Abstract

Background

In some settings pneumococcal antibiotic resistance is more prevalent among disease causing strains. As such it has been hypothesised that pneumococcal conjugate vaccine (PCV) introduction may reduce overall pneumococcal antibiotic resistance. We aimed to evaluate the presence of antibiotic resistance loci amongst pneumococci isolated from Nepalese children before and after programmatic PCV introduction in 2015.

Methods

DNA from 935 (508 pre-PCV10 and 427 post-PCV10) pneumococcal isolates obtained from Nepalese children in Kathmandu between 2005 and 2018, underwent whole-genome-sequencing on the Wellcome Sanger Institutes core sequencing pipeline. Whole-genome sequences for each isolate were screened for homology to known antibiotic resistance loci. The Clinical and Laboratory Standards Institute breakpoints were used to inform antibiotic resistance using this pipeline.

Results

When comparing the pre- with post-PCV10 periods a significant increase was observed in proportion of isolates with a locus conferring resistance to penicillin (76/432, 15% vs 138/289 32.3%, p<0.0001), cefuroxime (15/49, 3% vs 37/390, 8.7%, p=0.0002), erythromycin (79/429, 15.6% vs 196/231, 45.9%, p<0.0001), clindamycin (37/471, 7.3%) vs 110/317, 25.7%, p<0.0001), and tetracycline (172/336, 33.9% vs 212/215, 49.6%, p<0.0001). Resistance to co-trimoxazole was consistently high across the study periods (397/111, 78.1% vs 347/80, 81.3%). Resistance to amoxicillin was very limited in both study periods (0/508, 0% vs 3/424, 0.7%).

Conclusions

There is increasing prevalence of antibiotic resistance loci across a range of antimicrobial classes. First-line management of childhood community acquired pneumonia with amoxicillin remains a valid approach in this setting; however, co-trimoxazole is likely to be of limited utility.

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