1,721,112 research outputs found
An innovative population pharmacokinetic/pharmacodynamic strategy for attaining aggressive joint PK/PD target of continuous infusion ceftazidime/avibactam against KPC- and OXA-48- producing Enterobacterales and preventing resistance development in critically ill patients
No full textObjectives Ceftazidime/avibactam is a key antibiotic for carbapenemase-producing Enterobacterales (CPE) Gram-negative infections, but current dosing may be suboptimal to grant activity. This study explores the population pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) ceftazidime/avibactam for maximizing treatment efficacy in critically ill patients.Methods A retrospective analysis of adult patients receiving CI ceftazidime/avibactam and therapeutic drug monitoring (TDM) of both compounds was performed. Population PK/PD modelling identified the most accurate method for estimating ceftazidime/avibactam clearance based on kidney function and Monte Carlo simulations investigated the relationship between various CI dosing regimens and aggressive joint PK/PD target attainment of ceftazidime/avibactam.Results The European Kidney Function Consortium (EKFC) equation best described kidney function for ceftazidime/avibactam clearance. The findings challenge the current approach of only reducing the ceftazidime/avibactam dose based on kidney function by identifying dose adjustments in patients with augmented kidney function. Our CI ceftazidime/avibactam dosing strategies, adjusted by TDM, showed promise for achieving optimal aggressive joint PK/PD targets and potentially improving clinical/microbiological outcomes against KPC- and OXA-48-producing Enterobacterales. The risk of neurotoxicity associated with these strategies appears acceptable.Conclusions This study suggests that adjusting ceftazidime/avibactam dosing regimen based solely on eCLcr might be suboptimal for critically ill patients. Higher daily doses delivered by CI and adjusted based on TDM have the potential to improve aggressive joint PK/PD target attainment and potentially clinical/microbiological outcomes. Further investigations are warranted to confirm these findings and establish optimal TDM-guided dosing strategies for ceftazidime/avibactam in clinical practice
Rectal screening of carbapenemase-producing Enterobacteriaceae: a proposed workflow
Full text linkOBJECTIVES: Active screening is a crucial element for the prevention of carbapenemase-producing Enterobacteriaceae (CPE) transmission in healthcare settings. Here, we proposed a culture-based protocol for rectal swab CPE screening that combines the detection of CPE and the identification of carbapenamase type.
METHODS: The workflow integrates an automatic digital analysis of selective chromogenic media (WASPLab, Copan), with subsequent rapid tests for the confirmation of carbapenemase production (i.e. detection of Klebsiella pneumoniae KPC-specific peak by MALDI-TOF mass spectrometry; a multiplex immunochromatographic assay identifying the five commonest carbapenemase types). To in-depth evaluate the performance of this protocol, data about 21 162 rectal swabs submitted for CPE screening at the Microbiology of S. Orsola-Malpighi Hospital in Bologna were analyzed.
RESULTS: Considering its ability to correctly segregate plates with/without Enterobacteriaceae, WASPLab Image Analysis Software showed globally a sensitivity and a specificity of 100% and 79.4%, respectively. Out of the plates with a bacterial growth (n = 901), 76.9% were found positive for CPE by MALDI-TOF (specific KPC-peak for K. pneumoniae) or by the immunochromatographic assay. Only 2.8% of KPC-positive K. pneumoniae strains were missed by the specific MALDI-TOF MS algorithm, being detected by the immunochromatographic assay. The mean turn-around-time needed from the sample arrival to the final report ranged between 18 to 24 hours, with a significant time saving compared to a manual reading.
CONCLUSIONS:This workflow proved to be fast and reliable, being particularly suitable for KPC-K. pneumoniae endemic areas and for high-throughput laboratories
Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of KPC-producing Klebsiella pneumoniae
No full textWe evaluated a real-time single-peak (11.109-Da) detection assay based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Our results demonstrated that the 11.109-Da peak was detected in 88.2% of the KPC producers. Analysis of blaKPC-producing K. pneumoniae showed that the gene encoding the 11.109-Da protein was commonly (97.8%) associated with the Tn4401a isoform
Utility of a TDM-Guided Expert Clinical Pharmacological Advice Program for Optimizing the Use of Novel Beta-Lactam/Beta-Lactamase Inhibitor Combinations and Cefiderocol in a Tertiary University Hospital: An Interim Analysis
No full textBackground: This study assessed the utility of a therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program to optimize aggressive pharmacokinetic/pharmacodynamic (PK/PD) target attainment of novel beta-lactam/beta-lactamase inhibitor (BL/BLIc) combinations and cefiderocol. Methods: All hospitalized patients who received TDM-guided ECPA with BL/BLIc (ceftazidime-avibactam, ceftolozane-tazobactam, or meropenem-vaborbactam) or cefiderocol were assessed retrospectively. Three performance indicators were identified: the average number of ECPAs delivered per month of availability of the program and the ratio between the total number of ECPAs recommending dosing adjustment and the total number of ECPAs, at the first and at subsequent TDM assessments. The relationships between aggressive PK/PD target attainment and clinical and microbiological outcomes were assessed. Results: A total of 595 ECPAs were administered to 263 patients to optimize 319 treatment courses. Novel agents were mostly used for targeted therapy (79.6%) by continuous infusion (CI; 82.8%). In the first TDM assessment, dose increases were mostly required for patients receiving intermittent/extended infusion (II/EI) (51.9% vs. 6.4%; P < 0.0001), whereas dose decreases were mostly recommended for patients receiving CI (60.3% vs. 23.1%; P < 0.001). In subsequent TDM assessments, the overall proportion of ECPAs recommending dosing adjustments decreased in both groups (57.1% and 39.3% in the II/EI and CI groups, respectively). Aggressive PK/PD target attainment was associated with the highest microbiological eradication rate for ceftazidime-avibactam (79.6% out of 86.0%; P < 0.001), and the highest clinical cure rate for ceftazidime-avibactam (64.2% out of 78.1%; P < 0.001) and cefiderocol (50.0% out of 51.5%; P = 0.006). Conclusions: A dedicated TDM-guided ECPA program may be helpful for optimizing the use of novel agents in settings with a high prevalence of multidrug-resistant pathogens
Biliary pharmacokinetic/pharmacodynamic analysis of continuous infusion meropenem/vaborbactam in a case series of orthotopic liver transplant recipients
No full textObjective: To analyse the biliary pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) meropenem-vaborbactam (MEM-VBM) in a case series of orthotopic liver transplant (OLT) recipients being treated for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) related biliary tract infections (BTIs) or as preemptive therapy of KPC-Kp rectal colonization. Methods: Critical OLT recipients receiving CI MEM-VBM (2 g/2 g q8h over 8 h) because of KPC-Kp related BTIs or as preemptive therapy of KPC-Kp rectal colonization, having Kehr's tube positioned and undergoing simultaneous therapeutic drug monitoring of MEM and VBM in plasma and bile were retrospectively assessed. Bile-to-plasma ratio of free steady-state concentrations (fCss) of MEM and VBM was used for assessing biliary penetration. Optimal joint MEM-VBM PK/PD target attainment was defined as MEM fCss/MIC ratio >4 coupled with VBM free area under time-concentration curve (fAUC)/threshold concentration (CT) ratio >24. Results: Overall, four critical OLT recipients were included. Median bile-to-plasma ratio was 0.32 for MEM (range 0.21-0.79) and 0.40 for VBM (range 0.20-0.77). Biliary MEM-VBM joint PK/PD target attainment was optimal in 3/4 OLT recipients and quasi-optimal in the other one. Conclusions: The 1:1 proportion between MEM and VBM concentrations was maintained unchanged in the bile, allowing us to assume that the efficacy of MEM-VBM may be appropriate even in the treatment of BTIs. CI administration was an effective strategy for attaining aggressive biliary joint PK/PD targets against pathogens with an MIC up to 2 mg/L
Evaluation of an automated rapid phenotypic antimicrobial susceptibility testing (ASTar, Q-linea AB) applied directly on blood cultures bottles positive for Gram-negative pathogens
No full textWe evaluated the performance of a new rapid phenotypic antimicrobial susceptibility test (ASTar; Q-linea AB) on Gram-negative bacilli, directly from positive blood cultures bottles. MIC values obtained by the routine reference method (Microscan, Beckman Coulter) were compared to the ones provided by the tested method (ASTar). ASTar demonstrated an overall essential agreement of 98% and a category agreement of 96.1%. The overall rate of major errors and very major errors was 2.5% and 3.3%, respectively. ASTar can represent a rapid, simple, and reliable method to speed up information about antimicrobial susceptibility of Gram-negative pathogens from positive blood culture bottles
Antifungal susceptibility of a collection of Aspergillus fumigatus strains isolated from patients with invasive pulmonary aspergillosis and COVID-19 associated aspergillosis
Full text linkWe assessed the antifungal susceptibility of 86 Aspergillus fumigatus strains by a phenotypic test. Azole sensitivity was compared to a molecular test detecting cyp51A mutations. Azole resistance was quite limited, whereas strains from COVID-19 patients showed higher amphotericin B MICs. The molecular test showed a 100 %-agreement with the phenotypic assay
Evaluation of synergistic activity of fosfomycin in combination with novel ß-lactams/ß-lactamase inhibitor combinations (βL-βLICs) against KPC-producing Klebsiella pneumoniae clinical isolates
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Rapid increase of carbapenemase-producing Klebsiella pneumoniae strains in a large Italian hospital: surveillance period 1 March - 30 September 2010
No full textThe first case of carbapenemase-producing Enterobacteriaceae in Italy was reported in 2009. We performed a study over a period of seven months in 2010 to survey the circulation of Klebsiella pneumoniae carbapenemases (KPC) in a 1,500-bed university hospital in northern Italy and report the presence and rapid increase of these multidrug-resistant bacteria. The results raise a major concern about these pathogens and demonstrate the urgent need for infection control and antibiotic stewardship programmes
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