Even apparently insignificant chemical deviations among bioequivalent generic antibiotics can lead to therapeutic nonequivalence: the case of meropenem.

Several studies with animal models have demonstrated that bioequivalence of generic products of antibiotics like vancomycin, as currently defined, do not guarantee therapeutic equivalence. However, the amounts and characteristics of impurities and degradation products in these formulations do not violate the requirements of the U.S. Pharmacopeia (USP). Here, we provide experimental data with three generic products of meropenem that help in understanding how these apparently insignificant chemical differences affect the in vivo efficacy. Meropenem generics were compared with the innovator in vitro by microbiological assay, susceptibility testing, and liquid chromatography/mass spectrometry (LC/MS) analysis and in vivo with the neutropenic guinea pig soleus infection model (Pseudomonas aeruginosa) and the neutropenic mouse thigh (P. aeruginosa), brain (P. aeruginosa), and lung (Klebisella pneumoniae) infection models, adding the dihydropeptidase I (DHP-I) inhibitor cilastatin in different proportions to the carbapenem. We found that the concentration and potency of the active pharmaceutical ingredient, in vitro susceptibility testing, and mouse pharmacokinetics were identical for all products; however, two generics differed significantly from the innovator in the guinea pig and mouse models, while the third generic was therapeutically equivalent under all conditions. Trisodium adducts in a bioequivalent generic made it more susceptible to DHP-I hydrolysis and less stable at room temperature, explaining its therapeutic nonequivalence. We conclude that the therapeutic nonequivalence of generic products of meropenem is due to greater susceptibility to DHP-I hydrolysis. These failing generics are compliant with USP requirements and would remain undetectable under current regulations.

Molluscum contagiosum, involving the upper eyelids, in a child infected with HIV-1.

BACKGROUND: Infection with molluscum contagiosum has been reported in pediatric and adult patients with acquired immune deficiency syndrome (AIDS), but rarely affecting eyelids. We have studied the viral phenotype, HIV-1 plasma viremia, p24 antigenemia, alterations of cellular immune function, and the ophthalmological status in a 5-year old human immunodeficiency virus type 1 (HIV-1)-infected girl, who developed multiple molluscum lesions, bilaterally involving upper eyelids with extension over the face and nose. METHODS: Detailed ophthalmological examination and immunological and virological studies were performed in a pediatric patient with HIV-1 vertical infection having extensive infection with molluscum contagiosum. RESULTS: The pediatric patient was emetropic; tricomegalia was present bilaterally, and alteration of the microvessels of the conjunctiva (microangiopathy) was observable in both eyes and structural (fibrilar) degeneration of the vitreous architecture in both eyes. There was no ophthalmoscopic sign of infectious retinitis or retinal microangiopathy. She had lymphopenia, very low percentage and absolute number of CD4+ T cells but increased percentage of CD8+ T cells. The in vitro lymphocyte proliferative response to phytohemagluttinin (PHA) was depressed as compared to healthy controls. She had high levels of viral HIV RNA in her plasma and of p24 antigen in her serum, and the phenotype of the isolated HIV-1 was determined to be syncytium-inducing (SI). CONCLUSION: Although healthy persons may develop molluscum contagiosum, usually unilateral, as far as we are aware this report is the first to document a case of molluscum contagiosum with bilateral eyelid involvement in an HIV-1-infected pediatric patient. Our observations suggest that this type of infection may be present in HIV-infected children, associated with high viral load and possibly an SI viral phenotype, severe immunoregulatory abnormalities, and poor clinical status.

[The aging of the population in Latin America: demographic trends and the socioeconomic situation]. / Envejecimiento de la poblacion en America Latina: tendencias demograficas y situacion socioeconomica

"The paper analyzes the demographic aspects of the aging of the population in Latin America. Aging is still incipient in the great majority of countries of the region, but it will become generalized and will be accentuated especially after the year 2000. The dependency relationship will continue to decrease until higher levels of aging are reached; the proportion of the aged in the potentially dependent population will increase and the relationship between the population from 15 to 59 years of age and over 60 will decrease. "At present, the proportion of single women [over 60] is much higher than that of single men. From the information on participation in the labour force and the access that the aged have to income or pension benefits, the paper also shows that most of the aged that continue to work do so because they require an income for subsistence. "The paper finally includes some conclusions on the causes and consequences of the aging of the population and the actions that would be necessary to broaden knowledge for the formulation of policies." (summary in ENG)