Atovaquone-Proguanil in Combination with Artesunate to Treat Multidrug-Resistant P. falciparum Malaria in Cambodia: An Open-Label Randomized Trial

Background: Recent artemisinin-combination therapy failures in Cambodia prompted a search for alternatives. Atovaquone-proguanil (AP), a safe, effective treatment for multidrug-resistant Plasmodium falciparum (P.f.), previously demonstrated additive effects in combination with artesunate (AS). Methods: Patients with P.f. or mixed-species infection (n = 205) in Anlong Veng (AV; n = 157) and Kratie (KT; n = 48), Cambodia, were randomized open-label 1:1 to a fixed-dose 3-day AP regimen +/-3 days of co-administered artesunate (ASAP). Single low-dose primaquine (PQ, 15 mg) was given on day 1 to prevent gametocyte-mediated transmission. Results: Polymerase chain reaction-adjusted adequate clinical and parasitological response at 42 days was 90% for AP (95% confidence interval [CI], 82%-95%) and 92% for ASAP (95% CI, 83%-96%; P =. 73). The median parasite clearance time was 72 hours for ASAP in AV vs 56 hours in KT (P <. 001) and was no different than AP alone. At 1 week postprimaquine, 7% of the ASAP group carried microscopic gametocytes vs 29% for AP alone (P =. 0001). Nearly all P.f. isolates had C580Y K13 propeller artemisinin resistance mutations (AV 99%; KT 88%). Only 1 of 14 treatment failures carried the cytochrome bc1 (Pfcytb) atovaquone resistance mutation, which was not present at baseline. P.f. isolates remained atovaquone sensitive in vitro but cycloguanil resistant, with a triple P.f. dihydrofolate reductase mutation. Conclusions: Atovaquone-proguanil remained marginally effective in Cambodia (≥90%) with minimal Pfcytb mutations observed. Treatment failures in the presence of ex vivo atovaquone sensitivity and adequate plasma levels may be attributable to cycloguanil and/or artemisinin resistance. Artesunate co-administration provided little additional blood-stage efficacy but reduced post-treatment gametocyte carriage in combination with AP beyond single low-dose primaquine

Melioidosis in lower provincial Cambodia: A case series from a prospective study of sepsis in Takeo Province

<div><p>Melioidosis is a severe infectious disease caused by the gram-negative soil bacterium <i>Burkholderia pseudomallei</i>. Melioidosis is well known to be a major cause of morbidity and mortality in Southeast Asia, particularly in Thailand. However, melioidosis remains underreported in surrounding areas such as Cambodia. We report a case series of melioidosis in seven patients from Takeo Province, Cambodia. The patients, aged 24–65 years, were enrolled from May 2014 to May 2015 during a one year prospective study of sepsis at Takeo Provincial Hospital. They presented with fever, rigors, dyspnea, fatigue, diaphoresis, productive cough, and skin abscesses. Six of the seven patients were also hyponatremic. <i>B</i>. <i>pseudomallei</i> was cultured from the blood of six patients and the sputum of one patient. In this manuscript, we provide a detailed description of the clinical presentation, case management and laboratory confirmation of <i>B</i>. <i>pseudomallei</i>, as well as discuss the difficulties of identifying and treating melioidosis in low resource settings.</p></div

Study site.

<p>We used DIVA-GIS (<a href="http://diva-gis.org/" target="_blank">http://diva-gis.org/</a>) to create a map of Cambodia and surrounding areas. The red H indicates Takeo Provincial Hospital, the study site for this work. Dots indicate the location of the home village of seven melioidosis patients. Map is reflective of Cambodian Provincial borders during the time of patient enrollment.</p

Clinical isolate characteristics.

<p>Clinical isolate characteristics.</p

Initial management of and outcome in patients with pneumococcal bacteremia: a retrospective study at a Swiss university hospital, 2003-2009

PURPOSE: The aim of this quality control study was to assess the time to initial diagnostic procedures and the time to the first dose of antibiotics in patients with pneumococcal bacteremia, and to investigate whether the timeliness of these interventions influenced outcome. METHODS: We retrospectively studied patient characteristics, chronological sequence of diagnostic and therapeutic steps, and the course of disease of all patients with pneumococcal bacteremia at a Swiss university hospital between 2003 and 2009, and we analyzed associations between these factors and the length of hospital stay (LOS) and mortality. RESULTS: A total of 102 episodes of pneumococcal bacteremia in 98 patients were analyzed, of whom 15.7% died during hospitalization. The median time (interquartile range [IQR]) to the first antibiotic dose was 4.0 (2.0-5.9) h, and the median times (IQR]) to blood cultures, chest radiograph, lumbar puncture, and brain computed tomography (CT) scan or magnetic resonance imaging (MRI) were 1.4 (0.5-3.3), 2.5 (1.2-4.2), 4.2 (2.7-7.2), and 2.3 (0.6-6.2) h, respectively. The time to diagnostic procedures and therapy were not associated with LOS or death. Risk factors for death in the univariable analysis were: Charlson comorbidity index [odds ratio [OR] (95% confidence interval) per unit increase, 1.3 (1.1-1.6)], neutropenia [OR 10.1 (2.0-51.0)], human immunodeficiency virus (HIV) infection [OR 3.9 (1.1-13.8)], chronic respiratory disease [OR 4.4 (1.2-16.0)], chronic liver disease [OR 3.2 (1.0-9.7)], smoking [OR 3.8 (1.1-13.5)], injection drug use [OR 9.7 (1.5-63.7)], and antibiotic therapy within 6 months before admission [OR 4.0 (1.3-12.5)]. The multivariable analysis revealed age >60 years (P = 0.048) and alcoholism (P = 0.009) as risks for prolonged LOS. CONCLUSIONS: The outcome of pneumococcal bacteremia may be more influenced by patient characteristics than by minor differences in the timeliness of initial diagnostic and therapeutic measures within the first several hours after hospital admission