# Acute Otitis Media in Children--Challenges of Antibiotic Resistance in the Post-Vaccination Era
## 4 Discussions
In the United States of America, antibiotic non-susceptible invasive pneumococcal strains decreased between 2009 (immediately before PCV13 was introduced) and 2013, from 6.7 to 2.2 per 100,000 for all ages, and from 6.5 to 0.5 per 100,000 in children younger than 5 years [19]. According to the World Health Organization, the prevalence of nasopharyngeal carriage of _Streptococcus pneumoniae_ in infants and young children ranges from 27% to 85%, with higher rates among children in low- and middle-income countries [20]. A study of pediatric nasopharyngeal pneumococcal carriage rates in Romania found an incidence of 25%, with 59% of the serotypes isolated being covered by PCV13. Moreover, according to the most recent European Antimicrobial Resistance Surveillance Network data, the national incidence of penicillin non-susceptible pneumococcal in Romania increased from 27.9% in 2017 to 40% in 2018 [21]. Amoxicillin and amoxicillin-clavulanate represent the preferred therapeutic agents for AOM caused by _Streptococcus pneumoniae_, whereas cephalosporins (cefitime) are preferred in AOM caused by _Hemetophilus influenzae_ or _Moravella catarrhalis_[22]. Although the clinical practice guidelines provide a standardized and systematic approach on AOM management, the (locally) resistant strains, associated with treatment failure or severe cases of AOM, may require specific recommendations. When drafting a local guideline, it would be useful to consider the regional antimicrobial resistance patterns, since most of the otitis in children do not undergo routine tympanocentesis. In order to promote antibiotic stewardship, the WHO underlines the importance of guidelines with recommendations based on a regional antibiotic resistance profile. Many guidelines promote antibiotic stewardship, but only some (the United States of America, Australia, Belgium, Finland, Italy, Netherlands, Poland, Sweden, Portugal, Spain) of the guidelines take into consideration regional antimicrobial resistance patterns [23]. We have previously reviewed 20 AOM clinical practice guidelines on AOM management and noticed that the watchful waiting approach is preferred to immediate antibiotic treatment in 16 of the 20 guidelines, in order to decrease the antimicrobial resistance phenomenon. We noted that amoxicillin is the most recommended first-line treatment (16/20 guidelines). A high dose of 80 to 90 mg/kg/day of amoxicillin is encouraged in order to provide sufficient levels of antibiotic treatment in the middle ear fluid and to eradicate most of the _Streptococcus pneumoniae_ strains. Only three guidelines (Denmark, Norway and Sweden) encourage the utilization of oral penicillin as a first-line choice [23]. Nowadays, there is no global consensus on which is the best treatment for children with persistent and significant AOM symptoms despite at least 48 h of antibiotic treatment. Besides clinical reexamination and consideration of tympanocentesis, most of the examined guidelines recommend a high dose of amoxicillin-clavulanate [23]. Some guidelines recommend extending the duration of amoxicillin therapy with at least 5 days (the WHO),increasing the amoxicillin dose to a maximum of 90 mg/kg/day (Australia, Germany), switching to a second generation of cephalospororin such as cefuroxime (Italy, Portugal), to a third generation cephalospororin such as ceftaxone (Finland, France), or to trimethoprim/sulfamethoxazole (Norway). As the inefficiency of beta-lactamase inhibitors (in a standard dose) against penicillin-resistant _Streptococcus pneumoniae_ strains was proven, being based on different mechanisms of resistance and limited spectrum of action, higher doses are needed in order to overcome the resistance phenomenon [23]. Despite the availability of the guidelines, the misuse of broad-spectrum antibiotics continued [24]. In clinical practice, using broad-spectrum antimicrobials has proven its efficiency only in terms of reducing the rate of treatment failure, but with the price of increasing adverse effects and a negative impact on quality of life [25].