Global antibiotic resistance prevalence in paediatric Escherichia coli urinary tract infections and associations with routine use of primary care antibiotics: a systematic review and meta-analysis

AbstractThe majority of studies that link antibiotic usage and resistance focus on simple associations between the resistance against a specific antibiotic and the use of that specific antibiotic. However, the relationship between antibiotic use and resistance is more complex. Here we evaluate which antibiotics, including those mainly prescribed for respiratory tract infections, are associated with increased resistance among Escherichia coli isolated from urinary samples.Monthly primary care prescribing data were obtained from National Health Service (NHS) Digital. Positive E. coli records from urine samples in English primary care (n=888,207) between April 2014 and January 2016 were obtained from the Second Generation Surveillance System. Elastic net regularization was used to evaluate associations between prescribing of different antibiotic groups and resistance against amoxicillin, cephalexin, ciprofloxacin, co-amoxiclav and nitrofurantoin at the clinical commissioning group (CCG) level. England is divided into 209 CCGs, with each NHS practice prolonging to one CCG.Amoxicillin prescribing (measured in DDD/ 1000 inhabitants / day) was positively associated with amoxicillin (RR 1.03, 95% CI 1.01 – 1.04) and ciprofloxacin (RR 1.09, 95% CI 1.04 – 1.17) resistance. In contrast, nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin (RR 0.92, 95% CI 0.84 – 0.97). CCGs with higher levels of trimethoprim prescribing also had higher levels of ciprofloxacin resistance (RR 1.34, 95% CI 1.10 – 1.59).Amoxicillin, which is mainly (and often unnecessarily) prescribed for respiratory tract infections is associated with increased resistance against various antibiotics among E. coli causing urinary tract infections. Our findings suggest that when predicting the potential impact of interventions on antibiotic resistances it is important to account for use of other antibiotics, including those typically used for other indications.Author summaryAntibiotic resistance is increasingly recognised as a threat to modern healthcare. Effective antibiotics are crucial for treatment of serious bacterial infections and are necessary to avoid that complicated surgical procedures and chemotherapy becoming life-threatening. Antibiotic use is one of the main drivers of antibiotic resistance. The majority of antibiotic prescriptions are prescribed in primary care, however, a large proportion of these antibiotic prescriptions are unnecessary. Understanding which antibiotics are causing antibiotic resistance to what extent is needed to prevent under- or over-investment in interventions lowering use of specific antibiotics, such as rapid diagnostic tests for respiratory tract infection.We have statistically evaluated which antibiotics are associated with higher and lower levels of antibiotic resistance against common antibiotics among Escherichia coli bacteria sampled from the urinary tract by comparing antibiotic prescribing and resistance in different geographical areas in England. Our model shows that amoxicillin, the most commonly used antibiotic in England and mainly used for respiratory tract infections, is associated with increased resistance against several other antibiotics among bacteria causing urinary tract infections. The methods used in this study, that overcome several of the limitations of previous studies, can be used to explore the complex relationships between antibiotic use and antibiotic resistance in other settings.

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Virulence factors and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from urinary tract infections: A systematic review and meta-analysis

10.21203/rs.3.rs-366326/v1 ◽

2021 ◽

Author(s):

Gabriel Kambale Bunduki ◽

Eva Heinz ◽

Vincent Samuel Phiri ◽

Patrick Noah ◽

Nicholas Feasey ◽

...

Keyword(s):

Escherichia Coli ◽

Systematic Review ◽

Urinary Tract ◽

Antimicrobial Resistance ◽

Virulence Factors ◽

Urinary Tract Infections ◽

Meta Analysis ◽

Analysis Model ◽

Beta Lactams ◽

Tract Infections

Abstract Background Uropathogenic Escherichia coli (UPEC) are amongst the most frequent causes of urinary tract infections. We report a systematic review and meta-analysis of virulence factors and antimicrobial resistance of UPEC isolated from urinary tract infections. Methods A systematic review and meta-analysis were performed using PRISMA guidelines (Research Registry ref 5874). Data were extracted from PubMed/MEDLINE and ScienceDirect databases for studies published from January 1, 2000 to December 31, 2019. Studies reporting antimicrobial resistance and virulence factors of UPEC isolated in confirmed urinary tract infections (≥ 105CFU/ml) were eligible. Prevalence of antimicrobial resistance and virulence factors of UPEC were estimated using random-effects meta-analysis model. Estimates with 95% confidence intervals, I-square (I2) statistic, and Cochran’s Q test were computed using the score statistic and the exact binomial method by incorporating the Freeman-Tukey double arcsine transformation of proportions. Results Our search returned 2,504 hits, of which 13 studies were included in the meta-analysis, totalling 1,888 UPEC isolates. Highest antimicrobial resistance rates were observed among the antibiotic class of tetracycline in 69.1% (498/721), followed by sulphonamides in 59.3% (1119/1888), quinolones in 49.4% (1956/3956), and beta-lactams in 36.9% (4410/11964). Among beta-lactams, high resistance was observed in aminopenicillins in 74.3% (1157/1557) and first generation cephalosporins in 38.8% (370/953). Meanwhile, virulence factors with highest prevalence were immune suppressors (54.1%) followed by adhesins (45.9%). Taken individually, the most observed virulence genes were shiA (92.1%), CSH (80.0%), fimH/MSHA (75.3%), traT (75.1%), sisA (72.2%), iucD (65.7%), iutA (61.8%), kpsMTII (60.6%), and PAI (55.2%). Conclusions The increased antibiotic resistance of UPEC isolates was demonstrated and suggested a need for reassessment of empirical therapies in urinary tract infections treatment caused by this pathogen. In addition, this pathotype exhibited diverse surface and secreted virulence factors.

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Virulence factors and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from urinary tract infections: a systematic review and meta-analysis

BMC Infectious Diseases ◽

10.1186/s12879-021-06435-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gabriel Kambale Bunduki ◽

Eva Heinz ◽

Vincent Samuel Phiri ◽

Patrick Noah ◽

Nicholas Feasey ◽

...

Keyword(s):

Escherichia Coli ◽

Systematic Review ◽

Urinary Tract ◽

Antimicrobial Resistance ◽

Virulence Factors ◽

Urinary Tract Infections ◽

Meta Analysis ◽

Analysis Model ◽

Beta Lactams ◽

Tract Infections

Abstract Background Uropathogenic Escherichia coli (UPEC) are amongst the most frequent causes of urinary tract infections. We report a systematic review and meta-analysis of virulence factors and antimicrobial resistance of UPEC isolated from urinary tract infections. Methods A systematic review and meta-analysis were performed using PRISMA guidelines (Research Registry ref. 5874). Data were extracted from PubMed/MEDLINE and ScienceDirect databases for studies published from January 1, 2000 to December 31, 2019. Studies reporting antimicrobial resistance and virulence factors of UPEC isolated in confirmed urinary tract infections (≥105CFU/ml) were eligible. Prevalence of antimicrobial resistance and virulence factors of UPEC were estimated using random-effects meta-analysis model. Estimates with 95% confidence intervals, I-square (I2) statistic, and Cochran’s Q test were computed using the score statistic and the exact binomial method by incorporating the Freeman-Tukey double arcsine transformation of proportions. Results Our search returned 2504 hits, of which 13 studies were included in the meta-analysis, totalling 1888 UPEC isolates. Highest antimicrobial resistance rates were observed among the antibiotic class of tetracycline in 69.1% (498/721), followed by sulphonamides in 59.3% (1119/1888), quinolones in 49.4% (1956/3956), and beta-lactams in 36.9% (4410/11964). Among beta-lactams, high resistance was observed in aminopenicillins in 74.3% (1157/1557) and first generation cephalosporins in 38.8% (370/953). Meanwhile, virulence factors with highest prevalence were immune suppressors (54.1%) followed by adhesins (45.9%). Taken individually, the most observed virulence genes were shiA (92.1%), CSH (80.0%), fimH/MSHA (75.3%), traT (75.1%), sisA (72.2%), iucD (65.7%), iutA (61.8%), kpsMTII (60.6%), and PAI (55.2%). Conclusions The increased antibiotic resistance of UPEC isolates was demonstrated and suggested a need for reassessment of empirical therapies in urinary tract infections treatment caused by this pathogen. In addition, this pathotype exhibited diverse surface and secreted virulence factors.

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