Summary of studies, systematic reviews, and meta-analyses examining the effect of acute antimicrobial treatment on preventing chronic pain symptoms
| Study, Year | Study type | Conditions & populations | Results | Comments |
|---|---|---|---|---|
| Chen et al., 2014 [19] | Systematic review and meta-analysis | Herpes zoster, prevention of PHN; 6 included studies (n = 1,211) | Meta-analysis of 3 RCTs (n = 609) found no difference between acyclovir and control groups for incidence of PHN 4 months after acute herpetic rash (RR, 0.75; 95% CI, 0.51 to 1.11) or at 6 months based on 2 trials. In 4 trials (n = 692), there was some evidence for a reduction in pain 4 weeks after onset of rash. | One study (n = 419) for famciclovir found no evidence for 500 mg or 750 mg for reducing incidence of PHN compared to placebo. |
| Xie et al., 2022 [33] | Retrospective study in patients with at least 2 risk factors for “long Covid” and were not hospitalized after positive test | Prevention of long Covid in veterans; included 9,217 patients who received nirmatrelvir within 5 days of positive COVID test and 47,123 who did not. | Receiving treatment resulted in a reduced risk (HR, 0.74; 95% CI, 0.69, 0.81) of post-acute sequelae of COVID, including myalgia. | Published on a preprint server, without peer review. Among 12 variables examined, including muscle pain, the only 2 which did not decrease in incidence were cough and new-onset diabetes. |
| Byambasuren et al., 2023 [38] | Systematic review | Vaccination and prevention of long Covid; 16 observational studies included, comprising 614,392 patients. No RCTs identified. No meta-analysis due to heterogeneity of data. | OR values ranged widely and exceeded 1.0 (0.22 to 1.03 for one dose; 0.25–1.02 for two doses; 0.48–1.01 for any dose); CIs not available due to lack of meta-analysis. No clear pattern regarding whether additional vaccination doses confer greater protection. Five studies reported data on vaccine administration subsequent to infection, and OR values ranged from 0.38–0.91. | Unknown whether different vaccines (e.g., BNT 162b2, mRNA-1273, ChAdOx1 nCoV-1) confer different magnitudes of long Covid prevention. |
| Robertson et al., 2005 [44] | Meta-analysis of randomized or quasi-randomized studies comparing antibiotics to no antibiotics. | Prevention of rheumatic fever in patients treated for sore throat, with or without documentation of GAS infection. | In 10 trials (n = 7,665), antibiotics had a protective effect of 70% (RR, 0.32; 95% CI, 0.21–0.48). The absolute risk reduction was 1.67% with an NNT of 53. In the 9 studies evaluating penicillin, the protective effect was 80%. | Although pain is a prominent symptom of rheumatic fever, it was not evaluated separately. All studies were performed before 1962, with 8 of 10 including only adult males on military bases. Only 3 studies utilized a placebo. 9 studies evaluated penicillin, and 2 evaluated other antibiotic regimens (1 study evaluated 3 antibiotics versus placebo). |
| Lennon et al., 2009 [46] | Meta-analysis of RCTs, or trials of “before/after design,” that utilized penicillin for primary prophylaxis for rheumatic fever. | Prevention of rheumatic fever in school-aged children treated with penicillin via school- and/or community-based programs | Meta-analysis of 6 RCTs (n = 1,087,874; authors note that for one of the included studies, they adjusted the sample size “to allow for the unit of randomization being school [sic]” without further details given). Penicillin had a protective effect of approximately 60% (RR, 0.41; 95% CI, 0.23–0.70). | Although pain is a prominent symptom of rheumatic fever, it was not evaluated separately. Authors did not report an “unadjusted” total n value. Follow-up periods in some included studies were not clearly defined. |
| Lennon et al., 2009 [47] | RCT of schools in Auckland, New Zealand; entire schools, rather than individual students, were randomized. | Prevention of rheumatic fever in school-aged children (n = approximately 22,000; 86,874 person-years). Schools (n = 53) randomized to intervention (n = 27) received an onsite clinic that could diagnose and treat GAS pharyngitis. Children in schools randomized to control (n = 26) continued usual care via their primary care providers. | Using 1956 (probable) and 1965 (definite) Jones Criteria (“Analysis A”), risk reduction was 21% (incidence RR, 0.79; 95% CI, 0.41–1.52, P = 0.47). Using 1992 Jones Criteria and echocardiography (“Analysis B”), risk reduction was 28% (incidence RR, 0.72; 95% CI, 0.40–1.30, P = 0.27). In both analyses, the difference between the intervention and control group was non-significant. | Because school zoning allowed for a child to attend a control-group school and a younger or older sibling in the same family to attend an intervention-group school, any protective effects from the intervention might have been negated by household exposures to GAS. Pain-related symptoms were not evaluated separately. |
| Lennon et al., 2017 [48] | Prospective cohort study of school-aged children in Auckland, New Zealand. | Prevention of rheumatic fever in school-aged children (n = approximately 25,000) via the implementation of onsite sore throat clinics in schools (n = 61). | After two years of clinic availability, rates of rheumatic fever among 5–13 year-olds decreased by 58% (88 [95% CI, 79–111] per 100,000 pre-intervention to 37 [95% CI, 15–83] per 100,000). Pharyngeal GAS prevalence decreased from 22.4% (16.5–30.5) pre-intervention to 11.9% (8.6–16.5) and 11.4% (8.2–15.7) 1 or 2 years later (P = 0.005). | Onsite school clinics were established within geographic regions, reducing the likelihood of household contamination and spread if one sibling were to have access to a clinic while another did not. Clinics likely increased timely access to penicillin. Pain-related symptoms were not evaluated separately. |
PHN: post-herpetic neuralgia, RCT: randomized controlled trial, RR: risk ratio, CI: confidence interval, COVID: SARS-Cov-2 virus, HR: hazard ratio, OR: odds ratio, GAS: Group A Streptococcus, NNT: number needed-to-treat for one person to benefit.