[Off-label antibiotic use: malpractice or good clinical practice?]. / La prescrizione off-label di antibiotici: malpractice o buona pratica clinica?

In Italy, off-label drug use has been forbidden since 1998. However, Italian law allows off-label treatment for single cases only if treatment is considered irreplaceable, and completely under physician responsibility. To assess the consequences of such regulations for the infectious diseases specialist, we listed the indications of intravenous and oral antibiotics available in our hospital pharmacy service, and discussed them in a pool of nine infectious diseases specialists. Indications were compared with the recommended treatment of major bacterial syndromes as suggested by the major guidelines and textbooks. We found that standard treatment for several bacterial infections is off-label. The pool of specialists concluded that some off-label use of antibiotics is vital to daily practice in infectious diseases. Scientific societies should promote guidelines as the standard reference for good clinical practice, which should not be based only on the respect of drug labels.

Safety and efficacy of recombinant granulocyte colony-stimulating factor as an adjunctive therapy for Streptococcus pneumoniae meningitis in non-neutropenic adult patients: a pilot study.

Twenty-two non-neutropenic adult patients with Streptococcus pneumoniae meningitis received granulocyte-colony stimulating factor (G-CSF) (300-450 Ig/day subcutaneously for 6 days) in addition to cefotaxime plus dexamethasone (9-12 g/day for 10 days and 16 mg/day for 3 days iv, respectively). Patients recovered without evident sequelae in all cases but one (with bilateral hearing deficit). No adverse event was recorded. Improvement of inflammation indices in the cerebrospinal fluid was rapid. The most rapid improvement was seen in glucose concentration, which returned to normal ranges within 24-48 h of treatment. In this study G-CSF administration appeared to be safe and effective; further controlled clinical trials are justified.

Effect of ursodeoxycholic acid administration in patients with acute viral hepatitis: a pilot study.

BACKGROUND: Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases. AIM: To evaluate the effects of UDCA administration on acute viral hepatitis-related cholestasis and the course of acute viral hepatitis. METHODS: Seventy-nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A-E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals. RESULTS: No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed. CONCLUSIONS: Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness.

H. pylori infection in HIV-positive patients. A serohistological study.

Sixty-seven consecutive patients infected with the human immunodeficiency virus (HIV-1), 72% of which with overt AIDS, were examinated by upper endoscopy due to various indications and evaluated for the prevalence of H. pylori infection. The infection was studied by performing both histological examination of gastric biopsies and serological testing for anti-H. pylori IgG antibodies. The H. pylori prevalence rate was 55% in histology; no significant differences were observed in HIV-infected subjects and those with overt AIDS (52% vs 63%, respectively; P = NS). Positive histological testing appeared to be directly related to the peripheral CD4+ lymphocyte count (minimum rates of 43% were detected in patients with CD4+ < 100 x 10(6)/liter and maximum rates of 78% in patients with CD4+ > 200 x 10(6)/liter, respectively; P < 0.05) and inversely related to the frequency of antibiotic treatments performed over the six months prior to endoscopy. Low CD4+ counts were also apparently associated with low-grade H. pylori infection. Serological testing was positive for anti-H. pylori IgG antibodies in 39% of patients; compared to histology, serology displayed a sensitivity of 57% and a specificity of 81%. The discrepancy between histological and serological positive results for H. pylori was noted to be higher in the more advanced phases of HIV infection. Based upon our results, the serological testing for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positive patients.

Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea.

A prospective, randomized study comparing oral teicoplanin with oral vancomycin in the treatment of pseudomembranous colitis (PMC) and Clostridium difficile-associated diarrhea (CDAD) was performed. Teicoplanin was administered at a dosage of 100 mg twice a day for 10 days, and vancomycin was administered at a dosage of 500 mg four times a day for 10 days. CDAD was diagnosed by demonstrating both C. difficile and cytotoxin in the feces of symptomatic patients (more than three loose stools per day). The diagnosis of PMC was also based on colonoscopy. Cytotoxin assay and cultures were checked in all patients 7 to 10 days after discontinuation of therapy and 25 to 30 days thereafter. Of the 51 patients enrolled, 46 were judged to be assessable. Among these, 26 received teicoplanin and 20 received vancomycin. At enrollment, both groups were comparable in terms of age, sex, occurrence of PMC or CDAD, and previous antibiotic treatment. Eighteen of the 20 patients in the vancomycin group and 10 of the 26 patients in the teicoplanin group had previously undergone surgery (P = 0.0004). Treatment resulted in the clinical cure of 20 (100%) vancomycin and 25 (96.2%) teicoplanin patients (P = 0.56). After discontinuation of therapy, clinical symptoms recurred in four (20%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.21). Posttherapy asymptomatic C. difficile carriage (positive follow-up cultures without any clinical symptoms) occurred in five (25%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.11).Overall, 9 of 20 (45%) vancomycin patients and 5 of 26 (19.2%) teicoplanin patients (P=0.059) appeared not to be cleared of C. difficile after treatment. No adverse effects related to vancomycin or teicoplanin therapy were observed.

Clarithromycin-ciprofloxacin-amikacin for therapy of Mycobacterium avium-Mycobacterium intracellulare bacteremia in patients with AIDS.

A combination of clarithromycin, ciprofloxacin, and amikacin for the treatment of Mycobacterium avium-Mycobacterium intracellulare bacteremia was evaluated in 12 AIDS patients. Mycobacteremia cleared in all patients by 2 to 8 weeks of treatment, and symptoms resolved. Four patients died; all had negative blood cultures until death, and disseminated M. avium-M. intracellulare complex infection was not considered the primary cause of death.

Outbreak of Entamoeba histolytica and Giardia lamblia infections in travellers returning from the tropics.

Of 160 travellers from various regions in Italy who had taken part in a five-day organized trip to Phuket, Thailand, and been accommodated in the same luxury hotel, 17 showed either amebic abscess or colitis. A pretested questionnaire that focused on the consumption of foods and beverages well known to be a source of intestinal infection in endemic areas was available from these 17 patients as well as from 41 out of 74 asymptomatic travellers. Stool samples for parasitological examination were also available. In patients affected with amebic abscess, antibodies to Entamoeba histolytica were also determined. Overall, parasitological examinations were negative in eight (13.8%) patients, and 50 out of 58 (86.2%) were found to be positive. The prevalence of Giardia lamblia and E. histolytica infections was 67.2% and 72.4%, respectively, and 28 subjects (48.3%) were stool-positive for both of these protozoa. No other intestinal parasites were found. No particular food or beverage was consumed by all of the parasitized subjects and by none of the stool-negative individuals. However, the consumption of drinks with ice, ice cream and raw fruit in ice was significantly associated with E. histolytica and/or G. lamblia infections (Fisher's exact test, p ranging from 0.03 to 0.003).

Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery.

A total of 108 volunteers undergoing an elective surgical procedure were randomly given a single 2-g intravenous prophylactic dose of either a cephalosporin or mezlocillin. Stool samples were cultured for Clostridium difficile the day before the operation and later on postoperative days 4, 7, and 14. C. difficile was detected in 23.0% of patients who received a cephalosporin (cefoxitin, 8.3%; cefazolin, 14.3%; cefotetan, 20.0%; ceftriaxone, 25.0%; cefoperazone, 43.7%), in 3.3% of patients given mezlocillin, and in none of 15 control volunteers given no antimicrobial agent. No patient experienced diarrhea.