Azithromycin versus Ceftriaxone for Uncomplicated Typhoid Fever in Children: A Systematic Review and Meta-Analysis
Muhammad Umair Manzoor, Aqsa Anwar, Muhammad Owais, Syed Umar, Minahil Zameer, Amina Asif, Zakariye Isak Mohamed, and Abdinasir Adam Shidane systematically review and meta-analyze six randomized controlled trials comparing oral azithromycin to parenteral ceftriaxone for uncomplicated typhoid fever in children. This analysis finds comparable clinical efficacy and fever clearance times, with a potential benefit for azithromycin in reducing relapse rates. Despite the global burden of typhoid fever, the optimal antibiotic for children remains debated
Overview of Typhoid Fever
Typhoid fever, caused by Salmonella enterica serovar Typhi, continues to be a major infectious disease in low- and middle-income countries, particularly among children. Globally, an estimated 11–21 million cases and more than 100,000 deaths occur each year. The disease is most common in regions with poor sanitation, unsafe water supplies, and limited healthcare facilities, especially in South Asia, Southeast Asia, and sub-Saharan Africa.
Children between 2 and 15 years of age are particularly vulnerable, with school-aged children accounting for a large proportion of cases. Countries such as Pakistan, India, and Bangladesh continue to report a high burden of pediatric typhoid fever. Children with uncomplicated typhoid fever commonly present with persistent fever, abdominal pain, headache, weakness, and loss of appetite. Diagnosis is usually confirmed through blood culture or serological testing.
If treatment is delayed or ineffective, the disease may progress to severe complications such as intestinal perforation, gastrointestinal bleeding, encephalopathy, and sepsis. Therefore, timely and appropriate antibiotic therapy is essential to reduce complications and improve outcomes.
Historical Treatment and Emerging Resistance
Traditionally, chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole were widely used for the treatment of typhoid fever. However, the increasing emergence of multidrug-resistant (MDR) Salmonella Typhi strains reduced the effectiveness of these antibiotics and led to greater use of fluoroquinolones and third-generation cephalosporins.
More recently, the emergence of extensively drug-resistant (XDR) typhoid, particularly during the outbreak reported in Pakistan between 2016 and 2019, has further limited treatment options by reducing susceptibility to fluoroquinolones and several beta-lactam antibiotics. This changing pattern of resistance has created an urgent need for effective treatment alternatives for children.
Clinical Management Challenges Ceftriaxone is commonly used to treat typhoid fever and is considered an effective option, particularly in hospitalized patients. It has reliable activity against Salmonella Typhi and is associated with good clinical response rates. However, because ceftriaxone is administered…
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