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Carbapenems are considered the drugs of choice for first-line treatment of severe infections caused by carbapenem-susceptible, extended-spectrum β-lactamases (ESBL)-producing Enterobacterales, while piperacillin-tazobactam has been recommended as an alternative for treatment of non-severe infections. Temocillin is stable to ESBL and AmpC enzymes and may thus represent another treatment option. This study assessed the in vitro activity of piperacillin-tazobactam and temocillin against third-generation cephalosporin (3GC)-resistant and , as compared to 3GC-sle isolates of either species.One hundred and nine isolates from hospitalized patients with bloodstream and urinary tract infections were tested. All isolates were collected during the resistance surveillance study of the Paul-Ehrlich-Society for Chemotherapy in 2016/17. Minimum inhibitory concentrations (MICs) were determined by broth microdilution according to the standaO 20776-1 and interpreted using EUCAST clinical breakpoints (versio1.0).Seventy-nine isolates (, n=58; , n=21) were 3GC-resistant and 30 (, n=15; , n=15) were 3GC-se. Susceptibility to piperacillin-tazobactam was detected in 93.3% of 3GC-susceptible isolates (for both and ) and in 79.3% and 57.1% of the 3GC-resistant and , respectively. In contrast, 3GC-susceptible isolates were 100% susceptible to temocillin as were 94.8% and 90.5% of the 3GC-resistant and , respectively.In conclusion, temocillin demonstrated potent in vitro activity against carbapenem-susceptible, 3GC-resistant and from bloodstream and urinary tract infection samples, with susceptibility rates exceeding those of piperacillin-tazobactam.

This is the second chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2 updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Preliminary microbiological findings regarding the patient and their immediate environment are crucial for the calculation of treatment with antibiotics in each case, as well as the resistance situation of the ward on which the patient is being cared for. If such data is not available, regional or supra-regional data can be used as a fallback. This chapter describes the methods of susceptibility testing, informs about the resistance situation in Germany and describes the main resistance mechanisms of bacterial pathogens against antibiotics. Further, the chapter informs about collateral damage of antibiotics as well as medical measures against increasing resistance.

This is the first chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2 updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.This guideline is a revision of the recommendations published in 2010, taking into account recent substances and studies. As with previous revisions, the current situation of pathogen resistance and the results of new clinical trials are considered. The results are the present recommendations for parenteral calculated initial therapy of bacterial infections in adults. If several treatment options are mentioned, they are not always equivalent in their spectrum of microbiological activity. Therapeutic alternatives offer the opportunity to consider pathogen epidemiology, to avoid antibiotic intolerances or to escalate or de-escalate treatment in a manner suited to the situation. This article describes the different therapy options.

Given the rapidly changing landscape of antimicrobial resistance, continuous monitoring of antimicrobial susceptibility in clinically relevant bacterial isolates plays an important role in the management of infectious diseases. The Tigecycline Evaluation and Surveillance Trial (TEST) is an ongoing worldwide surveillance programme monitoring the in vitro activity of tigecycline and a panel of representative comparator antibiotics. We report longitudinal susceptibility data on a large set of isolates (n=36,044) from clinically significant bacterial species collected in laboratories from 2006 to 2014. Trends include a strong increase of carbapenem and levofloxacin resistance in spp., and smaller increasing rates of ESBL-producing and vancomycin-resistant enterococci. Across the reporting period, the tigecycline minimum inhibitory concentrations (MICs) at which 50% and 90% of isolates were inhibited remained stable and susceptibility rates were consistently high (93–100%) for all bacterial species.

Empirical treatment of hospital-acquired pneumonia (HAP) has increasingly been threatened by methicillin-resistant (MRSA) and multidrug resistant Gram-negative pathogens. In contrast, empirical treatment of community-acquired pneumonia (CAP) is primarily impeded by antimicrobial-resistant pneumococci. Ceftobiprole, recently approved for the treatment of HAP and CAP in Europe, is active against a broad-spectrum of Gram-positive and Gram-negative pathogens, including MRSA and . The objective of this study was to evaluate the susceptibility of ceftobiprole among 1,246 , , Enterobacteriaceae species and isolated from respiratory tract and blood.Isolates were collected in 25 laboratories across Germany, Switzerland and Austria. Minimum inhibitory concentrations (MICs) were determined using the microdilution method according to the standard ISO 20776-1:2006 and interpreted by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Two-thirds of the isolates were obtained from respiratory specimens and one third from blood. There were 544 intensive care unit (ICU) isolates and 702 non-ICU isolates. The share of MRSA in was 16%. Among pneumococci, 18.5% showed reduced susceptibility to penicillin. An extended-spectrum β-lactamase (ESBL) phenotype was confirmed for 18.4% of the and 16.7% of the isolates. Of the isolates, 20.7% were ceftazidime-resistant.MIC values of ceftobiprole for methicillin-susceptible (MSSA) and MRSA were 0.5/0.5 mg/L and 2/2 mg/L, respectively. All pneumococci were inhibited at 1 mg/L ceftobiprole. The activity of ceftobiprole against and was similar to that of ceftriaxone, but ceftobiprole showed superior activity against Enterobacteriaceae species known to produce chromosomally encoded AmpC-β-lactamases. MIC values of ceftobiprole for ceftazidime-susceptible (4/16 mg/L) and ceftazidime-resistant (16/>32 mg/L) were comparable to those of cefepime (4/8 mg/L and 32/>32 mg/L, respectively). These findings suggest that ceftobiprole may represent a suitable option for the empirical treatment of HAP and CAP.

According to WHO estimates, Neisseria gonorrhoeae accounted for illion infections in 2008, a number of cases approximately matching those of Chlamydia infections. Gonococcal infections thus represent one of the most common causes of sexually transmitted diseases worldwide, second only to trichomonas vaginalis infections.This guideline aims to improve patient care by optimizing the diagnosis and treatment of infections due to Neisseria gonorrhoeae and to raise awareness among medical professionals of current treatment options.

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 β-lactam class, including novel β-lactams combined with β-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-β-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-β-lactamase. [ABSTRACT FROM AUTHOR]

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 β-lactam-β-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 β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 2/4 mg/L (MIC range 0.125–16 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. [ABSTRACT FROM AUTHOR]