When strep throat is confirmed, amoxicillin (or penicillin) is the standard initial prescription. The responsible bacteria, Group A Streptococcus (Streptococcus pyogenes), has historically shown no true in vitro resistance to these antibiotics. The typical course is ten days, aiming to fully eradicate the organism and prevent long-term complications. If symptoms persist or return shortly after treatment, it suggests the bacteria were not eliminated. This scenario requires a specific medical response to ensure the infection is fully resolved.
Why Amoxicillin May Not Be Working
The most common reason for amoxicillin failure is often not a problem with the drug’s effectiveness against Group A Streptococcus. One frequent issue is misidentification, meaning the infection was not strep throat at all, but rather a viral infection like mononucleosis, or another bacterial cause that amoxicillin does not treat. If the infection was truly strep, a common cause of failure is non-adherence, where the patient stops taking the antibiotic once symptoms improve, allowing the remaining bacteria to multiply.
Beyond adherence, treatment failure can be caused by mechanisms that protect S. pyogenes from the antibiotic within the body, known as in vivo resistance. Some co-existing bacteria, such as Moraxella catarrhalis or Haemophilus influenzae, produce an enzyme called beta-lactamase, which inactivates amoxicillin in the local environment. S. pyogenes can also be internalized by human cells in the tonsils, where amoxicillin cannot reach and eliminate the bacteria because it does not penetrate cells well.
Another explanation is the “carrier state,” where a person carries the S. pyogenes bacterium in their throat without symptoms. If a carrier develops a concurrent viral infection, they will test positive for strep. The antibiotic treatment clears the asymptomatic bacteria, but the viral symptoms persist. In these cases, the lingering symptoms are due to the virus, not a treatment failure of the bacterial infection.
Medical Protocol for Treatment Failure
If symptoms persist or return 48 to 72 hours after starting amoxicillin, the patient should immediately return for re-evaluation. The first step is to confirm the Group A Streptococcus infection is still present, typically with a second rapid strep test or a throat culture. The physician will also assess medication adherence and rule out re-exposure to the bacteria, such as from an infected household member.
Once the persistent infection is confirmed, the physician will switch the patient to a different class of antibiotic. Preferred second-line options include cephalosporins, such as cephalexin, which often have superior bacterial eradication rates in these scenarios. Cephalosporins are generally not inactivated by the beta-lactamase enzyme that may have interfered with the initial treatment.
Clindamycin is another alternative, reserved for recurrent infection or when beta-lactamase-producing co-infecting bacteria are suspected. For patients with a true penicillin allergy, macrolide antibiotics like azithromycin or clarithromycin may be used, though resistance rates can vary by region. The full 10-day course of the new antibiotic must be completed to ensure eradication and prevent serious complications.
Serious Risks of Untreated Strep Infection
Eradicating Group A Streptococcus is necessary to prevent systemic complications that affect tissues far from the throat. The most significant is Acute Rheumatic Fever (ARF), an inflammatory condition that affects the joints, skin, and brain. Most dangerously, ARF can cause permanent damage to the heart valves. This is an autoimmune response resulting from a genetic predisposition combined with an untreated strep infection.
Another severe long-term complication is Post-Streptococcal Glomerulonephritis (PSGN), which causes inflammation in the kidneys. PSGN often presents one to two weeks after the throat infection, leading to symptoms like high blood pressure and blood in the urine. Unlike ARF, antibiotic treatment does not prevent its development once the infection is established.
In children, an untreated strep infection can be linked to Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). This occurs when the body’s immune response mistakenly targets the basal ganglia of the brain. The resulting symptoms are a sudden onset of obsessive-compulsive disorder or tic disorders.
Localized complications occur when the infection spreads directly to nearby tissues, such as a Peritonsillar Abscess. This is a collection of pus forming near the tonsils, requiring immediate drainage and further antibiotic treatment. Due to the risk of these severe complications, swift and successful treatment of strep throat is a public health priority.