Unusual effects of common antibiotics
ABSTRACT
Antibiotics are widely prescribed and have a generally favorable safety profile. Common adverse effects such as rash and diarrhea are well recognized, but less common ones may go unrecognized. This review highlights rare but potentially lethal complications associated with antibiotics.
KEY POINTS
- Piperacillin-induced encephalopathy and seizure can occur on a continuum, with progressive dysarthria, tremor, and confusion culminating in tonic-clonic seizures.
- Monocycline-induced lupus can present as myalgia, arthralgia, serositis, constitutional symptoms, and a positive antinuclear antibody titer. The effect is not dose-dependent.
- Acute tubular necrosis has been linked to cephalosporins and tetracyclines. Crystal nephropathy has been reported with quinolones and sulfonamides.
- QT-interval prolongation is a class effect of quinolones and is more likely to occur in patients with pre-existing QT prolongation, electrolyte abnormalities, organic heart disease, or bradycardia, or in women.
ENDOCRINE SYSTEM
Clarithromycin, sulfonamides, and quinolones are known to precipitate hypoglycemia by interacting with sulfonylureas. A study of Medicare patients age 66 or older who were taking glipizide or glyburide reported that female sex, older age, and a history of hypoglycemic episodes were associated with antibiotic-related hypoglycemia.27 The odds ratio for hypoglycemia was highest for clarithromycin (3.96), sulfamethoxazole-trimethoprim (2.56), metronidazole (2.11), and ciprofloxacin (1.62) when compared with antibiotics that do not cause hypoglycemia. There was no signal for levofloxacin-mediated hypoglycemia in this series.27
RESPIRATORY SYSTEM
Hypersensitivity lung disease has been reported with penicillin, ampicillin, cephalosporins, ciprofloxacin, and sulfonamides including sulfamethoxazole-trimethoprim.28 The lipopeptide daptomycin has been reported to cause acute eosinophilic pneumonia defined as fever for less than 5 days, pulmonary infiltrates, hypoxemia, and a bronchoalveolar lavage or biopsy study with eosinophils. Daptomycin should be stopped early in these cases, and the patient should not be rechallenged, as the reaction can be deadly.29
Nitrofurantoin has a long history of hypersensitivity pneumonitis in its acute form and a chronic allergic response. While more widely recognized, nitrofurantoin pulmonary toxicity is rare, occurring in 1 in 5,000 patients.30
RENAL SYSTEM
Acute interstitial nephritis has been reported with penicillins, cephalosporins, macrolides, quinolones, sulfonamides, and vancomycin.31–33 Acute tubular necrosis has been linked to cephalosporins and tetracyclines. Crystal nephropathy has been seen with quinolones and sulfonamides.
Advanced age is an important risk factor for renal dysfunction from quinolones,18 and penicillin G has been reported to cause glomerulonephritis.31
MUSCULOSKELETAL SYSTEM
Quinolones have been associated with arthropathy or tendinitis at a rate of 1%, including cases of Achilles tendon rupture.18 The US Food and Drug Administration announced in 2016 that the serious adverse events with fluoroquinolones outweigh the benefits in patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infection, and that they should be used only if there are no other options.34
Daptomycin is known to cause elevations of creatine kinase.34 Weekly monitoring is recommended based on postmarketing data reports of elevations in 2.5% of patients; myopathy is a rarer effect, occurring in 0.2% of patients.35
REPRODUCTIVE SYSTEM
Antibiotics have long been reported to interact with oral contraceptives, but the data are not compelling for commonly used antibiotics. The strongest association is with rifampicin, which reduces oral contraceptive efficacy and warrants an alternative mode of contraception.36
BACK TO OUR PATIENT
Antibiotics can have serious adverse effects, and it is important for clinicians to be cognizant of this. Our 60-year-old patient who was taking cefepime and vancomycin for pneumonia developed prolonged atypical absence seizures. When the cefepime was discontinued, his mental status improved, and no other seizures were observed.
