Silvia Boni

Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections

OBJECTIVES The increased incidence of nosocomial infections by multidrug-resistant organisms has motivated the re-introduction of colistin in combination with other antimicrobials in the treatment of infections. We describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Acinetobacter baumannii who were treated with a combination of colistin and rifampicin. PATIENTS AND METHODS Critically ill patients with pneumonia and bacteraemia caused by A. baumannii resistant to all antibiotics except colistin in medical and surgical intensive care units were enrolled. Clinical and microbiological responses and safety were evaluated. RESULTS Twenty-nine patients (47 +/- 14 years and APACHE II score 17.03 +/- 3.68), of whom 19 were cases of nosocomial pneumonia and 10 were cases of bacteraemia, were treated with intravenous colistin sulphomethate sodium (2 million IU three times a day) in addition to intravenous rifampicin (10 mg/kg every 12 h). All A. baumannii isolates were susceptible to colistin. The mean duration of treatment with intravenous colistin and rifampicin was 17.7 (+/-10.4) days (range 7-36). Clinical and microbiological responses were observed in 22 of 29 cases (76%) and the overall infection-related mortality was 21% (6/29). Three of the 29 evaluated patients (10%) developed nephrotoxicity when treated with colistin, all of whom had previous renal failure. No cases of renal failure were observed among patients with normal baseline renal function. No neurotoxicity was noted. CONCLUSIONS Colistin and rifampicin appears to be an effective and safe combination therapy for severe infections due to multidrug-resistant A. baumannii.

Natural killer cells in HIV controller patients express an activated effector phenotype and do not up-regulate NKp44 on IL-2 stimulation

Control of HIV replication in elite controller (EC) and long-term nonprogressor (LTNP) patients has been associated with efficient CD8+cytotoxic T-lymphocyte function. However, innate immunity may play a role in HIV control. We studied the expression of natural cytotoxicity receptors (NKp46, NKp30, and NKp44) and their induction over a short time frame (2–4 d) on activation of natural killer (NK) cells in 31 HIV controller patients (15 ECs, 16 LTNPs). In EC/LTNP, induction of NKp46 expression was normal but short (2 d), and NKp30 was induced to lower levels vs. healthy donors. Notably, in antiretroviral-treated aviremic progressor patients (TAPPs), no induction of NKp46 or NKp30 expression occurred. More importantly, EC/LTNP failed to induce expression of NKp44, a receptor efficiently induced in activated NK cells in TAPPs. The specific lack of NKp44 expression resulted in sharply decreased capability of killing target cells by NKp44, whereas TAPPs had conserved NKp44-mediated lysis. Importantly, conserved NK cell responses, accompanied by a selective defect in the NKp44-activating pathway, may result in lack of killing of uninfected CD4+NKp44Ligand+ cells when induced by HIVgp41 peptide-S3, representing a relevant mechanism of CD4+ depletion. In addition, peripheral NK cells from EC/LTNP had increased NKG2D expression, significant HLA-DR up-regulation, and a mature (NKG2A−CD57+killer cell Ig-like receptor+CD85j+) phenotype, with cytolytic function also against immature dendritic cells. Thus, NK cells in EC/LTNP can maintain substantially unchanged functional capabilities, whereas the lack of NKp44 induction may be related to CD4 maintenance, representing a hallmark of these patients.

Compliance to combination antiretroviral therapy in HIV-1 infected children

Adherence to antiretroviral therapy is considered one of the most important factors determining the success of treatment. Its crucial role in antiretroviral treatment has been proven in both adults and children [1–4]. Monitoring adherence to combination anti-HIV therapy is a crucial tool in improving compliance and consequently in obtaining a durable suppression of plasma viral load [5]. Many variables influence adherence to a single drug or to a more complex regimen: formulation of drugs, number of tablets, schedule of administration, taste, food interference with absorption, duration of treatment, adverse events (quality, quantity and frequency), clinical status and efficacy. Taste, palatability, liquid formulation, ease of administration, number of tablets and interactions with food are determinant features in the treatment of children. Such features can become great problems for their parents and their physicians if therapy is long term. Our cohort included 37 children with perinatally acquired HIV infection. Thirty four of them were on combination antiretroviral treatment at the time of the study. Twenty five consecutively treated children were enrolled in our study after written consent had been obtained from parents or guardians. A questionnaire was used to evaluate the degree of adherence to treatment and the main problems faced by people who had to give medicines to the children every day. Our form included a series of questions about antiretroviral treatment and was an adaptation of a similar one used in the USA in 1997–1998 [6]. Children of our cohort who were included in the study were mainly males (56%); their mean age was 8.2 years (median: 8 years). Each child took a mean of 7.36 tablets and/or syrup doses. Evaluation of the answers from the questionnaire gave the following results: 1. The mother was the main person giving medicines to the child (80%). 2. The father or grandmother were the other chief figures (16% each). 3. A written list of child’s medicines was kept by 24% of families and a full written schedule of the child’s treatment by 44% of families. 4. Twenty four percent of children had missed at least one dose in the 3 days before the visit and almost half the children (44%) had missed at least one dose since the last visit.

Clinical and virological survey of patients with hepatitis B surface antigen in an Italian region: clinical considerations and disease burden.

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non‐infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty‐five patients (71% male) were evaluated. Their median age was 48 years (range 5–84), and 83.4% were of Italian origin. Community‐acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion‐associated transmission (1.8%). Hepatitis B e‐antigen was present in 20.4% of the patients, while co‐infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir‐dipivoxil. Forty‐nine patients were co‐infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers. J. Med. Virol. 81:1882–1886, 2009.

Nutritional status changes in HIV-infected children receiving combined antiretroviral therapy including protease inhibitors

Maintaining linear growth and weight gain in HIV-infected children is often difficult. Nutritional evaluation and support are recognised as important factors to improve their quality of life. Combination antiretroviral therapy including protease inhibitors (HAART) reduces HIV-viral load and improves survival, quality of life and nutritional status. Our study aimed to determine changes in nutrional status based on body weight, height and nutritional habits, of HIV-infected children receiving HAART. Possible side effects of lipid metabolism were also studied. Twenty five children, 13 treated with HAART (group B) were followed up for 12 months. We did not observe statistically significant differences in nutritional status over that time or between groups A and B. Inadequate energy intake was more common in patients with advanced HIV-disease. Hyperlipidemia was found in 70% of children receiving ritonavir and in approximately 50% of children receiving nelfinavir. We observed an important although not statistically significative modification in the height of those in group B.

Therapeutic management of chronic hepatitis B in clinical practice: A region-wide survey

Goals: To characterize the clinical and treatment pattern in a large population of hepatitis B virus (HBV) patients managed at tertiary referral centers in clinical practice. Background: Successful treatment, either with interferon (IFN) or nucleos(t)ide analogs (NUCs), of chronic HBV infection is associated with improved long-term patient outcome. However, in clinical practice, the actual management of these patients is not well characterized, and data regarding treatment pattern in this setting are lacking. Methods: In this cross-sectional study, we evaluated 505 patients chronically infected with HBV alone and who had at least 1-year follow-up. We assessed indication to, rate of, and type of treatment as well as the characteristics of treated patients. Results: Overall prevalence of positivity for HBe antigen was 19.3%, and the majority of patients had chronic hepatitis (47.5%). Non-Italian patients represented approximately one third of the population (27.1%). Among patients with indication to antiviral therapy (n=318), treatment was actually carried out in 264 patients (83.0%), prevalently with NUCs (65.9%). IFN-treated patients were younger (P<0.001), more frequently male (P=0.025) and HBeAg positive (P=0.003), and less frequently cirrhotics (P<0.001) as compared with patients treated with NUCs. Conclusions: In a geographical area with a low positivity for HBe antigen, antiviral therapy is actually carried out in the majority of patients who have indication to treatment, prevalently with NUCs, whereas IFN treatment is more frequently carried out in young, HBe antigen–positive patients who do not have advanced liver disease.

Does HGV–HIV co-infection exist?

Hepatitis G virus (HGV) is a recently discovered virus belonging to the Flaviviridae family. Prevalence of HGV active infection (presence of HGV-RNA) in HIV-1-infected patients has been reported in various categories of patients. Our study aimed to find out its prevalence in our cohort of HIV-1-infected children. No investigated child presented with signs of HGV active infection notwithstanding the presence of many risk factors for HGV infection. Prevalence of HGV active infection in our cohort was <2.7%.

‘Emergency exit’ of bone-marrow-resident CD34 + DNAM-1 bright CXCR4 + -committed lymphoid precursors during chronic infection and inflammation

During chronic inflammatory disorders, a persistent natural killer (NK) cell derangement is observed. While increased cell turnover is expected, little is known about whether and how NK-cell homeostatic balance is maintained. Here, flow cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory disorders, both infectious and non-infectious, reveals the presence of a CD34+CD226(DNAM-1)brightCXCR4+ cell population displaying transcriptional signatures typical of common lymphocyte precursors and giving rise to NK-cell progenies with high expression of activating receptors and mature function and even to α/β T lymphocytes. CD34+CD226brightCXCR4+ cells reside in bone marrow, hardly circulate in healthy donors and are absent in cord blood. Their proportion correlates with the degree of inflammation, reflecting lymphoid cell turnover/reconstitution during chronic inflammation. These findings provide insight on intermediate stages of NK-cell development, a view of emergency recruitment of cell precursors, and upgrade our understanding and monitoring of chronic inflammatory conditions.