pharyngitis and fusobacterium

a recent article in the Annals of Internal Medicine looked at the causes of pharyngitis at the University of Alabama at Birmingham student health center (see pharyngitis fusobacterium annals 2015 in dropbox, or Ann Intern Med. 2015;162:241-247​). details:

--312 students aged 15-30 with acute pharyngitis were compared to 180 asymptomatic students (mean age 23, about 60% women, 74% white)

--PCR was done on the throat swabs to detect Fusobacterium necrophorum, Mycoplasma pneumoniae, and group A and  group C/G b-hemolytic streptococci. and the Centor score was calculated  (Centor, by the way, is the lead author of this study). the Centor score is 1 point for each of fever, lack of cough, tender anterior cervical nodes, and tonsillar exudates, with higher scores more likely to reflect group A strep infection.

--results:

    --F necrophorum in 20.5% of those with pharyngitis and 9.4% of the asymptomatic

    --group A strep in 10.3 vs 1.1%

    --group C/G strep in 9.0 vs 3.9%

    --M pneumoniae in 1.9 vs 0%

    --many patients had multiple infections (eg, of the total of 35% of patients who had an identified infection, 28% had a single organism and 7% had multiple

    --and, of course, "none" (ie, probably viral in those with pharyngitis) was found in 64.7 vs 86.1%.

    --in looking at the Centor scores: the numbers of patients in the different cells were small, but 37% (n=7) of those with a Centor score of 4 had F necrophorum, vs 11- 16% of the others, with n=2-3. and 26% with "none" had a Centor score of 4.  for Centor scores of 2-3, about 30% had F necrophorum (n=31), 20% with group A strep (n=20), and about 15% with the others (with n= about 16), though "none" was found in close to 60% (n=88)

--data from Europe have found that F necrophorum causes about 10% of cases of pharyngitis in those 15-30 yo

--concerns about this study:

    --the presence of the organism does not necessarily mean that it is the cause of the infection. the asymptomatic carriage rate for F necrophorum is quite high, and often multiple organisms were found in those with pharyngitis (and, which, if any, was causing the symptoms???). the parallel with group A strep is that the asymptomatic carriage rate can be very high at certain times of the year, as detected by culture or PCR, but the accepted evidence of infection is by an increase in the blood ASO titer or by changes in acute vs convalescent serum antibody levels, reflecting the systemic effect of the infection.  so, even in those with pharyngitis and positive strep PCR in this study, some may have had a viral infection and were just carriers of strep.

    --it is likely that these patterns of pharyngeal pathogen carriage are different in different areas and different times of the year

    --it is likely not to be generalizable to the majority of people coming in with pharyngitis (little kids)

--but this study does bring up several issues

    --as with other studies, the Centor score reflects a trend/a continuum. more likely to be strep if high, but still large % with probably viral infection. in this study, 85% of those with Centor score 0 had "none" identified, decreasing to 73% in those with Centor score 1, to 58% in those with 2 or 3, to 26% in those with score of 4. so, "none" (ie probably mostly viral infections) was still found in a majority of those with Centor scores up to 4, and only 11% of those with the maximum Centor score actually had Group A strep (though n was only 2). it should be pointed out that in larger studies, those with a score of 4 had a 50% chance of having Group A strep (see  Arch Intern Med. 2012; 172:847-52.)

   --it would be really useful to have region and age-specific data on the infection and carrier rates for the different organisms at different times of the year

    --this study reinforces using penicillin as the antibiotic of choice. it should be so anyway, since its spectrum of activity is relatively narrow and it is therefore less likely to cause bacterial resistance. and, it turns out, F necrophorum is sensitive to penicillin (and first generation cephalosporins) and not to azithromycin. (and we mere mortals do not even have access to tests for F necrophorum anyway, so best to just use penicillinif you are going to give antibiotics….). and it is worth keeping in mind: although only about 10% of adults with acute pharyingitis have strep, 60% receive antibiotics, and the rate of prescription for penicillin has decreased to about 10% -- really good drug company marketing!!: strep is pretty universally sensitive to penicillin, which is now less-prescribed than azithromycin to which strep is occasionally resistant, or other "big guns" (penicillin-b-lactamase inhibitors, third-generation cephalosporins...) -- see, for example, JAMA Intern Med. 2014; 174:138-40​.

    ​--although this study does not prove F necrophorum is the cause of the pharyngitis cases, there is reasonable argument that it should be treated, since it does appear to be the most common cause of peritonsillar abscess in those 15-30 years old and the primary cause (on the order of 80%) of Lemierre's syndrome (suppurative internal jugular thrombophlebitis with subsequent metastatic infections to the lung, brain, bone, often leading to ICU admission and significant morbidity/mortality -- although, again, there are no data that treating early F necrophorum decreases the likelihood of Lemierre's.