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PubMed2003

Comparative study of the prophylactic and therapeutic effects of paromomycin, recombinant IL-12 alone or in combination against Cryptosporidium parvum infection in immunosuppressed mice.

Administration of paromomycin (100 mg/kg orally) for 10 days, rIL-12 (0.5 ug/mouse s.c.) for 3 consecutive days or combination of both was evaluated before and after infection with C. parvum using immunosuppressed mice model. A total of 110 suckling albino mice were immunosuppressed by hydrocortisone acetate and infected with 10(6) Cryptosporidium oocysts. Assesment of drug efficacy was done by estimating the oocyst count in stool using modified Ziehl Neelsen technique, the histopathological examination of terminal ileum and determination of serum level of IFN-gamma and calculation of the cure rate. The combination of paromomycin and rIL-12 was more effective than either drug alone. The cure rate was 86.7% when the regimen used prophylactically and 73.3% when the combination administered. Regression of the histopathological changes in comparison to the control group was noted. Moreover the combination regimens produced significant higher level of IFN-gamma suggesting that both rIL-12 and Paromomycin can act additively or synergistically in the prevention of C. parvum infection most probably through activation of INF-gamma production.

Animals↗
PubMed1992

Treatment of cryptosporidiosis with paromomycin. A report of five cases.

Cryptosporidiosis continues to be one of the most devastating complications of the acquired immunodeficiency syndrome, causing severe, chronic diarrhea that is largely refractory to treatment. More than 60 drugs have been tried in the treatment of cryptosporidiosis, none of which have been consistently successful. We describe the successful treatment of cryptosporidiosis in five patients with acquired immunodeficiency syndrome with oral paromomycin at a dose of 1500 to 2000 mg/d. All five patients had resolution of symptoms and normalization of bowel movements, although one patient later relapsed while receiving paromomycin. Three of five patients cleared Cryptosporidium from the stool. Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted.

AIDS-Related Opportunistic Infections↗
PubMed1977

[Isolation and substrate specificity of neomycin (paromomycin)--phosphotransferase from Actinomyces fradiae, a producer of neomycin].

Neomycin (paromomycin) phosphotransferase was isolated from the mycelium and fermentation broth filtrates of Act. fradiae. The substance was partially purified by means of fractionation with ammonium sulphate followed by gel-filtration through Sefadex G-100. The extracellular and intracellular forms of the enzyme had the same substrate specificity and used only neomycin and paromomycin as substrates. The other aminoglycosides, including kanamycins A and B, lividomycin and ribostamycin were not used. The both forms had the same thermolability. The intracellular form of the enzyme was detected in the mycelium at the early stages of the organism development, while the extracellular form was found in detectable amounts in the culture medium only at the late stages of the actinomycete development. Therefore, the neomycin-producing organism, i.e. Act. fradiae had one enzyme which phosphorilated neomycin and paromomycin and was excreted from the mycellium into the culture medium during the fermentation process.

Adenosine Triphosphate↗
PubMed1983

[Effects of paromomycin sulfate on Diphyllobothrium latum infections].

About 50 mg/kg of paromomycin sulfate was administered orally in a single or 2 divided doses to patients with Diphyllobothrium latum infections. The following results were obtained. After the treatment with paromomycin sulfate mature strobilae were expelled in all of 7 patients with Diphyllobothrium latum infections. We couldn't find scolices in all cases. Although these stools were examined for 2 months after the treatment, the eggs of Diphyllobothrium latum were not identified. No side effects were observed in all cases. It was concluded that paromomycin sulfate was effective on the treatment of Diphyllobothrium latum infections.

Adult↗
PubMed1993

Paromomycin is effective as prophylaxis for cryptosporidiosis in dairy calves.

Of 16 experimentally infected neonatal dairy calves, 12 were fed paromomycin twice daily in their milk for 11 consecutive days beginning 1 day before oral inoculation with 1.5-2.0 x 10(6) oocysts of Cryptosporidium parvum. Four calves each in groups A, B, C, and D received total daily doses of 100, 50, 25, and 0 mg of paromomycin per kilogram of body weight, respectively. From birth until 28 days of age feces from each calf were examined for diarrhea, and oocysts were enumerated, rectal temperature was recorded, and weight gain was determined. Total days of diarrhea, severity of diarrhea, the total number of days oocysts were shed, and the number of oocysts shed were significantly less in group A than in the unmedicated group D. The severity of diarrhea was also significantly less in groups B and C than in group D. Oocysts were not detected in feces from calves in group A. Except for 1 calf, oocysts were not detected from calves in groups B and C during the first week the drug was administered and those calves that shed oocysts began shedding at or near the end of paromomycin administration or more than 1 wk after treatment ended. Frequency of fever and weight gains did not vary significantly between the unmedicated and medicated groups except for group C, calves of which gained significantly less weight than those in all other groups.

Animals↗
PubMed1984

Cloning and expression in Streptomyces lividans of a paromomycin phosphotransferase from Streptomyces rimosus Forma paromomycinus.

The paromomycin producing organism Streptomyces rimosus forma paromomycinus is resistant to this antibiotic and contains a phosphotransferase which inactivates paromomycin. The gene encoding this enzyme has been inserted in the Streptomyces vector pIJ702 and then cloned in Streptomyces lividans, selecting for paromomycin-resistance. Three plasmids have been isolated and one of them, pMJ1, contains a 2.2 kb insert with a single HindIII restriction site. Insertion of foreign DNA in this site blocks the expression of the phosphotransferase enzyme indicating that it is within the cloned gene. These findings provide a new dominant selective marker for Streptomyces cloning vectors with the versatility of insertional inactivation.

Cloning, Molecular↗
PubMed1977

[Physiology and biochemistry of streptomycetes. X. Biological degradation of paromomycin and alkaline phosphatase activity depending on antibiotic production by Streptomyces albus var. metamycinus nov. var].

After adding 14C-paromomycin to the fermentation broth we observed a varying course of decomposition of the antibiotic, which is dependent on the intensity of paromomycin biosynthesis running simultaneously. At a reduced rate of antibiotic biosynthesis, the activity of alkaline phosphatase is lower than with an increased rate of production. This applies for mycelium as well as for broth.

Alkaline Phosphatase↗
PubMed1991

Hygromycin- and paromomycin-resistant mutants of Aspergillus nidulans alter translational fidelity.

Mutants of Aspergillus nidulans resistant to the aminoglycoside antibiotics paromomycin and hygromycin B have been isolated and their growth characteristics are described here. Most paromomycin mutants were cross-resistant to hygromycin and geneticin. All the hygromycin-resistant mutants were slightly cross-resistant to geneticin. Out of the 15 mutants tested 14 had drug-resistant ribosomes in vitro and all 12 of those investigated further had reduced levels of translational misreading. Five new loci have been found--parA on linkage group I, hygA on III, hygB on IV, hygC on V, hygD on VI and parB on VIII. This increases, to at least 12, the number of translational fidelity loci in A. nidulans.

Aspergillus nidulans↗
PubMed1980

Search for ribosomal mutants in Podospora anserina: genetic analysis of mutants resistant to paromomycin.

It has recently been shown that paromomycin, an antibiotic of the aminoglycoside family, is also active on eukaryotic cytoplasmic ribosomes. In the fungus Podospora anserina, genetic analysis of ten mutants resistant to high doses of paromomycin shows that this resistance is caused by mutations in two different nuclear genes. These mutants display pleiotropic phenotypes (cold sensitivity, mycelium and spore appearance and coloration, cross-resistance to other antibiotics). Double mutants are either lethal or very altered and unstable. Moreover, the cytochrome spectra of these mutants seem to indicate that cytoplasmic protein synthesis is affected. The mutants also display a slight suppressor effect. We can therefore assume that these mutations affect cytoplasmic ribosomes.

Ascomycota↗
PubMed1982

Analysis of revertants of a ribosomal mutation in Podospora anserina: evidence for new ribosomal mutations which confer hypersensitivity to paromomycin.

This paper describes the analysis of cold-resistant revertants of a cold-sensitive mutant. Pm1-1 is a ribosomal mutation screened for its paromomycin resistance. Suppression of its cold sensitivity occurs with two kinds of external mutations localized in two different loci. One of them, PmB, is assumed to be a ribosomal gene. PmB mutations confer hypersensitivity to paromomycin in vivo as well as in vitro in a cell-free protein synthesis system.

Ascomycota↗
PubMed1994

[Successful topical treatment of chronic cutaneous leishmaniasis with paromomycin sulfate (15%) and methylbenzethonium chloride (12%)].

A 19-year-old male patient with chronic cutaneous leishmania is was treated topically with paromomycin sulphate (15%) and methylbenzethonium chloride (12%) in petrolatum album. After application twice daily for two periods of 32 and 44 days the lesions were completely healed. Previous treatment for 9 months with ketoconazole (400 mg/day) together with the topical application of thiabendazole (2.5%) in base had been unsuccessful. No major side effects were observed after paromomycin sulphate application.

Administration, Topical↗
PubMed2007

Comparative study of the efficacy of formulations containing fluconazole or paromomycin for topical treatment of infections by Leishmania (Leishmania) major and Leishmania (Leishmania) amazonensis.

The development of alternative therapeutic approaches for cutaneous leishmaniasis (CL) has received considerable attention in recent research, including the identification of formulations for topical treatment. In the present study, the activity of two formulations was evaluated in BALB/c mice experimentally infected with either Leishmania (Leishmania) major or L. (L.) amazonensis, a hydrophilic gel containing 10% paromomycin (PAHG) and a cream containing 1% fluconazole (FLUC). After development of ulcerated lesions, infected mice were divided into three groups of five animals each: (1) PA group: Lesions were covered with 50 microl of PAHG; (2) FLUC group: Lesions were covered with 50 microl of FLUC, and (3) placebo group: treated with gel without paromomycin. During and after treatment, the size of lesions was determined weekly using a caliper. The efficacy of PAHG was significantly higher than that observed for FLUC for both Leishmania species. The PAHG formulation was effective in promoting the healing of ulcers in all animals 28 days after the beginning of treatment, whereas none of the animals was cured by FLUC. These results suggest that the PAHG formulation could be suitable for clinical studies and may represent an alternative formulation for the topical treatment of CL.

Administration, Oral↗
PubMed1999

Efficacy of treatment with paromomycin, azithromycin, and nitazoxanide in a patient with disseminated cryptosporidiosis.

A 24-year-old HIV-positive heterosexual woman with disseminated cryptosporidiosis was monitored from January 1998 to May 1999. During this period, consecutive stool, sputum, and bile examinations showed the constant presence of Cryptosporidium oocysts. Although the patient was repeatedly treated with oral paromomycin and azithromycin and, finally, nitazoxanide, her condition continued to deteriorate. In order to monitor the in vitro susceptibility of the parasite, specimens from various sites were collected periodically. When the first clinical isolate was tested, the antimicrobial agents used (azithromycin at a concentration of 8 mg/l, paromomycin at of 1 mg/ml, and nitazoxanide at 10 mg/l) produced a decrease in parasite counts of 26.5%, 63.4%, and 67.2%, respectively. Subsequent isolates of Cryptosporidium parvum showed similar susceptibilities. This case demonstrates that failure of clinical treatment corresponded to inadequate growth inhibition of the parasite in vitro.

AIDS-Related Opportunistic Infections↗
PubMed1984

The effects of paromomycin on the fidelity of translation in a yeast cell-free system.

The effects of the aminoglycoside antibiotic paromomycin on the fidelity of translation of the synthetic template poly(U), and two natural mRNAs (rabbit globin mRNA and Brome Mosaic virus RNA), were examined in an mRNA-dependent cell-free system from the yeast Saccharomyces cerevisiae. At antibiotic concentrations that did not inhibit translation (100 microM) optimal mistranslation of all three templates was observed, with the effects declining at higher antibiotic concentrations. Synthesis of the opal termination read-through protein of rabbit beta-globin mRNA was induced by paromomycin, but only in lysates prepared from a [psi+] strain of yeast. The antibiotic did not induce detectable levels of either ochre or amber read-through, but did induce general misreading of Brome Mosaic virus RNA to the same degree in both [psi+] and [psi-] lysates. This misreading was enhanced by addition of the polyamine spermidine.

Animals↗
PubMed1995

Comparisons of ribosomal RNA sequences from amitochondrial protozoa: implications for processing, mRNA binding and paromomycin susceptibility.

The amitochondrial (a-mt) protozoa include four groups of organisms that are of interest as important human parasites and as probable descendents of the earliest branches of eukaryotic evolution. These organisms have not been directly compared in terms of structure and function of a specific molecule. We sequenced portions of their rRNA-encoding genes coding for the internal transcribed spacers (ITS1 and 2) and adjoining small subunit (SS), 5.8S and large subunit (LS) rRNAs. Included are sites for RNA processing, mRNA interaction and aminoglycoside binding, as well as potential protein-encoding genes. The ITS of all a-mt protozoa examined are relatively short, but otherwise diverse. They include one or two predominant nucleotides (A in Entamoeba and Trichomonas, T in Encephalitozoon and C in Giardia) and have minimal potential secondary structure, which may form the basis for the preferential processing of ITS sequences. The mechanism employed by a-mt protozoa to bind mRNA may be unique, since Giardia, Trichomonas and Entamoeba mRNAs have usually short 5' non-coding regions. In bacteria, the 3' terminus of the SS rRNA is involved in mRNA binding; analysis of Entamoeba and Trichomonas mRNA 5' non-coding sequences suggests an analogous mechanism involving potential base pairing to the loop of the terminal SS rRNA hairpin. Giardia sensitivity to paromomycin was previously correlated with the presence of a C:G bp near the decoding region of SS rRNA. This bp is also present in Entamoeba and Trichomonas, consistent with their susceptibility. Its absence in Encephalitozoon and other microsporidia predicts paromomycin resistance, and suggests a distinct evolutionary origin for this group.

Amino Acid Sequence↗
PubMed2001

Nitroimidazole-resistant vaginal trichomoniasis treated with paromomycin.

A 33-year old woman with nitroimidazole-resistant vaginal trichomoniasis is described. She was treated with intravaginal paromomycin (500 mg daily for 2 days). This cured the trichomoniasis but resulted in severe local side effects. Paromomycin may be useful for difficult cases of nitroimidazole-resistant Trichomonas vaginalis vaginitis. The exact dosage still has to be determined.

Adult↗
PubMed2001

Which aminoglycoside ring is most important for binding? A hydropathic analysis of gentamicin, paromomycin, and analogues.

The NMR structures of gentamicin and paromomycin in complex with the A-site of Escherichia coli 16S ribosomal RNA were modified with molecular modeling to 12 analogues. The intermolecular interactions between these molecules and RNA were examined using the HINT (Hydropathic INTeractions) computational model to obtain interaction scores that have been shown previously to be related to free energy. The calculations correlated well with experimental binding data, and the interaction scores were used to analyze the specific structural features of each aminoglycoside that contribute to the overall binding with the 16S rRNA. Our calculations indicate that, while ring I binds to the main binding pocket of the rRNA A-site, ring IV of paromomycin-based aminoglycosides contributes significantly to the overall binding.

Algorithms↗
PubMed1997

A randomized clinical trial of topical paromomycin versus oral ketoconazole for treating cutaneous leishmaniasis in Turkey.

An open-labeled, randomized clinical trial to evaluate the efficacy of paromomycin ointment as compared with ketoconazole was conducted on seventy-two patients of both sexes and different ages with the confirmed diagnosis of cutaneous leishmaniasis (CL). All patients had a complete clinical evaluation for other diseases. Patients were excluded if they were pregnant or nursing or if they had serious concomitant diseases. Patients were divided randomly into two treatment groups: in the first group 40 patients were treated with an ointment containing 15% paromomycin sulfate and 12% methylbenzothonium chloride in white soft paraffin (labeled as p-ointment by El-On1) twice daily for 15 days. Treated lesions were left uncovered. The second group consisted of 32 patients who received ketoconazole 400 mg/day orally for 30 days. This dosage was reduced to 200 mg/day for patients below 12 years of age. In all cases the diagnosis was based on positive smear and/or culture. Direct smears were prepared from the exudate obtained by a small incision made at the edge of the lesion with a sterile surgical blade or lancet and stained using the Giemsa method for leishmania bodies (Fig 1). In smear negative and suspected cases aspirates taken by puncturing the lesions were inoculated onto NNN (Novy, McNeal, Nicolle) medium for culture. The cultures were incubated at 28 degrees C and the development of motile promastigotes was observed. Clinical and parasitological evaluations of the patients were performed at the end of the treatment period and 4 weeks post-treatment. A cure was defined as complete healing and disappearance of the lesion or reversible hypopigmentation at the site of lesion. Incomplete or partial improvement was defined as a reduction in the size of a lesion and the absence of parasites on smear or culture. A treatment failure was defined as the absence of any changes in the lesion and persistence of parasites on smear or culture.

Administration, Oral↗