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Published on: February 23, 2014
The inoculum effect with gram-negative bacteria in vitro and in vivo
1New England Medical Center, Division of Geographic Medicine and Infectious Diseases, Boston, MA 02111.
Abstract:
The in-vitro MICs and MBCs of ciprofloxacin, cefoperazone, ceftazidime, ceftriaxone, gentamicin and imipenem were measured for five strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa with standard and high inocula. The MBC was raised more than the MIC at the higher inoculum for all the drugs except ciprofloxacin. However, the MBC of imipenem against P. aeruginosa was increased relatively little at the higher inoculum in contrast to the findings with other beta-lactam drugs. In a rabbit model of endophthalmitis both cefoperazone and imipenem were markedly more bactericidal against a high inoculum of K. pneumoniae than would have been predicted from the results of in-vitro time kill curve studies. We conclude that the therapeutic relevance of the inoculum effect remains to be proved.
Insights
The inoculum effect, where higher bacterial loads increase antibiotic minimum bactericidal concentrations (MBCs), was observed for most drugs against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Its clinical significance in treating infections requires further investigation.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The inoculum effect describes how higher bacterial concentrations can alter antimicrobial susceptibility testing results.
- Understanding this effect is crucial for predicting treatment efficacy, especially with common Gram-negative pathogens.
Purpose of the Study:
- To investigate the in-vitro inoculum effect on minimum inhibitory concentrations (MICs) and MBCs of various antibiotics against key Gram-negative bacteria.
- To evaluate the in-vivo bactericidal activity of selected antibiotics in a rabbit endophthalmitis model, considering inoculum size.
Main Methods:
- Standard and high inocula of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa strains were used to determine in-vitro MICs and MBCs.
- Antibiotics tested included ciprofloxacin, cefoperazone, ceftazidime, ceftriaxone, gentamicin, and imipenem.
- A rabbit model of endophthalmitis was employed to assess the in-vivo efficacy of cefoperazone and imipenem against K. pneumoniae.
Main Results:
- The MBC/MIC ratio increased at higher inocula for most tested antibiotics, except ciprofloxacin.
- Imipenem showed a less pronounced increase in MBC at higher inocula against P. aeruginosa compared to other beta-lactams.
- Cefoperazone and imipenem demonstrated greater in-vivo bactericidal activity against K. pneumoniae in a rabbit endophthalmitis model than predicted by in-vitro time-kill studies.
Conclusions:
- The inoculum effect influences the in-vitro activity of several antibiotics against Gram-negative bacteria.
- In-vivo efficacy in an endophthalmitis model may not always correlate directly with in-vitro predictions based on inoculum effects.
- The clinical relevance of the inoculum effect in antimicrobial therapy remains to be definitively established.
