Bioequivalence, antibacterial activity and therapeutic outcome of a generic meropenem (Mapenem).

BACKGROUND: The authors aimed to compare the bioequivalence and antibacterial activity of a generic meropenem with the original meropenem and studied its preliminary therapeutic outcome. MATERIAL AND METHOD: A randomized, open-label, crossover study was employed to assess the bioequivalence and antibacterial activity. Twenty-six healthy males were recruited at Siriraj Hospital, Thailand and randomized to firstly receive either a single intravenous 30-minute infusion of a generic (Mapenem) or original meropenem (Meronem) and vice versa for the second period. The washout period was one week. Ten milliliters of blood samples were collected before meropenem infusion and at 0, 10, 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 470 and 480 minutes after the beginning of the drug infusion. Blood samples were coded and separated into plasma and serum samples. Plasma samples were used to determine drug concentrations by HPLC-UV detector and the data were analyzed for Cmax, AUC0-t and AUC0-inf. Serum samples were assayed in triplicate for measuring generic and original meropenems' inhibitory activities of a meropenem-susceptible E. coli ATCC 25922 in the same agar plate. An open-label design was used to preliminarily study of the therapeutic outcome and adverse effects of the generic meropenem in 30 patients. RESULTS: All enrolled twenty-six volunteers completed the whole study. The statistical analysis of 90% confidence interval of Cmax, A UC0-t, and AUC0-inf of the generic and original meropenems were 87.7 to 101.7%, 96.3 to 102.4% and 96.3 to 102.3%, respectively. The results were within the standard range of bioequivalence acceptance criteria (80-125%) and the powers of the test were greater than 80%. Using E. coli ATCC 25922 in the blind assay of serum inhibition activity, the inhibitory zone sizes (mm) of the generic compared to original meropenems were not statistically different with respect to every time points of blood collections (p < 0.05). Correlation of mean values of serum meropenem levels and the widths of inhibitory zone sizes of the same samples collected at the same intervals showed good linear relationship with r = 0.891; R2 = 0.794 (p < 0.01) for the generic meropenem and r = 0.885; R2 = 0.784 (p < 0.01) for the original meropenem. The therapeutic result with the generic meropenem for various indications was successful or improved in 24 cases from 30 cases (80%) and the bacterial cure rate was 23 in 30 clinical isolates (76.7%). Adverse reactions probably related to the study medication were rash and elevated liver enzymes in 1 and 3 patients, respectively, and all resolved spontaneously. CONCLUSION: In the present study, the generic meropenem exhibited indifferent bioequivalence and antibacterial activity compared to the original meropenem. There was also a good correlation between serum levels and inhibitory zone sizes produced by the same serum samples in every periods of blood collection. Clinical efficacy of the generic meropenem was shown to be satisfactory without notable severe adverse reaction.

In vitro activity of ceftobiprole against hospital-acquired bacteria commonly causing infections in hospitalized patients at Siriraj Hospital.

Objective: To determine the in vitro activity of ceftobiprole against resistant bacteria commonly causing infections in hospitalized patients at Siriraj Hospital. Methods: The studied organisms were MRSA (32 isolates), Enterococcus sp. (30 isolates), ESBL-producing E.coli (20 isolates), ESBL-producing K.pneumoniae (20 isolates), MDR P.aeruginosa (30 isolates) and MDR A.baumannii (30 isolates). The susceptibility of ceftobiprole was determined by the disk diffusion test for all 162 isolates and the MIC was determined by the E-test method for 5 isolates of each organism. Results: All isolates of MRSA and 77% of Enterococcus sp. isolates were susceptible to ceftobiprole. All isolates of ESBL-producing E.coli and MDR A.baumannii were not susceptible to ceftobiprole. Only 10% to 20% of ESBL-producing K.pneumoniae and P.aeruginosa were susceptible to ceftobiprole. The MICs of ceftobiprole against all tested organisms were correlated with the inhibition zone diameters. Conclusion: Ceftobiprole is very active against MRSA and is moderately active against Enterococcus sp. Ceftobiprole is considered inactive or less active against ESBL-producing gram negatives, MDR P.aeruginosa and MDR A.baumannii.

Antibacterial activities of four Thai medicinal plants.

Medicinal plants have long been used and prescribed in Thailand for centuries. Some of them have been used for treating various diseases including infectious diseases. Pouzolzia pentandra Benn., Gelonium multiflorum A. Juss., Erycibe elliptilimba Merr. and Chun., Balanophora abbreviate Bl. are Thai medicinal plants from the Thai pharmacopoeia that have been prescribed for treating unknown fevers including some specific infectious diseases. This investigation demonstrated the effects of these Thai medicinal plants for their antibacterial activities by using the macrodilution assay. Based on the present study, the water methanol fraction (fraction 2) of Balanophora abbreviate Bl. showed the antibacterial activity at the MIC level of 250 microg/ml but the activity was bacteriostatic in its effects. Therefore, the use of these medicinal plants in controlling fever and infectious diseases appears to be justified and further investigations may be required to obtain more information.

Colonization of nosocomial pathogens on computer keyboards in patient care areas.

Objective: Nosocomial infections are an important cause of morbidity and mortality in hospitalized patients. The role of the hospital environment as a reservoir of nosocomial pathogens is controversial and has not been thoroughly investigated. In the past years at our institution, computers have been widely used in patient care areas, including general wards and intensive care units. There are studies which show that inanimate objects in the hospital environment constitute reservoirs of nosocomial pathogens. Hence, the study is designed to determine whether computer keyboards in the patient care areas in the Department of Medicine, Siriraj Hospital were reservoirs of nosocomial pathogens. Methods: Twenty-six computer keyboards from general medical wards (20) and intensive care units (6) and 26 computer keyboards from secretarial offices were studied from August to September 2003. All the keyboards were cultured for aerobic pathogens by cotton swab technique. Results: The overall colonization rate of pathogens on the keyboards was 96.2% from patient care areas and 92.3% from the offices (p=1). The colonization rates of non-fermentative gram negative bacilli on the keyboards located in the patient care areas and the offices were 11.5% and 0%, respectively (p=0.24). However, if the fungal isolate was considered a potential pathogen, its colonization rate on the keyboard was 4.3% in the patient care areas compared with 1.5 % in the offices (p=0.03). Conclusion: There was a trend in finding potential pathogenic organisms more often from the computer keyboards located in the patient care areas than from those in the offices. The computer keyboards located in the patient care areas should be periodically cleaned.

The outbreak of Serratia marcescens bacteremia in a pediatric ward, Siriraj Hospital 1997.

Between October 20 and November 11, 1997, Serratia marcescens bacteremia was identified in 8 patients in a pediatric ward at Siriraj Hospital. The organism was isolated from 17 blood and 3 bone marrow specimens. The only common associated factor in these patients was that they all had received an intravenous fluid infusion. In the attempt to investigate the source of S. marcescens implicated in the outbreak, 108 specimens of intravenous fluid, 3 intravenous fluid bottle caps, 4 specimens from intravenous fluid tubing sets, 21 specimens of antiseptics used on the ward, 28 specimens of rectal swabs from patients on the ward, 1 sample of blood culture media prepared by the hospital for routine use, and 62 environmental specimens including hand swabs of the medical personnel, refrigerator, air conditioning, milk samples, room air, water sink, wooden splint and adhesive tape used to immobilize the intravenous access. Of 227 specimens sent for culture, S. marcescens was isolated from only one specimen collected from the in-use intravenous fluid given to a patient with Serratia bacteremia. S. marcescens was not found in any other surveillance culture. The 8 patients were placed under quarantine in the same room with an exclusive nursing team. With the investigation and intervention including monitoring for meticulous hand washing of the ward staff, the outbreak was stopped within 7 days. Although the investigation failed to discover the environmental reservoir of S. marcescens in this outbreak, the data suggested that intravenous fluid was probably the route of transmission and the medical personnel played an important role in spreading the infection.

Antiseptics for preventing omphalitis.

BACKGROUND: Omphalitis may cause serious complications and contribute to neonatal morbidity and mortality. From January 1997 to August 1998, the incidence of omphalitis in the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital had been increased from 0.9 to 17.4 per 1,000 live births. A prospective randomized trial using antiseptic applied directly to the umbilical stump was conducted aiming to reduce an epidemic outbreak of omphalitis in the newborn nursery. OBJECTIVE: To determine which antiseptic is appropriate for preventing omphalitis in the newborn infants. PATIENTS AND METHOD: Newborn infants delivered in the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital were randomized into group A (Triple dye) or group B (70% Alcohol). The infant with omphalitis was assessed by a pediatrician or a neonatology fellow. At home, the same antiseptic will be continually applied to the umbilical stump daily until a few days after cord detachment. Relative risk was calculated and statistical significance was tested by Chi-square test. RESULTS: Four hundred and twenty-seven infants were enrolled. Birth weight, gestational age and gender of the infants in both groups were not different. There were no known maternal risk factors for omphalitis. Omphalitis was observed in 9/213 (4.2%) infants in group A and 23/214 (10.7%) infants in group B. The relative incidence rate between each group was statistically significant (p<0.01). Triple dye group was 60 per cent less likely to develop omphalitis compared to 70 per cent Alcohol group (RR 0.39, 95% CI: 0.19-0.83). The mean duration for cord detachment were 13.6 and 11.5 days in group A and group B, respectively. CONCLUSION: During an epidemic outbreak of omphalitis, Triple dye was the most appropriate and effective antiseptic to prevent omphalitis but could delay cord separation.

Efficacy of DESMANOL® for surgical hand scrub.

The comparative study of Desmanolฎ and Hibiscrubฎ was carried out in order to test the efficacies of eliminating microorganisms from surgeons’ hands. Thirty surgical residents of Siriraj Hospital were enrolled in the study. Each subject’s hands and forearms were scrubbed with Desmanol and Hibiscrub on different occasions few days apart by random sequence. Prior to each scrubbing, the hand and forearm were cultured quantitatively by cotton swab technique. The culture was repeated after scrubbing. The coagulase negative staphylococci, micrococci and bacillus were found in almost all the subjects’ hands before scrubbing with both solutions at the quantity of 104 cfu. The other organisms cultured from 10 to 20% of subjects’ hands were S. aureus and gram negative bacilli at 102 to 103 cfu. Seventy percent of the subjects’ hands in both groups had negative culture after scrubbing. The organisms cultured from 30% of the subjects were coagulase negative staphylococci, micrococci and bacillus. However, the colony counts of these organisms were 100-fold decrease from those before scrubbing. No strains of S. aureus or gram negative bacilli were cultured after scrubbing.

A model for testing antiseptic efficacy: A preliminary study on betadine and germidine.

Efficacy of povidone iodine antiseptic, betadine and germidine, was tested against normal skin flora and four pathogenic bacteria namely S. aureus. S. epidermidis, E. coli and Pseudomonas aeruginosa by a new medel. The study was performed on the volar surface of forearms of ten patients. First of all, the skin flora was cultured then 108 cu/ml. of the tested organisms were applied by a cotton swab and left dried for 1 minute before the culture was repeated. Betadine or germidine was applied over the area previously painted with the organism. The culture was taken 1 to 2 minutes thereafter. The results showed that this model was feasible and convenient. Betadine and germidine are efficacious against normal skin flora and pathogenic bacteria.