Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum.

Recent studies using laboratory clones have demonstrated that several antiretroviral protease inhibitors (PIs) inhibit the growth of Plasmodium falciparum at concentrations that may be of clinical significance, especially during human immunodeficiency virus type 1 (HIV-1) and malaria coinfection. Using clinical isolates, we now demonstrate the in vitro effectiveness of two HIV-1 aspartic PIs, saquinavir (SQV) and ritonavir (RTV), against P. vivax (n = 30) and P. falciparum (n = 20) from populations subjected to high levels of mefloquine and artesunate pressure on the Thailand-Myanmar border. The median 50% inhibitory concentration values of P. vivax to RTV and SQV were 2,233 nM (range, 732 to 7,738 nM) and 4,230 nM (range, 1,326 to 8,452 nM), respectively, both within the therapeutic concentration range commonly found for patients treated with these PIs. RTV was fourfold more effective at inhibiting P. vivax than it was at inhibiting P. falciparum, compared to a twofold difference in SQV sensitivity. An increased P. falciparum mdr1 copy number was present in 33% (3/9) of isolates and that of P. vivax mdr1 was present in 9% of isolates (2/22), but neither was associated with PI sensitivity. The inter-Plasmodium sp. variations in PI sensitivity indicate key differences between P. vivax and P. falciparum. PI-containing antiretroviral regimens may demonstrate prophylactic activity against both vivax and falciparum malaria in HIV-infected patients who reside in areas where multidrug-resistant P. vivax or P. falciparum is found.

Hospital acquired Janthinobacterium lividum septicemia in Srinagarind Hospital.

Nine patients admitted to the intensive care unit, Srinagarind Hospital, who had septicaemia by J. lividum were reported. Seven patients died, one directly of septicaemia, despite intensive antimicrobial therapy. Investigation revealed that the sources of infection were: special mouth wash solution, distilled water and normal saline used in the ward. After changing to uncontaminated solution and more meticulous care of medical equipment, there was no evidence of the micro-organism after one year follow-up.

Multicenter prospective randomized trial comparing ceftazidime plus co-trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole for treatment of severe melioidosis.

A prospective randomized trial was conducted at Srinagarind and Khon Kaen hospitals. Ceftazidime (100 mg/kg of body weight per day) and co-trimoxazole (trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) therapy was compared with conventional therapy (chloramphenicol, 100 mg/kg/day; doxycycline, 4 mg/kg/day; trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) in the treatment of 64 patients with bacteriologically confirmed cases of severe melioidosis who were admitted during September 1986 to January 1989. Of 61 evaluable patients (3 were excluded because of severe drug allergies), 42 were septicemic, and 31 of these patients had the most severe form, disseminated septicemic melioidosis. Their cumulative mortalities on day 7 were compared. There were significantly lower overall mortalities from melioidosis, septicemic melioidosis, and disseminated septicemic melioidosis in the group receiving the new treatment compared with those in the group receiving the conventional treatment (47 versus 18.5% [P = 0.039], 57.7 versus 25% [P = 0.039], and 82.3 versus 30.7% [P = 0.006], respectively); but the differences could have been influenced by the greater severity of illness, e.g., shock at initial presentation, in the patients who received the conventional treatment. Among patients with disseminated septicemia and initial shock, there was no significant difference in mortality between the regimens. Both regimens effectively eradicated bacteria from the circulation within 24 h (97 versus 96%, respectively). We recommend ceftazidime and co-trimoxazole as the drugs of choice for treatment of severe melioidosis, especially in those patients with disseminated septicemia.

Intervention of inappropriate antibiotic use at a university teaching hospital.

The magnitude of inappropriate antibiotic use is high (52.3%). In the empiric treatment group, 41.1 per cent were inappropriate, mostly due to no indication of use. In the surgical prophylaxis, 79.7 per cent were inappropriate, mostly due to delayed prophylaxis and length more than 3 days. In documented infection, 40.2 per cent were inappropriate, mostly due to wrong choice and too many drugs. Intervention by education decreased the overall inappropriate use, empiric inappropriate use and prophylactic use, while there was no change in inappropriate documented infection use and inappropriate economic use. We propose further interventions by other strategies, repeated education and a wider scale of intervention.

Rhinocerebral mucormycosis: a report of eleven cases.

Rhinocerebral mucormycosis (RCM) is a rare, fulminant fungal infection that usually occurs in diabetic or immunocompromised patients. The mortality rate has been reduced recently with the advent of amphotericin B combined with aggressive surgery. Eleven RCM patients have been treated over the past five years at Srinagarind Hospital. Eight had underlying diabetes, five had renal failure and three of them had both. In eight patients, the diagnosis was established by KOH preparation before histological confirmation. Only two cases revealed positive cultures for Rhizopus spp and Cunninghamella spp. All patients underwent surgical treatments (extensive debridement, 8 cases; sphenoidectomy, 7 cases; ethmoidectomy 8 cases; maxillectomy 5 cases and orbital exenteration, 6 cases). Amphotericin B was administered to all patients as soon as the diagnosis of RCM was made. Only three patients survived. Early diagnosis and cooperation among ophthalmologist, otolaryngologist and physician are the most important factors for the survival of patients with mucormycosis.

Discriminant analysis among septicemic melioidosis and other bacterial septicemia.

The clinical manifestations of septicemic melioidosis and other bacterial septicemia were studied at Srinagarind Hospital, Khon Kaen University. Forty-three cases of septicemic melioidosis and 68 non-melioidosis septicemia cases were analysed. By univariate analysis, the following clinical features are associated with septicemic melioidosis: male patients; age below 45 years; underlying diabetes mellitus or renal failure; pulmonary infection, impending respiratory failure and multiorgan involvement, while abdominal pain and urinary tract infection were more common in non-melioidosis septicemia. By using discriminant analysis and logistic regression, 3 features (diabetes mellitus, multiorgan involvement, and no abdominal pain or pulmonary infection) could discriminate the two groups with the accuracy of more than 85 per cent.

Neurogenic pulmonary edema associated with meningitis.

A 17-year-old man presented with acute febrile, obtundation, nuchal rigidity and CSF pleocytosis with polymorphonuclear cell predominate. He developed acute pulmonary edema which could not be explained by other mechanisms. Meningitis appears to be another cause of neurogenic pulmonary edema.

Community-acquired pneumonia in adults at Srinagarind Hospital.

A prospective study of community-acquired pneumonia in adults at Srinagarind Hospital, Khon kaen University was conducted from September 1987 to August 1988. Laboratory specimens were tested for bacterial and mycoplasmal culture, CIE for pneumococcal antigen and serological data for mycoplasma and P. pseudomallei. The results supported by clinical data were evaluated. We could identify the pathogens from 62 of 113 cases (55%). P. pseudomallei was the most frequent etiologic agent (32%) and S. pneumoniae was the second (27%). Overall mortality was 21 per cent and it was high in cases with bacteremia and pneumonia due to P. pseudomallei. Sixty-six per cent of the patients had associated diseases. Diabetes mellitus, chronic renal failure and renal calculi were commonly found in patients with pneumonia due to P. pseudomallei. The results of this study showed the relatively high prevalence of P. pseudomallei pneumonia in our region which was different from other reports.

Enzyme-linked immunosorbent assay for immunoglobulin M specific antibody for the diagnosis of melioidosis.

Indirect hemagglutination (IHA) is commonly used for serodiagnosis of melioidosis. However, in endemic areas, high background titers in normal populations and occasional low titers in patients with septicemic melioidosis prompted a search for a more sensitive and more specific method of serodiagnosis. An indirect fluorescent-antibody test for immunoglobulin M (IgM) specific antibody to Pseudomonas pseudomallei was more sensitive and more specific, but fluorescence microscopes are rarely available in the endemic areas. An enzyme-linked immunosorbent assay (ELISA) for IgM antibody is an attractive alternative. An indirect ELISA for IgM antibody (IgM ELISA) and an IgM antibody capture ELISA for melioidosis were developed. Both tests, together with IHA, were evaluated for 153 serum specimens from blood donors and 16 serum specimens from 16 melioidosis patients. It was found that IHA, the IgM ELISA, and the IgM antibody capture ELISA had sensitivities of 88, 88, and 75%, respectively, with specificities of 97.4, 92.2, and 91.5%, respectively. When IHA was combined with IgM ELISA, a sensitivity of 100% and a specificity of 95.4% were obtained. The IgM ELISA and IHA should be used in combination for serodiagnosis of melioidosis.

Antibiotic use at a university hospital. Antibiotic Working Group of Srinagarind Hospital.

A prospective survey of antibiotic use in 5 departments (MED, SURG, OB-GYN, PED, ORTHO) in Srinagarind Hospital was done during May 1988. The majority of prescribers were interns and residents, except in the department of OB-GYN. Out of 400 prescriptions, 52.3 per cent were inappropriate and 5 per cent were inappropriate for economic reasons. For empirical use, the inappropriateness was 42.3 per cent mostly due to no indication of use. For surgical prophylaxis, 82.4 per cent were inappropriate mostly due to delayed prophylaxis and excessive length of treatment of more than 72 hours. For the treatment of documented infection, 39.6 per cent were inappropriate, mostly due to wrong choice and too many drugs used. There were no statistical differences in mortality, total hospital stay, hospital stay after treatment between the appropriate and inappropriate use.