Effects of nifedipine, metronidazole, and nitric oxide donors on spore germination and cell culture infection of the microsporidia Encephalitozoon hellem and Encephalitozoon intestinalis.
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Two species of microsporidia, Encephalitozoon hellem and Encephalitozoon intestinalis, were isolated from AIDS patients and cultured in green monkey kidney cells. A spore germination assay and a cultured-cell infection assay were used to test the efficacy of candidate antiparasitic agents. The calcium channel blocker nifedipine, metronidazole, and two nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside, were tested in the two assays. Nifedipine (10(-8) M) significantly inhibited E. hellem spore germination in three of four germination media. Metronidazole (10(-5) M) inhibited germination weakly and significantly inhibited E. intestinalis germination in a single germination medium. The inhibitory effect of nifedipine and metronidazole used together was greater than the sum of the effects of the drugs used alone in all E. hellem germination assays. The NO donors also inhibited spore germination. The inhibitory effect of nifedipine and metronidazole could be reversed by washing the spores, while that of the NO donors was not reversible. In early cultured-cell infections, both nifedipine (10(-8) M) and metronidazole (10(-5) M) significantly reduced the number of cells being infected. As the infection spread, these agents were less effective. Some inhibition of the spread of the infection was also demonstrated with the NO donors at a concentration (10(-5) M) not obviously toxic to the cultured cells. These data suggest that combination drug therapy targeting spore germination and intracellular parasite development is promising. (+info)
Drug interactions in patients infected with human immunodeficiency virus.
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Patients with AIDS who are receiving optimal medical care, including combination therapy with antiretroviral agents and more effective prophylaxis and therapy for opportunistic infections and neoplasms, are surviving longer. However, the potential for drug interactions in these patients is increased because many of the currently used antibiotics and antiviral agents have profound effects on the hepatic cytochrome P-450 enzyme system, on renal tubular function, and on bone marrow function. In this AIDS Commentary, Dr. Piscitelli and colleagues have succinctly reviewed the current state of our knowledge regarding the potential for additive or synergistic drug interactions that can result in enhanced toxicity or, alternatively, augmented therapeutic benefit. Information on these interactions will become more important as more intensive and effective therapy becomes available for persons with far-advanced infection due to human immunodeficiency virus type 1. (+info)
Waterborne protozoan pathogens.
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Protozoan parasites were the most frequently identified etiologic agents in waterborne disease outbreak from 1991 to 1994. The waterborne parasites Giardia lamblia, Naegleria fowleri, Acanthamoeba spp., Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanesis, Isospora belli, and the microsporidia are reviewed. For each parasite, the review includes history, life cycle, incidence, symptoms, and therapy. Clinical detection methods are compared, and emerging technologies are discussed. Information on the association of these parasites with waterborne outbreaks is reviewed. Current information on protozoan parasites identified as etiological agents in waterborne outbreaks is discussed. Water industry issues related to recent disease outbreaks are examined in the context of water quality testing regulations for G. lamblia and those proposed for C. parvum. The review identifies the limitations of the American Society of Testing and Materials water-testing method for these parasites. An overview of federal regulations affecting the water industry and laboratories that test for water quality is also provided. The article highlights the importance of the clinical laboratory as a frontline defense for the detection of infectious organisms. The review points to the need for clinical laboratories, physicians, and public health personnel to cooperatively plan and assess the challenge of meeting this potential public health threat. (+info)
Infectious complications in left ventricular assist device recipients.
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The left ventricular assist device (LVAD) has revolutionized the care of patients with heart failure who are awaiting transplantation. Despite reports of significant infection rates associated with LVAD implantation, few data are available concerning the management of LVAD-related infections and their impact on transplantation. Eight (40%) of our first 20 LVAD recipients developed infections. LVAD-related bloodstream infection occurred in three (15%) patients; infection was due to Staphylococcus aureus in one case, coagulase-negative staphylococci in the second case, and S. aureus and Candida tropicalis in the third case. All three patients were treated with courses of antibiotics that were appropriate for prosthetic valve endocarditis and received antibiotics for at least 6 weeks. All infected patients underwent successful transplantation and had no evidence of recurrence of infection up to 16 months postoperatively. Our experience suggests that LVAD infections can be successfully treated without device removal and that cardiac transplantation can be performed in individuals with LVAD-related bloodstream infection. (+info)
Transient and selectable transformation of the parasitic protist Trichomonas vaginalis.
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We have developed methods to transiently and selectably transform the human-infective protist Trichomonas vaginalis. This parasite, a common cause of vaginitis worldwide, is one of the earlier branching eukaryotes studied to date. We have introduced three heterologous genes into T. vaginalis by electroporation and have used the 5' and 3' untranslated regions of the endogenous gene alpha-succinyl CoA synthetase B (alpha-SCSB) to drive transcription of these genes. Transient expression of two reporter proteins, chloramphenicol acetyltransferase (CAT) or luciferase, was detected when electroporating in the presence of 50 microg closed-circular construct. Optimal levels of expression were observed using approximately 2.5 x 10(8) T. vaginalis cells and 350 volts, 960 microFd for electroporation; however, other conditions also led to significant reporter gene expression. A time course following the expression of CAT in T. vaginalis transient transformants revealed the highest level of expression 8-21 hr postelectroporation and showed that CAT activity is undetectable using TLC by 99 hr postelectroporation. The system we established to obtain selectable transformants uses the neomycin phosphotransferase (neo) gene as the selectable marker. Cells electroporated with 20 microg of the NEO construct were plated in the presence of 50 microg/ml paromomycin and incubated in an anaerobic chamber. The paromomycin-resistant colonies that formed within 3-5 days were cultivated in the presence of drug and DNA was isolated for analyses. The NEO construct was shown to be maintained episomally, as a closed-circle, at between 10-30 copies per cell. The ability to transiently and selectably transform T. vaginalis should greatly enhance research on this important human parasite. (+info)
Comparative in vitro activity of meropenem versus other extended-spectrum antimicrobials against randomly chosen and selected resistant clinical isolates tested in 26 North American centers.
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The in vitro antibacterial activity of meropenem and up to nine other antimicrobials was compared in studies at 26 North American centers from 1989 to 1992 with use of standardized and controlled procedures for determining minimal inhibitory concentrations (MICs) against 12,483 recent clinical isolates and additional drug-resistant strains. Overall, carbapenems were the most active drugs. The antibacterial activity of meropenem was consistent against random isolates in all centers; however, inclusion of large proportions of multidrug-resistant gram-negative aerobes by some centers did increase MICs of meropenem and the comparators. Meropenem was 4-64 times more active than imipenem against gram-negatives, including Enterobacteriaceae organisms, Pseudomonas aeruginosa, Burkholderia cepacia, Neisseria meningiditis, and Haemophilus influenzae. Imipenem was up to 2-4 times more active than meropenem against some gram-positive cocci, including Enterococcus faecalis. Carbapenems were similarly active against anaerobes, and resistant strains were rarely encountered. Meropenem, unlike imipenem or ceftazidime, was bactericidal for all strains of Enterobacteriaceae, P. aeruginosa, and gram-positive cocci tested at < or = 8 times the MIC. A lack of antibiotic cross-resistance was frequently observed between comparator-resistant strains and meropenem. These data suggest the potential utility of meropenem as a monotherapeutic agent against a broad range of pathogens. (+info)
One week treatment for Helicobacter pylori infection.
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Helicobacter pylori is associated with primary antral gastritis, duodenal ulceration, and gastric cancer. Current regimens for treating infection in children using bismuth and antibiotics for two to six weeks are cumbersome. The aim of this study was to evaluate a one week course of treatment. All children undergoing endoscopy were assessed for the presence of H pylori by culture, histology, rapid urease test, and 13C urea breath test. Infected children received a one week course of colloidal bismuth subcitrate 480 mg/1.73 m2/day (maximum 120 mg four times a day), combined with metronidazole 20 mg/kg/day (maximum 200 mg three times a day), and clarithromycin 15 mg/kg/day (maximum 250 mg twice a day). To optimise compliance, drugs were dispensed in a 'Redidose' box containing a compartment for each day, and subcompartments marked 'breakfast', 'lunch', 'dinner', and 'bedtime'. Compliance and side effects were assessed immediately after treatment. A urea breath test was performed at least one month after treatment. Twenty two children infected with H pylori were entered into the study; 20 of these took all doses; two children suffered significant side effects (diarrhoea and vomiting). H pylori was eradicated in 21 of the 22 children (95.45%; 95% confidence interval 77% to 100%). This study shows that H pylori infection in children can be cleared by a one week course of treatment. (+info)
In vitro assessment of gastric mucosal transfer of anti-Helicobacter therapeutic agents.
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A novel animal model for studying antibiotic transfer across gastric mucosa was developed by using adult rats. Gastric corpus mucosa was mounted in an Ussing chamber system and bathed in oxygenated Krebs solution. Metronidazole flux from serosa to mucosa (J(S-->M)) was measured over 60 min under basal conditions and compared with mucosa-to-serosa flux (J(M-->S)). The effects of varying the chamber cross-sectional diameter and of stimulation by histamine and carbachol were assessed. Metronidazole J(M-->S) was measured with the mucosal pH at 2.2, 2.7, 3.2, and 7.4. Amoxicillin J(S-->M) under basal conditions was also measured and compared with metronidazole J(S-->M). Metronidazole J(S-->M) was proportional to serosal concentration (P < 0.001) under basal conditions, being 3.98 nmol x h(-1) x cm(-2) with a serosal concentration of 0.2 mmol/liter. Amoxicillin J(S-->M) was significantly lower under similar conditions at 0.50 nmol x h(-1) x cm(-2) (P < 0.01). Metronidazole J(S-->M) was not significantly different from J(M-->S), between chambers of different sizes, or following stimulation. When the mucosal pH was changed, J(M-->S) was proportional to the un-ionized concentration on the mucosal side (P < 0.001). Therefore, this model shows properties analogous to those of human gastric mucosa in vivo, with partitioning of metronidazole on the mucosal side according to pH, diffusion of metronidazole across the mucosa in both directions, and selectivity for different antibiotics, and it will be useful for the study of other therapeutic agents in the treatment of Helicobacter pylori. (+info)