Peritonsillar abscess: clinical aspects of microbiology, risk factors, and the association with parapharyngeal abscess.

PTA is a collection of pus located between the tonsillar capsule and the pharyngeal constrictor muscle. It is considered a complication of acute tonsillitis and is the most prevalent deep neck infection (approximately 2000 cases annually in Denmark) and cause of acute admission to Danish ENT departments. Teenagers and young adults are most commonly affected and males may predominate over females. However, no studies of age- and gender-stratified incidence rates have previously been published. Furthermore, smoking may be associated with increased risk of peritonsillar abscess (PTA) development, although the magnitude of the association has not been estimated. Complications are relatively rare. They include parapharyngeal abscess (PPA), upper airway obstruction, Lemierre´s syndrome, necrotizing fasciitis, mediastinitis, erosion of the internal carotid artery, brain abscess, and streptococcal toxic shock syndrome. The treatment consists of abscess drainage and antimicrobial therapy. There are three accepted methods of surgical intervension: needle aspiration, incision and drainage (ID), and acute tonsillectomy (á chaud). Internationally, there is a strong trend towards less invasive surgical approach to PTA treatment with avoidance of acute tonsillectomy, needle aspiration instead of ID, and in some cases even antibiotic treatment without surgical drainage. The preferred antibiotic regimen varies greatly between countries and centers. Group A streptococcus (GAS) is the only established pathogen in PTA. However, GAS is only recovered from approximately 20% of PTA patients. The pathogens in the remaining 80% are unknown. Culturing of PTA pus aspirates often yields a polymicrobial mixture of aerobes and anaerobes. As the tonsils of healthy individuals are already heavily and diversely colonized, the identification of significant pathogens is challenging. In addition, when studying PTA microbiology, one must consider diagnostic precision, collection, handling, and transportation of appropriate specimens, choice of methodology for detection and quantification of microorganisms, current or recent antibiotic treatment of patients, potential shift in significant pathogens during the course of infection, and factors associated with increased risk of PTA development.  The trend towards de-escalated surgical intervention and increasing reliance on antibiotic treatment, require studies defining the significant pathogens in PTA in order to determine optimal antibiotic regimens. Complications secondary to PTA may be avoided or better controlled with improved knowledge concerning the significant pathogens in PTA. Furthermore, identification of pathogens other than GAS, may lead the way for earlier bacterial diagnosis and timely intervention before abscess formation in sore throat patients. The identification and quantification of risk factors for PTA development constitutes another approach to reduce the incidence of PTA. As clinicians, we noticed that FN was recovered from PTA patients with increasing frequency and that patients infected with Fusobacterium necrophorum (FN) seemed to be more severely affected than patients infected with other bacteria. Furthermore, we occationally observed concomitant PPA in addition to a PTA, which made us hypothesize that PPA and PTA is often closely related and may share significant pathogens. Hence, our aims were: 1. To explore the microbiology of PTA with a special attention to Fusobacterium necrophorum (FN). 2. To elucidate whether smoking, age, gender, and seasons are risk factors for the development of PTA. 3. To characterize patients with PPA, explore the relationship between PPA and PTA, identify the pathogens associated with PPA, and review our management of PPA. In a retrospective study on all 847 PTA patients admitted to the ENT department at Aarhus University Hospital (AUH) from 2001 to 2006, we found that FN was the most prevalent (23%) bacterial strain in pus specimens. FN-positive patients displayed significantly higher infection markers (CRP and neutrophil counts) than patients infected with other bacteria (P = 0.01 and P < 0.001, respectively). In a subsequent prospective and comparative study on 36 PTA patients and 80 patients undergoing elective tonsillectomy (controls), we recovered FN from 58% of PTA aspirates. Furthermore, FN was detected significantly more frequently in the tonsillar cores of PTA patients (56%) compared to the tonsillar cores of the controls (24%) (P = 0.001). We also analysed sera taken acutely and at least two weeks after surgery for the presence of anti-FN antibodies. We found increasing levels (at least two-fold) of anti-FN antibodies in eight of 11 FN-positive (in the tonsillar cultures) PTA patients, which was significantly more frequent compared to none of four FN-negative PTA patients and nine of 47 electively tonsillectomized controls (P = 0.026 and P < 0.001, respectively). Blood cultures obtained during acute tonsillectomy mirrored the bacterial findings in the tonsillar specimens with 22% of patients having bacteremia with FN. However, bacteremia during elective tonsillectomy was at least as prevalent as bacteremia during quinsy tonsillectomy, which challenges the distinction made by the European Society of Cardiology between quinsy and elective tonsillectomy, namely that antibiotic prophylaxis is only recommended to patients undergoing procedures to treat an established infection (i.e. PTA). Using PCR analysis for the presence of herpes simplex 1 and 2, adenovirus, influenza A and B, Epstein-Barr virus (EBV), and respiratory syncytial virus A and B, we explored a possible role of viruses in PTA. However, our results did not indicate that any of these viruses are involved in the development of PTA. Privious studies have documented an association between EBV and PTA in approximately 4% of PTA cases. In addition to the involvement of GAS, the following findings suggest a pathogenic role for FN in PTA: 1. Repeated high isolation rates of FN in PTA pus aspirates. 2. Higher isolation rates in PTA patients compared to electively tonsillectomised controls. 3. Development of anti-FN antibodies in FN-positive patients with PTA. 4. Significantly higher inflammatory markers in FN-positive patients compared to PTA patients infected with other bacteria. We studied the smoking habits among the same 847 PTA patients admitted to the ENT department, AUH from 2001 to 2006. We found that smoking was associated with increased risk of PTA for both genders and across all age groups. The increased risk of PTA among smokers was not related to specific bacteria. Conclusions on causality cannot be drawn from this retrospective study, but the pathophysiology behind the increased risk of PTA in smokers may be related to, previously shown, alterations in the tonsillar, bacterial flora or the local and systemical inflammatory and immunological milieu. Studying all 1,620 patients with PTA in Aarhus County from 2001 to 2006 and using population data for Aarhus County for the same six years, age- and gender-stratified mean annual incidence rates of PTA were calculated. The incidence of PTA was highly related to age and gender. The seasonal variation of PTA was insignificant. However, the microbiology of PTA fluctuated with seasons: GAS-positive PTA cases were significantly more prevalent in the winter and spring compared to the summer, while FN-positive PTA patients exhibited a more even distribution over the year, but with a trend towards higher prevalence in the summer than in the winter. In a series of 63 patients with PPA, we found that 33 (52%) patients had concomitant PTA. This association between PPA and PTA was much higher than previously documented. We therefore suggest that combined tonsillectomy and intrapharyngeal incision in cases where PTA is present or suspected. The results of our routine cultures could not support a frequent role of FN in PPA. Based on our findings suggesting that FN is a frequent pathogen in PTA, we recommend clindamycin instead of a macrolide in penicillin-allergic patients with PTA. Furthermore, cultures made from PTA aspirates should include a selective FN-agar plate in order to identify growth of this bacterium. Recent studies of sore throat patients document an association between recovery of FN and acute tonsillitis. Studying the bacterial flora of both tonsils in study II, we found almost perfect concordance between the bacterial findings of the tonsillar core at the side of the abscess and contralaterally. This finding suggests that FN is not a subsequent overgrowth phenomenon after abscess development, but that FN can act as pathogen in severe acute tonsillitis. Future studies of patients with FN-positive acute tonsillitis focusing on the optimal methods (clinical characteristics, culture, polymerase chain reaction, or other) for diagnosis and whether antibiotics (and which) can reduce symptoms and avoid complications are warranted. Until further studies are undertaken, we recommend clinicians to have increased focus on acute tonsillitis patients aged 15-24 years with regards to symptoms and findings suggestive of incipient peritonsillar involvement. We have conducted a number of studies with novel findings: 1. FN is a significant and prevalent pathogen in PTA. 2. Bacteremia during abscess tonsillectomy is no more prevalent than during elective tonsillectomy. 3. The development of anti-FN antibodies in FN-positive PTA patients. We have used novel approaches as principles to suggest pathogenic significance of candidate microorganisms: 1. Comparative microbiology between PTA patients and "normal tonsils". 2. Measurements indicating larger inflammatory response compared to clinically equivalent infection.