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PubMed1994

Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial.

To test the effects of paromomycin, 10 patients with AIDS and cryptosporidiosis were randomized to paromomycin or placebo in a double-blind trial. After 14 days, patients were switched to the other treatment for 14 additional days. Measures included the number and character of each stool and weekly 24-h stool specimens for weight and oocyst excretion. During the paromomycin treatment phase, oocyst excretion decreased from 314 x 10(6) to 109 x 10(6)24 h (P < .02). Oocyst excretion increased for the 4 patients initially on placebo compared to a median decrease of 128 x 10(6)/24 h for the 6 initially treated with drug (P < .02). Stool frequency also decreased more in those treated with drug (3.6 fewer vs. 1.25 fewer/24 h, P < .05). Trends favored drug over placebo for stool weight, stool character, and Karnofsky score. Paromomycin treatment resulted in improvement in both clinical and parasitologic parameters in cryptosporidiosis in AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1994

A comparison of anticryptosporidial activity of paromomycin with that of other aminoglycosides and azithromycin in immunosuppressed rats.

Of six evaluated aminoglycosides, paromomycin was the only one that showed activity against Cryptosporidium parvum in immunosuppressed rats. Oral dosages > or = 200 mg/kg/day reduced the severity of ileal infections; however, paromomycin was ineffective against cecal and biliary tract infections at 400 mg/kg/day orally and 50 mg/kg/day intraperitoneally. Oral paromomycin (400 mg/kg/day) was also less effective than azithromycin (400 mg/kg/day) against Cryptosporidium infection involving the ileum, cecum, or biliary tract of immunosuppressed rats. The data suggest that paromomycin may be an effective treatment for acute cryptosporidiosis of the small intestine but is probably ineffective against large intestine or biliary tract infections in the immunosuppressed host.

Animals↗
PubMed1999

In-vitro synergy of paromomycin with metronidazole alone or metronidazole plus hydroxymetronidazole against Helicobacter pylori.

The in-vitro activities of paromomycin and metronidazole alone or paromomycin and metronidazole plus hydroxymetronidazole (2:1 ratio) were studied against 19 Helicobacter pylori isolates using an in-vitro chequerboard technique. Partial synergy was demonstrated for the majority of isolates (11/19) for both combinations tested. When hydroxymetronidazole was added to the parent compound, the number of metronidazole-sensitive isolates demonstrating synergy increased to 5/12, compared with 1/12 for the combination that did not include the metabolite. In metronidazole-resistant isolates there was a shift from an additive effect to partial synergy for the combination containing hydroxymetronidazole. The in-vitro activity of paromomycin and the synergic effect that is achieved in combination with metronidazole and hydroxymetronidazole render paromomycin suitable for further investigation as a treatment option for H. pylori infection.

Anti-Bacterial Agents↗
PubMed1982

Effect of paromomycin sulfate on endotoxemia in patients with cirrhosis.

We evaluated, in a randomized double-blind trial, the efficacy of oral paromomycin sulfate administration in the prevention of endotoxemia in 24 cirrhotic patients with endotoxemia. Renal function was evaluated by glomerular-filtration rate and renal plasma flow at the beginning and at the end of the study period. After the administration of paromomycin sulfate, 2 g/day for 4 weeks, endotoxemia disappeared in 10 out of 13 (76.9%) cirrhotic patients with endotoxemia, whereas it became negative in only 3 of the 11 (27.3%) treated with placebo, the difference being significant (P less than 0.05). With regard to correlation of endotoxemia with renal impairment, endogenous creatinine clearance and p-aminohippurate clearance were significantly improved (P less than 0.02) in those patients whose endotoxemia disappeared on paromomycin sulfate administration. We did not find significant improvement, however, neither in liver function or in blood coagulation tests in the same patients. Paromomycin sulfate seems to be effective in the prevention of endotoxemia and the associated renal impairment in cirrhosis in man.

Acute Kidney Injury↗
PubMedDate not supplied

Paromomycin therapy of endemic amebiasis in homosexual men.

A prospective evaluation was made of the therapeutic efficacy of paromomycin, an orally administered, nonabsorbable aminoglycoside, in 114 homosexual men with mild-to-moderate (nondysenteric) intestinal amebiasis. All patients received 25-35 mg/kg daily in three divided doses for seven days. Of the 80 patients with gastrointestinal complaints at the onset of therapy, 55 (80%) of 69 were asymptomatic within four to six weeks after completion of treatment; 11 patients were lost to follow-up. Paromomycin produced long-term eradication of intestinal Entameba histolytica infection in 92% of all men evaluated. The rate of microbiologic cure among patients with symptoms at the onset of therapy was comparable to that among asymptomatic individuals. Paromomycin was well tolerated, with mild diarrhea during therapy the only frequent adverse effect (67% of patients). Thus, paromomycin is an effective alternative to conventional multi-drug therapy for intestinal amebiasis, and it has the advantages of low toxicity, brief duration of therapy, and a high rate of patient compliance.

Adult↗
PubMed2005

Efficacy of paromomycin ointment in the treatment of cutaneous leishmaniasis: results of a double-blind, randomized trial in Isfahan, Iran.

Although pentavalent antimonials are often used in the first-line treatment of cutaneous leishmaniasis (CL), they have several adverse effects. Intralesional administration of antimonials and other antileishmanial drugs can be painful. In the present, double-blind, randomized study, to determine if topical treatment with paromomycin is effective in the treatment of CL, 35 cases of CL were treated, twice daily for 30 days, with a commercial skin-care lotion containing 10% urea (the placebo) and another 30 were similarly treated with the same lotion to which paromomycin sulphate had been added (to give a concentration of 15%). Each case was assessed clinically 7, 14, 21 and 30 days after treatment began, and parasitologically 30 and 60 days after the initiation of treatment. Five (17%) and five (17%) of the cases treated with paromomycin showed complete healing, with the apparent clearance of amastigotes from their lesions, 30 and 60 days after treatment began, respectively. At the same time-points, however, the lesions on six (17%) and seven (20%) of the cases in the placebo group, respectively, also appeared to have healed completely. Ointment containing 15% paromomycin therefore appears ineffective in the treatment of CL, at least when applied twice daily for 30 days to the lesions of cases from an endemic area of Isfahan, Iran.

Administration, Topical↗
PubMed2002

Anticryptosporidial prophylactic efficacy of enrofloxacin and paromomycin in chickens.

Two battery tests were conducted to study the anticryptosporidial prophylactic efficacy of the 2 commercially available antibiotics, enrofloxacin and paromomycin. The efficacy of enrofloxacin was 52% at the recommended level, which could not be increased, using twice the recommended dose. At the recommended levels, paromomycin reduced the oocyst output of birds by 67-82%, showing the highest efficacy of all drugs tested against avian cryptosporidiosis thus far. Moreover, the patent period was shortened by 12-23%. The body weight gain of paromomycin-treated chickens was almost identical with that of uninfected, untreated control birds irrespective of dosage, indicating the lack of toxicity. Although paromomycin is not registered for use in birds, in combination with sanitary procedures and disinfection, it may help in the control of cryptosporidiosis in some bird facilities.

Animals↗
PubMed1994

Paromomycin resistance in Leishmania tropica: lack of correlation with mutation in the small subunit ribosomal RNA gene.

The aminoglycoside antibiotic paromomycin is a potentially useful anti-leishmanial chemotherapeutic agent. Resistance to this antibiotic was studied using Leishmania tropica. Promastigotes resistant to 210 micrograms/ml of paromomycin were selected by exposing them to gradual increments of this drug. Previous work in Escherichia coli, Tetrahymena, and yeast mitochondrial mutants has demonstrated mutations in the E. coli small subunit ribosomal RNA at the 1409:1491 basepair position, or equivalent positions in other organisms, resulting in basepair disruption. When the nucleotide sequence at both the DNA and RNA levels of the resistant L. tropica promastigotes cultured in the presence of paromomycin was compared with those of the drug-sensitive parent, there was no sequence change at the putative mutation site. Paromomycin resistance in L. tropica is apparently due to other mechanisms.

Animals↗
PubMed1983

[Ultrastructural changes of the tegument on Diphyllobothrium erinacei and Hymenolepis nana treated with paromomycin sulfate in vitro].

The effects of paromomycin sulfate on Diphyllobothrium erinacei and Hymenolepis nana in vitro were examined morphologically with a scanning and a transmission electron microscope. D. erinacei was incubated for 3 and 6 hours at 37 degrees C in a culture medium, 0.85% physiological saline solution, containing 0.5% paromomycin sulfate. H. nana was incubated in the same medium for 3 hours only. The concentration of paromomycin sulfate was set basing on the results which Kitamoto (1968) reported as the concentration level in feces after administrations of this drug in a clinical survey. The effect of the drug on the surface structure in both worms appeared markedly in the neck region. Mechanisms of breakdown on the tegument were supposed as follows. First, microtriches were disconnected from the tegumental surface and many vesicles were formed in the cytoplasm of the tegument. Finally, the tegument layer was excoriated to exposed the basal lamina. In 6 hours incubation, this surface of the worm suffered more damage than that in 3 hours. The damage of the basal lamina as in the case of D. latum expelled from a man by paromomycin (Y. Tongu et al.), however, could not be observed in the present study in vitro. It suggests that the destruction of basal lamina usually observed with the expelled worms from clinically treated human might be due to the combined effect of digestive enzymes secreted from host and the mechanical impact of intestinal peristalsis. Some of the vesicles in the tegument may originate from mitochondria because the fine structure of cristae were occasionally observed remaining in the vesicles.

Animals↗
PubMed1983

[In vitro and in vivo effects of paromomycin sulfate on tapeworm, especially Diphyllobothrium ditremum, and clinical effects on diphyllobothriasis in man].

Plerocercoids of D. ditremum were obtained from the Japanese surfsmelt (Hypomesus pretiosus) and administered to Golden hamsters. The animals were treated with paromomycin sulfate on the 16th day of infection. Anthelmintic effect was imperfection after administration of 530 mg/kg in 4 divided doses. Kamala and bithionol, however, successfully expelled the worm at the doses of 80 and 160 mg/kg and 12.5--70 mg/kg, respectively. The balloon-like structures and the other morphological changes of the tegument such as exfoliation of microtriches were remarkably observed on the worms immersed in 2% solution of paromomycin sulfate. Four human cases of diphyllobothriasis were treated with paromomycin sulfate at the doses of 46--56 mg/kg. No side effects were observed. Stool examination made 1 month after treatment were negative to the eggs. From these results, an anthelmintic effect of paromomycin sulfate was shown in the concentration of 2% on D. ditremum in vitro and in the dosage of 46--56 mg/kg in diphyllobothriasis lata patients.

Adolescent↗
PubMed1983

[Diphyllobothrium latum infection in Akita Prefecture. Infections occurring from 1974 to 1981 and the clinical effect of paromomycin sulfate].

Forty-one patients, aged 2 to 68 years old, infected with Diphyllobothrium latum in Akita prefecture were treated using paromomycin sulfate from 1974 to 1981. Paromomycin sulfate was administered orally in a single dose of 20, 30 mg/kg or 50 mg/kg. Twenty-three cases expelled tapeworms. However, only 9 (28.1%) out of 32 tapeworms expelled had their scolex. It can be said that all cases were successfully treated with paromomycin sulfate, since they showed the egg-negative on 3 weeks or 1 month after the treatment. The drug was well tolerated and no side effects were encountered in any patients. It was suggested that paromomycin sulfate was effective and also safe therapeutic agent for the treatment of D. latum infection.

Adolescent↗
PubMed1983

[Efficacy of paromomycin sulfate in the elimination of Diphyllobothrium species and Taenia saginata in clinical cases].

Recently it has been known that paromomycin sulfate had marked anthelmintic activity against some species of tapeworms. In this investigation, paromomycin sulfate was used for treating 6 cases of diphyllobothriasis and 1 case of Taenia saginata infection. Paromomycin sulfate was administered orally in a single dose or 2 divided doses of 40--60 mg/kg, being followed by a purge about 1.5 hours later. Strobila or fragments of proglottids were expelled from 5 cases, of which only 1 scolex was found in a case of infection with marine species of Diphyllobothrium. In 1 case of diphyllobothriasis no worm or worm-fragment was found in the stool even after the second challenge of treatment. Nevertheless follow-up examination for more than 1 month showed no evidence of remaining infection in all cases. Transient dizziness was observed in only 1 case, disappearing within about 30 minutes. Serum- and urine-examinations detected no abnormal signs in all cases excepting 1 case of diphyllobothriasis with suspected hepatitis. It was concluded that paromomycin sulfate is effective therapeutic agent for the treatment of taeniasis and diphyllobothriasis including marine species.

Adult↗
PubMed1982

[Ultrastructural changes in Diphyllobothrium latum from a man treated with paromomycin sulfate].

The effect of paromomycin sulfate on Diphyllobothrium latum in vivo in man was examined morphologically with a scanning and a transmission electron microscope. The worm used for this study was expelled from a man by treatment with paromomycin sulfate at 1 dose of 50 mg/kg. The surface of the neck region suffered great damage. The effect of paromomycin sulfate resulted in the progressive breakup of the microtriches and the tegument. Even the basal lamina was lost in some parts. As a result, the muscle layers were exposed directly to the air. In the immature proglottid, the basal lamina remained as an outermost surface, although paromomycin sulfate caused a great loss of the tegument. The mature proglottid was lacking microtriches in some parts. However, most of the tegument was covered with microtriches. The gravid proglottid remained without any loss of microtriches.

Adult↗
PubMed1980

[Treatment of Diphyllobothrium latum infection with paromomycin sulfate (author's transl)].

Recently, it has been known that the treatment with paromomycin sulfate is effective against many kinds of tapeworm. Paromomycin sulfate was used for treating 56 patients with Diphyllobothrium latum aged 2 approximately 65 years old. Paromomycin was administered orally in the dose of 25 approximately 50 mg/kg. All cases with Diphyllobothriasis latum were successfully treated with paromomycin. The drug was well tolerated and no side effects were observed in any patients.

Adult↗
PubMed1994

Lactulose or paromomycin do not affect ammonia generation in the isolated perfused rat small intestine.

It has been hypothesized that the beneficial effect on hepatic encephalopathy of lactulose or neomycin might be exerted by their effect on intermediary glutamine metabolism and ammonia generation within enterocytes. We examined glutamine consumption and the production of alanine and ammonia (net substrate exchange in nmol min-1 g-1) in isolated vascularly and luminally perfused small intestine from rats with and without pretreatment with lactulose (2.0 g/kg) or paromomycin (60 mg/kg). Without pretreatment, 50 mM lactulose or 1 mM paromomycin were equally ineffective to significantly reduce the consumption of arterial glutamine (-92 +/- 5 vs. -80 +/- 6 vs. -71 +/- 6 for controls, lactulose, or paromomycin; mean +/- SEM, n = 6 each, n.s. by analysis of variance), and the production of alanine (41 +/- 3 vs. 44 +/- 3 vs. 61 +/- 7, n.s.) or ammonia (42 +/- 6 vs. 42 +/- 6 vs. 38 +/- 6, n.s.). Similarly, glutamine utilisation, and the release of alanine and ammonia were not different after pretreatment for 10 days. Also, both agents did not reduce glutamine absorption from the lumen (-170 +/- 9 vs. -171 +/- 6 vs. -219 +/- 25, n = 5 each) or the concomitant vascular release of metabolic products alanine (92 +/- 7 vs. 78 +/- 10 vs. 77 +/- 10 vs. 77 +/- 7, n.s.) and ammonia (73 +/- 6 vs. 69 +/- 7 vs. 65 +/- 8, n.s.). Our results do not support the hypothesis, that lactulose or paromomycin reduce ammonia generation by small intestinal mucosa through a specific effect on intermediary glutamine metabolism.

Amino Acids↗
PubMed1982

Intracellular accumulation of a fluorescent derivative of paromomycin in human fibroblasts.

Human fetal lung fibroblasts grown in the presence of dansyl-paromomycin (DNS-Pm), a fluorescent derivative of the aminoglycoside antibiotic, paromomycin, probably accumulate DNS-Pm in the lysosomes. The intracellular concentration of DNS-Pm is proportional to the extracellular concentration and to the length of time cells are exposed to the compound. The accumulation of DNS-Pm by human fibroblasts continued to increase for several days, reaching a saturation after 7 days. The kinetic data are consistent with the establishment of a steady state in the cell between fluid-phase pinocytosis and exocytosis of DNS-Pm. About 80% of the intracellular DNS-Pm ws released in 24 hr when fresh medium without the analogue was added. The residual 20% remained within the cells, suggesting that it may be irreversibly bound to the lysosomes, endoplasmic reticulum, or ribosomes. The uptake of paromomycin by cells in culture may be a useful means to study error propagation during growth and lifespan of cells in vitro.

Chemical Phenomena↗
PubMed1998

Paromomycin binding induces a local conformational change in the A-site of 16 S rRNA.

Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site (A-site) cause misreading of the genetic code and inhibit translocation. An A-site RNA oligonucleotide specifically binds to aminoglycoside antibiotics and the structure of the RNA-paromomycin complex was previously determined by nuclear magnetic resonance (NMR) spectroscopy. Here, the A-site RNA structure in its free form has been determined using heteronuclear NMR and compared to the structure of the paromomycin-RNA complex. As in the complex with paromomycin, the asymmetric internal loop is closed by a Watson-Crick base-pair (C1407.G1494) and by two non-canonical base-pairs (U1406.U1495, A1408.A1493). A1492 stacks below A1493 and is intercalated between the upper and lower stems. The comparison of the free and bound conformations of the RNA shows that two universally conserved residues of the A site of 16 S rRNA, A1492 and A1493, are displaced towards the minor groove of the RNA helix in presence of antibiotic. These changes in the RNA conformation place the N1 positions of A1492 and A1493 on the minor groove side of the A-site RNA and suggest a mechanism of action of aminoglycosides on translation.

Anti-Bacterial Agents↗
PubMed1994

Mistranslation of human phosphoglycerate kinase in yeast in the presence of paromomycin.

Missense errors in the translation of mRNAs in Saccharomyces cerevisiae were screened by looking for charge heterogeneity of proteins on two-dimensional gels resulting from the substitution of charged and neutral amino acids. No such mistranslation was detected in wild-type yeast strains grown in the presence of the translational error-inducing antibiotic paromomycin. However, paromomycin-induced mistranslation of a heterologous mRNA, encoding human phosphoglycerate kinase expressed in yeast, was seen. We suggest that the combination of error-prone translation of a heterologous mRNA, and growth in the presence of paromomycin, leads to an accumulation of mistranslated proteins that can be detected by two-dimensional gel electrophoresis.

Aldose-Ketose Isomerases↗