zithromax and miltefosine

On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009.. To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML).. We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers.. Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound.. We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome.. We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), bu. Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.

Topics: Administration, Oral; Adult; Antiprotozoal Agents; Azithromycin; BCG Vaccine; Female; Humans; Hyperthermia, Induced; Immunocompetence; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Meglumine Antimoniate; Pentoxifylline; Phosphorylcholine; Randomized Controlled Trials as Topic

Primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri is a rare and deadly disease that requires prompt treatment with multiple therapies. Although N. fowleri previously was only found in warmer areas, climate change appears to be contributing to its geographic spread. Clinicians should consider PAM when faced with a patient with meningitis, especially if the patient participates in outdoor water activities or practices nasal rinsing.

Topics: Amebicides; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiparasitic Agents; Azithromycin; Central Nervous System Protozoal Infections; Climate Change; Dexamethasone; Early Diagnosis; Early Medical Intervention; Fluconazole; Geography; Glucocorticoids; Humans; Hypothermia, Induced; Macrolides; Naegleria fowleri; Phosphorylcholine; Rifampin; United States; Ventriculostomy

We evaluated the efficacy of azithromycin (50 mg/kg, every 12 h [q12h] orally) and miltefosine (25 mg/kg, q24h orally) treatments in an experimental model of vascular/disseminated pythiosis in immunosuppressed mice. Azithromycin was the only treatment able to reduce mortality. The histopathological findings showed acute vascular inflammation, pathogen dissemination, necrotizing myositis, neuritis, and arteritis. The results suggest that azithromycin, but not miltefosine, may have clinical relevance in the treatment of vascular/disseminated pythiosis.

Topics: Animals; Antiprotozoal Agents; Azithromycin; Immunocompromised Host; Mice; Phosphorylcholine; Pythiosis; Pythium

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bridged Bicyclo Compounds, Heterocyclic; Clarithromycin; Diterpenes; Humans; Josamycin; Linezolid; Macrolides; Oomycetes; Oxazolidinones; Phosphorylcholine; Pleuromutilins; Polycyclic Compounds; Pythiosis; Pythium

Primary amoebic meningoencephalitis (PAM) is a rare and almost always fatal disease that is caused by Naegleria fowleri, a freshwater thermophilic amoeba. Our case involves an adolescent female who presented with fever of unknown origin. A lumbar puncture was performed, and the Wright-Giemsa and Gram stained cerebrospinal fluid (CSF) cytospin slides showed numerous organisms. Experienced medical technologists in the microbiology and hematology laboratories identified the organisms as morphologically consistent with Naegleria species. The laboratory made a rapid diagnosis and alerted emergency department care providers within 75 minutes. The patient was treated for PAM with amphotericin, rifampin, azithromycin, fluconazole and aggressive supportive therapy including dexamethasone. The Centers for Disease Control and Prevention (CDC) was contacted, and miltefosine, an investigational medication, was started. Additional treatment included an intraventricular shunt and controlled hypothermia in order to mitigate potential cerebral edema. Our patient is a rare success story, as she was diagnosed swiftly, successfully treated, and survived PAM.

Topics: Amebiasis; Amphotericin B; Antiprotozoal Agents; Azithromycin; Central Nervous System Protozoal Infections; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Child; Early Diagnosis; Female; Fluconazole; Humans; Hypothermia, Induced; Meningoencephalitis; Naegleria fowleri; Phosphorylcholine; Rifampin