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Antimicrobial resistance in uropathogens commonly causing urinary tract infections (UTIs) is a growing problem internationally. Pivmecillinam, the oral prodrug of mecillinam, has been used for over 40 years, primarily in Northern Europe and Canada. It is recommended in several countries as a first-line agent for the treatment of uncomplicated UTIs (uUTIs) and is now approved in the United States. We performed a structured literature search to review the available evidence on susceptibility of common uUTI-causing uropathogens to mecillinam. Among 38 studies included in this literature review, susceptibility rates for Escherichia coli to mecillinam—including resistant phenotypes such as extended-spectrum β-lactamase–producing E. coli —exceed 90% in most studies. High rates of susceptibility were also reported among many other uropathogens including Klebsiella spp. Enterobacter spp. and Citrobacter spp. In the current prescribing climate within the United States, pivmecillinam represents a viable first-line treatment option for patients with uUTI. [ABSTRACT FROM AUTHOR]

Objectives Most human infections caused by Vibrio spp. do not warrant antimicrobial treatment but in severe cases, targeted antimicrobial treatment can be lifesaving. For Vibrio spp. standardized antimicrobial susceptibility testing (AST) guidelines with EUCAST methodology are lacking. In this study, we aimed to produce data suitable for EUCAST to establish clinical MIC breakpoints and zone diameter correlates for Vibrio spp. Methods An intercontinental collection (N = 524) comprising five important Vibrio spp. (V. alginolyticus , V. cholerae , V. fluvialis , V. parahaemolyticus and V. vulnificus) was organized. All isolates were subjected to broth microdilution (BMD) against 11 antimicrobial agents according to ISO 20776-1 using unsupplemented Mueller–Hinton broth on freeze-dried Sensititre panels (Thermo Scientific, UK), and most isolates (n = 371) were also tested with disc diffusion according to EUCAST methodology for non-fastidious organisms. Results Aggregated results were used to generate MIC and zone diameter distributions and to prepare graphs of MIC-zone diameter correlation. Based on these results, the EUCAST Steering Committee determined clinical susceptible (S) and resistant (R) MIC (mg/L) breakpoints (S≤/R>) for the five Vibrio spp. for piperacillin/tazobactam (1/1), cefotaxime (0.25/0.25), ceftazidime (1/1), meropenem (0.5/0.5), ciprofloxacin (0.25/0.25), levofloxacin (0.25/0.25), azithromycin (4/4), doxycycline (0.5/0.5) and trimethoprim/sulfamethoxazole (0.25/0.25). The corresponding zone diameter breakpoints were identified. Conclusions We demonstrated the validity of using standard BMD and EUCAST disc diffusion methodology for AST of five Vibrio spp. and generated suitable data to allow EUCAST to determine clinical MIC and zone diameter breakpoints for five pathogenic Vibrio spp. including both non-toxigenic and toxigenic V. cholerae. [ABSTRACT FROM AUTHOR]

Objectives Antimicrobial resistance rates are continuously increasing, driving the need for rapid antimicrobial susceptibility testing (RAST) results, especially in the treatment of bloodstream infections. The EUCAST RAST method performed directly from positive blood cultures with incubation times from 4 to 8 h was developed in 2018 and is now used in many laboratories. To increase the practicality of the method, an extended incubation time of 16 and 20 h was evaluated in this study. Method Blood culture bottles were spiked with clinical isolates (n  = 325) of the seven most important sepsis pathogens. The EUCAST RAST method was performed, extending the incubation time to 16 and 20 h. Broth microdilution (BMD) was used as a reference, except for screening tests where standard disc diffusion or presence of resistance genes was used. Results Inhibition zones were possible to read for all species–agent combinations. For 16 and 20 h, the MIC zone diameter correlations were sufficiently similar to allow establishment of common breakpoints for the time interval of 16–20 h. The proportion of isolates in the area of technical uncertainty was, on average, 6% for all species and the number of errors were low, with <1% false-resistant and <0.5% false-susceptible results. Conclusions This study shows that, for EUCAST RAST, prolonging the recommended incubation to 16–20 h is possible and can be used as a complement when the intended shorter incubation is not possible to achieve. The introduction of the prolonged incubation will increase the usefulness of the EUCAST RAST method in clinical laboratories with limited opening hours. [ABSTRACT FROM AUTHOR]

Haemophilus influenzae is subdivided into encapsulated strains, which express different serotypes of capsular polysaccharide (designated types a-f), and nonencapsulated strains, which are designated nontypeable H. influenzae (NTHi) (1). Since the [...]

The antibiotic pipeline continues to diminish and the majority of the public remains unaware of this critical situation. The cause of the decline of antibiotic development is multifactorial and currently most ICUs are confronted with the challenge of multidrug-resistant organisms. Antimicrobial multidrug resistance is expanding all over the world, with extreme and pandrug resistance being increasingly encountered, especially in healthcare-associated infections in large highly specialized hospitals. Antibiotic stewardship for critically ill patients translated into the implementation of specific guidelines, largely promoted by the Surviving Sepsis Campaign, targeted at education to optimize choice, dosage, and duration of antibiotics in order to improve outcomes and reduce the development of resistance. Inappropriate antimicrobial therapy, meaning the selection of an antibiotic to which the causative pathogen is resistant, is a consistent predictor of poor outcomes in septic patients. Therefore, pharmacokinetically/pharmacodynamically optimized dosing regimens should be given to all patients empirically and, once the pathogen and susceptibility are known, local stewardship practices may be employed on the basis of clinical response to redefine an appropriate regimen for the patient. This review will focus on the most severely ill patients, for whom substantial progress in organ support along with diagnostic and therapeutic strategies markedly increased the risk of nosocomial infections., Author(s): Matteo Bassetti [sup.1] [sup.14], Jan J. De Waele [sup.2], Philippe Eggimann [sup.3], Josè Garnacho-Montero [sup.4], Gunnar Kahlmeter [sup.5], Francesco Menichetti [sup.6], David P. Nicolau [sup.7], Jose Arturo Paiva [sup.8], [...]

Objectives: Pivmecillinam, the oral version of mecillinam, represents one of the major recommended and used antibiotics for empiric and targeted treatment of urinary tract infections in primary care in Denmark, Norway and Sweden. Mecillinam resistant mutants in Escherichia coli develop easily in vitro, but their fitness cost has been shown to be high.Methods: We revisited the resistance and consumption data from the monitoring programmes in the three countries and compared pivmecillinam with ciprofloxacin from 2010 to 2020.Results: Mecillinam resistance rates in Escherichia coli remained around 6% in Denmark and Norway relative to a constant consumption in Norway of 1.6-1.8 DID (defined daily doses per 1000 inhabitants per day), and even increasing in Denmark from 1.6 to 2.3 DID. In Sweden resistance was significantly lower at 4% related to the lower consumption of 0.5 DID. For ciprofloxacin, resistance rates fluctuated around 6%-12%, highest in Sweden with the highest consumption (0.8-0.6 DID) and lowest in Denmark (0.55-0.35 DID) and Norway (0.7-0.3 DID), although consumption declined significantly in all three countries.Conclusions: Pivmecillinam is an example of an antibiotic, which easily develops resistance in vitro, but apparently can be used broadly in primary care without increase in resistance rates. [ABSTRACT FROM AUTHOR]