Positive clinical experience with paromomycin sulfate in treatment of Balantioides coli (=Balantidium coli) natural infection in zoo-kept Mandrill monkeys (Mandrillus sphinx) and Western lowland gorillas (Gorilla gorilla gorilla).

Balantioides coli (=Balantidium coli), a large ciliated protozoan, is reported in multiple free-ranging and captive primate species, often in association with a clinical presentation that requires medical intervention. This report describes the clinical effectiveness of paromomycin sulfate against B.coli in zoo-kept mandrill monkeys (Mandrillus sphinx, at orally doses of 8-31 mg/kg, once daily (SID) for 7 days) and gorillas (Gorilla gorilla gorilla, at orally doses of 1.4-3.1 mg/kg, SID for 5 days).

Population pharmacokinetics of a combination of miltefosine and paromomycin in Eastern African children and adults with visceral leishmaniasis.

OBJECTIVES: To improve visceral leishmaniasis (VL) treatment in Eastern Africa, 14- and 28-day combination regimens of paromomycin plus allometrically dosed miltefosine were evaluated. As the majority of patients affected by VL are children, adequate paediatric exposure to miltefosine and paromomycin is key to ensuring good treatment response. METHODS: Pharmacokinetic data were collected in a multicentre randomized controlled trial in VL patients from Kenya, Sudan, Ethiopia and Uganda. Patients received paromomycin (20 mg/kg/day for 14 days) plus miltefosine (allometric dose for 14 or 28 days). Population pharmacokinetic models were developed. Adequacy of exposure and target attainment of paromomycin and miltefosine were evaluated in children and adults. RESULTS: Data from 265 patients (59% ≤12 years) were available for this pharmacokinetic analysis. Paromomycin exposure was lower in paediatric patients compared with adults [median (IQR) end-of-treatment AUC0-24h 187 (162-203) and 242 (217-328) µg·h/mL, respectively], but were both within the IQR of end-of-treatment exposure in Kenyan and Sudanese adult patients from a previous study. Cumulative miltefosine end-of-treatment exposure in paediatric patients and adults [AUCD0-28 517 (464-552) and 524 (456-567) µg·day/mL, respectively] and target attainment [time above the in vitro susceptibility value EC90 27 (25-28) and 30 (28-32) days, respectively] were comparable to previously observed values in adults. CONCLUSIONS: Paromomycin and miltefosine exposure in this new combination regimen corresponded to the desirable levels of exposure, supporting the implementation of the shortened 14 day combination regimen. Moreover, the lack of a clear exposure-response and exposure-toxicity relationship indicated adequate exposure within the therapeutic range in the studied population, including paediatric patients.

Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers.

BACKGROUND: In endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation. METHODS: Travelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months. RESULTS: Medical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group. DISCUSSION: In this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials.

Cost-effective In Vivo and In Vitro Mouse Models for Evaluating Anticryptosporidial Drug Efficacy: Assessing Vorinostat, Docetaxel, and Baicalein.

BACKGROUND: Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and specialized breeding/housing requirements limit in vivo drug testing. Numerous anticryptosporidial lead compounds identified in vitro remain untested in vivo. METHODS: Cryptosporidium tyzzeri, a natural mouse parasite closely related to Cryptosporidium parvum and Cryptosporidium hominis, was isolated to establish an infection model in immunocompetent mice. The model was validated using classic anticryptosporidial drugs (paromomycin and nitazoxanide) and then employed to assess the efficacy of 3 new leads (vorinostat, docetaxel, and baicalein). An in vitro culture of C. tyzzeri was also developed to complement the animal model. RESULTS: Chronic C. tyzzeri infection was established in chemically immunosuppressed wild-type mice. Paromomycin (1000 mg/kg/d) and nitazoxanide (100 mg/kg/d) demonstrated efficacy against C. tyzzeri. Vorinostat (30 mg/kg/d), docetaxel (25 mg/kg/d), and baicalein (50 mg/kg/d) were highly effective against C. tyzzeri infection. In vitro, nitazoxanide, vorinostat, docetaxel, and baicalein exhibited low to submicromolar efficacy against C. tyzzeri. CONCLUSIONS: Novel in vivo and in vitro models have been developed for cost-effective anticryptosporidial drug testing. Vorinostat, docetaxel, and baicalein show potential for repurposing and/or optimization for developing new anticryptosporidial drugs.

Development and validation of an ultra-high performance liquid chromatography coupled to tandem mass spectrometry method for the quantification of the antileishmanial drug paromomycin in human skin tissue.

Bioanalytical assay development and validation procedures were performed to quantify antiprotozoal drug paromomycin in human skin tissue by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. Paromomycin, an aminoglycoside drug, is administered intra-muscularly and used in the treatment of multiple clinical presentations of the neglected tropical disease leishmaniasis. It is currently studied in the treatment of post-kala-azar dermal leishmaniasis, a disease where the Leishmania parasites divide and reside in the skin. We present a target-site bioanalytical method to accurately quantify paromomycin in human skin tissue, with the clinical purpose of quantifying paromomycin in skin biopsies from post-kala-azar dermal leishmaniasis patients originating from Sudan. Enzymatic digestion using collagenase A incubated at 37 °C overnight was employed as homogenization method to produce skin tissue homogenates. Further sample preparation was performed by protein precipitation using trichloroacetic acid and a dilution step. Final extracts were injected onto a C18 analytical column and isocratic heptafluorobutyric acid ion-pair separation and elution were employed. The chromatography system was coupled to a triple quadrupole mass spectrometer for detection. The method was validated in digestion solution over a linear range from 5 to 1000 ng/mL (r2 ≥ 0.9967) with the assay performance of accuracy and precision within acceptable criteria values as stated by the EMA guidelines. Furthermore, matrix effects were observed in human skin tissue and were corrected by the multiple deuterated paromomycin internal standard. No substantial IS-normalized matrix effect was detected along with relatively high sample preparation recovery. Consequently, digestion solution matrix serving as the preparation of calibration standards can be used as surrogate matrix for human skin tissue, which is convenient given the limited availability of control matrix. Finally, paromomycin was accurately quantified in skin of post-kala-azar dermal leishmaniasis patients originating from clinical trials in Sudan.

Isolation, typing, and drug susceptibility of Leishmania (Leishmania) infantum isolates from dogs of the municipality of Embu das Artes, an endemic region for canine leishmaniasis in Brazil.

The parasitic protozoa Leishmania (Leishmania) infantum is the etiological agent of human visceral leishmaniasis and canine leishmaniasis in South America, where Brazil is the most affected country. This zoonotic disease is transmitted by the bite of an infected phlebotomine sand fly and dogs constitute the main domestic reservoir of the parasite. In this study, we screened 2348 dogs of the municipality of Embu das Artes, Brazil, for antibodies against the parasite. Prevalence for canine leishmaniasis seropositivity was 2.81%, as assessed using a Dual-Path Platform rapid test for canine leishmaniasis. Twenty-five seropositive dogs were euthanized for parasite isolation and 14 isolates were successful obtained. Nucleotide sequencing of the internal transcribed spacer confirmed the isolates to be L. (L.) infantum, and very low sequence variability was observed among them. The in vitro susceptibility to miltefosine and paromomycin was assessed and moderate variation in paromomycin susceptibility was found among the isolates in the promastigote and intracellular amastigote stages. On the other hand, in vitro susceptibility to miltefosine of these isolates was homogenous, particularly in the amastigote stage (EC50 values from 0.69 to 2.07 µM). In addition, the miltefosine sensitivity locus was deleted in all the isolates, which does not corroborate the hypothesis that the absence of this locus is correlated with a low in vitro susceptibility. Our findings confirm that the municipality of Embu das Artes is endemic for canine leishmaniasis and that isolates from this region are susceptible to paromomycin and miltefosine, indicating the potential of these drugs to be clinically evaluated in the treatment of human visceral leishmaniasis in Brazil.

Directrices para el tratamiento de las leishmaniasis en la región de las américas - 2 ed / Guidelines for the treatment of leishmaniasis in the region of the Americas - 2 ed

Las leishmaniasis son enfermedades infecciosas desatendidas de gran importancia en la Región de las Américas debido a su morbilidad, mortalidad y amplia distribución geográfica. De las tres formas clínicas principales, la cutánea es la más común y la visceral es la forma más grave, ya que puede causar la muerte de hasta 90% de las personas que no reciban tratamiento. En el 2013, la Organización Panamericana de la Salud (OPS) elaboró recomendaciones para el tratamiento de las leishmaniasis en la Región de las Américas utilizando la metodología de clasificación de la valoración, la elaboración y la evaluación de las recomendaciones (GRADE, por su sigla en inglés). No obstante, dada la evidencia acumulada desde entonces, se hizo necesario revisar esas recomendaciones. En esta segunda edición se presentan las recomendaciones actualizadas sobre el tratamiento de las leishmaniasis, y se detallan los esquemas y los criterios de indicación del tratamiento en el contexto regional. Estas directrices presentan modificaciones sustanciales con respecto a la primera edición. En el caso de la leishmaniasis cutánea, se ha eliminado el ketoconazol de las opciones terapéuticas, el número de especies de Leishmania para las que hay evidencia sólida de la eficacia de la miltefosina ha aumentado de dos a cuatro y la recomendación de administrar antimoniales intralesionales ahora es fuerte. Con respecto a la leishmaniasis mucosa, se incluye una recomendación fuerte sobre el uso de antimoniales pentavalentes con o sin pentoxifilina oral. Por lo que respecta a la leishmaniasis visceral, la recomendación fuerte sobre el uso de antimoniales pentavalentes y desoxicolato de anfotericina B ahora es condicional. También hay evidencia contundente en contra del uso de miltefosina en pacientes con leishmaniasis causada por Leishmania infantum. Otros cambios importantes son el desglose de las recomendaciones según si se trata de pacientes adultos o pediátricos, la inclusión de las especies de Leishmania y, en el caso de los pacientes inmunocomprometidos, la introducción de una recomendación fuerte contra el uso de antimoniales pentavalentes. Esta segunda edición es una versión revisada de la publicación Leishmaniasis en las Américas: recomendaciones para el tratamiento: https://iris.paho.org/handle/10665.2/7704

Treatment of Cutaneous Leishmaniasis in a Nonendemic Country: A Case Series of Children in Australia.

We describe 4 cases of cutaneous leishmaniasis in children in Australia. Treatment is challenging given lack of firm guidelines and limited access to conventional modalities used in endemic countries. Topical paromomycin or oral fluconazole were effective outpatient-based first-line treatments, however, topical paromomycin use was limited by expense to import or compound locally.

Amebiasis and Amebic Liver Abscess in Children.

Although rare in the developed world, amebiasis continues to be a leading cause of diarrhea and illness in developing nations with crowding, poor sanitation, and lack of clean water supply. Recent immigrants or travelers returning from endemic regions after a prolonged stay are at high risk of developing amebiasis. A high index of suspicion for amebiasis should be maintained for other high-risk groups like men having sex with men, people with AIDS/HIV, immunocompromised hosts, residents of mental health facility or group homes. Clinical presentation of intestinal amebiasis varies from diarrhea to colitis and dysentery. Amebic liver abscess (ALA) is the most common form of extraintestinal amebiasis. Various diagnostic tools are available and when amebiasis is suspected, a combination of stool tests and serology should be sent to maximize the yield of testing. Treatment with an amebicidal drug such as metronidazole/tinidazole and a luminal cysticidal agent such as paromomycin for clinical disease is indicated. However, for asymptomatic disease treatment with a luminal cysticidal agent to decrease chances of invasive disease and transmission is recommended.

Assessment of serum amylase, lipase and associated factors among patients with visceral leishmaniasis treated with sodium stibogluconate/paromomycin at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

BACKGROUND: Visceral leishmaniasis (VL) is a life-threatening parasitic disease next to malaria, which is responsible for the death of 50,000 patients annually. It has three major clinical stages, including visceral, cutaneous, and mucocutaneous leishmaniasis. Ethiopia is one of the east African countries commonly affected with leishmanisis disease. There are many drugs for leishmaniasis, including sodium stibogluconate and paromomycin combined therapy. However, the adverse effect of those combined drugs is not well-defined. Therefore, the purpose of this study was to assess serum amylase, lipase, and associated factors among patients with VL treatment with those combined drugs. METHODS: Hospital-based cross-sectional study was conducted at the University of Gondar Comprehensive Specialized Hospital Leishmaniasis Research and Treatment Center from February to September 2020 G.C. Simple random sampling technique was utilized to select study participants. The study participants who fulfill the inclusion criteria were included in the study with written informed consent. 5 ml of blood was withdrawn by an experienced health professional to analyze serum amylase and lipase level. Descriptive data was presented by tables, charts and graphs. Data was cleared, entered by Epi-data version 3.1 then transfer to STATA 14.1 SE version and for analysis paired t-test was used, for factors correlation and regression was used. Those factor variable who have p-value <0.25 was filtered and goes to multivariate regression and p-value <0.05 was considered as significant variables. RESULTS: The result of this study showed that there was a significant mean difference between serum pancreatic amylase and lipase before and after treatment. The mean ± SD level of serum amylase after treatment showed a statistically significant elevation (P<0.001) as compared to its level before treatment. Similarly, the mean ± SD level of serum lipase after treatment showed a statistically significant elevation (P<0.001) as compared to its level before treatment. There was also significant association between age and baseline serum amylase as compared to serum amylase after treatment. Similarly, there was also significant relation of age and serum lipase with serum lipase after treatment. CONCLUSION: In this study, the level of serum amylase and lipase at treatment of cure was higher and there was an increase in mean serum amylase and lipase after a patient taking sodium stibogluconate and paromomycin combined drugs. Consequently, the elevated result of these biochemical profiles mainly associated with drug induced adverse effect and associated risk factors in VL patients.

Treatment of human intestinal cryptosporidiosis: A review of published clinical trials.

The global burden of diarrhea caused by Cryptosporidium parasite is underestimated. In immunocompromised hosts, chronic and severe presentation of intestinal cryptosporidiosis can result in long-term morbidity and high illness costs. The evidence of effective treatments for cryptosporidiosis has been lacking. We reviewed the published clinical trials to bring forward the feasible therapeutic options of human cryptosporidiosis in various populations and settings according to clinical improvement and parasite clearance rates. A total of 42 studies consisting of the use of nitazoxanide, paromomycin, macrolides, somatostatin analogues, letrazuril, albendazole, rifaximin, miltefosine, clofazimine, and colostrum were included in the review. The trials were mostly conducted in small number of individuals infected with human immunodeficiency virus (HIV), and there is inadequate data of controlled trials to suggest the use of these treatment modalities. Nitazoxanide was reported to be highly efficacious only in immunocompetent hosts and was found to be superior to paromomycin in the same group of patients. Macrolides showed no effective results in both clinical and parasitological improvement. Human bovine colostrum should possibly be administered as one of complementary therapeutic modalities along with other antimicrobials to reach optimal parasite eradication. Other trials of therapeutic modalities were terminated due to futility. Currently, available data is intended to aid the development of strategies for improving access to treatments in different clinical settings, as well as to help guide further studies on treatments of human intestinal cryptosporidiosis.

Geographical Variability in Paromomycin Pharmacokinetics Does Not Explain Efficacy Differences between Eastern African and Indian Visceral Leishmaniasis Patients.

INTRODUCTION: Intramuscular paromomycin monotherapy to treat visceral leishmaniasis (VL) has been shown to be effective for Indian patients, while a similar regimen resulted in lower efficacy in Eastern Africa, which could be related to differences in paromomycin pharmacokinetics. METHODS: Pharmacokinetic data were available from two randomized controlled trials in VL patients from Eastern Africa and India. African patients received intramuscular paromomycin monotherapy (20 mg/kg for 21 days) or combination therapy (15 mg/kg for 17 days) with sodium stibogluconate. Indian patients received paromomycin monotherapy (15 mg/kg for 21 days). A population pharmacokinetic model was developed for paromomycin in Eastern African and Indian VL patients. RESULTS: Seventy-four African patients (388 observations) and 528 Indian patients (1321 observations) were included in this pharmacokinetic analysis. A one-compartment model with first-order kinetics of absorption and elimination best described paromomycin in plasma. Bioavailability (relative standard error) was 1.17 (5.18%) times higher in Kenyan and Sudanese patients, and 2.46 (24.5%) times higher in Ethiopian patients, compared with Indian patients. Ethiopian patients had an approximately fourfold slower absorption rate constant of 0.446 h-1 (18.2%). Area under the plasma concentration-time curve for 24 h at steady-state (AUCτ,SS) for 15 mg/kg/day (median [interquartile range]) was higher in Kenya and Sudan (172.7 µg·h/mL [145.9-214.3]) and Ethiopia (230.1 µg·h/mL [146.3-591.2]) compared with India (97.26 µg·h/mL [80.83-123.4]). CONCLUSION: The developed model provides detailed insight into the pharmacokinetic differences among Eastern African countries and India, however the resulting differences in paromomycin exposure do not seem to explain the geographical differences in paromomycin efficacy in the treatment of VL patients.

Paromomycin Sulfate Treatment in Histomoniasis Outbreaks in Three Commercial Turkey Flocks in the Fraser Valley of British Columbia, Canada.

Over the last couple of years, the number of histomoniasis cases in commercial turkeys has increased substantially in British Columbia, particularly in the Fraser Valley. Due to a lack of approved efficacious preventive or curative drugs in Canada, histomoniasis outbreaks have had significant economic and animal welfare impacts on the commercial turkey industry. In July 2020, Health Canada conditionally approved the treatment use of paromomycin sulfate on a case-by-case basis via an emergency drug release authorization. Three flocks infected with Histomonas meleagridis were treated with labeled-dose paromomycin sulfate in the feed shortly after presumptive diagnosis. Despite the treatment, two out of three flocks suffered significant losses. One flock suffered over 67% mortality by the eighth day of treatment. Due to significant production loss and animal welfare concerns, the flock was shipped early for mercy cull; thus sustained 100% production loss. Another flock experienced over 38% mortality by the end of the fourth week of treatment and was slaughtered early to minimize production loss. The treatment response in two out of three cases suggests that any curative effect of paromomycin is limited. Thus, future field evaluation should carefully consider the prophylactic use of paromomycin sulfate, especially on farms with recurrent outbreaks.

Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs.

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.

Paromomycin: A potential dual targeted drug effectively inhibits both spike (S1) and main protease of COVID-19.

OBJECTIVES: With the increasing number of people suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dire need to look for effective remedies against this pandemic. Drug repurposing seems to be the solution for the current situation. METHODS: In a quest to find a potential drug against this virus, 15 antimalarial drugs (including chloroquine) and 2413 US Food and Drug Administration-approved drugs were investigated for activity against both the protease and spike proteins of SARS-CoV-2 using an in silico approach. Molecular docking analysis followed by molecular dynamics simulation was performed to estimate the binding and stability of the complexes. RESULTS: This study identified a single drug - paromomycin - with activity against two targets of SARS-CoV-2, i.e., spike protein (S1) and protease domain. Paromomycin was found to have strong binding affinity for both targets of coronavirus. The results also showed that no antimalarial drug exhibited effective binding for either S1 or protease. CONCLUSIONS: This study found that paromomycin may be an effective dual targeting drug against coronavirus, as it binds not only to the protease domain of the virion, but also to the spike domain, with high stability. Furthermore, none of the antimalarial drugs showed strong binding affinity for either protease or the receptor binding domain (RBD).

A randomized, blinded, controlled clinical trial comparing the efficacy of aminosidine (paromomycin)-allopurinol combination with the efficacy of meglumine antimoniate-allopurinol combination for the treatment of canine leishmaniosis due to Leishmania infantum.

The aim of this 6-month, randomized, blinded, controlled clinical trial was to compare the efficacy and safety of aminosidine-allopurinol combination with that of meglumine antimoniate-allopurinol combination for the treatment of leishmaniosis in dogs without stage III or IV chronic kidney disease. Forty client-owned dogs were randomly assigned to group A [n = 20; aminosidine (15 mg/kg, subcutaneously, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)] or group B [(n = 20; meglumine antimoniate (100 mg/kg SC, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)]. Clinical and clinicopathological evaluations, parasitic load measurement (lymph node and bone marrow microscopy, bone marrow real-time PCR), specific serology and leishmanin skin test (LST) were performed at baseline (time 1) and after 14 (time 2), 28 (time 3), 60 (time 4) and 180 (time 5) days. Both treatments were safe and resulted in significant clinical and clinicopathological improvement, reduction of parasitic load and of indirect immunofluorescence antibody test (IFAT) titer and induction of positive LST. There was no significant difference between groups with regards to the primary outcome measures of the trial that included the proportion of dogs that presented severe treatment-related side effects, were cured and were parasitologically negative at time 5. However, some (proportion of dogs that presented no clinical signs, no hyperglobulinemia and negative serology at time 5) secondary outcome measures showed significant differences in favor of the meglumine antimoniate-allopurinol treatment arm. Treatment-related death occurred in one dog in each group, while injection site reactions appeared at a similar frequency in both groups. Due to the differences in some secondary outcome measures in association with the low power of this trial, it cannot be definitively concluded that the two treatments are equally effective. Therefore, the aminisodine-allopurinol combination cannot be proposed as a first-line treatment of CanL but rather as a second-line treatment that may be particularly useful to avoid repeated administration of meglumine antimoniate and in countries where the latter is not available or registered.

Comparison of in vitro Resistance of Wild Leishmania Isolates, Which are Resistant to Pentavalent Antimonial Compounds, Against Drugs Used in the Treatment of Leishmaniasis

Objective: Meglumine antimoniate (Glucantime®) and Sodium stibogluconate (Pentostam®) are used for the treatment of cutaneous leismaniasis in Turkey. There is a reported resistance to these drugs in recent years. The aim of the present study was to compare the in vitro sensitivities of resistant Leishmania isolates against Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin and Sodium Stibogluconate. Methods: Five Leishmania isolates of patients with cutaneous leishmaniasis, who showed no clinical recovery despite two consecutive meglumine antimoniate treatments, which were stored in the Parasite Bank in Manisa Celal Bayar University Medical Faculty were selected. They were genotyped with Real-Time PCR using specific primers and probes to ITS1 region. Drug resistance levels of each Leishmania isolate were analysed for Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin, and Sodium Stibogluconate at concentrations of 500, 250, 125, 50, 25 µg/mL with XTT method and hemocytometer. Results: It was observed that the resistant Leishmania tropica isolates showed no resistance to Amphotericin B, and were sensitive to Miltefosine, Sodium Stibogluconate, Paromomycin and Meglumin Antimonate, respectively. In addition, Leishmania tropica (MHOM/AZ/1974/SAF-K27) isolate of the control group could stay viable in none of the drug concentrations of five agents in the study. Conclusion: It was determined that none of the selected resistant L. tropica isolates showed resistance to Amphotericin B and that was also shown statistically (p<0.05). The results of this study are important in guiding clinicians and researchers who conduct studies on drugs and search for new drug molecules.

Entamoeba histolytica liver abscess case: could stool PCR avoid it?

Background Liver abscess is the most common extraintestinal manifestation of Entamoeba histolytica. Clinical manifestations could appear after returning from an endemic area or several years after the exposure. The diagnosis usually requires microbiological confirmation. Case presentation We present a case of a 55-year-old woman diagnosed with Crohn's disease treated with immunosuppressive drugs, who was admitted to the Emergency Service with liver parenchyma abscesses. Computed tomography (CT)-guided puncture showed pus, and both Gram staining and fresh parasite visualization were negative. Hepatic pus bacteriological culture was reported as negative and parasite multiplex polymerase chain reaction (PCR) was performed, being positive for E. histolytica. The same PCR was performed on blood, pleural fluid and stool samples, all of them being positive for E. histolytica. Conclusions Reviewing the clinical history of this patient, it was observed that parasite detection in three stool samples was negative 2 months before the current admission. Due to the lack of sensitivity of the microscopy techniques, we propose to routinely perform parasite detection in stools using molecular techniques, especially in immunocompromised patients.