Pentamidine, recently released for clinical use, is effective in therapy for the hemolymphatic stage of Gambian trypanosomiasis, antimony-resistant leishmaniasis, and Pneumocystis carinii pneumonia. The mechanism of action is unclear and may differ for different organisms. Trypanosomes actively transport pentamidine intracellularly, and the drug may then interfere with DNA biosynthetics. However, pentamidine appears to kill nonreplicating P. carinii. The mechanism of killing is unexplained. The pharmacokinetics of pentamidine has been incompletely studied in humans. The estimated volume of distribution is 3 liters/kg. Levels in plasma of pentamidine range from 0.3-1.4 microgram/ml after standard 4 mg/kg dosing, with no appreciable increase in drug levels on successive dosing and no correlation between levels and creatinine clearance or adverse reactions. The drug appears to be concentrated in the kidney and excreted in the urine, with levels detectable six to eight weeks after cessation of therapy. Immediate adverse reactions have included hypotension, nausea, and vomiting. Local pain or abscess formation at an injection site, mild azotemia, leukopenia, abnormal findings from liver function tests, and hypoglycemia may also occur.

https://www.jstor.org/stable/pdfplus/4453716.pdf

[Visceral Leishmaniasis (Kala-Azar)].

Pentamidine: A Review

Pentavalent antimony (Sbv), formulated as sodium stibogluconate or meglumine antimoniate, is the standard treatment for the leishmaniases. In 16 of 17 consecutive, prospectively observed patients in Washington D.C., serum levels of amylase and lipase rose to abnormal values after therapy with sodium stibogluconate was started; 12 of 17 had symptoms of pancreatitis. Sbv therapy was continued to completion in 7 of 17 patients and interrupted in 10 of 17. Pancreatitis improved in every patient after Sbv therapy was stopped. Sbv treatment was resumed after brief interruptions in 6 of 10 patients. All six of these patients had flares of pancreatitis, but each completed therapy. Subsequently, we measured amylase and lipase levels in stored sera from 32 patients treated in Peru with either sodium stibogluconate or meglumine antimoniate for mucosal leishmaniasis. In all 32 Peruvian patients, serum amylase and lipase rose to abnormal levels during Sbv therapy; 11 of 32 had symptoms of pancreatitis. Standard Sbv regimens induce pancreatitis in almost all patients, but continued therapy is often tolerated; pancreatitis subsides when therapy is stopped, and rechallenge may be tolerated after a brief halt in treatment.

Pancreatitis Induced by Pentavalent Antimonial Agents During Treatment of Leishmaniasis

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients.

/pdf/bacterial-sepsis-in-patients-with-visceral-leishmaniasis-in-3djhyo2aua.pdf

Bacterial sepsis in patients with visceral leishmaniasis in Northwest Ethiopia.

Treatment with liposomal amphotericin B of a child affected with drug-resistant visceral leishmaniasis

Repurposing azole antifungals into antileishmanials: Novel 3-triazolylflavanones with promising in vitro antileishmanial activity against Leishmania major.