Cephalosporins and carbapenems, Glycopeptide antibiotics, Metronidazole, Quinolones

When are oral cephalosporins typically used?

As 2nd or 3rd-line options for UTIs, pneumonia, and other RTIs.

When are parenteral cephalosporins and carbapenems used?

For very severe or complicated infections or those caused by antibiotic-resistant organisms.

How does cephalosporin activity change across generations?

Increasing gram-ve activity (including Pseudomonas) with variable Gram-positive coverage.

Why are cephalosporins and carbapenems more β-lactamase resistant than penicillins?

Structural modifications: dihydrothiazine ring (cephalosporins) and hydroxyethyl side chain (carbapenems).

What class of antibiotics are cephalosporins and carbapenems?

β-lactam antibiotics.

Are cephalosporins and carbapenems bactericidal or bacteriostatic?

Bactericidal.

How do cephalosporins and carbapenems kill bacteria?

By inhibiting enzymes that cross-link peptidoglycans in the bacterial cell wall, causing lysis.

What serious GI complication can result from β-lactam antibiotics ?

C. difficile–associated colitis.

What rare neurological adverse effect may occur with parenteral β-lactam therapy?

Seizures.

In which patients should cephalosporins and carbapenems be used cautiously?

Those at risk of C. difficile infection, especially older or hospitalised patients.

What is the main contraindication to cephalosporins and carbapenems?

True β-lactam allergy, especially immediate-type hypersensitivity.

When is dose adjustment of β-lactams required?

In renal impairment.

How do cephalosporins and carbapenems interact with warfarin?

They enhance anticoagulant effect by reducing vitamin K-producing gut flora.

Which antiepileptic drug is significantly affected by carbapenems?

Valproate (reduced plasma levels and efficacy).

Give an example of an oral cephalosporin.

Cefalexin.

How are carbapenems administered?

Intravenously only (e.g. meropenem).

Why is ceftriaxone useful for ambulatory IV treatment?

Broad coverage and long half-life allowing once-daily dosing.

When are glycopeptide antibiotics used?

Severe gram +ve infections, especially when penicillins cannot be used due to allergy or resistance (e.g. MRSA)

Which infections are commonly treated with glycopeptides?

Complicated skin and soft tissue infections, bone and joint infections, infective endocarditis.

What is vancomycin first-line treatment for?

C. difficile colitis.

Are glycopeptides active against gram -ve bacteria?

No.

Are glycopeptide antibiotics bactericidal or bacteriostatic?

Bactericidal.

How do glycopeptide antibiotics inhibit bacterial growth?

By inhibiting peptidoglycan synthesis and cross-linking in the cell wall.

Why are glycopeptides ineffective against Gram-negative bacteria?

Gram-negative bacteria have a lipopolysaccharide cell wall structure.

How can bacteria develop resistance to glycopeptides?

By modifying cell wall structure to prevent antibiotic binding.

What infusion-related adverse effect is common with vancomycin?

Pain and thrombophlebitis.

What is vancomycin flushing syndrome ("red man syndrome")?

Histamine-mediated flushing and pruritic erythematous rash due to rapid infusion.

Is red man syndrome an allergic reaction?

No, it is non-immune histamine release.

What are the main dose-related toxicities of glycopeptides?

Nephrotoxicity and ototoxicity.

Name rare idiosyncratic adverse effects of glycopeptides.

Neutropenia, thrombocytopenia, and severe cutaneous adverse reactions.

Which patients are at higher risk of glycopeptide toxicity?

Those with renal impairment, neonates, older adults, and people with hearing impairment.

Is there cross-reactivity between vancomycin and teicoplanin?

Yes, cross-sensitivity can occur.

Which drugs increase nephrotoxicity or ototoxicity with glycopeptides?

Loop diuretics, aminoglycosides, NSAIDs, and ciclosporin.

How are glycopeptides administered in systemic infections?

Parenterally (not absorbed orally).

How is vancomycin given for C. difficile colitis?

Orally (e.g. 125 mg every 6 hours for 10 days) as the intended site of action is the gut itself.

Why should vancomycin not be given IM?

Risk of muscle necrosis.

How fast should vancomycin be infused IV?

No faster than 10 mg/min and over at least 60 minutes.

What vancomycin plasma concentration is typically targeted?

Trough level of ~10–20 mg/L (depending on local guidance).

What safety parameters should be monitored glycopeptide therapy?

Renal function, hearing changes, and blood counts (for prolonged courses).

What types of organisms does Metronidazole mainly treat?

Anaerobic bacteria and protozoa.

Which oropharyngeal infections commonly require metronidazole?

Dental infections, infected human/animal bites, and aspiration pneumonia.

How is metronidazole used in H. pylori eradication?

In combination with a PPI and either amoxicillin or clarithromycin.

Which protozoal infections are treated with metronidazole?

Trichomoniasis vaginal infection, amoebic dysentery, and giardiasis.

When is metronidazole used for C. difficile infection?

When IV treatment is required (otherwise vancomycin or fidaxomicin is preferred).

Is metronidazole bactericidal or bacteriostatic?

Bactericidal.

How does metronidazole enter bacterial cells?

By passive diffusion.

What happens to metronidazole inside anaerobic bacteria? How does iy kill bacteria?

It is reduced to a nitroso free radical- damages DNA, inhibiting synthesis and causing cell death.

Why are aerobic bacteria resistant to metronidazole?

They cannot reduce it to its active free radical form.

What are mechanisms of metronidazole resistance?

Reduced drug uptake and reduced nitroso free radical generation.

What neurological adverse effects may occur with high-dose or prolonged use of metronidazole?

Peripheral neuropathy, optic neuropathy, seizures, and encephalopathy.

Why should metronidazole dose be reduced in severe liver disease?

It is metabolised by hepatic CYP enzymes.

Why must alcohol be avoided with metronidazole?

Metronidazole inhibits the enzyme acetaldehyde dehydrogenase (clears the alcohol metabolite from the body).

Combination causes an unpleasant reaction including flushing, headache, nausea, and vomiting.

How does metronidazole interact with warfarin?

Inhibits metabolism → increased bleeding risk.

What is the interaction between metronidazole and phenytoin?

Increased phenytoin toxicity; phenytoin can also reduce metronidazole levels.

How do CYP inducers affect metronidazole?

Increased metabolism resulting in reduced plasma concentrations and impaired antimicrobial efficacy.

What happens when metronidazole is combined with lithium?

Increased risk of lithium toxicity.

What monitoring is required for metronidazole treatment >10 days?

FBC and liver enzymes.

Ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin are all examples of...?

Quinolones

When should systemic quinolones generally be used?

Reserved for severe bacterial infections when other options are limited.

What types of infections are quinolones used in?

1) UTIs (gram -ve).

2) Severe gastroenteritis (due to Shigella, campylobacter).

3) LRTIs incl. infective exacerbation of COPD and pneumonia

What is the general antimicrobial spectrum of quinolones?

Broad spectrum, particularly strong against gram -ve bacteria.

Which oral quinolone has activity against P. aeruginosa?

Ciprofloxacin.

Which quinolones have enhanced gram +ve activity?

Levofloxacin and moxifloxacin.

Which quinolones are preferred for LRTIs?

Levofloxacin and moxifloxacin.

MOA of quinolones?

By inhibiting DNA synthesis (bactericidal effect).

What are key mechanisms of quinolone resistance?

Reduced permeability, increased efflux, and mutations in target enzymes.

How does quinolone resistance spread rapidly between bacteria?

Via plasmid-mediated horizontal gene transfer.

Which antibiotics are most commonly associated with C. difficile colitis?

Quinolones and cephalosporins.

What neurological adverse effects can quinolones cause?

Seizures and peripheral neuropathy.

What musculoskeletal adverse effects are associated with quinolones?

Tendon damage and tendon rupture.

What cardiovascular adverse effects are linked to quinolones?

QT prolongation, valvular regurgitation, and aortic aneurysm/dissection.

Why are quinolone adverse effects particularly concerning?

They may be disabling, long-lasting, or irreversible.

In which groups should quinolones be used with caution?

Pregnancy, children/young adults, adults >60, renal impairment.

Why are quinolones cautioned in children and young adults?

Risk of arthropathy (joint disease).

Why are quinolones cautioned in adults over 60?

Increased risk of tendon damage.

In which comorbidities should quinolones be used cautiously?

Neurological and cardiovascular disease.

Which substances reduce quinolone absorption?

Divalent cations (calcium, iron, antacids).

Which quinolone inhibits CYP enzymes and increases theophylline toxicity?

Ciprofloxacin.

Which drugs increase seizure risk when combined with quinolones?

NSAIDs.

Which drug increases tendon rupture risk when combined with quinolones?

Prednisolone.

Which drug classes increase QT prolongation risk with quinolones?

Antiarrhythmics, antipsychotics, macrolides, SSRIs, quinine.

Why is oral quinolone therapy usually preferred over IV?

Excellent oral absorption achieves high plasma concentrations.

How should oral quinolones be taken with respect to calcium and iron?

Separated by at least 2 hours.

Why should ciprofloxacin not be taken with dairy products?

Calcium reduces absorption and efficacy.

In what non-systemic forms can quinolones be prescribed?

Eye drops, ear drops, and nebulised inhalation.

Which antibiotics are frequently combined to cover anaerobes and gram -ve aerobes, respectively, providing comprehensive coverage during procedures involving gut flora?

Metronidazole and gentamicin.

Which antibiotic does NOT need to be renally dose adjusted if CrCl is 25 mL/min in an adult?

Ceftriaxone: advises maximum 2 g daily if CrCl < 10 mL/min.

What is the distinguishing feature of meropenem compared to ceftriaxone?

Broad-spectrum activity including anaerobic bacteria

Which antibiotics are used in the treatment of severe hospital-acquired pneumonia?

Ceftriaxone and meropenem.