Antimicrobial resistance of clinical Enterobacterales isolates from urine samples, Germany, 2016 to 2021

Abstract

Introduction Empirical therapy for the treatment of urinary tract infections should be tailored to the current distribution and susceptibility of potential pathogens to ensure optimal treatment. Aim We aimed to provide an up-to-date overview of the epidemiology and susceptibility of Enterobacterales isolated from urine in Germany. Methods We retrospectively analysed antimicrobial susceptibility data from 201,152 urine specimens collected between January 2016 and June 2021 from in- and outpatients. Multiple logistic regression analysis was used to evaluate the association between year of investigation and antibiotic resistance, adjusted for age, sex and species subgroup. Subgroup analyses were performed for midstream urine samples obtained from (i) female outpatients aged 15 to 50 years, (ii) female outpatients older than 50 years and (iii) male outpatients. Results Resistance rates of less than 20% were observed for nitroxoline (3.9%), fosfomycin (4.6%), nitrofurantoin (11.7%), cefuroxime (13.5%) and ciprofloxacin (14.2%). Resistance to trimethoprim/sulfamethoxazole (SXT) (20.1%), amoxicillin-clavulanic acid (20.5%), trimethoprim (24.2%), pivmecillinam (29.9%) and ampicillin (53.7%) was considerably higher. In the subgroup of outpatient women aged 15–50 years, resistance rates were generally lower. Resistance rates of all antibiotics decreased from 2016 to 2021. Multiple logistic regression revealed the lowest adjusted odds ratio (ORadj) of 0.838 (95% confidence interval (CI): 0.819–0.858; p < 0.001) for pivmecillinam and the highest ORadj of 0.989 (95% CI: 0.972–1.007; p = 0.226) for nitrofurantoin. Conclusions Resistance has generally decreased over the past years, independent of sex, age and causative pathogen. Our data provide an important basis for empirical antibiotic recommendations in various settings and patient collectives.

Nitroxoline resistance is associated with significant fitness loss and diminishes in vivo virulence of Escherichia coli

“…Notably, among our small panel, we identified two clinical isolates that exhibited susceptibility exclusively to NTX, while being resistant to all other tested drugs. Recently, Stolditis-Claus et al demonstrated that NTX has the lowest resistance rate (3.9%, 48 out of 1,246 NTX data sets) among all commonly used antibiotics against Enterobacteriales (FOS 4.6%, NFT 11.7%, CIP 14.2%, TMP 24.2%, and PIV 30%) isolated from urine samples in Germany (total number of isolates n = 201,152) and concluded that its effectiveness has not decreased in recent years ( 9 ). Hof et al ( 20 ) evaluated 477 isolates from urine samples and described excellent activity of NTX against E. coli with only 1 out of 277 isolates being resistant.…”

“…Hence, it seems that only low-level resistance against NTX can be achieved with MIC values still below the maximal concentration of NTX determined in urine samples ( 28 ), making the reduced susceptibility of in vitro generated mutants less of a concern. Other common drugs used for the treatment of UTI were characterized by mutants developing at a higher frequency with high levels of resistance (over 2,000-fold shifts in MIC) which can explain increased resistance rates in clinical samples ( 9 ). Thus, in this head-to-head comparison, we found NTX clearly superior in terms of its resistance development properties in vitro .…”

“…It is important to mention that in vitro FoR does not necessarily reflect in vivo resistance development, which might be especially prominent for Mecillinam, which is characterized by a very high FoR in vitro but still good efficiency in clinical application, where resistance development generally seems to be rare ( 29 – 31 ). However, the most recent study from Germany identified that almost 30% of tested UTI isolates were resistant to PIV (25,850 out of 86,371) ( 9 ) raising doubts regarding the clinical efficiency of PIV.…”

“…Other recommended treatment options are fosfomycin (FOS), nitrofurantoin (NFT), pivmecillinam (PIV), or trimethoprim (TMP), whereas the latter is only recommended with reservations due to increasing resistance rates ( 5 ). Despite being in use longer than several other clinically relevant antibiotics, Nitroxoline resistance (NTX R ) does not seem to be a major clinical problem, and it is still recommended as first-line treatment option ( 5 – 9 ).…”

Nitrofuran Derivatives Cross-Resistance Evidence—Uropathogenic Escherichia coli Nitrofurantoin and Furazidin In Vitro Susceptibility Testing

“…Figure 1 summarizes the resistance rate to nitrofurantoin among strains of E. coli causing UTI. The results come from studies performed in different regions of the world, in different periods, and in groups of different sizes [ 2 , 7 , 8 , 10 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. In most cases, the percentage of resistance to nitrofurantoin was low and often did not exceed 3%.…”