Phagocytes, Antibiotics, and Self-Limiting Bacterial Infections

• Published in: Trends in microbiology (Regular ed.) Vol. 25; no. 11; pp. 878 - 892
• Main Authors: Levin, Bruce R., Baquero, Fernando, Ankomah, Peter (Pierre), McCall, Ingrid C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2017; Elsevier Science Ltd
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotic resistance; Antibiotics; Bacteria; Bacterial infections; Bacterial Infections - drug therapy; Bacterial Infections - immunology; Constraining; Drug Resistance, Bacterial; Heuristic; Heuristics; Humans; Immune clearance; Infections; Leukocytes; Mathematical models; Mice; Models, Theoretical; Morbidity; Phagocytes; Phagocytes - immunology; Phagocytosis; Phagocytosis - immunology; Pharmacodynamics; Pharmacology; Studies
• ISSN: 0966-842X; 1878-4380
• DOI: 10.1016/j.tim.2017.07.005

Most antibiotic use in humans is to reduce the magnitude and term of morbidity of acute, community-acquired infections in immune competent patients, rather than to save lives. Thanks to phagocytic leucocytes and other host defenses, the vast majority of these infections are self-limiting. Nevertheless, there has been a negligible amount of consideration of the contribution of phagocytosis and other host defenses in the research for, and the design of, antibiotic treatment regimens, which hyper-emphasizes antibiotics as if they were the sole mechanism responsible for the clearance of infections. Here, we critically review this approach and its limitations. With the aid of a heuristic mathematical model, we postulate that if the rate of phagocytosis is great enough, for acute, normally self-limiting infections, then (i) antibiotics with different pharmacodynamic properties would be similarly effective, (ii) low doses of antibiotics can be as effective as high doses, and (iii) neither phenotypic nor inherited antibiotic resistance generated during therapy are likely to lead to treatment failure. With a sufficiently high rate of phagocytosis: antibiotics with very different pharmacodynamic properties, bactericidal and bacteriostatic, can be similarly effective; phenotypic resistance (persistence) will have little effect on the rate of clearance; minority populations of genetically resistant bacteria will not ascend to dominance; and lower doses of antibiotics will be as effective as higher doses. As the rate of phagocytosis declines, bactericidal drugs will be increasingly more effective than bacteriostatic ones, persistence will play an increasingly important role in the course of therapy, minority populations of resistant bacteria will ascend to dominance, and higher doses of antibiotics will be more effective than lower doses.