# Acute Otitis Media in Children--Challenges of Antibiotic Resistance in the Post-Vaccination Era
## 4 Discussions
Effective strategies of implementation are needed in order to reduce the threat of the worrying number of cases with an unjustified use of antibiotics [26]. Geographical differences regarding antimicrobial susceptibility patterns have been reported, emphasizing the role of regional surveillance studies in antibiotic prescriptions [4]. In Europe, there are limited data regarding antibiotic resistance in otitis media. However, in Greece, [PERSON] et al. suggest that the non-susceptibility rates of _Streptococcus pneumoniae_ to penicillin increased in the post-vaccination era [27]. In Bulgaria, [PERSON] et al. report a 68.1% rate of penicillin-resistant strains [28], whereas in Spain, the reported percentage is only 6.5% [29]. These differences are based on variations of vaccination rates, adherence to guidelines and even laboratory testing methods. Moreover, the last update on NICE (The National Institute for Health and Care Excellence) AOM management guideline (March 2022) underlines the importance of antibiotic stewardship and includes new recommendation on analgesic eardrops for children who do not need immediate antibiotics (AOM with no perforation or otorrhoea) in order to reduce the local inflammation and to decrease the antibiotic consumption [30]. Regarding the antimicrobial resistance of microorganisms found in middle ear samples from children with AOM, [PERSON] et al., in a systematic review including 19 studies (10,560 children), reported that _Streptococcus pneumoniae_, _Haemophilus influenzae_ and _Stablyococcus aureus_ were the most prevalent microorganisms, with 76% of positive cultures [31]. The antimicrobial resistance reports were limited to _Streptococcus pneumoniae_, with a non-susceptibility rate (resistant or intermediate strains) ranging from 0% to 65.8%. These large variations are based on different vaccination rates, accessibility to medical services or geographical specific patterns (e.g., high AOM rates in indigenous Australians) [32]. In our sample, the highest frequency of resistance in isolated pneumococcal was recorded for trimethoprim/sulfamethoxazole (64/70 strains), followed by macrolides (61/70 strains) and limcosamides (54/70 strains), while the lowest incidence was recorded for fluoroquinolones and vancomycin (0/70 strains). Various mechanisms of resistance have been discussed regarding these antibiotic classes: dihydroproteoate synthase gene mutation, which is responsible for the occurrence of resistance to trimethoprim/sulfamethoxazole [33], and ribosomal demethylation or mutations of the ribosomal target site in macrolides [34]. The high proportion of the pneumococcal isolates' resistance to trimethoprim/sulfamethoxazole (91.42%) is consistent with another retrospective study based on microbiological testing in children with AOM from our country: the highest non-susceptibility rate was also reported for trimethoprim/sulfamethoxazole (75%), but with lower non-susceptibility rates for macrolides (58.3% vs. 87.6% in our sample) and limcosamides (35.4% vs. 77.14% in our sample) [35]. Similarly, multidrug resistance of _Streptococcus pneumoniae_ strains was detected in most cases (68.7% vs. 82.85% in our sample) [35]. However, based on the results of a meta-analysis of the studies on the antimicrobial resistance patterns in AOM in children, the recommendation of using amoxicillin as a first choice in treating children with AOM is still reasonable as the resistance of _Streptococcus pneumoniae_ to penicillin is not usually associated to resistance to amoxicillin [36]. The culture-negative cases who required hospitalization due to positive criteria for acute otitis media (acute onset of the symptoms--fever, irritability, otalgia or otorrhea and middle ear effusion confirmed by otoscopy) raised particular awareness to us. It has been stated that conventional culture methods detect AOM pathogens in only 60% to 70% of cases [37].