cloxacillin
Regulatory sources consulted
Approved indications
- Serious susceptible staphylococcal infections, including skin and soft tissue, mastitis, osteoarticular infections, sepsis, endocarditis, and meningitis.
Contraindications
Absolute
- Hypersensitivity to cloxacillin or a history of a severe immediate reaction to another beta-lactam.
Clinical warnings
- Major warning · It may cause severe hypersensitivity or anaphylaxis. Review any history of immediate beta-lactam reactions before use and discontinue if an allergic reaction occurs. — CIMA/AEMPS, ficha técnica 63636
- Major warning · It may cause Clostridioides difficile-associated diarrhea during or after treatment; assess significant diarrhea and avoid antiperistaltic drugs if colitis is suspected. — CIMA/AEMPS, ficha técnica 63636
- Major warning · Use with particular caution in neonates with jaundice. — CIMA/AEMPS, ficha técnica 63636
- Major warning · High doses, especially with renal impairment, may cause neurotoxicity and seizures; adjust and monitor. — CIMA/AEMPS, ficha técnica 63636
Drug interactions
- ModerateProbenecid
Mechanism: It reduces renal tubular secretion and may increase and prolong antibiotic exposure.
Recommendation: Avoid the combination unless deliberately indicated and monitor toxicity.
CIMA/AEMPS, ficha técnica 63636
- ModerateBacteriostatic antibiotics
Mechanism: They may antagonize cloxacillin bactericidal activity.
Recommendation: Avoid the combination when possible.
CIMA/AEMPS, ficha técnica 63636
- ModerateOral contraceptives
Mechanism: Contraceptive effectiveness may be reduced.
Recommendation: Use an additional contraceptive method during treatment.
CIMA/AEMPS, ficha técnica 63636
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
Use during pregnancy only when clearly indicated. Small amounts pass into milk; monitor the infant for diarrhea, candidiasis, or sensitization and assess continuation according to the product.
Recent literature (PubMed)
Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear. In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days. This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%). In patients with methic
Although widely used, cefazolin efficacy for the treatment of meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia has not thus far been investigated in a clinical trial. In this study, we aimed to compare the efficacy and safety of cefazolin with that of cloxacillin in patients with MSSA bacteraemia. We conducted an open-label, non-inferiority, randomised clinical trial in 21 university and non-university hospitals in France in adults (aged ≥18 years) with MSSA bacteraemia, without intravascular implant or suspicion of CNS infection. Participants were randomly assigned (1:1) to receive intravenously cefazolin (25-50 mg/kg every 8 h) or cloxacillin (25-50 mg/kg every 4-6 h) for the first 7 days of therapy using computer-generated blocks of various sizes and stratification on vascular-access associated bacteraemia and centre. Subsequent treatment was left to the choice of the investigator (total duration ≥14 days). The primary endpoint was a composite of sterile blood cultures at day 3 (day 5 for endocarditis) without relapse of bacteraemia, survival, and clinical success at day 90, and was assessed in the intention-to-treat population. A non-inferiority margin of 12% was chosen. This trial is registered on ClinicalTrials.gov (NCT03248063) and is complete. Between Sept 5, 2018, and Nov 16, 2023, 315 participants were enrolled and assigned to cefazolin (n=158) or cloxacillin (n=157); 12 participants were excluded from analysis in the cefazolin group, and 11 in the cloxacillin group (final population of 146 in each group). Mean age was 62·7 years (SD 16·4), 215 (74%) participants were male, and race or ethnicity data were not collected. Median Pitt score was 0 (IQR 0-0). The primary endpoint was met in 109 (75%) of 146 participants in the cefazolin group versus 108 (74%) of 146 participants in the cloxacillin group (treatment difference -1%; 95% CI -11 to 9; p=0·012). At the end of study treatment, 22 (15%) of 146 participants assigned to cefazolin and 40 (2
There is debate on whether cefazolin or antistaphylococcal penicillins should be the first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Ongoing trials are investigating whether cefazolin is non-inferior to (flu)cloxacillin, but it remains uncertain whether these findings apply to other antistaphylococcal penicillins. We conducted a systematic review and meta-analysis comparing cefazolin with each of the individual antistaphylococcal penicillins for MSSA bacteraemia. Data sources: We updated a 2019 systematic review but specifically focused on evaluating outcomes by individual antistaphylococcal penicillins. Study eligibility criteria include comparative observational studies. Participants include patients with MSSA bacteraemia. Interventions include cefazolin vs. the antistaphylococcal penicillins. Assessment of risk of bias involved the risk of bias in non-randomized studies of interventions tool. The primary outcome was 30-day all-cause mortality and we assessed for non-inferiority of cefazolin using a pre-specified non-inferiority margin of a pooled OR <1.2 using raw unadjusted data. Secondary outcomes were 90-day mortality, treatment-related adverse events (TRAEs), discontinuation due to toxicity, and nephrotoxicity. No randomized data have been published. A total of 30 observational studies at moderate or high risk of bias were included, which comprised 3869 patients who received cefazolin and 11 644 patients who received antistaphylococcal penicillins (flucloxacillin = 6721, unspecified = 2440, nafcillin = 1305, cloxacillin = 1258, and oxacillin = 120). Cefazolin was associated with a reduced odds of 30-day all-cause mortality (OR = 0.73, 95% CI: 0.62-0.85) compared with antistaphylococcal penicillins, meeting pre-specified non-inferiority. This effect was consistent vs. flucloxacillin (OR = 0.92, 95% CI: 0.73-1.16), nafcillin (OR = 0.58, 95% CI: 0.28-1.17), cloxacillin (OR = 0.42, 95% CI: 0.11-1.58), and oxacillin (OR =
This study systematically evaluated and ranked the efficacy of first- and second-line antibiotics antibiotic options for the clinical management of cellulitis and erysipelas through a network meta-analysis approach. From inception to July 04, 2024, a search for relevant randomized clinical trials (RCTs) was carried out using several databases. Antibiotics including azithromycin, cefaclor, cephalexin, cloxacillin, erythromycin, cephalexin plus trimethoprim-sulfamethoxazole, cephalexin plus placebo, flucloxacillin, clindamycin, ceftriaxone, penicillin, roxithromycin, and pristinamycin were assessed regarding cure rate, the eradication of baseline pathogens, diarrhea or vomiting, and rash. In total, 10 RCTs with 1,936 cellulitis or erysipelas patients were eligible for inclusion. There were no significant differences in the cure rates for cellulitis among the antibiotics analysed, with cefaclor demonstrating the most favorable profile for curative outcomes. In terms of side effects, ceftriaxone was identified as the least likely to induce diarrhea or vomiting. For erysipelas, pristinamycin showed the most promising results in achieving cure rates. Although a comparison of the three antibiotics revealed no significant differences in rash as a side effect in erysipelas, pristinamycin was observed to carry the highest risk for rash. Our findings indicate no significant differences in cure rates among antibiotics for cellulitis. However, ceftriaxone had the fewest gastrointestinal side effects. Pristinamycin showed the highest cure rates for erysipelas but with a higher risk of rash. Future research should focus on optimizing antibiotic selection for cellulitis and erysipelas.