β-lactam antibiotic concentrations during continuous renal replacement therapy

Introduction

The use of standard doses of β-lactam antibiotics during continuous renal replacement therapy (CRRT) may result in inadequate serum concentrations. The aim of this study was to evaluate the adequacy of unadjusted drug regimens (i.e., similar to those used in patients with normal renal function) in patients treated with CRRT and the influence of CRRT intensity on drug clearance.

Methods

We reviewed data from 50 consecutive adult patients admitted to our Department of Intensive Care in whom routine therapeutic drug monitoring (TDM) of broad-spectrum β-lactam antibiotics (ceftazidime or cefepime, CEF; piperacillin/tazobactam; TZP; meropenem, MEM) was performed using unadjusted β-lactam antibiotics regimens (CEF = 2 g q8h; TZP = 4 g q6h; MEM = 1 g q8h). Serum drug concentrations were measured twice during the elimination phase by high-performance liquid chromatography (HPLC-UV). We considered therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration (MIC) of Pseudomonas aeruginosa during optimal periods of time for each drug (≥70% for CEF; ≥ 50% for TZP; ≥ 40% for MEM). Therapy was considered as early (ET) or late (LT) phase if TDM was performed within 48 hours of antibiotic initiation or later on, respectively.

Results

We collected 73 serum samples from 50 patients (age 58 ± 13 years; Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission 21 (17–25)), 35 during ET and 38 during LT. Drug concentrations were above 4 times the MIC in 63 (90%), but above 8 times the MIC in 39 (53%) samples. The proportions of patients with adequate drug concentrations during ET and LT were quite similar. We found a weak but significant correlation between β-lactam antibiotics clearance and CRRT intensity.

Conclusions

In septic patients undergoing CRRT, doses of β-lactam antibiotics similar to those given to patients with normal renal function achieved drug levels above the target threshold in 90% of samples. Nevertheless, 53% of samples were associated with very high drug levels and daily drug regimens may need to be adapted accordingly.     

Investigation of β-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR)

We could not detect hetero-vancomycin-intermediate resistant Staphylococcus aureus (hetero-VISA), according to the definition of hetero-VISA, from the clinical isolates of 140 methicillin-resistant S. aureus (MRSA) strains. However, 15 -lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) strains were detected from the same strains. We screened 1882 MRSA clinical isolates obtained in 2002 from 21 institutes throughout Japan. The detection rate of blood-isolated BIVR was 12.6% (19/151), and that of nonblood-isolated BIVR was 4.9% (85/1731; P < 0.001; 2 test). Uridine-diphosphate-N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-lysine, used as the peptidoglycan material of S. aureus, showed the same results as -lactam antibiotics in BIVR.     

Which regimen is better for stem cell mobilization of lymphoma patients?

Although chemotherapy combined with G-CSF is an effective method for hematopoietic stem cell mobilization, standard chemotherapy protocol leading to best stem cell yield is not defined. In our study, we aimed to assess the impact of chemotherapy choice on mobilization outcome in lymphoma patients. Patients were mobilized with cyclophosphamide (n:15), ASHAP (n:11) or VGEPP (n:12) protocols. Groups were similar according to collected CD34+ cell count, total nucleated cell count and median apheresis days. Five out of fifteen (33%) patients could not be mobilized in Cy group but there was only one failed mobilization attempt in both salvage groups (9% with ASHAP vs 8% with VGEPP). In conclusion, we showed that VGEPP and ASHAP are safe protocols in terms of stem cell mobilization and have similar mobilization capacity as cyclophosphamide alone.     

Who supports elderly African Americans in adhering to their healthcare regimen?

Knowing who supports elderly African Americans in adhering to their healthcare regimen is vital information. This study found that the majority of elderly individuals discussed their chronic illnesses and problems related to managing their illnesses with family members rather than with formal providers. Additionally, family members were also significant in coordinating transportation; assisting with managing medications, diet, and exercise regimens; and monitoring symptoms of chronic illnesses. These findings provide direction on how to develop effective care plans and affect positive outcomes for elderly African American clients.     

Pharmacokinetic–pharmacodynamic modeling to support doripenem dose regimen optimization for critically ill patients

Dose regimen selection in late-phase clinical trials is critical for successful drug development, the well-being of individual patients, and given the ongoing emergence of antimicrobial resistance, society as a whole. Herein we describe some of the animal pharmacokinetics-pharmacodynamics, human pharmacokinetic, and in silico modeling work that was conducted in an effort to maximize the probability of a positive clinical response to therapy and minimize the likelihood for exposure-related toxicity for doripenem in phase 3 clinical studies. Some of the dosing regimens identified have been validated as effective in phase 3 clinical studies (500 mg infused over 1 h every 8 h for complicated intra-abdominal infections), whereas others (1000 mg infused over 4 h every 8 h for hospital-acquired pneumonia) are undergoing clinical evaluation.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock

Introduction

Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum β-lactam concentrations when standard dosages are administered. Previous studies on β-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock.

Methods

Open, prospective, multicenter study in four Belgian intensive care units. All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom treatment with the study drugs was indicated, were included. Serum concentrations of the antibiotics were determined by high-pressure liquid chromatography (HPLC) before and 1, 1.5, 4.5 and 6 or 8 hours after administration.

Results

80 patients were treated with piperacillin-tazobactam (n = 27), ceftazidime (n = 18), cefepime (n = 19) or meropenem (n = 16). Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 × MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 μg/mL), 45% for ceftazidime (MIC = 32 μg/mL), 34% for cefepime (MIC = 32 μg/mL), and 33% for piperacillin-tazobactam (MIC = 64 μg/mL). The number of patients who attained the target PK profile was 12/16 for meropenem (75%), 5/18 for ceftazidime (28%), 3/19 (16%) for cefepime, and 12/27 (44%) for piperacillin-tazobactam.

Conclusions

Serum concentrations of the antibiotic after the first dose were acceptable only for meropenem. Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

The nervous system adverse effect induced by β-lactam antibiotics in patients on hemodialysis

Objective To discuss the reasonable utilization of β-lactam antibiotics in patients with renal failure on hemedialysis. Methods The clinical characteristics of patients with renal failure on hemodylysis,who de-veloped the adverse effect of nervous system and psychiatric symptom while being treated with β-lactam antibiotics,were retrospectively analyzed. Results The adverse effect of nervous system and psychiatric symptom showed dur-ing and after hemodialysis,including: mental confusion,hyperexcitabiliy,incoherent speech,lethargy and amyestasia in two cases. Physical examination did not show signs of cerebral focal injury in all cases. Computed tomography of brain in 7 patients did not show acute lesions. The symptoms completely disappeared after withdrawal of β-lactam antibiotics but bemodialysis or hemodiafiltration continued. Conclusion β-lactam antibiotics used in conventional dose could cause temporary adverse effect of nervous system in patients with renal failure on bemodialysis,which is related to prolongation of drug half life.     

Locally advanced non-small cell lung cancer: what is the optimal concurrent chemoradiation regimen?

The optimal chemoradiation regimen for patients with locally advanced non-small cell lung cancer (NSCLC) has yet to be defined. Disease and patient heterogeneity prevent a "one size fits all" approach to treatment. Concurrent chemoradiation up front is the definitive strategy for patients with unresectable stage III NSCLC; the addition of consolidation chemotherapy following definitive treatment has produced conflicting results with respect to overall survival. Biologic therapies have yet to show value as add-on treatment to chemoradiation.