ABSTRACT: Meropenem is a broad-spectrum antibacterial that is usually used in the treatment of serious lower respiratory tract infections (LRTIs). However, there is a lack of published studies exploring the correlation between the population pharmacokinetics of meropenem, the clinical pharmacodynamics of the drug and the response to the drug in Chinese patients with LRTIs, especially in the elderly.
The aim of this study was to develop a pharmacokinetic model of meropenem using patient data and use this to explore the clinical pharmacodynamics of meropenem in the treatment of LRTIs in elderly Chinese patients.
We measured serum meropenem concentrations in patients who had received meropenem 0.5 or 1.0 g infused over 0.5 hours every 8 or 12 hours, respectively. The pharmacokinetic analysis of meropenem was performed using nonlinear mixed-effects modelling (NONMEM®) software. The minimum inhibitory concentration (MIC) of meropenem against Gram-negative bacilli was tested by the E-test method. The pharmacodynamic parameters of percentage of time above MIC (%T>MIC), the ratio of the drug area under the serum concentration-time curve to MIC (AUC/MIC), the ratio of the maximum serum concentration of the drug to MIC (Cmax/MIC) and the ratio of the minimum serum concentration of the drug to MIC (Cmin/MIC) were analysed for their association with clinical and bacteriological outcomes.
A total of 284 serum meropenem concentration measurements were obtained from 75 patients (aged 63-95 years). A two-compartment model fitted the concentration data best. The covariates creatinine clearance (CLCR) and Acute Physiology and Chronic Health Evaluation (APACHE) II score had the most significant effects on meropenem pharmacokinetics. Forty-five patients were enrolled in the pharmacodynamic study, including 25 clinical responders and 21 patients with bacteriological eradication. All of the 45 patients had Gram-negative bacilli isolated from tracheal aspirate or sputum. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values for the 25 clinical responders were significantly higher than those for the nonresponders (all p<0.05). However, logistic regression analysis showed that only %T>MIC independently influenced clinical outcome (p=0.001, odds ratio [OR]=1.065). The cut-off value for predicting clinical success using %T>MIC was 76%; the sensitivity and specificity of %T>MIC for predicting a successful response were 84% and 85%, respectively. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values, and the serum level of albumin, for the 21 patients with bacteriological eradication were significantly higher than those for patients with bacteriological treatment failure (all p<0.05). Logistic regression analysis showed that %T>MIC (p=0.008, OR=1.047) and serum level of albumin (p=0.033, OR=1.434) independently influenced bacteriological eradication.
To our knowledge, this is the first study to investigate the population pharmacokinetics and clinical pharmacodynamics of meropenem in elderly Chinese. CLCR and APACHE II score have significant influences on meropenem pharmacokinetics. In LRTI patients, the cut-off value of 76% for %T>MIC can be applied to optimize their meropenem dose regimen to achieve clinical success.
Drugs & Aging 11/2011; 28(11):903-12. · 2.67 Impact Factor
ABSTRACT: To assess the genetic relationship of clinical isolates of carbapenem-resistant A. baumannii(resistant to both imipenem and meropenem) from January 2007 to March 2008 in Peking University Third Hospital for measures to decrease the isolates; to investigate the characteristics of patients with carbapenem-resistant A.baumannii colonization or infection and to evaluate antibiotic treatment for health care-associated infections caused by carbapenem-resistant A.baumannii.
The medical records of patients with carbapenem-resistant A. baumannii colonization or infection were reviewed. Antibiotic susceptibilities of the isolates were determined by the standardized disk-diffusion method and the clonal relationship of the isolates was analyzed by pulsed-field gel electrophoresis.
A total of 49 carbapenem-resistant A. baumannii strains were isolated from the 49 patients hospitalized during the study period and pulsed-field gel electrophoresis typing yielded 7 different patterns. A total of 45 (91.8%) genotyped strains showed clonal relationship. The most frequently identified predisposing factors were intensive care unit stay, invasive procedures, and hypoalbuminemia. Chronic obstructive pulmonary disease (12 cases) and cerebrovascular disease (10 cases) were the most common comorbid conditions. The mortality of patients with carbapenem-resistant A. baumannii infection was 38.1% (8 of 21 patients), and the acute physiology and chronic health evaluation II score, initial antibiotic therapy failure rate and the presence of hypoalbuminemia were significantly increased in the death group. Combination therapy regimens had higher success rates than monotherapy regimens(11/13, 84.6% vs. 3/17, 17.6%).
There has been clonal spread of carbapenem-resistant A. baumannii strains among patients in our hospital since 2007. Intensive care unit stay, invasive procedures, hypoalbuminemia, chronic obstructive pulmonary disease and cerebrovascular disease were common in patients with carbapenem-resistant A. baumannii colonization or infection. Antibiotic combination therapy may be effective for carbapenem-resistant A. baumannii infection.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 04/2011; 43(2):213-21.
ABSTRACT: To investigate the risk factors, prognosis and resistance to antibiotics in patients with extended-spectrum b-lactamase (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection.
A retrospective study was conducted in patients with Escherichia coli and Klebsiella pneumoniae bloodstream infection isolated from Jan. 2004 to Dec. 2005 in Peking University Third Hospital. Those with ESBLs-producing sepsis were case patients, while non-ESBLs-producing sepsis were control patients. The unpaired Student's t-test or non-parametric test and Chi-square test was used for comparison of risk factors, prognosis and resistance to antibiotics between the two groups.
A total of 265 (265/748, 35.4%) strains of ESBLs-producing Escherichia coli and 56 (56/266, 21.1%) strains of Klebsiella pneumoniae were isolated between 2004 and 2005, respectively. There were 15 patients with ESBLs-producing sepsis (M/F: 8/7, age 11 - 82 yr) and 16 with non-ESBLs-producing sepsis (M/F: 5/11, age 7 d-84 yr). The frequent origins of infection in the 2 groups were respiratory system, peritoneal cavity and reproductive system. No statistical difference was found between the 2 groups in clinical symptoms such as temperature, fever type, respiratory rate, heart rate, shock, white blood cells. Pitt bacteremia score and APACHE II score (all P > 0.05). No statistical difference was found between the 2 groups in risk factors such as length of hospital stay before pathogen isolation, length of ICU stay, use of mechanical ventilation, duration of mechanical ventilation, use of central venous catheter, glucocorticosteroids or immunosuppressants, histamine-2-receptor agonists, urinary catheter, operation, gastric tube, total parenteral nutrition, previous hospital admission, anemia and hypoalbuminemia (all P > 0.05). However, the number of use of third-generation cephalosporin given 2 weeks before strains isolation was 9 in case patients (9/11) and 3 in control patients (3/10, chi(2) = 5.743, P < 0.05). The antibiotic resistance rate of ESBLs-producing Escherichia coli and Klebsiella pneumoniae increased significantly, including piperacillin (9 vs. 5, chi(2) = 7.013, P < 0.01), cefepime (7, 0, chi(2) = 7.467, P < 0.01), ceftazidime (9, 1, chi(2) = 11.317, P < 0.01), cefoperazone/sulbactam (11, 2, chi(2) = 11.780, P < 0.01), levofloxacin (12, 7, chi(2) = 5.662, P < 0.05). Five in case patients (5/15) and 2 in control patients (2/16) died.
Use of third-generation cephalosporin is an important risk factor for ESBLs-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection. It is of great clinical significance in supervising ESBLs epidemiology and the third-generation cephalosporin usage.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 11/2008; 31(11):815-9.
ABSTRACT: To investigate the changes and clinical implications of serum procalcitonin in exacerbation of chronic obstructive pulmonary disease (COPD).
We have evaluated PCT measurement in 45 patients with an exacerbation of COPD (group A) and 25 patients with stable COPD (group B), quantitative sputum culture was performed, too. PPMs were only regarded as significant if they reached a growth of > or =10(7) cfu/mL, indicating the presence of bacterial infection.
In patients with an exacerbation, 15 patients, sputum yielded a high (> or =10(7) cfu/mL) bacterial load (group A1), 30 patients, sputum yielded a low (<10(7) cfu/mL) bacterial load or a negative bacterial culture (group A2). The levels of procalcitonin in sera from patients of group A1 were significantly higher than those from group A2 and group B [0.24 (0.17, 0.28) microg/L vs. 0.125 (0.10, 0.18) microg/L vs. 0.12 (0.10, 0.145) microg/L, P= 0.000, 0.000]. The levels of procalcitonin in sera from patients of group A2 were similar to those from group B (P>0.05). Using a cut-off point of 0.155 microg/L for PCT, the sensitivities and specificities for bacterial infection in patients with an exacerbation of COPD were 93.3% and 60% respectively.
Serum procalcitonin measurements in patients of an exacerbation of chronic obstructive pulmonary disease play a role in the diagnosis of bacterial infection.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 09/2006; 38(4):389-92.
ABSTRACT: To investigate the changes and clinical implications of serum procalcitonin (PCT) in acute exacerbations of chronic obstructive pulmonary disease (COPD).
A total of 45 patients with an acute exacerbation of COPD were studied. On presentation, serum PCT concentrations were measured, and quantitative sputum culture was also performed. The patients were reevaluated when they had returned to their stable clinical state. Potentially pathogenic microorganism (PPM) was only regarded as significant if they reached a growth of >or= 10(7) CFU/ml, indicating the presence of bacterial exacerbation of COPD.
(1) On presentation, sputum samples from 21 (46.7%) patients yielded PPM. When reevaluated in stable clinical state, sputum samples from 9 (20%) patients had a positive PPM culture [2.8 x 10(6) (1.3 x 10(6), 1.9 x 10(7)) CFU/ml], but with a significantly lower bacterial load than on presentation [7.0 x 10(7) (4.5 x 10(7), 7.1 x 10(8)) CFU/ml, Z = -2.666, P = 0.008]. (2) The patients were classified into two groups: group A included patients with bacterial exacerbation of COPD (n = 15), group B included patients with nonbacterial exacerbation of COPD (n = 30). The levels of PCT for patients of group A [0.24 (0.17, 0.28) microg/L] were significantly higher than group B [0.13 (0.10, 0.18) microg/L, Z = -3.531, P = 0.000]. When they had returned to their stable state, the levels of PCT for patients of group A decreased to 0.12 (0.10, 0.14) microg/L, which was significantly lower than in exacerbation [0.24 (0.17, 0.28) microg/L, Z = -3.298, P = 0.001]; But compared with exacerbation [0.13 (0.10, 0.18) microg/L], the levels of PCT for patients of group B did not changed [0.13 (0.10, 0.15) microg/L, Z = -1.614, P = 0.107]. In the stable state, there were no differences in the PCT measurement between the two groups (Z = -0.382, P = 0.703).
In patients presented with an acute exacerbation of COPD, the elevation of serum PCT is associated with bacterial infection.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 08/2006; 29(7):444-7.