Table 1.

Adverse effects of antibiotics: Items in bold text are included in FDA boxed warnings; risk is indicated using CIOMS categories (Table 2)22 where rates of adverse events were not available.

DRUGSALLERGIC REACTIONSSELF-LIMITING AND USUALLY TRANSIENT REACTIONSSERIOUS HARMS
β-lactams
Penicillins
  • Penicillin V potassium

  • Skin rash or hives

  • Itching2

  • Uncommon: true anaphylaxis hypersensitivity (0.01%)23

  • Common: allergy (9%)3

  • Uncommon: gastrointestinal effects—vomiting

  • Nausea, diarrhea, bloating, indigestion, abdominal pain, and loss of appetite (0.1% to 1% of patients)23

  • Fatal anaphylaxis (0.0015% to 0.002%)3

  • Very rare: drug-induced anemia, renal inflammation, and serum sickness2,23

  • Clostridium difficile infection24

  • Amoxicillin

  • Rash (5% to 10%)3

  • Anaphylaxis

  • Common: allergy3

  • Common: gastrointestinal effects25

  • Diarrhea (about 2%)25

  • Candidiasis (OR = 7.77, NNH = 27)25,26

  • Diaper rash (50%)27,28

  • Skin rash in patients with mononucleosis29,30

  • Anaphylaxis30

  • C difficile infection30,31

  • Hematuria25

  • Amoxicillin plus clavulanate

Same as for amoxicillin, plus the following:
  • Rash

  • Hives2

Same as for amoxicillin, plus the following:
  • Common: gastrointestinal effects

  • Headache32

  • Diarrhea (OR = 3.30, NNH = 10)25,33

  • Candidiasis (OR = 7.77, NNH = 20)25,26

Same as for amoxicillin, plus the following:
  • Rare: drug-induced mixed hepatitis32

  • C difficile infection (RR = 15.50)10,31

  • Cloxacillin

  • Very rare: rash

  • Very rare: hives

  • Very rare: anaphylaxis2

  • Gastrointestinal effects34

  • Neutropenia with eosinophilia34

Cephalosporins
  • Cephalexin (first generation), cefuroxime (second generation), and cefixime (third generation)35,36

  • Common: dermatologic effects (rash, 1% to 2%)2

  • Common: allergy (1.3%)2

  • Common: gastrointestinal effects seen in more cases with third generation vs first generation (2.5% for first; 4.5% to 15% for third)

  • Common: headaches, neurologic symptoms (dizziness, paresthesias) (1% to 2%)

  • Prolonged prothrombin time (4%)

  • Serum sickness–like syndrome (0.024% to 0.2%)2

  • Thrombophlebitis (1% to 2%)

  • Uncommon: hematologic toxicities (< 1%)

  • C difficile infection (third generation; RR = 15.33)10

Non–β-lactams
Fosfomycin37,38
  • Rash (1.4%)

  • Rare: angioedema

  • Diarrhea (10.4%)

  • Nausea (5.2%)

  • Headache (10.3%)

  • Vaginitis (7.6%)

  • Rhinitis (4.5%)

  • Back pain (3.0%)

  • Dysmenorrhea (2.6%)

  • Menstrual disorder (< 1%)

  • Pharyngitis (2.5%)

  • Dizziness (2.3%)

  • Abdominal pain (2.2%)

  • Pain (2.2%)

  • Dyspepsia (1.8%)

  • Lymphadenopathy (< 1%), aplastic anemia, asthma (exacerbation), cholestatic jaundice, hepatic necrosis, and toxic megacolon38

Lincosamides
  • Clindamycin

  • Very rare: allergy2

  • Very common: gastrointestinal effects—diarrhea most common (12% to 14%)39

  • Dermatologic effects (red skin, rash)

  • C difficile reaction (RR = 29.97)10,39

Linezolid40
  • Common: rash (2%) and hives

  • Very rare: allergic reactions

  • Nausea (6.2%), constipation (2.2%), vomiting, diarrhea (8.3%)

  • Fever (1.6%)

  • Dizziness (2.0%)

  • Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia; some irreversible. Monitor CBC weekly during treatment)

  • C difficile infection

  • Peripheral and optic neuropathy (some irreversible)

  • Hypertension, convulsions, lactic acidosis

  • Serotonin syndrome (weak MAO inhibitor) when taking MAO inhibitors or serotonergic drugs, especially SSRIs or SNRIs, but also other drugs

Macrolides
  • C difficile infection (RR = 5.8)10

  • Erythromycin, clarithromycin, and azithromycin

  • Rare: skin allergic reaction41,42

  • Gastrointestinal effects: stomach pain (NNT = 17), diarrhea (NNT = 19), nausea (NNT = 19), and vomiting (NNT = 45)41

  • Irregular heart rhythms (irreversible; especially with underlying QT prolongation)42

  • Hearing loss (irreversible)41

  • Rare: cardiovascular deaths (azithromycin)43

  • Drug-induced mixed hepatitis (idiosyncratic)32

  • C difficile infection: erythromycin (RR = 10.03), clarithromycin (RR = 7.49), and azithromycin (RR = 2.88)

Methenamine44
  • Rash and hives (2% to 5%)

  • Gastrointestinal effects (3.5%)

  • Urologic effects with large doses (eg, dysuria, changes in frequency, hematuria, albuminuria)

  • NA

Metronidazole45
  • Dermatologic effects (3%)

  • Gastrointestinal effects: mostly nausea (12%)

  • Metallic taste

  • Secondary Candida species infection

  • Carcinogenic in rats and mice

  • Seizures (with prolonged use; reversible)

  • Peripheral neuropathy (with prolonged use; irreversible)

  • Pancytopenia (reversible with discontinuation)

  • Reproductive system effects (dyspareunia, pelvic pressure, proctitis, vaginal dryness, decreased libido; reversible)

  • Urologic effects (eg, dysuria, polyuria, incontinence, darkened urine [1 in 100 000]; reversible)

  • Others: arthralgias, nasal congestion (reversible)

Nitrofurantoin
  • Dermatologic effects such as rash and DRESS2

  • Gastrointestinal effects such as vomiting, diarrhea, and stomach pain46

  • Nausea (8%), headache (6%), and flatulence (1.5%)46

  • Pulmonary toxicity: chronic pulmonary reactions; diffuse interstitial pneumonitis, pulmonary fibrosis, or both (irreversible)46

  • Drug-induced liver injury32

  • Aplastic anemia46

  • Peripheral neuropathy (irreversible)46

  • Hemolytic anemia46

Quinolones
  • Norfloxacin, ciprofloxacin, levofloxacin, and moxifloxacin

  • Rare: allergic reactions3

  • Flushing, itching, and angioedema2

  • Gastrointestinal effects47

  • Headaches12,47

  • Arthralgias and myalgias47

  • Neuropathies (numbness, tingling)47

  • Confusion47

  • Tendonitis and Achilles tendon rupture, especially in those >60 y or with current corticosteroid use12,47,48

  • Increased risk of abdominal aorta rupture12,49

  • Persistent peripheral neuropathy (irreversible)12,47

  • Dysglycemia, hypoglycemic coma47

  • Neurologic or psychiatric disturbances50

  • Exacerbation of myasthenia gravis

  • C difficile infection10: levofloxacin (RR = 1.93), ciprofloxacin (RR = 8.03), and moxifloxacin (RR = 1.2)

  • Rare: retinal detachment (4 per 10 000)51

  • Drug-induced mixed hepatitis52

  • Moxifloxacin: fulminant hepatitis and toxic epidermal necrolysis52

Sulfonamides and related drugs
  • Single-entity trimethoprim

  • Higher rate of allergic reaction effects with trimethoprim-sulfamethoxazole vs single-entity trimethoprim (3.9% to 5% vs < 2%)53,54

  • Nausea54

  • NA

  • Trimethoprim-sulfamethoxazole

  • Uncommon: severe allergic reactions that can lead to death53

  • Gastrointestinal effects (3%)

  • Hyperkalemia (about 3%)55

  • Hypersensitivity reactions (0.09%): includes anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness–like syndrome, lupuslike syndrome, pneumonitis, hepatitis, interstitial nephritis, vasculitis, and pancytopenia55

  • Rare: drug-induced mixed hepatitis32

  • C difficile infection (RR = 3.32)10,55

Tetracyclines
  • Might cause permanent discoloration of the teeth during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 y)56

  • Can cause fetal harm when administered to a pregnant woman56

  • C difficile-associated diarrhea56

  • Doxycycline

  • Rash (1%)57

  • Hives57

  • Cutaneous adverse reactions58

  • Gastrointestinal effects (up to 20%)57

  • Phototoxicity (3% for 100 mg/d, 20% for 150 mg/d, 42% for 200 mg/d, 7.5% overall incidence)58

  • Abnormal weight gain (23% in Q fever endocarditis)58

  • Esophagitis59

  • Esophageal ulceration59

  • Hypersensitivity reaction57

  • Serum sickness–like reaction57

  • C difficile infection (RR = 7.23)10

  • Minocycline

  • Rash2

  • Hives2

  • Gastrointestinal effects (25%)59

  • Neurologic effects (vertigo, ataxia, dizziness, weakness)57

  • Hypersensitivity reaction57

  • Serum sickness–like reaction57

  • Drug-induced lupus57

  • Pneumonitis57

  • Skin hyperpigmentation (irreversible)58

  • Tetracycline

  • Rash2

  • Hives2

  • Gastrointestinal effects59

  • Hypersensitivity reaction57

  • Serum sickness–like reaction57

  • C difficile (RR = 14.04)10

Vancomycin60
  • Rash

  • Nausea (17%), abdominal pain (15%), vomiting (9%), diarrhea (9%), flatulence (8%)

  • Fatigue (5%)

  • Back pain (6%)

  • Headache (7%)

  • Nephrotoxicity: reports of renal failure (5%), especially in those > 65 y (some irreversible)

  • Hypokalemia (13%)

  • Peripheral edema (6%)

Azoles
  • Fluconazole61

  • NA

  • Gastrointestinal effects (up to 7%)

  • Neurologic effects (up to 3%; eg, dizziness, headache, dysgeusia)

  • Severe or fatal hepatic injury (sometimes irreversible)

  • Anaphylaxis

  • Others: asthenia, seizures, metabolic disturbances (lipid levels), myalgia, insomnia, severe skin rashes, alopecia (more frequent in persons with HIV infection)

  • Itraconazole62

  • Dermatologic effects (up to 3%)

  • Gastrointestinal effects (up to 11%)

  • Systemic effects (up to 9%; eg, fatigue, fever, malaise)

  • Neurologic effects (up to 10%; eg, dizziness, headache, somnolence, abnormal dreams)

  • Decreased libido, impotence (1%)

  • Cardiac or renal effects (up to 2%; eg, hypertension, hypokalemia)

  • Elevated liver enzyme levels (4%)

  • Nasal, sinus, and respiratory symptoms (up to 9%)

  • Hepatotoxicity: fatal liver failure

  • Hypersensitivity reactions

  • Transient or permanent hearing loss (irreversible)

  • Others: cytopenias, neuropathies, visual disturbances, dysgeusia, pulmonary edema, severe skin rashes (eg, Stevens-Johnson syndrome, vasculitis), edema

  • Ketoconazole63

  • Rash

  • Nausea and vomiting (3%), pruritus (1.7%), abdominal pain (1.3%)

  • Hepatotoxicity 3.6% (95% CI 3.2 to 4.2)

  • CBC—complete blood count, CIOMS—Council for International Organizations of Medical Sciences, DRESS—drug rash with eosinophilia and systemic symptoms, FDA—Food and Drug Administration, MAO—monoamine oxidase, NA—not applicable, NNH—number needed to harm, NNT—number needed to treat, OR—odds ratio, RR—relative risk, SNRI—serotonin-norepinephrine reuptake inhibitor, SSRI—selective serotonin reuptake inhibitor.