Abstract
ObjectivesMannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.MethodsWe conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (≥7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.ResultsPatients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P = 0.019 and P = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83–196.37; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19–29.57; P = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12–63.39; P = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03–4.26; P = 0.040).ConclusionsThis is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.
Highlights
Staphylococcus aureus bacteremia is one of the most common serious bacterial infections with high morbidity and mortality
The persistent bacteremia and resolving bacteremia groups were similar in age, underlying conditions, severity of underlying disease, severity of bacteremia, and presence or absence of eradicable foci
There were no significant differences between the two groups in the removal of eradicable foci (100% in persistent versus 95.5% in resolving bacteremia group; P.0.999) or time to removal of eradicable foci
Summary
Staphylococcus aureus bacteremia is one of the most common serious bacterial infections with high morbidity and mortality. Several clinical and microbiological characteristics such as retention of infected devices, endovascular infection, metastatic infection, methicillin resistance, vancomycin minimal inhibitory concentration (MIC) of 2 mg/L, agr dysfunction, and resistance to host defense cationic peptides have been suggested as risk factors for persistent bacteremia [1,2,3,4,5,6,7]. These clinical and microbiological factors were not consistent among studies and could explain only a part of persistent S. aureus bacteremia. Because S. aureus infection is a consequence of the dynamic interaction between bacteria and host defense, some factors related with host response to S. aureus may contribute to persistent bacteremia
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