Antibiotic adverse effects

Drugs causing decreased renal acid excretion - hypokalemic hyperchloremic metabolic acidosis

• Ketoconazole (interfere with aldosterone synthesis)
• Amphotericin B (binds to sterol in mammalian cell membranes forming intramembranous pores which increase permeability and back diffusion of H +)

Drugs causing decreased renal acid excretion - hyperkalemia and metabolic acidosis

• Pentamidine
• Trimethoprim

Drugs causing Fanconi syndrome and proximal renal tubular acidosis

• Anti-viral/HIV drugs (e.g., lamivudine, stavudine and tenofovir)
• Outdated tetracycline
• Aminoglycoside (accumulation in proximal tubule would lead to nephrotoxicity with an unclear mechanism; however, the incidence decreased recently due to a better monitoring strategy)

Drugs causing increased endogenous acid production - Lactic acidosis

• Nucleotide reverse transcriptase inhibitor (NRTI)-based regimens: didanosine, stavudine, lamivudine, zidovudine, and abacavir.
• Linezolid
• Isoniazid

Drugs causing external base loss - Renal loss of bicarbonate

• Sulphonamide class of drugs (topical use in burns).

Ref: Amy Quynh Trang Pham et al, Drug-Induced Metabolic Acidosis, Version 1. F1000Res. 2015; 4: F1000 Faculty Rev-1460.

Antiretrovirals - NRTI
Zalcitabine (Highest risk), Didanosine, Stavudine, Lamivudine (rare)

Low CD4 count, HIV neuropathy, Alcohol are risk factors
Causes distal axonal-type sensory neuropathy
Due to the inhibition of γ-DNA polymerase leading to mitochondrial dysfunction.

Antitubercular - Isoniazid

Risk factors - alcohol, elderly, pregnancy, diabetes, HIV
Causes - Sensory peripheral neuropathy.
Due to interference with vitamin B6 synthesis.

Antitubercular - ethambutol

Risk factors - old age, high dose, prolonged use, poor renal function, DM, preexisting optic neuropathy.
Causes - optic neuritis
Due to - zinc chelation affecting mitochondrial metal-containing enzymes and excitotoxic pathway.

Linezolid

Risk factors - prolonged use, high dose
Causes - Painful reversible/irreversible sensory peripheral neuropathy and optic neuropathy (loss of colour perception and vision usually after 4-10 months, but could be after a shorter duration. Usually reversible).
Due to - Unknown, could be related to protein inhibition and mitochondrial toxicity.

Metronidazole

Risk factors - prolonged use, high dose
Causes - Motor and Sensory peripheral neuropathy, optic and autonomic neuropathy.
Due to - Axonal degeneration, shown to bind to neuronal RNA

Nitrofurantoin

Risk factors - renal impairment, anaemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency and debilitating disease.
Causes - peripheral neuropathy (including optic neuritis) - non-dose-dependent and of a sensorimotor, primarily axonal neuropathy - could be irreversible.

Azoles - voriconazole and itraconazole

Risk factor - Diabetes, high dose
Causes - peripheral neuropathy
Due to - unclear; mitochondrial-dependent mechanism (?)/ genetic polymorphism (?)

Chloroquine

Colistin

Dapsone

Chloramphenicol

Risk factors are prolonged treatment (>6 weeks) and a cumulative dose of >100 g.
Causes subacute visual loss with centrocaecal scotoma

Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)

Ref: Jones et al, Drug-Induced Peripheral Neuropathy: A Narrative Review, Curr Clin Pharmacol. 2020 Apr; 15(1): 38–48.
Vilholm, O.J., Christensen, A.A., Zedan, A.H. and Itani, M. (2014), Drug-Induced Peripheral Neuropathy. Basic Clin Pharmacol Toxicol, 115: 185-192. https://doi.org/10.1111/bcpt.12261