Subretinal abscess due to nocardia in an immunosuppressed patient: a case report.

Systemic nocardiosis is a rarely occurring pathology, but its hematogenous spread across the eye is even less likely to occur, with only a few recorded cases. Therefore, it is not usually taken into account when a subretinal abscess is being considered for a diagnosis. However, when confronting a case with a history of immunosupression and pulmonary disease, the examination of the ocular fundus may be a very successful approach. With such aim we introduce the case of a 45-year-old immunosupressed male, without a history of pulmonary disease, whose subretinal mass evolution is accordant with an abscess. In the end, being etiologically diagnosed by means of a vitrectomy, it was concluded that the abscess was due to an infection of nocardia cyriacigeorgica, an emergent pathogen. Thus the aforementioned case is to be considered in the present study, along others, in order to shed more light on a disease which may not be readily diagnosed on account of its infrequency.

Characterization of HIV isolates arising after prolonged zidovudine therapy.

Human immunodeficiency virus type 1 (HIV-1) was isolated from five patients with late-stage disease treated with zidovudine (ZDV) for more than 1 year. Peripheral blood mononuclear cells (PBMCs) were used for all virus isolations and to assay for drug resistance. The isolates exhibited a 10- to 100-fold decrease in ZDV susceptibility compared to pretreatment isolates. Multiple clones of a 618 bp segment of the HIV reverse transcriptase gene encompassing codons 60-250 were sequenced for each isolate. The association of alterations at codons Asp67----Asn, Lys70----Arg, Thr215----Phe or Tyr, and Lys219----Gln with ZDV resistance has been previously noted (ref. 5). In this study, the most frequent alterations was Thr215----Tyr although genotypic mixtures of Thr/Tyr and Phe/Tyr were also observed. One isolate with a Tyr215 alteration and unaltered codons at 67, 70, and 219 had high-level ZDV resistance. Alterations at codons 67, 70, and 219 did not appear to increase resistance when seen in combination with Tyr215. Virus isolates obtained from each patient by cultivation with either 0 or 4 microM ZDV were compared and found to have similar alterations at codons 67, 70, 215, and 219, although one instance of apparent in vitro selection for Tyr215 over Phe215 was observed. Assays using PBMCs for virus propagation will permit susceptibility testing of HIV isolates from most patients on antiretroviral drugs to investigate the clinical significance of drug resistance.

Tetracyclines, macrolides, lincosamides & chloramphenicol.

Macrolides, lincosamides, tetracyclines and chloramphenicol are structurally unrelated antibiotics which share protein synthesis inhibition as their common mechanism of action. Despite their individual differences, they can all be considered broad spectrum antibiotics with practical use for a wide variety of infections. Due to their similarities in function, however, concurrent or sequential administration of these agents must be undertaken with caution in order to prevent antagonism and induction of bacterial resistance. Full understanding of their function and potential interactions are, therefore, important. Indications, interactions, mechanisms of function, side effects and contraindications are fully discussed.

Aminoglycosides: therapeutics, ototoxicity and hypersensitivity of mitochondrial genetic origin.

Aminoglycosides such as streptomycin or gentamycin are employed to treat stubborn infections. In México, tuberculosis patients are successfully treated with 1 g/day for over 6 months. Ototoxicity is often seen as a consequence of prolonged treatment with aminoglycosides. In young people STP damages the vestibule of the ear; in elder patients it diminishes hearing and balance. These effects are due to streptidine, a metabolite of STP produced in elder patients and detected in blood by liquid chromatography. On occasion, sudden deafness is established after only a short treatment period as the result of the presence of a single nucleotide mutation in the mitochondrial 12S rRNA gene. In patients with this polymorphism, aminoglycosides produce a stereotypic conformation similar to the bacterial 16S rRNA thus inhibiting the synthesis of proteins. Many aminoglycoside-sensitive mutations have been described in several ethnic groups, causing sudden deafness. We started similar studies in Mexican individuals, treated or not with an aminoglycoside, to determine whether similar alterations could be detected. To date in over 60 individuals analyzed we found only one case of polymorphism in a streptomycin treated patient. We developed a simple method to identify such mitochondrial gene in a larger population to make recommendations to use an alternative treatment which do not cause ototoxicity in the mutation bearing patient.

mtDNA mutations, hearing loss and aminoglycoside treatment in Mexicans.

UNLABELLED: Streptomycin and aminoglycoside derivatives are commonly used to treat tuberculosis and other stubborn infections; these drugs may alter auditory and/or vestibular function. Mutations in mitochondrial DNA have been associated with hypersensitivity to aminoglycosides; no studies have been conducted in Mexicans, which are very prone to such alterations because aminoglycosides have been prescribed carelessly for many years, irrespective of the ailment to be treated. AIM: We investigated "hot spot" mutations described previously as causing inner ear alterations. METHODS: Hot spot mutations at the 12S rRNA gene and the tRNA Serine (UCN) gene were screened by PCR-RFLP and sequencing in 65 subjects undergoing audiological and vestibular testing. STUDY DESIGN: Experimental. RESULTS: 32 individuals had healthy auditory and vestibular function, whereas 33 subjects had auditory affections. We found none of the previously reported mutations related to aminoglycoside hypersensitivity, or non-syndromic hearing loss. Two hearing-impaired patients that had been treated with streptomycin had the T1189C variant of the mitochondrial 12S rRNA region. CONCLUSION: Mutations related to hearing loss in other ethnic backgrounds were not found in Mexicans. However, the T1189C variant is possibly a putative mutation related to aminoglycoside hypersensitivity and was present in 2 patients.

Quantitative relationship of circulating p24 antigen with human immunodeficiency virus (HIV) RNA and specific antibody in HIV-infected subjects receiving antiretroviral therapy. The RV43 Study Group.

To better understand the biologic meaning and potential clinical utility of p24 antigen measurements in human immunodeficiency virus (HIV) infection, p24 antigen and antibody and HIV RNA were quantitated in parallel. Specimens (n = 311) were analyzed from 74 participants in a zidovudine treatment study. Parallel antigen and RNA measurements revealed the frequent occurrence of two types of discordant results. First, p24 antigen was often not detected in samples with high antibody levels even when > 10(6) RNA copies/mL were present. Second, in specimens in which p24 antigen was detected, the concentration was greater than expected on the basis of HIV RNA values. These results suggest that optimal use of serum p24 antigen values will require consideration of both specific antibody levels and non-virion associated antigen.

Therapy with efavirenz plus indinavir in patients with extensive prior nucleoside reverse-transcriptase inhibitor experience: a randomized, double-blind, placebo-controlled trial.

A randomized, double-blind, placebo-controlled trial compared efavirenz (600 mg every 24 h) plus indinavir (1000 mg every 8 h) with placebo (every 24 h) plus indinavir (800 mg every 8 h) among 327 nucleoside analogue reverse-transcriptase inhibitor (NRTI)-experienced human immunodeficiency virus (HIV)-infected adults. Patients received 50 cells/mm(3), >10,000 plasma HIV-1 RNA copies/mL, and no prior protease inhibitor or non-NRTI therapy. Patients had a mean of 2.8 years of prior NRTI therapy. At 24 weeks, plasma HIV-1 RNA level was <400 copies/mL in 68.2% of efavirenz versus 52.4% of placebo recipients (P=.004). CD4 cell count increases were 104+/-9 cells/mm(3) and 77+/-10 cells/mm(3) in efavirenz and placebo recipients, respectively (P=.023). Responses in efavirenz recipients were sustained at 48 weeks. Thus, efavirenz plus indinavir with concomitant NRTIs is effective therapy for NRTI-experienced patients.

Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team.

BACKGROUND: Efavirenz is a nonnucleoside reverse-transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). We compared two regimens containing efavirenz, one with a protease inhibitor and the other with two nucleoside reverse-transcriptase inhibitors, with a standard three-drug regimen. METHODS: The study subjects were 450 patients who had not previously been treated with lamivudine or any nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. In this open-label study, patients were randomly assigned to one of three regimens: efavirenz (600 mg daily) plus zidovudine (300 mg twice daily) and lamivudine (150 mg twice daily); the protease inhibitor indinavir (800 mg every eight hours) plus zidovudine and lamivudine; or efavirenz plus indinavir (1000 mg every eight hours). RESULTS: Suppression of plasma HIV-1 RNA to undetectable levels was achieved in more patients in the group given efavirenz plus nucleoside reverse-transcriptase inhibitors than in the group given indinavir plus nucleoside reverse-transcriptase inhibitors (70 percent vs. 48 percent, P<0.001). The efficacy of the regimen of efavirenz plus indinavir was similar (53 percent) to that of the regimen of indinavir, zidovudine, and lamivudine. CD4 cell counts increased significantly with all combinations (range of increases, 180 to 201 cells per cubic millimeter). More patients discontinued treatment because of adverse events in the group given indinavir and two nucleoside reverse-transcriptase inhibitors than in the group given efavirenz and two nucleoside reverse-transcriptase inhibitors (43 percent vs. 27 percent, P=0.005). CONCLUSIONS: As antiretroviral therapy in HIV-1-infected adults, the combination of efavirenz, zidovudine, and lamivudine has greater antiviral activity and is better tolerated than the combination of indinavir, zidovudine, and lamivudine.