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Bacteria are a major cause of superficial eye infections, especially in children. The present study aimed to (i) determine the antimicrobial susceptibility patterns of ocular bacterial pathogens recovered in 20 laboratories during the period 2020-2021 and (ii) compare these results to those from three studies of the same design conducted in 2004, 2009, and 2015 in Germany. Cut-off values defined by EUCAST were used as breakpoints. A total of 1366 bacterial isolates were collected. The most frequent ocular specimens were conjunctival smears (54.3%). Susceptibility rates of Staphylococcus aureus (n = 594), Haemophilus influenzae (n = 178), and Streptococcus pneumoniae (n = 149) to chloramphenicol, gentamicin, kanamycin, neomycin, levofloxacin, ofloxacin, and oxytetracycline were >90% each. Overall, only minor changes in resistance levels were observed in the period since 2004. Therefore, all tested antimicrobials can still be recommended for local therapy of ocular surface infections.
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Infecções por Escherichia coli , Infecções Urinárias , Humanos , Andinocilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: According to German AWMF S3 guideline nitroxoline is recommended as one of the first-choice antibiotics for treatment of acute uncomplicated cystitis (UC) in women. Under real-world conditions the clinical efficacy of nitroxoline should be checked in a noninterventional, prospective and multicenter study (NIS) and the prevalence of nitroxoline resistance in E. coli be monitored. MATERIALS AND METHODS: Female patients with UC treated with nitroxoline (recommended dosage 250â¯mg tid for 5 days) were included by urologists, general practitioners (GPs), and internists in family medicine throughout Germany from April-December 2022 and followed for 21-28 days. The diagnosis and course of therapy were judged by the Acute Cystitis Symptom Score (ACSS) questionnaire and laboratory investigations (leukocyturia etc). Separately, a nationwide resistance surveillance was performed during 2019-2020 in collaboration with 23 laboratories to collect urinary E. coli isolates and test their susceptibility to nitroxoline. RESULTS: Of the 316 patients with mean (SD) age of 57.2 (±20.4 [median 62.5]) years who were included in the NIS, 193/248 (86.3%) in the per-protocol group and in 193/263 (81.44%) in the intention-to-treat group were clinically successful. Furthermore, 96% of the patients rated the tolerability of nitroxoline as "very good" or "good". All 272 E. coli isolates tested were susceptible to nitroxoline. CONCLUSIONS: Nitroxoline showed very good clinical results in the NIS, and 100% of the tested E. coli urine isolates were susceptible to nitroxoline. Nitroxoline can still be recommended as one of the first-choice antibiotics for treatment of UC in women.
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Cistite , Infecções Urinárias , Humanos , Feminino , Pessoa de Meia-Idade , Infecções Urinárias/tratamento farmacológico , Escherichia coli , Estudos Prospectivos , Antibacterianos , Cistite/diagnósticoRESUMO
Background: Cefiderocol is a novel siderophore cephalosporin with potent activity against multi-drug-resistant Gram-negative pathogens including carbapenem-resistant Acinetobacter baumannii (CRAB). Methods: The susceptibility of 313 non-duplicate CRAB isolates with defined carbapenem resistance mechanisms from a global collection to cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, ciprofloxacin, colistin, imipenem/relebactam, meropenem, meropenem/vaborbactam, minocycline, and piperacillin/tazobactam was determined using the broth microdilution method. Isolates were obtained from various body sites from patients in 47 countries in five world regions between 2012 and 2016. The identification of carbapenem resistance mechanisms and assignment to A. baumannii international clonal lineages were based on whole genome sequencing. Results: Cefiderocol showed greater activity than comparator antimicrobials of the ß-lactam class, including novel ß-lactams combined with ß-lactamase inhibitors, ciprofloxacin, and minocycline. Cefiderocol MIC50 and MIC90 values were 0.5 mg/L and 4 mg/L, respectively, while colistin had comparable activity with a higher MIC50 at 1 mg/L and a lower MIC90 value of 2 mg/L. Many isolates with elevated cefiderocol MICs ≥ 4 mg/L represented A. baumannii international clone (IC) 1 and harbored a metallo-ß-lactamase. Conclusions: While cefiderocol is a useful addition to the limited armamentarium of drugs targeting this problematic pathogen, a considerable part of CRAB isolates had elevated MIC values in a range of 4 -> 32 mg/L, including all isolates with a metallo-ß-lactamase.
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Antimicrobial resistance poses a global threat to public health. Of great concern are Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales with resistance to carbapenems or third-generation cephalosporins. The aim of the present study was to investigate the in vitro activity of the novel siderophore cephaloporin cefiderocol (CID) and four comparator ß-lactam-ß-lactamase-inhibitor combinations and to give insights into the genetic background of CID-resistant isolates. In total, 301 clinical Enterobacterales and non-fermenting bacterial isolates were selected for this study, including randomly chosen isolates (set I, n = 195) and challenge isolates (set II, n = 106; enriched with ESBL and carbapenemase producers, as well as colistin-resistant isolates). Isolates displayed CID MIC50/90 values of 0.12/0.5 mg/L (set I) and 0.5/1 mg/L (set II). Overall, the CID activity was superior to the comparators against A. baumannii, Stenotrophomonas maltophilia and set II isolates of P. aeruginosa. There were eight CID-resistant isolates detected (MIC > 2 mg/L): A. baumannii (n = 1), E. cloacae complex (n = 5) and P. aeruginosa (n = 2). Sequencing analyses of these isolates detected the acquired ß-lactamase (bla) genes blaNDM-1,blaSHV-12 and naturally occurring blaOXA-396, blaACT-type and blaCMH-3. In conclusion, CID revealed potent activity against clinically relevant organisms of multidrug-resistant Enterobacterales and non-fermenters.
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This cross-sectional in-vitro resistance surveillance study involving 10 medical laboratories was conducted in 2018. Each study site was asked to collect 30 consecutive nonduplicate isolates per species from hospitalized patients with documented infections. Minimum inhibitory concentrations were determined at a central laboratory. European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used for interpretation. A total of 860 isolates were collected, including 298 Escherichia coli, 268 Klebsiella pneumoniae, and 294 Pseudomonas aeruginosa. Fifty (16.8%) E. coli and 63 (23.5%) K. pneumoniae isolates were found to be resistant to third-generation cephalosporins. Resistance to carbapenems (imipenem and/or meropenem) was identified in 5 (1.9%) K. pneumoniae and 64 (21.8%) P. aeruginosa, but not in E. coli. Thirty-three (11.2%) P. aeruginosa isolates were resistant to both carbapenems and 30 (10.2%) P. aeruginosa showed resistance to ≥3 antimicrobials/antimicrobial groups (among piperacillin-tazobactam, ceftazidime, tobramycin, carbapenems, and fluoroquinolones). The susceptibility rates of these multidrug-resistant (MDR) phenotypes to ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam were 70-100%, with the exception of carbapenem-resistant K. pneumoniae. Only two K. pneumoniae and four P. aeruginosa isolates were resistant to all three beta-lactam/beta-lactamase-inhibitor combinations. However, this favorable result should be viewed in light of the relatively low prevalence of MDR organisms that require these agents in Germany.
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Antibacterianos , Infecções por Pseudomonas , Humanos , Antibacterianos/farmacologia , Ceftazidima/farmacologia , Pseudomonas aeruginosa , Klebsiella pneumoniae , Escherichia coli , Estudos Transversais , Infecções por Pseudomonas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Cefalosporinas/farmacologia , Tazobactam/farmacologia , Combinação de Medicamentos , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , Carbapenêmicos/farmacologia , Imipenem/farmacologiaRESUMO
OBJECTIVES: To characterize the genetic environment of metallo-ß-lactamases (MBL) in carbapenem-resistant clinical Acinetobacter pittii isolates. METHODS: Seventeen carbapenem-resistant A. pittii isolates harbouring an MBL were collected between 2010 and 2015 in Germany. Antimicrobial susceptibility testing was performed using agar dilution. Presence of MBLs was confirmed by PCR and their genetic location determined by S1-pulsed-field gel electrophoresis followed by Southern blot hybridization. Whole-genome sequencing was performed using the Miseq and MinION platforms. Isolates were typed using an ad hoc core genome MLST scheme. Conjugation into A. baumannii was tested by broth mating. RESULTS: In 10 isolates the MBL was plasmid-encoded and in seven isolates chromosomally encoded. blaGIM-1 and blaVIM-2 were plasmid-encoded, blaVIM-4 was chromosomally encoded, while blaNDM-1 was chromosomally encoded in four and plasmid-encoded in three isolates. Seven of ten plasmids were conjugative into A. baumannii. Although most isolates were unrelated, the backbones of the MBL-encoding plasmid showed >99% similarity and only differed in the MBL-encoding area. blaNDM-1-harbouring plasmids were highly similar to other plasmids from Acinetobacter isolates worldwide while the blaVIM-2- and blaGIM-1-encoding plasmids have not been described. CONCLUSIONS: These data show the existence of a promiscuous plasmid circulating in A. pittii isolates in Germany that differs only in the MBL-encoding region. Its plasmid backbone has been found globally among multiple Acinetobacter spp. These data should raise awareness of an epidemic conjugative plasmid that has independently acquired MBLs. We should also consider that future comparative plasmid analysis will look beyond solely the resistome and include the mobile elements carrying the resistance genes.
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Acinetobacter baumannii , Acinetobacter , beta-Lactamases/genética , Tipagem de Sequências Multilocus , Acinetobacter/genética , Carbapenêmicos/farmacologia , Plasmídeos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Acinetobacter baumannii/genéticaRESUMO
BACKGROUND: Escherichia coli is the leading pathogen of community-acquired urinary tract infections. Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene oral antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action that confers activity against most strains of target pathogens, such as E. coli, Staphylococcus saprophyticus and Neisseria gonorrhoeae, including those resistant to other antibiotics. OBJECTIVES: This study assessed the in vitro activity of gepotidacin in comparison with ciprofloxacin and other oral standard-of-care antibiotics using a large collection of urine isolates of E. coli obtained from outpatients in Germany. METHODS: Four hundred and sixty E. coli collected from 23 laboratories during a surveillance study in 2019/2020 were tested. Forty-six isolates (10.0%) produced an ESBL of the CTX-M family, half of which belonged to MDR clonal subgroups of E. coli ST131. Antibiotic susceptibilities were tested at a reference laboratory by broth microdilution according to the standard ISO 20776-1. RESULTS: Fifty-three (11.5%) isolates were ciprofloxacin resistant, 25 (47.2%) of which also produced an ESBL. Overall, MIC50/90 values for gepotidacin were 2/4â mg/L (MIC range 0.125-16â mg/L), with no differences in activity between ciprofloxacin-susceptible and ciprofloxacin-resistant isolates, ESBL-producing and non-ESBL isolates, O25b-ST131 isolates, and isolates susceptible or resistant to fosfomycin, mecillinam or nitrofurantoin. CONCLUSIONS: Gepotidacin showed promising in vitro activity against urine isolates of E. coli, including ciprofloxacin-resistant isolates, ESBL-producing isolates and isolates resistant to oral standard-of-care antibiotics.
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The aim of this study was to investigate and compare the molecular epidemiology and carbapenem resistance determinants in clinical Acinetobacter baumannii isolates collected during four multicentre surveillance studies conducted by the Paul-Ehrlich-Society for Infection Therapy. Isolates were collected prospectively from hospital in-patients at 17 medical centres in Germany over four periods of three- to six-months starting in October of each of 2010, 2013, 2016 and 2019. Species identification was performed by MALDI-TOF, gyrB multiplex polymerase chain reaction (PCR), and detection of the intrinsic blaOXA-51-like gene. Minimum inhibitory concentrations were determined by broth microdilution. The prevalence of carbapenemase-encoding genes was investigated by OXA-multiplex PCR and whole-genome sequencing. Molecular epidemiology was examined by rep-PCR and core-genome multi-locus sequence typing. A total of 302 A. baumannii isolates were collected. Resistance to imipenem and/or meropenem was detected in 58 isolates (19.2%) from 14 centres. The proportion of carbapenem-resistant isolates increased from 21.3% in 2010 to 33.3% in 2013, and then decreased to 13.8% in 2016 and 12.3% in 2019. Forty-six of these isolates were associated with the international clonal lineage IC2 and five with IC1. The most prevalent carbapenemase gene detected was blaOXA-23-like (n=51). Further carbapenem-resistance determinants were blaOXA-40-like (n=1), blaOXA-58-like (n=3) and blaNDM-1 (n=2). In one isolate, ISAba1 was detected upstream of blaOXA-51-like. In conclusion, IC2 was the most prevalent clonal lineage detected in this study. Interestingly, in Germany, carbapenem resistance seems to have decreased in A. baumannii between 2013 and 2019.
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Infecções por Acinetobacter , Acinetobacter baumannii , Carbapenêmicos , Humanos , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , beta-Lactamases/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Imipenem/farmacologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Resistência Microbiana a Medicamentos/genéticaRESUMO
Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Escherichia coli is by far the leading cause of community-acquired UTIs. Pivmecillinam, the oral prodrug of the penicillin derivative mecillinam (amdinocillin), was re-introduced in Germany in March 2016 for first-line treatment of acute uncomplicated cystitis. This study aimed to evaluate the prevalence of resistance to mecillinam in comparison to nine other antibiotics used for oral treatment in E. coli urine isolates after the re-introduction of pivmecillinam. A total of 460 isolates were collected at 23 laboratories of clinical microbiology between October 2019 and March 2020. Forty-six isolates (10.0%) produced an extended-spectrum ß-lactamase (ESBL) of the CTX-M family. Resistance to amoxicillin (43.3%) was most widespread, followed by resistance to trimethoprim-sulfamethoxazole (27.0%), amoxicillin-clavulanic acid (18.0%), cefuroxime (11.3%), and ciprofloxacin (11.1%). Twenty-four E. coli isolates (5.2%) were resistant to mecillinam. The concentrations of mecillinam needed to inhibit 50/90% of the ESBL-producing isolates and the remaining isolates were 1/4 mg/L and 0.5/4 mg/L, respectively. The findings support the recommendation to regard pivmecillinam as a first-line option for the treatment of uncomplicated lower UTIs.
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OBJECTIVES: The aim of this study was to evaluate the occurrence of glycopeptide resistance in enterococci and coagulase-negative staphylococci (CoNS) and to determine the susceptibilities of the identified glycopeptide-resistant isolates to dalbavancin. METHODS: Twenty-two medical laboratories participated in the study conducted in 2016/17 by the Paul-Ehrlich-Society for Chemotherapy. Each laboratory was asked to collect 30 Enterococcus spp. (limited to Enterococcus faecalis and Enterococcus faecium) and 30 CoNS isolates consecutively from hospitalised patients with a proven or suspected infection. RESULTS: A total of 1285 isolates were collected, comprising 364 E. faecalis, 291 E. faecium and 630 CoNS. No E. faecalis isolates (0%) but 76 E. faecium isolates (26.1%) were vancomycin-resistant, of which 21 showed the VanA type and 55 the VanB type. The proportion of vancomycin-resistant strains among E. faecium isolates from patients in intensive care units (21.6%) was significantly lower than that from patients on regular wards (30.5%). Among the CoNS, 67 isolates (10.6%) were teicoplanin-resistant but none were vancomycin-resistant, with resistance only detected in Staphylococcus epidermidis (12.2%), Staphylococcus haemolyticus (17.9%) and Staphylococcus hominis (13.2%). Dalbavancin at ≤0.25 mg/L inhibited all VanB-type enterococci and 95.5% of teicoplanin-resistant CoNS. CONCLUSION: The level of glycopeptide resistance in E. faecalis remains very low in Germany but achieved 26% in E. faecium and was >10% in CoNS. Dalbavancin appears to be a feasible option for treating infections caused by VanB-type vancomycin-resistant E. faecium and teicoplanin-resistant CoNS.
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Enterococcus , Teicoplanina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Coagulase , Glicopeptídeos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Staphylococcus , Teicoplanina/análogos & derivados , Teicoplanina/farmacologia , Vancomicina/farmacologiaRESUMO
Introduction. Gram-negative bacteria are a common source of infection both in hospitals and in the community, and antimicrobial resistance is frequent among them, making antibiotic therapy difficult, especially when these isolates carry carbapenem resistance determinants.Hypothesis/Gap Statement. A simple method to detect all the commonly found carbapenemases in Germany was not available.Aim. The aim of this study was to develop a multiplex PCR for the rapid and reliable identification of the most prevalent carbapenemase-encoding genes in Gram-negative bacteria in Germany.Methodology. Data from the German Gram-negative reference laboratory revealed the most prevalent carbapenemase groups in Germany were (in order of prevalence): bla VIM, bla OXA-48, bla OXA-23, bla KPC, bla NDM, bla OXA-40, bla OXA-58, bla IMP, bla GIM, bla GES, ISAba1-bla OXA-51, bla IMI, bla FIM and bla DIM. We developed and tested two multiplex PCRs against 83 carbapenem-resistant Gram-negative clinical isolates. Primers were designed for each carbapenemase group within conserved regions of the encoding genes obtained from publicly available databases. Multiplex-1 included the carbapenemase groups bla VIM, bla OXA-48, bla OXA-23, bla KPC, bla NDM and bla OXA-40, while multiplex-2 included bla OXA-58, bla IMP, bla GIM, bla GES, ISAba1-bla OXA-51 and bla IMI.Results. In the initial evaluation, all but one of the carbapenemases encoded by 75 carbapenemase-positive isolates were detected using the two multiplex PCRs, while no false-positive results were obtained from the remaining eight isolates. After evaluation, we tested 546 carbapenem-resistant isolates using the multiplex PCRs, and all carbapenemases were detected.Conclusion. A rapid and reliable method was developed for detection and differentiation of 12 of the most prevalent carbapenemase groups found in Germany. This method allows for the rapid testing of clinical isolates prior to species identification and does not require prior phenotypical characterization, constituting a rapid and valuable tool in the management of infections in hospitals.