FormalPara Key Summary Points

Why carry out this study?

Group A streptococcal (GAS) pharyngitis is the most common bacterial cause of sore throat in children. Although international guidelines consistently recommend narrow-spectrum β-lactams as first-line therapy, substantial variability in antibiotic prescribing persists in primary care.

Data on the clinical course, recurrence patterns, complications, and real-world antibiotic management of GAS pharyngitis in children remain limited, particularly in the post-pandemic period characterized by increased GAS circulation.

This study aimed to characterize the clinical features, recurrences, complications, and outpatient antibiotic management of GAS pharyngitis in a large nationwide cohort of Italian children followed by primary care pediatricians.

What was learned from the study?

Among 1464 episodes of microbiologically confirmed GAS pharyngitis, the clinical course was predominantly benign, with only seven episodes (0.5%) developing complications. Importantly, all complications occurred during the first episode of infection, and recurrent infections were not associated with an increased risk of complications.

Despite clear guideline recommendations, only 51.5% of episodes were managed according to recommended antibiotic choice and treatment duration. Broad-spectrum antibiotics, including cephalosporins and amoxicillin–clavulanate, were frequently prescribed without evidence of improved clinical outcomes.

The discrepancy between evidence-based recommendations and real-world prescribing practices highlights the need to strengthen antimicrobial stewardship strategies in paediatric primary care and to promote the preferential use of “Access” antibiotics whenever clinically appropriate.

Introduction

Group A Streptococcus pharyngitis accounts for approximately one-quarter of paediatric sore throat episodes [1,2,3]. Although most infections have a favorable course, a minority of cases progress to chronic and acute complications. Acute rheumatic fever (ARF) is the most important chronic sequela and remains highly prevalent in low-income countries (374 per 100,000 children); it is also the main antecedent of rheumatic heart disease (RHD) which affects over 33 million people worldwide and is responsible for approximately 319,000 deaths each year [3]. Antibiotic therapy reduces the relative risk of ARF by about two-thirds, thereby also reducing RHD-related mortality [1, 4]. Acute complications include suppurative conditions such as peritonsillar and retropharyngeal abscesses, cervical lymphadenitis, and invasive disease, whereas antibiotic treatment is associated with a lower risk of acute otitis media and peritonsillar abscess [1, 5]. In Italy, recent (2024) guidelines have been published for the management of acute and recurrent streptococcal pharyngitis (Supplementary material Table S1), and the literature provides evidence supporting the effectiveness of amoxicillin therapy in reducing acute and chronic complications [1]. Despite this, substantial heterogeneity persists in the management of group A streptococcal (GAS) pharyngitis in children by primary care pediatricians. This heterogeneity may be partially attributable to differences in international recommendations [6]. Most European guidelines (including those from Italy, Finland, and European Society of Clinical Microbiology and Infectious Diseases, ESCMID) support etiological diagnosis before treatment and recommend narrow-spectrum beta-lactams for 10 days [6]. In contrast, France recommends amoxicillin as first-line therapy for a shorter course, typically 6 days, while Germany recommends 5–7 days. The UK adopts a more restrictive approach: National Institute for Health and Care Excellence (NICE) guidelines consider pharyngitis largely self-limiting, do not routinely recommend rapid antigen detection tests or throat cultures, and reserve antibiotics for patients with high clinical scores (Centor ≥ 3 or FeverPAIN ≥ 4) or severe disease, often using delayed (“backup”) prescriptions; when prescribed, treatment lasts 5–10 days [6]. Finally, in Australia and New Zealand, recommendations are explicitly risk-stratified: in populations at high risk of ARF, empiric antibiotic therapy is recommended on the basis of clinical suspicion, even before microbiological confirmation, and continued for 10 days [6].

Since 2023, an increase in the rate of recurrent acute streptococcal pharyngotonsillitis and invasive GAS infection has been observed in Italy [7, 8]. The causes of recurrence may include poor adherence to antibiotic therapy, the presence in the pharynx of other β-lactamase-producing microorganisms that may protect group A streptococci from the activity of β-lactam antibiotics, the ability of group A streptococci to survive within epithelial cells, and the formation of biofilms [9,10,11]. According to Munck et al. treatment failure is more likely than reinfection in children with a short interval between completion of antibiotic therapy and recurrence [9]. The management of recurrent streptococcal pharyngotonsillitis remains controversial and is poorly supported by high-quality evidence [1]. Current guidelines agree that antibiotics should not be routinely used to prevent long-term recurrences and should be reserved for selected cases, particularly in children with short-term recurrences and in children who are GAS carriers and candidates for tonsillectomy [1].

The aim of our study is to characterize the clinical manifestation, recurrences, and complications of streptococcal pharyngitis in a population of Italian children followed by primary care paediatricians. The study aims to describe the outpatient therapeutic management of streptococcal pharyngitis in children who developed acute or chronic complications, as well as in those with early and multiple recurrences during the observation period, and to assess the management strategies adopted by primary care paediatricians across the national territory. The study period coincided with a documented increase in the circulation of GAS infections in Italy and other European countries during the post-pandemic phase [8]. Recent national surveillance data have reported a resurgence not only of streptococcal pharyngotonsillitis but also of invasive GAS infections in children following the COVID-19 pandemic, likely related to changes in population immunity and pathogen transmission dynamics [7, 8]. This epidemiological context may have contributed to the relatively high number of observed episodes and recurrences in our cohort, potentially reflecting increased exposure and reinfection rates at the community level.

Methods

Study Design

We conducted a multicenter prospective observational study coordinated by the Italian Society of Primary Care Paediatrics (SICuPP) aimed at collecting epidemiological and clinical data and management of infections by GAS in children referred to Italian Primary Care Paediatricians during the period from August 1, 2024 to June 30, 2025.

Participants and Inclusion Criteria

Sixty-six paediatricians were identified and invited to participate in the study. Eligibility criteria for primary care paediatricians included membership in the SiCuPP, a uniform geographic distribution across Italy, and a declared commitment to collect study data and actively participate in the project. Furthermore, participating paediatricians were selected on the basis of their routine use of rapid antigen detection tests (RADTs) for group A Streptococcus and their demonstrated ability to perform and interpret these tests in accordance with national and international guidelines.

Children were enrolled after clinical evaluation and positive result of RADT for group A beta-hemolytic streptococcus (GABHS) in the presence of symptoms suggestive of streptococcal infection, in accordance with the recommendations outlined in the recent Italian intersociety guidelines [1]. In a minority of cases, RADT positivity was complemented by throat culture based on clinical judgment, such as in recurrent episodes, in cases with atypical clinical presentation where a false-positive RADT was suspected, or in more severe presentations where strain characterization was considered relevant. Culture results were interpreted according to the clinical context of each case.

Inclusion criteria were as follows:

  • Age between 1 and 18 years.

  • A diagnosis of GAS pharyngitis was established in accordance with current guidelines [1] and required at least one positive RADT for group A beta-hemolytic streptococcus.

  • Written informed consent obtained from a parent or legal guardian.

Exclusion criteria were:

  • Age > 18 years.

  • Alternative diagnosis.

  • Children with known or suspected immunodeficiency, as well as those receiving immunosuppressive therapies.

Aim of the Study

The aim of this study was to analyze the clinical, microbiological, and therapeutic characteristics of paediatric streptococcal pharyngotonsillitis, with a specific focus on therapeutic failure, complications, recurrences, and early relapses. For the purposes of this study, the primary unit of analysis was an episode of streptococcal pharyngitis, as each clinical presentation was considered an independent event in terms of symptoms, management, and outcomes. However, to account for repeated infections within the same child, episodes were linked at the patient level using unique identifiers. Recurrences were defined and classified at the patient level as early (≤ 4 weeks) or late (> 4 weeks) based on the time interval from the previous episode [1, 9]. Complications were attributed to the specific episode in which they occurred, and analyses comparing complication rates between recurrent and non-recurrent infections were therefore conducted at the episode level. This approach allowed us to capture both the clinical characteristics of individual episodes and the longitudinal pattern of infections within the same patient.

Specifically, the objectives of the study were:

  • To evaluate the management of streptococcal pharyngitis at the first episode observed during the study period.

  • To analyze streptococcal infections with therapeutic failure that resulted in acute and/or chronic complications (Tables 1, 2. Supplementary material Table S2)

  • To analyze early relapses of streptococcal pharyngitis, to assess whether specific antibiotic classes or regimens were associated with early relapse (Tables 3, 4).

  • To analyze antibiotic treatment for the management of the multiple clinically significant recurrences of streptococcal pharyngitis (Tables 3, 4).

Table 1 Demographic characteristics, clinical features, and laboratory findings of episodes of streptococcal pharyngotonsillitis with and without development of complications
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Table 2 Type and duration of antibiotic therapy prescribed for streptococcal pharyngotonsillitis in uncomplicated and complicated cases
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Table 3 Type of antibiotic used in the treatment of recurrent streptococcal pharyngitis
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Table 4 Antibiotic treatment of streptococcal pharyngitis recurrence within 4 weeks after completion of therapy versus antibiotic therapy in non-recurrent streptococcal pharyngitis
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Laboratory Tests

Each paediatrician used an approved and standardized rapid diagnostic kit for the detection of pharyngeal group A beta-hemolytic streptococcal infection, following the manufacturer’s instructions [12].

Definitions

Acute streptococcal pharyngitis was defined as an acute episode of pharyngotonsillar inflammation with clinical features consistent with bacterial infection (such as fever, sore throat, tonsillar exudate, and tender anterior cervical lymphadenopathy) and microbiological confirmation of GAS infection by RADT or throat culture, executed according to the Italian guidelines’ recommendation [1, 13].

Early recurrence refers to the reappearance of symptomatic streptococcal pharyngitis with microbiological evidence of group A Streptococcus (positive pharyngeal RADT or culture) within a short time after completion of appropriate antibiotic therapy, usually within 4 weeks [1, 9], and may reflect either treatment failure, reinfection, or persistence of Streptococcus in the pharynx [1, 9].

Multiple clinically significant recurrences of streptococcal pharyngitis refer to repeated, well-documented episodes of acute streptococcal pharyngitis occurring over months or years, after exclusion of alternative diagnoses and of a chronic carrier state [1].

A (late) recurrence was defined as the reappearance of symptomatic streptococcal pharyngitis with a positive RADT or throat culture for GAS occurring more than 4 weeks after completion of antibiotic therapy for the previous episode [1, 9].

An asymptomatic chronic GAS carrier was defined as a child with persistent pharyngeal colonization by group A Streptococcus, documented by repeated positive throat cultures or RADTs, in the absence of clinical signs or symptoms of acute pharyngitis, who is unlikely to transmit infection or to develop suppurative or non-suppurative complications [1, 13]. Specifically, children presenting with repeat positive RADTs were evaluated by the primary care pediatrician for the presence of clinical features consistent with acute streptococcal pharyngitis. Only episodes characterized by compatible symptoms (e.g., fever, sore throat, tonsillar exudate, cervical lymphadenopathy) with positive RADTs were classified as true recurrences and included in the analysis. Conversely, cases with positive RADTs in the absence of clinical signs or with features suggestive of viral infection (e.g., rhinitis, cough, absence of fever) were considered suggestive of a carrier state and were not classified as clinically significant recurrences, in line with current guidelines.

Data Collection

Data were entered into a dedicated database collecting demographic and professional information of participating physicians and clinical cases.

For each enrolled children, the following anonymized data were collected:

  • Demographic information, including age and region of origin.

  • Clinical symptoms at the time of presentation included fever [(duration of fever (days); maximum temperature (°C)], sore throat; odynophagia; pharyngeal erythema; tonsillar exudate; tonsillar hypertrophy; lymphadenopathy; rhinitis; palatal petechiae; strawberry tongue; scarlatiniform rash. Other type of skin manifestation (e.g. glove-like desquamation, hemorrhagic rash, etc.). Gastrointestinal symptoms: vomiting, diarrhea, abdominal pain. It also included asthenia and cough.

  • Results of diagnostic tests, including RADT and throat culture; for throat cultures, antibiotic susceptibility profiles were also collected.

  • Details of antibiotic therapy, including the type of antibiotic prescribed, duration of treatment, and dosage.

All enrolled children were followed for the entire duration of the study period (August 1, 2024 to June 30, 2025), corresponding to a maximum follow-up of approximately 11 months per patient, depending on the timing of enrollment. The minimum follow-up duration was at least 1 month, even for episodes recorded at the end of the study period, allowing for the detection of both acute and early non-suppurative complications. Follow-up was conducted within routine clinical practice and included both telephone contact and clinical reassessment when needed. In asymptomatic children, no scheduled in-person follow-up visits were performed. In contrast, in the presence of new symptoms suggestive of recurrence or complications, children were re-evaluated by their primary care pediatrician, who decided whether to perform further diagnostic testing (including RADT or throat culture) according to national and international guidelines [1]. Recurrences and complications were identified through this continuous clinical surveillance and through review of the patient’s medical records. No patients were lost to follow-up. This was possible due to the structure of the Italian primary care paediatric system, in which each child is continuously followed by their designated family paediatrician, who is responsible for longitudinal care and maintains the complete clinical history. The follow-up assessments were therefore conducted within the enrolling pediatrician’s practice. However, as the primary care paediatrician acts as the central coordinator of care, clinically relevant events occurring in other healthcare settings (e.g., emergency departments or specialist consultations) are routinely reported back and recorded, allowing their inclusion in the dataset. This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.

The present study is a low-risk observational study exclusively on anonymized and aggregated clinical data. In all cases, written informed consent was obtained from the caregivers for the use of data related to each episode of pharyngitis. Data collection complied with the European General Data Protection Regulation (GDPR 2016/679). The study was approved by the SiCupp Scientific Review Board (protocol # SBEASICUPP1902024).

Statistical Analysis

Categorical variables were expressed as absolute numbers and percentages. Continuous variables, such as age, were categorized to enable comparisons across groups. Categorical data were compared using the chi-square test or Fisher’s exact test, as appropriate, to assess statistically significant differences between children with streptococcal pharyngitis with or without complications. In addition, differences in antibiotic therapy between groups were evaluated using the chi-square test. All statistical analyses were performed using Stata Statistical Software, Release 18 (StataCorp LLC, College Station, TX, USA). Statistical significance was defined as a two-sided p value < 0.05.

Results

A total of 66 family paediatricians voluntarily participated in the study and were distributed across all 20 regions of Italy. Specifically, 11.5% of children were enrolled from southern regions, 16.3% from central regions, and 72.2% from northern regions.

We enrolled 1187 children; 910 (76.6%) experienced a single episode of streptococcal pharyngitis, whereas 277 (23.4%) had at least one recurrence during the study period. Among the 1187 children included in the study, 342 (28.8%) were aged < 5 years, 509 (42.9%) were aged 5–8 years, 257 (21.6%) were aged 9–11 years, and 79 (6.7%) were aged 12–18 years.

A total of 1464 episodes of streptococcal pharyngotonsillitis diagnosed by a positive RADT for GAS in 1187 children were included in the analysis. A total of 910 children (76.6%) experienced a single episode of GAS pharyngitis, whereas 61 children (5.1%) had one recurrence within 4 weeks of the previous episode, and 160 children (13.4%) experienced 216 recurrences occurring more than 4 weeks after the previous episode (Supplementary material Tables S2–S3). Throat culture was performed in a minority of cases (25/1464 episodes, 1.7%). Among these, 17 cultures were positive (68%), while 8 were negative (32%). Of the 1464 episodes, 1457 (99.5%) had an uncomplicated course, whereas 7 episodes in 7 children (0.5%) developed at least one acute or chronic streptococcal-related complication (Table 1, Supplementary material Tables S2–S3).

Only 24 children (2.2%) corresponding to 26 episodes (1.7%) had a suspected or confirmed beta-lactam allergy. Amoxicillin was prescribed as first-line therapy in 77.5% of uncomplicated episodes, and overall, 51.5% of cases were fully adherent to guideline recommendations [1]. Non-adherence was attributable to inappropriate antibiotic selection in 22.9% of episodes and to an incorrect duration of antibiotic therapy in 25.6% of episodes (Table 2).

Clinical Characteristics and Antibiotic Therapy of Streptococcal Pharyngitis Who Developed Complications

Overall, seven cases (0.5%) of complicated streptococcal pharyngitis were observed among 1464 recorded episodes during the study period. Importantly, all complications occurred during the initial episode of infection, whereas no complications were documented in recurrent episodes.

Clinical features at presentation of all episodes of streptococcal pharyngitis with and without development of complications are summarized in Table 1 and Supplementary material Table S2. Gastrointestinal manifestations were significantly more frequent among children who subsequently developed complications compared with those with an uncomplicated course (p = 0.03), no other significant clinical difference was observed between the two groups of children. Recurrent infections, whether occurring shortly after treatment or over longer intervals, were not associated with an increased development of complications (p = 0.75) (Table 1, Supplementary material Table S2).

Acute complications included pneumonia, sinusitis, cellulitis, suppurative cervical lymphadenitis, and peritonsillar/retropharyngeal abscess. One case of post-streptococcal glomerulonephritis was observed (Supplementary material Table S2).

Among children with uncomplicated streptococcal pharyngitis, amoxicillin was prescribed as first-line therapy in 77.4% of cases, with a median dosage of 50 mg/kg/day for a median duration of 10 days (IQR 7–10 days), while amoxicillin–clavulanic acid was used in 13% of cases. In contrast, among children who developed complications, amoxicillin was prescribed in 28.6% of cases, whereas amoxicillin–clavulanic acid was used in 71.4% (p = 0.0001). Antibiotic management and duration therapy of streptococcal pharyngitis with and without complications is summarized in Table 2. No significant differences were observed in dosage or duration of therapy between the two groups (Tables 1, 2).

Three children required hospitalization: one for cellulitis, one for suppurative lymphadenitis, and one for a peritonsillar abscess. All patients recovered completely without sequelae. Notably, all three children had received oral antibiotic therapy with amoxicillin–clavulanate at a dosage of 50 mg/kg/day prior to hospitalization (Supplementary Material Table S2).

According to the collected data, 17.3% of episodes of streptococcal pharyngotonsillitis (GAS infection) in patients without complications and 14.3% of episodes in patients with complications occurred without fever, suggesting that these may have represented intercurrent viral infections. Therefore, we repeated the analysis after excluding these afebrile episodes; however, no statistically significant differences were observed (Supplementary material Tables S4–S5).

Antibiotic Resistance

A throat culture was performed in 25 episodes (1.7%). Among those with a positive culture (n = 17), antibiotic resistance was detected in approximately 23.5% of isolates. Resistance was observed to clindamycin (n = 1), erythromycin (n = 2), and levofloxacin (n = 1) (Table 1). All GAS isolates were susceptible to amoxicillin.

Antibiotic Therapy of Short-Term Recurrence (< 4 Weeks)

A total of 61 episodes (5.1%) were classified as early recurrence of streptococcal pharyngitis.

All cases of short-term recurrences were treated with antibiotic therapy (Tables 3, 4). When the antibiotic treatment used during the first episode in children who developed an early recurrence was compared with that used in those who did not, amoxicillin and amoxicillin–clavulanic acid were the most frequently prescribed agents in both groups (90.1% in early recurrences and 93.0% in non-recurrent episodes). However, children who subsequently developed an early recurrence had received a 5-day course of cephalosporins more frequently during the first episode, with a statistically significant difference compared with children without early recurrence (p = 0.043) (Table 4). During short-term recurrence, only 26 episodes (42.6%) of streptococcal pharyngitis were treated with amoxicillin; 14 (23.0%) with amoxicillin–clavulanic acid, 7 (11.5%) with cephalosporins, 3 (4.9%) with azithromycin, and 9 (14.8%) with antibiotic therapy combined with rifampicin (Table 3).

Multiple Recurrent Streptococcal Pharyngitis

Among 160 children (13.5%) who experienced multiple symptomatic recurrence, 45 children (3.8%) experienced two symptomatic recurrences and 12 children (1%) experienced three or more recurrences.

With regard to antibiotic therapy at the first recurrence, amoxicillin was the most frequently prescribed antibiotic (62.5%), followed by amoxicillin–clavulanic acid (18.8%). About 11% of primary care pediatricians switched antibiotic therapy to a cephalosporin, a macrolide, or a combination of amoxicillin and rifampicin. At the second recurrence amoxicillin was used only in 62.2% of episodes, whereas at the third or subsequent recurrences amoxicillin–clavulanic acid became the most frequently prescribed antibiotic (41%) (Table 3).

Episodes presenting with clinical features of scarlet fever were found to have a significantly higher risk of recurrence. Specifically, recurrence occurred in 57 of 175 episodes associated with scarlet fever and in 116 of 324 episodes presenting with strawberry tongue (p < 0.001). These findings suggest that GAS infections characterized by scarlet fever manifestations may be associated with an increased likelihood of subsequent recurrence (Supplementary Material Table S6).

Discussion

More than 1000 children with streptococcal pharyngitis managed by 66 primary care pediatricians uniformly distributed across Italy were analyzed. Despite the increased circulation of GAS, the clinical severity of disease in our cohort remained low, with complications reported in only 0.5% of cases. Furthermore, the lack of association between recurrences and complications observed in our study suggests that even in a setting of heightened GAS transmission, repeated infections do not necessarily translate into more severe clinical outcomes. These findings reinforce the concept that, although epidemiological fluctuations may influence incidence and recurrence patterns, they do not appear to significantly modify the overall risk profile of GAS pharyngitis in children managed in primary care.

Consistent with international data showing that suppurative complications are uncommon [13, 14], in our study 99.5% of episodes presented an uncomplicated clinical course.

According to national and international guidelines [1, 13, 15, 16], first-line therapy of streptococcal pharyngitis is orally administered amoxicillin (Supplementary material Table S1). In other countries penicillin V remains an appropriate narrow-spectrum option for GAS pharyngitis. However, penicillin V is not available in Italy and therefore amoxicillin is the recommended first-line treatment [1], considering palatability, availability, and ease of administration. Antibiotic resistance patterns strongly support the preferential use of narrow-spectrum beta-lactams; GAS remains universally susceptible to penicillin and amoxicillin, and resistance leading to clinical failure has never been documented. This contrasts with rising resistance to macrolides and lincosamides in many countries, as also observed in our study, where strains resistant to clindamycin, erythromycin, and levofloxacin were isolated [1, 13, 14]. Moreover, in our cohort, children who later developed complications were more frequently treated with amoxicillin–clavulanic acid, with no differences in dosage or duration. This does not imply a causal role of the antibiotic; rather, it underscores that broad-spectrum agents do not offer superior protection against complications. This finding is consistent with the 2021 Cochrane Review on antibiotic treatments for GAS pharyngitis, which analyzed 19 randomized controlled trials including 5839 participants [16]. The review concluded that no alternative antibiotic class—including cephalosporins, macrolides, azithromycin, or carbacephems—demonstrated clinically meaningful superiority over amoxicillin in terms of symptom resolution, prevention of relapse, or reduction of complication. Notably, macrolides were associated with higher rates of side effects [16].

In our study, only 77% of streptococcal pharyngitis episodes were treated with amoxicillin; however, among these, slightly more than half (754/1129; 66%) received the recommended 10-day course. Although some studies have suggested that shorter antibiotic regimens may achieve clinical outcomes comparable to the traditional 10-day course [17, 18], current Italian intersociety guidelines [1] continue to recommend 10 days of amoxicillin for GAS pharyngotonsillitis, primarily to prevent acute rheumatic fever. Given the lack of contemporary population-based epidemiological data and the absence of a national registry for acute rheumatic fever in Italy, the actual burden of rheumatic disease remains uncertain. Therefore, adherence to the recommended 10-day regimen appears to be a prudent approach until more robust national data become available.

Overall, only half of streptococcal pharyngitis episodes were treated correctly, while the remaining children (48.5%) received inappropriate therapy, either because of an incorrect antibiotic choice or an inadequate duration of treatment. In our study 84 (5.7%) episodes were treated with a cephalosporin, and among these, cefixime was used in 70% of cases. Although many primary care pediatricians favor cefixime as a first-line oral antibiotic because of its convenient once-daily dosing regimen, it is important to emphasize that narrow-spectrum β-lactams can also be administered once daily in selected clinical settings. Notably, the US Centers for Disease Control and Prevention (CDC) recommends oral administration of amoxicillin at a dose of 50 mg/kg once daily as a first-line treatment for streptococcal pharyngitis [19]. Cefixime is not considered an optimal therapeutic option for Gram-positive pathogens such as GAS; in patients with non-immediate penicillin hypersensitivity, the CDC recommends first-generation cephalosporins such as cephalexin and cefadroxil, which have a relatively narrow antibacterial spectrum [19]. This approach is consistent with the principles of antimicrobial stewardship and aligns with the WHO AWaRe framework, which encourages preferential use of Access antibiotics and the judicious use of broader-spectrum Watch agents, thereby limiting unnecessary selective pressure for antimicrobial resistance [20]. However, cefaclor has also demonstrated good clinical efficacy against GAS infections. In a randomized trial including 256 children with GAS tonsillitis, Li et al. showed that a 5-day course of cefaclor achieved clinical success rates comparable to those obtained with the standard 10-day course of amoxicillin (92.4% vs. 91.0%, respectively). Moreover, bacteriological eradication rates were similar (89.9% vs. 88.5%), as were pathogen recurrence rates at follow-up (7.0% vs. 5.9%) [21]. The recent Italian intersociety consensus recommends, in patients with low-risk allergy to amoxicillin, a short course of a third-generation cephalosporin, such as cefpodoxime proxetil, or alternatively a macrolide [1]. Clindamycin is reserved for GAS carriers with multiple clinically significant recurrences who are being considered for tonsillectomy [1]. In our cohort, the use of short-course cephalosporins, particularly cefixime, was significantly associated with early recurrence of streptococcal pharyngitis. Although causality cannot be established because of the observational design of the study, pharmacokinetic considerations may partially explain this finding. Cefixime has relatively low and variable oral bioavailability (approximately 40–50%), which may lead to lower and less sustained antibiotic concentrations in target tissues compared with other β-lactams [22]. Suboptimal antibiotic exposure at the pharyngeal level may contribute to incomplete eradication of group A Streptococcus and favor early relapse or persistence of infection [23, 24]. However, these observations should be interpreted with caution, as the observed association may also reflect confounding by indication, whereby physicians may have preferentially prescribed cephalosporins to children perceived with more severe clinical presentations, or with a history of previous treatment failure. In addition, no data on treatment adherence or antibiotic concentrations were available in our study. Therefore, this association should be considered a hypothesis-generating finding rather than evidence of a causal relationship, and further prospective and interventional studies are needed to validate this observation and clarify the underlying mechanisms.

Broad-spectrum cephalosporins, particularly third-generation agents, are recognized as important drivers of antimicrobial resistance compared with narrow-spectrum penicillins, mainly because their widespread use exerts a stronger selective pressure on bacterial populations [25]. Their extensive prescription has been associated with the emergence and dissemination of resistant pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, which are able to hydrolyze third-generation cephalosporins and are often carried on transferable plasmids [25].

Several factors may contribute to variability in antibiotic selection and duration in primary care, including physician experience and preferences, local prescribing culture, concerns about treatment failure, reported or suspected drug allergies, and parental expectations [26, 27]. In addition, previous studies have shown that clinical decision-making in paediatric respiratory infections is often influenced by contextual and behavioral factors that extend beyond guideline recommendations alone [28]. Therefore, while our findings highlight discrepancies between recommended and real-world practice, they should not be interpreted solely as inappropriate prescribing. Rather, they reflect the complexity of clinical decision-making in primary care settings. Further research is needed to better understand the determinants of antibiotic prescribing and to develop targeted antimicrobial stewardship interventions.

This study represents one of the few available investigations addressing recurrent streptococcal pharyngitis. Sixty-one children experienced early relapses of streptococcal pharyngitis, presenting with typical symptoms and a positive RADT for GAS. Approximately one-third of the study population was younger than 5 years of age, an age group in which recurrent GAS pharyngitis is generally considered uncommon. Nevertheless, an increasing number of studies have reported that GAS pharyngitis can occur in preschool-aged children [29]. Therefore, we cannot completely exclude the possibility that a proportion of these children with positive RADT results were actually pharyngeal GAS carriers experiencing concomitant viral upper respiratory tract infections rather than true recurrent streptococcal pharyngitis. However, because RADT was performed according to the McIsaac criteria, which improve the pre-test probability of GAS infection, it is reasonable to assume that such misclassification, if present, was limited and unlikely to have substantially affected our findings. The subgroup of children who developed early relapse showed a significantly higher use of cephalosporins (cefaclor and cefixime). According to the Infectious Diseases Society of America guidelines 2025 a short-interval recurrence of streptococcal pharyngitis should be treated with amoxicillin for 10 days, or appropriate alternatives in case of allergy, when the patient presents with typical clinical features and laboratory confirmation of GAS [13]; indeed this most likely represents a new or persistent true infection rather than asymptomatic carriage [13, 15, 16]. In our study, all children with short-term recurrence were treated with antibiotic therapy; however, only 42% received amoxicillin, 22.9% were treated with amoxicillin–clavulanate, and 14.5% received a combination regimen including rifampicin. The remaining children were treated with a cephalosporin (12%) or a macrolide (5%). Within this cohort, streptococcal throat swab testing was overused: in 32% of cases it was performed despite the absence of fever and based only on the isolated presence of a single clinical sign, namely sore throat, tonsillar hypertrophy, or pharyngeal hyperemia.

In our study, 160 children (13.5%) experienced 216 recurrent episodes occurring more than 4 weeks after the previous episode. All children were treated with antibiotic therapy; however, only 60% of first recurrences were treated with amoxicillin. In the remaining cases, primary care pediatricians switched therapy to a cephalosporin, a macrolide, or a combination of amoxicillin and rifampicin, not in agreement with the Italian intersociety guidelines [1]. In addition, considering that multiple GAS recurrences are likely to be repeated viral infections in GAS carries, and do not require antimicrobial therapy. Consequently, each episode should be carefully assessed by the primary care pediatrician, as inappropriate use of RADTs may lead to the identification of streptococcal pharyngitis in chronic carriers who are experiencing viral infections [15, 16].

Eradication of carriage should be reserved only for selected special circumstances, such as outbreaks of acute rheumatic fever or invasive GAS disease and a personal or family history of rheumatic fever [15, 16]. In our study, one out of four family paediatricians adopted an eradication antibiotic regimen including rifampicin at the time of the first recurrent episode. A recent Italian intersociety consensus suggests that in cases of relapsing GABHS tonsillitis, including Paradise’s criteria, eradication therapy with antibiotics may be considered in patients who are candidates for tonsillectomy, as an attempt to avoid surgery (Supplementary material Table S2) [1]. The use of alternative antibiotic regimens in recurrent GAS pharyngitis is not primarily driven by antimicrobial resistance of Streptococcus pyogenes, which remains uniformly susceptible to penicillin. Rather, it is based on the hypothesis that recurrent episodes may be sustained by bacterial persistence, pharyngeal carriage, or the presence of β-lactamase-producing copathogens within the tonsillopharyngeal microbiota. In this context, systematic reviews and randomized trials have suggested that antibiotics such as amoxicillin–clavulanate, clindamycin, or penicillin combined with rifampicin may achieve higher eradication rates and reduce further recurrences compared with penicillin alone, although the overall quality of evidence remains limited [30,31,32,33,34,35]. These findings may explain why broader-spectrum agents are occasionally selected in patients with recurrent disease despite the preserved susceptibility of GAS to narrow-spectrum penicillins [1, 9, 30,31,32,33,34,35].

Limitations

This study has several limitations. Antibiotic susceptibility testing was performed in only a small subset of cases, and no molecular characterization (e.g., emm typing) was available, limiting microbiological interpretation. The use of RADT without systematic throat culture may have led to misclassification, particularly in distinguishing true infection from carriage, which was not formally ruled out with standardized protocols. A further limitation is the very low rate of throat culture confirmation (1.7%). Consequently, some recurrent episodes classified as GAS pharyngitis may have represented GAS carriage associated with a concomitant viral infection rather than true recurrent streptococcal infection. This potential misclassification could have led to an overestimation of recurrence rates and, to a lesser extent, GAS-related complications. However, throat culture is not routinely performed in Italian primary care practice, and our findings therefore reflect real-world clinical management. The observational design and low number of complications limited stratified analyses on antibiotic choice and duration. In addition, factors such as treatment adherence, timing of therapy, and pharmacokinetics were not assessed. Although follow-up was ensured by primary care pediatricians, some events managed in other settings may have been underreported. Finally, voluntary participation of experienced SICuPP pediatricians may introduce selection bias and limit generalizability.

Conclusions

This prospective observational study provides a comprehensive overview of the clinical course and outpatient management of pediatric streptococcal pharyngitis in Italy. Most episodes were benign and uncomplicated, and complications were rare. Recurrent infections, whether early or late, were not associated with an increased risk of complications.

Despite the availability of clear national and international guidelines, substantial variability in clinical practice was observed. Only three-quarters of episodes were treated with first-line amoxicillin, and adherence to the recommended 10-day course was suboptimal, with only about half of cases managed according to guidelines. Broad-spectrum antibiotics were frequently prescribed without clear clinical indication, despite the low prevalence of beta-lactam allergy and lack of evidence of superior efficacy.

In children with recurrent pharyngitis, diagnostic testing was often performed in low-probability clinical scenarios, potentially leading to unnecessary antibiotic use. Overall, these findings highlight a gap between evidence-based recommendations and real-world practice, underscoring the need to strengthen antimicrobial stewardship in primary care.