# Cephalosporins

> Cephalosporins for MBBS Pharmacology — generations with examples, spectrum, CSF penetration and adverse effects for exams.

- Canonical URL: https://prepelephant.com/topics/mbbs/pharmacology/cephalosporins
- Exam / course: MBBS · Subject: Pharmacology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-02
- Last updated: 2026-10-02
- How to cite: "Cephalosporins", PrepElephant, https://prepelephant.com/topics/mbbs/pharmacology/cephalosporins

## Direct answer

Cephalosporins are beta-lactam antibiotics organised into five generations in which gram-positive cover gradually yields to gram-negative, anaerobic and antipseudomonal activity. Like penicillins they bind penicillin-binding proteins and kill by blocking cell-wall cross-linking. Third-generation agents such as ceftriaxone penetrate inflamed meninges and are mainstays for bacterial meningitis, typhoid and gonorrhoea, while ceftaroline, the fifth generation, uniquely covers MRSA.

## What you must remember

- First generation — cefazolin, cephalexin, cefadroxil, cephradine: strong staphylococcal and streptococcal cover with modest gram-negative activity; cefazolin remains standard surgical prophylaxis; largely renal excretion gives high urinary levels.
- Second generation — cefuroxime, cefaclor, cefprozil plus the anaerobe-active cefoxitin and cefotetan: better gram-negative cover; cefoxitin covers Bacteroides fragilis, suiting intra-abdominal and pelvic infections.
- Third generation — ceftriaxone, cefotaxime, ceftazidime, cefoperazone, oral cefixime and cefpodoxime: expanded gram-negative spectrum, beta-lactamase stability and good cerebrospinal fluid entry; ceftazidime adds Pseudomonas.
- Fourth generation — cefepime and cefpirome: zwitterionic structure improves outer-membrane penetration, retaining gram-positive activity plus antipseudomonal cover, useful for febrile neutropenia.
- Fifth generation — ceftaroline: binds PBP2a of methicillin-resistant Staphylococcus aureus and also covers gram-negatives, though not Pseudomonas.
- Key pharmacology: ceftriaxone is given once daily, excreted mainly in bile so renal adjustment is rarely needed, and must not be mixed with calcium-containing infusions in neonates because of precipitate formation; cefoperazone carries a methylthiotetrazole side chain causing hypoprothrombinaemia and disulfiram-like reactions with alcohol.
- Adverse effects: hypersensitivity similar to penicillins with low true cross-reactivity, pain on intramuscular injection, phlebitis and, rarely, positive Coombs test; ceftriaxone can cause biliary sludging in children.

## Common confusion

The trap is memorising generations as a simple rising gram-negative, falling gram-positive ladder and forgetting the two named exceptions — ceftazidime, a third-generation drug with antipseudomonal activity, and ceftaroline, the only cephalosporin active against MRSA. Candidates also overstate penicillin-cephalosporin cross-reactivity; genuine allergic cross-reaction is uncommon, and the old figure of ten per cent is now considered a substantial overestimate.

## Exam-focused takeaway

Theory answers should tabulate generations orally in terms of spectrum with at least two examples each, then mention mechanism and toxicity. Viva examiners ask why ceftriaxone suits meningitis and out-patient parenteral therapy and which cephalosporin treats MRSA. MCQs test cefazolin for surgical prophylaxis, cefoxitin for anaerobes, ceftazidime for Pseudomonas, ceftriaxone for typhoid and gonorrhoea, and the disulfiram-like reaction of cefoperazone.

## Frequently asked questions

### Which cephalosporin is used for surgical prophylaxis?

Cefazolin, first generation, given shortly before incision for clean and clean-contaminated surgery because of its staphylococcal cover and suitable pharmacokinetics.

### Which cephalosporins penetrate the cerebrospinal fluid?

Third-generation agents, particularly ceftriaxone and cefotaxime, achieve reliable CSF levels when meninges are inflamed and are first-line for pneumococcal and meningococcal meningitis.

### What is special about ceftazidime?

It is a third-generation cephalosporin with clinically useful Pseudomonas aeruginosa activity, distinguishing it from ceftriaxone and cefotaxime.

### Can a cephalosporin be given in penicillin allergy?

Generally yes for non-anaphylactic histories, as true cross-reactivity is low; an alternative class is preferred where the reaction was severe or recent.

### Why is ceftriaxone avoided with calcium infusions in neonates?

Ceftriaxone-calcium precipitates can deposit in lungs and kidneys, so concurrent intravenous calcium is contraindicated in this age group.