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Clinical consequences of development of resistance to third generation cephalosporins
F Follath1, E Costa, A Thommen
1Department of Medicine, University Hospital (Kantonspital), Basel, Switzerland.
Abstract:
Eighteen patients are described in whom initially sensitive microorganisms were replaced by resistant isolates during administration of ceftriaxone (n = 8), cefoperazone (n = 5), moxalactam (n = 4), cefotaxime (n = 2) or ceftazidime (n = 1), despite combination with aminoglycosides. All patients had documented gram-negative infections; in 12 patients underlying haematological diseases were present. Resistant strains of Enterobacter cloacae (14), Serratia marcescens (4), Klebsiella oxytoca (3), Pseudomonas aeruginosa (2) and Citrobacter freundii (2) emerged within 2 to 19 (mean 9) days after the beginning of treatment. In 12 patients relapse or secondary infections occurred. Seven of the patients with haematological disorders died. Resistance development was seen in 8 of 29 patients on ceftriaxone and 4 of 10 patients on moxalactam during prospective evaluations; the other drugs were used sporadically. Thus, selection of resistant bacteria is relatively frequent and may have serious clinical consequences in patients with impaired host-defense mechanisms.
Insights
Third-generation cephalosporins can lead to resistant gram-negative bacteria, especially in immunocompromised patients. This resistance development during treatment has serious clinical consequences.
Area of Science:
- Clinical Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Gram-negative bacterial infections pose a significant clinical challenge.
- The emergence of antimicrobial resistance is a growing concern in healthcare settings.
- Patients with hematological disorders often have compromised immune systems, increasing susceptibility to infections and complications.
Purpose of the Study:
- To investigate the development of antimicrobial resistance during treatment with third-generation cephalosporins.
- To identify the specific resistant bacterial strains that emerge.
- To assess the clinical consequences of resistance development in patients, particularly those with impaired host-defense mechanisms.
Main Methods:
- Retrospective analysis of 18 patients with documented gram-negative infections.
- Patients received various third-generation cephalosporins (ceftriaxone, cefoperazone, moxalactam, cefotaxime, ceftazidime), often in combination with aminoglycosides.
- Monitoring of bacterial isolates for changes in susceptibility patterns during antibiotic administration.
Main Results:
- Initially sensitive gram-negative microorganisms became resistant during cephalosporin therapy in 18 patients.
- Resistant strains included Enterobacter cloacae, Serratia marcescens, Klebsiella oxytoca, Pseudomonas aeruginosa, and Citrobacter freundii.
- Resistance emerged within 2-19 days of treatment. Relapse or secondary infections occurred in 12 patients, with 7 deaths among those with hematological disorders.
Conclusions:
- Third-generation cephalosporins can select for resistant gram-negative bacteria, even when combined with aminoglycosides.
- Resistance development is relatively frequent and can have severe clinical outcomes, especially in patients with compromised immune systems.
- Careful monitoring for resistance is crucial in vulnerable patient populations undergoing treatment for gram-negative infections.