Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital

Abstract

Cefazolin is an essential antibiotic used for treating bacteremia; in particular, it is recommended as a first-line agent for infections caused by methicillin-susceptible Staphylococcus aureus (MSSA). In March 2019, problems with a major antibiotic supplier caused a critical shortage of cefazolin in Japan; however, the impact of the cefazolin shortage on clinical outcomes remains unknown. This study aimed to evaluate the effect of the cefazolin shortage in patients with MSSA bacteremia. Data from 75 patients were compared between the pre-shortage (March 2018–January 2019, n = 39) and post-shortage (March 2019–January 2020, n = 36) periods. There were no significant differences in the demographic characteristics between the two groups, and the cefazolin shortage did not worsen clinical outcomes such as adverse drug reactions, treatment failure, and 30-day mortality. In the post-shortage group, ampicillin/sulbactam and benzylpenicillin were more frequently administered as alternative antibiotics for empirical and definitive therapy (10% vs. 31%, p = 0.042; 0% vs. 19%, p = 0.004, respectively). Multivariate analysis revealed that the broad-spectrum antibiotics for definitive therapy, such as antipseudomonal penicillin, were associated with treatment failure in patients with MSSA bacteremia (OR = 17, p = 0.003). Hence, narrow-spectrum antibiotics should be prescribed for MSSA bacteremia as alternatives during a cefazolin shortage.

Sustained Improvements in Antimicrobial Therapy and Clinical Outcomes following a Pharmacist-Led Antimicrobial Stewardship Intervention: Uncontrolled Before–After Study

“…In contrast, there was a significant increase in the use of non-antipseudomonal penicillins, secondgeneration cephalosporins, and non-antipseudomonal third-generation cephalosporins between the baseline and post-intervention periods. These agents and broad-spectrum antibiotics, such as fluoroquinolones and anti-MRSA agents, are listed as alternative antimicrobials for cefazolin by the Ministry of Health, Labour and Welfare of Japan [30]; however, in the present study, we had a rational antimicrobial strategy for treating bacteremia due to methicillin-susceptible S. aureus [29], which may prevent an increase in the use of broad-spectrum antibiotics.…”

“…Owing to a national shortage of cefazolin in Japan, the prescription of cefazoline has been restricted in our hospital since March 2019 [29]. Therefore, the use of first-generation cephalosporins significantly decreased during the post-intervention period.…”

Comparative Effectiveness of Ampicillin/Sulbactam versus Cefazolin as Targeted Therapy for Bacteremia Caused by Beta-Lactamase-Producing Methicillin-Sensitive Staphylococcus aureus: A Single-Center Retrospective Study

“…Although prior studies revealed that the administration of alternative broad-spectrum drugs is associated with worse clinical outcomes [ 18 , 19 ], we could avoid worse deterioration in patient outcomes even in an antimicrobial shortage period. Moreover, based on a multivariate analysis, Uda et al, reported that administration of broad-spectrum antibiotics, such as piperacillin/tazobactam, as definitive therapy was associated with treatment failure in patients with MSSA bacteremia during the CFZ shortage period (odds ratio = 17, p = 0.003) [ 20 ]. Therefore, careful and restricted intervention via an AST physician is vital during critical antimicrobial shortages, in addition to avoiding prescription of broad-spectrum antibiotics for the treatment of BP-MSSA bacteremia.…”

Cefazolin access and use in Ethiopia: A policy implication

“…These shortages have confused the drug choice and resulted in increased use of third-generation cephalosporins like ceftriaxone and cefotaxime, from the watch category according to WHO AWaRe classification [5,8,9]. Japan's studies had also indicated a poor treatment outcome and increased cost due to the use of such alternative agents [3,5,10].…”

“…In all these studies, ceftriaxone alone or in combination with metronidazole are the major drugs used in place despite the guideline recommending cefazolin. Unlike the experiences in Japan, the effect of such alternative broad-spectrum antimicrobial use is not studied in Ethiopia [5,8,10]. However, other studies had shown a high burden of surgical site infections in Ethiopian hospitals despite extensive prescribing of prophylactic agents [19,20].…”