Adverse effects of antibiotics

Common adverse effects of antibiotics

Aminoglycosides: Nephrotoxicity, neuromuscular blockade (higher risk with succinylcholine and curare-like drugs), ototoxicity (cochlear and vestibular)

Fluoroquinolones: GI upset, headache, dizziness, mood changes, impaired glucose tolerance, retinopathy, bone and cartilage anomalies (e.g., Achilles tendon rupture), prolongation of QTc, pseudomembranous colitis, photosensitivity, exacerbates myasthenia gravis

Chloramphenicol: Aplastic anemia, “gray baby” syndrome, optic and peripheral neuritis

Macrolides: Increased GIT motility, diarrhea, hypersensitivity reactions, erythromycin shows QTc prolongation, cholestatic jaundice, tinnitus and deafness; clarithromycin and erythromycin are potent inhibitors of cyt P450

Telithromycin: Exacerbates myasthenia gravis (hence contraindicated), liver failure, hepatitis, prolongation of QTc, inhibits CYP3A4

Colistin and Polymyxin B: Nephrotoxicity (ATN, hematuria, casts), neurotoxicity, paresthesias, vertigo, ataxia, visual defects, neuromuscular blockade, hypersensitivity, chest tightness, bronchoconstriction

Tetracyclines: Yellowing of teeth, vestibular problems (e.g., dizziness, vertigo), pseudomembranous colitis, photosensitivity, fatty liver, risk of esophageal ulcerations; increase the effect of oral anticoagulants

Tigecycline: GI upset, diarrhea, hepatotoxicity, photosensitivity

Sulfonamides: Stevens-Johnson syndrome, crystalluria, kernicterus

Trimethoprim plus sulfamethoxazole: All adverse effects of sulfonamides plus folate deficiency, hyperkalemia, renal insufficiency; increases levels of warfarin, phenytoin, rifampin, and methotrexate; causes hypoglycemia when combined with sulfonylureas

Rifampin: Orange-red discoloration of skin and body fluids, jaundice, monitor LFTs

Metronidazole: Neuropathy, GI upset, headache, seizures, disulfiram-like effect with alcohol, dark urine, reduce dose in liver disease, increases anticoagulant effect of warfarin

Linezolid: Increased serum lactic acid, myelosuppression, neuropathy, serotonin syndrome, optic neuritis

Lincosamides: Neuromuscular blockade, C.difficile colitis

Isoniazid: Hepatitis, jaundice

Clindamycin: Pseudomembranous colitis, esophagitis and esophageal ulceration, hypersensitivity

Daptomycin: Myopathy, increased creatine kinase, eosinophilic pneumonia

Carbapenems: GI upset, seizures (imipenem), adjust dose of ertapenem and meropenem in renal insufficiency

Cephalosporins: Pseudomembranous colitis, hypersensitivity reactions, leukopenia, thrombocytopenia, Coombs positive hemolytic anemia; cefotetan shows disulfiram-like effect with ethanol and elevates PT, INR and PTT

*Penicillins: Hypersensitivity reactions, rashes, anaphylaxis, urticaria, angioedema, serum sickness, exfoliative dermatitis, seizures, nephritis, pseudomembranous colitis, Coombs positive hemolytic anemia, leukopenia, thrombocytopenia, GI upset; ticarcillin causes bleeding tendency in patients with renal failure

Monobactam (aztreonam): Phlebitis, rash, elevated LFTs, adjust dose in renal failure

Quinupristin/Dalfopristin: Phlebitis, arthralgia, myalgia, hyperbilirubinemia, decrease dose in liver disease

Vancomycin: Hypersensitivity reactions (e.g., rash, fever, neutropenia), phlebitis, “red man” syndrome due to histamine release, monitor renal function

*Patients who are allergic to penicillin may show 2-10% cross reactivity to cephalosporins. Cross reactions may also rarely occur to monobactams, carbapenems and penicillamine.

Following are the mechanisms employed by bacteria to acquire resistance to antibiotics.

1. Efflux pumps: These are proteins located in the cytoplasmic membrane that pump out antibiotics, so they fail to achieve a critical concentration within the bacterial cell. They are multidrug transporters and pump out macrolides, tetracyclines, and fluoroquinolones.

2. Modification of drug target: Mutations in bacterial genes change the target site of antibiotics, making them ineffective. Examples include:

   • Alterations in 30S and 50S ribosomes cause resistance to drugs like aminoglycosides, tetracyclines, chloramphenicol, streptogramins, macrolides, etc.
   • Changes in penicillin binding proteins cause reduced affinity of PBP to beta lactam antibiotics (e.g., E.faecium to ampicillin and S.pneumoniae to penicillin).
   • In S.aureus, the mecA gene codes for an altered PBP called PBP2a that confers resistance to beta lactams.
   • Mutations in DNA gyrase and topoisomerase IV lead to fluoroquinolone resistance.
   • Alteration of D-alanyl-D-alanine to D-alanyl-D-lactate confers resistance to vancomycin and teicoplanin in enterococci, which is coded by van A gene.

3. Inactivation of antibiotic: Bacterial enzymes that inactivate antibiotics include beta lactamases (inactivate all beta lactams like penicillins, cephalosporins, monobactams and carbapenems); aminoglycoside modifying enzymes inactivate aminoglycosides, while chloramphenicol acetyl transferases inactivate chloramphenicol.