In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of current combination therapies for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. However, their low genetic barriers against resistance development, cross-resistance and serious side effects can compromise the benefits of the first generation compounds in this class (efavirenz and nevirapine). To study potential pathways leading to resistance against the novel diphenylether NNRTI, RO-0335, sequential passage experiments at low multiplicity of infection (MOI) were performed to solicit a stepwise selection of resistance mutations. Two pathways to loss of susceptibility to RO-0335 were observed, containing patterns of amino acid changes at either V106I/A plus F227C (with additional contributions from A98G, V108I, E138K, M230L and P236L) or V106I/Y188L (with a potential contribution from L100I, E138K and Y181C). Characterization of the observed mutations by site-directed mutagenesis in the isogenic HXB2D background demonstrated that a minimum of two or more mutations were required for significant loss of susceptibility, with the exception of Y188L, which requires a two-nucleotide change. Patterns containing F227C or quadruple mutations selected by RO-0335 showed a low relative fitness value when compared to wild-type HXB2D.

Antimicrobial susceptibility of 840 clinical isolates of Haemophilus influenzae collected in four European countries in 2000-2001.

In 2000-2001, 840 clinical isolates of Haemophilus influenzae were collected from laboratories in France, Germany, Italy and Spain (210 isolates/country). Beta-Lactamase production among the isolates varied considerably by country, ranging from 8.1% in Germany to 34.8% in France. H. influenzae from patients or=18 years (16.5%). All isolates were susceptible to amoxicillin-clavulanate, ciprofloxacin and levofloxacin; 99.6% and 98.9% of isolates were susceptible to azithromycin and cefuroxime, respectively. Among the macrolides tested, azithromycin (MIC90, 2 mg/L) was eight-fold more potent than clarithromycin (MIC90, 16 mg/L) and roxithromycin (MIC90, 16 mg/L). Despite variations in beta-lactamase production between different countries, > 99% of all isolates were susceptible to amoxicillin-clavulanate, ciprofloxacin, levofloxacin, and azithromycin.

Macrolide susceptibility and beta-lactamase production among haemophilus influenzae isolates in the United States, 1996-1997.

In 1996 and 1997, 68 hospital laboratories throughout the United States determined the beta-lactamase production and susceptibility to macrolides of 1,998 isolates of Haemophilus influenzae obtained from patients with community-acquired respiratory tract infections. The MICs at which 90% of the isolates are inhibited of azithromycin, erythromycin, and clarithromycin were 4, 8, and 16 microgram/ml, respectively. By National Committee for Clinical Laboratory Standards interpretive criteria, 99 and 78% of the isolates were susceptible to azithromycin and clarithromycin, respectively. The prevalence of beta-lactamase production was 32%.

Pseudomonas folliculitis.

Previous reports of Pseudomonas folliculitis in children identified heated pools, hot tubs or spa baths as the source of the infection. This report presents a 4-year-old female with Pseudomonas folliculitis acquired from the family bath tub. The source of the infection was contaminated bath toys and bath plug.

Bindii dermatitis.

Bindii dermatitis is a distinctive eruption involving the palms, soles, elbows and knees. Most patients are young boys engaged in vigorous outdoor activities. The eruption represents a reaction to traumatic impregnation of the skin with the spine of the bindii seed. It can easily be misdiagnosed by dermatologists unfamiliar with the condition.

Atopic eczema in children: what to do when treatment fails to work.

Atopic eczema in infants and children usually responds to a management programme involving patient education, the avoidance of environmental irritants, the regular use of emollients and the application of topical steroids. If a child fails to respond to this management programme, the dermatologist should initially ensure that the diagnosis is correct and exclude a coexistent disease process (for example, infection or immunodeficiency) that may be hampering response to treatment. The next step is to ensure that environmental irritants have been identified and eliminated from the child's environment and that prescribed medication is being used as instructed. Allergy assessment and ancillary therapy are reserved for those infants and children with severe disease not responding to basic therapy.

Viral exanthems in childhood.

Viral exanthems can be classified as erythematous vesicular and papular. The majority are erythematous with the most common viral causes being non polio enteroviruses, respiratory viruses, acute. Epstein-Barr virus, human herpes viruses 6 and 7, and parvovirus B-19. Measles, rubella, mumps, acute GMV, hepatitis viruses. HIV seroconversion, Ross River and Barmah Forest viruses are less commonly seen. The differential diagnosis includes drug eruption, erythematous bacterial exanthems and Kawasaki's syndrome.

Meso-diencephalic infarction: a not so rare form of stroke.

26 patients admitted with clinical pictures consistent with meso-diencephalic infarction were studied using computerized axial tomography, magnetic resonance imaging and angiography. All of the patients presented symptoms in two of three major categories which comprise the "top of the basilar" syndrome. Lesions in the territory of the basilar-communicating artery were demonstrated in 22 of them. The remaining patients died before adequate neuroimaging documentation was obtained. Overall prognosis appeared relatively good since 80% of the patients recovered completely or incompletely from the ictus. Meso-diencephalic infarction is a very important and not uncommon subtype of cerebrovascular disorder.

Altered sensorium, confusion, and vertical gaze paresis: the top of the basilar syndrome.

The term "top of the basilar" has been used in reference to a group of signs and symptoms of midbrain, diencephalic, and posteroinferior hemispheric dysfunction. It has been attributed to ischemia in the territory of second- and third-order vessels that arise from the uppermost portion of the basilar artery. We report our experience with four patients who had alteration of consciousness, confusion, and vertical gaze paresis accompanied by other physical abnormalities. Extensive evaluation did not help in documenting the lesions or in understanding their pathogenesis. The top of the basilar syndrome is a not uncommon form of stroke and carries a variable prognosis. Treatment by anticoagulation may prevent further infarction in selected patients who are seen early.

Unilateral Moya Moya disease in an adult--a case history.

A case of ischemic infarction in a young woman who also had angiographic findings consistent with "Moya Moya" disease is presented. Unusual features of the case, such as the presentation as an infarction rather than subarachnoid hemorrhage and the unilaterality of the angiographic abnormalities, are discussed. The literature is reviewed and emphasis is directed to the importance of the inclusion of this entity in the differential diagnosis of cerebral ischemic events in young adults, owing to the possible therapeutic implications.