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Broad-spectrum beta-lactam resistance in Enterobacter: emergence during treatment and mechanisms of resistance
Abstract:
Of three patients with Enterobacter mediastinitis treated with cefamandole, two failed initial treatment due to emergence of strains resistant to cefamandole and third generation cephalosporins. Extracts of the sensitive strains showed inducible hydrolysis of cephalothin; resistant strains (wild and laboratory derived) showed constitutive hydrolysis of cephalothin and cefamandole and bound but did not hydrolyze cefotaxime and latamoxef (moxalactam). In one mutant, increased latamoxef resistance appeared due to non-enzymatic mechanism(s). The Enterobacter strain from the patient who was treated successfully with cefamandole yielded only low level resistant mutants with lower cephalosporin binding than obtained with the other strains.
Insights
Two of three patients with Enterobacter mediastinitis failed cefamandole treatment due to resistant strains. Resistant strains hydrolyzed cephalosporins, while sensitive strains showed inducible resistance, impacting antibiotic efficacy.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Enterobacter infections can lead to mediastinitis, a serious condition.
- Cefamandole and third-generation cephalosporins are used to treat such infections.
Observation:
- Two out of three patients with Enterobacter mediastinitis treated with cefamandole experienced treatment failure.
- Treatment failure was associated with the emergence of bacterial strains resistant to cefamandole and third-generation cephalosporins.
Findings:
- Sensitive Enterobacter strains exhibited inducible hydrolysis of cephalothin.
- Resistant strains, both wild and laboratory-derived, showed constitutive hydrolysis of cephalothin and cefamandole.
- Resistant strains bound but did not hydrolyze cefotaxime and latamoxam (moxalactam).
- One mutant displayed increased latamoxam resistance via non-enzymatic mechanisms.
- The successfully treated patient's Enterobacter strain produced low-level resistant mutants with reduced cephalosporin binding.
Implications:
- Bacterial resistance mechanisms, such as inducible and constitutive hydrolysis of cephalosporins, can compromise treatment efficacy.
- Understanding these resistance patterns is crucial for selecting effective antibiotics against Enterobacter infections.
- Further research into non-enzymatic resistance mechanisms and cephalosporin binding is warranted.