Common adverse effects of antibiotics
Aminoglycosides:
Nephrotoxicity, neuromuscular blockade (higher risk with (succinylcholine, curare-like drugs), ototoxicity (cochlear and vestibular)
Fluoroquinolones:
GI upset, headache, dizziness, mood changes, impaired glucose tolerance, retinopathy, bone and cartilage anomalies like 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 like 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 like 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.
- Efflux pumps: These are proteins located in the cytoplasmic membrane that pump out antibiotics so that they fail to achieve a critical concentration within the bacterial cell. They are multidrug transporters and pump out macrolides, tetracyclines and fluoroquinolones.
- Modification of drug target: Mutations in the bacterial genes change the target site of antibiotics making them ineffective. Examples are alterations in 30S and 50S ribosomes cause resistance to drugs like aminoglycosides, tetracyclines, chloramphenicol, streptogramins, macrolides etc. Changes in penicillin binding proteins causes reduced affinity of PBP to beta lactam antibiotics like E.faecium to ampicillin and S.pneumoniae to penicillin. Similarly, in S.aureus, mecA gene codes for 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.
- 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.
