Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.

OBJECTIVE: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. MATERIALS AND METHODS: Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. RESULTS: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. CONCLUSION: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.

[Applications of the polymerase chain reaction (PCR) to the diagnosis of central nervous system infections]. / Aplicaciones de la reacción en cadena de polimerasa (PCR) al diagnóstico de infecciones del sistema nervioso central.

The utility of polymerase chain reaction (PCR) is described for the diagnosis in three patients suffering from central nervous system infections, tuberculous meningitis, herpetic encephalitis and cerebral toxoplasmosis. PCR was performed in the cerebrospinal fluid after processing the specimen by two methods, proteinase K digestion and phenol extraction of DNA. Amplification was realized using primers previously described that amplify specific DNA fragments of each microorganisms (insertion sequence IS6110 of Mycobacterium tuberculosis, B1 gene of Toxoplasma gondii, and DNA polymerase gene of Herpes simplex virus). In all three cases, PCR was positive after amplification of the specimen extracted with proteinase K, as well as when a complete DNA extraction with phenol was realized. In all cases a band of amplified products was observed in agarose gels. In conclusion, in all three patients described, PCR would had allowed the diagnosis in seven hours, and PCR should be consider a rapid sensitive and relatively simple method.

Rapid diagnosis of pleural tuberculosis by polymerase chain reaction.

We have investigated the use of polymerase chain reaction (PCR) for the rapid diagnosis of pleural tuberculosis. The study was composed of 21 patients with pleural tuberculosis, confirmed by culture or pleural biopsy, and 86 control subjects. The PCR assay was based on detecting a 123-bp DNA segment belonging to the insertion sequence IS6110, specific of Mycobacterium tuberculosis complex. In 21 patients diagnosed with pleural tuberculosis, Ziehl-Neelsen staining was positive in three (14%) (95% CI, 7 to 21%) and pleural fluid culture in 11 (52%) (95% CI, 43 to 61%). Pleural biopsy revealed granulomas with caseous necrosis in 72%, and the culture was positive in 67% of the patients. Adenosine deaminase activity determination was positive (> 45 IU/L) in 86% (95% CI, 79 to 93%). The sensitivity and specificity for PCR was 81% (95% CI, 74 to 88%) and 100% (95% CI, 95 to 100%), respectively. All culture-positive specimens were PCR positive. We conclude that PCR is a rapid, sensitive, and specific method for the diagnosis of pleural tuberculosis. However, further prospective studies are required to properly evaluate the yield of the technique.

The utility of polymerase chain reaction (PCR) in the diagnosis of pulmonary tuberculosis.

A fragment of DNA of 123 bp belonging to insertion sequence IS6110, specific of Mycobacterium tuberculosis complex, was amplified by polymerase chain reaction (PCR) of respiratory samples, for the diagnosis of pulmonary tuberculosis. A total of 314 samples (286 sputum and 28 bronchoalveolar lavages) from 242 patients were evaluated by PCR, and the results were compared with the those obtained by acid-fast-stained smears, culture, and clinical diagnosis. Mycobacterium tuberculosis was detected by PCR in 102 of 105 patients with clinical diagnosis of pulmonary tuberculosis. All smear and culture-positive samples were PCR positive. The sensitivity of PCR, culture, and staining was 97%, 88%, and 65%, respectively, and the specificity was 100% in all cases. In ten patients with old residual lesions, but no active disease, M tuberculosis genome was detected by PCR. In our experience, PCR proved to be a useful method for the rapid diagnosis of pulmonary tuberculosis.

[Usefulness of IgG and IgM detection against antigen 60 in the diagnosis of thoracic tuberculosis]. / Utilidad de la determinación de IgG e IgM frente al antígeno 60 para el diagnóstico de la tuberculosis torácica.

We conducted a prospective study in order to assess the use of the "ELISA" method (Anda-Tb) for the detection of antibodies IgG and IgM against antigen 60 in mycobacterias for the initial diagnosis of thoracic tuberculosis. 215 serum samples from 44 patients with tuberculosis and 171 control cases were studied. The threshold value for IgG in our environment is 200 U, resulting in a specificity of 98% and a sensitivity of 34%. The IgM test has a low sensitivity, although when combined with the IgG, the sensitivity of the test increases while its specificity is reduced. This method is not useful in patients with HIV infection and immunodepression (AIDS). We have not observed any relationship between the serology and the response to PPD intradermorreaction. We conclude that this method could be used in our environment as a supplementary test, but in any case as a substitute of the traditional microbiological diagnosis.

[Description of a school micro-epidemics of tuberculosis]. / Descripción de una microepidemia escolar de tuberculosis.

BACKGROUND: Despite the progressive decrease in the incidence of tuberculosis, this disease continues to be a problem of Public Health Care, maintaining endemic levels which sporadically allow the appearance of epidemic outbreaks, particularly among the young population. A small outbreak of tuberculosis among COU (high school) students is presented. METHODS: Following the detection of a case of open, cavitary pulmonary tuberculosis, the authors studied 47 students and 12 teachers who were distributed into two groups according to the number of weekly class hours shared with the index case (group A 4 hours and group B 21 hours). RESULTS: The index case began with respiratory symptomatology in the month of September 1990 and was not diagnosed of tuberculosis until January 1991, having shared classes with school mates for 3 months. In April 1991 two patients were diagnosed with pleural tuberculosis and it was at this time that the study was initiated. A prevalence rate of positive tuberculin of 59% was detected among the students of group A and 93% among those of group B, with an incidence of tuberculous disease of 12% and 20% in the two groups respectively. No teachers were found to have the disease and the tuberculin test was heavily influenced by previous BCG vaccination. CONCLUSIONS: Both the prevalence of infection and the incidence of tuberculosis was very high in all two groups. The authors consider that the development of this small outbreak in a school was due to deficiencies in primary health care (low index of suspicion and excessive delay), specialized care (delay in declaration of cases) and epidemiologic departments (deficient study of contacts).

[Empyema due to Moraxella (Branhamella) catarrhalis]. / Empiema por Moraxella (Branhamella) catarrhalis.

We present a case of empyema by Moraxella (Branhamella) catarrhalis in a patient affected by a bronchogenic epidermoid carcinoma. We describe the basic clinical characteristics of the infection by Moraxella (Branhamella) catarrhalis and we confirm the low incidence of empyema by such germ.

Lactobacillus pneumonia in a patient with oesophageal carcinoma.

We report a case of necrotizing pneumonia caused by Lactobacillus secondary to a tracheo-oesophageal fistula created by an oesophageal carcinoma. We emphasize the presence of resistance of Lactobacillus to clindamycin and cotrimoxazole, previously reported to be effective.