Eur J Clin Microbiol Infect Dis (2013) 32:71–78 DOI 10.1007/s10096-012-1715-6
ARTICLE
A cost-effectiveness analysis of identifying Fusobacterium necrophorum in throat swabs followed by antibiotic treatment to reduce the incidence of Lemierre’s syndrome and peritonsillar abscesses S. Bank & K. Christensen & L. H. Kristensen & J. Prag
Received: 20 June 2012 / Accepted: 24 July 2012 / Published online: 11 August 2012 # Springer-Verlag 2012
Abstract The main purpose of this paper was to estimate the cost per quality-adjusted life year (QALY) saved by identifying Fusobacterium necrophorum in throat swabs followed by proper antibiotic treatment, to reduce the incidence of Lemierre’s syndrome and peritonsillar abscesses (PTA) originating from a pharyngitis. The second purpose was to estimate the population size required to indicate that antibiotic treatment has an effect. Data from publications and our laboratory were collected. Monte Carlo simulation and one-way sensitivity analysis were used to analyse costeffectiveness. The cost-effectiveness analysis shows that examining throat swabs from 15- to 24-year-olds for F. necrophorum followed by antibiotic treatment will probably be less costly than most other life-saving medical interventions, with a median cost of US$8,795 per QALY saved. To indicate a reduced incidence of Lemierre’s syndrome and PTA in Denmark, the intervention probably has to be followed for up to 5 years. Identifying F. necrophorum in throat swabs from 15- to 24-year-olds followed by proper antibiotic treatment only requires a reduction of 20–25 % in the incidence of Lemierre’s syndrome and PTA to be costeffective. This study warrants further examination of the effect of antibiotic treatment on the outcome of F. necrophorum acute and recurrent pharyngitis, as well as the effect on Lemierre’s syndrome and PTA. S. Bank (*) : L. H. Kristensen : J. Prag Department of Clinical Microbiology, Viborg Hospital, Heibergs Allé 4, 8800 Viborg, Denmark e-mail:
[email protected] K. Christensen School of Economics and Management, CREATES, University of Aarhus, 8000 Aarhus C, Denmark
Introduction Pharyngitis is usually a self-limiting condition, whether caused by bacteria or viruses [1]. However, pharyngitis caused by group A streptococci (GAS) can, if untreated, develop into peritonsillar abscesses (PTA) and rheumatic fever, a potentially life-threatening disease, especially in children. GAS has, therefore, been considered as the most important bacterial cause of pharyngitis. GAS pharyngitis is usually treated with penicillin to cure the tonsillitis and to prevent rheumatic fever and PTA [1]. Group C streptococci (GCS) and group G streptococci (GGS) can also cause pharyngitis [2, 3]; however, unlike Fusobacterium necrophorum or GAS pharyngitis, no serious complications have been reported as a consequence of GCS or GGS pharyngitis, although GCS can rarely cause PTA [4]. Accumulating evidence suggests that the Gram-negative, anaerobic rod F. necrophorum can cause acute and recurrent pharyngitis [5–7]. Recent studies, furthermore, suggest that F. necrophorum is the most common bacterial cause of PTA [4]. In addition F. necrophorum pharyngitis can, although rarely, develop into Lemierre’s syndrome, a severe and lifethreatening infection which has been estimated to have a higher incidence, mortality and morbidity than rheumatic fever in adolescents and young adults [8]. The patients are mostly previously healthy young adults [9]. Review articles indicate that almost 75 % [10] of patients with Lemierre’s syndrome originating from the throat are 16–25 years old and almost 90 % [11] are 10–35 years old. Lemierre’s syndrome is rare, with a yearly incidence of 14.4 per 1,000,000 persons 15– 24 years old [9]. However, when it does occur, it often requires prolonged hospitalisation [9, 12]. The mortality of Lemierre’s syndrome has been reported to be between 5 and 17 % [8, 9, 11–14] and up to 10 % of the surviving patients develop severe permanent sequelae [9]. Early treatment leads to better outcomes [9, 13]. Almost all strains of F. necrophorum are
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sensitive to penicillin [15] and the recommended treatment of Lemierre’s syndrome is a combination treatment with amoxicillin and metronidazole [9]. No one has yet examined the optimal treatment of F. necrophorum pharyngitis. Most patients have pharyngitis several days before Lemierre’s syndrome develops [8, 16], often accompanied by unilateral internal jugular venous thrombosis, followed by septicaemia and metastatic abscesses, typically in the lungs, caused by F. necrophorum [10]. Early oral antibiotic treatment of patients with pharyngitis may reduce the incidence of Lemierre’s syndrome [8, 10, 11, 16–19], as an increase in this disease has been noted to coincide with a decrease in the prescription of antibiotics against upper respiratory tract infections [11, 12, 16, 17]. Furthermore, there was a drastic decrease of reported cases of Lemierre’s syndrome shortly after the Second World War, where penicillin was used widely for upper respiratory tract infections [10–12, 14, 17, 19]. Likewise, it is believed that the antibiotic treatment of pharyngitis can reduce the incidence of PTA, as a rise in PTA has also been noted to coincide with a decrease in antibiotic prescription for upper respiratory tract infections [4]. We have found that the incidence of pharyngitis, which may be caused by F. necrophorum, follows the same age and gender pattern as Lemierre’s syndrome [20]. It is, therefore, likely that the antibiotic treatment of F. necrophorum pharyngitis will reduce the incidence of Lemierre’s syndrome. Anaerobic culture of throat swabs is usually not performed routinely, and even if performed, the isolation and identification of F. necrophorum from the normal flora of the throat has, so far, proved difficult and time-consuming [17]. However, a selective agar for F. necrophorum has been developed which does not require experienced laboratory technicians and allows the identification of F. necrophorum within 3 days [21]. We focus on the cost to the society for examining throat swabs for F. necrophorum in an attempt to reduce the incidence of PTA and Lemierre’s syndrome. The effect of the intervention on the duration of acute or recurrent pharyngitis was not included in the analysis, as no study has yet examined the effect of the antibiotic treatment of F. necrophorum pharyngitis. Furthermore, we estimate the population size required to indicate an effect of the intervention.
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contained F. necrophorum. In Denmark, with a population of 5.3 million, there are 600,000 (11.3 %) 14–23-year-olds (http://www.statistikbanken.dk). Extrapolating these numbers yields 24,753 throat swabs received from general practitioners per year per 1,000,000 14–23-year-olds. The isolation rate of F. necrophorum from patients with sore throats has previously been reported to be between 5 and 10 %, and highest among adolescents and young adults [5, 6]. The higher isolation rate in our hospital could be because a selective agar has been developed [21] or it may be due to geographic differences. Severity of sequelae The sequelae of Lemierre’s syndrome was compared to asthma and bronchitis, which reduces the quality-adjusted life year (QALY) to 0.857 [22]. Life expectancy The average life expectancy was set to 79 years [23]. Adverse effect of antibiotic treatment It has been estimated that 1 in 10,000 patients treated with antibiotics will develop a severe allergic reaction, of whom 10 % carry the risk of dying [24]. Cost All costs were adjusted to 2010 US$. Cost of culture If F. necrophorum was not identified, the materials cost, including selective agar and anaerobic incubation, was estimated to be US$2.5 and wages to be US$1.7 (range US$1.4–US$4.1). If F. necrophorum was identified, the materials cost was estimated to be US$7 and wages to be US$8.2 (range US$8.1–US$8.8). The calculations were based on 5 (1–10) plates being processed simultaneously. Wages, at the highest salary grade including pension, were estimated to be US$31 per hour based on a salary index.
Materials and methods Cost of real-time PCR All incidences and costs are summarised in Table 1. F. necrophorum From 2007 to 2009, the department of clinical microbiology in Viborg, Denmark, with a catchment population of 230,000, received 1,930 throat swabs from general practitioners from patients who were 15 to 24 years old. Of those, 429 (22 %)
Real-time polymerase chain reaction (PCR) is a rapid test which can be performed in 4–5 h, with hands-on time of less than 2 h and can be used as an alternative to culture. Wages was estimated to be US$4.7. The materials cost was based on 2 (1–8) samples being processed simultaneously and was estimated to be US$15 (range US$10–US$22). Real-time PCR was performed as described by Jensen et al. [20].
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Table 1 Variables used to calculate the cost-effectiveness of identifying Fusobacterium necrophorum from throat swabs on selective agar followed by antibiotic treatment in 15–24-year-old patients Incidence variables
Per 1,000,000/yeara
Baseline
Lowb
Highb
Type of distributionc
PTA caused by F. necrophorum per 106/year [4]d Lemierre’s syndrome, per 106/year [9]d Permanent sequelae [9]d Severity of sequelae, QALY [22] Mortality, Lemierre’s syndrome [10]d Mortality, antibiotics, per 105 treated [24] Throat swabs per 106/yeard Positive throat swabsd Negative throat swabsd Avoidable cases of PTA [4] Avoidable cases of Lemierre’s syndrome [9] Utility variables, QALY Remaining life span (years) of 15–24-year-olds [23]
92.5 14.4 1.47 – 0.92 0.05 24,753 5,502 19,251 – –
92.5 14.4 10.2 % 0.857 6.4 % 1 24,753 5,502 19,251 50 % 50 %
81.1 9.5 2.1 % 0.905 2.6 % 0.67 23,896 5,024 18,872 40 % 40 %
105 21.1 22.0 % 0.786 12.8 % 1.5 25,617 6,020 19,597 60 % 60 %
Triangular Triangular Triangular Uniform Triangular Triangular Triangular Triangular Triangular Uniform Uniform
–
59
54
64
Uniform
Mortality, Lemierre’s syndrome, per 106/year Sequelae, per 106/year Mortality, antibiotics, per 106/year PTA, 5 days (2–8) [4] Lemierre’s syndrome, hospitalisation, 21 days (14–28) [9] Cost variables, 2010 US$ Lemierre’s syndrome, hospitalisation cost [9] PTA, hospitalisation cost [24, 29, 32] Cost of culturing and antibiotic treatment Cost of negative throat culturee Cost of positive throat culturee
54.4 14.1 3.1 1.3 0.8
54.4 14.1 3.1 0.014 0.057
13.3 1.2 1.3 0.0055 0.038
172.9 90.0 6.0 0.022 0.077
Triangular Triangular Triangular Triangular Triangular
434,376 242,073
30,165 2,617
20,110 1,745
45,248 5,658
Triangular Triangular
77,875 80,256
4.2 15.2
3.9 15.1
6.6 15.8
Triangular Triangular
Cost of calling prescription [29] Cost of antibiotics Cost of treating adverse effect of antibiotics [24]
7,339 76,718 1,186
1.4 14.5 2,247
0.9 14.5 1,123
2.1 51.4 4,494
Triangular Triangular Triangular
a
Calculated from baseline values
b
Low and high were used in the Monte Carlo simulation and were based on a 95 % confidence interval when possible
c
The distribution used in the Monte Carlo simulation. Triangular: highest probability of picking a number around the baseline value with decreasing probability towards high and low. Uniform: equal probability of picking a number between high and low
d
Based on a 95 % confidence interval
e
Including wages
Cost of antibiotics In Denmark, 24 tablets of amoxicillin 500 mg and 24 tablets of metronidazole 500 mg cost US$14.5 and US$11.2, respectively. Clindamycin was not considered, as the cost of 20 tablets is US$117 in Denmark. Cost of treating Lemierre’s syndrome Patients are hospitalised, on average, for 21 days [9] and, of those, 10 days are spent in intensive care. Based on a price index, excluding administration cost (http://www.sst.dk),
the daily cost of hospitalisation was estimated to be US $591 and US$2,205 for intensive care. These estimates correspond well with the cost reported by others [25]. Economical evaluation The median cost of more than 300 other life-saving medical interventions have been calculated by Tengs et al. to be US $28,665 (2010 US dollars) per QALY saved [26]. To be considered as economical reasonable, the cost per QALY should be less than US$50,000 which is a threshold often cited [27].
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Assumptions
run 10,000 times to obtain a distribution of the cost per QALY saved. The data were analysed from a societal perspective.
Several simplifying conditions were made: &
&
&
It was assumed that 50 % of Lemierre’s syndrome [9] and PTA [4] are unpreventable, as approximately 50 % of the patients are hospitalised after the first medical contact. Thus, it was assumed that up to 7.2 cases of Lemierre’s syndrome and 46.3 cases of PTA caused by F. necrophorum could be prevented. It was assumed that the departments of clinical microbiology at the hospitals culture throat swabs from adolescents and young adults on F. necrophorum selective agar, as described by Bank et al. [21]. It was assumed that the practitioners do not change their practice, except for prescribing antibiotics, if F. necrophorum was identified.
Decision analysis Two strategies were compared in an attempt to identify the most cost-effective approach. The cost per QALY saved was calculated by using a Monte Carlo simulation. Sensitivity analysis In the sensitivity analysis, uncertainty in costs and incidences, which has the largest impact on the cost-effectiveness analysis, was considered. The variables which had the largest impact on the cost-effectiveness analysis were based on the results of the tornado diagram (Fig. 2). The cost per QALY saved was calculated by using a Monte Carlo simulation.
Omitted Statistical analysis & & &
Reduced duration of symptoms caused by treating F. necrophorum pharyngitis has been omitted, as no study has yet examined the effect experimentally. The cost of transporting the throat swabs was not considered, as the throat swabs had already been received by the hospitals for bacteriological examination. The reduction to the cost of the rapid test if omitted in adolescents and young adults was not considered.
The χ2 test was used to calculate the population size required to indicate an effect of examining throat swabs for F. necrophorum followed by antibiotic treatment. The statistical analysis was performed using SPSS for Windows version 16.0 (SPSS Inc., Chicago, IL, USA).
Results Base case analysis Base case analysis The base case analysis was used to describe a simplified model, where antibiotic treatment had an equal effect in reducing the incidence of Lemierre’s syndrome, PTA, mortality and permanent sequelae. In the base case analysis, the baseline values in Table 1 were used and uncertainty in incidence and cost were not considered. The data were analysed from a societal perspective. Tornado diagram In the tornado diagram, all but one of the parameters in the base case analysis were kept constant (Table 1) and the required reduction in incidence of Lemierre’s syndrome, PTA, mortality and permanent sequelae for the cost per QALY saved to be US$50,000 was calculated. The tornado diagram shows which parameters had the largest impact on the cost-effectiveness analysis based on their weight in the analysis and the uncertainty of the parameter. Monte Carlo simulation A Monte Carlo simulation was used to vary all parameters independently of each other and took into account the uncertainty in incidence and cost. The Monte Carlo simulation was
To be considered as economically reasonable, a reduction of preventable Lemierre’s syndrome, PTA, death and permanent sequelae by 20 % was required, as illustrated in Fig. 1. A reduction of 26 % was required for the culturing of throat swabs for F. necrophorum followed by antibiotic treatment to be comparable to the median cost of other life-saving medical interventions. A reduction by 75 % would reduce the total cost to the society, meaning that the cost of culturing throat swabs and treating patients with antibiotics will be less than the reduced cost due to fewer hospitalisations. Tornado diagram The tornado diagram shows that uncertainty in the incidence of mortality and the incidence of Lemierre’s syndrome has the largest impact on the cost-effectiveness analysis, followed by the cost of antibiotic treatment, as shown in Fig. 2. Avoidable cases of Lemierre’s syndrome, incidence of mortality caused by antibiotics and incidence of permanent sequelae also have some effect on the model. The rest of the variables are only changing the effect for the intervention to be economically reasonable from 20 % in the baseline model to between 19 and 22 %.
Eur J Clin Microbiol Infect Dis (2013) 32:71–78 70000 Cost, in US$, per quality adjusted life year saved
Fig. 1 Cost per quality adjusted life year (QALY) saved by identifying Fusobacterium necrophorum in throat swabs from 15–24-year-olds followed by antibiotic treatment. Base case analysis
75 Prevented cases
60000 50000
Economical reasonable
40000
Median cost of other life-saving medical interventions
30000 20000 10000 0 -10000 10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Reduced incidence of preventable Lemierre´s syndrome, peritonsillar abscesses , death and sequela.
Monte Carlo simulation
Lemierre’s syndrome
Strategy one: culture and antibiotic treatment
The incidence of Lemierre’s syndrome may be as high as 21.1 per 1,000,000 per year, in which case the median cost per QALY saved would be US$3,963. If the incidence of Lemierre’s syndrome was 7.5 or 5.0 per 1,000,000, then the median cost per QALY saved would be US$29,671 and US $48,821, respectively.
In the first strategy, the throat swabs were cultured on selective agar and, if F. necrophorum was identified, the patients were treated with antibiotics. The median cost per QALY saved was US$8,795 [95 % confidence interval (CI) −US$2,566; US$40,917).
Avoidable cases Sensitivity analysis: incidence As the baseline, it was assumed that 50 % of the incidence of Lemierre’s syndrome, PTA, mortality and permanent sequelae was unavoidable. If 72 or 80 % cases were unavoidable, then the median cost per QALY saved would be US$29,209 and US$50,178, respectively.
Mortality The mortality could be as low as 2.6 % or as high as 12.8 %, in which case the median cost per QALY saved would be US$21,196 and US$5,077, respectively.
0,35 Reduced incidence required to be economical reasonable.
Fig. 2 Tornado diagram. Base case analysis
0,30 0,25 0,20 0,15 0,10
t e la s la re bs cos om tics ue u ltu om iotic ue wa dr o q q i n n s c se se ve t ib t ib tio sy e m sy of nt an an tiv iti ´s iza s e f of l y a s ´ e y t n r o b a ita po eg ve ri ce r re o st ier sp rm of n ed of en mie e m o s e C d e h e S p u c , f st Le fL nc In ca m eo of Co de dro ty so i i c l e e c s c n ta en In or sy ca en cid s m e id n l c f I ´ o ab In rre ce ie oid n v m e A Le cid In lity
ta or
r nd
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If all cases of Lemierre’s syndrome, PTA, mortality and permanent sequelae were avoidable, then the median cost per QALY saved would be −US$1,105. Permanent sequelae The incidence of permanent sequelae could be as low as 2.1 % or as high as 22 %, in which case, the median cost per QALY saved would be US$11,064 and US$7,379, respectively. Sensitivity analysis: cost Antibiotic treatment If patients were treated for up to 20 days with both amoxicillin and metronidazole 500 mg three times a day, then the median cost per QALY saved would be US$17,742. If antibiotic treatment is reduced to 8 days with amoxicillin 500 mg three times a day, then the median cost per QALY saved would be US$4,988. Real-time PCR If the real-time PCR cost US$40 or US$25, including wages, then the median cost per QALY saved would be US$49,497 and US$30,019, respectively. If the real-time PCR cost US$9, then it would be comparable to culture, with a median cost per QALY saved of US$9,022. Strategy two: empirical treatment In the second strategy, the patients were empirically treated with amoxicillin 500 mg three times a day for 8 days if they had symptoms of pharyngitis. In this strategy, the throat swabs were not cultured for F. necrophorum. The median cost per QALY saved was US$25,226 or US$53,855 if 22,000 or 25,000 patients per 1,000,000 adolescents and young adults were empirically treated, respectively. Population size required to prove an effect Effect of antibiotic treatment on PTA The number of PTA can be extracted from the hospital databases. A reduction of PTA from 92 to 66, a reduction by 28 %, can be proven with 95 % confidence, which requires a population of one million 15–24-year-olds during a 1-year study or a smaller population of 15–24-year-olds during a longer study period.
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change in the incidence of the disease. However, positive blood cultures with F. necrophorum are registered. Although all F. necrophorum bacteraemias do not develop into Lemierre’s syndrome, a decrease in positive blood cultures with F. necrophorum is an indicator that antibiotic treatment has an effect on the incidence of Lemierre’s syndrome. A reduction of positive blood cultures from 43 to 25, a reduction by 42 %, can be proven with 95 % confidence, which requires a population of three million 15–24-year-olds during a 1-year study. Another possibility would be to examine the number of lung abscesses caused by F. necrophorum. However, lung abscesses are not registered directly in the hospital databases.
Discussion When considering the strategy for treating pharyngitis, GAS has, so far, been the only important bacterial pathogen recognised to cause complications [1]. However, complications caused by F. necrophorum pharyngitis can be estimated to be responsible for more deaths and permanent sequelae in adolescents and young adults in the western world, as described in Table 2 [8]. Seen from a historical perspective [8, 10–12, 16, 19], it is reasonable to believe that the antibiotic treatment of F. necrophorum pharyngitis will reduce the incidence of PTA and Lemierre’s syndrome. The base case analysis shows that the cultivation of throat swabs from 15–24-year-olds for F. necrophorum followed by antibiotic treatment only needs to reduce the incidence of preventable Lemierre’s syndrome, PTA, death Table 2 Comparison of complications caused by group A streptococci (GAS) and Fusobacterium necrophorum pharyngitis in 15–24-year-olds
Pharyngitis, caused by PTA, untreated pharyngitis PTA prevented by antibiotics Complications of GAS and F. necrophorum pharyngitis Incidence Complications/permanent sequelae Mortality Antibiotics prevent a
Effect of antibiotic treatment on Lemierre’s syndrome Lemierre’s syndrome is not registered as a disease in the hospital databases, which makes it difficult to monitor any
GAS
F. necrophorum
5 % [1] 1–2.4 % [24, 29] 84–89 % [24, 29]
22a % 2a % Unknown
Acute rheumatic fever
Lemierre’s syndrome
1:1,000,000 [33] 10 % [24]
14.4:1,000,000 [9] 10.2 % [9]
1 % [24] 70–90 % [24]
6.4 % [10] Unknown
Estimated.
Complications of F. necrophorum pharyngitis can be estimated to cause more than 50 times as many deaths and be responsible for more than 10 times as many permanent sequelae as complications of GAS pharyngitis in adolescents and young adults in the western world
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and permanent sequelae by approximately 20 % to be considered economical reasonable and by approximately 25 % to be less costly than other life-saving medical interventions, as illustrated in Fig. 1. The tornado diagram shows that uncertainty in the incidence of mortality and the incidence of Lemierre’s syndrome has the largest influence on the cost-effectiveness analysis. However, the mortality of adolescents and young adults can be expected to be slightly higher than the baseline incidence, which is an average of all age groups, as this age group is usually more severely affected by Lemierre’s syndrome than adults [9]. The incidence of Lemierre’s syndrome used in this analysis was based on a study in Denmark from 1998 to 2001 [9]. A smaller but more recent study in Denmark from 2004 to 2007 indicates that the incidence of Lemierre’s syndrome could be more than three times as high, which would have a very large impact on the cost-effectiveness analysis [28]. Furthermore, shorter duration of symptoms or prevention of recurrent pharyngitis by treating F. necrophorum pharyngitis was not considered in the cost-effectiveness analysis, as no study has examined the effect. The incentive for examining throat swabs for F. necrophorum in adolescents and young adults is, therefore, higher than that indicated in this article. Two different strategies were compared in the Monte Carlo simulation. Culture and antibiotic treatment can be expected to be less costly than most other life-saving medical interventions. Real-time PCR is a valid option, although it is more expensive than culture. However, by using realtime PCR, the physician can obtain the result already by the next day, whereas culturing takes 3 days, which might have an effect on the outcome of the intervention. The empiric treatment of patients with symptoms of pharyngitis might be economically reasonable but will probably be the least costeffective strategy. The conservative use of antibiotics against pharyngitis in recent years is mainly to prevent complications caused by antibiotic treatment, such as Clostridium difficile diarrhoea, and to prevent pathogens from developing antibiotic resistance [16, 29]. However, penicillin has been used against GAS pharyngitis for more than half a century and GAS is still susceptible to penicillin [30]. C. difficile diarrhoea has not been considered in other cost-effectiveness analyses of the management of pharyngitis, and is not considered to be a major problem among otherwise healthy adolescents and young adults [24, 29]. When considering the traditional management of pharyngitis, the cost-effectiveness analysis indicates that, in paediatrics, either the rapid antigen test against GAS [31] or culture [29] could be the most cost-effective method [32]. The cost-effectiveness analysis indicates that culture and rapid test against GAS for the management of pharyngitis in adults have very similar effectiveness and cost, slightly
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favouring culture [24]. If it is proven that culture for F. necrophorum followed by antibiotic treatment can reduce the incidence of Lemierre’s syndrome and PTA, then rapid tests against GAS should probably be reserved for paediatric patients, whereas culture without a rapid test against GAS in adolescents and adults will probably be the most costeffective method, unless a rapid test against F. necrophorum is developed. To be able to prove that examining throat swabs for F. necrophorum has an effect on the incidence of Lemierre’s syndrome, a population equal to that of the Danish population of 5.3 million should be adequate to indicate an effect within a few years. However, it will be very difficult to prove a reduction of the mortality and permanent sequelae caused by Lemierre’s syndrome, as neither are registered in the hospital databases. In conclusion, this study warrants further examination of the effect of antibiotic treatment against F. necrophorum pharyngitis on the outcome of acute and recurrent pharyngitis, as well as the effect on PTA and Lemierre’s syndrome. However, even if the duration of F. necrophorum pharyngitis is not reduced, the cost-effectiveness analysis shows that the intervention will be cost-effective if only a few cases of Lemierre’s syndrome can be prevented. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Conflict of interest The authors declare that they have no conflict of interest.
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