Journal of Antimicrobial Chemotherapy最新文献

Objectives: Cefiderocol is a new siderophore cephalosporin for treating severe bacterial infections by Gram-negative pathogens in adults. Significant elimination of the drug will probably occur as a result of kidney replacement therapy, but there are currently insufficient pharmacokinetic data to guide dosing during prolonged intermittent kidney replacement therapy (PIKRT) or the use of the pathogen adsorber Seraph 100.

Materials and methods/case reports: Pharmacokinetic data were obtained from two critically ill patients undergoing PIKRT and hemoperfusion with the pathogen adsorber Seraph 100. Cefiderocol levels in plasma and dialysate samples were quantified using liquid chromatography with tandem mass spectrometry to evaluate the impact of extracorporeal therapy modalities on cefiderocol pharmacokinetics.

Results: The median cefiderocol dialyser clearance was 80.94 (38.7-87) mL/min, while the Seraph 100 showed no significant clearance [-1.8 (-7.9 to 3.6) mL/min]. The cefiderocol concentration in the total spent dialysate suggests a total elimination of 1350 and 400 mg of cefiderocol, or 68% and 40% of the administered dose.

Conclusion: Cefiderocol is substantially eliminated by PIKRT, but not during hemoperfusion with the Seraph 100. Consequently, dosage adjustments may be necessary depending on the intensity of the PIKRT procedure. Doses used for patients with normal renal function may be required to prevent underdosing during intensive PIKRT.

Despite a decrease in disease severity since the emergence of the severe acute respiratory syndrome coronavirus 2 Omicron variant, coronavirus disease-2019 (COVID-19) continues to pose a significant threat to patients with haematological malignancies (HM). Although repeated booster vaccinations enhance protection against severe illnesses in immunocompromised individuals, they remain at heightened risk of adverse outcomes. This underscores the crucial need for effective pharmacologic strategies to prevent and treat infection. This review examines current strategies for preventing severe COVID-19 in patients with HM, focusing on pre-exposure prophylaxis and early treatment of COVID-19. New monoclonal antibodies have been developed, offering effective pre-exposure prophylaxis. Antiviral agents and monoclonal antibodies demonstrated efficacy in limiting severe COVID-19 outcomes in patients with HM, though some patients, particularly the elderly, remain at risk of critical illness and death. Prolonged infection over months is also common, particularly in patients with lymphoid malignancies. Sustained viral shedding and ongoing mutation may be associated with chronic symptoms and is the likely source of several novel variants of concern that prolonged the pandemic. While HM subtype and advanced age are risk factors for severe or persistent COVID-19, there are no accurate tools for predicting individual risk. Given this uncertainty, prompt medical consultation, timely prescription of antiviral agents, and close monitoring are essential to minimize the risk of adverse outcomes in this vulnerable population.

Background: Although self-administered outpatient parenteral antimicrobial therapy (S-OPAT) has several advantages over nurse-administered therapy, it remains underused. A comprehensive understanding of the determinants of S-OPAT-the factors that hinder or promote its use-is essential to improve the quality of care and increase uptake.

Objective: This systematic review aimed to identify and synthesize determinants influencing the entire S-OPAT patient care pathway, from the offer of S-OPAT to its acceptance, training and performance, considering the perspectives of healthcare professionals, patients and their caregivers.

Methods: We systematically searched PubMed, Embase, PsycINFO and CINAHL for original articles published between January 2000 and July 2024 on determinants influencing decision-making and experiences regarding S-OPAT and other self-administered intravenous therapies. Determinants were thematically analysed to construct overarching themes. This review was registered in PROSPERO (CRD42022311294).

Results: In 23 studies reporting behavioural determinants (11 on S-OPAT), a total of 238 determinants were identified to influence the offer, acceptance, training and performance of self-administration. A limited number of studies explored determinants influencing the offer of S-OPAT and the caregiver's perspective. The overarching themes included stakeholders' cognitions or affect, collaboration and communication, context, resources and skills and capabilities, which influenced all steps in the patient care pathway. Many determinants were identified regarding cognitions or affect and collaboration and communication, stressing the importance of considering stakeholders' opinions on self-administration and improving transmural collaboration.

Conclusions: This review revealed key behavioural determinants shaping the success of S-OPAT. Targeting these factors can overcome implementation barriers and improve access, caregiver engagement and quality of care.

Objective: Omadacycline, a novel aminomethylcycline antibiotic for community-acquired bacterial infections, lacks comprehensive real-world safety data. We evaluated its adverse drug reactions (ADRs) using the FDA Adverse Event Reporting System (FAERS).

Methods: A comprehensive analysis of post-marketing ADR reports submitted to FAERS between the first quarter of 2020 and the fourth quarter of 2024 was conducted. Disproportionality signals were assessed via four methods: reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker.

Results and conclusion: Among 4541 omadacycline-related reports, 577 distinct ADRs were identified. The most frequently reported ADRs were nausea (221 cases, 14.1%), vomiting (129), diarrhoea (93), dyspnoea (56) and rash (52). The strongest safety signals (ROR) included tooth discolouration (ROR = 184.33, 95% CI = 96.79-351.06), tongue discolouration (159.88, 101.76-251.25) and Mycobacterium avium complex infection (73.30, 40.15-133.78). Hepatic events (e.g. elevated transaminases) and mortality (49 cases) also demonstrated significant signals. Omadacycline is associated with gastrointestinal disturbances, dental discolouration and respiratory complications. Vigilance for hepatic injury and mortality is warranted, especially in elderly comorbid patients. Ongoing pharmacovigilance integrating real-world evidence is essential.

Objectives: Antimicrobial-resistant Neisseria gonorrhoeae is a serious threat to global health. Current N. gonorrhoeae antimicrobial susceptibility testing (AST) is laborious and time consuming (≥2 days) leading to overprescription of last-resort, broad-spectrum antibiotics. In this proof-of-principle study, we developed a fast (<8 h) phenotypic, impedance-based AST for N. gonorrhoeae against frontline and experimental antibiotics.

Methods: WHO N. gonorrhoeae reference strains F, K, O, V, X and Y were exposed to EUCAST susceptibility breakpoint concentrations of ceftriaxone, ciprofloxacin and azithromycin for up to 5 h and to doubling dilutions of antibiotics for 4 h. The % cell count of antibiotic exposed compared with unexposed control samples, as measured by an impedance-based Fast Antimicrobial Susceptibility Test (iFAST®), was used to differentiate between susceptible and non-susceptible strains. Responses to novel antimicrobial compounds, including zoliflodacin and gepotidacin, were also measured by iFAST® and compared with published MICs.

Results: The protocol reported susceptibility profiles concordant with published data for all strain-drug combinations after 4 h of exposure. Dose-response curves generated using iFAST® for most strain-drug combinations were in essential agreement with published Etest MIC values. Novel compounds assessed using iFAST® showed higher antimicrobial activity than ciprofloxacin in the high-level resistant strain WHO X.

Conclusions: iFAST® AST results were concordant with the current clinical standards and measured in under 8 h. This method is therefore promising for the development of a rapid and accurate phenotypic N. gonorrhoeae antimicrobial susceptibility test.

Objectives: This study aimed to gain a better understanding of the role of insertional mutations in the integrase (IN)-coding sequence of 13 HIV-1-infected people.

Results: Here, we present the first documentation of amino acid insertion in the IN-coding sequence of HIV-1-infected people at positions 168, 253, 255 and 260. The consequences of these mutations in terms of viral replication and resistance to INSTIs were analysed using virological and biochemical assays and 3D modelling. Analysis of viral genomes by quantitative PCR demonstrated that insertional mutations reduce reverse transcription efficiency and had different impacts on viral integration. Taken together, we showed that mutants were delayed in their replication. Virological assays using two potent strand-transfer inhibitors (INSTIs), raltegravir and dolutegravir, demonstrated that no resistance to INSTIs was observed.

Conclusions: Our study has revealed that the mutations observed in people living with HIV-1 do not confer resistance to anti-integrase compounds but are detrimental to viral replication.

Background: Ceftazidime/avibactam (CZA) is recognized as an efficacious treatment modality against multidrug-resistant Pseudomonas aeruginosa. Nevertheless, it encounters the challenge of escalating antimicrobial resistance. Employing combination regimens involving ceftazidime/avibactam may confer advantages.

Methods: Checkerboard titration, time-kill assays, and an in vitro pharmacodynamic model were employed to investigate the effectiveness of ceftazidime/avibactam alone and in combination in vitro. Additionally, an intraperitoneal infection mouse model was established to assess the efficacy of combination therapy in vivo.

Results: In the in vitro pharmacodynamic model, administration of ceftazidime/avibactam plus polymyxin B resulted in a significant reduction in colony-forming units of all four strains, whereas ceftazidime/avibactam plus aztreonam only reduced the colonies of three strains. Significant or trending declines in mortality and tissue colony counts of infected mice were observed in groups treated with ceftazidime/avibactam plus polymyxin B. Conversely, ceftazidime/avibactam combined with aztreonam only reduced mortality and tissue colonies in MBL-positive P.aeruginosa-infected mice.

Conclusion: Combining ceftazidime/avibactam with polymyxin B might represent a potentially effective option against MDR-P.aeruginosa. Although the synergistic effect in vitro might not be readily apparent due to the potent bactericidal effect of aztreonam alone, the combination of ceftazidime/avibactam and aztreonam demonstrated promising synergistic effects on MBL-positive P.aeruginosa strains in vivo.