JAC-Antimicrobial Resistance最新文献

Background: Community pharmacies in England offer convenient and safe disposal of unwanted medicines, including antimicrobials, and better uptake of this service could limit environmental antimicrobial resistance. However, there is limited information on the extent and nature of antibiotic returns to community pharmacies. The impact of an antibiotic amnesty campaign promoting antibiotic disposal through community pharmacies was evaluated with the intention of collecting detailed information on the antibiotics returned.

Methods: An antibiotic amnesty campaign was delivered by community pharmacies in the Midlands (England) with an audit of returned antibiotics conducted in 19 community pharmacies in Leicestershire. Detailed information on antibiotics returned for disposal was gathered during the month-long amnesty campaign and again 3 months later in the same pharmacies.

Results: Antibiotics accounted for 3.12%-3.35% of all returned medicines. The amnesty campaign led to a significant increase in defined daily doses of returned antibiotics compared to the post-amnesty period (P = 0.0165), but there was no difference in the overall number of returned medicines. Penicillins were the most commonly returned antibiotics in both periods (29.3% and 42.5% of packs, respectively), while solid oral dose formulations predominated. A total of 36.6% of antibiotics returned during the amnesty period were expired, increasing to 53.4% in the post-amnesty period. Amnesty conversations had a significant impact on the number of antibiotic returns but campaign posters did not.

Conclusions: Antibiotic conversations can increase the amount of antibiotics returned to community pharmacies for safe disposal, and passive campaign materials had limited impact. More research is needed to identify the most effective interventions to increase returns.

Background: Many patients with Enterococcus faecalis endocarditis are clinically stable and able to leave hospital before completing antibiotic treatment, but data are lacking regarding some outpatient treatment options.

Objectives: To assess the outcomes for adults with E. faecalis endocarditis receiving outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion IV benzylpenicillin plus bolus/continuous infusion IV ceftriaxone.

Patients and methods: We retrospectively reviewed adults who received at least 2 weeks duration of OPAT for E. faecalis endocarditis with the above treatment regimen in the Auckland and Christchurch regions between July 2019 and September 2022.

Results: Forty-four patients met inclusion criteria. Fifteen were female (34%). The median age was 80 (IQR 71.5 to 84) years. Twenty-two (50%) had prosthetic valve (PV), 15 (34%) native valve (NV), 3 (7%) NV and/or cardiac implantable electronic device (CIED) infection, 3 (7%) PV and/or CIED infection, and 1 (2%) repaired valve endocarditis. Patients received a median of 16.5 days inpatient and 28 days OPAT antibiotic treatment. The 12 month outcome was cure (n = 25; 57%), antibiotic suppression (n = 9; 20%), relapse (n = 2; 5%; both possible) or death (n = 8; 18%). Compared with a historical cohort treated with OPAT continuous infusion IV benzylpenicillin plus bolus IV gentamicin, there was no difference in the relapse rate.

Conclusions: This study adds to the accumulating evidence supporting the treatment of E. faecalis endocarditis with OPAT continuous infusion IV benzylpenicillin plus bolus/continuous infusion IV ceftriaxone. This is an option for patients requiring further antibiotic treatment at the time of hospital discharge.

Objectives: Cefiderocol is a novel siderophore-conjugated cephalosporin developed for the treatment of multidrug-resistant Gram-negative bacterial (GNB) infections. However, the current gold standard for cefiderocol susceptibility testing, broth microdilution (BMD) using iron-depleted cation-adjusted Mueller-Hinton broth, presents challenges for many microbiology laboratories. In this study, we evaluate the real-world performance of disc diffusion (DD) and a commercial BMD method (ComASP^®) to test cefiderocol susceptibility in a series of isolates collected prospectively from severely ill patients in a multicentre study.

Methods: The susceptibilities of 1472 isolates (632 Enterobacterales, 532 Pseudomonas aeruginosa, 84 Acinetobacter spp. and 224 Stenotrophomonas maltophilia) collected in 60 Spanish hospitals were analysed following the EUCAST 2023 and 2024 criteria. We assessed the performance of DD (cefiderocol 30 μg disc, Liofilchem) and a commercial BMD method (ComASP^® Cefiderocol, Liofilchem).

Results: A total of 1408 and 1450 isolates were susceptible by DD and ComASP^® BMD, respectively. Overall, the agreement between both methods was 96.9%. Forty-four isolates were resistant by DD but susceptible by ComASP^® BMD, and two were susceptible by DD but resistant by ComASP^® BMD (Acinetobacter baumannii isolates). Adoption of the updated 2024 EUCAST DD breakpoints and areas of technical uncertainty (ATUs) led to a decrease in susceptibility among Enterobacterales (95.3% versus 92.6%).

Conclusions: DD is a straightforward, rapid and accessible method for routine determination of cefiderocol susceptibility in real-world practice. ComASP^® BMD shows a high agreement with DD in susceptible isolates and may help to resolve DD interpretability concerns in isolates with susceptibility results within the ATU, but caution is warranted when testing resistant isolates.

Background: Dalbavancin is a lipoglycopeptide antibiotic with a wide spectrum of activity against Gram-positive bacteria, including MDR isolates. Its pharmacokinetic properties and administration patterns could be useful for the treatment of bone and joint infections, especially prosthetic joint infections (PJIs).

Introduction: We report the case of an 80-year-old man who experienced an acute periprosthetic joint infection of his right total knee arthroplasty (TKA). A DAIR procedure was done with tissue sampling, which allowed identification of a linezolid-resistant MDR S. epidermidis (LR-MDRSE) strain. The patient was then treated with dalbavancin (four injections).

Methods: We studied the phenotypic and genomic evolution of the strains and plasma through concentrations of dalbavancin at different points in time.

Results: After four injections (1500 mg IV) of dalbavancin over a 6 month period, the dalbavancin MIC increased 4-fold. Calculated fAUC_0-24/MIC ratios were 945, 1239 and 766.5, respectively, at Days 49, 71 and 106, assuming an MIC of 0.032 mg/L. The PFGE dendrogram revealed 97% similarity among all the isolates. These results suggest acquisition by the S. epidermidis strain of dalbavancin resistance when the patient underwent dalbavancin treatment. A 4-amino-acid deletion in the walK gene coinciding with the emergence of phenotypic resistance was revealed by WGS without any other relevant indels.

Conclusions: Despite dalbavancin treatment with pharmacokinetic management, emerging dalbavancin resistance in S. epidermidis was observed, resulting in treatment failure. This outcome led to a prosthesis revision and long-term suppressive antibiotic therapy, with no recurrence of PJI after an 18 month follow-up.

Background: Chronic bronchopulmonary infection due to MRSA in people with cystic fibrosis (pwCF) has been associated with accelerated decline in lung function, increased hospitalizations and increased mortality.

Material and methods: We studied microbiological and genomic characteristics of MRSA isolates recovered from pwCF in two Spanish multicentre studies (2013, 2021). Antimicrobial susceptibility was performed. WGS was carried out to determine population structure [MLST, spa-typing, staphylococcal cassette chromosome mec (SCCmec)], resistome and virulome. Clinical charts of MRSA-infected and MRSA-non-infected pwCF were also reviewed.

Results: MRSA infection prevalence decreased between 2013 (29/341, 8.5%) and 2021 (21/326, 6.4%) (P = 0.378). Differences in lung function were observed between infected and non-infected patients (P < 0.005). A higher prevalence of hospital-acquired (HA) clones was found compared with community-acquired (CA) clones (2013: 67% versus 33%; and 2021: 71% versus 29%). Overall, we noted clustering of isolates based on year of sampling, type of acquisition and clonal complex (CC). HA-MRSA population was dominated by CC5, with ST125-MRSA-IVc-t067 the most prevalent lineage (37%). A higher clonal diversity was detected among CA-MRSA. One Panton-Valentine leucocidin (PVL)-positive strain (ST8-MRSA-IV) and three strains of porcine origin (two ST398-MRSA-V-t011, one ST398-MRSA-V-t8567) were found. Additionally, acquired resistance genes (n = 24) were detected, including the cfr gene conferring linezolid resistance. A higher gentamicin resistance was found in 2021 (42%) compared with 2013 (7%) (P = 0.046), associated with the aac(6')-aph(2″) gene.

Conclusions: Despite a decrease in MRSA prevalence, we showed its potential impact on CF severity and progression. Moreover, we observed great genotypic and phenotypic diversity in MRSA isolates from pwCF as well as an MDR trait.

Objectives: To describe the real-life use of temocillin for non-urinary tract infections, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure.

Method: Retrospective multicentric study in 14 tertiary care hospitals, including all patients who received at least one dose of temocillin for ESBL infections from 1 January 2016 to 31 December 2021 for non-urinary tract infections. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. Logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure.

Results: Data on 163 infection episodes were collected; 133 were due to ESBL-producing Enterobacterales and 128 were included in the effectiveness analysis. Median (IQR) age was 61 (53-70) years and 61.7% of patients were male. Main indications were lower respiratory tract infection (LRTI; 28.9%), intra-abdominal infections (IAI; 28.1%) and cutaneous infections (12.5%). The main bacteria involved were Klebsiella pneumoniae (48.4%), Escherichia coli (25.0%) and Enterobacter cloacae (24.2%). Polymicrobial infections occurred in 45.3% of cases. Temocillin was used as monotherapy in 86/128 (67.2%). Failure was found in 36/128 (28.1%) cases. In multivariable analysis, the only factor associated with failure was initial severity of the episode [adjusted OR 3.0 (95% CI: 1.06-8.69)].

Conclusions: During non-urinary tract infections, the main use of temocillin was for LRTIs and IAIs due to ESBL-producing E. coli and K. pneumoniae. The main risk factor for failure was initial severity of the disease.

Background: Growing antimicrobial resistance represents serious public health threat. With the increasing presence of online/e-pharmacies in India, public access to medicines has increased. Easy access coupled with lack of adequate and authentic drug information can undermine rational antibiotic use.

Objectives: The present study aimed at exploring the availability of antibiotics for online sale and comparing the e-pharmacies on key characteristics influencing safe and rational use of antibiotics.

Methods: A cross-sectional study was conducted over a period of 3 months using the websites of 10 popular e-pharmacies in India. Availability of antibiotics for online sale was assessed in context of the National List of Essential Medicines, 2022 and WHO-AWaRe (Access, Watch, Reserve) categories. Three separate questionnaires were developed to extract and compare relevant information from e-pharmacies pertaining to their safety and authenticity (in light of the expected standards laid down in draft e-pharmacy rules, 2018), availability of drug product and consumer awareness information for promoting prudent antibiotic use. Data were summarized using descriptive statistics.

Results: Out of the 17 antibiotics studied; antibiotics belonging to all WHO-AWaRe categories i.e. Access (83.33%), Watch (88.33%) and Reserve (78%) groups were available through e-pharmacies. Wide variation exists among the e-pharmacies regarding compliance to studied parameters under three questionnaires.

Conclusions: Increased access to Watch and Reserve groups of antibiotics can translate into antibiotic misuse. It is therefore crucial that the regulatory gaps concerning e-pharmacies are addressed urgently and consumers are educated regarding safe and rational use of antibiotics.

Background: Outpatient parenteral antimicrobial therapy (OPAT) is safe, effective and increasingly available. While OPAT in Norwegian healthcare has been rare, a new continuous ambulatory delivery device (CADD) allowing multiple daily dosing treatments has been innovated making OPAT more accessible.

Objectives: To describe the clinical outcome and safety using CADD in an OPAT setting.

Methods: Adult patients in need of parenteral antibiotic treatment were offered OPAT and discharged with a programmable digital infusion pump allowing multiple daily dosings.

Results: Altogether, 170 patients were included in the study, among which 21% of all patients (36 of 170) were readmitted to hospital while receiving OPAT or within 30 days after end of intravenous antibiotics. None of the 170 patients died due to OPAT and allergies were not noticeable as a problem.

Conclusions: We have developed a safe and clinically effective programme offering OPAT in accordance with Norwegian antibiotic treatment guidelines.

Background: In Tanzania, ceftriaxone is one of the most commonly prescribed antibiotics. However, there is quite a significant variation in cost for numerous ceftriaxone brands, leading to the perception that pricier options are more effective. Yet, limited empirical data support this perception.

Methods: Five ceftriaxone brands with a wide price range were tested in vitro against a ceftriaxone-sensitive Escherichia coli clinical isolate using microdilution and spectrophotometry. Brands were evaluated across a spectrum of concentrations. Bacterial growth inhibition was measured using optical density. Analysis of variance was used to compare the bacterial optical densities among the brands.

Results: All brands were comparable at all tested concentrations, with peak inhibition above 1.95 mg/L.

Conclusions: Despite significant price disparities, low-cost and high-cost ceftriaxone brands demonstrated similar in vitro performance against E. coli. This challenges the notion that higher-priced options offer better performance. Further, in vivo studies are recommended to validate these findings.

Background: Surgical site infections (SSIs) are on the rise and are a global concern as they complicate the recovery of patients postoperatively. Bacterial colonization of the patient's skin and alimentary tract are known to be major contributing sources to SSIs. However, Zambia lacks data relating to carriage rates of antibiotic-resistant rectal Escherichia coli among surgical patients.

Methods: This was a cross-sectional study aimed at determining the preoperative (preop) and postoperative (postop) carriage and antimicrobial susceptibility patterns of rectal ESBL-producing E. coli (ESBL-Ec) in elective surgery patients at the highest tertiary hospital in Lusaka, Zambia. Phenotypic methods were used in the identification of E. coli. Antibiotic susceptibility patterns and identification of ESBL-Ec was determined by Kirby-Bauer disc diffusion.

Results: A total of 120 study participants were recruited, of which 75 were followed up at least 72 h after surgery. From 195 rectal swabs cultured, 177 (90.8%) were positive for E. coli, of which 53 (29.9%) were ESBL-Ec, with a significantly (P < 0.0001) higher proportion in postop (47.9%) than preop (17.3%) participants. Overall, ESBL-Ec isolates showed higher resistance in postop than preop to cefotaxime (100% versus 88.9%, respectively), ampicillin (100% versus 94.4%), ciprofloxacin (88.3% versus 83.3%), amoxicillin/clavulanic acid (80% versus 66.7%) and cefepime (80% versus 77.8%). MDR ESBL-Ec strains were more frequent in postop than in preop participants (91.4% versus 88.9%).

Conclusions: The study showed a significantly higher rate of antimicrobial-resistant rectal E. coli in postop than preop participants. There is a need to ascertain the source of the resistance and to institute robust infection control measures, preop screening of surgical patients for ESBL-Ec, and to raise awareness on prudent use of antibiotics.