Clara Stecca

Amphotericin B as Primary Therapy for Cryptococcosis in Patients with AIDS: Reliability of Relatively High Doses Administered over a Relatively Short Period

Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/[kg.d] for 14 days); 26 patients also received flucytosine (100-150 mg/[kg.d], given either intravenously or orally). Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis. After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned. Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis. Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis. Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five. No deaths due to cryptococcosis were documented during primary therapy. Treatment failed in two cases. During a mean observation period of 10.7 months, three relapses of the underlying infection occurred. Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated.

Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee replacement procedures: study of pharmacokinetics and tissue penetration.

Twenty-four patients undergoing monolateral or bilateral total knee replacement (TKR) procedures were randomized to receive teicoplanin (T) either systemically or regionally. Subjects scheduled for systemic prophylaxis and undergoing monolateral (six patients) or bilateral (five patients) TKR received a single 800-mg dose of T in 100 ml of saline as a 5-min infusion into a forearm vein 2.5 h before surgery. For regional prophylaxis, patients undergoing monolateral surgery (eight subjects) received 400 mg of T in 100 ml of saline as a 5-min infusion into a foot vein of the leg to be operated on immediately after the tourniquet was inflated. For the five patients scheduled for bilateral operation and regional prophylaxis, the administration of T was also repeated for the second knee operation. The tourniquet, as the standard TKR surgical technique, was inflated to 400 mm Hg (c. 50 kPa) in all 24 patients immediately before the beginning of surgery and kept in place for the duration of the operation. Samples of serum, bone, skin, synovia, and subcutaneous tissue were collected at timed intervals during surgery. They were microbiologically assayed for T by using Bacillus subtilis as the test organism. Overall, the mean T concentrations obtained with regional route prophylaxis were found to be 2 to 10 times higher than those achieved following systemic prophylaxis. Moreover, peak levels in different tissues after regional prophylaxis were significantly higher (P < 0.05). None of the patients experienced adverse effects due to regional or systemic T administration; no prosthetic or wound infections were observed in the follow-up period (from 12 to 26 months).

HCV infection after accidental needlestick injury in health-care workers

HBV (1) and HIV (2) infections can be transmitted to healthcare workers after accidental exposure to infected blood. According to recent reports [3,4], in a hospital setting, HCV infection can also occur following the same modalities of transmission. However, the extent of this is still poorly documented. We report the results of an observational study of accidental exposure to infected blood among the health-care personnel in our hospital. From the 1st of October 1989 to the 30th of September 1990, immediate notification was received of 225 risk exposures to infection in 206 subjects among the 2,347 health-care workers (108 needlestick injuries and 117 extensive cutaneous and/or mucous contacts with blood). On notification, all the injured health-care workers were tested for HBV markers (ELISA, Organon Teknika, Belgium) and anti-HIV-1 (ELISA, Organon Teknika, Belgium); 129 out of 225 (57.33%) were also tested for anti-HCV (Ortho HCV ELISA Test System, N. J., USA) and RIBA (Chiron RIBA HCV Test System, CA, USA) confirmed. Two out of 206 (0.97%) and one out of 129 (0.77%) health-care workers were found to be positive for HBsAg or anti-HCV, respectively, according to blood samples drawn at the time of notification (i.e. within a few hours of injury). None of them was found to be positive for HIV-1 or Delta antibodies. The presumed sources of infection were also examined on notification in 166 out of 225 cases. Of these, 19 of 166 (11.44%) were i.v. drug abusers. The pattern of serological markers in the presumed sources of infection is shown in Table 1. Up to March 1991, 117 out of the 206 (56.80%) health-care workers accidentally exposed were followed up for at least six months. Three cases of HCV seroconversion and none of either HBV or HIV-1 have been observed so far. The first seroconversion occurred in an orthopedic surgeon (

Prevalence of anti-HCV and risk factors for hepatitis C virus infection in healthy pregnant women

1) who suffered a needlestick injury from a needle used in an anti-HCV-positive posttransfusional CAH. Five weeks later S1 developed acute hepatitis and 14 weeks later he seroconverted to anti-HCV. The second case occurred in a surgeon (

Postoperative Infections Following Total Knee Replacement: An Epidemiological Study

2) who was injured with a needle used in an anti-HIV-1and anti-HBs-positive i.v. drug abuser [4]. At the time of the accident, the HCV serology status Table 1 : Pattern of serological markers in presumed sources of infections (PSIs) and i.v. drug abusers PSIs (IVDAs-PSIs).

Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

SummaryThe prevalence of anti-HCV antibodies and the risk factors for HCV infection were assessed in 5,672 pregnant women living in North Italy. All reactive sera were confirmed by RIBA-2 test. Anti-HCV positive pregnant women together with an anti-HCV negative control group, were interviewed by standardised questionnaire to identify “known” or “potential” risk factors for HCV infection. The anti-HCV prevalence was 0.7% (40/5,672), higher than that observed among blood donors in the same geographical area (0.2%). The RIBA-2 assay was positive in 60% (24/40) of cases, indeterminate in 10% (4/40) and negative in 30% (12/40). As for “known” risk factors, considering RIBA-2 positivity, intravenous drug use was by far the main risk factor for HCV infection, resulting in a significantly higher risk than in the control group (50% versus 5.9% [O. R. 15.8, CI 5.4–45.5]). The ten RIBA-2 positive women without histories of transfusion or IV drug use had a significantly higher frequency of “sexual contacts with IV drug users” compared to controls (50% vs 4.9% [O. R. 19.0, CI 3.6–94.0]). In conclusion, our study provides evidence that in our geographical area the anti-HCV antibody prevalence is higher in pregnant women than in blood donors and that IV drug use and sexual contacts with IV drug users represent the most important risk factors for HCV infection among young women in North Italy.ZusammenfassungBei 5672 Schwangeren, die in Norditalien leben, wurden anti-HCV Prävalenz und Risikofaktoren für eine HCV-Infektion bestimmt. Alle reaktiven Seren wurden mit dem RIBA-2-Test nachgetestet. Anti-HCV positive Frauen und eine anti-HCV-negative Kontrollgruppe wurden mit einem Standardfragebogen interviewt, um „bekannte“ oder „mögliche“ Risikofaktoren für eine HCV-Infektion zu identifizieren. Die Prävalenz von anti-HCV-Antikörpern lag bei 0,7% (40/5672) und war höher als bei Blutspendern aus derselben Gegend (0,2%). Bei 60% (24/40) war der RIBA-2-Test positiv, bei 10% (4/40) unbestimmt und bei 30% (12/40) negativ. Bezogen auf RIBA-2 positive Fälle fand sich unter den „bekannten“ Riskofaktoren intravenöser Drogengebrauch als Hauptrisikofaktor, wobei das Risiko signifikant höher war als in der Kontrollgruppe (50% versus 5,9%; OR 15,8; CI 5,4–45,4). Die zehn RIBA-2 positiven Frauen ohne Vorgeschichte einer Transfusion oder i.v. Drogenmißbrauchs hatten signifikant häufiger sexuelle „Kontakte mit i.v. Drogenabhängigen“ als Kontrollen (50% gegenüber 4,9%; OR 19,0, CI 3,6–94,0). Aus den Daten ist zu schließen, daß die Prävalenz von anti-HCV-Antikörpern bei schwangeren Frauen höher ist als bei Blutspendern und daß intravenöser Drogengebrauch und sexuelle Kontakte mit intravenös Drogenabhängigen die wichtigsten Risikofaktoren für eine HCV-Infektion bei jungen Frauen in Norditalien sind.

Fibrogenesis serum markers in patients with chronic hepatitis C treated with α-IFN

Abstract From January 1991 to June 1997 217 patients undergoing monolateral or bilateral total knee replacement (TKR) were consecutively enrolled in a prospective study on the incidence of postoperative infections and related risk factors. Regional antimicrobial prophylaxis (teicoplanin 400 mg) was used in 263 (95%) prostheses implanted; in the remaining 14 implants (5%) periopera-tive antibiotic prophylaxis (teicoplanin 800 mg) was administered as usual by systemic route. None of the patients experienced local or systemic adverse effects. Over the 2-year follow-up period, 8 (2.9%) primary site infectious complications were recorded, i.e. 4 superficial infections, which were cured without involvement of the prostheses, and 4 deep infections, which required prosthesis removal. Six infections occurred in patients who had undergone previous surgery of the same knee joint, and 2 in patients undergoing primary TKR (p=0.0005); diabetic patients had infections (13%) more frequently than non-diabetic patients (1.9%, p=0.01). Staphylococci were the leading organisms isolated from infections; however 3 strains of Escherichia coli were isolated from patients who had undergone a previous prosthesis implantation at the same knee joint. Regional administration of teicoplanin appears to be a safe and valuable prophylactic technique; however, in patients at risk of infection a prophylactic regimen which is also active against Gram-negative bacteria should probably be considered.

HGV/GBV-C in liver tissue and in sera from patients with chronic hepatitis C

BackgroundMany case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively.ObjectivesTo evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis.MethodsThe clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed.ResultsHyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 %) and 10/45 (22.2%), respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05).ConclusionsHyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

Alcohol is an important co-factor for both steatosis and fibrosis in Northern Italian patients with chronic hepatitis C

Abstract: The correlation between therapeutic response and liver fibrogenesis was studied in serum and liver specimens taken from 31 patients treated with α-interferon (IFN) (14 sustained responders and 17 non-responders) for chronic hepatitis C. Serum samples, collected before therapy, and at further 6-month intervals over 2 years, were tested for markers of liver neofibrogenesis. Serum N-terminal procollagen III peptide (PIIINP) displayed a significant and persistent decrease (P < 0.05) in sustained responders but not in non-responders; significantly lowered (P < 0.05) mean levels of C-terminal procollagen I peptide (PICP) were transiently observed in both patient groups, apparently as a result of IFN administration. Serum laminin (Lam) levels remained unchanged. One year after the cessation of treatment, liver biopsy re-testing showed an improvement in necro-inflammatory scores only in sustained responders, with the histological fibrosis scores remaining unaltered in both groups. IFN treatment seemed to exert an influence on serum levels of markers of hepatic connective tissue turnover even in patients that did not respond to therapy, while no effect was observed on preexistent liver fibrosis.

ACUTE PANCREATITIS ASSOCIATED WITH THE ADMINISTRATION OF MEGLUMINE ANTIMONATE FOR THE TREATMENT OF VISCERAL LEISHMANIASIS

SummaryForty-eight persons (M=45, F=3; age range=20–53, mean=32.2) affected with chronic hepatitis C were tested for HGV/GBV-C RNA and HCV-RNA by nested PCR and DEIA in serum and in liver specimens to evaluate the prevalence and the impact of HGV/GBV-C coinfection in patients with chronic HCV-related hepatitis. Sera were also assayed for antibodies to HGV/GBV-C E2 protein. Serum HGV/GBV-RNA could be detected in nine (19%) patients, and anti-E2 antibodies in 22 (46%) patients. The presence of HGV/GBV-C RNA or anti-E2 antibodies was mutually exclusive. The cumulative prevalence of HGV/GBV-C infection was 65% (31/48); the majority of these patients (26/31, 84%) were intravenous drug users (IVDUs). In eight of nine patients viraemic for HGV/GBV-C, RNA positivity could be revealed even in liver specimens; these eight patients were also positive for HCV-RNA both in serum and the liver and did not exibit any specific association with HCV genotype. HGV/GBV-C RNA negative strand RT-PCR testing was negative in all of the eight liver specimens, providing little support to the hypothesis that liver represents the primary site of HGV/GBV-C replication. Moreover, patients with HGV/GBV-C and HCV coinfection were comparable to those with HCV infection alone in terms of biochemistry and liver histology.