Excessive antimicrobial use, environmental factors, and bacterial evolutionary dynamics contribute to antimicrobial resistance. This study aimed to describe and analyze factors related to resistance in Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae.

Resistance profile data were provided by the Adolfo Lutz Institute. Minimum inhibitory concentration cutoffs followed CLSI guidelines until 2021 and the Brazilian Committee on Antimicrobial Susceptibility Testing from 2022 onward. Isolates were classified as “susceptible” or “susceptible, increased exposure” versus “resistant.” Binary logistic regression was performed to assess factors associated with resistance. Results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) and α < 0.05.

For N. meningitidis, 2,008 isolates were included, with 3/1,984 resistant to ciprofloxacin and penicillin, and 6/1,981 to rifampicin. For H. influenzae (n = 1,274), male sex was associated with ampicillin resistance (OR: 1.46; 95%CI: 1.08–2.00). Resistance to sulfamethoxazole-trimethoprim (SMX-TMP) was higher in bronchoalveolar lavage samples (OR: 1.65; 95%CI: 1.02–2.64) and lower in cerebrospinal fluid samples (OR: 0.65; 95%CI: 0.45–0.92). For S. pneumoniae (n = 9,706), progressive resistance increases were observed for all antimicrobials, peaking in 2022–2023. The highest resistance rates were seen for ceftriaxone (OR: 8.47; 95%CI: 4.60–17.2), clindamycin (OR: 4.63; 95%CI: 3.65–5.91), erythromycin (OR: 5.16; 95%CI: 4.17–6.43), oxacillin (OR: 2.28; 95%CI: 1.89–2.75), SMX-TMP (OR: 1.64; 95%CI: 1.37–1.97), and tetracycline (OR: 2.57; 95%CI: 2.12–3.11). Children under 12 years had higher odds of resistance to all antimicrobials. Female sex was associated with resistance to clindamycin (OR: 1.19; 95%CI: 1.08–1.32), oxacillin (OR: 1.15; 95%CI: 1.05–1.26), and SMX-TMP (OR: 1.11; 95%CI: 1.01–1.21).

Factors associated with antimicrobial resistance varied by microorganism and drug tested. Sex, age, and year of isolation were significant determinants of the increasing bacterial resistance observed in Brazil from 2013 to 2023.