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In a survey of 247 HIV-infected patients which received at least six months of combined antiretroviral therapy including the protease inhibitor nelfinavir during the last two years (2000-2001), the specific primary genotypic mutation D30N (with or without the minor mutation N88D), was detected in only four of the 149 (2.7%) subjects who received genotypization after virological failure. Three of these cases of primary nelfinavir resistance occurred among the 84 patients who were protease inhibitor- and/or non-nucleoside reverse transcriptase inhibitor-na ve, while the last episode was registered in a female patient treated since five years, who received an indinavir-based therapy of nearly 12-month duration (interrupted because of untoward kidney effects). During the subsequent follow-up, the substitution of nelfinavir had a favourable laboratory and clinical outcome in all reported patients who continued a different highly active anti-HIV treatment, while a significantly less positive virological and immunological response was seen in all the remaining subjects, and especially in those who experienced virological failure after undergoing at least two prior changes of combined antiretroviral therapy, and were borne by a broad spectrum of protease gene mutations (save those regarding codons 30 and 88). Due to its exclusive resistance pattern, nelfinavir may represent a favorable first-line choice among protease inhibitor-based regimens, since it may spare further treatment options even in the same pharmacological class. In fact, cross-resistance with other protease inhibitors may be limited also in patients experiencing prior long-term antiretroviral therapy, from second-line to rescue regimens, provided that they were pre-treated with drugs other than nelfinavir.

An extraordinarily rare case report of mixed fat redistribution syndrome associated with osteopenia but not with relevant metabolic abnormalities is documented in a prepubertal child with congenital HIV infection treated with antiretroviral therapy since the age of six months, up to the present age of 12 years and two months. The possible relationship with prior and present antiretroviral treatment, and with the most recent literature evidences published in both adults and children with HIV disease are discussed, in order to focus these emerging adverse effects of long-term antiretroviral therapy in the paediatric population, and stimulate further investigation in this field.

In order to assess the frequency, and epidemiological and microbiological features, of respiratory and blood stream infection due to methicillin-resistant Staphylococcus aureus in high-risk patients, all S. aureus strains cultured from reliable clinical specimens (respiratory secretions obtained by tracheo-bronchial aspirate or bronchoalveolar lavage, or blood cultures), were prospectively evaluated over a three-year period, in six inpatient wards selected on the ground of an elevated frequency of severe and/or nosocomially-acquired infections, because of the prevalence of immunocompromised patients, organ transplant recipients, or need of intensive care. Repeatedly positive cultures obtained from a single patient within 30 days were considered as one isolate. Of 507 S. aureus strains responsible for pneumonia or sepsis in the selected wards, 317 (62.5%) proved methicillin-resistant, in absence of significant variations throughout the study period, and according to the specimen origin. Methicillin-resistant S. aureus strains prevailed over sensitive ones in all examined wards (from a 95% rate of the respiratory intensive care unit, to 55.9% of the pneumology department), save the neonatal and pediatric intensive care unit (41.4%). Most of methicillin-resistant S. aureus isolates were recovered from lower airways, compared with blood cultures (p<.0001). The majority of the 317 methicillin-resistant strains were found in the general intensive care unit (42.6%), followed by the pneumology department (18%), and the respiratory intensive care unit (16.4%). Among methicillin-resistant S. aureus strains, a broad variation of sensitivity to other antimicrobial agents was observed: from 3.3% of erythromycin, to 76.9% of chloramphenicol, and 79.7% of cotrimoxazole; glycopeptide antibiotics remained effective against all cultured strains. In our three-year survey of more than 500 episodes of documented staphylococcal infection involving high-risk patients, methicillin resistance was a very common feature, observed at a greater frequency than that reported in literature studies focusing on surgical, pneumological, or intensive care settings. A long-term microbiological monitoring of high-risk inpatient wards may allow a continued update of local antimicrobial susceptibility maps, and significantly add to both chemoprophylaxis and empiric treatment strategies of patients which are either immunocompromised or hospitalized for a long period.

Objective: To determine the efficacy of efavirenz introduction in first-line HAART compared with salvage multidrug regimens., Patients and Methods: Prospective 15 month comparison of 107 consecutive HIV-infected patients starting efavirenz, according to laboratory and clinical outcome of first-line versus rescue drug use, therapeutic history and association of selected antimicrobial agents: naive patients were compared with nucleoside reverse transcriptase inhibitor (NRTI)-experienced patients in the first group, and patients in the second group who had one or more NRTI changed when starting a rescue treatment containing one or more novel protease inhibitors (PIs) were compared with those who did not., Results: Efavirenz was administered with one or more novel NRTIs to 55 patients (27 antiretroviral-naive and 28 patients experienced with NRTIs only), compared with 52 patients who needed a multidrug salvage regimen after two or more failures of a 15-40 month PI-containing regimen. In an intention-to-treat analysis, con-sidering early interruption or an unsatisfactory virological course as a failure, only one patient on salvage therapy completed a favourable 15 month follow-up, compared with 31 patients experiencing first-line efavirenz-based HAART (P < 0.0001). The immunological response was less affected in both intensity and duration in patients undergoing rescue therapy. While no significant outcome difference was detected in the first group between naive and NRTI-experienced patients, among the salvage subjects the change of one or more NRTIs seemed to significantly improve virological and immunological outcome. Viral genotyping detected at least the K103N mutation in 41% of the 78 evaluable patients, despite lack of exposure to efavirenz and related compounds. Salvage patients had a significantly greater frequency of non-nucleoside RTI (NNRTI) resistance compared with the first-line group (P < 0.0001), in proportion to the extent of mutations affecting other drug classes (P < 0.0001)., Conclusion: An efavirenz-based initial triple drug HAART proved significantly more effective than efavirenz adjunct to a rescue treatment performed after repeated failures of PI-based regimens. The unsatisfactory response of the salvage group was probably due to diffuse cross-resistance descending from previous therapy, even when NNRTIs were never administered.

Background: Cellulitis and soft tissue infection are underestimated complications of HIV disease., Patients and Methods: Sixty-seven bacteriologically proven consecutive episodes were identified among 2221 HIV-infected patients hospitalized in a 10-year period, and assessed according to several epidemiological, microbiological and clinical variables., Results: Staphylococcus aureus was the most frequently cultured pathogen (50% of 92 isolates), followed by Pseudomonas spp., Escherichia coli and Streptococcus pyogenes; a polymicrobial infection was present in 38.1% of episodes. Drug addiction (p < 0.003) and male gender (p < 0.04) were significantly associated with the occurrence of these complications, which were community-acquired in 83.6% of cases. While a remarkable variation in the severity of underlying immunodeficiency was shown, hematogenous dissemination occurred in 25.4% of episodes, and proved significantly related to a low CD4+ lymphocyte count, and neutropenia. A 21.7% methicillin-resistance rate was shown among S. aureus isolates. All episodes were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam-aminglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in four patients only., Conclusion: Skin and soft tissue infections are continuing causes of morbidity in HIV-infected patients, even in the highly active antiretroviral therapy era.

Although HIV infection is often associated with several rheumatic diseases, the coexistence of this retroviral infection and systemic lupus erythematous is extremely uncommon. Etiopathogenetic relationship between these disorders is very complex and still problematic, so that diagnostic workout, because of their extensive clinical and serological overlap. Generally, HIV-related immunosuppression improves lupus-associated symptoms, and antiretroviral therapy may lead to an autoimmune disease flare, subsequent to the increase of circulating CD4+ cell number. A HIV-infected female patient with systemic lupus erythematosus, occurred few months after the highly active anti-retroviral therapy initiation, is described.

Streptococcus intermedius, included in the 'milleri group', is a commensal of the mouth and upper respiratory tract but it has often been associated with various pyogenic infections, such as endocarditis, pneumonia, abdominal or cerebral abscess, rarely with osteomyelitis, and exceptionally with muscular abscess. The first observed case of iliac osteomyelitis with gluteal muscle abscess caused by S. intermedius is reported. It is essential to recognise members of the 'milleri group' as possible agents of bone and muscle pyogenic infection because its management requires a timely diagnosis and prolonged antimicrobial treatment to achieve complete clinical and radiological recovery.