Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America

Abstract

BackgroundBacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use.MethodsOver 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant Gram-negative bacilli (GNB). Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR) mutations.ResultsIn the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01). Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine.ConclusionsIn these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.

Characterisation of extended-spectrum β-lactamases among Klebsiella pneumoniae isolates causing bacteraemia and urinary tract infection in Mozambique

“…On the other hand, antibiotics used as second-line treatment such as carbapenems, which are still effective in vitro in the Manhiça area, are not available in most developing countries. Use of fluoroquinolones could be compromised in areas with a high prevalence of malaria that use chloroquine as treatment owing to the selection of quinolone resistance during antimalarial therapy in the absence of quinolone exposure [32], although, actually, in Manhiça chloroquine is not in use.…”

Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria

“…The development of clinical drug resistance in malarial parasites poses a major obstacle in conventional chemotherapy (9). Importantly, the overuse of chloroquine (CQ) for Plasmodium infection treatment leads to quinolone resistance in commensal Escherichia coli strains in humans (10). To obviate drug resistance, efforts are being made to develop artemisinin-based combination therapies (ACTs), develop new drugs, and improve the efficiency of drug delivery vehicles of existing antimalarial drugs.…”

Neurotoxizität von chinolinhaltigen Antiinfektiva: eine unterschätzte Belastung der Gesundheitssysteme Afrikas?

“…Auch gilt es für die Suchbegriffe "interactions praziquantel and ciprofloxacin", "interactions praziquantel and mefloquin" sowie die allgemeineren Begriffe "Medikamentenwechselwirkungen Chinoline" und "psychotropic interactions quinolines". Die wenigen Treffer die es hier gab, bezogen sich nicht auf neuropsychologische, sondern auf kardiologische und infektiologische Wechselwirkungen (QTc-Verlängerung [10], Resistenz von E. Coli gegen Ciprofloxacin nach Chloroquintherapie [11]). Erst wenn der Suchbegriff mit "interactions quinolines" sehr weit gefasst wurde, fanden sich 1724 Treffer.…”