Roberto Manfredi

Reactivation of severe, acute pulmonary tuberculosis during treatment with pegylated interferon-alpha and ribavirin for chronic HCV hepatitis

The unexpected observation of severe pulmonary tuberculosis after a 7-month combined pegylated interferon-ribavirin for chronic hepatitis C, prompted us to search an eventual immunodeficiency (lymphopenia and/or depletion of CD4+ T-lymphocytes. The retrieval of a chest radiograph incidentally performed 11 y before and showing a probable primary tuberculosis, paralleled a negligible clinical history. The enlargement of interferon indications needs careful evaluation for prior (usually missed) tuberculosis, to prevent or avoid its possible reactivation. Latent tuberculosis is increasingly reported because of extended life expectancy, immigration, and recent availability of cure for multiple chronic disorders, which are often borne by primary-secondary immunodeficiency.

Clinical Comparative Study of Azithromycin versus Erythromycin in the Treatment of Acute Respiratory Tract Infections in Children

The efficacy and tolerability of azithromycin and erythromycin in the treatment of acute respiratory tract infections in children were compared in an open, multicenter, randomized trial. A total of 151 children, aged from 2 months to 14 years, suffering from upper airways infections (60), or lower respiratory tract infections (91), were randomized to be treated either with azithromycin, 10 mg/Kg/day per os once daily for 3 or 10 mg/Kg/day 1 and 5 mg/Kg/days 2-5 (77 patients) or with erythromycin, 50 mg/Kg/day thrice daily for at least 7 days (74 patients). The two treatment groups did not significantly differ as to sex, age, weight, type and severity of infection, and infecting pathogens. Clinical evaluation was performed prior to therapy, on treatment days 1, 3, 5 and 7, and on day 10. Microbiological and laboratory assessment were carried out at baseline and after the end of therapeutic course. Chest X-ray and serologic assays for Mycoplasma pneumoniae infection were obtained in patients suspected to have lower respiratory tract infections. At the end of therapy, clinical cure was achieved in 73 out of 77 patients (94.8%) in the azithromycin group, and in 60/72 evaluable subjects (83.3%) in the erythromycin group. A significantly more rapid remission of several illness-related signs and symptoms was observed in patients treated with azithromycin. A total of 75 bacterial pathogens were isolated at baseline microbiological examination; at the end of the therapeutic course bacteriological eradication was obtained in 34/34 cases (100%) treated with azithromycin, and in 40/41 children (97.5%) treated with erythromycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Pegylated Interferon and Ribavirin for the Management of Chronic Hepatitis C in a Prison Setting

The elevated frequency of chronic hepatitis C virus (HCV) infection found among prison inmates, and the availability of improved pharmacological cure for this potentially life-threatening disorder, make investigations conducted in this somewhat neglected area very relevant, since only a few, open-label experiences have been reported till now. In the metropolitan prison of Bologna (Italy), HCV seroprevalence was found to be over 31% in 2003, so that a pilot feasibility study based on treatment with pegylated interferon plus ribavirin was initiated, after careful counseling carried out by a joint commission of health care personnel of the correctional facility and infectious diseases consultants. Thirty-nine patients were enrolled, and despite expected dropouts due to difficulty in maintaining the same level of counseling pressure over time, and the particularly unfavorable climatic conditions during Summer 2003, a sustained virological response was obtained for 8 out of the 21 patients who remained evaluable after the first three month follow-up, although we need to take into account that a high percentage of subjects (67%) were selected for therapy due to their favorable HCV genotypes (types 2 and 3). Our preliminary experience shows that an intrinsically complicated therapy, such as the administration of pegylated interferon plus ribavirin, can attain a relatively high success rate, even in a very unfavorable and uncomfortable context, such as a prison, where only enforced counseling, active participation of institutional health care operators, and patients willingness to maintain an elevated level of co-operation and adherence, can overcome most structural and relational difficulties.

Primary Cytomegalovirus infection in otherwise healthy adults with Fever of Unknown Origin: a 3-year prospective survey

Background:Primary cytomegalovirus disease is probably still underestimated or missed in common clinical practice, and further prevalence studies should be performed, in particular in the setting of fever of underdetermined origin (FUO) in adults.Patients and Methods:In a 3-year prospective survey of 123 consecutive adult patients referred for FUO often associated with a broad spectrum of constitutional signs and symptoms, 18 patients (14.6%) were found to have a primary cytomegalovirus infection, after a clinical, instrumental and laboratory workup.Results:In the majority of cases, this syndrome was consistently associated with altered white blood cell count, abnormal T-lymphocyte subsets and ultrasonography-confirmed hepatosplenomegaly. On the other hand, altered white blood cell differential and serum hepatic enzymes, and constitutional signs and symptoms were absent in 11.1–27.8% of cases, and an initial laboratory cross-reaction with anti-Epstein-Barr IgM antibodies was detected in 44.4% of episodes. Non-specific signs and symptoms were the only features in 27.8% of patients with adult cytomegalovirus disease, thus, confirming that this disorder may be still clinically underestimated, until virologic assays are performed. A prolonged and varied spectrum of subjective disturbances (similar to those encountered in infectious mononucleosis), which often limited daily activities, involved nearly 30% of subjects, and lasted for 3–15 months after recovery of acute cytomegalovirus disease.Conclusion:In the clinical, laboratory, and instrumental workup for FUO, rapid recognition of a primary cytomegalovirus disease is useful to exclude alternative diagnoses, avoid non-necessary exposure to antibiotics, and reassure patients of their self-limiting, benign disorder.

Moraxella catarrhalis pneumonia during HIV disease

Abstract To assess the role of Moraxella catarrhalis complications in the setting of HIV disease, and to evaluate their occurrence and outcome according to several epidemiological, clinical, and laboratory parameters, the clinical records of 2123 consecutive HIV-infected patients hospitalized in a 9-year period were retrospectively reviewed, and 4 cases of community-acquired M. catarrhalis pneumonia were identified. Three adult patients had a diagnosis of AIDS and severe concurrent immunodeficiency (with a CD4+ lymphocyte count below 60 cells/uL), while the fourth case involved a child with vertical HIV disease. Leukopenia and neutropenia were never present, but no patient received a potent antiretroviral regimen at the time of disease onset. A concurrent respiratory infection by Streptococcus pneumoniae and Mycobacterium tuberculosis was recognized in 2 of 4 patients. Isolated M. catarrhalis strains were susceptible to all tested antimicrobial compounds (save ampicillin in 2 cases), and appropriate antimicrobial treatment led to clinical and microbiological cure in all described episodes. Only 8 cases of HIV-associated Moraxella spp. disease have been reported to date in seven different literature reports (6 cases of pneumonia, and 1 of septicemia). According to our experience, M. catarrhalis may be responsible for appreciable morbidity among patients with advanced HIV infection, especially when a low CD4+ cell count or coexisting respiratory disease are present. Clinicians and microbiologists who care for HIV-infected patients should carefully consider the potential pathogenic role of Moraxella spp. organisms.

Capnocytophaga spp. brain abscess in an immunocompetent host: problems in antimicrobial chemotherapy and literature review.

Abstract The fourth case report of a brain abscess due to the fastidious Gram-negative organism Capnocytophaga spp. is described and discussed on the grounds of clinical, microbiological, and therapeutic evidence. A probable origin from a cat bite and/or an underlying severe mandibulary granuloma is suspected. Due to lack of clinical and neuroradiological response to neurosurgery and a combination of imipenem-amikacin-clindamycin-fluconazole, second-line empiric linezolid treatment proved rapidly successful, in the absence of further microbial isolations. In vitro antimicrobial susceptibility testing is often unpredictable for Capnocytophaga spp., and agents usually active on Gram-positive organisms may also be effective, both in vitro and in vivo. Due to its favorable brain penetration and its dual mode of administration, linezolid may be an alternative option for patients with multiple risk factors, brain abscess of suspected polymicrobial origin, and lack of response to empiric or culture-driven therapeutic attempts.

Listeria monocytogenes Meningitis and Multiple Brain Abscesses in an Immunocompetent Host. Favorable Response to Combination Linezolid-Meropenem Treatment

Central nervous system (CNS) listeriosis outside of pregnancy, the neonatal period, and immunodeficiency, is uncommon in the general population. Although Listeria sepsis-bacteremia, endocarditis, gastroenterit is, and focal infection has been described, meningitis and especially CNS abscess lead to major diagnostic and therapeutic concerns 1,2. CNS involvement should follow bacteremia, and meningitis represents the most common CNS manifestation, with brain abscesses being <1% of episodes of Listeria CNS involvement 3. Multiple predisposing factors have been described in anecdotal reports and small adult and pediatric series of patients suffering from hematologic or solid organ malignancies 1,2,4, collagen vascular disease and chronic intestinal disorders, while HIV disease is not considered a supporting factor. Isolated episodes of L. monocytogenes CNS infection were also reported in immunocompetent patients 5,6, where differential diagnosis and treatment are hampered by a low clinical suspicion. A literature review from 1945 to 1984 retrieved 45 cases of listeriosis, 54% of them occurring in apparently immunocompetent hosts, Journal of Chemotherapy Vol. 18 n. 3 (331-333) 2006

Long-term statin use does not act on the temporal trend of CD4 cell count in patients on virologically effective HAART.

Pleiotropic features are attributed to statins and fibrates, and effects on laboratory markers of HIV disease progression have been claimed. To assess whether statins/fibrates have long-term effects on the immune recovery of patients on virologically effective HAART, a prospective, comparative study was conducted on 267 dyslipidemic patients treated with either statins, fibrates, or on a dietary exercise programme only. Quarterly assessment of CD4 cell counts showed no differences between groups, thus excluding in-vivo negative immunological effects during effective HAART.

Pentamidine Isethionate as Treatment and Secondary Prophylaxis for Disseminated Cutaneous Leishmaniasis During HIV Infection: Case Report

Abstract Leishmaniasis is emerging as a common and serious opportunistic infection in HIV-infected patients in endemic areas (such as Mediterranean countries), and may occur with various clinical presentations, ranging from typical visceral forms to atypical cases, including cutaneous disease. Although pentavalent antimony compounds have been the mainstay of antileishmanial treatment for half a century, new drugs seem today reliable, including liposomal ampho-tericin B and pentamidine isethionate. However, the most effective therapy is still unknown. An HIV-infected i.v. drug abuser patient with a very uncommon disseminated cutaneous leishmaniasis, following an initial visceral disease, is described. Primary and recurrent visceral forms of protozoan infection have been treated with liposomal amphotericin B, while pentamidine isethionate was successfully employed as treatment for subsequent cutaneous relapse and as secondary prophylaxis.

Bladder carcinoma and HIV infection during the highly active antiretroviral therapy era: A rare, but intriguing association. Two case reports and literature review

Two very rare case reports of bladder transitional cell carcinoma associated with HIV infection in patients treated with combined antiretroviral therapy are described, and discussed on the ground of the most relevant and updated literature resources. Only 13 cases of vesical carcinoma have been reported to date in the setting of HIV infection, but only 3 anecdotal single reports (the last in the y 2001) described clinical, therapeutic, and outcome issues of this rare disease association in some detail. In our patients, micro- or macro- haematuria was the clue for in-depth diagnosis and prompt treatment, which was limited to multiple local interventions in 1 case, but finally required a radical cystectomy in the second patient. No relationship was found with the very favourable underlying HIV-related virological and immunological status, and the present 8–12-month follow-up did not show disease relapses.