Antimicrobial Therapy

Introduction to Cephalosporins

• Cephalosporins are a class of antimicrobial agents used to treat various infections, with different generations having distinct antimicrobial properties and clinical applications 1, 2, 3

Cephalosporin Selection

• Cefepime, a fourth-generation cephalosporin, is recommended for low-risk mortality cases of hospital-acquired pneumonia, while ceftazidime, a third-generation cephalosporin, is recommended when Pseudomonas aeruginosa infection is suspected 2
• Both cefepime and ceftazidime require combination with metronidazole for anaerobic coverage in intra-abdominal infections, due to their lack of anti-anaerobic activity 1, 3
• Cefepime is effective against AmpC-producing organisms, but neither cefepime nor ceftazidime provides adequate anaerobic coverage alone 1

Resistance and Susceptibility

• Extended-spectrum beta-lactamases (ESBLs) are enzymes produced by bacterial isolates that hydrolyze beta-lactam antibiotics, rendering them ineffective, with a minimum inhibitory concentration (MIC) greater than 1 μg/mL for cefotaxime indicating resistance 4, 5
• The use of ceftazidima and cefotaxima in antibiograms allows for the identification of specific resistance phenotypes, particularly the production of ESBL 4
• Resistance to both cephalosporins, along with additional tests, may suggest the presence of carbapenemases, requiring confirmatory tests such as Carba NP or PCR for definitive identification 6

Treatment of ESBL-Producing Organisms

• The Infectious Diseases Society of America recommends avoiding cephalosporins for treating ESBL-producing organisms due to poor clinical outcomes, and instead recommends carbapenems, such as meropenem, imipenem, and ertapenem, as the preferred treatment for serious infections 4, 5
• In selected cases, ceftazidima-avibactam may be an option for organisms producing ESBL and KPC, as recommended by some guidelines 7

Infection Control and Epidemiology

• ESBL-producing organisms often require contact precautions to prevent transmission in healthcare settings, and surveillance is important for epidemiological tracking and infection control purposes, as recommended by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) 4
• Phenotypic tests like the combined disk test (CDT) have high sensitivity for detecting carbapenemases, and detecting these phenotypes is crucial for implementing appropriate infection control measures and enabling epidemiological surveillance of resistance patterns 6, 4

Diagnostic Considerations

• Current CLSI breakpoints for ceftazidima (≤ 4 μg/mL) and cefepima (≤ 8 μg/mL) do not identify all ESBL-producing strains, highlighting the need for consideration of additional tests and characterization methods, such as synergy tests with beta-lactamase inhibitors 4
• The following table summarizes the CLSI breakpoints for ceftazidima and cefepima: