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学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

Comparative Effectiveness of Cefazolin versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study

Comparative Effectiveness of Cefazolin versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study

Clin Infect Dis. 2017 Mar 31.  PMID: 28379314

Comparative Effectiveness of Cefazolin versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort StudyTreatment for MSSA Bacteremia | Clinical Infectious Diseases | Oxford Academic

 

MSSA菌血症に対して、CEZ と Nafcillin または Oxacillin を比較した研究で、非常に興味深いです。

 

 

 

 

P : Patients were included if they had a blood culture positive for MSSA

   3,167 patients

 

E : definitive therapy with cefazolin

 

C : definitive therapy with nafcillin, or oxacillin

 

O : 

cefazolin  > nafcillin or oxacillin

30-day mortality (Hazard ratios (HR): 0.63; 95% Confidence Intervals (CI): 0.51-0.78)

90-day mortality (HR: 0.77; 95% CI: 0.66-0.90)

 

cefazolin  ≒ nafcillin or oxacillin

The odds of recurrence (Odds Ratio: 1.13; 95% CI: 0.94-1.36)

 

T : 

retrospective study

119 Veterans Administration hospitals from 2003 to 2010.

 

感想

私は、nafcillin or oxacillinの方が良い結果になるだろうと考えていたため、とても意外でした。

レトロスペクティブからプロスペクティブな検討、さらにはRCTが望まれます。

本論文の解説もとても面白いです。

 

Definitive Treatment for Methicillin-sensitive Staphylococcus aureus Bacteremia: Data versus a definitive answer? PMID: 28379366

 

"In spite of the authors’ vigorous efforts to adjust statistically for baseline severity of infection, comorbidity, and clinical indications, confounding by recognized and unrecognized variables may persist. Furthermore, this study included only 28% of the available MSSA bacteremia cohort. Potentially important data were unavailable: the efficacy of empiric therapy, source control, the adequacy of antibiotic dosing, and total duration of antibiotic treatment.
Most significantly, can we generalize from these data to treatment for those infections at highest risk for cefazolin failure, those caused by MSSA with the type A Bla–cefazoln inoculum effect phenotype? Of particular concern are infections with high bacterial burden and limited source control. Notably, endocarditis was infrequent in the study population (cefazolin 52 (4%) and ASP 168 (8%) patients) and other high bacterial burden, deep-seated infections were not defined."

 

 

 

ちなみに、Type A Bla とは

 

"Recently the potential in vivo consequence of Bla hydrolysis of cefazolin and the inoculum effect has been suggested more strongly. An MSSA strain, which had been recovered from a patient with native valve endocarditis who failed cefazolin therapy, produced a type A Bla that rapidly degraded cefazolin and produced a striking inoculum effect (an MIC with an inoculum of 5 x 10 5 cfu/mL of 0.5 μg/mL increased to 128 μg/mL with an inoculum of 5 x 107cfu/mL). Notably, this strain did not degrade nafcillin nor demonstrate an inoculum effect. Curing this MSSA strain of its Bla gene produced an isogenic derivative that no longer produced Bla nor a cefazolin inoculum effect but that retained infectivity comparable to the parent strain in the rabbit endocarditis model. In that model compared to nafcillin, cefazolin treatment with doses chosen to simulate human dosing was ineffective against infection caused by the Bla producing parent strain. In contrast, cefazolin treatment was effective and comparable to nafcillin against infection caused by the Bla negative derivative MSSA strain. These findings suggest that production of type A Bla and the resultant inoculum effect may be associated with reduced cefazolin efficacy."

 

引用

 

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