Table 1.
Summary of studies investigating the treatment of different types of infection caused by methicillin-susceptible Staphylococcus aureus with oxacillin or cefazolin.
| Author, Year and Reference | Study Design | No. of Patients | Antibiotic and Dosing | Source of Infection | Isolates | Severity | Clinical Outcomes | Relapse Rate—Resistance Development | Comments |
|---|---|---|---|---|---|---|---|---|---|
| Oxacillin or Cefazolin | |||||||||
| Rindone et al., 2018 | Systematic review with meta-analysis | 10 observational studies (one prospective and nine retrospective) | CEF 3–8 g/day vs. OXA 10–12 g/day |
BSIs caused by MSSA Secondary BSI:BJI 9–59% CR-BSI 3–38% SSTI 3–34% LTRI 1–18% IE 0–27% |
Significantly lower mortality rate was found with cefazolin vs. oxacillin (RR 0.78; 95%CI 0.69–0.88). Additionally, cefazolin showed significant higher clinical cure rate (RR 1.09; 95%CI 1.02–1.17) and lower risk of withdrawal for AEs (RR 0.27; 95%CI 0.16–0.47). No difference between cefazolin and oxacillin in terms of relapse BSIs was found (RR 1.29; 95%CI 0.96–1.74). | ||||
| Davis et al., 2018 | Multicentric retrospective cohort | 7312 (6520 flucloxacillin vs. 792 CEF) |
flucloxacillin vs.CEF |
CR-BSI33.2–37.1% SSTI 18.2–18.7% BJI 16.2–18.3% primary 12.4–12.5% IE 5.9–8.0% deep abscess 2.5–2.8% CNS 1.5–2.5% |
100% MSSA | ICU admission 13.5–13.9% IHD 8.9–20.8% |
30-day mortality rate:11.2% (flucloxacillin) vs. 10.7% (cefazolin)(OR 0.93; 95%CI 0.72–1.17) 30-day mortality rate in propensity adjusted analysis: aOR 0.86 (95%CI 0.65–1.14) |
NA | Cefazolin is likely to have equivalent or superior outcomes to ASPs for MSSA bacteraemia. |
| McDanel et al., 2017 | Multicentric retrospective cohort | 3167 (1163 CEF vs. 2004 NAF/OXA) |
CEF vs. NAF/OXA |
SSTI 23–25% BJI 12–13% IE 4–7% |
100% MSSA | ICU admission 17.6% APACHE III score > 34 52–56% |
30-day mortality rate:aHR 0.63 (95%CI 0.51–0.78) 90-day mortality rate:aHR 0.77 (95%CI 0.66–0.90) |
Recurrence: aOR 1.13 (95%CI 0.94–1.36). 90-day MSSA relapse: 2% (CEF) vs. 1% (NAF/OXA)p = 0.47 1-year MSSA relapse: 3% (CEF) vs. 2% (NAF/OXA)p = 0.07 |
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. |
| Beganovic et al., 2019 | Retrospective cohort | 212 (105 NAF/OXA vs. 107 CEF) |
NAF/OXA vs. CEF |
SSTI 21.7% BJI 12.3% surgical site 11.3% IE 7.1% UTI 6.1% LRTI 4.6% |
100% MSSA | ICU admission 5.2% Median APACHE score 22–25.5 |
30-day mortality rate:4.6% vs. 6.8% HR 0.67 (95%CI 0.11–4.00) Discharge: 97.7% vs. 93.2% HR 0.80 (95%CI 0.44–1.44) |
30-day readmission: 20.9% vs. 19.5%HR 0.75 (95%CI 0.26–2.16) 30-day reinfection: 9.3% vs. 0.0% p = NS |
In hospitalized patients with BSIs caused by MSSA, no difference in mortality was observed between NAF/OXA and CEF. |
| Rao et al., 2015 | Multicentric retrospective cohort | 161 (103 CEF vs. 58 OXA) |
CEF vs. OXA |
CR-BSI24.1–45.6% SSTI 14.6–22.4%BJI 13.8–20.4%IE 18.0% LRTI 1.7–1.9% UTI 1.7–1.9% CNS 0.0–1.7% |
100% MSSA | ICU admission 32.8–41.8% | Treatment failure rate for deep-seated MSSA infections: 15.6% vs. 20%p = 0.72 In-hospital mortality:1% vs. 5.2% p = 0.13 |
BSI recurrence: 4.9% vs. 5.2% p = 0.99 |
Treatment with cefazolin or oxacillin was not independently associated with treatment failure (aOR 3.76; 95%CI, 0.98 to 14.4). Cefazolin was not associated with higher rates of treatment failure and appears to be an effective alternative to oxacillin for treatment of deep-seated MSSA BSI. |
| Bai et al., 2021 | Retrospective cohort | 98 (50 CEF vs. 48 cloxacillin) |
CEF vs. cloxacillin |
Spinal epidural abscesses 100% | 100% MSSA | Septic shock 11.2% | 90-day mortality rate:8% vs. 13% p = 0.52 Failure rate: 12% vs. 19% p = 0.21 |
Recurrence rate: 2% vs. 9% p = 0.20 Serious AEs: 0% vs. 4% p = 0.24 |
Cefazolin is likely as effective as an ASP and may be considered as a first-line treatment for MSSA spinal epidural abscesses. |
| Li et al., 2014 | Multicentric retrospective cohort | 93 (59 CEF vs. 34 OXA) |
CEF 2–8 g/day II or CIvs. OXA 10–12 g/day II or CI |
100% complicated BSIBJI 41% IE 20% SSTI 10% CR-BSI 8% UTI 6% LRTI 4% Unknown 11% |
100% MSSA | ICU admission 11% Immunosuppression 6% |
Clinical cure at EOT:95% vs. 88%p = 0.25 30-day mortality rate:0% vs. 3% p = 0.37 Overall failure at 90-day: 24% (CEF) vs. 47% (OXA) p = 0.04 |
BSI recurrence:2% vs. 6% p = 0.55 AEs rate: 3% vs. 30% p < 0.001 |
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. |
| Corsini Campioli et al., 2021 | Retrospective cohort | 79 (45 CEF vs. 34 ASPs) |
CEF 2 g q8 h vs. OXA 2 g q4 h or NAF 2 g q4 h |
Spinal epidural abscesses 100% | 100% MSSA | ICU admission 19% | 30-day mortality rate:2% vs. 5.9% p = 0.57 6-week clinical failure: 75.6% vs. 82.4% p = 0.58 12-week clinical failure: 33.3% vs. 44.1% p = 0.35 |
90-day recurrence: 11.4% vs. 9.4%p = 0.99 |
Cefazolin was equally as effective as ASPs, suggesting that it can be an alternative to ASPs in the treatment of MSSA spinal epidural abscesses. |
| Lefevre et al., 2021 | Retrospective cohort | 73 (35 ASPs vs. 38 CEF) |
ASPs 12 g/day vs. CEF 6 g/day |
IE 100% | 100% MSSA | Septic shock 30.1% | 90-day mortality rate:28.6% (ASPs) vs. 21.1% (CEF) p = 0.57 |
Relapse 0.0% vs. 5.3%p = 0.49 |
Efficacy and safety did not statistically differ between ASPs and cefazolin for MSSA-IE treatment. |
| Le Turnier et al., 2020 | Retrospective cohort | 17 (8 CEF vs. 9 cloxacillin) |
CEF 2 g q6 h CI vs. cloxacillin 2 g q4 h CI |
CNS 100% | 58.8% MSSA 35.3% MSSE 5.9% S. lugdunensis |
NA | Ratio concentration CSF/plasma: 4.3% (CEF) vs. 1.8% (cloxacillin) |
Clinical failure:0% (CEF) vs. 22.2% (cloxacillin) | Patients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of CEF achieved therapeutic concentrations in CSF. CEF appears to be a therapeutic candidate which should be properly evaluated in this indication. |
| Hughes et al., 2009 | Retrospective cohort | 107 | CI OXA (78 patients) vs.II OXA (29 patients) |
IE 100% | 100% MSSA | IHD 7% | 30-day mortality rate:8% (CI) vs. 10% (II) p = 0.7 30-day microbiological cure: 94% (CI) vs. 79% (II)p = 0.03 |
NA | CI emerged as the only independent variable associated with 30-day microbiological cure at multivariate analysis (p = 0.01). CI oxacillin is an effective alternative to II oxacillin for the treatment of IE caused by MSSA and may improve microbiological cure. This convenient and pharmacodynamically optimized dosing regimen for oxacillin deserves consideration for patients with IE caused by MSSA. |
AE: adverse event; ASP: anti-staphylococcal penicillins; BJI: bone and joint infection; BSI: bloodstream infection; CEF: cefazolin; CI: continuous infusion; CNS: central nervous system; CR-BSI: catheter-related bloodstream infection; CSF: cerebrospinal fluid; EOT: end of treatment; HR: hazard ratio; ICU: intensive care unit; IE: infective endocarditis; IHD: intermittent hemodialysis; II: intermittent infusion; LRTI: lower respiratory tract infection; MSSA: methicillin-susceptible S. aureus; MSSE: methicillin-susceptible S. epidermidis; NAF: nafcillin; NA: not assessed; NS: not significant; OR: odds ratio; OXA: oxacillin; RR: risk ratio; SSTI: skin and soft tissue infection; UTI: urinary tract infection.