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Butanol and dilute sulfuric acid were used to extract paromomycin and gentamicin from Aquaphilic-based formulated creams. The extraction procedure was validated over different antibiotic concentration ranges for linearity, precision, accuracy, limited specificity, sensitivity and solution stability.
We report two cases of cryptosporidiosis after CD34-selected PBSCT for lymphoma. While the first patient died of pulmonary cryptosporidiosis, treatment with paromomycin, azithromycin and subcutaneous low-dose rhIL-2 to improve numerical and functional T lymphocyte defects completely eliminated infection in the second patient. We conclude, that the removal of mature T lymphocytes by positive selection of CD34+ cells bears the risk of a delayed immune reconstitution resulting in an increased incidence of severe and sometimes fatal opportunistic infections. IL-2 might be useful in this situation by accelerating immune reconstitution and reducing the danger of opportunistic infections.
A procedure for the extraction of paromomycin from different animal feed matrices (rabbit, chicken, pig feeds) and its subsequent determination via a reversed-phase ion-pair HPLC separation coupled with pulsed amperometric detection is described. The procedure optimised in terms of the extracting solvent and the solid phase extraction stationary phase allows the total recovery of the aminoglycoside antibiotic. The criteria used for the validation of the analytical method applied to the cited matrices are the linear dynamic range of the response, the detection limit, the repeatability, the intermediate repeatability and the accuracy. A comparison with a method described in the literature for the bulk analysis of this antibiotic is made.
Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL). Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases. This could be attributed to the low skin penetration of PA. Liposomal formulations usually provide sustained and enhanced drug levels in skin. The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial. Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method. Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method. The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1). The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells. The PA entrapment in LUV liposomes (20.4 +/- 2.2%) was higher than that observed for MLV liposomes (7.5 +/- 0.9%). Drug entrapment was 41.9 +/- 6.2% and 27.2 +/- 2.4% for PC and PC:CH LUV, respectively. The skin permeation was 1.55 +/- 0.31%, 1.29 +/- 0.40%, 0.20 +/- 0.08%, and 0.50 +/- 0.19% for PC LUV, PC:CH LUV, empty LUV +/- PA and aqueous solution, respectively. Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.
With the spread of the human immunodeficiency virus in the early 1980s, cryptosporidiosis was regarded as an AIDS-defining disease. As an opportunistic pathogen, the intestinal parasite Cryptosporidium parvum became an important cause of chronic diarrhoea, leading to high morbidity and mortality in immunocompromised patients. To date, no effective chemotherapy is available. With the introduction of protease inhibitors (PIs) in highly active antiretroviral therapy (HAART), the incidence of cryptosporidiosis in AIDS patients has declined substantially in western countries. We have therefore tested the effect of five PIs used in HAART on the excystation, invasion and development of the parasite in a cell culture system. The human ileocaecal adenocarcinoma cell line HCT-8 served as a host cell. None of the substances had an effect on the excystation rate, and only nelfinavir moderately, but statistically significantly, inhibited the host cell invasion over a period of 2 h. There were more pronounced inhibitory effects when PIs were present over the total time of intracellular development (48 h). Indinavir, nelfinavir and ritonavir inhibited parasite development significantly. The inhibitory effect was increased when the aminoglycoside paromomycin was combined with the PIs indinavir, ritonavir, and to a lesser extent saquinavir, compared to the PIs alone.
Aminoglycoside antibiotics in Escherichia coli and yeast can cause ribosomes to read through stop codons during translation. This can result in the phenotypic suppression of nonsense mutations. We show here for the first time that the aminoglycosides G-418 and paromomycin have similar effects in monkey (COS-7) cells in vivo. Suppression of an amber mutation (TAG) by aminoglycosides can restore the activity of a mutant gene transfected into COS-7 cells to almost 20% of wild type levels.
The antiprotozoan activity of secnidazole was studied in Cercocebus t. torquatus, Cercopithecus campbelli, Erythrocebus patas (Cercopithecidae), and Gorilla gorilla (Pongidae) compared with that of paromomycin in Cercocebus t. lunulatus (Cercopithecidae), E. patas, and G. gorilla (Pongidae) by coprological analysis. The antiprotozoan activity of both drugs depended on the parasite species and the host species. The drugs acted in a similar way on Entamoeba coli parasitising C. t. torquatus, and E. patas. This activity was different from that observed on I. buestchlii from the same host species. Nevertheless, E. coli parasitising cercopithecids and pongids responded to drugs differently.
Encouraged by in vitro results, we have assessed the in vivo activity of paromomycin (PRM) against Mycobacterium tuberculosis, multidrug-resistant (MDR) M. tuberculosis (resistant to isoniazid, rifampin, and streptomycin), and Mycobacterium avium complex in C57BL/6 mice and their beige counterparts. In all these experiments, PRM was effective in preventing mortality from a mycobacterial infection and was significantly more active than the drug-free control (P < 0.0005) in reducing the CFU relative to the mean log CFU in the lungs, livers, and spleens of infected animals. In the drug-susceptible M. tuberculosis experiment, PRM given at 100 and 200 mg/kg of body weight was significantly less active than isoniazid at 25 mg/kg (P < 0.0005) in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. In the MDR M. tuberculosis experiment, PRM given at 200 mg/kg was effective, relative to the drug-free control, in reducing the mean log CFU of an isolate of M. tuberculosis resistant to isoniazid, rifampin, and streptomycin. In the M. avium complex experiment, PRM given at 200 mg/kg was as effective as amikacin at 50 mg/kg in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. On the basis of our experiments, we believe that PRM has promising activity in vivo in the treatment of infections caused by M. tuberculosis, MDR M. tuberculosis, and M. avium complex.
Susceptibility testing was performed on Dientamoeba fragilis ATCC 30948 in a dixenic culture with Klebsiella pneumoniae and Bacteroides vulgatus. D. fragilis was cocultured with the bacteria in TYGM-9 medium (ATCC medium 1171). The activities of antiparasitic drugs were assessed by counting viable D. fragilis trophozoites with a hemacytometer by trypan blue exclusion. The minimal amebicidal concentrations of the following four drugs were determined: iodoquinol at 128 micrograms/ml, paromomycin at 16 micrograms/ml, tetracycline (questionably) at 32 micrograms/ml, and metronidazole at 32 micrograms/ml.
Spermidine-deficient Saccharomyces cerevisiae cells are much more sensitive to paromomycin than nondeficient cells, resulting in cessation of growth and cell death.
Management of a 42 year old female patient diagnosed with trichomoniasis is described. She failed to respond to recommended oral and high dose oral and topical metronidazole. Various options used in previously reported cases of metronidazole resistant trichomoniasis also failed to cure her condition. MIC showed the organism to be resistant to metronidazole. Cure was achieved with the use of topical intravaginal paromomycin.
A prospective, controlled-blind field trial was conducted to evaluate the efficacy and safety of paromomycin sulphate, given for 10 days from birth, in preventing natural cryptosporidiosis in calves. In the untreated control group, oocyst shedding and diarrhoea followed the pattern that had occurred on the farm before the trial, consistent with a perinatal infection, whereas in the treated group, the prepatent period was significantly longer than in the control group (P < 0.01) and oocyst shedding and diarrhoea started only after the drug was withdrawn. However, the regimen did not reduce the incidence of disease in the treated group.
The fifth case of human infection with Mesocestoides in the United States is reported in a 17-month-old child living in Mississippi. The child was asymptomatic and the source of the infection in unknown. Stools examined after treatment with paromomycin sulfate (Humatin) revealed no further evidence of infection. This is the 18th case of Mesocestoides infection in man reported in the literature.
OBJECTIVE: To compare the parasitological and clinical efficacy of four weeks versus two weeks of treatment with aminosidine (paromomycin) ointment in patients with cutaneous leishmaniasis caused by Leishmania major in the Islamic Republic of Iran. METHODS: Double-blind, randomized trial of four weeks of aminosidine ointment (n = 108) vs two weeks of aminosidine ointment and two weeks of placebo (n = 108). Patients were assessed on days 15, 29, 45, and 105 for clinical cures and clinical and parasitological cures. FINDINGS: Four weeks' treatment gave significantly better cure rates than two weeks' treatment: on day 29, there were 80/108 (74%) vs 64/108 (59%) clinical cures (P = 0.05) and 47 (44%) vs 26 (24%) clinical and parasitological cures (P = 0.005). By day 45, fewer patients who received four weeks' treatment had required rescue treatment with antimonials than those who received two weeks' treatment: 20 (19%) vs 36 (33%) (P = 0.02). On day 105, the results still favoured those who had been allocated four weeks of active treatment, but the differences were no longer as clearly significant. No side-effects were observed or reported. CONCLUSION: Approximately two-thirds of patients given ointment for four weeks were cured clinically. Although about half of those cured might have recovered spontaneously even without treatment, four weeks of aminosidine ointment could become the first-line treatment for uncomplicated cutaneous leishmaniasis due to L. major, with antimonials needed in only the one-third of patients not cured by the end of treatment with aminosidine. This would considerably reduce the costs and side-effects associated with antimonial drugs.
We have determined the complete sequence of the nuclear gene encoding the small subunit (17 S) rRNA of the ciliated protozoan Tetrahymena thermophila. The gene encodes an RNA molecule which is 1753 nucleotides in length. The sequence of the Tetrahymena small subunit rRNA is homologous to those of other eukaryotes, and the predicted secondary structure for the molecule includes features which are characteristic of eukaryotic small subunit rRNAs. We have also determined the nature of two different mutations in the Tetrahymena 17 S gene which result in resistance to the aminoglycoside antibiotics paromomycin and hygromycin. In each case we have identified a single base change near the 3' end of the rRNA, within a region that is highly evolutionarily conserved in both sequence and secondary structure. Analysis of the effects of these mutations on rRNA structure, and of the impact of these drugs on translation, should help to elucidate the role of the small subunit ribosomal RNA in ribosome function.
156 patients undersent colorectal surgery during a prospective blind study at the Städt. Krankenhaus München-Harlaching. The study showed that administration of 4,0 g Paromomycin (= Humatin) on each of the two preoperative days combined with mechanical cleansing of the intestine has a beneficial effect. Our test group showed significantly lower incidence of wound complications at the abdominal laparotomies (p less than 0,05; X2) and at the anastomoses (p less than 0,01; X2 than the control group. Anastomic leakage (major leaks) and following septical complications occurred nearly exclusively in our "Not-Humatin-group". The lethality of the entire group was 13,1% (n = 20).
Through the use of the Limulus test research has been carried out on gram-negative endotoxin in patients with hepatic cirrhosis, chronic hepatitis, acute hepatitis, and in a control group. The positivity of this test in patients with cirrhosis and chronic hepatitis was 93.3% and in cases of acute hepatitis it was 90.9%. The effect of the combined administration of lactulose and paromomycin on endotoxin blood levels has been evaluated in a group of 9 patients with acute hepatitis, 8 with cirrhosis, 1 in hepatic coma, and 1 patient with chronic persistent hepatitis: in 18 of the 19 patients the Limulus test became negative. The results have been discussed in relation to clinical and laboratory data, and to recent data concerning the interaction between intestinal bacterial flora, endotoxin, and liver. Hypotheses have been proposed regarding the hepatocellular c-AMP mediated mechanism of endotoxin action.
Distribution of radioactivity in paromomycin ascertained after application of 14C-D-glucose, 14C-D-glucosamine, 14C-2-deoxystreptamine, respectively, 14C-D-ribose is taken as basis for a biosynthesis scheme: While ribose bound in the antibiotic originates from glucose by oxidation and following decarboxylation, glucosamine is formed via fructose-6-phosphate. Paromose I arises from glucosamine, but not the cyclohexan derivative 2-deoxystreptamine, whose biosynthesis pathway is directly branching off glucose.