What is Flomoxef?
An oxacephem antibiotic that has been semi-synthesized, Flomoxef was developed in Japan in the 1980s. It's a structure-based cousin of -lactam antibiotics, though its oxacephem core makes it stand out among cephalosporins. Flomoxef is distinguished by broad-spectrum action against several bacterial infections including multidrug-resistant (MDR) strains. It's highly attracted to penicillin-binding proteins (PBPs), so it knocks out the production of bacterial cell walls and kills cells. Most importantly, Flomoxef has shown activity against ESBL-producing Enterobacteriaceae in vitro, so it's an attractive candidate for treating resistant bacterial infections.
What is the Classification of Flomoxef?
Flomoxef is in the oxacephem family of β-lactam antibiotics. In contrast to other cephalosporins, the oxacephems have an oxygen atom instead of a sulfur atom in the dihydrothiazine ring. It has been adapted so that it is more stable against -lactamase enzymes, especially those of ESBLs, but still bactericidal. Flomoxef is a parenteral antibiotic indicated for severe systemic infections caused by Gram-positive and Gram-negative pathogens.
What is the Mechanism of Action of Flomoxef?
Flomoxef acts as a bactericidal agent mostly because it is highly active against PBPs, enzymes involved in the construction of the cell wall. Through PBP inhibition, Flomoxef also interferes with peptidoglycan cross-linking, fraying the bacterial cell wall and creating osmotic instability. That kills the cells and lysis them.
Although Flomoxef has powerful activity against many of these bacteria, it has been blamed for the formation of resistance systems in some strains. In Klebsiella pneumoniae, for example, Flomoxef treatment was associated with the formation of porin defects and the inheritance of blaDHA-1, a gene that codes for AmpC β-lactamase. These can confer resistance not just to Flomoxef, but also to carbapenems like ertapenem. This kind of resistance mechanism emphasizes the importance of antimicrobial use sparingly and combination therapy where indicated.
Fig.1 Sepsis-related mortality among patients with bacteraemia caused by extended-spectrum β-lactamase (ESBL)-producing isolates. Cases are grouped according to treatment with flomoxef (FLO) or a carbapenem (CAB) and are further stratified by FLO minimum inhibitory concentrations (MICs). Numbers of cases with mortality among the total case numbers in the respective group are indicated[1].
Flomoxef vs. Other Antibiotics
There are pros and cons to Flomoxef as compared with other β-lactam antibiotics for treating infections by ESBL-producing Enterobacteriaceae.
Advantages:
- Effectiveness Against ESBL Producers - Flomoxef is bactericidal against ESBL-producing strains, even at high minimum inhibitory concentrations (MICs).
- A Safe Alternative to Carbapenems - As someone who is sensitive to the idea of carbapenem abuse and its attendant resistance, Flomoxef is a good choice in conditions that require care for carbapenems.
Limitations:
- Broad-Spectrum Nature - As a broad-spectrum β-lactam, Flomoxef may be less effective in terms of cure rates and survival outcomes when compared to carbapenems, cephamycins, or fluoroquinolones.
- Inoculum Effect - High bacterial loads can limit the efficacy of Flomoxef, particularly in severe infections where achieving adequate drug concentrations is challenging.
The table below summarizes Flomoxef's comparative profile:
| Parameter | Flomoxef | Carbapenems | Fluoroquinolones |
| Activity Against ESBLs | High | Very High | Moderate |
| Risk of Resistance | Moderate | Low | Moderate |
| Effectiveness in Severe Infections | Moderate | High | Moderate |
| Spectrum of Activity | Broad | Broad | Narrower (Gram-negative focus) |
Conclusion
Flomoxef continues to be a useful tool against multidrug-resistant bacteria, such as the ESBL-producing Enterobacteriaceae. Its structural specialization and bactericidal potency make it an attractive substitute for carbapenems in certain clinical situations. However, drawbacks like resistance development and poor efficacy in severe infections emphasize the need for use in the right dosage. Additional studies into combination therapy and stewardship will help refine the place of Flomoxef in modern antibiotic protocols.
Reference
- Lee C-H., et al. Comparative effectiveness of flomoxef versus carbapenems in the treatment of bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae with emphasis on minimum inhibitory concentration of flomoxef: a retrospective study. International Journal of Antimicrobial Agents (2015).
