Leonardo Calza

Efavirenz versus nevirapine in current clinical practice: a prospective, open-label observational study.

Abstract:An open-label, observational, prospective 18-month survey was conducted to compare the efficacy and tolerability of the 2 available nonnucleoside reverse transcriptase inhibitors (NNRTIs) in all possible indications of current clinical practice. A broad range of clinical and laboratory variables accounting for drug efficacy and tolerability (with special emphasis on metabolic and hepatic toxicity) were measured in 287 evaluable patients treated with efavirenz, compared with 258 subjects taking nevirapine for 18 months. A separate efficacy analysis was performed in 154 antiretroviral-naive subjects, 298 patients experienced with 2–7 prior anti-HIV lines who abandoned protease inhibitors (PIs), and 103 subjects entering a salvage regimen containing at least 4 drugs, including PIs. Antiretroviral-naive patients experienced greater efavirenz activity at 3–12 months (maximum HIV RNA drop = −2.4 log10 copies/mL), associated with a significantly higher rate of complete viral suppression, while immunologic results proved significant only after 6–9 months. When assessing experienced patients and those on rescue regimens, a similar and progressively blunted laboratory response was achieved, on the ground of a worse baseline virologic and immunologic profile, and duration of prior anti-HIV therapy. Both first-month (4.2 and 4.3% for efavirenz and nevirapine, respectively) and overall discontinuation rates (11.5 and 12%, respectively) proved similar, but a profound difference emerged as to the different spectrum of untoward events: central nervous system (CNS) disturbances, persisting metabolic abnormalities, and possibly gynecomastia and laboratory pancreatic abnormalities for efavirenz vs. immediate allergy and increased hepatotoxicity (regardless of chronic infection with hepatitis B or C virus and methadone use) for nevirapine. A limited virologic and immunologic advantage of efavirenz was observed in the first 12-month assessment of antiretroviral-naive patients, whereas all other examined situations did not disclose relevant efficacy differences between efavirenz and nevirapine throughout the 18-month comparison. Although the short- and long-term toxicity and withdrawal rates of the 2 drugs were comparable, the different pathways prompting allergic, metabolic, liver, and CNS disturbances observed with NNRTIs deserve careful investigation, to prevent toxicity of these relevant antiretroviral compounds.

First-line efavirenz versus lopinavir-ritonavir-based highly active antiretroviral therapy for naive patients

Ninety-seven consecutive patients started anti-HIV therapy based on efavirenz (46) or lopinavir-ritonavir (51) in an observational study. Despite the significantly more compromised immunological-clinical baseline conditions of patients starting lopinavir-ritonavir, a mean clinical-laboratory follow-up of 17 months showed a comparable laboratory response and therapy interruption or change rate, although the toxicity profile of the two compounds proved significantly different. Randomized studies comparing these two recommended first-line treatments are warranted, particularly from a pharmacoeconomic viewpoint.

Epidemiological, clinical and therapeutic features of AIDS‐related Mycobacterium kansasii infection during the HIV pandemic: an 11‐year follow‐up study

Optimal diagnosis and timely treatment of atypical mycobacteriosis, and especially Mycobacterium kansasii disease, remain a serious challenge for clinicians engaged in the management of the immunocompromised host.

Chron's disease, rare association with selective IgA immunodeficiency, and development of life-threatening bacterial infections

Life-threatening necrotizing fasciitis and relapsing Lemierre syndrome associated with Fusobacterium necrophorum septicaemia occurred in young adults with a moderate Chrons disease and a missed profound IgA deficiency. This unexpected association of a chronic bowel inflammatory syndrome with prominent IgA abnormalities and severe bacterial infection deserves careful attention by physicians faced with young patients with Chrons disease.

A Decade Surveillance Study of Mycobacterium xenopi Disease and Antimicrobial Susceptibility Levels in a Reference Teaching Hospital of Northern Italy: HIV-Associated Versus Non-HIV-Associated Infection

Abstract Objective and Method: The aim of our survey is to investigate the epidemiology and in vitro antimicrobial susceptibility levels of 35 consecutive Mycobacterium xenopi strains responsible for confirmed disease at a University Hospital from 1993 to 2002 and to identify eventual differences in the in vitro sensitivity profile between the 17 strains isolated from patients with HIV disease and the 18 isolates cultured from non-HIV-infected individuals. Results: The involvement of lower airways accounted for 88.6% of cases; but atypical pulmonary findings, including cavitation and a prominent inflammatory reaction, recently emerged in HIV-infected patients successfully treated with HAART, which raises the possible role of immune reconstitution syndrome in the clinical pathomorphism of this opportunistic disease. When compared with non-HIV-infected patients, patients with HIV disease had a lower mean age and a tendency to suffer from late relapses. The greatest overall in vitro sensitivity rate was registered for capreomycin and protionamide (100% of strains) followed by kanamicin (96.6%), whereas susceptibility rates for the first-line compounds such as ethambutol, isoniazid, and rifampicin were slightly lower (85.7% to 91.4%). No temporal variation in the susceptibility index was seen over the study decade. Non-HIV-infected patients experienced a higher frequency of M. xenopi isolates that proved to be resistant to at least one tested compound compared with HIV-associated episodes, despite the heavy and prolonged exposure of HIV-infected patients to broad spectrum antimicrobials, which included agents effective on atypical mycobacteria. Only one HIV-positive patient developed rifampicin resistance in his third disease recurrence. Conclusion: A rapid diagnosis, a reliable differentiation between colonization and disease, and an optimal therapeutic choice for atypical mycobacterial disease (including M. xenopi one) are still serious challenges for clinicians and bacteriologists who treat immunocompromised patients, such as those with HIV disease. In the immunocompromised host, diagnostic difficulties posed by late identification and eventually concurrent opportunistic disorders add their negative effects to therapeutic problems due to the unpredictable in vitro susceptibility profile of atypical mycobacteria, such as M. xenopi.

Extra-Western European citizens in the setting of infectious diseases: A rapidly evolving trend in Northern Italy

Immigration is a relatively new phenomenon in Italy, and the unexpected arrival of hundreds of thousands of foreign individuals seeking work, usually political refugees and their families including children, is of real concern in our country (1 /7), due to the frequent and multiple social, economical, cultural, and health care issues. A retrospective survey of clinical data of all patients admitted to our infectious disease ward and day-hospital service in Bologna (Italy), was performed on data from the year 2000, in order to assess extra-Western European patients compared with those from Italy and Western Europe, according to country of origin and several epidemiological, and clinical, features. Our infectious disease unit (the only dedicated infectious disease division in our metropolitan area), had 8 double rooms from January 2000 to 2 June 2002, but 17 double rooms and 1 single room were available from 3 June 2002. The number of day-hospital beds remained 4 throughout the followup period. The rate of inpatients coming from countries other than Western Europe rose from 8% out of 374 hospitalizations in the year 2000, to 11.3% of 326 in the year 2001, 15.2% of 507 in 2002, and 22.5% of 333 admissions in the period ranging from January to July 2003 (p B/.0001 through the examined period, Mantel-Haenszel x test) (Table I). Africa was the most represented continent with over 55.7% of inpatient admissions (Morocco, Tunisia, Eritrea, Ethiopia, Somalia, Algeria, Nigeria, Senegal, Mozambique, Zaire, and Mali), followed by Eastern Europe (Ukraine, Russia, Belarus, Croatia, Poland, Serbia-Montenegro, and Bosnia), Asia (Pakistan, Sri-Lanka, Bangladesh, India, and China), and the Americas (Argentina, Uruguay, United States, and Santo Domingo). No significant differences were found regarding duration of admission and health care intensity in the majority of discharge diagnoses between Italian and extra-Western European citizens (mostly HIVrelated diseases, acute-chronic hepatitis, central nervous system infection, hyperpyrexia, and respiratory tract infection) (data not shown). However, a greater prevalence of pulmonary and extrapulmonary tuberculosis, skin soft tissue bacterial and fungal infection, infectious exanthems, sexually-transmitted diseases, intestinal parasite illnessess, and malaria, was found among patients coming from outside Western Europe compared with Italian and Western European inpatients (p B/0.05, up to p B/.0001 for tuberculosis). Since most hospitalized foreigners came with acute illnesses from the emergency room/service of our hospital (82.6% of cases compared with 78.9% of other admissions), the increasing frequency of hospitalizations proved more evident among inpatients, although the same phenomenon occurred later and to a lesser extent also at our day-hospital infectious disease service. Only 4% of the 326 dayhospital patients originated from countries outside Western Europe in the year 2000, compared with 6.6% of 320 in 2001, 9% of 332 in 2002, and up to 9.8% of 225 patients, in the January / July period of the y 2003 (p B/.007) (Table I). The very significant increase in patients coming from countries other than Western Europe has had a remarkable impact on infectious disease hospital units. In an early study carried out in Como (Italy), immigrants represented only 0.5% of over 47,000 hospital admissions between 1994 and 1998 (8). Further waves of immigration followed in the y since 1998, and the present situation appears significantly changed and suffers from continued, further development, and therefore controlled data regarding health care problems of immigrants are still fragmentary. The major effect on inpatient wards is caused by the frequent condition of clandestine, irregular or refugee immigrants coming directly from the emergency room, but the phenomenon is progressively also involving dayhospital and ambulatory care. Tuberculosis (1, 9, 10), HIV infection and related disorders (1, 4, 7), sexually transmitted diseases (3), and tropical disorders (2, 5), represent the most investigated infectious illnesses affecting immigrants, but most data are still anecdotal, and we lack of a national epidemiological structure. Permanent monitoring of the broad spectrum of admission features at infectious disease units is urgently needed, in order to ensure a better allocation of future health care resources (6, 11, 12), on the grounds of the

A 2-year survey of bacteriologic profile and antimicrobial susceptibility levels of Enterococci in a large Italian teaching hospital.

Background: Antimicrobial susceptibility levels of enterococci (including those to glycopeptides) are borne by a broad range of variations, due to the numerous involved variables. Methods: To assess the epidemiology and antimicrobial resistance profile of enterococci identified in all clinical specimens cultured at the bacteriology laboratory of a large Italian teaching hospital in a 2-year period, with special attention deserved to differences between Enterococcus faecalis and Enterococcus faecium and the role of novel compounds effective on multiresistant gram-positive cocci (dalfopristin-quinupristin, linezolid, and levofloxacin), 4628 E. faecalis strains and 648 E. faecium isolates were examined. Results: Compared with the year 2000, during the year 2001, a proportional increase of E. faecium isolates was found opposed to E. faecalis (P < 0.0001), associated with a greater involvement of cardiovascular (P < 0.0001), intra-abdominal (P < 0.0001), and genital tract (P < 0.003). When considering the in vitro susceptibility pattern, E. faecalis proved more sensitive to penicillin, ampicillin, and amoxicillin, and also to nitrofurantoin, levofloxacin, and streptomycin (P < 0.0001). On the other hand, E. faecium had a significantly more elevated susceptibility to gentamicin and dalfopristin-quinupristin (P < 0.0001). Tetracyclines showed a comparable activity against E. faecalis and E. faecium (around 30% of tested strains), as well as linezolid (nearly 99%) and glycopeptides-these last drugs, together with linezolid, showed the greatest activity against enterococci as a whole, as only 2 E. faecalis strains recovered from urine were resistant (0.04% of the 4628 tested strains), and all the 648 E. faecium isolates were susceptible to both teicoplanin and vancomycin. When comparing antimicrobial susceptibility levels, no significant difference was found between years 2000 and 2001, when excluding a slight increase of sensitivity to penicillin, ureidopenicillins, gentamicin, streptomycin, nitrofurantoin, and linezolid for E. faecalis, and penicillin, tetracyclines, and linezolid for E. faecium. Discussion: Our experience of microbiologic monitoring conducted on over 5000 Enterococcus spp. strains evaluated during 24 months pointed out an increased amount of isolates in the year 2001, especially involving E. faecium. The in vitro susceptibility studies confirmed a significantly different profile of E. faecalis opposed to E. faecium. When E. faecalis is of concern, penicillin and ureidopenicillins are still highly effective, but are not in the case of E. faecium, an emerging pathogen in our experience. The maintained in vitro efficacy of nitrofurantoin, gentamicin, and streptomycin is of particular interest. Among recently introduced molecules, linezolid proves effective against around 99% of examined strains, including multiresistant E. faecium isolates. On the other hand, dalfopristin-quinupristin and levofloxacin are characterized by a significantly greater activity against E. faecium and E. faecalis, respectively. Glycopeptides showed lower resistance levels compared with most of literature series and therefore remain the reference compounds for the entire Enterococcus spp., especially when multiresistant baterial strains are of concern. A permanent surveillance of the epidemiology of these organisms in both hospital-acquired and community-acquired infections, the assessment of specific risk factors, the evolution of antibiotic sensitivity levels, and eventual consequences on morbidity and mortality rates are the mainstay of adequate programs of control and prevention. The initial spread of resistance against recently available molecules (last-generation quinolones, streptogramines, and linezolid) recommends a prudent exploitation of older therapeutic resources, which remain effective against most enterococci.