Notes

Modulation of Medicine Resistance by simply Limonene: Inhibition of Efflux Pumps throughout Staphylococcus aureus Ranges RN-4220 as well as IS-58.
The COVID-19 pandemic, meanwhile, had no effect on AMR but raised awareness on preventive measures. However, this was a temporary rather than long-term outcome. Thus, different policies, strategies, and measures should be designed to advocate prevention of AMR in the COVID-19 era.Antibiotics misuse and overuse are concerning issues worldwide, especially in low middle-income countries. These practices contribute to the increasing rates of antimicrobial resistance. One efficient strategy to avoid them is antimicrobial stewardship programs. In this review, we focus on the possible approaches to spare the prescription of polymyxins and carbapenems for the treatment of Acinetobacter baumannii, carbapenem-resistant Enterobacterales, and Pseudomonas aeruginosas infections. Additionally, we highlight how to implement cumulative antibiograms and biomarkers to a sooner de-escalation of antibiotics.The global escalation of severe infections due to carbapenemase-producing Enterobacterales (CPE) isolates has prompted increased usage of parenteral colistin. Considering the reported difficulties in assessing their susceptibility to colistin, the purpose of the study was to perform a comparative evaluation of six phenotypic assays-the colistin broth disc elution (CBDE), Vitek 2 Compact (bioMérieux SA, Marcy l'Etoile, France), the Micronaut MIC-Strip Colistin (Merlin Diagnostika GMBH, Bornheim-Hensel, Germany), the gradient diffusion strip Etest (bioMérieux SA, Marcy l'Etoile, France), ChromID Colistin R Agar (COLR) (bioMérieux SA, Marcy l'Etoile, France), and the Rapid Polymyxin NP Test (ELITechGroup, Signes, France)-versus the reference method of broth microdilution (BMD). All false resistance results were further assessed using population analysis profiling (PAP). Ninety-two nonrepetitive clinical CPE strains collected from two hospitals were evaluated. The BMD confirmed 36 (39.13%) isolates susceptible to colistin. According to the BMD, the Micronaut MIC-Strip Colistin, the CBDE, and the COLR medium exhibited category agreement (CA) of 100%. In comparison with the BMD, the highest very major discrepancy (VMD) was noted for Etest (n = 15), and the only false resistance results were recorded for the Rapid Polymyxin NP Test (n = 3). Only the PAP method and the Rapid Polymyxin NP Test were able to detect heteroresistant isolates (n = 2). Thus, there is an urgent need to further optimize the diagnosis strategies for colistin resistance.Urinary tract infections (UTIs) represent a common pathology among female patients, leading to overprescribing antibiotics, globally. The emergence of the COVID-19 pandemic has dramatically increased the incidence of this particular viral pneumonia with secondary bacterial superinfection, resulting in continuous therapeutic or prophylactic recommendations of antibiotic treatment; thus, an updated analysis of current antimicrobial resistance among uropathogens is mandatory. This cross-sectional retrospective study conducted in two university hospitals in Bucharest, Romania analyzed 2469 positive urine cultures, among two different periods of 6 months, before and during the COVID-19 pandemic. The most common pathogen was Escherichia coli 1505 (60.95%), followed by Klebsiella spp. 426 (17.25%). Enterococcus spp. was the leading Gram-positive pathogen 285 (11.54%). In gram negative bacteria, in almost all cases, an increased in resistance was observed, but the highest increase was represented by quinolones in Klebsiella spp., from 16.87% to 35.51% and Pseudomonas from 30.3% to 77.41%; a significant increase in resistance was also observed for carbapenems. Surprisingly, a decrease in resistance to Penicillin was observed in Enterococcus spp., but the overall tendency of increased resistance is also maintained for gram positive pathogens. The lack of data on the influence of the COVID-19 pandemic on uropathogens' resistance promotes these findings as important for every clinician treating UTIs and for every specialist in the medical field in promoting reasonable recommendations of antibiotic therapies.(1) Background Ceftriaxone is a potential alternative for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) in acute care and outpatient parenteral antimicrobial therapy (OPAT) settings. We evaluated the effectiveness and safety of ceftriaxone for the treatment of MSSA BSIs. (2) Method We searched PubMed, Embase, and Cochrane Library from their inception to October 30th 2021. Our outcomes included clinical cure, microbiological cure, 30- and 90-day mortality, 90-day hospital readmission, and adverse drug reactions (ADRs). We compared ceftriaxone against standard of care (SOC) therapy. We used the random-effects model for the meta-analysis, and our estimated effects were reported as odds ratios (ORs) with 95% confidence intervals (CI). (3) Results Twelve retrospective cohort studies were included, comprising 1037 patients in the ceftriaxone arms and 2088 patients in the SOC arms. The clinical cure rate of the ceftriaxone regimen was not statistically different from SOC OR 0.65 (95% CI 0.29-1.45). Ceftriaxone was also not statistically different from SOC in microbiological cure OR 1.48 (95% CI 0.29-7.51); 30-day mortality OR 0.79 (95% CI 0.14-4.65); 90-day mortality OR 0.82 (95% CI 0.38-1.80); 90-day hospital readmission OR 1.20 (95% CI 0.92-1.56); and ADRs OR 0.92 (95% CI 0.39-2.18). (4) Conclusion Ceftriaxone could provide an alternative for the treatment of MSSA BSIs in acute care and OPAT settings (except in patients whose BSIs were due to infective endocarditis).Donkeys (Equus asinus) are in decline in Europe. Occupational exposure to farm animals has been associated with increased staphylococci carriage. We aimed to isolate S. aureus and coagulase-negative staphylococci (CoNS) from donkeys and handlers and characterize the antimicrobial resistance profiles and genetic lineages of S. aureus strains. Oral and nasal swab samples were collected from 49 Miranda donkeys and 23 handlers from 15 different farms. Staphylococci species were identified by MALDI-TOF MS. The presence of antimicrobial resistance genes and virulence factors was investigated by PCR. Molecular typing was performed in S. aureus isolates. From the 49 donkey samples, 4 S. aureus (8.2%) and 21 CoNS (42.9%) were isolated. Ten handlers (43.5%) were carriers of S. aureus and 4 (17.4%) carried CoNS. The CoNS isolates showed resistance to several classes of antimicrobials encoded by the mecA, aph (3')-IIIa, ant (4')-Ia, tetM, tetK, lnuA, ermB, ermC, dfrA and dfrG genes. S. aureus isolates were resistant to penicillin, aminoglicosides and tetracycline harboring the blaZ, aph (3')-IIIa, tetL, tetM and tetK genes. All S. aureus isolates from donkeys belonged to ST49 and spa-type t208 while the strains isolated from the handlers were ascribed to 3 STs and 7 spa-types. However, human isolates were from different STs than the donkey isolates. Donkeys are mainly colonized by methicillin-resistant S. sciuri. S. aureus transmission between donkeys and their handlers appears not to have occurred since the isolates belonged to different genetic lineages.
The aim of this study was to describe our experience of a combination treatment including meropenem/vaborbactam (M/V) plus aztreonam (ATM) for bloodstream infections (BSIs) due to ceftazidime/avibactam-resistant
(CAZ/AVI-R-
), for which gene typing was not available at the time the blood culture (BC) results were obtained.

Between 20 July and 22 August 2021, in our hospital laboratory, the molecular test for carbapenemase gene typing was not available. All Gram-negative bloodstream infections were recorded, and characteristics of patients were analysed. Among them, three patients had positive BCs for CAZ/AVI-R-
, and the empirical therapy was switched to M/V plus ATM pending phenotypic testing of sensitivity to M/V. Therapy was subsequently targeted on the basis of the results of this test.

KPC and NDM represent the most prevalent carbapenemases in our polyclinic. Three patients with CAZ/AVI-R-
sepsis were treated with M/V plus ATM not knowing the carbapenemase gene. Two had an NDM-
infection for which, upon obtaining the result of sensitivity to M/V, combination therapy was maintained. The third had KPC-
infection for which ATM was discontinued, after the acquisition of an antibiogram reporting full sensitivity to M/V (MIC = 0.25 mg/L). One patient with NDM-
infection died due to complications of the underlying disease for which he was hospitalised.

Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-
infections when carbapenemase gene typing is not rapidly available.
Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-Kp infections when carbapenemase gene typing is not rapidly available.Antimicrobial resistance is a major public health issue caused by antibiotic overuse and misuse. Antimicrobial stewardship (AMS) has been increasingly endorsed worldwide, but its effect has been studied scarcely in urologic settings. A before-after study was performed from 2018 through 2020 to evaluate changes in antimicrobial prescription, resistance rates and clinical safety upon implementation of an AMS audit and feedback program in the Urology Department of a large German academic medical center. The primary endpoints were safety clinical outcomes the rate of infection-related readmissions and of infectious complications after transrectal prostate biopsies. Resistance rates and antimicrobial consumption rates were the secondary endpoints. The AMS team reviewed 196 cases (12% of all admitted in the department). The overall antibiotic use dropped by 18.7%. Quinolone prescriptions sank by 78.8% (p = 0.02) and 69.8% (p > 0.05) for ciprofloxacin and levofloxacin, respectively. The resistance rate of E. coli isolates declined against ceftriaxone (-9%), ceftazidime (-12%) and quinolones (-25%) in the AMS period. No significant increase in infection-related readmissions or infectious complications after prostate biopsies was observed (p = 0.42). Due to the potential to reduce antibiotic use and resistance rates with no surge of infection-related complications, AMS programs should be widely implemented in urologic departments.Koch attempted to treat tuberculosis in the late 1800s by administering an antigenic extract derived from the pathogen to patients. He hoped to bolster the patient's protective immunity. The treatment had diverse results. In some, it improved the patient's condition and in others led to a worsening state and even to death. Koch stopped giving his experimental treatment. I consider here three issues pertinent to realizing Koch's vision. Rational immunotherapy requires a knowledge of what constitutes protective immunity; secondly, how on-going immune responses are regulated, so the patient's immunity can be modulated to become optimally protective; thirdly, a simple methodology by which treatment might be realized. I deliberately cast my account in simple terms to transcend barriers due to specialization. The proposed immunotherapeutic treatment, if realizable, would significantly contribute to overcoming problems of treatment posed by antibiotic resistance of the pathogen.
My Website: