Which antibiotics do not prolong the QT (quinidine and testosterone) interval?

Antibiotics That Do Not Prolong the QT Interval

Penicillins (including penicillin V, amoxicillin, and benzathine penicillin G) and narrow-spectrum cephalosporins (cefadroxil, cephalexin) are the safest antibiotic choices with no significant QT prolongation risk. 1

First-Line Safe Antibiotics

Penicillins

• Penicillin V and amoxicillin are recommended as first-line agents with no QT prolongation concerns 1
• Benzathine penicillin G (intramuscular) carries no QT risk 1
• These agents should be prioritized whenever clinically appropriate for susceptible infections 1

Narrow-Spectrum Cephalosporins

• Cefadroxil and cephalexin are preferred cephalosporins with no QT prolongation 1
• These are much safer than broad-spectrum cephalosporins for cardiac safety 1
• Suitable for penicillin-allergic patients without immediate hypersensitivity reactions 1

Clindamycin

• Clindamycin is a reasonable alternative with no QT prolongation risk 1
• Resistance rates remain low (approximately 1% for Group A Streptococcus) 1
• Appropriate for penicillin-allergic patients 1

Antibiotics to AVOID Due to QT Prolongation

High-Risk Macrolides and Azalides

• Erythromycin and clarithromycin cause dose-dependent QT prolongation and should be avoided in at-risk patients 1, 2
• Azithromycin also prolongs QT interval and increases risk of sudden death, particularly in elderly and female patients 1, 2
• These agents are listed as definite causes of torsades de pointes 1
• Drug interactions with cytochrome P-450 3A inhibitors (azole antifungals, HIV protease inhibitors, SSRIs) significantly increase risk 1

Fluoroquinolones - Variable Risk

• Moxifloxacin carries the greatest QT prolongation risk among fluoroquinolones and should be avoided 2, 3
• Levofloxacin has moderate risk 2, 3
• Ciprofloxacin appears to have the lowest risk among fluoroquinolones and does not significantly prolong mean QTc interval in clinical studies 3, 4
• Older fluoroquinolones like ciprofloxacin have limited activity against some pathogens but better cardiac safety profiles 1, 4

Antifungals

• Ketoconazole and other imidazole antimycotics prolong QT interval 2
• These should be avoided in patients with baseline QT prolongation or other risk factors 2

Critical Risk Factors Requiring Extra Caution

When selecting antibiotics, assess for these high-risk features that increase torsades de pointes risk:

• Female sex, advanced age (>65 years), and baseline QTc >450 ms (men) or >470 ms (women) 1, 2
• Hypokalemia (K+ <4.5 mEq/L) or hypomagnesemia 1, 2
• Bradycardia or recent conversion from atrial fibrillation 2
• Congestive heart failure or structural heart disease 2
• Concomitant use of other QT-prolonging medications 1, 2

Monitoring Recommendations When QT-Prolonging Antibiotics Are Unavoidable

If macrolides or fluoroquinolones must be used:

• Obtain baseline ECG before initiating therapy 1, 5
• Repeat ECG after 1 month of therapy or 7 days after any dose change 6, 5
• Discontinue immediately if QTc >500 ms or increases >60 ms from baseline 1, 6, 5
• Correct electrolyte abnormalities (potassium, magnesium) before starting treatment 1, 2
• Avoid combining multiple QT-prolonging drugs 1, 2

Common Pitfalls to Avoid

• Do not assume azithromycin is safer than other macrolides - while it causes less QT prolongation than erythromycin or clarithromycin, it still carries significant risk 1
• Intravenous administration of any antibiotic carries higher cardiac risk than oral dosing due to rapid drug exposure 2
• Broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) should be avoided in favor of narrow-spectrum agents when possible 1
• Do not overlook drug interactions that can increase levels of QT-prolonging antibiotics 1