Are azithromycin (Z-pack) prescriptions decreasing in popularity?

From the Guidelines

Z-Packs (azithromycin 5-day treatment packs) are indeed falling out of favor among medical professionals for many common infections due to growing concerns about antibiotic resistance and their often inappropriate prescription for viral infections. This shift is supported by recent evidence, such as a 2024 study published in the Journal of the American Academy of Dermatology 1, which highlights the association of oral tetracycline-class antibiotic use, including azithromycin, with inflammatory bowel disease, pharyngitis, Clostridium difficile infection, and Candida vulvovaginitis. Furthermore, the study notes that azithromycin is a broad-spectrum macrolide antibiotic that covers respiratory and other infections, and its increasing use could lead to increased antibiotic resistance.

The move away from Z-Packs is also driven by the recommendation for more targeted antibiotic choices based on specific infections rather than using broad-spectrum antibiotics like azithromycin as a default option. For instance, doxycycline has been shown to be more effective than azithromycin in reducing total lesion counts in certain conditions, with a greater reduction seen in doxycycline versus azithromycin at 12 weeks (MD in the change from baseline, 6.0 [-11.63,0.37] in 1 RCT) 1.

Key points to consider in the declining use of Z-Packs include:

• Growing concerns about antibiotic resistance
• Evidence of often inappropriate prescription for viral infections
• Recommendations for more targeted antibiotic choices
• Association of azithromycin with various adverse effects, including cardiac side effects and interactions with other medications
• Availability of alternative antibiotics, such as doxycycline, which may be more effective for certain conditions

In the context of COPD management, a 2015 guideline from the American College of Chest Physicians and Canadian Thoracic Society 1 suggests the use of macrolides, including azithromycin, for preventing acute exacerbations in patients with a history of exacerbations, but with an awareness of potential adverse effects and the need for strategies to mitigate these effects. However, this guideline is less recent and less directly relevant to the general trend of Z-Packs falling out of favor compared to the 2024 study 1.

Overall, the trend away from Z-Packs reflects a move towards better antibiotic stewardship, aiming to reduce the overuse of broad-spectrum antibiotics and mitigate the risks of antibiotic resistance and adverse effects. The most recent and highest quality evidence supports a cautious approach to the use of azithromycin, prioritizing its use based on specific clinical indications and weighing the benefits against the potential risks.

From the Research

Azithromycin Usage and Resistance

• Azithromycin, also known as a Z-pack, is a macrolide antibiotic that has been widely used to treat various bacterial infections 2.
• However, the increasing prevalence of azithromycin resistance has raised concerns about its effectiveness in treating certain infections 3, 4.
• Studies have shown that azithromycin resistance is spreading globally, and synergistic combinations with other drugs are recommended to treat different pathogens 3.

Clinical Implications and Treatment Outcomes

• The efficacy of azithromycin in treating Mycoplasma genitalium infections has been shown to be poor due to increasing antibiotic resistance 4.
• Treatment outcomes with azithromycin are associated with minimum inhibitory concentrations (MICs), and men infected with isolates having high AZM MICs are more likely to experience microbiologic and clinical treatment failure 4.
• In contrast, doxycycline MICs are not correlated with treatment efficacy, suggesting that doxycycline may be a more reliable treatment option for certain infections 4.

Alternative Treatment Options and Future Directions

• Other antibiotics, such as levofloxacin and doxycycline, have shown efficacy in preventing and treating Ureaplasma lung infections in immunosuppressed mice 5.
• The use of mass drug administration (MDA) of azithromycin has been recommended by the WHO to prevent childhood mortality, but concerns about antibiotic resistance need to be addressed 6.
• Continuous monitoring of azithromycin resistance and the development of more rapid diagnostic assays are urgently needed to ensure effective treatment of bacterial infections 3.