zithromax and chloroquine-diphosphate

There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.. To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.. This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon.. Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days).. Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4.. Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%).. The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19.. ClinicalTrials.gov Identifier: NCT04323527.

Topics: Adult; Aged; Anti-Bacterial Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Brazil; Chloroquine; Coronavirus Infections; COVID-19; Disease Outbreaks; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Oseltamivir; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tertiary Care Centers

Topics: Angiotensin-Converting Enzyme 2; Anti-Bacterial Agents; Antimalarials; Arrhythmias, Cardiac; Azithromycin; Cardiovascular Diseases; Chloroquine; Comorbidity; COVID-19; COVID-19 Drug Treatment; Drug Interactions; Humans; Hydroxychloroquine; Long QT Syndrome; Myocytes, Cardiac; Receptors, Coronavirus; SARS-CoV-2; Torsades de Pointes

A 60-year-old female patient living in Southeast China presented with persistent fever, chills, night sweats, fatigue, and dizziness of 12-day duration. Blood tests showed neutropenia, thrombocytopenia, and active hemolytic anemia, with elevated C-reactive protein. Broad-spectrum antibiotics were administered for a possible diagnosis of sepsis, without any response. Malaria was initially diagnosed after visualizing intraerythrocytic ring-shaped parasites in bone marrow and blood smears. The patient resided in an area of unstable endemicity for Plasmodium falciparum. Blood samples were sent to the Centers for Disease Control and Prevention and a definitive diagnosis of human babesiosis was made using Babesia microti-specific PCR. Chloroquine phosphate and clindamycin were started and the patient became normothermic. However, due to the intolerable adverse effects of the antibiotics, intravenous azithromycin was given as an alternative. The patient recovered from fever and hemolysis, and repeated peripheral blood smears showed hemoparasite clearance. Cases of human babesiosis are rarely reported and probably under-diagnosed in China; therefore, improving our understanding of this disease as a newly emerging public health threat is imperative.

Topics: Administration, Intravenous; Anemia, Hemolytic; Anti-Bacterial Agents; Azithromycin; Babesiosis; C-Reactive Protein; China; Chloroquine; Clindamycin; Female; Fever; Humans; Middle Aged; Neutropenia; Thrombocytopenia

: The in vitro assays for susceptibility of Plasmodium falciparum to antimalarial drugs are important tools for monitoring drug resistance. During the present study, efforts were made to establish long-term continuous in vitro culture of Indian field isolates of P. falciparum and to determine their sensitivity to standard antimalarial drugs and antibiotics.. Four (MZR-I, -II, -III and -IV) P. falciparum isolates were obtained from four patients who showed artemisinin-based combination therapy (ACT) from Mizoram, a north-eastern State of India, and characterized for their in vitro susceptibility to chloroquine diphosphate (CQ), quinine hydrochloride dehydrate, mefloquine, piperaquine, artemether, arteether, dihydro-artemisinin (DHA), lumefantrine and atovaquone and antibiotics, azithromycin and doxycycline. These patients showed ACT treatment failure. Two-fold serial dilutions of each drug were tested and the effect was evaluated using the malaria SYBR Green I fluorescence assay. K1 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) reference strains were used as controls.. Growth profile of all field isolates was identical to that of reference parasites. The IC50 values of all the drugs were also similar against field isolates and reference parasite strains, except K1, exhibited high IC50 value (275±12.5 nM) of CQ for which it was resistant. All field isolates exhibited higher IC50 values of CQ, quinine hydrochloride dihydrate and DHA compared to reference strains. The resistance index of field isolates with respect to 3D7 ranged between 260.55 and 403.78 to CQ, 39.83 and 46.42 to quinine, and 2.98 and 4.16 to DHA, and with respect to K1 strain ranged between 6.51 and 10.08, 39.26 and 45.75, and 2.65 and 3.71. MZR-I isolate exhibited highest resistance index.. As the increase in IC50 and IC90 values of DHA against field isolates of P. falciparum was not significant, the tolerance to DHA-piperaquine (PPQ) combination might be because of PPQ only. Further study is required on more number of such isolates to generate data for a meaningful conclusion.

Topics: Anti-Bacterial Agents; Antimalarials; Artemether; Artemisinins; Atovaquone; Azithromycin; Chloroquine; Doxycycline; Ethanolamines; Fluorenes; Humans; India; Lumefantrine; Malaria, Falciparum; Mefloquine; Plasmodium falciparum; Quinine; Quinolines

Prolongation of the electrocardiogram QT interval by some, but not all drugs, has been associated with increased incidence of sudden cardiac death. Current preclinical regulatory assays cannot discriminate the arrhythmia liability of these drugs. Consequently, many new medications that prolong the QT interval are not developed despite their potential therapeutic benefit. Alternans (action potential duration alternations) is a measure of cardiac instability in humans and animals associated with the onset of ventricular fibrillation. Due to potential arrhythmia risk from observed QT prolongation, alternans was assessed in the anesthetized guinea pig after azithromycin or chloroquine alone and after combination treatment at clinically relevant concentrations proposed for the management of malaria. Chloroquine alone, but not azithromycin, caused a profound increase in action potential duration but with only minimal effects on alternans (approximately 10 ms). Azithromycin alone and in combination with chloroquine showed no increase in alternans beyond vehicle baseline responses indicating no additional arrhythmia liability.

Topics: Action Potentials; Anesthesia; Animals; Antimalarials; Arrhythmias, Cardiac; Azithromycin; Blood Pressure; Chloroquine; Dose-Response Relationship, Drug; Guinea Pigs; Heart; Heart Rate; Male