Time to negative throat culture following initiation of antibiotics for pharyngeal group A Streptococcus: a systematic review and meta-analysis to inform public health control measures

BackgroundPublic health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12-24 hours from antibiotic initiation to prevent onward transmission requires a strong evidence-base. MethodsWe conducted a systematic review (PROSPERO CRD42021290364) and meta-analysis to estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics. We searched Ovid MEDLINE (1946-), EMBASE (1974-) and the Cochrane library. We included interventional or observational studies with ten or more participants reporting rates of GAS throat culture during antibiotics for culture confirmed GAS pharyngitis, scarlet fever, and asymptomatic pharyngeal GAS carriage. We did not apply age, language, or geographical restrictions. FindingsOf 5,058 unique records identified, 43 were included; 37 (86%) randomised controlled studies, three (7%) non-randomised controlled trials and three (7%) before-and-after studies. The proportion of individuals who remained culture-positive at day 1, day 2, and day 3-9 were 6.9% (95% CI 2.7-16.8%), 5.4% (95% CI 2.1-13.3%) and 2.6% (95% CI 1.6-4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI 2.5-16.1%) and 1.6% (95% CI 0.04-42.9%) respectively. Overall, for 9.1% (95% CI 7.3-11.3), throat swabs collected after completion of therapy were GAS culture-positive. InterpretationOur review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 hours but highlights the need for further research given the methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and for asymptomatic individuals.