Le Thi Anh Thu

Selective high-performance liquid chromatographic determination of artesunate and α- and β-dihydroartemisinin in patients with falciparum malaria

Abstract A novel solid-phase extraction and a robust high-performance liquid chromatographic (HPLC) separation procedure for artesunate and α- and β-dihydroartemisinin, using post-column alkali decomposition and UV detection, is described. Extraction was performed with Bond-Elut Phenyl solid-phase extraction cartridges and analysis by HPLC was carried out using a Waters Symmetry C8 5-μm 150 × 3.9 mm I.D. column. The mobile phase was 50% acetonitrile in 0.1 M acetate buffer (pH 4.8) delivered at a flow-rate of 0.7 ml/min. The column eluate was mixed with 1.2 M potassium hydroxide in 90% methanol delivered at 0.3 ml/min, in a 1-ml reaction coil at 69°C, to form UV-absorbing chromophores which were detected at 290 mm. The recovery of all analytes was greater than 80%. There was no significant difference in the peak-area ratio of α- and β-dihydroartemisinin in plasma. Preliminary pharmacokinetic data from six adult Vietnamese patients who received 120 mg of artesunate by intravenous injection for the treatment of acute falciparum malaria are presented. Despite limited data, the mean half-life of artesunate was approximately 3.5 min while that for dihydroartemisinin was 34 min. These data confirm the relatively rapid clearance of both artesunate and its principal active metabolite, dihydroartemisinin.

Glucose and lactate turnover in adults with falciparum malaria: effect of complications and antimalarial therapy

Hypoglycaemia and lactic acidosis are potentially life-threatening, poorly understood sequelae of Plasmodium falciparum infections. We investigated relationships between clinical status, treatment, and glucose and lactate kinetics during management of falciparum malaria in 14 Vietnamese adults. Nine had severe malaria, of whom 4 were administered quinine (Group 1a) and 5 artesunate (Group 1b). Five uncomplicated cases received artesunate (Group 2). Glucose and lactate turnover were studied on 3 occasions: (i) immediately after initial antimalarial treatment, (ii) at parasite clearance a median of 3 days later, and (iii) at discharge from hospital a median of 9 days post-admission. Steady-state glucose and lactate kinetics were derived from plasma isotopic enrichment during a primed-continuous infusion of D-[6,6-D2]glucose and a parallel infusion of L-[1-13C]lactate. Group 1a patients had the lowest plasma glucose concentrations in the admission study (median [range] 3.9 [3.6-5.1] vs 6.3 [4.9-7.1] and 4.5 [4.3-5.5] mmol/L in Groups 1b and 2 respectively; P < 0.05 vs Group 1b), but glucose production rates and serum insulin concentrations that were similar to those in the other groups (P > 0.17). This was also the case at parasite clearance and suggested an inappropriate beta cell response. Group 1a patients had the highest admission lactate production (60 [36-77] vs 26 [21-47] and 22 [4-31] mumol/kg.min in Group 1b and 2 respectively; P < 0.05 vs Group 2). Amongst the 9 severe cases, there was an inverse association between plasma glucose and lactate production at admission and parasite clearance (P < 0.05), but no correlation between admission lactate production and serum bicarbonate (P = 0.73). The present data confirm previous studies showing that quinine depresses plasma glucose through stimulation of insulin secretion. It is hypothesized that the low plasma glucose activates Na+,K(+)-ATPase through increased plasma catecholamine concentrations, leading to accelerated glycolysis and increased lactate production in well-oxygenated tissues. In some severely ill patients with falciparum malaria, a raised plasma lactate on its own may, therefore, be an unreliable index of a developing acidosis.

Microbiology of Surgical Site Infections and Associated Antimicrobial Use Among Vietnamese Orthopedic and Neurosurgical Patients

OBJECTIVES To determine the pathogens associated with surgical site infections (SSIs) and describe patterns of antimicrobial use and resistance in orthopedic and neurosurgical patients in a large university hospital in Vietnam. DESIGN Prospective cohort study. SETTING Cho Ray Hospital, Ho Chi Minh City, Vietnam. PATIENTS All patients who had operations during a 5-week study period. RESULTS Of 702 surgical patients, 80 (11.4%) developed an SSI. The incidence of SSI among orthopedic patients was 15.2% (48 of 315), and among neurosurgical patients it was 8.3% (32 of 387). Postoperative bacterial cultures of samples from the surgical sites were performed for 55 (68.8%) of the 80 patients with SSI; 68 wound swab specimens and 10 cerebrospinal fluid samples were cultured. Of these 78 cultures, 60 (76.9%) were positive for a pathogen, and 15 (25%) of those 60 cultures yielded multiple pathogens. The 3 most frequently isolated pathogens were Pseudomonas aeruginosa (29.5% of isolates), Staphylococcus aureus (11.5% of isolates), and Escherichia coli (10.3% of isolates). Ninety percent of S. aureus isolates were methicillin resistant, 91% of P. aeruginosa isolates were ceftazidime resistant, and 38% of E. coli isolates were cefotaxime resistant. All but 1 of the 702 patients received antimicrobial therapy after surgery, and the median duration of antimicrobial therapy was 11 days. Commonly used antimicrobials included aminopenicillins and second- and third-generation cephalosporins. Two or more agents were given to 634 (90%) of the patients, and most combination drug regimens (86%) included an aminoglycoside. CONCLUSIONS Our data indicate that the incidence of SSI is high in our study population, that the main pathogens causing SSI are gram-negative bacteria and are often resistant to commonly used antimicrobials, that the use of broad-spectrum antimicrobials after surgery is widespread, and that implementation of interventions aimed at promoting appropriate and evidence-based use of antimicrobials are needed in Vietnam.

Cost-effectiveness of a hand hygiene program on health care-associated infections in intensive care patients at a tertiary care hospital in Vietnam.

BACKGROUND The cost-effectiveness of a hand hygiene (HH) program in low- and middle-income countries (LMICs) is largely unknown. We assessed the cost-effectiveness of a HH program in a large tertiary Vietnamese hospital. METHODS This was a before and after study of a hand hygiene program where HH compliance, incidence of hospital-acquired infections (HAIs), and costs were analyzed.The HH program was implemented in 2 intensive care and 15 critical care units. The program included upgrading HH facilities, providing alcohol-based handrub at point of care, HH campaigns, and continuous HH education. RESULTS The HH compliance rate increased from 25.7% to 57.5% (P < .001). The incidence of patients with HAI decreased from 31.7% to 20.3% (P < .001) after the intervention. The mean cost for patients with HAI was

Dissemination of clonal complex 2 Acinetobacter baumannii strains co-producing carbapenemases and 16S rRNA methylase ArmA in Vietnam

1,908, which was 2.5 times higher than the costs for patients without an HAI. The mean attributable cost of an HAI was

GLUCURONIDATION OF DIHYDROARTEMISININ IN VIVO AND BY HUMAN LIVER MICROSOMES AND EXPRESSED UDP-GLUCURONOSYLTRANSFERASES

1,131. The total cost of the HH program was

A pharmacokinetic and pharmacodynamic study of intravenous vs oral artesunate in uncomplicated falciparum malaria

12,570, which equates to a per-patient cost of

Oral bioavailability of dihydroartemisinin in Vietnamese volunteers and in patients with falciparum malaria

6.5. The cost-effectiveness was estimated at -

The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria

1,074 or

Delayed Parasite Clearance in a Splenectomized Patient with Falciparum Malaria Who Was Treated with Artemisinin Derivatives

1,074 saved per HAI prevented. The intervention remained cost savings under various scenarios with lower HAI rates. CONCLUSION The HH program is an effective strategy in reducing the incidence of HAIs in intensive care units and is cost-effective in Vietnam. HH programs need to be encouraged across Vietnam and other LMICs.