Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort

Abstract

Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 μg/ml with a high inoculum (∼5 × 10 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76-12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.

Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea

“…However, there are limited data concerning the impact of the CIE in clinical practice. A previous study by our group dealt with this issue regarding the CIE, but the study failed to prove its clinical implications [18,25]. In this study, we demonstrated that the CIE was associated with treatment failure of MSSA bacteraemia when the patients were treated with cefazolin.…”

“…The CIE of MSSA isolates obtained from the cases was measured as described elsewhere [19,25]. Briefly, the cefazolin MICs obtained with a high inoculum (HI,~5 Â 10 7 CFU/mL) were compared with those obtained with a standard inoculum (SI,~5 Â 10 5 CFU/mL) to identify the strains with CIE, which was defined as an increase in the MIC to !16 mg/mL with a high inoculum from the susceptible range of the MIC with a standard inoculum [19].…”

Meta‐analysis of trials comparing cefazolin to antistaphylococcal penicillins in the treatment of methicillin‐sensitive Staphylococcus aureus bacteraemia

“…This study may have been underpowered to show such differences. Another report described 303 cases of MSSA bacteraemia and demonstrated that cefazolin may be used successfully in high-inoculum infections if the isolate is sensitive to either clindamycin or erythromycin [21]. Our analysis demonstrated that fewer patients on cefazolin stopped therapy due to adverse events than those receiving ASP, although only four trials were included.…”

“…This study may have been underpowered to show such differences. Another report described 303 cases of MSSA bacteraemia and demonstrated that cefazolin may be used successfully in high‐inoculum infections if the isolate is sensitive to either clindamycin or erythromycin .…”

Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a narrative review

“…In our review, the prevalence of β-lactamase ranges from 77 to 92% while Type A represents 15-34% and a cefazolin inoculum effect was found in 13 to 58% of the MSSA isolates. It seems that no significant association exists between inoculum effect positivity and demographic factors, underlying disease or site of infection [17] even though one study found that osteomyelitis is highly associated with cefazolin inoculum effect in South American hospitals [14]. Five studies assessed the clinical outcomes of the patients from whom MSSA isolates were collected depending on the presence of an inoculum effect.…”