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.

Fulminating influenza pneumonia in the elderly: a case demonstration.

An 82-year-old male Bangkokian with hypertension, diabetes mellitus, end-stage renal disease, and coronary artery disease for many years, was hospitalized due to deterioration of a 3-day influenza-like-illness with one-day chest oppression and respiratory failure. At the emergency room, oxygen saturation was 79% on room air Chest X-ray revealed bilateral diffuse pulmonary infiltrates. He was intubated and hemodialysis was initiated. Emergency coronary angiography revealed patent coronary artery. Sputum gram stain revealed numerous leukocytes with no bacteria. On day three of hospitalization, empiric treatment with oseltamivir and clarithromycin was administered Seventy-two hours later his clinical condition began to improve and fever subsided 7 days later Rapid test of tracheal secretion with immunofluorescence assay was positive for moderate amount of influenza A virus. Viral isolation yielded influenza A virus subtype H1N1. Review of in-patient records at this hospital using ICD-10 codes as J10 and J11 during 1995-2005, discovered 32 cases with claim diagnosis of influenza. However this is the first case with proven influenza pneumonia that was given empiric oseltamivir. Rapid deterioration of influenza-like illness due to human influenza virus in the elderly and pathogenesis of pulmonary in this case are discussed to alert physicians to recognize this dreadful illness and treat it in timely fashion.

Pneumococci: drug susceptibilities and preliminary epidemiological studies by penicillin binding protein genotyping.

A collection of 307 pneumococcal isolates form 84 children and 223 adults admitted to Siriraj Hospital were separated into two groups, penicillin-susceptible (PSSP) and penicillin-nonsusceptible (PNSP). Each group was tested for susceptibilities to 12 drugs (cefuroxime, amoxicillin, chloramphenicol, tetracycline, cefotaxime, ceftriaxone, imipenem, meropenem, ciprofloxacin, ofloxacin, erythromycin and co-trimoxazole). PSSP were susceptible to cefuroxime (87.5%), amoxicillin (100%), chloramphenicol (84.7%), tetracycline (45.8%), cefotaxime (99%), ceftriaxone (99%), imipenem (99%), meropenem (100%), ciprofloxacin (76%), ofloxacin (99%), erythromycin (94.8%) and co-trimoxazole (61.5%). PNSP were resistant to most drugs, except for amoxicillin (99%), ofloxacin (99%) and ciprofloxacin (86.3%). Twenty-two pneumococcal isolates belonging to the three most common serotypes (6, 19, 23) were randomly selected for studies of the pbp2b gene with RFLP. There were 7 distinct pbp2b RFLP patterns. RFLP pattern 1 was the most predominant resistant pattern. The RFLP pattern 2 was found only in PSSP.

Etiologies of acute undifferentiated febrile illness in Thailand.

BACKGROUND: Acute pyrexia of unknown origin (Acute PUO) was reported to affect approximately 200,000-400,000 patients each year reported by the national Annual Epidemiological Surveillance Report. The patients usually present with fever of less than two-week duration and non-specific symptoms such as malaise, myalgia, headache and loss of appetite. Its mortality rate is less than 0.02 percent. It would be interesting to find the etiologies and propose a management plan if the etiologies are discovered. OBJECTIVE: This prospective epidemiologic study aimed to discover the etiologies of acute undifferentiated febrile illness in a tropical region like Thailand. SUBJECTS AND METHOD: Ten community-based hospitals were chosen as representatives in each part of Thailand to enroll patients into the study. Patients aged over two years old who presented with fever at the participating hospitals during year 1991-1993 were eligible for the study. Entry criteria of acute undifferentiated febrile illnesses (AUFI) included oral temperature over 38.3 degrees C within the last 24 hours, duration of fever ranging from 3-14 days, no specific single organ involvement by history taking and physical examination, normal or non-specific results of the following investigations: complete blood count, thick film for malaria, urinalysis and chest roentgenogram. The patients were hospitalized and a preset diagnostic protocol was performed. Other diagnostic procedures deemed necessary by attending physicians were perform. Patients were followed up within one month after hospital discharge. RESULTS: 1,240 patients were enrolled but only 1,137 case records and results of the serological tests were available for analysis. Etiologies could be found in 471 cases (38.7%). Primary bacteremia was detected in 36 cases (3.2%). E. coli, streptococci, salmonella, Enterobacter spp. and S. aureus were the five most common blood isolates. Serological studies revealed positive results for scrub typhus (7.5%), influenza (6.0%), dengue fever (5.7%), murine typhus (5.3%), enteric fever (1.9%), chikunkunya infection (1.1%), leptospirosis (1.1%) and melioidosis (0.9%). Thirteen cases succumbed (1.1%) in this study. CONCLUSION: The etiologies in the majority (61.3%) of AUFI remained unknown. Rickettsial infection, influenza and dengue fever are the most common identifiable diseases in a tropical country like Thailand especially during the rainy season. A management guideline for diagnosis and treatment of the AUFI with emphasis on primary bacteremia and antimicrobial-treatable AUFI was proposed.

Bacterial isolation with on-site inoculation of ascites fluid into hemoculture bottle in spontaneous bacterial peritonitis.

OBJECTIVE: To compare the on-site bacterial inoculation of ascites fluid into hemoculture bottle with routine method in the patients who were preliminary diagnosed of SBP. MATERIAL AND METHOD: A retrospective analysis of case records during January-December 2001. RESULTS: A total of 673 specimens from 325 patients were retrieved from the data records at the Department of Microbiology, Siriraj Hospital in 2001. The neutrocytic ascites were found in 163 specimens (94 patients). The routine method and on-site inoculation into the hemoculture bottle were employed in 107 and 56 specimens respectively. Culture-positive neutrocytic ascites was found in the routine method 16 (14.9%) specimens and in the on-site inoculation 26 (46.4%) specimens (p < 0.0001). Among these samples, the two methods were simultaneously performed in 42 specimens of which 18 paired specimens were eligible for analysis. Positive culture was found in 2 samples in which the routine method and in an additional 5 samples in which on-site inoculation into hemoculture bottle method. Using Kappa analysis (e score = 0.328, 95% CI = -0.172 to 0.829) that can be interpreted the on-site inoculation method had a higher yield than the routine technique. Moreover, 21 cases also had their blood and ascites samples simultaneously collected and cultured. 4 of ten (19%) and 5 of eleven (23.8%) cases were found in the routine and on-site and direct inoculation groups respectively. These finding suggested that the severity of infection in among two groups were similar and unlikely to be the cause of the difference of the positive isolation rate in both groups. CONCLUSION: The on-site and direct inoculation of ascites into hemoculture bottle method had a significantly higher isolation rate than routine method (i.e. 46.4% versus 14.9% p < 0.0001) either with separated or paired samples of ascites.

Completion of in-patients’ illness summary from within three working days.

A management system was set up in Department of Medicine with aim to shorten the duration of filling the patients’ illness summary form by attending physicians to within three working days. An office was assigned to contact by telephone or meet physicians in charge of the hospitalized patients who had been discharged and requested them to complete the patients’ illness summary form provided by Health or Life Assurance Co. Ltd. Within three working days. If the physician was unable to do so, the officer contacted another physician who could either be the chair or physicians belonged to the same Division of the attending physician or other physician within Department of Medicine to fill the summary form in due time. The system was implemented in April 2003 and durations of completing the patients’ illness summary form were collected since then until August 2003. A total of 344 medical records were sent to physicians and numbers of patients’ illness summary forms that were completely recorded and returned to the officer within 3 and 4-5 working days were written by the attending physicians themselves, the numbers of patients’ illness summary forms that were completely recorded within 3 and 4-5 working days were 208 (62.1%) and 55 (16.4%) respectively. In conclusion, the implemented system significantly shortened the duration of completing in-patients’ illness summary forms. Key factors to the success of this system depended on direct contract, a responsible and assigned officer and good co-operation of all attending physicians in and outside Department of Medicine.

Management pattern and hospital charge of repairing cleft palate at Siriraj Hospital.

Management pattern and hospital charge for repairing cleft palate at Siriraj Hospital during 1996-1999 were studied retrospectively. From the examination of 100 patient records, four cases were excluded since no surgical correction was performed during hospitalization. Fifty-nine percent were female and the average age was 5.54 years old. Fever and otitis media were associated with two and three cases respectively. Other underlying diseases included hypothyroidism, patent ductus arteriosus and ventricular septal defect were found one in each case. The cleft palate was successfully repaired in all cases. Surgical correction was done in 84 percent of cases within the first five days of hospitalization. The average length of stay was 5.89 + 2.85 days and ranged from 2-20 days. The hospital charge for cleft palate repair was 7,031.22 + 1,365.33 Baht per case. This study illustrate that a small variation is practiced in the management of a reasonably straight forward condition and better preparation of the patients before hospitalization could reduce the hospital stay or avoid unnecessary hospitalization.

Characters of a dean of the autonomous University.

Opinion about the appropriate characters of a dean of the autonomous university, regarding the academic level, administrative ability and method of selection was elicited in a survey among selected academic staff of Mahidol University during June 15-30, 1998. A questionnaire was designed and distributed to all administrators (n=302) of the University and to a random sample of 471 from 2,360 academic staff who did not have administrative position. A total response rate of 46.1 percent was achieved. Sixty-two percent of the responders were administrators and 80 percent of them were older than 40 years of age. Our study revealed that no sexual preference for a dean in 93.6 percent. The dean should be at least 40 years old (61%) but the one who retired, were not suitable (54%). Seventy-seven percent agreed that the dean’s profession should be the same kind as of officials of that faculty and a talent outsider is still unacceptable (58%). Previous experience in university administrative ability before being chosen. Sixty-five percent preferred to have equal ability in administration and academic achievement though 31 percent preferred the former to the latter. Academic level of associate preferable or higher with master degree or higher of relevant profession to the Faculty is preferred in 63 and 85 percents respectively. Publication in a peer reviewed international journal is required in 59 percent with emphasis on citation in international journal in 47 percents. Election by faculty staff is preferable to selection by a search committee and the selected candidate must be accepted by more than 50 percent of the faculty staff. All members of the search committee should have good reputation and accountability. The opinion about the academic level of the dean by administrators who had academic level of lecturer and assistant professor was different from other groups. The former voted the academic rank of the dean to be any ranks from lecturer while the latter preferred associate professor and professor to other lower ranks.

Citation rate of articles published by staffs of faculty of medicine Siriraj Hospital during 1991-1995.

Articles published by staff of the Faculty of Medicine Siriraj Hospital, which were referred to in international journals during 1991-1995, were retrieved from the Medline database. The citation rates were calculated in terms of reference articles per year and per person per year for each department. The total number of references was 1,185 during the period reviewed, or 192, 180, 235, 288, and 290 times in the year 1991, 1992, 1993, 1994 and 1995 respectively. Accordingly, the citation rates per person per year were calculated to be 0.29, 0.27, 0.35, 0.43 and 0.43 times. The Department of Immunology gained the highest average rate during the dive-year review period, which was 3.71 times per person per year. The Departments of Medicine and Dermatology posted the second and third highest rates which were 1.31 and 1.03 respectively. When the citation rate was calculated separately by per-clinical and clinical departments and year, the citation rates were found be higher for the per-clinical department every year, The average citation rate over the whole five years for the Faculty was 0.35 times per person per year, which indicates an increasing trend when compared with 0.243 times per person per years during 1985-1994.

Articles published by staffs of faculty of medicine Siriraj Hospital during 1992-1995.

Articles published by faculty staffs during 1992-1995 in various journals were collected and analysed. Total number of the articles published during the 4-year period was 1,387 articles. Four hundred and twenty-five, 446, 295, and 221 articles were published in 1992, 1993, 1994 and 1995 respectively or 0.66, 0.69, 0.46 and 0.34 article per person per year. On average, clinical departments published more articles than preclinical departments. Her Majesty’s Cardiac Centre, Department of Pediatrics, Department of Medicine, Department of Dermatology, department of Blood Transfusion and Medicine and Department of Microbiology published more than one article per person per year. The most common journal that published articles of the faculty staffs was Siriraj Hospital Gazette. The top three peer-reviewed journals that published articles from the faculty staff, were Journal of the Medical Association of Thailand, Southeast Asian Journal of Tropical Medicine and Public Health and Asian Pacific Journal of Allergy and Immunology. Department of Medicine, Department of Pediatrics and Department of Orthopaedics and Rehabilitation contributed for 20.5, 10.6 and 9.1 percents of the publications in these journals respectively.