[Community acquired acute bacterial meningitis--a 10 year review]. / Meningite bacteriene comunitare: analiza pe 10 ani.

UNLABELLED: Bacterial meningitis is still an important topic for the infectious diseases specialist, due to it's high incidence, severity and it's high mortality rate. MATERIAL AND METHOD: We retrospectively studied 679 patients diagnosed with community acquired bacterial meningitis in the Infectious Diseases Hospital Iasi, Romania between 1998 and 2007. RESULTS: The annual number of admissions slightly decreased in the last years. Most patients were males (62.1%). Predisposing factors were present in 34.9% of cases. Seizures were described in 19.6% of cases, more frequent in children. The CSF was purulent only in 69.4% of patients, 29.6% of them receiving antibiotics prior to admission; the albumin level in the CSF of pneumococcal meningitis was higher than in other meningitis. The etiology was established in 51.6% of cases, more frequent in sucklings (68.1%). N. meningitidis was the most common cause of community acquired acute bacterial meningitis (CABM) (28.5%) followed by S. pneumoniae (14%). S. pneumoniae was susceptible to penicillin in 79% of cases. The mean mortality rate was 13.1%. CONCLUSION: Factors associated with a poor prognosis were: pneumococcal etiology, age over 60, and the presence of seizures or coma at admission.

[Antimicrobial resistance profile of E. coli and Klebsiella spp. from urine in the Infectious Diseases Hospital Iasi]. / Profilul de rezistenta al E. coli si Klebsiella spp. din infectii urinare in Spitalul de Boli Infectioase Iasi.

UNLABELLED: The increasing frequency of extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae among nosocomial and community-acquired infections is an important problem for both microbiologists and clinicians, because of the difficulty in correctly detecting, reporting and treating such infections. RESULTS: In the Clinical Hospital of Infectious Diseases Iasi the most frequent etiological agents of urinary tract infections were: E. coli - 64%, Klebsiella spp. 11% and Enterococcus spp - 5%. The resistance rate of E. coli and Klebsiella spp. was 41% and 60%, respectively to amoxicillin-clavulanic acid, 29.6% and 72.5%, respectively to third generation cephalosporins, 26% and 24%, respectively to ciprofloxacin. The most active antimicrobial agents against cephalosporins resistant strains of E. coli and Klebsiella spp were carbapenems (susceptibility rate 99% and 94%, respectively) and colimycin (susceptibility rate 89% and 83%, respectively).

[Clinical and biological study of acute diarrhea with mixed etiology in 48 patients]. / Studiu clinico-biologic al diareei acute cu etiologie mixta pe un lot de 48 pacienti.

OBJECTIVES: The study of incidence, clinical manifestation and treatment of acute diarrhea with mixed etiology. MATERIAL AND METHOD: Study of 48 patients with acute diarrhea with mixed etiology admitted in the Hospital of Infectious Diseases of Iasi during 1995-1998. RESULTS: 12 cases (24%) were mixed bacterial infections with the following microorganisms associations: Salmonella + Shigella (10 cazuri); Salmonella + Yersinia enterocolitica (1 case); Salmonella + Rotavirus (1 case). 16 cases (44%) had mixed digestive infections with parasites, in double or triple associations: Giardia intestinalis + Ascaris lumbricoides (10 cases); Giardia intestinalis + Ascaris lumbricoides + Entamoeba coli (1 case); Giardia intestinalis + Enterobius vermicularis (3 cases); Ascaris lumbricoides + Trichiuris trichiura (2 cases). The rest of 20 cases presented mixed infections with bacteria and parasites: Salmonella + Rotavirus + Giardia (2 cases), Salmonella + Shigella + Giardia intestinalis or Ascaris lumbricoides (6 cases), Salmonella + Giardia intestinalis (8 cases); Salmonella + Entamoeba coli (3 cases); Shigella + Trichiura trichiuris + Entamoeba coli (1 case). The majority was male patients from rural areas with age between 5 month and 56 years, the majority being children, 4 cases were found in immunosupressed patients. The clinical symptomatology was dominated by diarrheal syndrome (100%) and the diagnosis was established by clinical characters and confirmed by coproculture and parasitologic exam. The ethiological therapy was guided by antibiogram, in the majority of cases we used fluorochinolones (associated with ceftriaxone in severe cases), together with antiparasitic medications. CONCLUSIONS: In this study predominated the bacterial and parasitic infections, most frequently being isolated Salmonella, Shigella and Giardia intestinalis; the therapy associated fluorochinolones with antiparasitic medication.

Spinal epidural abscess.

In a retrospective study, 68 patients with Spinal Epidural Abscess (SEA) were reviewed. Of these, 66% had different predisposing factors such as staphylococcal skin infections, surgical procedures, rachicentesis, trauma, spondilodiscitis. Abscess had a lumbar region location in 53% of cases. Staphylococcus aureus was the most frequent etiological agent (81%). The overall rate of mortality in SEA patients was 13.2%.

Pharmacokinetic-pharmacodynamic relationships between pirarubicin exposure and hematotoxicity: clinical application using only one blood sample.

The objective of the present study was to evaluate the relationship between the pharmacokinetic parameters of pirarubicin and of its metabolite doxorubicin measured in plasma and whole blood, and the hematologic toxicity of this drug, in order to evaluate the predictability of changes in white blood cells (WBC) by single measurement of drug concentrations. This pharmacokinetic-pharmacodynamic relationship was studied in a total of 45 patients with different tumor types treated by combined chemotherapy containing pirarubicin, administered as short infusion (10+/-2 min) at doses ranging from 50 to 90 mg. In 45 courses performed in 24 patients, we established the relationship between the half-product of pirarubicin level in whole blood at the end of the infusion and the duration of this infusion, which represents an estimate of the area under the time x concentration curve (AUC(PIRA,wb,ei) = C(PIRA,wb,ei) x duration of infusion/2), the age of the patients and the relative fall in WBC counts. These results allowed us to establish a predictive formula in order to anticipate the number of WBC that the patient will obtain about 12 days after treatment, at the nadir of the counting. WBCnadir = 0.032404 x Age + 2.005 + WBCinitial x e(-0.009316 x AUC(PIRA,wb,ei) + 4.202265), WBC being expressed as x 10(3) cells/microl and AUC(PIRA,wb,ei) in ng/ml x h. In a second step, the validation of the prediction was carried out in 43 courses from 21 patients treated in the same conditions, for which WBC(predicted nadir) was compared by linear regression to WBCcounted. We obtained a highly significant correlation: r = 0.656; p<0.0001). Therefore, we show in this paper that the hematological toxicity, especially the WBC nadir count, can be predicted from single-sample blood HPLC analysis. This rapid and easy prediction of leukopenia can help the clinician in anticipating important hematological toxicities and in deciding to start early prophylactic treatment with hematopoietic growth factors.

[Chemical stability of pirarubicin in its use for continuous infusion]. / Stabilité chimique de la pirarubicine en vue de son utilisation en perfusion continue.

The aim of this study was to examine the chemical stability of pirarubicin in conditions close to ambulatory continuous infusions (infusor). The analyses were performed using an HPLC method in two infusion fluids (G5% and water), in different conditions of conservation (light and obscurity) and at different temperatures (+35 degrees C and +4 degrees C). The results demonstrated that light did not increase the chemical degradation of pirarubicin in doxorubicin which occurred more rapidly in G5% than in water. On the other hand, the temperature was a comparably major influence (> than 80% of deterioration in 7 days). In conclusion, the use of pirarubicin in continuous infusion (5 days infusors) is currently impossible without leading to a fast and important outcome of doxorubicin, which present different therapeutic activity and different toxicity.

A limited sampling strategy for the study of pirarubicin pharmacokinetics in humans.

Pirarubicin (4'-O-tetrahydropyranyldoxorubicin, THP-Adriamycin) is a new anthracycline antibiotic that has recently been developed because its reduced cardiac toxicity is associated with an antitumour efficacy similar to that of doxorubicin. Pirarubicin is characterised by strong haematological toxicity, which has been shown to be correlated with pharmacokinetic parameters, especially the area under the time-concentration curve. To obtain routine pharmacokinetic evaluations of pirarubicin for dose monitoring we developed a limited sampling strategy relying on three blood samples taken at the end of the infusion and at 12 and 24 h post-infusion. The characteristics of interindividual variability were assessed on the first courses of treatment performed in 18 patients; the model was then validated on 10 independent first courses of treatment performed in 10 other patients. The main pharmacokinetic parameters (half-lives, total volume of distribution, total plasma clearance) were estimated in the test group by maximum-likelihood estimation using all samples and by Bayesian estimation using three samples. The concordance between the two estimates was correct (the bias and precision for clearance were 2.3% and 12.1%, respectively), which shows that this limited sampling strategy can be used in routine drug monitoring.

Pharmacokinetics and metabolism of pirarubicin in humans: correlation with pharmacodynamics.

The pharmacokinetic monitoring of anthracycline-containing regimens is warranted because of the important toxicity of these drugs and because pharmacokinetic-pharmacodynamic relationships have been clearly established. We studied the pharmacokinetics of the new anthracycline pirarubicin in 80 courses of treatment performed in 27 patients, using a limited sampling protocol we had previously validated. We observed (for 47 of these courses) a significant correlation between the leucocyte cell kill and the pirarubicin area under the time x concentration curve, but the most significant correlation was obtained using the plasma concentration of doxorubicin, a metabolite of pirarubicin, at the end of the infusion. On the basis of this value, it is possible to predict for pirarubicin haematological toxicity in a way that can help the clinician in identifying patients at risk for toxicity.

New data on the pharmacokinetics of adriamycin and its major metabolite, adriamycinol.

Twenty-two days after administration by intravenous bolus, of 50 mg of adriamycin to several patients we found concentrations of adriamycin and adriamycinol of the order of 100 pcg/ml. In theory, however, with a terminal half-life of 30 h, the plasma levels of adriamycin and adriamycinol should be close to 0.1 pcg/ml. Further pharmacokinetic investigation was therefore necessary. We have retained for this study nine male patients, aged between 53 and 69 years who received 25 to 50 mg of adriamycin by slow intravenous injection. The HPLC method permitted the detection of 50 pcg/ml of adriamycin and adriamycinol, with the possibility of monitoring their elimination during 120 h (and in one case during 160 h). The terminal half-lives of elimination estimated in 8 patients were respectively 110 +/- 52 h for adriamycin and 92 h 50 min +/- 43 h for adriamycinol. Surface ratios under adriamycinol curves against calculated adriamycin was 1.10 +/- 0.26. Plasma levels found during the To in certain patients correspond to the end of the drug elimination of the previous treatment. It is difficult with a half-life to 110 h to predict the effects of residual concentrations of adriamycin and adriamycinol.