Numerous observational studies and meta-analyses have suggested that combination therapy consisting of piperacillin–tazobactam (TZP) and vancomycin (VAN) augments acute kidney injury (AKI) risk when ...compared to viable alternatives, such as cefepime–vancomycin (FEP–VAN) and meropenem–VAN. However, the exact pathophysiological mechanisms of this phenomenon are still unclear. One major limitation of the existing studies is the utilization of serum creatinine to quantify AKI since serum creatinine is not a sufficiently sensitive and specific biomarker to truly define the causal relationship between TZP–VAN exposure and nephrotoxicity. Even so, some preventive measures can be taken to reduce the risk of AKI when TZP–VAN is preferred. These measures include limiting the administration of TZP–VAN to 72 h, choosing FEP–VAN in place of TZP–VAN in appropriate cases, monitoring the VAN area under the curve level rather than the VAN trough level, avoiding exposure to other nephrotoxic agents, and minimizing the prescription of TZP–VAN for patients with a high risk of AKI. More data are needed to comment on the beneficial impact of the extended-infusion regimen of TZP on nephrotoxicity. Additionally, TZP and teicoplanin can be reasonable alternatives to TZP–VAN for the purpose of lowering AKI risk. However, the data are scarce to advocate this practice convincingly.
Recipients of hematopoietic stem cell transplantation (HSCT) are at substantial risk of bacterial, fungal, viral, and parasitic infections depending on the time elapsed since transplantation, ...presence of graft-versus-host disease (GVHD), and the degree of immunosuppression. Infectious complications in HSCT recipients are associated with high morbidity and mortality. Bacterial infections constitute the major cause of infectious complications, especially in the early post-transplant period. The emergence of antibacterial resistance complicates the management of bacterial infections in this patient group. Multidrug-resistant bacterial infections in this group of patients have attracted considerable interest and may lead to significant morbidity and mortality. Empirical antibacterial therapy in patients with HSCT and febrile neutropenia has a critical role for survival and should be based on local epidemiology. This review attempts to provide an overview of risk factors and epidemiology of emerging resistant bacterial infections and their management in HSCT recipients.
This study evaluates the functional capacity of CD4
and CD8
terminally-differentiated effector (T
), central memory (T
), and effector memory (T
) cells obtained from the volunteers vaccinated with ...an aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac). The volunteers were followed for T cell immune responses following the termination of a randomized phase III clinical trial. Seven days and four months after the second dose of the vaccine, the memory T cell subsets were collected and stimulated by autologous monocyte-derived dendritic cells (mDCs) loaded with SARS-CoV-2 spike glycoprotein S1. Compared to the placebo group, memory T cells from the vaccinated individuals significantly proliferated in response to S1-loaded mDCs. CD4
and CD8
memory T cell proliferation was detected in 86% and 78% of the vaccinated individuals, respectively. More than 73% (after a short-term) and 62% (after an intermediate-term) of the vaccinated individuals harbored T
and/or T
cells that responded to S1-loaded mDCs by secreting IFN-γ. The expression of CD25, CD38, 4-1BB, PD-1, and CD107a indicated a modulation in the memory T cell subsets. Especially on day 120, PD-1 was upregulated on CD4
T
and T
, and on CD8
T
and T
cells; accordingly, proliferation and IFN-γ secretion capacities tended to decline after 4 months. In conclusion, the combination of inactivated whole-virion particles with aluminum adjuvants possesses capacities to induce functional T cell responses.
Although new-generation antimicrobials, in particular β-lactam/β-lactamase inhibitors, have largely replaced polymyxins in carbapenem-resistant Gram-negative bacterial infections, polymyxins are ...still needed for carbapanem-resistant
infections and in settings where novel agents are not readily available. Despite their potent in vitro activity, the clinical utility of polymyxins is significantly limited by their pharmacokinetic properties and nephrotoxicity risk. There is significant interest, therefore, in developing next-generation polymyxins with activity against colistin-resistant strains and lower toxicity than existing polymyxins. In this review, we aim to present the antibacterial activity mechanisms, in vitro and in vivo efficacy data, and toxicity profiles of new-generation polymyxins, including SPR206, MRX-8, and QPX9003, as well as the general characteristics of old polymyxins. Considering the emergence of colistin-resistant strains particularly in endemic regions, the restoration of the antimicrobial activity of polymyxins via PBT2 is also described in this review.
Background: In May 2022, the monkeypox virus outbreak in multiple countries on various continents marked a potential resurgence of the disease as a global health issue. Considering the crucial role ...of physicians in mitigating the monkeypox outbreak, we sought to evaluate physicians’ knowledge, attitude, concerns, and vaccine acceptance for monkeypox, in the shadow of the COVID-19 pandemic. Methods: A large-scale, cross-sectional survey was conducted among 283 physicians between 20 August−2 September 2022, in Turkey. The participants’ sociodemographic characteristics, knowledge, attitudes, concerns, and vaccine acceptance toward monkeypox infection were collected via a questionnaire. Results: Our study revealed that 32.5% of physicians achieved a good level of knowledge; similarly, 31.4% of the physicians planned to have the monkeypox vaccine. Multivariate binary logistic regression analysis showed that female physicians (p = 0.031) and older people (≥30 vs. <30) were more likely to be knowledgeable about monkeypox (p = 0.007). We found that participants from divisions of internal medicine (p = 0.033) who knew about the monkeypox disease during medical school or residency (p = 0.005) and were previously exposed to COVID-19 disease (p = 0.005) were more likely to have a good knowledge score of monkeypox. We also found that physicians with a good knowledge score were more worried about monkeypox compared to COVID-19 (AOR: 2.22; 95% CI:1.13−4.33; p = 0.019). Additionally, those who had information on monkeypox during medical education (AOR = 2.16, 95% CI = 1.10−4.21; p = 0.024) were more likely to receive the smallpox vaccine to prevent monkeypox viral infection when available. Conclusions: The present study pointed out that physicians in Turkey have unsatisfactory levels of knowledge about the emerging monkeypox. This study results can impede attempts to detect and manage cases of monkeypox and should be addressed through appropriate and timely awareness and educational programs, alerts, and seminars. These might serve as the basis for policymakers’ decisions about promoting national monkeypox vaccination strategies and addressing potential vaccine hesitancy and misinformation when needed.
The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only ...remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram-positive agents. Data on the use of these agents in leukemic patients are scanty, with only linezolid subjected to formal trials. The Expert Group of the 4(th) European Conference on Infections in Leukemia has developed guidelines for their use in these patient populations. Targeted therapy should be based on (i) in vitro susceptibility data, (ii) knowledge of the best treatment option against the particular species or phenotype of bacteria, (iii) pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk-benefit balance. For infections due to resistant Gram-negative bacteria, these agents should be preferably used in combination with other agents that remain active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs in the near future should lead us to limit the use of these drugs to situations where no alternative exists.
Fungemia caused by uncommon
Candida
species (UCS) (other than
C.albicans
,
C.glabrata
,
C.parapsilosis
,
C.tropicalis
,
C.krusei
) is a rare but emerging threat with their potential to exhibit ...reduced susceptibility or resistance to antifungal agents. We identified 25 patients with UCS fungemia (9
C.kefyr
, 8
C.lusitaniae
, 4
C.dubliniensis
, 2
C.guilliermondii
, 1
C.pelliculosa
, 1
C.rugosa
) through January 2011 and August 2018. Echinocandins were the most common administered agents, followed by fluconazole. Overall mortality was 44%. Echinocandins and voriconazole showed sufficient activity against all tested isolates. High fluconazole MICs among
C.guilliermondii
,
C.pelliculosa
, and
C.rugosa
were determined. MIC value of
C.pelliculosa
was above the epidemiological cut-off proposed for fluconazole.
A prospective, multicentre observational cohort study of carbapenem-resistant
Klebsiella
spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred ...eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.
The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been ...associated with favourable response.
The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0-24/MIC ratio) >400 (assuming MIC ≤1 mg/L).
Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0-24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0-24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5).
This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in critically ill patients is needed to more rapidly and consistently achieve sufficient vancomycin exposure.
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