JAC-Antimicrobial Resistance最新文献

Objectives: Viridans streptococci (VS) are opportunistic oral commensals and a common cause of bacteraemia in neutropenic patients. In this retrospective single centre cohort study, we investigated the prevalence of ceftriaxone resistance in VS (CRO-R VS) blood isolates between January 2005 and December 2022 from patients treated at a tertiary care hospital.

Methods: Blood culture isolates were identified using biochemicals and mass spectrometry. Susceptibility testing was performed by Kirby-Bauer and Epsilometer tests. Demographic data, clinical outcomes and antimicrobial use were assessed through electronic medical record review.

Results: Among 791 patients with VS bacteraemia, 31 (4%) had confirmed CRO-R VS bacteraemia over the 18-year period; 20/31 (65%) were patients also treated at the Fred Hutchinson Cancer Center and were the focus of this study. Of these 20 patients, 18 (90%) had a known haematologic malignancy; 14 (70%) had undergone haematopoietic cell transplant (HCT); 18 (90%) were neutropenic at the time of culture. Two (10%) patients died within 30 days of CRO-R VS bacteraemia. All the CRO-R isolates (20/20) were members of the Streptococcus mitis group, 12 were multi-drug resistant; all were susceptible to vancomycin. Most patients received vancomycin once blood cultures were positive for a Gram-positive organism.

Conclusions: During the study period, the frequency of VS isolate susceptibility testing increased; however, there was no concomitant increase in the percentage of CRO-R isolates at our facility. These data are important in an era where cefepime monotherapy is often used and reinforces the importance of routine resistance testing among VS bacteraemia.

Objectives: To describe antimicrobial use (AMU) in patients admitted to hospitals in Timor-Leste.

Methods: In 2020 and 2021, we undertook antimicrobial prescribing point prevalence surveys across all six hospitals in Timor-Leste (one national and five municipal) to describe AMU and appropriateness in admitted patients.

Results: In 2020, 291/394 (73.9%) surveyed patients had been prescribed antimicrobials, compared with 260/403 (64.5%) in 2021 (P = 0.004). Most (309/551; 56.1%) were prescribed one antimicrobial, and 179/551 (32.5%) were prescribed two. The most commonly prescribed antibiotics were ceftriaxone (38.5% in 2020, 41.5% in 2021) and ampicillin (35.7% in 2020, 32.3% in 2021), followed by gentamicin, metronidazole and cloxacillin. Reserve antibiotics like meropenem and vancomycin were minimally used. Of all antimicrobial prescriptions, 70.8% were deemed appropriate in 2020 and 69.1% in 2021. Antimicrobial prescriptions for surgical and post-partum prophylaxis were frequently deemed inappropriate [37/50 (74.0%) and 39/44 (88.6%) prescriptions, respectively].

Conclusions: Most patients admitted to hospital in Timor-Leste are prescribed antimicrobials, and approximately one-third of these prescriptions are inappropriate. However, this was in the context of limited local guideline availability at the time of surveys and limited microbiological culture capacity outside of the capital, Dili. Improved microbiological guidance, iterative guideline revisions based on local antimicrobial resistance (AMR) surveillance data, and enhanced stewardship activities including further point prevalence studies, could improve antimicrobial use, optimize patient outcomes and reduce AMR in Timor-Leste.

Background: The widespread emergence of antibiotic resistance including MDR in Gram-negative bacterial pathogens poses a critical challenge to the current antimicrobial armamentarium.

Objectives: To create a novel drug-Fc conjugate (DFC) that can be delivered at sustained and prolonged levels while simultaneously activating the host immune response to combat MDR Gram-negative infections.

Methods: The Cloudbreak™ platform was used to develop DFCs consisting of a targeting moiety (TM) (a polymyxin-derived dimer) attached via a non-cleavable linker to an effector moiety (EM) (the Fc domain of human IgG1). In vitro activities of the DFCs were assessed by MIC testing. Neutropenic mouse models of thigh infection, septicaemia and pneumonia were used to evaluate in vivo efficacy. Pharmacokinetics were evaluated in mice and cynomolgus monkeys.

Results: A single prophylactic dose of our lead DFC, CTC-177, resulted in significantly decreased bacterial burdens and reduced inflammation comparable to daily treatment with colistin in septicaemia and pneumonia mouse models. Furthermore, CTC-177 prophylaxis was able to restore colistin efficacy in colistin-resistant septicaemia, reducing bacterial burdens beyond the limit of detection. Finally, CTC-177 displayed a long terminal half-life of over 24 and 65 h in mice and cynomolgus monkeys, respectively.

Conclusions: These data support the continued development of Cloudbreak™ DFCs as broad-spectrum prophylactic agents against Gram-negative infections.

Background and objectives: Antibiotic use in paediatric surgical specialties is understudied. We investigated the antibiotic prescribing practices of paediatric general and cardiovascular surgical teams in a tertiary hospital in South India.

Methods: Mixed-methods study including observations from ward rounds, semi-structured interviews, and review of antibiotic prescribing. Field notes from observations and interview transcripts were coded using NVivo and thematically analysed. Data collection and analysis were iterative and continued until thematic saturation. Quantitative data were analysed using descriptive statistics.

Results: Data included 62 h of observation, 24 interviews, one case study and 200 patient chart reviews (100/specialty). Senior surgeons make key decisions, referring to their own experience when prescribing antibiotics. Being outcome-driven, the doctors often prescribe antibiotics at the earliest indication of infection with a reluctance to de-escalate, even when an infection is not diagnosed. This practice is more acute among surgeons who consider themselves responsible for their patients' health and attribute the consistently low surgical site infection rates to this practice.In general surgery, 83.3% (80/96; 4 lost to follow-up) of patients were prescribed antibiotics for the duration of their stay with oral antibiotics prescribed at discharge. The surgeons use antibiotics prophylactically for patients who may be vulnerable to infection. The antimicrobial stewardship team was considered to have limited influence in the decision-making process.

Conclusions: Outcome-driven decision-making in surgery leads to overprescription of antibiotics and prolonged surgical prophylaxis. The rationale for suboptimal practices is complicated by the surgeons' beliefs about the contextual determinants of health in India.

Background: There are limited data describing outcomes of patients treated with ceftaroline for infections with CNS or ocular involvement.

Objectives: To describe outcomes of patients treated with ceftaroline for methicillin-resistant staphylococcal infections involving the CNS or eye.

Patients and methods: This was a retrospective review of 10 patients at an academic medical centre who received ceftaroline for CNS or ocular infections.

Results: All patients were treated with ceftaroline as part of a combination for salvage therapy. Four patients died, whereas six patients experienced clinical cure. Only one experienced microbiological recurrence.

Conclusions: These preliminary data suggest that ceftaroline may be an option for salvage therapy of severe staphylococcal infections when used in combination.

Objectives: We performed a multicentre study (2020-2022) to compare the in vitro activity of ozenoxacin and comparator agents against Staphylococcus aureus and Streptococcus pyogenes clinical isolates from skin and soft-tissue infections (SSTI).

Methods: A total of 1725 isolates (1454 S. aureus and 271 S. pyogenes) were collected in 10 centres from eight countries between January 2020 and December 2022. Antimicrobial susceptibility testing was determined (microdilution-SENSITITRE). Results were interpreted following European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 (clinical breakpoints, ECOFF) and CLSI criteria.

Results: Ozenoxacin exhibited high in vitro activity against S. aureus (MIC_50/90 = 0.002/0.12 mg/L) and S. pyogenes (MIC_50/90 = 0.015/0.03 mg/L), inhibiting 99% of the isolates at MIC ≤ 0.5 mg/L and at MIC ≤ 0.06, respectively. The most active comparators against S. aureus were retapamulin (MIC₉₀ = 0.12 mg/L), fusidic acid (MIC₉₀ = 0.25 mg/L) and mupirocin (MIC₉₀ = 0.5 mg/L); and against S. pyogenes were retapamulin (MIC₉₀ = 0.03 mg/L), clindamycin (MIC₉₀ = 0.12 mg/L) and mupirocin (MIC₉₀ = 0.25 mg/L). Ciprofloxacin and methicillin resistant rates for S. aureus were 31.3% (455/1454) and 41% (598/1454), respectively. Additionally, 62% (373/598) of the MRSA were also ciprofloxacin non-susceptible, whereas only 10% (23/271) of the MSSA were ciprofloxacin resistant. Ozenoxacin was more active against ciprofloxacin-susceptible S. aureus than against ciprofloxacin-resistant isolates, and showed a slightly higher MIC in MRSA isolates than in MSSA. However, ozenoxacin activity was comparable in both ciprofloxacin-resistant MSSA and MRSA subsets. On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant S. pyogenes isolates.

Conclusions: Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin.

Objectives: To better understand the source and potential transmission routes of antibiotic-resistant bacteria infecting injured service members in Ukraine.

Methods: Phenotypic and genomic characterizations were performed on 11 Gram-negative pathogens cultured from war wounds at an intermediate evacuation hospital in Dnipro.

Results: The analysis revealed both susceptible and extensively drug-resistant strains present in cultures, including high-risk global clones carrying carbapenemases.

Conclusions: Globally distributed carbapenemase-producing lineages are being acquired early in the medical evacuation process.