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Biomedical subjects

N Aswapokee

Publications and source records attributed to N Aswapokee.

At least 19 recordsLinked to original sources

The failure of a preprinted order form to alter physicians' antimicrobial prescribing pattern.

Use of antimicrobial agents is highly effective in reduction of morbidity and mortality due to infectious disease. There is, however, evidence that the use of such agents is frequently inappropriate worldwide. Several methods were tried to rationalize the use, and, among these, the preprinted order form (P.O.F.) offered the simplest and most efficient way. We studied the use of the P.O.F. in Siriraj Hospital, Bangkok Thailand, where there was overuse of antimicrobial agents using a historical-controlled intervention study. In period I (no P.O.F.), the antimicrobial overuse was 35 per cent, and this was not reduced by using the P.O.F. in period II (32%), which was one year apart. There was no difference in overuse after adjustment for differences in base-line characteristics which were thought to affect antimicrobial prescriptions i.e. physicians' workload, physicians' knowledge and the method of diagnosis of infectious disease. Reasons for failure of the P.O.F. in unclear. Misdiagnosis was unlikely since the correct diagnosis as revised by attending physicians and specialists was as high as 83 per cent. The fear of malpractice suits was also not the reason because defensive medicine is not a problem in Thailand. The nature of the diseases, which lower the threshold to treat, the clinical immaturity and other unknown factors were thought to play a part in deviation from responsibility to perform according to written-justification.

Adult

In vitro antimicrobial activity of cefodizime, a third generation cephalosporin.

Cefodizime is one of the new broad-spectrum cephalosporins. It is an aminothiazolyl iminomethoxy cephalosporin which is metabolically stable and has a prolonged serum half life. Cefodizime was primarily active against gram-negative bacilli and at the concentration of 0.5 mg/L, it inhibited 90 per cent of Enterobacteriaceae. P. mirabilis was the most susceptible species tested (MIC90 of 0.02 mg/L). E.coli, K.pneumoniae, Salmonella spp., Shigella spp. and M. morganii were also very sensitive to cefodizime, with the MIC90 of 0.25-0.5 mg/L. Cefodizime, however, was not active against most gram-negative bacilli possessing Type I beta-lactamases of Richmond and Sykes, namely, Enterobacter spp., P. aeruginosa and A. anitratus (MIC90 of > 128 mg/L). Among gram-positive bacteria, only S.pyogenes was highly susceptible (MIC90 of 0.05 mg/L), while S. aureus (methicillin-sensitive) was moderately susceptible and Enterococcus spp. was resistant. Cefodizime appeared to be bactericidal and was not affected by serum. High inoculum (10(7) cfu/ml) of K.pneumoniae and Enterobacter spp. resulted in increase of the MIC of cefodizime. This study shows that local bacterial isolates in a university hospital in Bangkok, Thailand were not different in susceptibility pattern from those reported in developed countries. The in vitro activity of cefodizime as a third generation cephalosporin, with its good pharmacokinetic property, and the property of the agent as a biological response modifier, should prove that this is a promising new agent in treating serious infections especially in immunosuppressed hosts.

Cefotaxime

Leukocyte and neutrophil counts in differential diagnosis of acute febrile conditions.

Leukocyte and neutrophil counts are two of the commonest laboratory tests used in clinical medicine. The usefulness of the tests is still controversial. It has been found that the tests were useful to a limited extent. We performed leukocyte and neutrophil counts in patients manifesting acute febrile illness, to identify the best cut-off point in differential diagnosis of underlying disorders causing such conditions. Patients were enrolled randomly on the basis of acute febrile illness. Those who suffered from diseases affecting myeloproliferative system were excluded. Leukocyte and neutrophil counts were performed by the standard method. Diagnosis of target organ disorder was obtained from the house staff's final diagnosis. Both laboratory and clinical performance were assessed in double blind fashion. Patients were divided into 2 groups. Group 1 consisted of 47 patients with acute bacterial infections and group 2 consisted of 53 cases with acute febrile conditions caused by diverse, non-bacterial disease. Various cut off points ranging from 5,000-25,000/mm3 and 10-100 per cent were used for leukocyte and neutrophil counts. Sensitivity, specificity and Youden index for each cut off point were determined. Receiver operating characteristic (ROC) curves were constructed. It was found that sensitivity and specificity for each cut off point for both leukocyte and neutrophil counts displayed perfect trade-offs and the Youden indices were similar. The ROC curves for both counts were depicted as a 45-degree lines of non-discrimination. Leukocyte and neutrophil counts were proved to be non-discriminate of acute febrile conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Survival of Pseudomonas pseudomallei in human phagocytes.

Pseudomonas pseudomallei causes the disease melioidosis, with protean manifestations, protracted clinical course and unpredictable response to antimicrobial treatment. Intracellular location of the organism is suspected to be the cause of these properties. This study was undertaken to examine the intracellular growth of this bacterium. Intracellular growth and survival was assessed at different time intervals, by Gram's stain and electronmicroscopic examination. During the first 5 h, the numbers of P. pseudomallei within phagocytes did not change significantly. By 18-21 h, gram-stained preparations revealed that P. pseudomallei cells completely filled the phagocytes and electronmicroscopy showed evidence of binary fission. During that time the number of cfu of P. pseudomallei growing simultaneously in vitro increased by log10 2-3. The phagocytes remained viable throughout the observation period and retained their capacity to produce an oxidative burst for the first hour of incubation. The ability of P. pseudomallei to survive and multiply in phagocytes shows that it is a facultative intracellular bacterium. This finding is relevant to the selection of antimicrobial regimens, and the management of the disease.

Colony Count, Microbial

Ciprofloxacin in severe infections.

Ciprofloxacin is the most potent post-marketing fluoroquinolone. In vitro activity and pharmacokinetic properties of this agent, together with clinical trials of the drug may be very promising in the treatment of severe infections, especially when the bacteria involved are resistant to other conventional agents. We performed an open clinical trial of this agent in hospitalized patients with severe infections in a university hospital in Bangkok, Thailand. A total of 25 patients were enrolled on the basis of clinical diagnosis of severe bacterial infections. Six of these patients were dropouts (3 of which proved to be non-bacterial infections, 2 patients each had only anaerobic infection and nocardiosis. One suffered from a severe psychotic attack). The remaining 19 patients were evaluated. There were 12 males and 7 females, the age ranged from 13 to 77 years old (43.2 +/- 20.1). Most had severe underlying illnesses (17 out of 19). There were 23 infections in 19 patients. Septicemia was the most common infection treated. Other infections included complicated urinary infection, upper respiratory tract infection, skin/skin structure infection. P. aeruginosa was the most common pathogen infected. Other organisms were E.coli, Enterobacter, P.mirabilis, S.aureus, A.antitratus and mycobacterium. Ciprofloxacin was given as an initial 100 mg twice daily as intravenous infusion, and this was switched to an oral form of 500 mg b.i.d./at approximately day 4 to day 6. The overall cure rate was 68 per cent. There were 2 improvements, 2 relapses/reinfections and one failure. Toxic effect included one psychotic attack necessitating discontinuation of the drug. Other adverse drug reactions were mild and transient. These included elevation of transaminase and LDH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

In vitro activities of antimicrobial combination against Pseudomonas pseudomallei.

P pseudomallei infection was treated empirically with an antimicrobial combination without hard evidence of a more favorable outcome over single drug regimens. The so-called "conventional' agents, namely kanamycin (K), chloramphenicol (C), doxycycline (D) and sulfamethoxazole/trimethoprim (SMZ/TMP) are often combined. We determined the effects of the combination of these agents by standard time-kill curve. Six combinations were tested, i.e. K and C, K and D, K and SMZ/TMP, C and D, C and SMZ/TMP, and lastly, D and SMZ/TMP. Three recent clinical isolates of P. pseudomallei were used. The antimicrobial concentration in the combination selected was one-fourth of the minimal inhibiting concentration (MIC). Colony counts were performed at times 0, 2, 4, 6 and 24 hours. The results were interpreted using standard definition, as synergistic, additive and antagonistic effects. It was found that at time 0 to 6 hours, all of the combinations only acted additively. At 24 hours, however, there were 3 effects observed. These were (1) synergistic effects for K and D, and C and D; (2) additive effect for K and C, K and SMZ/TMP, and D and SMZ/TMP; and (3) antagonistic effect for C and SMZ/TMP. None of the combinations showed rapid killing rates. The results, although subjected to precautious extrapolation of in vitro to in vivo situations, suggested that the combined regimens of "conventional' drugs often acted additively, and none of these combinations offered fast killing.

Anti-Bacterial Agents

Viral infections in beta-thalassemia/hemoglobin E patients.

One hundred ten patients with beta-thal/Hb E disease and 60 normal controls matched for age and socioeconomic status were followed for 1.5 years. They were examined clinically, and blood and plasma were studied for Coxsackie B viruses and others. The findings suggest that the patients are more susceptible to Coxsackie B virus but not to rubella, herpes simplex, cytomegalovirus, adenovirus, and M. pneumoniae. In contrast to bacterial infections, splenectomized patients did not show evidence of increased viral infections.

Antibodies, Viral

HR 756, a new cephalosporin active against gram-positive and gram-negative aerobic and anaerobic bacteria.

The in vitro activity of HR 756, 7-[2-(2-amino-4-thiazolyl)-2-(Z)-(methoximino)acetamido] cephalosporanic acid, was investigated against 659 isolates. HR 756 inhibited Neisseria and Haemophilus species at concentrations similar to those needed with ampicillin. It inhibited beta-lactamase-producing N. gonorrhoeae and H. influenzae. HR 756 was the most active compound tested against members of the Enterobacteriaceae, inhibiting most isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella, Enterobacter, and Shigella at concentrations of less than 0.1 mug/ml. It was twice as active as carbenicillin against Pseudomonas aeruginosa and inhibited Bacteroides fragilis as well as cefoxitin. HR 756 killed E. coli, Staphylococcus aureus, and P. aeruginosa at rates similar to other beta-lactam antibiotics.

Aerobiosis

In vitro activity and beta-lactamase stability of cefazaflur compared with those of beta-lactamase-stable cephalosporins.

The in vitro activity of cefazaflur, a parenteral cephalosporin, was determined against 590 clinical isolates. Cefazaflur inhibited the majority of gram-positive cocci at concentrations below 1 mug/ml except for enterococci. The agent was as active as cefamandole or cefoxitin against most Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Although it inhibited a number of strains of Enterobacter, indole-positive Proteus, and Serratia resistant to cephalothin, it was much less active against these organisms than were cefamandole or cefoxitin.

Bacteria

Antibacterial activity of a new 1-oxa cephalosporin compared with that of other beta-lactam compounds.

The in vitro activity of (6R,7R)-7-{[carboxy(4-hydroxyphenyl)acetyl]amino}-7-methoxy-3-[[(1-methyl -1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-oxa-1-azabicyclo-[4.2.0]oct-2-ene -2-carboxylic acid was tested against isolates of gram-positive and negative bacteria and compared with those of cephalothin, cefuroxime, cefamandole, cefoxitin, cefotaxime, and carbenicillin. The compound was less active than the other compounds when tested against Staphylococcus aureus and Staphylococcus epidermidis. It had equal or slightly less activity than did cefotaxime when tested against members of the Enterobacteriaceae, but was 8- to 32-fold more active than the other cephalosporins against the Enterobacteriaceae, inhibiting most isolates at concentrations less than 0.5 mug/ml. The compound was twofold more active than cefotaxime and cefoxitin against Bacteroides, and it was twofold more active than cefotaxime and fourfold more active than carbenicillin against Pseudomonas aeruginosa. In vitro activity did not correlate with either the presence or type of beta-lactamase in either Enterobacteriaceae or Pseudomonas. The compound showed minimal synergy when combined with aminoglycosides or carbenicillin.

Bacteria

Comparative activity and beta-lactamase stability of cefoperazone, a piperazine cephalosporin.

The in vitro activity and beta-lactamase stability of 7-[d(-)-alpha-(4-ethyl-2,3-dioxopiperazino-carbonylamino) -p-hydroxyphenylacetamido]-3-[(1-methyl)-5-tetrazolylthiomethyl] -Delta(3)-cephem-4-carboxylic acid (cefoperazone), a cephalosporin analog of piperacillin, were compared with the activities and stabilities of other cephalosporins and cephamycins. The compound was less active than cephalothin or cefamandole in inhibiting Staphylococcus aureus; it was as active as cefamandole and cefoxitin against most of the Enterobacteriaceae but less active than cefotaxime. It was more active than carbenicillin or piperacillin against Pseudomonas aeruginosa. In general, the compound was not active against Bacteroides. It was hydrolyzed by the beta-lactamases of some Escherichia coli which hydrolyzed cefamandole, but was stable to most plasmid-mediated, chromosomally mediated, inducible beta-lactamases in the Enterobacteriaceae and Pseudomonas.

Bacteria

Diffusion disk susceptibility testing with cefotaxime.

The diffusion disk susceptibility of Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa to cefotaxime was determined. A 30-mug disk provided data for the susceptibility of P. aeruginosa, but yielded extremely large zones of inhibition against Enterobacteriaceae. A 5-mug disk seemed to provide the most useful susceptibility data for S. aureus and Enterobacteriaceae.

Cephalosporins

In vitro activity and beta-lactamase stability of BL-S786 compared with those of other cephalosporins.

In vitro activity of BL-S786, a new parenterally semisynthetic cephalosporin, was investigated against 570 bacterial isolates. BL-S786 inhibited most Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella. It inhibited some Enterobacter and indole-positive Proteus, but it was less active against these later species than was cefamandole, cefuroxime, or cefoxitin. It was not active against Serratia marcescens, Pseudomonas aeruginosa, or Bacteroides fragilis. BL-S786 was the least active new cephalosporin tested against staphylococci and was less active than cephalothin against streptococcal species. The activity of BL-S786 was not altered by the type of assay medium nor by 50% serum. The size of the test inoculum altered the minimal inhibitory and bactericidal concentrations for inhibition of some organisms, particularly those with Richmond type I beta-lactamases. BL-S786 was not hydrolyzed by the R-factor-mediated, Richmond type III beta-lactamase, but it was hydrolyzed by type I beta-lactamases.

Amidohydrolases

A sulfone beta-lactam compound which acts as a beta-lactamase inhibitor.

CP-45,899 [3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3,2,0)heptane-2-carboxylic acid, 4,4-dioxide [2S-(2alpha,5alpha)]] has low intrinsic activity against most Gram-positive cocci, Enterobacteriaceae and Pseudomonas. It inhibits Neisseria at concentrations of 0.1 approximately 6.2 microgram/ml. The combination of CP-45,899 and ampicillin inhibited Staphylococcus aureus and Enterobacteriaceae resistant to ampicillin by virtue of beta-lactamase activity. Combination of CP-45,899 and cephalothin was synergistic less often, and CP-45,899 did not act synergistically with carbenicillin or ticarcillin against Pseudomonas resistant to these agents. CP-45,899 acted synergistically with ampicillin against Bacteroides. Synergy of CP-45,899 and ampicillin was demonstrated at varying concentrations suggesting that it may significantly enlarge the antibacterial activity of ampicillin against resistant bacteria.

Anti-Bacterial Agents

Disseminated strongyloidiasis: report of seven cases.

Disseminated strongyloidiasis with associated infection from various organisms in 7 cases on corticosteroid therapy are reported. Either respiratory or abdominal symptoms or both without other obvious etiological factors are its usual clinical manifestations. The highly motile filariform larvae of Strongyloides stercoralis were demonstrated in sputum, gastric content, peritoneal fluid as well as in stool. Associated infection from various organisms were found in 6 cases and it is believed that these contributed to immediate cause of death since disseminated strongyloidiasis had been eradicated before death. Only one case survived. Thiabendazole therapy in conventional dosage is adequate in eradicating disseminated strongyloidiasis.

Adult