pumps that expel it, and reduced permeability.

The scale: the 2022 Lancet Global Burden of Antimicrobial Resistance study estimated 1.27 million deaths directly attributable to bacterial antimicrobial resistance in 2019, and 4.95 million associated with it. That is more than HIV or malaria. Projections to 2050 vary widely and are all bad.

The organisms that worry people most: carbapenem-resistant Enterobacteriaceae, MRSA, drug-resistant Neisseria gonorrhoeae (now approaching untreatable in some strains), multi-drug resistant tuberculosis, and Candida auris (a fungus, but the same story).

What drives it:

The pipeline problem: developing a new antibiotic costs as much as any other drug, and the resulting product is used sparingly, for short courses, and reserved as a last resort. That is excellent stewardship and terrible economics, so most large companies have left the field. Various "pull incentive" schemes (subscription payment models, market entry rewards) are being trialled.

4. The "finish the course" question

The traditional instruction was that failing to complete a course leaves surviving bacteria that become resistant.

A 2017 BMJ analysis by Martin Llewelyn and colleagues challenged this, arguing that:

• The evidence for the traditional advice is weak and largely historical.
• For most common infections, resistance is driven by the amount of antibiotic exposure, so longer courses generate more resistance, not less.
• Course lengths were often set arbitrarily, in round numbers, without trial evidence.
• Trials in pneumonia, urinary tract infection, cellulitis, and several other conditions have found shorter courses non-inferior to longer ones.

What that does and does not mean:

• It does not mean stop when you feel better. Feeling better does not mean the infection is cleared, and for some infections (tuberculosis above all, plus endocarditis, osteomyelitis, and deep abscesses) completing a long course is essential and stopping early is dangerous.
• It does mean the evidence base for course lengths is being revised, and many guidelines have shortened them.

Practical position: take the course you were prescribed, and if you are better well before it ends, ask your prescriber or pharmacist whether it can be stopped rather than deciding yourself. They will know which infection is which.

5. What antibiotics do not treat

Viruses. This is the single most important clinical fact in the chapter.

Green or yellow mucus does not indicate bacterial infection. The colour comes from myeloperoxidase in neutrophils, and it appears in ordinary viral illness. This belief is extraordinarily persistent and drives a great deal of unnecessary prescribing.

Delayed prescriptions are a useful compromise: the prescriber gives a prescription with instructions to fill it only if things do not improve within a set time. Trials find this substantially reduces antibiotic use without worsening outcomes.

6. Side effects

Common across the class:

• Gastrointestinal upset: nausea, diarrhoea, abdominal pain. Very common, especially with co-amoxiclav and macrolides.
• Thrush (oral and vaginal), from disrupting normal flora.
• Rash.

Clostridioides difficile colitis is the important one. Antibiotics wipe out the colonic flora that normally keep C. difficile in check; it proliferates and produces toxins, causing severe diarrhoea and potentially life-threatening colitis. Highest risk with clindamycin, fluoroquinolones, cephalosporins, and co-amoxiclav; risk is higher in hospital, in older people, and with PPI use. Faecal microbiota transplantation is highly effective for recurrent cases and is an approved therapy.

Class-specific effects worth knowing:

7. Penicillin allergy: the most consequential mislabelling in medicine

Around 10 percent of people report a penicillin allergy, and on formal testing over 90 percent of them are not allergic.

Why the label is usually wrong:

• A childhood rash during an illness, often caused by the virus rather than the drug.
• Ordinary side effects (nausea, diarrhoea) recorded as allergy.
• A true IgE allergy wanes over time: roughly 80 percent of genuinely allergic people lose it after ten years.

Why it matters, and this is not trivial. People labelled penicillin-allergic receive second-line antibiotics that are broader-spectrum, less effective for some infections, more toxic, and more expensive. Studies consistently find they have higher rates of MRSA and C. difficile, longer hospital stays, and worse surgical outcomes.

What to do: if you carry a penicillin allergy label, ask about de-labelling. Formal evaluation (history, sometimes skin testing, often a supervised oral challenge) is increasingly offered and is safe in low-risk patients. A large proportion of people are cleared.

A genuine allergy looks like: hives, swelling of face or throat, wheeze, or anaphylaxis, within an hour of a dose. Or a severe delayed reaction: widespread blistering rash, mucosal involvement, fever, organ involvement (SJS/TEN, DRESS). Those are absolute and permanent contraindications.

Cross-reactivity with cephalosporins was long taught as roughly 10 percent and is now understood to be far lower, around 1 to 2 percent and mostly limited to agents sharing a similar side chain.

8. Interactions

9. Practical guidance

• Do not ask for antibiotics for a cold, flu, or ordinary cough. They will not help, and they will cause side effects.
• Take them exactly as prescribed, at even intervals, and ask before stopping early.
• Never save leftovers or take someone else's. Different infections need different drugs, and self-prescribing drives resistance.
• Take doxycycline sitting or standing, with a full glass of water, and not at bedtime, because it causes oesophageal ulcers if it lodges.
• Separate tetracyclines and quinolones from dairy, antacids, and iron by 2 to 4 hours.
• No alcohol with metronidazole. The general "no alcohol with antibiotics" rule is a myth for most agents, and this one is real.
• Get your penicillin allergy label checked.
• Take probiotics if you like; the evidence for Saccharomyces boulardii and some Lactobacillus strains reducing antibiotic-associated diarrhoea is reasonable (Chapter 14).
• Vaccination reduces antibiotic use by preventing the infections that lead to it, which is an under-appreciated part of resistance strategy.

10. The bottom line

• Antibiotics work by exploiting differences between bacterial and human cells. They have no effect whatever on viruses, which cause most respiratory illness.
• Resistance already causes over a million deaths a year directly, driven by unnecessary prescribing, agricultural use, and poor infection control, and the development pipeline is economically broken.
• "Always finish the course" is being revised, because longer exposure generates more resistance and shorter courses are non-inferior for many infections. Ask your prescriber rather than deciding yourself, and never stop early for tuberculosis or deep infections.
• Fluoroquinolones now carry serious restrictions for tendon, nerve, and aortic effects. Metronidazole and alcohol produce a genuine violent reaction. Tetracyclines need water, upright posture, and separation from dairy.
• Over 90 percent of people labelled penicillin-allergic are not, and the label leads to worse antibiotics and worse outcomes. Ask to have it tested.

👉 Next: antivirals, antifungals, and antiparasitics.