SN4 SHORT NOTE 5M ★ High-yield

Describe vancomycin and the other drugs used against MRSA and resistant gram-positive organisms.

Pharmacology · 2nd Professional — Para-Clinical

Vancomycin

Vancomycin is a glycopeptide that binds the D-alanyl-D-alanine terminus of the peptidoglycan precursor, preventing its incorporation and cross-linking. It is bactericidal and acts only on gram-positive organisms.

Gram-negatives are intrinsically resistant, because the molecule is too large to cross the outer membrane
Not absorbed orally — which is exactly why oral vancomycin is used for clostridioides difficile colitis, where it acts in the gut lumen; systemic infection requires intravenous administration
Excreted unchanged by the kidney; the dose must be adjusted and levels monitored
Time-dependent killing — efficacy relates to trough level and total exposure

Adverse effect	Details
"red man" syndrome	Flushing, erythema and pruritus of the face, neck and upper trunk, with hypotension, during rapid infusion. It is direct histamine release, not an allergy — managed by slowing the infusion (over at least 60 minutes) and antihistamine pretreatment, and does not preclude further use
Nephrotoxicity	Especially with aminoglycosides or piperacillin-tazobactam
Ototoxicity	Uncommon with modern preparations
Neutropenia, thrombophlebitis	With prolonged use

CLINICAL PEARL

Red man syndrome is an infusion-rate problem, not an allergy, and the distinction matters. Labelling the patient allergic to vancomycin removes one of very few options for MRSA. The correct response is to slow the infusion and premedicate — not to abandon the drug.

Drugs for Mrsa and Resistant Gram-positives

Drug	Mechanism and features
Vancomycin	The standard agent; intravenous for systemic infection
Teicoplanin	Similar; longer half-life allowing once-daily dosing, and can be given intramuscularly
Linezolid	Oxazolidinone; binds the 50S subunit and prevents initiation. Excellent oral bioavailability (about 100%), so it allows oral treatment of serious infection. Causes reversible myelosuppression with prolonged use (over 2 weeks), peripheral and optic neuropathy, and is a weak MAO inhibitor — risking serotonin syndrome with SSRIs and a tyramine reaction
Daptomycin	Lipopeptide; disrupts the membrane. Inactivated BY pulmonary surfactant, so it cannot be used for pneumonia. Causes myopathy — creatine kinase must be monitored
Clindamycin, co-trimoxazole, doxycycline	Useful oral options for community-acquired MRSA skin infection
Ceftaroline	The fifth-generation cephalosporin with MRSA activity
Tigecycline	Broad, including MRSA and VRE; poor blood levels, so it is unsuitable for bacteraemia; associated with increased mortality in some trials
Mupirocin	Topical; nasal decolonisation of MRSA carriers

Clindamycin and Metronidazole for Anaerobes

Clindamycin — binds the 50S subunit; active against gram-positive cocci and anaerobes above the diaphragm; excellent bone and abscess penetration. It inhibits toxin production, which is why it is added in necrotising fasciitis and toxic shock syndrome. The classical cause of clostridioides difficile colitis
Metronidazole — a prodrug reduced to a cytotoxic intermediate only in anaerobic conditions, which is the basis of its selectivity; active against anaerobes below the diaphragm and against protozoa (amoebiasis, giardiasis, trichomoniasis). Causes a metallic taste, nausea, peripheral neuropathy with prolonged use, and a disulfiram-like reaction with alcohol

Applied Aspects

Monitor vancomycin trough levels and renal function; under-dosing is as much a problem as toxicity and leads to treatment failure and resistance
Oral vancomycin for C. Difficile, intravenous for everything else — the routes are not interchangeable, and giving intravenous vancomycin for colitis does not work
Linezolid allows oral treatment of serious resistant infection, which can avoid prolonged hospital stay — a real advantage where beds and intravenous access are limited
Never use daptomycin for pneumonia
Warn patients on metronidazole to avoid alcohol during and for 48 hours after the course
MRSA rates in Indian hospitals are high, and infection control — hand hygiene, screening and decolonisation — matters more than the availability of any particular drug

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