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.

Microbial contamination of antiseptics and disinfectants.

OBJECTIVE: To study the bacterial contamination of antiseptics and disinfections in-use and the risk factors for contamination. MATERIAL AND METHOD: Bacterial contamination of antiseptics and disinfectants was done by culturing in-use solutions. Eight commonly used solutions were studied: alcohol 70%, chlorhexidine 4%, and 0.5%, povidone iodine 7.5% and 10%, tincture iodine 1-2%, lysol 2% and sodium hypochlorite 0.5%. RESULTS: The following risk factors for contamination were found : preparation by unskilled personnel, improper containers and prolonged use. Contamination with bacteria were found in 1.8% of 16,142 samples tested Highest rate of contamination was found in Lysol 2%. There was no contamination of povidone iodine 10% and tincture iodine 1-2%. Bacterial contamination of antiseptics and disinfectants was highest in provincial hospitals and was not found in university hospitals. The rates of contamination correlated with the duration of use. Most bacteria isolated were those found in the environment. CONCLUSION: The contamination of in-use antiseptics and disinfectants was as high as 1.8%. Risk factors for contamination were improper preparation and prolonged use.

Bacterial flora--A potential source of endophthalmitis after cataract surgery.

OBJECTIVES: To study bacteria from eye lids and conjunctival sac of patients undergoing cataract surgery before and after the application of antiseptics. MATERIAL AND METHOD: Patients undergoing elective cataract extraction in one university hospital were randomly enrolled. Cultures for bacteria and candida were done by swabbing the eye lids before and after cleaning with 4% chlorhexidine gluconate. Subsequently 10% povidone iodine was applied on eye lids and conjunctival sacs. Cultures of specimens from eye lids and conjunctival sac were taken after the application of 10% povidone iodine and at the end of the operation. RESULTS: Fifty-one patients were enrolled. Positive cultures were found in 90.2% and 82.4% before and after cleaning the face with 4% chlorhexidine. After topical application of 10% povidone iodine, only 19.6% had positive cultures from eye lids and conjunctival sac; a significant reduction (p=0.001). At the end of the operation, positive cultures were found from eye lids in 10 patients and from the conjunctival sac in 4 patients. Isolates were skin flora and candida species in 2 patients. None of the patients had endophthalmitis. CONCLUSION: Cleaning eye lids with 4% chlorhexidine followed by applying 10% povidone iodine was effective in decreasing skin flora in cataract surgery. The organisms were not completely eliminated. Postoperative follow-up to detect infectious complications is warranted.

Development of national guidelines for the prevention and control of nosocomial infections.

OBJECTIVE: To develop a national evidence-based guidelines for the prevention and control of nosocomial infection. MATERIAL AND METHOD: Draft guidelines for the prevention and control of nosocomial infection were developed by the researchers and reviewed by a 10 member panel of experts. The guidelines were modified by brainstorming of 55 practitioners in July 2002. The guidelines were tested for their applicability in 20 hospitals across the country in 2002. The participants gave suggestions on the guidelines which were modified accordingly. The guidelines were finalized by brainstorming of the 55 practitioners in August 2003. RESULTS: National guidelines for the prevention and control of nosocomial infections were developed. Twenty-one topics were included. Modifications of the drafted guidelines were made four times according to the opinions of 10 experts, twice by brainstorming of 55 practitioners and by the suggestions of participants from 20 hospitals where they were tested. The practices in hospitals with different facilities were also suggested in the guidelines. CONCLUSION: National guidelines for prevention and control of nosocomial infection were formulated. Their application for use in every hospital and periodic reviews are expected.

Prevalence and effectiveness of an education program on intestinal pathogens in food handlers.

OBJECTIVES: To assess the prevalence of intestinal pathogens and the effectiveness of an education program in food handlers in a tertiary care hospital. MATERIAL AND METHOD: The prevalence of intestinal pathogens in food handlers was done by stool cultures for bacteria and microscopy for parasites. Treatment was given to those who had a positive stool examination. An education program on the acquisition of the pathogens and their prevention were given by lecture and distribution of handouts. Efficacy of the education program was evaluated by assessing the knowledge and the presence of pathogens before and after the education program. RESULTS: The study was done from January 2002 to March 2004. Risk factors for acquiring intestinal pathogens among food handlers were high regarding education level, housing, food hygiene and personal hygiene. Diarrheal diseases were common in food handlers and their relatives. Before the education program, 40.8% had intestinal pathogens, bacteria and parasites in almost similar proportions. Most common bacteria were Vibrio parahemolyticus, Plesiomonas shigelloides and Salmonella spp.; Blastocystis hominis, Giardia lambria and Endolimax nana were the frequently found intestinal parasites. Food handlers with the pathogens in stool were treated. After the education program subsequent investigation showed a significant reduction in stool pathogens and parasites but their knowledge and hand hygiene practice did not improve. CONCLUSION: The present study showed a high prevalence rate of intestinal pathogens in food handlers of a tertiary care hospital. The education program failed to improve their knowledge and hand hygiene practice for the prevention of the pathogens.

Prevention and treatment of infectious diseases in healthcare workers.

OBJECTIVES: To study the prevention and treatment of infectious diseases offered to healthcare workers (HCWs) in Thailand. MATERIAL AND METHOD: Data were collected by interviewing in 2002. RESULTS: A total 1,218 HCWs in 33 hospitals were interviewed. Nurses and doctors were the majority group, accounting for 31.5% and 30.5% respectively. Pre-employement health screenings were done by physical examination in 56.0% and chest X-ray in 55.7% and immunization against hepatitis B and tubuculosis were offered in 17.7% and 11.4% respectively. Annual physical examination and chest x-ray were done in 66.3% and 76.9%. Reported infection with hepatitis A hepatitis B, tuberculosis in HCWs were as high as 16.8%, 4.0% and 2.6% respectively. Only 3.5% to 24.3% of HCWs ever read guidelines on the prevention of infection. Existing laws allowed the implementation of prevention, treatment and compensation in case of occupationally acquired infection in HCWs. CONCLUSION: Prevention of infection in HCWs was implemented far below the ideal level. They should be better protected under existing laws.

Development of quality indicators of nosocomial infection control.

OBJECTIVES: To study the rates of catheter associated urinary tract infection (CAUTI), Ventilator-associated pneumonia (VAP), Central venous catheter blood stream infection (CVCBSI) and surgical site infection (SSI) in Thai hospitals. The rates of the infections will be used as quality indicators. MATERIAL AND METHOD: Active surveillance in 38 hospitals in Thailand during 2003-2004. Risk stratification of NI rates and utilization of devices were calculated. Results: The rates of CAUTI, VAP, CVCBSI and SSI were obtained. Pooled means, and rates of NI at 10, 25, 50, 75 and 90 percentiles were calculated for CAUTI, VAP, CVCBSI. The infection rates were also presented for each type of hospital. The above NI rates were comparable to those reported by the National Nosocomial Infection Surveillance System (NNIS) in the United States. Surgical site infection was studied in 21 procedures with risk index categories 0-2. The rates of SSI in the present study was lower than those in the U.S. study due to different methods of study. CONCLUSION: The risk stratified rates of CAUTI, VAP, CVCBSI and SSI were obtained. They were similar to a larger scale of study in the United States. The NI rates could be used for evaluating the efficacy of NI control in Thai hospitals.

Antimicrobial susceptibility of community and hospital acquired bacteria.

OBJECTIVES: To study the antibiotic susceptibility of common community- and hospital-acquired bacteria in Thailand. MATERIAL AND METHOD: Eight common bacterial pathogens were studied in 24 hospitals across Thailand in 2002-2003. Isolates of clinically proven infections were tested for their susceptibility by agar-based disc diffusion method. RESULTS: A total of 9,091 isolates of target bacteria were studied. Community and hospital acquired bacteria accounted for 54.9% and 45.1% respectively. Community acquired Escherichia coli, Klebsiella pneumoniae, Acinetobacter spp., Enterobacter spp., Staphylococcus aureus were more susceptible to antimicrobials compared to hospital acquired strains. The difference in susceptibility of community-acquired vs hospital acquired Pseudomonas aeruginosa, Coagulase-negative staphylococci and Enterococcus spp. was less impressive indicating the spread of hospital strains into the community. Bacteria isolated from the blood stream were more susceptible to antimicrobials compared to those from the lower respiratory tract, urinary tract and surgical sites. Acinetobacter spp. and Enterococcus spp. were less susceptible to antimicrobials compared to others. CONCLUSION: Decreased susceptibility to antimicrobials was found in all bacteria tested. The susceptibility to commonly used antimicrobials of community-acquired bacteria decreased to a critical level indicating the widespread resistant bacteria to the community.

Estimated economic losses of hospitalized AIDS patients at Siriraj Hospital from January 2003 to December 2003: time for aggressive voluntary counseling and HIV testing.

This retrospective study was performed to explore the pattern of adult HIV-infected patients admitted to Siriraj Hospital from January 2003 to December 2003 and estimated the economic losses of these patients. Two hundred and forty four medical records were available for review. The proportion of male to female was 2 to 1. Mean age of patients was 36.64 +/- 9.72 years. The mean CD4 count among 112 patients was 82.79 +/- 96.49 cell/mm3. One hundred and twenty four (50.82%) were newly diagnosed of HIV infection. The three most common opportunistic infections were Tuberculosis (42.62%), Pneumocystis carinii pneumonia (14.75%), and cryptococcosis (13.11%). The mean duration of admission was 15.72 +/- 15.11 days. The mean expense per admission was 38,194.58 +/- 32,354.86 Baht. Fifty four patients (22.13%) died during admission. The mean income of these patients was 3,903.5 +/- 3,841.42 baht per month. The estimated economic losses of 54 patients who died during admission including medical care expense and income losses due to premature death was 69,769,739.32 baht. However, the expected medical expense of antiretroviral medications in these 54 patients if they had been diagnosed earlier and their lives had been saved would have been 42,214,608 baht. Therefore, vigorous voluntary counseling and HIV testing in patients aged 13-70 years when they have any risk factors for HIV infection regardless of symptoms might be more cost effective than diagnosis when they get sick.

HIV infection/acquired immunodeficiency syndrome at Siriraj Hospital, 2002: time for secondary prevention.

The authors retrospectively reviewed the medical records of HIV/AIDS patients who were admitted to the medical service, Siriraj Hospital from January 1, 2002 through December 31, 2002. Demographics, CD4 lymphocyte counts, discharge diagnoses, the incidence of Pneumocystis carinii pneumonia (PCP), cerebral toxoplasmosis and cryptococcosis in patients who received and did not receive appropriate chemoprophylaxis against those opportunistic infections when indicated, and outcome of the patients were collected. Three hundred medical records of 286 HIV/AIDS patients were available for review. One hundred and seventy two patients (60.1%) were male. Mean age of the patients was 36.8 +/- 9.91 years (range 14-74). The mean CD4 lymphocyte count that was determined in 165 patients was 74.7 +/- 134.21 cells/mm3 (range 0-894). Of the 300 admissions, 36 per cent were newly diagnosed HIV infection. Only 23 (7.7%) patients had received antiretroviral drugs at the time of hospitalization. The leading HIV-related diseases were tuberculosis (29.3%), Pneumocystis carinii pneumonia (18.7%), and cryptococcosis (15.7%). The rest of them included cytomegalovirus diseases (6.3%), lymphoma (6.3%), Salmonella bacteremia (6%), cerebral toxoplasmosis (5.7%), cryptosporidiosis (5.3%), disseminated Mycobacterium avium complex infection (1.0%), extrapulmonary histoplasmosis (1.0%), Candida esophagitis (1.0%), progressive multifocal leukoencephalopathy (1.0%), and rhodococcosis (0.7%). Among those for whom HIV infection was established and chemoprophylaxis for PCP, cerebral toxoplasmosis and cryptococcosis were indicated, 9.8 per cent vs 28.2 per cent, 3.6 per cent vs 5.1 per cent, and 10 per cent vs 15.2 per cent of whom received and did not receive the appropriate chemoprophylaxis developed PCP, cerebral toxoplasmosis and cryptococcosis respectively. One hundred and ninety (63.3%) patients were alive at discharge, 84 (28.0%) had died, 21 (7%) were referred to other hospitals, and 5 (1.7%) left hospital against medical advice. The mortality rate in newly diagnosed HIV and in known HIV without antiretroviral treatment were comparable but much lower in known HIV-infected patients who received antiretroviral therapy. Secondary prevention by detection of HIV-infected patients while they are asymptomatic and providing them with appropriate chemoprophylaxis against specific opportunistic infections as well as appropriate antiretroviral treatment would decrease morbidity, mortality, and improve the quality of life of HIV-infected patients in Thailand.

Disseminated penicilliosis marneffei in immunocompetent hosts.

Two cases of disseminated Penicilliosis marneffei are reported; both were middle-aged female patients from the central part of Thailand who presented with multiple cystic skin lesion. Their systemic symptoms included chronic fever, weight loss, malaise, anemia, cervical lymphadenopathy and osteolytic bone lesions. They had no underlying disease causing immunosupression and both were HIV-negative. Skin manifestations occurred frequently in disseminated penicilliosis and abscesses were the most common manifestation in HIV-negative patients whereas umbillicated papules were common in HIV-positive ones. A biopsy from the skin lesions was good specimens for histopathological study and frequently yielded positive culture results. The characteristic histopathological feature is granulomatous inflammation with macrophages containing yeast-like organisms with septa which show a lack of budding. The characteristic mycologic feature of P.marneffei is a thermally dimorphic fungus which produces a mycelial phase colony appearing within 2 days at room temperature (25-30oC) and which produces a bright, purple-red, water-soluble pigment into the surrounding agar. The yeast form grows at 37oC as a whitish colony produced in 4 days and this produces less red pigment compared with the mycelial form. The first case was treated with oral itraconazole intermittently as a result of multiple recurrent episodes until she died of the disease after one year. The second case was treated with amphotercin B intravenously followed by oral itraconazole with a satisfactory result.