Successful ceftolozane/tazobactam treatment of chronic pulmonary infection with pan‐resistant Pseudomonas aeruginosa

The treatment of chronic Pseudomonas aeruginosa infections is challenging, with resistance and antibiogram diversity accumulating during successive therapies. Some isolates are resistant to all licensed agents, creating treatment problems and an urgent need for new therapies. Among antibiotics in advanced development, ceftolozane/tazobactam has potent in vitro antipseudomonal activity, with low MICs even for strains with AmpC β‐lactamase‐, impermeability‐ and efflux‐mediated resistance to other β‐lactams

Antimicrobial stewardship: the need to cover all bases

Increasing antimicrobial resistance has necessitated an approach to guide the use of antibiotics. The necessity to guide antimicrobial use via stewardship has never been more urgent. The decline in anti-infective innovation and the failure of currently available antimicrobials to treat some serious infections forces clinicians to change those behaviors that drive antimicrobial resistance. The majority of antimicrobial stewardship (AMS) programs function in acute-care hospitals, however, hospitals are only one setting where antibiotics are prescribed. Antimicrobial use is also high in residential aged care facilities and in the community. Prescribing in aged care is influenced by the fact that elderly residents have lowered immunity, are susceptible to infection and are frequently colonized with multi-resistant organisms. While in the community, prescribers are faced with public misconceptions about the effectiveness of antibiotics for many upper respiratory tract illnesses. AMS programs in all of these locations must be sustainable over a long period of time in order to be effective. A future with effective antimicrobials to treat bacterial infection will depend on AMS covering all of these bases. This review discusses AMS in acute care hospitals, aged care and the community and emphasizes that AMS is critical to patient safety and relies on government, clinician and community engagement

Recollections by Ben Shlaes

https://openspace.dmacc.edu/pioneerrecollections/1082/thumbnail.jp

The 1930s as black mirror: Visions of historical repetition in the global financial press, 2007-2009

Media coverage of the recent financial crisis has referred extensively to various past crises, and in particular to the events of the 1930s. This article suggests that the idea of the Great Depression has effectively come to function as a kind of historical ‘black mirror’ – a quasi-object within which conjuncture and historical representation interact to produce an image of capitalist history itself. Focusing on the journalistic output of four key financial publications, I trace how portrayals of the 1930s have evolved over the course of the crisis. I find that while the 1930s are frequently and consistently invoked in ways that purport to reveal the historicity of the crisis, these representations produce an oscillation between different visions of historical repetition, which in turn underpin competing interpretations of the crisis as it unfolds. In so doing, I argue, appeals to the 1930s have simultaneously served to conceal and disclose the constitutive relation of historical imagination to historical process – a double move that has had the paradoxical effect of both securing and undermining the reproduction of finance capitalism as we have come to know it

Synthesis and Evaluation of N-Phenylpyrrolamides as DNA Gyrase B Inhibitors

ATP-competitive inhibitors of DNA gyrase and topoisomerase IV are among the most interesting classes of antibacterial drugs that are unrepresented in the antibacterial pipeline. We developed 32 new N-phenylpyrrolamides and evaluated them against DNA gyrase and topoisomerase IV from E.coli and Staphylococcus aureus. Antibacterial activities were studied against Gram-positive and Gram-negative bacterial strains. The most potent compound displayed an IC50 of 47 nm against E.coli DNA gyrase, and a minimum inhibitory concentration (MIC) of 12.5 mu m against the Gram-positive Enterococcus faecalis. Some compounds displayed good antibacterial activities against an efflux-pump-deficient E.coli strain (MIC=6.25 mu m) and against wild-type E.coli in the presence of efflux pump inhibitor PA beta N (MIC=3.13 mu m). Here we describe new findings regarding the structure-activity relationships of N-phenylpyrrolamide DNA gyrase B inhibitors and investigate the factors that are important for the antibacterial activity of this class of compounds.Peer reviewe

Patterns of antimicrobial resistance in a surgical intensive care unit of a university hospital in Turkey

BACKGROUND: Several studies have reported higher rates of antimicrobial resistance among isolates from intensive care units than among isolates from general patient-care areas. The aims of this study were to review the pathogens associated with nosocomial infections in a surgical intensive care unit of a university hospital in Turkey and to summarize rates of antimicrobial resistance in the most common pathogens. The survey was conducted over a period of twelve months in a tertiary-care teaching hospital located in the south-eastern part of Turkey, Gaziantep. A total of 871 clinical specimens from 615 adult patients were collected. From 871 clinical specimens 771 bacterial and fungal isolates were identified. RESULTS: Most commonly isolated microorganisms were: Pseudomonas aeruginosa (20.3%), Candida species (15%) and Staphylococcus aureus (12.9%). Among the Gram-negative microorganisms P. aeruginosa were mostly resistant to third-generation cephalosporins (71.3–98.1%), while Acinetobacter baumannii were resistant in all cases to piperacillin, ceftazidime and ceftriaxone. Isolates of S. aureus were mostly resistant to penicillin, ampicillin, and methicillin (82–95%), whereas coagulase-negative staphylococci were 98.6% resistant to methicillin and in all cases resistant to ampicillin and tetracycline. CONCLUSION: In order to reduce the emergence and spread of antimicrobial-resistant pathogens in ICUs, monitoring and optimization of antimicrobial use in hospitals are strictly recommended. Therefore local resistance surveillance programs are of most value in developing appropriate therapeutic guidelines for specific infections and patient types

Monitoring Antimicrobial Use and Resistance: Comparison with a National Benchmark on Reducing Vancomycin Use and Vancomycin-Resistant Enterococci

To determine if local monitoring data on vancomycin use directed quality improvement and decreased vancomycin use or vancomycin-resistant enterococci (VRE), we analyzed data from 50 intensive-care units (ICUs) at 20 U.S. hospitals reporting data on antimicrobial-resistant organisms and antimicrobial agent use. We compared local data with national benchmark data (aggregated from all study hospitals). After data were adjusted for changes in prevalence of methicillin-resistant Staphylococcus aureus, changes in specific prescriber practice at ICUs were associated with significant decreases in vancomycin use (mean decrease -48 defined daily doses per 1,000 patient days, p<0.001). These ICUs also reported significant decreases in VRE prevalence compared with those not using unit-specific changes in practice (mean decrease of 7.5% compared with mean increase of 5.7%, p<0.001). In this study, practice changes focused towards specific ICUs were associated with decreases in ICU vancomycin use and VRE prevalence

Vancomycin and Home Health Care

Microbiologic diagnosis before hospital discharge and physician education may limit inappropriate vancomycin use in homecare patients

Mononuclear ruthenium(ii) theranostic complexes that function as broad-spectrum antimicrobials in therapeutically resistant pathogens through interaction with DNA

Six luminescent, mononuclear ruthenium(II) complexes based on the tetrapyridophenazine (tpphz) and dipyridophenazine (dppz) ligands are reported. The therapeutic activities of the complexes against Gram-negative bacteria (E. coli, A. baumannii, P. aeruginosa) and Gram-positive bacteria (E. faecalis and S. aureus) including pathogenic multi- and pan-drug resistant strains were assessed. Estimated minimum inhibitory and bactericidal concentrations show the activity of the lead compound is comparable to ampicillin and oxacillin in therapeutically sensitive strains and this activity was retained in resistant strains. Unlike related dinuclear analogues the lead compound does not damage bacterial membranes but is still rapidly taken up by both Gram-positive and Gram-negative bacteria in a glucose independent manner. Direct imaging of the complexes through super-resolution nanoscopy and transmission electron microscopy reveals that once internalized the complexes' intracellular target for both Gram-negative and Gram-positive strains is bacterial DNA. Model toxicity screens showed the compound is non-toxic to Galleria mellonella even at exposure concentrations that are orders of magnitude higher than the bacterial MIC