Appendix- 1: AWaRe Classification- WHO (updated on 2021)

Access Group

This group includes antibiotics that have activity against a wide range of commonly encountered susceptible pathogens while also showing lower resistance potential than antibiotics in the other groups. Selected Access group antibiotics are recommended as essential first or second choice empiric treatment options for infectious syndromes reviewed by the EML Expert Committee and are listed as individual medicines on the Model Lists of Essential Medicines to improve access and promote appropriate use.

Antibiotic	Class	Adverse reactions
Amikacin	Aminoglycosides	Ototoxicity (Neurotoxicity – vestibular and permanent bilateral auditory ototoxicity), Nephrotoxicity, Neuromuscular blockade
Amoxicillin	Penicillins	Antibiotic-associated diarrhea (Non-Clostridioides difficile) diarrhea, nausea, vomiting, Clostridioides difficile infection (CDI) – CDAD and colitis, hypersensitivity reactions (immediate and delayed)- skin rash/anaphylaxis, SJS, TEN, DRESS
Amoxicillin-clavulanate	Beta-lactam/beta-lactamase inhibitor	Antibiotic-associated diarrhea (Non-Clostridioides difficile) diarrhea, nausea, vomiting, Clostridioides difficile infection (CDI) – CDAD and colitis, hypersensitivity reactions (immediate and delayed)- skin rash/anaphylaxis, SJS, TEN, DRESS, DILI (Cholestatic hepatitis)
Ampicillin	Penicillins	Hypersensitivity, brain disease (penicillin induced),GI side effects, agranulocytosis
Ampicillin-sulbactam	Beta-lactam/beta-lactamase inhibitor	Pain at injection site, phlebitis, skin rash, diarrhea
Benzathine penicillin G	Penicillins	NOT FOR IV or DO NOT mix with other IV solutions, Allergy, CDAD, increased risk of seizures, Nicolau syndrome (tissue necrosis at injection site)
Benzylpenicillin	Penicillins	Thrombophlebitis, hypersensitivity , CDAD, neutropenia, Jarisch-Herxheimer reaction, increased risk of seizure in renal impairment, electrolyte imbalance in high doses
Cefadroxil	First-generation-cephalosporins	Diarrhea, hypersensitivity, CDAD
Cephalexin	First-generation-cephalosporins	CDI, hemolytic anemia, hypersensitivity reactions, dose adjustment in severe renal impairment
Cefazolin	First-generation-cephalosporins	Hypersensitivity reactions, CDI, hypotension, GI side effects, vulvovaginal pruritus, oral candidiasis
Cefradine	First-generation-cephalosporins	Diarrhea, flu like symptoms, hypersensitivity reactions
Chloramphenicol	Amphenicols	Blood dyscrasias, Gray baby syndrome, confusion, delirium, rash, diarrhea, hypersensitivity reactions, optic neuritis, caution in G6PD deficient
Clindamycin	Lincosamides	CDAD, colitis, AAD, hypersensitivity reactions, hypotension, renal impairment, thrombophlebitis (IV)
Cloxacillin	Penicillins	GI side effects, hypersensitivity reactions, hypotension, thrombophlebitis, melanoglossia, agranulocytosis
Doxycycline	Tetracyclines	Bone growth suppression, esophageal injury (PO), skin photosensitivity, skin hyperpigmentation, dental discoloration, diarrhea, hypersensitivity
Flucloxacillin	Penicillins	Nausea, diarrhea, hypersensitivity reaction, thrombophlebitis
Gentamicin	Aminoglycosides	Nephrotoxic, neurotoxicity/otoxicity, phlebitis, neuromuscular blockade, edema, CDAD, dyselectrolytemia
Metronidazole	Imidazoles	Carcinogenic in mice and rats, CNS (peripheral neuropathy, aseptic meningitis, ataxia), disulfiram like reaction, nausea, vaginitis, headache, genital pruritus, metallic taste
Nitrofurantoin	Nitrofuran-derivatives	Nausea, vomiting, CDI, DILI, peripheral neuropathy, pulmonary toxicity, headache, dizziness, loss of appetite
Ornidazole	Imidazoles	Headache, nausea, vomiting, dizziness, poor coordination, taste disturbances, skin reactions
Phenoxymethylpenicillin	Penicillins	Melanoglossia, diarrhea, nausea, oral candidiasis, vomiting, hypersensitivity
Procaine-Benzylpenicillin	Penicillins	Hypersensitivity, CNS toxicity, fibrosis/atrophy at injection site, methemoglobinemia, procaine neuropsychiatric reactions
Secnidazole	Imidazoles	Carcinogenicity in mice, nausea, dysgeusia, vulvovaginal candidiasis
Sulfadiazine	Sulfonamides	Blood dyscrasias, dermatologic reactions, hepatic necrosis, ‘sulfa’ allergy, superinfection
Tetracycline	Tetracyclines	Increased BUN, intracranial hypertension, photosensitivity, superinfection, rash, epigastric discomfort, pericarditis, HSP, anogenital lesion, hepatotoxicity, exacerbation of SLE, nail discoloration, enamel hypoplasia and discoloration of permanent tooth in infants and young children, aplastic anemia, abnormal bone growth, conjunctival discoloration
Tinidazole	Imidazoles	Carcinogenicity likely, seizures and peripheral neuropathy, menorrhagia, GI side effects, dysuria, pelvic pain, vulvovaginal disease, dysgeusia, fatigue, hairy tongue, thrombocytopenia, bronchospasm
Trimethoprim	Trimethoprim-derivatives	Rash, diarrhea, vomiting, photo toxicity, pruritus, hyperkalemia, hyponatremia, transaminitis, methemoglobinemia, cytopenia, eosinophilia, megaloblastic anemia, glossitis, fever, hypersensitivity reactions
Trimethoprim-sulfamethoxazole	Sulfonamide-Trimethoprim-combinations	CDI, DILI, blood dyscrasias, hyperkalemia, hypoglycemia, hyponatremia, hypersensitivity reactions, kernicterus, GI side effects, toxic nephrosis (oliguria/anuria), tinnitus, fever, pulmonary injury

Watch Group

Antibiotic	Class	Adverse reactions
Azithromycin	Macrolides	QT prolongation, CDI, DILI, hypersensitivity reactions, otoxicity, diarrhea, nausea, abdominal pain, vaginitis, pain at injection site (in IV), caution in Myasthenia gravis
Cefepime	Fourth-generation cephalosporins	CDI, hypersensitivity, neurotoxicity, positive DCT (without hemolysis), GI side effects, hypophosphatemia, phlebitis, eosinophilia, transaminitis
Cefixime	Third-generation cephalosporins	Diarrhea, dyspepsia, Immune-mediated hemolytic anemia, dermatologic reactions, hypersensitivity, superinfection
Cefoperazone	Third-generation cephalosporins	GI side effects, hypersensitivity, neutropenia, transaminitis, transient rise in creatinine, seizure in renal impairment, superinfection
Cefotaxime	Third-generation cephalosporins	Arrhythmia, granulocytopenia, allergy, superinfection, GI side effects, eosinophilia, phlebitis, fever
Cefpodoxime	Third-generation cephalosporins	Diaper rash, diarrhea, nausea, abdominal pain, vaginitis, allergy, headache
Ceftazidime	Third-generation cephalosporins	Elevated INR, hemolytic anemia, hypersensitivity, superinfection, increased LDH/GGT, eosinophilia, positive DCT, transaminitis, phlebitis, blood dyscrasias, seizure, increased serum creatinine
Ceftriaxone	Third-generation cephalosporins	Ceftriaxone-calcium precipitation, CDI, hemolytic anemia, hypersensitivity reactions, kernicterus (displaces bilirubin from albumin- Do not use in hyperbilirubinemic neonates), local skin tightness in IM, flushing, diaphoresis, pruritus, GI side effects, vaginitis, casts in urine, blood dyscrasias, transaminitis, candidiasis, phlebitis, chills, headache, dizziness, increased serum creatinine
Cefuroxime	Second-generation cephalosporins	Elevated INR, hypersensitivity, superinfection, diarrhea (duration dependent), phlebitis, diaper rash, nausea, vomiting, unpleasant taste, vaginitis, decreased hemoglobin, eosinophilia, transaminitis, Jarisch-Herxheimer reaction
Ciprofloxacin	Fluoroquinolones	Tendinopathy and tendon rupture, peripheral neuropathy, CNS effects, exacerbation of myasthenia gravis, aortic aneurysm/aortic dissection, arthropathy/arthralgia, CDI, dysglycemia, hepatotoxicity, hypersensitivity reactions, skin photosensitivity, QT prolongation, GI side effects, fever
Clarithromycin	Macrolides	Arrhythmia, QT prolongation, hepatitis, hypersensitivity, superinfection, headache, insomnia, dysgeusia, GI side effects, increased BUN
Ertapenem	Carbapenems	Hypersensitivity reactions, CNS effects, superinfection, diarrhea, arrhythmias, phlebitis, dermatitis, dyselectrolytemia, GI side effects, hematuria, proteinuria, blood dyscrasias, transaminitis, arthralgia, bronchoconstriction, fever
Erythromycin	Macrolides	Arrhythmia, QT prolongation, superinfection, seizure, skin rash, hypersensitivity, GI side effects, hearing loss, interstitial nephritis
Imipenem- cilastatin	Carbapenems	Hematological abnormalities, transaminitis, proteinuria and seizures in children, phlebitis, GI side effects, CNS effects, hypersensitivity
Levofloxacin	Fluoroquinolones	Tendinopathy and tendon rupture, peripheral neuropathy, CNS effects, exacerbation of myasthenia gravis, aortic aneurysm/aortic dissection, arthropathy/arthralgia, CDI, dysglycemia, hepatotoxicity, hypersensitivity reactions, skin photosensitivity, QT prolongation, GI side effects, cytopenia
Meropenem	Carbapenems	CNS toxicity, CDI, hypersensitivity reactions, peripheral vascular disease, pruritus, hypoglycemia, GI side effects, anemia, hypervolemia, jaundice, asthenia, backache, pharyngitis, phlebitis
Moxifloxacin	Fluoroquinolones	Tendinopathy and tendon rupture, peripheral neuropathy, CNS effects, exacerbation of myasthenia gravis, aortic aneurysm/aortic dissection, arthropathy/arthralgia, CDI, dysglycemia, hepatotoxicity, hypersensitivity reactions, skin photosensitivity, QT prolongation, GI side effects, fever
Ofloxacin	Fluoroquinolones	Tendinopathy and tendon rupture, peripheral neuropathy, CNS effects, exacerbation of myasthenia gravis, aortic aneurysm/aortic dissection, arthropathy/arthralgia, CDI, dysglycemia, hepatotoxicity, hypersensitivity reactions, skin photosensitivity, QT prolongation, GI side effects, fever
Piperacillin-tazobactam	Beta-lactam/beta-lactamase-inhibitor	CDI, DITP, myelosuppression, hypersensitivity reactions, nephrotoxicity (more if used with vancomycin), neurotoxicity, diarrhea, phlebitis, pruritus, rash, GI side effects, headache, insomnia, myalgia, fever, positive DCT, consider sodium content in patients requiring sodium restriction
Rifampicin	Rifamycins	Hepatotoxicity, CDI, blood dyscrasias, disorder of hemostasis, hypersensitivity reactions, pulmonary toxicity, facial edema, flushing, adrenocortical insufficiency, GI side effects, hematuria, ataxia, psychosis, myasthenia, myopathy, paradoxical reaction, fever, staining of tooth
Rifaximin	Rifamycins	Peripheral edema, nausea, ascites, dizziness, fatigue, pruritus, skin rash, abdominal pain, anemia, depression, headache, arthralgia, muscle spasm, myalgia, dyspnea, nasopharyngitis, fever
Roxithromycin	Macrolides	GI side effects, hypersensitivity reactions, abdominal pain, vaginitis, headache, anorexia
Spiramycin	Macrolides	Arrhythmias, paresthesia, pruritus, rash, urticarial, GI side effects, hepatotoxicity, hypersensitivity, HSP
Streptomycin	Aminoglycosides	Neuromuscular blockade and respiratory paralysis, neurotoxicity, nephrotoxicity, hypotension, fever, dermatitis, eosinophilia, cytopenia, arthralgia, amblyopia, hypersensitivity reactions
Teicoplanin	Glycopeptides	Phlebitis, fever, hypersensitivity reactions, dizziness, headache, diarrhea, vomiting, nausea, otoxicity
Vancomycin (IV)	Glycopeptides	Hypersensitivity (Anaphylaxis, delayed), CDI, Drug induced ITP (DITP), Nephrotoxicity, cytopenia, otoxoxicity, Vancomycin infusion reaction, myalgia, HSP

Reserve Group

This group includes antibiotics and antibiotic classes that should be reserved for treatment of confirmed or suspected infections due to multi-drug-resistant organisms. Reserve group antibiotics should be treated as “last resort” options.

Antibiotic	Class	Adverse reactions
Colistin (IV)	Polymyxins	Nephrotoxicity, neurotoxicity, hypersensitivity, paresthesia, seizures, respiratory distress, fever, superinfection
Daptomycin	Lipopeptides	CDI, Eosinophilic pneumonia, hypersensitivity reactions, myopathy, rhabdomyolysis, peripheral neuropathy, vomiting, chest pain, edema, hypertension, diaphoresis, pruritus, vomiting, diarrhea, pharyngolaryngeal pain, fever, headache, insomnia
Linezolid	Oxazolidinones	CDI, lactic acidosis, myelosuppression, neuropathy (peripheral and optic), serotonin syndrome, diarrhea, leukopenia, increase lipase, GI side effects, transaminitis, dizziness, DO NOT USE within 2 weeks of MAO inhibitors use
Minocycline (IV)	Tetracyclines	Pruritus, dizziness, fatigue, skin photosensitivity, rash, tooth discoloration, enamel hypoplasia, autoimmune syndromes, benign intracranial hypertension, hepatotoxicity
Polymyxin-B	Polymyxins	Use only in hospitalized, nephrotoxicity, neurotoxicity, Neuromuscular blockade, Safety not established in pregnancy, thrombophlebitis, CDAD, facial flushing, hypocalcemia, hypochloremia, hypokalemia, hyponatremia
Tigecycline	Glycylcyclines	Increased risk of mortality, Use with caution, Diarrhea, Nausea, vomiting, phlebitis, anemia, transaminitis, hypersensitivity reaction, headache, dizziness