Impact of intermittent preventive treatment in pregnancy with azithromycin-containing regimens on maternal nasopharyngeal carriage and antibiotic sensitivity of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus - a cross-sectional survey at delivery
Sulphadoxine-pyrimethamine (SP) plus azithromycin (AZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe paediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus at delivery amongst 854 women participating in a randomised controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery of S. pneumoniae (SPAZ: 7.2% [30/418] vs. SPCQ: 19.3% [84/436], P <0.001) and H. influenzae (2.9% [12/418] vs. 6.0% [26/436], P = 0.028), but not S. aureus, was significantly reduced amongst women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small, but increased in the SPAZ group (13.3% [4/30] vs. SPCQ 2.2% [2/91], P = 0.033). The proportion of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine was similar (SPAZ: 10.3% [3/29] vs. SPCQ: 17.6% [16/91], P = 0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage of S. pneumoniae and H. influenzae observed in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistant S. pneumoniae and other pathogenic bacteria in both mothers and infants, and assess the clinical significance of their circulation.