Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria.

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS: Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.

[Pharmacokinetics of meropenem administered with prolonged infusion time in patients receiving continuous veno-venous hemofiltration].

OBJECTIVE: To demonstrate the pharmacokinetic profile of meropenem when administered by 3-hour infusion in patients undergoing continuous veno-venous hemofiltration (CVVH). METHODS: The study was conducted in 10 patients, who were treated with CVVH. Each subject received meropenem in 3-hour infusion of 500 mg every 6 hours. Blood samples were collected before infusion (0 hour) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6 hours (just before the infusion of the next dose) after the beginning of the fourth infusion. The concentrations of meropenem in plasma were measured by high-performance liquid chromatography method, and mean serum meropenem concentration-time curve was plotted. RESULTS: Peak plasma drug concentrations measured 3 hours post-infusion were (25.05 ± 5.64) mg/L, and trough levels after 6 hours of infusion were (13.03 ± 3.01) mg/L. The area under the plasma concentration-time curve (AUC) was (118.42 ± 26.78) mg x h⁻¹ x L⁻². The elimination half-life (T1/2) was (3.74 ± 0.55) hours. The mean residence time (MRT) was (4.99 ± 0.84) hours. The volume of distribution (Vb) was (22.85 ± 9.85) L and clearance of meropenem (CL) was (4.49 ± 1.32) L/h. The percentage of time that the serum drug concentration was above the minimum inhibitory concentration (MIC) accounting for the interval time of infusion (%T>MIC) was 100% (MIC 8 mg/L) in all the 10 patients. CONCLUSION: Based on these data, we concluded that satisfactory pharmacodynamic parameters could be attained in CVVH patients treated with meropenem by a prolonged infusion time of 3 hours with a dosage of 500 mg for every 6 hours.

Relationship between time to positivity of blood culture with clinical characteristics and hospital mortality in patients with Escherichia coli bacteremia.

BACKGROUND: Previous studies indicated that the time to positivity (TTP) of blood culture is a parameter correlating with degree of the bacteremia and outcome in patients with bloodstream infections caused by Escherichia coli (E. coli). The objective of this study was to further investigate the diagnostic and prognostic power of using TTP to predict E. coli bacteremia. METHODS: A retrospective cohort study at two university hospitals was conducted. We retrieved all the medical records of those with E. coli bloodstream infection according to the records generated by their microbiology departments. Univariate and multivariate analyses were applied to identify clinical factors correlating with fast bacterial growth and significant prognostic factors for hospital mortality. RESULTS: Medical records of 353 episodes of E. coli bacteremia diagnosed between January 1, 2007 and December 31, 2009 were retrieved in the investigation. Univariate analysis demonstrated that the TTP ≤ 7 hours group is associated with higher incidence of active malignancies (41.7% vs. 27.2%, P = 0.010), neutropenia (30% vs.14.3%, P = 0.007), primary bacteremia (55.0% vs. 33.4%, P = 0.002), and poorer outcome (hospital mortality 43.3% vs.11.9%, P = 0.000) than the TTP > 7 hours group. Multivariate analysis revealed that the significant predictors of hospital mortality, in rank order from high to low, were TTP (for TTP ≤ 7 hours, odds ratio (OR): 4.886; 95% confidence interval (CI): 2.572 - 9.283; P = 0.000), neutropenia (OR: 2.800; 95%CI: 1.428 - 5.490; P = 0.003), comedication of steroids or immunosuppressive agents (OR: 2.670; 95%CI: 0.971 - 7.342; P = 0.057). CONCLUSIONS: Incidence of malignancies, neutropenia and primary bacteremia correlates with fast bacterial growth in patients with E. coli bacteremia. The parameter of TTP has been identified as a variable of highest correlation to hospital mortality and therefore can be potentially utilized as a mortality prognostic marker.

[Correlation between in vitro bacterial growth velocity of blood of patients with clinical parameters and prognosis in patients with Escherichia coli bacteremia].

OBJECTIVE: To identify the clinical and laboratory parameters correlating with speed of bacterial growth in culture and independent risk factors of in-hospital mortality in patients with Escherichia coli bacteremia. METHODS: This retrospective study was conducted at Beijing University Third Hospital. The medical records and microbiological database of the patients diagnosed as Escherichia coli bacteremia between January 2007 and December 2009 were collected. The parameter of time to positivity (TTP) was used to be a surrogate marker of bacterial growth. Univariate analysis was used to identify relationship between clinical parameters and the speed of bacterial growth. Logistic multivariate analysis was used to identify risk factors of in-hospital mortality. RESULTS: The medical records of 112 patients during the study period were collected, 25 patients died during hospital stay, the overall in-hospital mortality rate was 22.3%. Univariate analysis indicated the rapid-growth (TTP≤7 hours) group (n=20) had higher incidence of neutropenia (40.0% vs. 15.2%), higher incidence of primary bacteremia (40.0% vs. 18.5%) and higher in-hospital mortality rate (45.0% vs. 17.4%) than those with slow bacterial growth (TTP>7 hours) group (n =92, all P<0.05). The death group (n=25) was found to have a higher incidence of TTP≤7 hours (36.0% vs. 12.6%), higher incidence of active malignancies (44.0% vs. 24.1%), higher incidence of neutropenia (36.0% vs. 14.9%), higher rate of isolation of extended spectrum ß lactamases (ESBL)-producing strains (48.0% vs. 24.1%) than the survival group (n=87, all P<0.05). Logistic multivariate analysis suggested the significant predictors of in-hospital mortality included TTP≤7 hours [odds ratio (OR)=3.412, 95% confidence interval (95% CI)=1.1819.856, P=0.023], ESBL-producing strains (OR=2.545, 95% CI=0.9776.625, P=0.056). CONCLUSION: In vitro Escherichia coli growth speed in the blood culture correlates with the incidence of neutropenia and primary bacteremia, and TTP≤7 hours and ESBL-producing strains may be the strong, independent risk factors of a worse prognosis in patients with Escherichia coli bacteremia.

[Assessment of severity of acute pancreatitis in early stage].

OBJECTIVE: To assess the accuracy of indexes for predicting severe acute pancreatitis (SAP). METHODS: Thirty-nine patients suffering from acute pancreatitis (AP) were randomly selected, including 20 SAP cases and 19 mild acute pancreatitis (MAP) cases. The levels of polymorphonuclear leucocyte-elastase (PMN-E), serum phospholipase A2 (PLA2), pancreatic PLA2 (Pan-PLA2), PLA2 catalytic activity (CA-PLA2), amylase, as well as C-reactive protein (CRP) were determined Acute Physiology and chronic health evaluation II (APACHE II) was scored in every patient. Sensitivity and specificity of all the parameters were assessed, and receiver operator characteristic curve (ROC) was plotted. Positive predictive value, negative predictive value, and overall accuracy were then analyzed. RESULTS: PMN-E, CRP and CA-PLA2 were obviously higher in SAP than in MAP, and were indicative of the severity of the disease (all P < 0.01). Pan-PLA2 and amylase of AP patients raised at the onset of the disease, and they showed no difference between the SAP groups and MAP groups. When SAP was predicted by PMN-E, sensitivity was 94.5%, specificity was 99.4%, positive predictive value was 97.8%, negative predictive value was 99.4%, overall accuracy was 98.7%, higher than other indexes. When SAP was Predicted by CRP, the overall accuracy was also high and reached 84.0%. CONCLUSION: PMN-E, CA-PLA2, CRP, and APACHE II are all indexes for the diagnosis of SAP. PMN-E is found to be the best index in predicting SAP.