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Review
. 2018 Aug 7;16(1):126.
doi: 10.1186/s12916-018-1109-4.

Resistance Decay in Individuals After Antibiotic Exposure in Primary Care: A Systematic Review and Meta-Analysis

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Free PMC article
Review

Resistance Decay in Individuals After Antibiotic Exposure in Primary Care: A Systematic Review and Meta-Analysis

Mina Bakhit et al. BMC Med. .
Free PMC article

Abstract

Background: Antibiotic resistance is an urgent global problem, but reversibility is poorly understood. We examined the development and decay of bacterial resistance in community patients after antibiotic use.

Methods: This was a systematic review and meta-analysis. PubMed, EMBASE and CENTRAL (from inception to May 2017) were searched, with forward and backward citation searches of the identified studies. We contacted authors whose data were unclear, and of abstract-only reports, for further information. We considered controlled or times-series studies of patients in the community who were given antibiotics and where the subsequent prevalence of resistant bacteria was measured. Two authors extracted risk of bias and data. The meta-analysis used a fixed-effects model.

Results: Of 24,492 articles screened, five controlled and 20 time-series studies (total 16,353 children and 1461 adults) were eligible. Resistance in Streptococcus pneumoniae initially increased fourfold after penicillin-class antibiotic exposure [odds ratio (OR) 4.2, 95% confidence interval (CI) 3.5-5.4], but this fell after 1 month (OR 1.7, 95% CI 1.3-2.1). After cephalosporin-class antibiotics, resistance increased (OR 2.2, 95%CI 1.7-2.9); and fell to (OR 1.6, 95% CI 1.2-2.3) at 1 month. After macrolide-class antibiotics, resistance increased (OR 3.8, 95% CI 1.9-7.6) and persisted for 1 month (OR 5.2, 95% CI 2.6-10.3) and 3 months (OR 8.1, 95% CI 4.6-14.2, from controlled studies and OR 2.3, 95% CI 0.6-9.4, from time-series studies). Resistance in Haemophilus influenzae after penicillins was not significantly increased (OR 1.3, 95% CI 0.9-1.9) initially but was at 1 month (OR 3.4, 95% CI 1.5-7.6), falling after 3 months (OR 1.0, 95% CI 0.5-2.2). Data were sparse for cephalosporins and macrolides. Resistance in Enterobacter increased post-exposure (OR 3.2, 95% CI 0.9-10.8, from controlled studies and OR 7.1, 95% CI 4.2-12, from time-series studies], but was lower after 1 month (OR 1.8, 95% CI 0.9-3.6).

Conclusions: Resistance generally increased soon after antibiotic use. For some antibiotic classes and bacteria, it partially diminished after 1 and 3 months, but longer-term data are lacking and urgently needed.

Trial registration: PROSPERO CRD42015025499 .

Conflict of interest statement

Not applicable.

Not applicable.

The authors declare that they have no competing interests.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flow chart
Fig. 2
Fig. 2
a. Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included studies. b. Risk of bias summary: review authors’ judgements about each risk of bias item for each included study. RCT randomised controlled trial
Fig. 3
Fig. 3
Pooled odds ratios for resistance in respiratory tract bacteria (Streptococcus pneumoniae) and antibiotic exposure by class. Studies grouped by time from the end of antibiotic exposure. CI confidence interval, df degrees of freedom, RCT randomised controlled trial
Fig. 4
Fig. 4
Pooled odds ratios for resistance in respiratory tract bacteria (Haemophilus influenzae) and antibiotic exposure by class. Studies grouped by time from the end of antibiotic exposure. CI confidence interval, df degrees of freedom
Fig. 5
Fig. 5
Pooled odds ratios for resistance in gastrointestinal tract bacteria and any antibiotic exposure. Studies grouped by time from the end of antibiotic exposure. -ve, negative, CI confidence interval, df degrees of freedom, SMX sulfamethoxazole, TMP trimethoprim
Fig. 6
Fig. 6
Odds ratio of resistance in other respiratory isolates post-exposure to different antibiotic classes. Shaded areas indicate trials with a control group. Unshaded areas indicate time-series studies (before and after). NGS non-groupable streptococci, M. catarrhalis Moraxella catarrhalis, S. aureus Staphylococcus aureus, S. mitis Streptococcus mitis, Telithro telithromycin, Amoxi-clav amoxicillin-clavulanate, ß-lactams beta-lactams, Azi azithromycin, Levo levofloxacin
Fig. 7
Fig. 7
Co-resistance data reported among the included studies. Shaded areas indicate trials with a control group. Unshaded areas indicate time-series studies (before and after). TMP trimethorprim, TMP-SMX trimethoprim-sulfamethoxazole, Erthro erythromycin, Erthro-sulf erythromycin-sulfisoxazole, Telithro telithromycin, Amoxi-clav amoxicillin-clavulanate. *Data could not be extracted from three studies
Fig. 8
Fig. 8
Funnel plots of comparison

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