Hydroxychloroquine (HCQ), also known by its trade name Plaquenil®, has been used for over 50 years as a treatment for malaria, systemic lupus erythematosus, and rheumatoid arthritis. As the COVID-19 pandemic emerged in the United States and globally in early 2020, HCQ began to garner attention as a potential treatment and as prophylaxis against COVID-19. Preliminary data indicated that HCQ as well as chloroquine (CQ) possessed in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early clinical data from China and France reported that HCQ and CQ were associated with viral load reduction and clinical improvement in patients with COVID-19 compared to control groups; however, an overwhelming number of randomized controlled trials, meta-analyses, and systematic reviews have since concluded that HCQ used alone, or in combination with azithromycin (AZ), provides no mortality or time-to-recovery benefit in hospitalized patients with COVID-19. Additionally, these same trials reported adverse events including cardiac, neuropsychiatric, hematologic, and hepatobiliary manifestations in patients with COVID-19 whom had been treated with HCQ. This review article summarizes the available data pertaining to the adverse events associated with HCQ use, alone or in combination with azithromycin, in patients with COVID-19 in order to fully assess the risk versus benefit of treating COVID-19 patients with these agents. The results of this review lead us to conclude that the risks of adverse events associated with HCQ use (with or without AZ) outweigh the potential clinical benefits and thus recommend against its use in the treatment or prevention of COVID-19.
Acute and chronic bacterial prostatitis in outpatients is commonly treated with oral fluoroquinolones; however, the worldwide dissemination of multidrug-resistant (MDR) Escherichia coli has resulted in therapeutic failures with fluoroquinolones. We reviewed the literature regarding the use of oral fosfomycin in the treatment of acute and chronic prostatitis caused by MDR E. coli . All English-language references on PubMed from 1986 to June 2017, inclusive, were reviewed from the search “fosfomycin prostatitis.” Fosfomycin demonstrates potent in vitro activity against a variety of antimicrobial-resistant E. coli genotypes/phenotypes including ciprofloxacin-resistant, trimethoprim-sulfamethoxazole-resistant, extended-spectrum β -lactamase- (ESBL-) producing, and MDR isolates. Fosfomycin attains therapeutic concentrations (≥4 μ g/g) in uninflamed prostatic tissue and maintains a high prostate/plasma ratio up to 17 hours after oral administration. Oral fosfomycin’s clinical cure rates in the treatment of bacterial prostatitis caused by antimicrobial-resistant E. coli ranged from 50 to 77% with microbiological eradication rates of >50%. An oral regimen of fosfomycin tromethamine of 3 g·q 24 h for one week followed by 3 g·q 48 h for a total treatment duration of 6–12 weeks appeared to be effective. Oral fosfomycin may represent an efficacious and safe treatment for acute and chronic prostatitis caused by MDR E. coli .
Fosfomycin is a bactericidal agent that inhibits cell wall synthesis using a mechanism of action distinct from β -lactams or other antimicrobial agents. It is a broad-spectrum agent that is frequently active against antimicrobial-resistant bacterial pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Enterobacteriaceae, and some isolates of MDR Pseudomonas aeruginosa . Intravenous fosfomycin has been prescribed for a wide variety of infections in many countries for >40 years. It is most frequently used in combination with other antimicrobial agents (e.g., β -lactams, carbapenems, and aminoglycosides) and has an excellent safety profile, including in neonates and children, even with long-term administration (weeks). Fosfomycin achieves extensive tissue distribution including difficult to reach compartments such as aqueous humor, vitreous humor, abscess fluid, and CSF. Available data, to date, suggest no clinically relevant pharmacological interactions between fosfomycin and other agents, including drugs, stimulants, or food. Intravenous fosfomycin’s role in therapy in Canada is likely as an agent used alone or in combination for complicated urinary tract infections in hospitalized patients as well as hospitalized patients with MDR infections who have not responded to first-, and potentially, second-line antimicrobials or in patients who cannot tolerate (due to adverse effects) first- and second-line antimicrobials.
