Blog | Monday, December 4, 2017

The challenge of 'evidence based' sore throat guidelines

In 2007, Matthys and colleagues published a classic article: Matthys J, De Meyere M, van Driel ML, De Sutter A. Differences among international pharyngitis guidelines: not just academic. Ann Fam Med. 2007;5:436-43. [PMID: 17893386]

From the abstract of that paper: RESULTS We included 4 North American and 6 European guidelines. Recommendations differ with regard to the use of a rapid antigen test and throat culture and with the indication for antibiotics. The North American, French, and Finnish guidelines consider diagnosis of group A streptococcus essential, and prevention of acute rheumatic fever remains an important reason to prescribe antibiotics. In 4 of the 6 European guidelines, acute sore throat is considered a self-limiting disease and antibiotics are not recommended. The evidence used to underpin these guidelines was different in North America and Europe. North American guidelines cited more North American references than did European guidelines (87.2% vs 48.0%; odds ratio, 4.6–11.9; P<.001).
CONCLUSION Although the evidence for the management of acute sore throat is easily available, national guidelines are different with regard to the choice of evidence and the interpretation for clinical practice. Also a transparent and standardized guideline development method is lacking. These findings are important in the context of appropriate antibiotic use, the problem of growing antimicrobial resistance, and costs for the community.

We assume that the word “evidence” is all inclusive. How can nine guidelines on one subject differ significantly? The first problem occurs in selecting the evidence. Like defense and prosecution lawyers, guideline committees judge the potential evidence and decide which evidence meets their standards.

This leads to the problem of confirmation bias. These committees have biases. What is confirmation bias? Shane Parrish of the Farnam Street Blog has a wonderful article on confirmation bias. His definition: “Confirmation bias is our tendency to cherry pick information which confirms pre-existing beliefs or ideas. This is also known as myside bias or confirmatory bias. Two people with opposing views on a topic can see the same evidence, and still come away both validated by it. Confirmation bias is pronounced in the case of ingrained, ideological, or emotionally charged views.”

One does not have to impute bad intentions to the committees when considering confirmation bias. As Nietzsche famously said, “There are no facts, only interpretations.”

What do we know about acute sore throats? We know that group A streptococcal (GAS) sore throats can (and in the industrialized world rarely in 2017) lead to acute rheumatic fever. That risk is decreased with antibiotic treatment. GAS can lead to suppurative complications (especially peritonsillar abscess). It is highly contagious. It occasionally causes streptococcal shock syndrome with the rare death. Treatment probably decreases duration of symptoms in adolescents and young adults, but not significantly in childhood. Some Europeans now consider GAS sore throat a self-limited disease that we need not treat. They discount the ARF risk and thus view the potential negative side effects from antibiotics a greater problem.

We know that in adolescents and young adults, group C/G streptococcus and Fusobacterium necrophorum are found in endemic pharyngitis. They do not differ clinically from GAS in this age group (exudates, adenopathy, fever, lack of cough). They rarely occur in childhood (pre-adolescent). We have great disagreement as to the importance of group C/G and F. necrophorum.

What evidence do we have for each of these bacteria?

GCS (groups C and G are the same bacteria) can cause ASO titer rises. Some authors have speculated that this bacteria causes a significant amount of rheumatic fever. This bacteria clearly causes suppurative complications. In Zwart's study of patients 15 and older, penicillin decreased symptom duration by 1 day.

F. necrophorum causes high percentage of peritonsillar abscess (PTA) in the 15-30 age group (the age group with the highest percentage of PTA). This organism causes the great majority of the Lemierre syndrome (sore throat followed by internal jugular septic thrombophlebitis and septic emboli). Again this devastating syndrome occurs primarily in the 15-30 age group.

What evidence do we have that treatment prevents these suppurative complications? According to the Cochrane Collaboration article on antibiotics for sore throats: “Antibiotics reduced the incidence of acute otitis media within 14 days (RR 0.30; 95% CI 0.15 to 0.58); acute sinusitis within 14 days (RR 0.48; 95% CI 0.08 to 2.76); and quinsy within two months (RR 0.15; 95% CI 0.05 to 0.47) compared to those taking placebo.” (Quinsy is an English word for peritonsillar abscess.)

So when I consider sore throats, I focus on the 15-30 age group, but most guidelines focus primarily on children. I believe these are almost different diseases. GAS is the primary consideration in childhood. But in the adolescent/young adult age group we have other potentially dangerous bacteria.

Pharyngitis guidelines generally focus only on the question of whether the patient has a GAS infection. “Experts” argue that we have no evidence that we should treat GCS or Fusobacterium necrophorum. However, we do not have any evidence against treating these sore throat patients and perhaps preventing suppurative complications.

What makes me so passionate? Why is my bias for antibiotics for adolescent/young adults with Centor scores of 3 or 4?

Imagine an infectious disease that responds to standard antibiotics. Like endocarditis it causes septic emboli. This infection often causes diagnostic errors, because few physicians see a patient while in training, or have the disease even discussed.

The Lemierre Syndrome is that devastating disease. Over half the patients require intensive care for an average of 7-10 days. Up to 5% of the patients die. Many others have long standing complications. The ICU stay can cause PTSD and generalized anxiety.

Could we potentially prevent this disease?

Some authors argue that it is a very rare disease. But in the most recent Danish epidemiologic study it occurred in approximately 1 in 70,000 people in the 15-30 age group. How much certainty do we need to give empirical narrow antibiotics to patients in this age group with severe sore throats (and high Centor scores)?

My bias is to try to prevent this disease, as well as peritonsillar abscess (not as devastating a disease, but still worth preventing). The Centor score does a good job of identifying patients who do not need antibiotics. Virtually all experts agree to withhold testing and antibiotics for scores of 0 and 1. We should concentrate on these patients to reduce antibiotic use.

What are the unintended consequences of the IDSA policy? Some patients with severe sore throats get labelled as have a viral infection. Despite clear symptoms of worsening, too many physicians do not give appropriate antibiotics to these patients.

So the discussion is complex. We all want to reduce unnecessary antibiotic use, but we disagree on the definition of necessary.

And that is the problem with pharyngitis guidelines.

db is the nickname for Robert M. Centor, MD, FACP. db stands both for Dr. Bob and da boss. He is an academic general internist at the University of Alabama School of Medicine, and is the Regional Associate Dean for the Huntsville Regional Medical Campus of UASOM. He still makes inpatient rounds over 100 days each year. This post originally appeared at his blog, db's Medical Rants.