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PubMed2004

The bacterial paromomycin resistance gene, aphH, as a dominant selectable marker in Volvox carteri.

The aminoglycoside antibiotic paromomycin that is highly toxic to the green alga Volvox carteri is efficiently inactivated by aminoglycoside 3'-phosphotransferase from Streptomyces rimosus. Therefore, we made constructs in which the bacterial aphH gene encoding this enzyme was combined with Volvox cis-regulatory elements in an attempt to develop a new dominant selectable marker--paromomycin resistance (PmR)--for use in Volvox nuclear transformation. The construct that provided the most efficient transformation was one in which aphH was placed between a chimeric promoter that was generated by fusing the Volvox hsp70 and rbcS3 promoters and the 3' UTR of the Volvox rbcS3 gene. When this plasmid was used in combination with a high-impact biolistic device, the frequency of stable PmR transformants ranged about 15 per 106 target cells. Due to rapid and sharp selection, PmR transformants were readily isolated after six days, which is half the time required for previously used markers. Co-transformation of an unselected marker ranged about 30%. The chimeric aphH gene was stably integrated into the Volvox genome, frequently as tandem multiple copies, and was expressed at a level that made selection of PmR transformants simple and unambiguous. This makes the engineered bacterial aphH gene an efficient dominant selection marker for the transformation and co-transformation of a broad range of V. carteri strains without the recurring need for using auxotrophic recipient strains.

Drug Resistance↗
PubMed1994

Bacteriostatic and bactericidal activities of paromomycin against Mycobacterium avium complex isolates.

The MICs and MBCs of paromomycin for 32 Mycobacterium avium complex (MAC) strains isolated from patients with the acquired immunodeficiency syndrome were determined by a radiometric broth dilution method. The MICs for the majority of strains were either 8 or 16 mg/L and the MBCs were four- to eight-fold higher. Paromomycin merits further evaluation as oral prophylaxis against disseminated MAC infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Case report: inhalation therapy of paromomycin is effective for respiratory infection and hypoxia by cryptosporidium with AIDS.

A 24-year-old man with AIDS and hemophilia A had intractable diarrhea and fever. Upon examination of stool and of a sigmoidal biopsy specimen, cryptosporidium was revealed. Approximately 2 months after admission, respiratory infection with hypoxia due to cryptosporidium developed. Paromomycin inhalation was effective therapy. To the authors' knowledge, this is the first case of respiratory cryptosporidiosis treated successfully by paromomycin inhalation.

AIDS-Related Opportunistic Infections↗
PubMed2007

Treatment of Dientamoeba fragilis infection with paromomycin.

Treatment with paromomycin (25-35 mg/kg/d for 7 days) was evaluated prospectively in 15 children with Dientamoeba fragilis infection after 1-month follow-up. At the end of the study, parasitologic effectiveness and clinical improvement were observed in 12/15 (80%) and 13/15 (87%) patients, respectively. Paromomycin appears to be an effective drug for treatment of D. fragilis infection in children.

Adolescent↗
PubMed1993

Effect of topical paromomycin on cell-mediated immunity during cutaneous leishmaniasis.

BACKGROUND: The aim of this study was to evaluate the effect of topical paromomycin treatment on the development of immunity during cutaneous leishmaniasis. METHODS: Three parameters of immunity were measured in the course of the disease: leishmanicidal effector activity, lymphocyte proliferation (cell-mediated immunity), and antibody levels (humoral immunity). Peripheral blood specimens of 55 treated and 36 untreated patients were tested. RESULTS: The main results of this study showed that there was a significant delay in the development of leishmanicidal effector activity and to a lesser extent also a delay in the development of antigen-specific proliferative response in the treated compared with the untreated group. No difference was observed between the groups regarding the values achieved in the various tests. CONCLUSIONS: These results suggest that topical paromomycin treatment delays the development of cell-mediated immunity but does not affect the levels of immunity that are eventually achieved.

Administration, Cutaneous↗
PubMed1999

Treatment of cutaneous leishmaniasis with 20% paromomycin ointment.

Cutaneous leishmaniasis is an infectious disease caused by flagellate protozoa of the genus Leishmania. In Mediterranean countries, the most common causative agents are Leishmania (L.) major, L. infantum and L. tropica. In Croatia, cutaneous leishmaniasis is a rare disease, the last case being reported in 1988. Our patient was a 5-year-old boy with a left cheek skin lesion in the form of papule with central exulceration, hyperkeratotic crust and erythema of a 6-month duration. The diagnosis of cutaneous leishmaniasis was based on history data (stay in the southernmost region of Croatia and multiple mosquito bites), light microscopic histology (dense infiltrates of large histiocytes with extracellular bodies), and positive Montenegro (leishmanin) test. A new therapy with aminosidine (paromomycin), an aminoglycoside antibiotic, in the form of ointment at a concentration of 20%, was for the first time used in Croatia. Four-week therapy resulted in complete regression of the skin lesions with residual hyperpigmentation. During therapy, no local or systemic side effects were observed. Thus, topical therapy with paromomycin could be considered an efficient therapeutic alternative in the management of cutaneous leishmaniasis.

Administration, Cutaneous↗
PubMed1995

Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model.

In the dexamethasone-treated rat model of cryptosporidiosis, paromomycin was effective at a dosage of 50 mg/kg/day or more for ileal infection and 200 mg/kg/day or more for cecal infection. At 1 and 3 weeks after treatment, a persistent infection was demonstrated in all rats. These results confirm the anticryptosporidial activity of paromomycin and underscore the limitations of this compound because of its potential toxicity at such high dosages and its inability to eradicate the infection.

Animals↗
PubMed1997

Synergistic anticryptosporidial potential of the combination alpha-1-antitrypsin and paromomycin.

The combined effect of the serine protease inhibitor alpha-1-antitrypsin (AAT) and the aminoglycoside paromomycin on Cryptosporidium parvum infection in vitro was investigated. AAT and paromomycin were mixed with C. parvum oocysts as either single or combined treatments and used to inoculate epithelial cell cultures. Single- and combined-treatment groups had significantly lower (P < 0.01) parasite numbers than untreated controls. The mean fractional inhibitory concentration indices suggested significant synergistic activity.

Animals↗
PubMed2005

Pulmonary cryptosporidiosis in an AIDS patient: successful treatment with paromomycin plus azithromycin.

Extra-intestinal cryptosporidiosis, especially of the biliary and respiratory tract, is likely in the course of an intestinal involvement, whereas it is rare without such a localization. We report a case of pulmonary cryptosporidiosis without apparent intestinal involvement in an AIDS patient, with favourable outcome after antimicrobial combination therapy with paromomycin plus azithromycin. The successful response to antimicrobial treatment was subsequently maintained by effective highly active antiretroviral therapy (HAART). We suggest that respiratory cryptosporidiosis should be investigated in HIV-infected patients with pulmonary symptoms and low CD4 cell count, and, if detected, treatment should include HAART plus the combination of paromomycin and azithromycin.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

[The treatment of cryptosporidiosis in AIDS patients using paromomycin].

The authors treated with paromomycin 25 patients, with AIDS and cryptosporidiosis. The drug was given orally in a doses of 500 mg qid, for a period of 14 days. Tolerance was good, with just two cases of mild side-effects. Clinical improvement was obtained in 19 (76%) patients. Parasitological cure, however, occurred only in a low percentage (25%). In some cases where initial success was observed, recrudescence occurred after some weeks or few months, but with retreatment again clinical improvement was obtained. Even if it does not lead to frequent parasite eradication, the good clinical results and tolerance permit us to consider paromomycin one of the few drugs effective for the treatment of cryptosporidial diarrhea in AIDS patients. Studies with maintainance therapy are indicated.

AIDS-Related Opportunistic Infections↗
PubMed1995

A randomized, placebo-controlled trial in Tunisia treating cutaneous leishmaniasis with paromomycin ointment.

A randomized, placebo-controlled, double-blind trial was carried out in 1992 in central Tunisia to assess the tolerability and efficacy of paromomycin ointment against zoonotic cutaneous leishmaniasis caused by Leishmania major. One hundred fifteen patients, 2--60 years of age, with a single lesion of parasitologically confirmed cutaneous leishmaniasis, were included in the trial. The ointment was applied twice a day from day 1 through day 14. Clinical and parasitologic evaluations of lesions were done at days 0, 15, 45, and 105. Fifty-seven patients were allocated the treatment and 58 the placebo. Based on local toxicity and laboratory evaluation, there was no difference in tolerability between the two groups. Parasitologic evaluation at day 15 showed that 74.5% of the treated group had negative smears compared with 56.4% among controls (P = 0.06). This difference was no longer apparent at days 45 and 105. Clinical evaluation at days 15, 45, and 105 did not indicate any difference between the two groups. The clinical evaluation at day 15 was a good predictor of the final prognosis of the lesion in the two groups when analyzed separately, suggesting no clinical relapse in either group. These findings suggest that paromomycin ointment should not be used in the present formulation as a treatment for zoonotic cutaneous leishmaniasis in Tunisia.

Adolescent↗
PubMed2001

Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala.

A double-blind, randomized trial was undertaken in Guatemala to determine the therapeutic efficacy of an ointment for the treatment of cutaneous leishmaniasis that contained 15% paromomycin and 12% methylbenzethonium chloride and that was applied twice a day for 20 days. The treatment group included 35 patients, and the placebo group included 33 patients. The initial clinical response rate (13 weeks after completing the treatment) was 91.4% in the treatment group and 39.4% in the placebo group. The final clinical response rate at the 12-month follow-up examination was 85.7% (31 of 35) in the treatment group and 39.4% (13 of 33) in the placebo group (P < or = 0.001). In general, the treatment was well tolerated and was never interrupted because of adverse effects. The number of adverse effects reported in the placebo group was lower than in the treatment group (16 events versus 30 events). All adverse effects reported by patients disappeared within 1 week of completing the treatment. Our findings show that the combination of paromomycin with methylbenzethonium chloride for 20 days is a good alternative for antimonial treatments of cutaneous leishmaniasis in Guatemala.

Adolescent↗
PubMedDate not supplied

Orthograde whole gut irrigation with mannite versus paromomycine + lactulose as prophylaxis of hepatic encephalopathy in patients with cirrhosis and upper gastrointestinal bleeding: results of a controlled randomized trial.

BACKGROUND/AIMS: In patients with liver cirrhosis and upper gastrointestinal bleeding development of hepatic encephalopathy is a major problem. The aim of the present study was to evaluate the efficacy of the mannite lavage in a controlled randomized trial with respect to the Child-Pugh classification. METHODOLOGY: After initial gastroscopy (+/- sclerotherapy) 39 patients with cirrhosis (18 F, 21 M; age: 57.5 +/- 11.9 yr; Child A: 6, Child B: 16, Child C: 17) and upper gastrointestinal-bleeding were classified according to the Child-Pugh-criteria (A,B,C) and randomized in 2 groups (A,B) for each Child-Pugh level. Patients in group A (n = 18) were initially treated with 2000 mL mannite solution (10%) during the first 2 hours using a naso-gastric tube. Treatment was continued using 2000 mL mannite solution (10%) per day until no rectal blood could be observed. Patients in group B (n = 21) were treated with paromomycine ter in die (1 g tid) and lactulose (10 mL tid). There were no statistical differences between both groups concerning age, sex, Child-Pugh-scores, severity or source of bleeding, initial hemoglobin-levels, number of given blood-transfusions or number of patients with sclerotherapy. RESULTS: Patients in group A were treated with a total of 3325 +/- 1897 mL mannite solution. The application was well tolerated. In addition, kinetics of serum creatinine, potassium and sodium levels did not show any significant changes. No significant differences between both groups could be shown with respect to clinical criteria of encephalopathy according to O'Grady and the length of intensive care unit treatment. Moreover, kinetic of ammonia-levels showed a pronounced decrease (P = 0.05) on day 2 versus day 1 in group A (110.0 +/- 24.2 vs. 156.4 +/- 98 mg/dL) as compared to group B (210.0 +/- 52.7 vs. 162.0 +/- 45 mg/dL). In group A, 6 patients (33.3%) died during the study as compared to 3 patients (14.3%) in group B (P > 0.05). The lethality rate was strongly associated with the larger proportion of Child-C-patients in group A. CONCLUSIONS: The data indicate that whole gut irrigation with mannite is equally efficacious as compared to standard treatment for prophylaxis of hepatic encephalopathy after upper gastrointestinal bleeding in liver cirrhosis. In contrast to previously published controlled studies, no impact of the lavage on the mortality rate or duration of intensive care unit treatment could be shown. With respect to the lower costs for the mannite solution as compared to paromomycine and lactulose (ROTE LISTE, Germany), the mannite lavage should be recommended for the prophylaxis of hepatic encephalopathy after upper gastrointestinal bleeding in patients with liver cirrhosis.

Adult↗
PubMedDate not supplied

Comparison of topical paromomycin sulfate (twice/day) with intralesional meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by L. major.

This is an open study to compare the cure rate of cutaneous leishmaniasis caused by L. major and treated with either paromomycin sulfate or intralesional injection of meglumine antimoniate. Sixty parasitologically proven cases with 1-3 lesions were included and divided randomly into two equal groups; one group received 1 ml of meglumine antimonate intradermally every other day for 20 days, the other group received the ointment containing 15% parmomycin sulfate in urea twice daily for 20 days. The patients were clinically evaluated at 1 and 6 weeks after treatment was completed. The results of clinical evaluation at 1 week after treatment completed showed a cure rate of 18 out of 27 (66%) in the meglumine antimonate injected group and 20 out of 29 (68%) in the paromomycin sulfate treated group. The chi square test was used to compare the cure rate between the two groups and showed no significant difference (p = 0.85).

Administration, Topical↗
PubMed1983

[Therapeutic effect of paromomycin sulfate in the treatment of Diphyllobothrium latum infections and an observation on the worm tissues affected by the drug].

Paromomycin sulfate (aminosidine) at a single dose of 32 to 53 mg/kg was orally given to 24 cases with proven diphyllobothriasis. Evaluation of efficacy of the drug was based on stool examination for the eggs after 3--4 weeks of treatment. The cure rate was obtained as 96% (23/24), and 30 worms were expelled from 24 patients. Only 1 unsuccessfully treated case of 34-year-old man was retreated at the same dose of the drug 3 weeks later to obtain the cure. Thirty worms were composed of a single worm each from 21 patients, 2 worms from a patient, 3 from 1, and 4 from 1. Scolices of 7 (23.3%) out 30 worms were found. Vomiting as side effect of the drug was observed in only a case of 4-year-old girl at 40 minutes after administration of the drug but it was mild and transient. Clinical symptoms or complaints before treatment were as follows; abdominal discomfort in 12 cases, abdominal pain in 7, diarrhea in 4, fatigue in 2, tinnitus, vomiting and frequent stool in 1 each. Seven cases were almost asymptomatic. Morphological changes of the worms immersed in paromomycin solution (aminosidine) (1.66 mg/ml) for 1, 2 and 3 hours were observed in comparison with worms kept in physiological saline solution. The destructive effects were fragmentation, dissolution and desquamation of the outer cuticle and basement membrane with PAS stain at 3 hours of the experiment. The damages were also demonstrated in subcuticular tissues composing of muscle layer and parenchymal cells.

Adolescent↗
PubMed1983

[Therapeutic effect of paromomycin sulfate on the 13th case of Mesocestoides lineatus infection found in Japan].

Mesocestoides tapeworm is a common cestode in carnivorous mammals, but human infection with the tapeworm of this genus have been infrequent. We have recently observed the 13th case of human infection with Mesocestoides lineatus in Japan. A 35-year-old man living in Gifu prefecture was admitted to our University Hospital with chief complaints of general fatigue and discharge of cestode segments in his stool. The patient gave a history of drinking blood and eating the raw liver of a snake Agkistrodon halys for medicinal purposes as same as the previous cases of all reported in Japan. The segments were identified as those of M. lineatus. He was treated orally 3 g of paromomycin sulfate. Stool examination after treatment with paromomycin sulfate revealed no evidence of parasitism. The present case may be the 2nd to have been successfully treated with paramomycin sulfate and the 21st case of Mesocestoides tapeworm infection in man described in the literature.

Adult↗
PubMed1994

AIDS-associated cryptosporidiosis with gastric stricture and a therapeutic response to paromomycin.

AIDS-associated cryptosporidiosis has been associated with severe, watery diarrhea and with multifocal biliary stricture. Gastric involvement has not been reported prominently. We report here the case of a 28-yr-old AIDS patient who developed typical watery diarrhea, followed by subtotal gastric obstruction secondary to antral stricturing. Biopsy of the stricture revealed severe inflammation and marked cryptosporidial infestation. Extensive workup excluded causes of stricture. He was empirically treated with paromomycin, with a surprisingly positive therapeutic response and clinical resolution of obstruction. Antral stricture may be another manifestation of cryptosporidial infection in AIDS. Paromomycin deserves further evaluation as an agent for treatment of this infection.

AIDS-Related Opportunistic Infections↗