International Journal of Antimicrobial Agents最新文献

Background: Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear.

Objectives: To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam.

Methods: This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed.

Results: A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013-1.093), presence in the ICU (aOR 2.704, 95% CI 1.071-6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797-11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n=77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089-1.155).

Conclusions: In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.

Antibiotic resistance is one of the most important concerns in global health today. Thus, a growing number of different infections are becoming harder to treat with conventional drugs and this is aggravated by the fact that fewer new antibiotics are being developed. In this context, strategies based on blocking or attenuating virulence pathways could position as very interesting therapeutic approaches since they do not focus on bacteria eradication, which should reduce the selective pressure exerted on the pathogen. This virulence depletion can be achieved by inhibiting the conserved quorum sensing (QS) system, a mechanism that enables bacteria to communicate one another in a density dependent manner. QS regulates gene expression leading to the activation of some important processes such as virulence and biofilm formation among others. Therefore, this review points out the approaches reported so far for disrupting different steps of the QS system of the multiresistant pathogen Pseudomonas aeruginosa. With this aim, the authors describe different types of molecules (enzymes, natural and synthetic small molecules, antibodies…) already identified as P. aeruginosa quorum quenchers (QQs) or QS inhibitors (QSIs) grouped according to the QS circuit that they block (Las, Rhl, Pqs and some examples from the controversial pathway Iqs). The importance of the discovery of new QSIs and QQs is expected to help on reducing antibiotic doses or at least to act as adjuvants to increase antibiotic treatment effect. Moreover, this article also highlights the advantages and possible drawbacks of each strategy and it also summarizes future perspectives in the field.

Nontypeable Haemophilus influenzae (NTHi), once considered a harmless commensal, has emerged as a significant concern due to the increased prevalence of multidrug-resistant (MDR) strains and their association with invasive infections. This study aimed to explore the epidemiology and molecular resistance mechanisms of 51 NTHi isolates collected from patients with invasive infections in northern Taiwan between 2011 and 2020. This investigation revealed substantial genetic diversity, encompassing 29 distinct sequence types and 18 clonal complexes. Notably, 68.6% of the isolates exhibited ampicillin resistance, with 28 categorized as MDR and four isolates were even resistant to up to six antibiotic classes. Among the MDR isolates, 18 pulsotypes were identified, indicating diverse genetic lineages. Elucidation of their resistance mechanisms revealed 18 β-lactamase-producing amoxicillin-clavulanate-resistant (BLPACR) isolates, 12 β-lactamase-producing ampicillin-resistant (BLPAR) isolates, and 5 β-lactamase-nonproducing ampicillin-resistant (BLNAR) isolates. PBP3 analysis revealed 22 unique substitutions in BLPACR and BLNAR, potentially contributing to cephem resistance. Notably, novel transposons, Tn7736-Tn7739, which contain critical resistance genes, were discovered. Three strains harboured Tn7739, containing seven resistance genes [aph(3')-Ia, bla_TEM-1, catA, sul2, strA, strB, and tet(B)], while four other strains carried Tn7736, Tn7737, and Tn7738, each containing three resistance genes [bla_TEM-1, catA, and tet(B)]. The emergence of these novel transposons underscores the alarming threat posed by highly resistant NTHi strains. Our findings indicated that robust surveillance and comprehensive genomic studies are needed to address this growing public health challenge.

Objective: We analyze the effectiveness of short courses of adequate treatment in patients with episodes of carbapenemase-producing Enterobacterales bloodstream-infections (CPE-BSI).

Methods: Patients with first monomicrobial CPE-BSI episodes who received ≥72h of appropriate treatment from 2014-2022 were selected. Detection of CPE was established on the basis of phenotypic antibiogram and confirmation by PCR and/or immunochromatographic methods. Patients were classified in short treatment group (STG) those who received 3-10 days of appropriate treatment, and long treatment (LTG) those receiving >10 days. Unfavorable outcome consisted in a composite of global 30-day mortality and/or persistent bacteremia and/or recurrent bacteremia. Inverse probability of treatment weighting (IPTW) analysis was performed to compare the outcome between the two study groups.

Results: We included 105 CPE-BSI episodes: 99 were caused by OXA-48-like, 4 VIM and 2 KPC carbapenemases. Thirty-nine patients (37.1%) were included in the STG and 66 (62.9%) in LTG. The STG group presented frequent treatment with ceftazidime-avibactam (43.6% vs. 24.2%, p=0.03) and lower in-hospital stay (21 days vs. 32 days, p=0.02). Overall, 28 patients (26.7%) presented unfavorable outcome: IPTW analysis showed no differences in the outcome between STG to LTG groups (24.2% vs. 30.8%, weighted-risk difference 6.6%, p=0.44). Patients with unfavorable outcome presented more frequently source other than urinary-biliary (46.4% vs. 23.4%, p=0.02), received less frequently ceftazidime-avibactam (14.3% vs. 37.7%, p=0.02) and presented frequently with absence of source control when indicated (28.6% vs. 13.0%, p=0.06).

Conclusions: Short treatment durations for CPE-BSI episodes may be effective, as long as they are appropriate and source control is performed.

Background: Data about de-escalation in sepsis associated to bloodstream caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated to early de-escalation and to analyse the impact of de-escalation in mortality of patients with Enterobacterales BSI with a SOFA score ≥ 2.

Material and methods: A prospective, multicenter cohort study including episodes of BSI due to Enterobacterales and SOFA score ≥2 receiving an active antipseudomonal beta-lactam was performed; the isolate should be susceptible to at least one narrower-spectrum antibiotic. Variables associated to de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated; confounding was controlled by calculating a propensity score used as covariate, as matching variable and for inverse probability treatment weighting (IPTW).

Results: Of 582 cases included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted OR: 0.37; 95%CI 0.18-0.75), central venous catheter (aOR: 0.52; 95%CI 0.32-0.83) and ESBL-producing isolate (aOR: 0.28; 95%CI 0.17-0.48) were negatively associated to de-escalation, and urinary tract source was positively associated (aOR: 2.27; 95%CI 1.56-3.33). Thirty-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated (relative risk, 0.63; 95%CI 0.44-0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (aOR: 0.98; 95% CI 0.39-2.47) and was protective in urinary or biliary tract source (aOR: 0.31 95%CI: 0.09-1.06). Matched and IPWT analysis showed similar results.

Conclusions: These results suggest that early de-escalation from antipseudomonal beta-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥2.