What evidence is there for oxacillin vs cefazolin for epidural abscess treatment?

Comment by InpharmD Researcher

Limited data are available comparing oxacillin and cefazolin specifically for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) spinal epidural abscesses. One retrospective study found that cefazolin was as effective as antistaphylococcal penicillins (oxacillin and nafcillin), suggesting it is a reasonable alternative for this indication (see Table 1). Outside of spinal epidural abscesses, comparative data are primarily focused on MSSA bacteremia, where cefazolin has generally demonstrated comparable or improved clinical outcomes and a more favorable safety profile than oxacillin and other antistaphylococcal penicillins. Overall, although direct evidence for spinal epidural abscesses is limited, the broader MSSA literature supports cefazolin as an effective and well-tolerated alternative to antistaphylococcal penicillins.
Background

A 2017 comparative review analyzed the efficacy and safety of cefazolin versus antistaphylococcal penicillins (ASPs) for the treatment of MSSA bacteremia. The review synthesized findings from multiple retrospective and comparative studies to assess clinical outcomes, with a particular focus on concerns regarding cefazolin’s susceptibility to hydrolysis by type A β-lactamases and the inoculum effect. Oxacillin and cefazolin appear to have broadly comparable clinical efficacy for MSSA bacteremia, including complicated infections, when adequate source control is achieved and dosing is optimized. Oxacillin has traditionally been favored as an antistaphylococcal penicillin because of historical concerns that cefazolin may be less reliable in high-inoculum infections such as endocarditis, deep abscesses, or other deep-seated foci due to the cefazolin inoculum effect. However, the clinical relevance of this concern appears uncertain, and outcomes seem to be driven more by infection severity, duration of bacteremia, metastatic infection, and source control than by whether oxacillin or cefazolin is selected. Cefazolin offers several practical advantages over oxacillin, including easier dosing, lower sodium and fluid burden, potential for rapid IV administration, lower acquisition cost, and generally better tolerability. Safety is a major differentiator: oxacillin is associated with higher rates of adverse drug reactions, especially hepatotoxicity, rash, renal dysfunction, cytopenias/neutropenia, and discontinuation during prolonged therapy. Overall, cefazolin is a reasonable alternative to oxacillin for most MSSA bloodstream infections outside of CNS infection, with greater caution in severe deep-seated infections such as endocarditis, where risk-benefit assessment, source control, and aggressive cefazolin dosing are especially important. Cefazolin and oxacillin demonstrated broadly similar effectiveness for MSSA bacteremia, but cefazolin had more favorable tolerability and cost data, with reported clinical cure rates of 95% vs 88%, lower 90-day treatment failure in one complicated bacteremia comparison, fewer ADRs than oxacillin (3% vs 30%), lower discontinuation due to ADRs (3% vs 21%), and lower acquisition cost. [1]

Additionally, a 2025 systematic review and meta-analysis included 30 observational studies comparing cefazolin with the antistaphylococcal penicillins flucloxacillin, nafcillin, cloxacillin, and oxacillin for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia. Compared with oxacillin, cefazolin was associated with similar 30-day all-cause mortality (odds ratio [OR] 0.31; 95% confidence interval [CI] 0.03 to 2.75), meeting the prespecified noninferiority criteria. Overall, cefazolin was also associated with fewer treatment-related adverse events, lower nephrotoxicity, and fewer treatment discontinuations than antistaphylococcal penicillins. The authors concluded that cefazolin was noninferior to antistaphylococcal penicillins for mortality and may offer a more favorable safety profile based on observational evidence. [2]

Background References: [1] Li J, Echevarria KL, Traugott KA. β-Lactam Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Comparative Review of Cefazolin versus Antistaphylococcal Penicillins. Pharmacotherapy. 2017;37(3):346-360. doi:10.1002/phar.1892
[2] Prosty C, Noutsios D, Lee TC, et al. Cefazolin vs. antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2025;31(9):1272-1282. doi:10.1016/j.cmi.2025.04.045
Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

What evidence is there for oxacillin vs cefazolin for epidural abscess treatment?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-6 for your response.

 

Antistaphylococcal Penicillin vs Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Spinal Epidural Abscesses
Design

Single-center, multisite retrospective cohort study

N= 79
Objective To compare clinical outcomes associated with cefazolin vs ASPs to treat MSSA spinal epidural abscesses
Study Groups

Cefazolin (n= 45)

Nafcillin or Oxacillin (n= 34)
Inclusion Criteria Adult patients (≥18 years of age) diagnosed with MSSA spinal epidural abscesses from January 1, 2014, to July 31, 2020, at Mayo Clinic sites
Exclusion Criteria Patients who received another antibiotic in addition to cefazolin or ASP for >50% of the total treatment duration
Methods Patients were allocated to either the cefazolin or ASP group if they received cefazolin or an ASP for >50% of the total treatment duration. Data were collected from electronic health records and clinical microbiology laboratory databases. Cefazolin was administered at 2 g every 8 hours, oxacillin at 2 g every 4 hours, or nafcillin at 2 g every 4 hours.
Duration January 1, 2014, to July 31, 2020
Outcome Measures

Treatment failure at week 6 and week 12
Baseline Characteristics   Cefazolin (n= 45) Nafcillin or Oxacillin (n= 34)
Age, y 64.5 (55–73.2) 59.6 (47.2–64)
Male 26 (57.7%) 19 (55.9%)
Body mass index, kg/m2 27.7 (23.4–33.8) 30.6 (24.9–35.7)
Results   Cefazolin (n= 45) Nafcillin/Oxacillin (n= 34) p-Value
Hospital length of stay, d 9 (5.5–15.5) 13 (6–25) 0.52
Treatment failure at week 6 - Antibiotic extension due to clinical failure 34 (75.6) 28 (82.4) 0.58
Treatment failure at week 12 - Antibiotic extension due to clinical failure 15 (33.3) 15 (44.1) 0.35
Mortality - Overall, d 290 (38–1301)

114 (11.75–1348)

 0.52
Adverse Events No significant differences in treatment failure, mortality, or recurrence rates between cefazolin and ASPs groups
Study Author Conclusions Cefazolin was equally as effective as ASPs in treating MSSA spinal epidural abscesses, suggesting it can be an alternative to ASPs
Critique The study's retrospective nature and small sample size limit its ability to detect differences in treatment outcomes. Additionally, more patients in the ASPs group were admitted to the ICU, which could introduce confounding bias.
Table 1 References:
[3] Corsini Campioli C, Go JR, Abu Saleh O, Challener D, Yetmar Z, Osmon DR. Antistaphylococcal Penicillin vs Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Spinal Epidural Abscesses. Open Forum Infect Dis. 2021;8(3):ofab071. Published 2021 Feb 16. doi:10.1093/ofid/ofab071

Treatment Outcomes with Cefazolin versus Oxacillin for Deep-Seated Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections
Design

Retrospective cohort study

N= 161
Objective

To evaluate and compare treatment outcomes using cefazolin or oxacillin for Methicillin-Susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI), including deep-seated sources of infection
Study Groups

Cefazolin (n= 103)

Oxacillin (n= 58)
Inclusion Criteria

Adult patients who received in-hospital definitive treatment with cefazolin or oxacillin within 48 h of finalized blood cultures with MSSA
Exclusion Criteria

Patients <18 years of age, received antibiotics other than cefazolin or oxacillin for definitive treatment, received ≥5 days of an empirical antibiotic agent active against MSSA prior to definitive treatment, documented penicillin or cephalosporin allergy, or had polymicrobial bacteremia
Methods

Patient demographics, comorbidities, infection characteristics, antimicrobial treatment, treatment duration, source control, time to first negative blood culture, adverse drug events, therapy changes, and organ dysfunction were retrospectively extracted from electronic medical records, pharmacy databases, and microbiology databases by trained reviewers. Treatment failure was defined as a change in MSSA-directed therapy when documentation indicated clinician opinion that cefazolin or oxacillin was ineffective; in-hospital mortality secondary to infection also counted as treatment failure. Deep-seated MSSA BSI included infective endocarditis or bone/joint infection, deep-seated abscesses, osteomyelitis, pneumonia, or unresolved vascular graft infection. Outcomes were analyzed according to initial definitive therapy. Multivariate logistic regression evaluated adjusted odds of treatment failure, with treatment group forced into all models; secondary analyses included mortality, deep-seated infection outcomes, bacteremia duration, and adverse events.
Duration

January 2010 to April 2013
Outcome Measures

Primary: Covariate-adjusted odds of treatment failure

Secondary: All-cause in-hospital mortality, treatment failure rates among deep-seated infections, duration of MSSA BSI, incidence of documented adverse events
Baseline Characteristics  

Cefazolin (n= 103)

 Oxacillin (n= 58)

Mean age, years 

 53.3 ± 16.7 53.6 ± 18.4

Male

 60 (58.3%) 36 (62.1%)

Race

African-American

Caucasian

 

46 (44.7%)

37 (35.9%)

 

14 (24.1%)

33 (56.9%)

Mean m-APACHE score day 0

 13 ± 6.3 10.3 ± 5.8

Intensive care unit admission

 43 (41.8%) 19 (32.8%)

Renal dysfunction

 51 (49.5%) 17 (29.3%)
Results  

Cefazolin (n= 103)

 Oxacillin (n= 58) p-value
Treatment failure

6 (5.8%)

 7 (12.1%) 0.16
In-hospital mortality

1 (1.0%)

 3 (5.2%) 0.13

In secondary clinical outcomes, cefazolin and oxacillin were associated with generally similar results.

Median time to treatment failure was 6.5 days with cefazolin versus 10 days with oxacillin (p= 0.61), while median duration of bacteremia was identical between groups at 3 days (interquartile range [IQR] 2-4; p= 0.57).

Median treatment duration was also comparable with cefazolin and oxacillin (29 vs 32.5 days; p= 0.35), and reinfection after clearance occurred in 4.9% versus 5.2% of patients, respectively (p> 0.99).

Among patients with deep-seated infections, treatment failure occurred in 15.6% of cefazolin-treated patients and 20.0% of oxacillin-treated patients (p= 0.72), with similar rates of deep-seated infection resolution (84.4% vs 80.0%; p= 0.72) and endocarditis resolution (76.5% vs 83.3%; p> 0.99).

The only statistically significant between-group difference was a higher rate of change to an alternate agent with oxacillin compared with cefazolin (43.1% vs 20.4%; p= 0.002). In adjusted analysis, oxacillin treatment was not a statistically significant independent predictor of treatment failure compared with cefazolin, although the estimate numerically favored cefazolin and approached significance (adjusted odds ratio [OR] 3.76; 95% confidence interval [CI] 0.98-14.4; p= 0.053).
Adverse Events

Adverse events were rare. Composite of all recorded adverse drug events was numerically but not significantly higher among patients receiving cefazolin (7.8%) than those receiving oxacillin (3.4%).
Study Author Conclusions

Cefazolin produced clinical outcomes similar to those of standard-of-care therapy with oxacillin for the treatment of MSSA BSI. Our study suggests that patients with culture-proven MSSA BSI, including deep-seated infection, can be effectively managed with cefazolin as definitive therapy in combination with source control and close monitoring. Oxacillin and other semisynthetic penicillins will continue to play a major role in the setting of treatment failure and in infections for which cefazolin has poor distribution (i.e., central nervous system infections). Until larger prospective trials can provide additional insight into the comparative effectiveness of cefazolin and semisynthetic penicillins across the spectrum of clinical diseases, we suggest that these two therapeutic approaches may be considered interchangeable for the majority of MSSA BSI.
Critique

This retrospective cohort directly compares cefazolin and oxacillin for MSSA BSI and includes a clinically relevant deep-seated infection subgroup, which is applicable to epidural abscess only indirectly because “deep-seated abscesses” were included but epidural abscess was not reported as a separate source. Cefazolin showed similar treatment failure, bacteremia duration, mortality, and deep-seated infection resolution compared with oxacillin, but interpretation is limited by retrospective design, nonrandomized treatment selection, between-group baseline differences, and lack of isolate genotyping for β-lactamase/inoculum effect.
Table 2 References:
[4] Rao SN, Rhodes NJ, Lee BJ, et al. Treatment outcomes with cefazolin versus oxacillin for deep-seated methicillin-susceptible Staphylococcus aureus bloodstream infections. Antimicrob Agents Chemother. 2015;59(9):5232-5238. doi:10.1128/AAC.04677-14

Cefazolin versus cloxacillin as definitive antibiotic therapy for methicillin-susceptible Staphylococcus aureus spinal epidural abscess: a retrospective cohort study
Design

Retrospective cohort study

N= 98
Objective To compare the effectiveness of cefazolin and cloxacillin as definitive antibiotic therapy for methicillin-susceptible Staphylococcus aureus (MSSA) spinal epidural abscess (SEA)
Study Groups

Cefazolin (n= 50)

Cloxacillin (n= 48)
Inclusion Criteria Diagnosis of SEA based on spine CT or MRI, or intra-operative findings; isolation of MSSA from a blood culture or intra-operative tissue culture; treatment with cefazolin or cloxacillin as definitive antibiotic therapy
Exclusion Criteria Palliation within 72 h of diagnosis; repatriation to another hospital immediately after surgery resulting in no post-operative follow-up
Methods Patients with MSSA SEA were identified from two academic hospitals. Cefazolin and cloxacillin were compared as definitive antibiotic therapies. 
Duration January 2014 to January 2021
Outcome Measures

Primary: 90-day all-cause mortality, antibiotic failure, serious adverse reactions, recurrence

Secondary: Neurological outcomes at the end of follow-up
Baseline Characteristics   Cefazolin (N = 50) Cloxacillin (N = 48) P-value
Age [median (IQR)] 57.00 (46.25–69.75) 57.00 (50.75–71.00) 0.81
Female sex 11 (22%) 22 (46%) 0.02
Weight ≥120 kg 6 (12%) 3 (6%) 0.49
Charlson comorbidity index 0 27 (54%) 22 (46%) 0.67
Immunocompromised 4 (8%) 1 (2%) 0.36
Injection drug use 10 (20%) 18 (38%) 0.07
Septic shock 2 (4%) 9 (19%) 0.03
Bacteremia 41 (82%) 46 (96%) 0.05
Results   Cefazolin (N = 50) Cloxacillin (N = 48) Unadjusted risk difference (95% CI) Risk difference after propensity score adjustment (95% CI)
90-day all-cause mortality 4 (8%) 6 (13%) –5% (–19% to 10%) –1% (–10% to 8%)
Antibiotic failure 6 (12%) 9 (19%) –7% (–23% to 9%) 1% (–12% to 14%)
Serious adverse reactions 0 (0%) 2 (4%) –4% (–15% to 5%) –5% (–11% to 2%)
Recurrence 1 (2%) 4 (8%) –6% (–19% to 5%) –18% (–36% to –1%)
Adverse Events Serious adverse reactions were 0% in the cefazolin group and 4% in the cloxacillin group
Study Author Conclusions Cefazolin is likely as effective as an antistaphylococcal penicillin and may be considered as a first-line treatment for MSSA SEA
Critique The study is strengthened by its large sample size and detailed data collection, allowing for a precise estimate of outcomes. However, the retrospective design may introduce selection bias, as sicker patients might have been preferentially treated with cloxacillin. Despite using propensity scores to adjust for prognostic factors, residual confounding may still exist. Additionally, the lack of standardization in surgical interventions could affect outcomes, and the study's observational nature limits the ability to establish causality.
Table 3 References:
[5] Bai AD, Findlater A, Irfan N, Singhal N, Loeb M. Cefazolin versus cloxacillin as definitive antibiotic therapy for methicillin-susceptible Staphylococcus aureus spinal epidural abscess: a retrospective cohort study. Int J Antimicrob Agents. 2021 Nov;58(5):106429. doi:10.1016/j.ijantimicag.2021.106429

 

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

Retrospective cohort study

N= 3167
Objective To compare definitive therapy with cefazolin vs nafcillin or oxacillin among patients with MSSA infections complicated by bacteremia
Study Groups

Cefazolin (n= 1163)

Nafcillin or Oxacillin (n= 2004)
Inclusion Criteria Patients admitted to 119 VA hospitals from 2003 to 2010 with a blood culture positive for MSSA and received definitive therapy with cefazolin, nafcillin, or oxacillin
Exclusion Criteria Patients admitted to a VA hospital with <25 cases of S. aureus infections complicated by bacteremia throughout the study period
Methods Patients were included if they had a blood culture positive for MSSA and received definitive therapy with cefazolin, nafcillin, or oxacillin. Cox proportional hazards regression and ordinal logistic regression were used to identify associations between antibiotic therapy and mortality or recurrence. A recurrent infection was defined as an MSSA blood culture between 45 and 365 days after the first MSSA blood culture.
Duration 2003 to 2010
Outcome Measures

30-day all-cause mortality, 90-day all-cause mortality
Baseline Characteristics   Cefazolin (n= 1163) Nafcillin or Oxacillin (n= 2004) p-Value
Male sex 1133 (97%) 1974 (99%) 0.031
Age, ≤55 296 (25%) 474 (24%) 0.715
APACHE III score ≥34 651 (56%) 1040 (52%) 0.027
Charlson comorbidity index score, median (IQR) 2 (1–3) 2 (1–3) 0.013
Dialysis and/or ESRD 176 (15%) 168 (8%) <0.001
Hospital-onset infection 241 (21%) 489 (24%) 0.018
Admission to intensive care unit 178 (15%) 378 (19%) 0.011
Diabetes 465 (40%) 668 (33%) <0.001
30-d mortality 113 (10%) 307 (15%) <0.001
90-d mortality 231 (20%) 502 (25%) 0.001
Results

The findings demonstrated that cefazolin treatment was associated with a 37% reduction in 30-day mortality (hazard ratio [HR]: 0.63; 95% confidence interval [CI] 0.51-0.78) and a 23% reduction in 90-day mortality (HR 0.77; 95% CI: 0.66-0.90) compared with nafcillin or oxacillin. The odds of recurrence did not differ significantly between treatment groups (odds ratio [OR]1.13; 95% CI 0.94-1.36), indicating that cefazolin did not increase the likelihood of recurrent MSSA bacteremia. Additionally, a sub-analysis restricted to patients receiving dialysis showed a similar mortality benefit with cefazolin (HR: 0.48 for 30-day mortality and HR: 0.60 for 90-day mortality).
Adverse Events N/A
Study Author Conclusions In this large, multicenter study, patients who received cefazolin had a lower risk of mortality and similar odds of recurrent infections compared with nafcillin or oxacillin for MSSA infections complicated by bacteremia. Physicians might consider definitive therapy with cefazolin for these infections.
Critique The study's large sample size and multicenter design strengthen its findings. However, potential confounding by indication and lack of data on source control, dose of therapy, and adverse events are limitations. The study's retrospective nature may also introduce bias, and the results may not be generalizable to all patients with MSSA infections complicated by bacteremia.
Table 4 References:
[6] McDanel JS, Roghmann MC, Perencevich EN, et al. 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;65(1):100-106. doi:10.1093/cid/cix287

Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus
Design

Retrospective cohort study

N= 93
Objective

To compare clinical outcomes of cefazolin versus oxacillin in the treatment of complicated methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia
Study Groups

Cefazolin (n= 59)

Oxacillin (n= 34)
Inclusion Criteria

Patients ≥18 years of age, received definitive treatment with either cefazolin or oxacillin, and met criteria for complicated MSSA bacteremia, defined as ≥1 positive blood culture and at least one of the following: positive follow-up blood cultures within 5 days of therapy initiation, evidence of metastatic spread, infected prostheses not removed within 4 days, and presence of endocarditis
Exclusion Criteria

Uncomplicated or polymicrobial bacteremia, received empirical antibiotics for ≥72 h, or received other antibiotics active against MSSA during treatment
Methods

Patients with MSSA bacteremia treated at 2 tertiary care hospitals in San Antonio, Texas, between January 2008 and June 2012 were identified through computerized records. Only the first MSSA bacteremia episode per patient was included. Definitive therapy was cefazolin or oxacillin. Primary infection source was determined using microbiologic specimens from suspected sites or compatible clinical/radiographic evidence. Complicated infections included high-burden/deep-seated sources such as osteoarticular infection, endovascular infection/endocarditis, abscesses, metastatic infection, and retained infected prostheses. Cefazolin became increasingly recommended as the preferred MSSA therapy beginning in October 2009; by mid-2010, oxacillin was mainly reserved for central nervous system infections or cefazolin intolerance. A matched subgroup analysis was also conducted, matching cefazolin- and oxacillin-treated patients by age, ICU admission, source, surgical intervention, and metastatic foci.
Duration

January 2008 to June 2012
Outcome Measures

Primary: Clinical cure at the end of therapy (CEOT)

Secondary: Overall treatment failure, duration of bacteremia, time to defervescence, 30-day and 90-day all-cause mortality, rates of adverse drug events (ADEs), and discontinuation of therapy due to ADE
Baseline Characteristics  

Oxacillin (n= 34)

 Cefazolin (n= 59)
Mean age, years

51 ± 14

 51 ± 10
Male

28 (82%)

 44 (75%)
Mean weight, kg

77 ± 18

 83 ± 16
End-stage renal disease

0

 15 (25%)
Admission to intensive care unit

6 (18%)

 4 (7%)
Osteoarticular source

20 (59%)

 18 (31%)
Endovascular source

4 (12%)

 15 (25%)
Results  

Oxacillin (n= 34)

 Cefazolin (n= 59) p-value
Clinical cure at end of therapy

32 (88%)

 56 (95%) 0.25
Overall treatment failure

16 (47%)

 14 (24%) 0.04
Median duration of bacteremia, days (IQR)

4 (3-7)

 4 (2-5) 0.20
Persistent bacteremia

7 (44%)

 6 (43%) 0.55
Progression of infection on therapy

5 (31%)

 4 (29%) 0.16
Relapse of infection

3 (19%)

 4 (29%) 1.0
Death

1 (6%)

 0 (0%) 0.37

Abbreviations: IQR, interquartile range.
Adverse Events

Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; p= 0.0006). Elevated transaminases were the most common ADE with oxacillin (18%). Discontinuation rates due to ADEs were higher in the oxacillin group (21% versus 3%; p= 0.01).
Study Author Conclusions

Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation.
Critique

This study is directly useful for comparing cefazolin versus oxacillin in complicated MSSA bacteremia and includes high-burden/deep-seated infections relevant to epidural abscess; however, it was retrospective, nonrandomized, and not designed specifically for epidural abscess. Cefazolin showed similar clinical cure and lower adverse-event-related discontinuation than oxacillin, but epidural abscess-specific conclusions are limited because only individual epidural abscess cases were reported within the broader complicated bacteremia cohort.
Table 5 References:
[7] Li J, Echevarria KL, Hughes DW, Cadena JA, Bowling JE, Lewis JS 2nd. Comparison of cefazolin versus oxacillin for treatment of complicated bacteremia caused by methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 2014;58(9):5117-5124. doi:10.1128/AAC.02800-14

 

Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible Staphylococcus aureus Bloodstream Infection
Design

National retrospective cohort study

N=428
Objective To compare effectiveness of anti-MSSA therapies among bacteremia patients exclusively exposed to one antimicrobial
Study Groups

Nafcillin/oxacillin (n=105)

Cefazolin (n=107)

Piperacillin/tazobactam (n=113)

Fluoroquinolones (n=103)
Inclusion Criteria Aged 18 years or older; hospitalized in Veterans Affairs medical centers with MSSA bacteremia from January 1, 2002, to October 1, 2015; treated exclusively with nafcillin, oxacillin, cefazolin, piperacillin/tazobactam, or fluoroquinolones
Exclusion Criteria Patients receiving combination therapy or with a change in therapy
Methods Patients were assessed for 30-day mortality, time to discharge, inpatient mortality, 30-day readmission, and 30-day S. aureus reinfection. Hazard ratios and 95% confidence intervals were calculated using propensity-score matched Cox proportional hazards regression model
Duration January 1, 2002, to October 1, 2015
Outcome Measures

Primary: 30-day mortality

Secondary: Time to discharge, inpatient mortality, readmission
Baseline Characteristics   Cefazolin (n=107) Nafcillin or oxacillin (n=105) p-Value
Age, years, mean ± SD 64.0 ± 12.8 60.3 ± 12.4 0.03
Male sex, n (%) 105 (98.1) 103 (98.1) 1.0
Body mass index, kg/m2, mean ± SD 27.9 ± 7.0 28.0 ± 7.3 0.95
Obese, n (%) 41 (38.3) 35 (33.3) 0.45
Charlson comorbidity index, median (IQR) 2 (1–4) 2 (1–4) 0.61
Chronic kidney disease 44 (41.1) 29 (27.6) 0.04
Results   Nafcillin/oxacillin Cefazolin HR (95% CI)
30-day mortality 2/44 (4.6%) 3/44 (6.8%) 0.67 (0.11 to 4.0)
Inpatient mortality 1/44 (2.3%) 3/44 (6.8%) -
Discharge 43/44 (97.7%) 41/44 (93.2%) 0.80 (0.44 to 1.44)
30-day readmission 9/43 (20.9%) 8/41 (19.5%) 0.75 (0.26 to 2.16)
Adverse Events Not specifically evaluated in the study
Study Author Conclusions In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between nafcillin/oxacillin and cefazolin or fluoroquinolones. However, higher mortality was observed with piperacillin/tazobactam as compared with nafcillin/oxacillin/cefazolin, suggesting it may not be as effective as a monotherapy in MSSA bacteremia
Critique The study's strength lies in its focus on monotherapy, allowing for clearer attribution of outcomes to specific antibiotics. However, the retrospective design and exclusion of patients with changes in therapy may limit the generalizability of the findings. Additionally, the study did not evaluate safety outcomes, which are crucial for comprehensive treatment assessment
Table 6 References:
[8] Beganovic M, Cusumano JA, Lopes V, LaPlante KL, Caffrey AR. Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible Staphylococcus aureus Bloodstream Infection. Open Forum Infect Dis. 2019;6(7):ofz270. Published 2019 Jun 6. doi:10.1093/ofid/ofz270