The evolution of knowledge for treating Gram-negative bacterial infections

Abstract

Este artículo revisa la evolución histórica y científica del tratamiento de las infecciones causadas por bacilos gramnegativos desde finales del siglo XIX hasta la actualidad. Los autores describen cómo microorganismos inicialmente considerados comensales o de baja patogenicidad se han convertido en los principales agentes de infección nosocomial, impulsados por el uso masivo de antibióticos, el aumento de pacientes inmunodeprimidos y la complejidad creciente de la medicina moderna. Se analizan los hitos terapéuticos clave, incluyendo la introducción de sulfonamidas, betalactámicos, aminoglucósidos, fluoroquinolonas, tetraciclinas y polimixinas, así como el impacto reciente de los nuevos inhibidores de betalactamasas y antibióticos de última generación. El artículo aborda también el papel de la terapia combinada, las dificultades terapéuticas en nichos específicos como sistema nervioso central y próstata, y las opciones tópicas. Finalmente, se discuten alternativas emergentes como la terapia con bacteriófagos y se subraya la necesidad de diagnósticos rápidos, uso racional de antimicrobianos y desarrollo de nuevos tratamientos para hacer frente a la resistencia antimicrobiana en bacilos gramnegativos.

Purpose of review: Infections caused by nonprimarily pathogenic Gram-negative bacilli (GNB) have been increasingly reported from the second half of the 20th century to the present. This phenomenon has expanded during the antibiotic era and in the presence of immunodeficiency.Before the discovery of sulphonamides and penicillin G, infections caused by GNB were rare compared to Gram-positive infections. The advent of anticancer therapy, the expansion of surgical procedures, the use of corticosteroids, and the implantation of prosthetic materials, along with better control of Gram-positive infections, have promoted the current increase in GNB infections.GNB have similar antimicrobial targets to Gram-positive bacteria. However, only antibiotics that can penetrate the double membrane of GNB and remain in them for a sufficient duration have antibacterial activity against them.

Recent findings: Sulphonamides and early penicillins had limited activity against GNB. Ampicillin and subsequent beta-lactams expanded their spectrum to treat GNB. Aminoglycosides may re-surge with less toxic drugs, as highly resistant to beta-lactams GNB rise. Polymyxins, tetracyclines, and fluoroquinolones are also used for GNB. Combinations with other agents may be needed in specific cases, such as in the central nervous system and prostate, where beta-lactams may have difficulty reaching the infection site.Alternatives to current treatments must be sought in the discovery of new drug families and therapies such as phage therapy combined with antibiotics.

Summary: Narrower-spectrum immunosuppressive therapies and antibiotics, antimicrobials that minimally intervene with the human microbiota, and instant diagnostic methods are necessary to imagine a future where currently dominant bacteria in infectious pathology lose their preeminence