Evidence of emerging Plasmodium falciparum resistance to artemisinin-based combination therapies, documented in western Cambodia, underscores the continuing need to identify new antimalarial combinations. Given recent reports of the resurgence of chloroquine-sensitive P. falciparum parasites in Malawi, after the enforced and prolonged withdrawal of this drug, and indications of a possible synergistic interaction with the macrolide azithromycin, we sought to further characterize chloroquine-azithromycin combinations for their in vitro and in vivo antimalarial properties. In vitro 96-h susceptibility testing of chloroquine-azithromycin combinations showed mostly additive interactions against freshly cultured P. falciparum field isolates obtained from Mali. Some evidence of synergy, however, was apparent at the fractional 90% inhibitory concentration level. Additional in vitro testing highlighted the resistance reversal properties of amlodipine for both chloroquine and quinine. In vivo experiments, using the Peters 4-day suppressive test in a P. yoelii mouse model, revealed up to 99.9% suppression of parasitemia following treatment with chloroquine-azithromycin plus the R enantiomer of amlodipine. This enantiomer was chosen because it does not manifest the cardiac toxicities observed with the racemic mixture. Pharmacokinetic/pharmacodynamic analyses in this rodent model and subsequent extrapolation to a 65-kg adult led to the estimation that 1.8 g daily of R-amlodipine would be required to achieve similar efficacy in humans, for whom this is likely an unsafe dose. While these data discount amlodipine as an additional partner for chloroquine-based combination therapy, our studies continue to support azithromycin as a safe and effective addition to antimalarial combination therapies.
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MEDLINE (1966-1997), EMBASE (1974-1997), Current Contents, and Science Citation Index searches were conducted to identify randomized controlled trials of the treatment of acute otitis media in children with antibiotics of different durations.
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Larsen and Toubro Microbiology Research Centre, Vision Research Foundation, Sankara Nethralaya, Chennai, Retrospective study.
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In this systematic review we present information relating to the effectiveness and safety of the following interventions: aciclovir; antituberculosis prophylaxis; atovaquone; azithromycin (alone or plus rifabutin); clarithromycin (alone, or plus rifabutin and ethambutol); discontinuing prophylaxis for CMV, MAC, and PCP; ethambutol added to clarithromycin; famciclovir; fluconazole; isoniazid; itraconazole; oral ganciclovir; rifabutin (alone or plus macrolides); trimethoprim-sulfamethoxazole; and valaciclovir.
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The objective of this study was to provide a robust and practical method for the prediction of drug interactions mediated by CYP3A4 using minimal in vivo information from drug-interaction studies, which are often carried out early in the course of drug development.
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This study describes the epidemiology and ethnography of an outbreak of infectious syphilis in Vancouver, British Columbia. Between 1996 and 1999, British Columbias's rate of infectious syphilis rose from 0.5 to 3.4 per 100,000, with a dense concentration of cases among sex trade workers, their clients, and street-involved people in the downtown eastside area of Vancouver. Sexual networks were imported cases with secondary spread (dyads and triads), large densely connected dendritic networks of sex trade workers and clients, or occasional starburst networks among gay men. Only 232 of 429 partners were documented as having been treated (54% of those named, or 0.9 per case). The geographical and demographic concentration of this outbreak led to consideration of a programme of focused mass treatment with single dose azithromycin.
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To evaluate the efficacy and safety of azithromycin compared with rifampin for eradication of nasopharyngeal carriage of Neisseria meningitidis
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The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy.
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Lymphogranuloma venereum (LGV) is sexually transmitted infection caused by serovars of Chlamydia trachomatis, mostly seen among HIV-positive men who have sex with men. The first three reports of possible LGV in Slovenia were from April to June 2015, followed by a confirmed case of LGV in August 2015. We present the case of an HIV-positive MSM that presented with an anorectal abscess, discharge, lymphadenopathy, and unusual perianal plaque. Gonococcal proctitis was assumed and he received empirical antibiotic treatment, after which only intermittent improvement occurred. After a positive test result for chlamydial infection, but without a response to azithromycin treatment, LGV was suspected. Treatment according to the guidelines was introduced. When doxycycline therapy started, rapid improvement was observed, and it was therefore assumed that the LGV infection had been successfully treated. Two similar cases with an unusual anorectal presentation and an excellent response to antibiotic therapy for LGV were observed at the same center shortly thereafter. While pointing out possible delays and limitations in diagnostic procedures at self-pay facilities, the need for better access to high quality STI management in public and in private services is emphasized. Enhanced surveillance and testing guidelines could reveal a hidden LGV epidemic among MSM in Slovenia.
Among primary outcomes (clinical failure, microbiological failure, and relapse), compared with chloramphenicol, fluoroquinolones were not statistically significantly different for clinical failure (594 participants) or microbiological failure (378 participants), but they reduced clinical relapse (OR 0.14, 95% CI 0.04 to 0.50; 467 participants, 6 trials). We detected no statistically significant difference versus co-trimoxazole (82 participants, 2 trials) or azithromycin (152 participants, 2 trials). Fluoroquinolones reduced clinical failure compared with ceftriaxone (OR 0.08, 95% CI 0.01 to 0.45; 120 participants, 3 trials), but not microbiological failure or relapse. Versus cefixime, fluoroquinolones reduced clinical failure (OR 0.05, 95% CI 0.01 to 0.24; 238 participants; 2 trials) and relapse (OR 0.18, 95% CI 0.03 to 0.91; 218 participants, 2 trials).