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

Background Public 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. Methods We 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. Findings Of 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. Interpretation Our 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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Participant identifiable data were not collected or held for this study. Data collected for the study may be made available on request.