Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón.
Medicine Department, School of Medicine, Universidad Complutense de Madrid.
Curr Opin Infect Dis. 2024 Dec 1;37(6):573-581. doi: 10.1097/QCO.0000000000001055. Epub 2024 Sep 27.
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.
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.
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.
自 20 世纪下半叶至今，非主要致病性革兰氏阴性杆菌（GNB）引起的感染报道日益增多。这种现象在抗生素时代和免疫缺陷存在的情况下有所扩大。在发现磺胺类药物和青霉素 G 之前，与革兰氏阳性感染相比，GNB 引起的感染较为罕见。抗癌治疗的出现、手术范围的扩大、皮质类固醇的使用以及假体材料的植入，以及革兰氏阳性感染控制的改善，促进了目前 GNB 感染的增加。GNB 与革兰氏阳性菌具有相似的抗菌靶点。然而，只有能够穿透 GNB 双层膜并在其中保持足够时间的抗生素对其具有抗菌活性。
磺胺类药物和早期青霉素对 GNB 的活性有限。氨苄西林和随后的β-内酰胺类药物扩大了它们的治疗谱，可用于治疗 GNB。氨基糖苷类药物可能会随着对β-内酰胺类药物高度耐药的 GNB 的增加而重新流行。多粘菌素、四环素类和氟喹诺酮类也可用于 GNB。在某些情况下，如中枢神经系统和前列腺，β-内酰胺类药物可能难以到达感染部位，可能需要与其他药物联合使用。
在发现新的药物家族和治疗方法（如噬菌体治疗与抗生素联合使用）时，必须寻找替代当前治疗方法的方案。
需要更窄谱的免疫抑制治疗和抗生素、对人类微生物群影响最小的抗菌药物以及即时诊断方法，以想象一个目前在感染病理学中占主导地位的细菌失去优势的未来。
