RESUMO
Aerococcus urinae and Aerococcus sanguinicola have been increasingly recognized as causative agents of urinary tract infection (UTI) during the last decade. Nitroxoline achieves high urinary concentrations after oral administration and is recommended in uncomplicated UTI in Germany, but its activity against Aerococcus spp. is unknown. The aim of this study was to assess the in vitro susceptibility of clinical Aerococcus species isolates to standard antibiotics and to nitroxoline. Between December 2016 and June 2018, 166 A. urinae and 18 A. sanguinicola isolates were recovered from urine specimens sent to the microbiology laboratory of the University Hospital of Cologne, Germany. Susceptibility to standard antimicrobials was analyzed by disk diffusion (DD) according to EUCAST methodology, nitroxoline was tested by DD and agar dilution. Susceptibility of Aerococcus spp. to benzylpenicillin, ampicillin, meropenem, rifampicin, nitrofurantoin, and vancomycin was 100% and resistance was documented only against ciprofloxacin (20 of 184; 10.9%). MICs of nitroxoline in A. urinae isolates were low (MIC50/90 1/2 mg/L) while significantly higher MICs were observed in A. sanguinicola (MIC50/90 64/128 mg/L). If the EUCAST nitroxoline breakpoint for E. coli and uncomplicated UTI was applied (16 mg/L), 97.6% of A. urinae isolates would be interpreted as susceptible while all A. sanguinicola isolates would be considered resistant. Nitroxoline demonstrated high activity against clinical A. urinae isolates, but low activity against A. sanguinicola. Nitroxoline is an approved antimicrobial for UTI and could be an alternative oral drug to treat A. urinae urinary tract infection, yet clinical studies are needed to demonstrate this potential in vivo. IMPORTANCE A. urinae and A. sanguinicola have been increasingly recognized as causative agents in urinary tract infections. Currently, there are few data available on the activity of different antibiotics against these species and no data on nitroxoline. We demonstrate that clinical isolates in Germany are highly susceptible to ampicillin, while resistance to ciprofloxacin was common (10.9%). Additionally, we show that nitroxoline is highly active against A. urinae, but not against A. sanguinicola, which based on the presented data, should be considered intrinsically resistant. The presented data will help to improve the therapy of urinary tract infections by Aerococcus species.
RESUMO
Purpose: To investigate the susceptibility of carbapenemase-producing Enterobacterales (CPE) to mecillinam based on the recently updated European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for uncomplicated Urinary Tract Infection (uUTI). Methods: The challenge collection consisted of 105 molecularly characterized Enterobacterales [Klebsiella spp. (N = 49), Escherichia coli (N = 30), Enterobacter cloacae (n = 13), Citrobacter freundii (N = 9), Proteus mirabilis (N = 3), and Raoultella ornithinolytica (N = 1)]. Isolates produced OXA-48 (N = 18), OXA-48-like (N = 18), VIM (N = 22), NDM (N = 22), KPC (N = 12), IMI (N = 9), IMP (N = 6), GES (N = 1), OXA-58 (N = 2) or combinations thereof (N = 5). MICs of carbapenems were determined by agar gradient diffusion (AGD). MICs of mecillinam were assessed by agar dilution (reference method) and compared to disk diffusion (DD) and AGD. Results: Overall 23/105 CPE (21.9%) were susceptible to mecillinam. Susceptibility was observed in E. coli (N = 12), E. cloacae (N = 7), and Klebsiella pneumoniae (N = 4) producing IMI, OXA-48, OXA-48-like, and NDM-1 carbapenemases. MIC50 for mecillinam in all isolates was 128 mg/L while MIC50 for meropenem was 8 mg/L. Lower MICs for mecillinam were found in IMI (MIC50 8 mg/L) and OXA-48-like (MIC50 16 mg/L) producers. The comparison of the different susceptibility methods showed very major errors of 12.2% with AGD and 8.5% with disk diffusion when compared to the reference method. Conclusion: Mecillinam susceptibility was restricted to isolates producing IMI-, OXA-48-like, and NDM-1 carbapenemases and was documented despite high carbapenem MICs in some isolates. Mecillinam could be a promising oral antimicrobial in uUTI caused by E. coli and E. cloacae isolates carrying IMI- and OXA-48-like carbapenemases; however, susceptibility testing by AGD and disk diffusion remains problematic.