Objectives: To determine antibiotic susceptibility of community-acquired respiratory tract infection (CA-RTI) isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2015-18 from Tunisia, Kenya and Morocco. Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: S. pneumoniae isolates from Tunisia (n = 79), Kenya (n = 44) and Morocco (n = 19) and H. influenzae isolates (n = 74) from Tunisia only were collected and analysed. Low antibiotic susceptibility was observed in S. pneumoniae from Tunisia, with >90% susceptible only to the fluoroquinolones (all breakpoints), penicillin (CLSI IV and EUCAST high-dose) and ceftriaxone (CLSI, EUCAST high-dose and PK/PD breakpoints). In addition, isolate susceptibility in Kenya was >90% to amoxicillin and amoxicillin/clavulanic acid (CLSI and PK/PD breakpoints). Antibiotic activity was highest in Morocco, where ≥89.5% of pneumococci were susceptible to most antibiotics, excluding trimethoprim/sulfamethoxazole (68.4% by CLSI or PK/PD and 79%-84.2% by EUCAST), macrolides (79%-84.2% by all breakpoints) and cefaclor (0% by EUCAST and 52.6% by PK/PD). The majority (≥86.5%) of H. influenzae isolates from Tunisia were susceptible to most antibiotics by all available breakpoints, except ampicillin and amoxicillin (almost one-third were b-lactamase positive), trimethoprim/sulfamethoxazole (51.4%-56.8%), cefaclor (1.4% by PK/PD), cefuroxime (4.1% by EUCAST), macrolides (1.4%-2.7% by PK/PD) and cefdinir (66.2% by PK/PD). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Conclusions: Low antibiotic susceptibility was observed in S. pneumoniae from Tunisia, but susceptibility was higher in isolates from Kenya and highest in those from Morocco. H. influenzae from Tunisia were highly susceptible to most antibiotics. These factors are important in decision making for empirical therapy of CA-RTIs.