Rare or Unusual Non-Fermenting Gram-Negative Bacteria: Therapeutic Approach and Antibiotic Treatment Options

Abstract

Non-fermenting Gram-negative bacteria (NFGNB) are a heterogeneous group of opportunistic pathogens increasingly associated with healthcare-associated infections. While Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia are well known, rarer species such as Burkholderia cepacia complex, Achromobacter spp., Chryseobacterium spp., Elizabethkingia spp., Ralstonia spp., and others pose emerging therapeutic challenges. Their intrinsic and acquired resistance mechanisms limit effective treatment options, making targeted therapy essential. Objectives: This narrative review summarizes the current understanding of rare and unusual NFGNB, their clinical significance, resistance profiles, and evidence-based therapeutic strategies. Methods: A literature review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies on the epidemiology, antimicrobial resistance, and treatment approaches to rare NFGNB. Results: Rare NFGNB exhibits diverse resistance mechanisms, including β-lactamase production, efflux pumps, and porin modifications. Treatment selection depends on species-specific susceptibility patterns, but some cornerstones can be individuated. Novel β-lactam/β-lactamase inhibitors and combination therapy approaches are being explored for multidrug-resistant isolates. However, clinical data remain limited. Conclusions: The increasing incidence of rare NFGNB requires heightened awareness and a tailored therapeutic approach. Given the paucity of clinical guidelines, antimicrobial stewardship and susceptibility-guided treatment are crucial in optimizing patient outcomes.

Keywords: antibiotic treatment; antimicrobial resistance; non-fermenter bacteria; non-fermenting Gram-negative bacteria; rare pathogens; therapeutic strategies.

Figure 1

Bacteroidota taxonomical classification of the principal human pathogens.

Figure 2

Pseudomonadota taxonomical classification of the principal human pathogens.

Figure 2

Pseudomonadota taxonomical classification of the principal human pathogens.

Figure 3

Intrinsic resistance/expected resistant phenotypes in non-fermenter bacteria. R = resistant [27].

Figure 4

Achromobacter xylosoxidans colonies on tryptic soy agar (TSA) with a pale pink to whitish coloration. The colonies are moderately sized, circular, and have a smooth, glistening surface with no evident hemolysis halo.

Figure 5

Elizabethkingia anophelis colonies on TSA appear large, mucoid, and translucent, with an irregular and wavy growth pattern. They have a glistening, moist texture without visible hemolysis.

Figure 6

Moraxella catarrhalis colonies on TSA appear pale and whitish. The colonies are medium-sized, irregular, and slightly rough in texture, with a matte or granular surface and without visible hemolysis.