Related Experiment Video
Updated: May 10, 2026

Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Cefazolin high-inoculum effect in methicillin-susceptible Staphylococcus aureus from South American hospitals
Sandra Rincón1, Jinnethe Reyes, Lina Paola Carvajal
1Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Carrera 7B Bis No. 132-11, Bogotá, Colombia.
Objectives:
Clinical failures with cefazolin have been described in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) producing type A β-lactamase. We investigated the prevalence of the cefazolin inoculum effect (InE) in MSSA from South American hospitals, since cefazolin is used routinely against MSSA due to concerns about the in vivo efficacy of isoxazolyl penicillins.
Methods:
MSSA isolates were recovered from bloodstream (n = 296) and osteomyelitis (n = 68) infections in two different multicentre surveillance studies performed in 2001-02 and 2006-08 in South American hospitals. We determined standard-inoculum (10(5)cfu/mL) and high-inoculum (10(7) cfu/mL) cefazolin MICs. PFGE was performed on all isolates that exhibited a cefazolin InE. Multilocus sequence typing (MLST) and sequencing of part of blaZ were performed on representative isolates.
Results:
The overall prevalence of the cefazolin InE was 36% (131 isolates). A high proportion (50%) of MSSA isolates recovered from osteomyelitis infections exhibited the InE, whereas it was observed in 33% of MSSA recovered from bloodstream infections. Interestingly, Ecuador had the highest prevalence of the InE (45%). Strikingly, 63% of MSSA isolates recovered from osteomyelitis infections in Colombia exhibited the InE. MLST revealed that MSSA isolates exhibiting the InE belonged to diverse genetic backgrounds, including ST5, ST8, ST30 and ST45, which correlated with the prevalent methicillin-resistant S. aureus clones circulating in South America. Types A (66%) and C (31%) were the most prevalent β-lactamases.
Conclusions:
Our results show a high prevalence of the cefazolin InE associated with type A β-lactamase in MSSA isolates from Colombia and Ecuador, suggesting that treatment of deep-seated infections with cefazolin in those countries may be compromised.
Insights
The cefazolin inoculum effect (InE), a challenge in treating Staphylococcus aureus infections, is prevalent in South America. This effect, linked to beta-lactamase production, may compromise cefazolin treatment for deep-seated infections in Colombia and Ecuador.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Cefazolin is a common treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections.
- Clinical failures have been noted in high-inoculum infections caused by MSSA producing type A beta-lactamase.
- The cefazolin inoculum effect (InE) is a phenomenon where higher bacterial concentrations reduce cefazolin susceptibility.
Purpose of the Study:
- To determine the prevalence of the cefazolin inoculum effect (InE) in MSSA isolates from South American hospitals.
- To investigate the association between InE and beta-lactamase production in MSSA.
- To assess the potential impact of InE on cefazolin treatment efficacy in the region.
Main Methods:
- Collected MSSA isolates from bloodstream and osteomyelitis infections across South American hospitals (2001-2008).
- Determined cefazolin Minimum Inhibitory Concentrations (MICs) at standard (10^5 cfu/mL) and high (10^7 cfu/mL) inoculums.
- Utilized Pulsed-Field Gel Electrophoresis (PFGE), Multilocus Sequence Typing (MLST), and blaZ sequencing for isolate characterization.
Main Results:
- The overall prevalence of cefazolin InE was 36%, with higher rates in osteomyelitis (50%) than bloodstream infections (33%).
- Ecuador (45%) and Colombia (63% in osteomyelitis) showed particularly high InE prevalence.
- Prevalent beta-lactamases were Type A (66%) and Type C (31%), correlating with InE.
Conclusions:
- A significant prevalence of cefazolin InE was observed in MSSA from Colombia and Ecuador, often associated with Type A beta-lactamase.
- The findings suggest that cefazolin treatment for deep-seated MSSA infections in these countries may be less effective.
- Further surveillance and consideration of alternative antibiotics are warranted for MSSA infections in high-InE prevalence areas.
Related Concept Videos
Clinical Significance of Antibiotic Resistance
Mechanism of Antibiotic Resistance in MRSA
Staphylococcal Skin Infections
Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

