Efficacy and safety of twice daily administration of cefpirome in the empiric treatment of sepsis.

Cefpirome is a fourth-generation cephalosporin with good activity against both gram-positive and gram-negative bacteria. A multicentre trial was performed to study the efficacy and safety of cefpirome 2 g twice daily in the treatment of sepsis. Sixty-three cases were recruited from 10 hospitals from April 1996 to January 1998. Fifty seven cases could be evaluated according to the protocol. The APACHE II score was used to measure severity of illness, with 46.9 per cent of patients having APACHE II score more than 10 and two patients more than 20; both were cured. The most common pathogens were gram-negative bacteria with E. coli predominating 16/40 (40.0%), followed by Klebsiella 8/40 (20.0%). The overall clinical success rates were 54 out of 57 patients (94.7%). In patients with positive blood culture, the clinical cures were achieved for 20/22 (90.9%). Cefpirome showed good efficacy and safety in the empirical treatment of suspected bacteremia or sepsis.

Empirical antibiotic therapy in febrile neutropenic patients with single-daily dose amikacin plus ceftriaxone.

Hematologic malignancies and cancer patients who become neutropenic as a result of disease or myelosuppressive cytotoxic therapy are at a high risk of developing life-threatening infections, and hence empirical antibiotic therapy is administered promptly. We investigated once daily regimen of amikacin, for dose-dependent bactericidal activity and post-antibiotic effects, plus ceftriaxone, with a long-half life to maximise time-dependent bactericidal activity. Microbiologically proven septicemia were 11 out of 49 febrile episodes (22.5%) and 10 (91%) of these were due to gram-negative bacilli, mostly Enterobacteriaceae. The overall success of the regimen was 63.3 per cent of patients, with no significant toxicity. In conclusion, our findings suggest that once-daily administration of amikacin plus ceftriaxone in the initial treatment of febrile episodes in neutropenic patients produces satisfactory results and more cost-effective compared with other antibiotic regimens requiring 3-4 doses a day.

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.

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.

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)

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)

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.

Persistent bacterial endocarditis caused by three isolates of satellite streptococci.

Three isolates of satellite streptococci were cultivated from the blood of a patient affected persistent bacterial endocarditis. They had distinguishable ultrastructural abnormalities. Their cell wall architecture changed from a fuzzy coat (first isolate) to a thick electron transparent layer covered with a rough fuzzy coat (second isolate), and to electron dense globular material which detached from the wall in small patches (third isolate). The antibiotics probably played an important role in changing their architecture. These three isolates were probably derived from the same strain, since they had common biochemical characteristics and they were isolated from the same patient during the course of his endocarditis.

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.

Disseminated nocardiosis after pulmonary collapse: a case report.

A 24-year-old Thai woman receiving corticosteroid treatment for systemic lupus erythematosus, developed pulmonary nocardiosis after pulmonary collapse. The correct diagnosis was reached when dissemination had occurred which was characterized by two subcutaneous abscesses and acute uveitis of the right eye. Gram stain of sputum and pus revealed delicate, branching, Gram-positive filamentous mycelia which were identified as Nocardia asteroides on culture. Subcutaneous abscesses and exophthalmos disappeared after one week of therapy and she made an uneventful recovery.

Pulmonary nocardiosis in a patient receiving immunosuppressive agent.

A 20-year-old woman receiving corticosteroid treatment for systemic lupus erythematosus developed pulmonary nocardiosis with hydrophneumothorax. The organism identified as Nocardia asteroides resisted to sulfonamide and cotrimoxazole but sensitive to chloramphenicaol and streptomycin in vitro. She seemed to respond to chloramphenicol but subsequently had peritonitis and succumbed later.