BACKGROUND: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia.
METHODS: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality.
RESULTS: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic.
CONCLUSIONS: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.

Antistaphylococcal penicillins and cefazolin are the treatments of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, requiring multiple doses daily. At Parkland, eligible uninsured patients with MSSA bloodstream infections (BSI) receive self-administered outpatient parenteral antimicrobial therapy (S-OPAT). Ceftriaxone was used in a cohort of S-OPAT patients for ease of once-daily dosing.
A retrospective study was conducted to evaluate clinical outcomes for patients discharged with ceftriaxone versus cefazolin to treat MSSA BSI.
A retrospective cohort noninferiority study design was used to assess treatment efficacy of ceftriaxone versus cefazolin among Parkland S-OPAT patients treated from April 2012 to March 2020. Demographic, clinical, and treatment-related adverse events data were collected. Clinical outcomes included treatment failure as defined by repeat positive blood culture or retreatment within 6 months, all-cause 30-day readmission rates, and central line-associated bloodstream infection (CLABSI) rates.
Of 368 S-OPAT patients with MSSA BSI, 286 (77.7%) received cefazolin, and 82 (22.3%) received ceftriaxone. Demographics and comorbidities were similar for both groups. There were no treatment failures in the ceftriaxone group compared with 4 (1%) in the cefazolin group (P = 0.58). No difference in 30-day readmission rate between groups was found. The CLABSI rates were lower in ceftriaxone group (2%) compared with cefazolin (11%; P = 0.02). Limitations include retrospective cohort design.
Ceftriaxone was found to be noninferior to cefazolin in this study. Our findings suggest that ceftriaxone is a safe and effective treatment of MSSA BSI secondary to osteoarticular or skin and soft tissue infections when used in the S-OPAT setting.
OFID on 2018 Nov; 5(Suppl 1): S316: doi: 10.1093/ofid/ofy210.894.

The aim of this trial was to assess the effectiveness of quality improvement collaboratives to implement large-scale change in the National Health Service (NHS) in the UK, specifically for improving outcomes in patients undergoing primary, elective total hip or knee replacement.
We undertook a two-arm, cluster randomised controlled trial comparing the roll-out of two preoperative pathways: methicillin-sensitive Staphylococcus aureus (MSSA) decolonisation (infection arm) and anaemia screening and treatment (anaemia arm). NHS Trusts are public sector organisations that provide healthcare within a geographical area. NHS Trusts (n = 41) in England providing primary, elective total hip and knee replacements, but that did not have a preoperative anaemia screening or MSSA decolonisation pathway in place, were randomised to one of the two parallel collaboratives. Collaboratives took place from May 2018 to November 2019. Twenty-seven Trusts completed the trial (11 anaemia, 16 infection). Outcome data were collected for procedures performed between November 2018 and November 2019. Co-primary outcomes were perioperative blood transfusion (within 7 days of surgery) and deep surgical site infection (SSI) caused by MSSA (within 90 days post-surgery) for the anaemia and infection trial arms, respectively. Secondary outcomes were deep and superficial SSIs (any organism), length of hospital stay, critical care admissions and unplanned readmissions. Process measures included the proportion of eligible patients receiving each preoperative initiative.
There were 19,254 procedures from 27 NHS Trusts included in the results (6324 from 11 Trusts in the anaemia arm, 12,930 from 16 Trusts in the infection arm). There were no improvements observed for blood transfusion (anaemia arm 183 (2.9%); infection arm 302 (2.3%) transfusions; adjusted odds ratio 1.20, 95% CI 0.52-2.75, p = 0.67) or MSSA deep SSI (anaemia arm 8 (0.13%); infection arm 18 (0.14%); adjusted odds ratio 1.01, 95% CI 0.42-2.46, p = 0.98). There were no significant improvements in any secondary outcome. This is despite process measures showing the preoperative pathways were implemented for 73.7% and 61.1% of eligible procedures in the infection and anaemia arms, respectively.
Quality improvement collaboratives did not result in improved patient outcomes in this trial; however, there was some evidence they may support successful implementation of new preoperative pathways in the NHS.
Prospectively registered on 15 February 2018, ISRCTN11085475.

Surgical site infections (SSIs), which are a potential complications in surgical procedures, are associated with prolonged hospital stays and increased postoperative mortality rates, and they also have a significant economic impact on health systems. Data in literature regarding risk factors for SSIs in pediatric age are scarce, with consequent difficulties in the management of SSI prophylaxis and with antibiotic prescribing attitudes in the various surgical procedures that often tend to follow individual opinions. The lack of pediatric studies is even more evident when we consider surgeries performed in subjects with underlying conditions that may pose an increased risk of complications. In order to respond to this shortcoming, we developed a consensus document to define optimal surgical antimicrobial prophylaxis (SAP) in neonates and children with specific high-risk conditions. These included the following: (1) colonization by methicillin-resistant Staphylococcus aureus (MRSA) and by multidrug resistant (MDR) bacteria other than MRSA; (2) allergy to first-line antibiotics; (3) immunosuppression; (4) splenectomy; (5) comorbidity; (6) ongoing antibiotic therapy or prophylaxis; (7) coexisting infection at another site; (8) previous surgery in the last month; and (9) presurgery hospitalization lasting more than 2 weeks. This work, made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, represents, in our opinion, the most up-to-date and comprehensive collection of recommendations relating to behaviors to be undertaken in a perioperative site in the presence of specific categories of patients at high-risk of complications during surgery. The application of uniform and shared protocols in these high-risk categories will improve surgical practice with a reduction in SSIs and consequent rationalization of resources and costs, as well as being able to limit the phenomenon of antimicrobial resistance.

Periprosthetic joint infection (PJI) causes significant morbidity. Methicillin sensitive Staphylococcus aureus (MSSA) is the most frequent organism, and the majority are endogenous. Decolonisation reduces PJIs but there is a paucity of evidence comparing treatments. Aims; compare 3 nasal decolonisation treatments at (1) achieving MSSA decolonisation, (2) preventing PJI.
Our hospital prospectively collected data on our MSSA decolonisation programme since 2013, including; all MSSA carriers, treatment received, MSSA status at time of surgery and all PJIs. Prior to 2017 MSSA carriers received nasal mupirocin or neomycin, from August 2017 until August 2019 nasal octenidine was used.
During the study period 15,958 primary hip and knee replacements were performed. 3200 (20.1%) were MSSA positive at preoperative screening and received decolonisation treatment, 698 mupirocin, 1210 neomycin and 1221 octenidine. Mupirocin (89.1%) and neomycin (90.9%) were more effective at decolonisation than octenidine (50.0%, P < 0.0001). There was no difference in PJI rates (P = 0.452).
Mupirocin and neomycin are more effective than octenidine at MSSA decolonisation. There was poor correlation between the MSSA status after treatment (on day of surgery) and PJI rates. Further research is needed to compare alternative MSSA decolonisation treatments.

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized for pediatric sepsis unresponsive to steroids and inotropic support. Outcomes of children with sepsis are influenced by the type of pathogen causing their illness. Objective: To determine if the outcomes of children with Staphylococcus aureus sepsis receiving ECMO differed according to microbial sensitivity (Methicillin-resistant Staphylococcus aureus [MRSA] vs. Methicillin-sensitive Staphylococcus aureus [MSSA]). Methods: Retrospective case-matched cohort study of children (0-<18 years) with Staphylococcus aureus sepsis reported to the ELSO registry from more than 995 centers. Inclusion criteria were age 0-18 years, laboratory diagnosis of Staphylococcal infection, clinical diagnosis of sepsis, and ECMO deployment. Exclusion criteria were no laboratory diagnosis of Staphylococcal infection. We compared patient demographics, pre-ECMO management and outcomes of those with MRSA vs. MSSA using Chi-Square test, with independent samples t-test used to test to compare continuous variables. Results: In our study cohort of 308 patients, 160 (52%) had MSSA and 148 (48%) MRSA with an overall survival rate of 41.5%. There were no differences in the age group (p = 0.76), gender distribution (p = 0.1) or racial distribution (p = 0.58) between the two groups. P value for racial distribution should be 0.058. There were 91 (56.8%) deaths in the MSSA group and 89 (60.1%) deaths (p = 0.56) in the MRSA group. Duration on ECMO (p = 0.085) and the time from intubation to ECMO (p = 0.37) were also similar in the two groups. Survival with MSSA sepsis and MRSA sepsis did not improve significantly over the 20 years evaluated despite an increase in ECMO utilization. Conclusion: In this multi-center retrospective study, there were no differences in outcomes for children receiving ECMO support with Staphylococcus aureus sepsis according to microbial methicillin sensitivity. There was no significant increase in survival among patients with MRSA and MSSA infections receiving ECMO in the last 20 years.

OBJECTIVE: We compared the effectiveness of cefazolin and cloxacillin as definitive antibiotic therapy for methicillin-susceptible Staphylococcus aureus (MSSA) spinal epidural abscess (SEA).
METHODS: This retrospective cohort study included patients with MSSA SEA from two academic hospitals in Hamilton, Ontario, Canada, between 2014 and 2020. Patients treated with cefazolin were compared to those treated with cloxacillin. Co-primary outcomes included 90-day mortality, antibiotic failure, adverse reactions and recurrence. Inverse probability of treatment weighting using propensity scores was used to balance important prognostic factors and to estimate an adjusted risk difference.
RESULTS: Of 98 patients with MSSA SEA, 50 and 48 patients were treated with cefazolin and cloxacillin, respectively. Mortality at 90 days was 8% and 13% in the cefazolin and cloxacillin groups, respectively (P = 0.52). The antibiotic failure rate was 12% and 19% in the cefazolin and cloxacillin groups, respectively (P = 0.41). The serious adverse reactions rate was 0% and 4% in the cefazolin and cloxacillin groups, respectively (P = 0.24). The recurrence rate was 2% and 8% in the cefazolin and cloxacillin groups, respectively (P = 0.20). The adjusted risk difference for mortality at 90 days was -1% [95% confidence interval (CI) -10% to 8%] favouring cefazolin. The adjusted risk differences for antibiotic failure, adverse reactions and recurrence were 1% (95% CI -12% to 14%), -5% (95% CI -11% to 2%) and -18% (-36% to -1%) respectively.
CONCLUSIONS: Cefazolin is likely as effective as an antistaphylococcal penicillin and may be considered as a first-line treatment for MSSA SEA.

UNASSIGNED: Staphylococcus aureus (S. aureus) is an important causative pathogen in human infections. The production of biofilms by bacteria is an important factor, leading to treatment failures. There has been significant interest in assessing the possible relationship between the multidrug-resistant (MDR) status and the biofilm-producer phenotype in bacteria. The aim of our present study was to assess the biofilm-production rates in clinical methicillin-susceptible S. aureus [MSSA] and methicillin-resistant S. aureus [MRSA] isolates from Hungarian hospitals and the correlation between resistance characteristics and their biofilm-forming capacity.
UNASSIGNED: A total of three hundred (n=300) S. aureus isolates (corresponding to MSSA and MRSA isolates in equal measure) were included in this study. Identification of the isolates was carried out using the VITEK 2 ID/AST system and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method and E-tests, confirmation of MRSA status was carried out using PBP2a agglutination assay. Biofilm-production was assessed using the crystal violet (CV) tube-adherence method and the Congo red agar (CRA) plate method.
UNASSIGNED: There were significant differences among MSSA and MRSA isolates regarding susceptibility-levels to commonly used antibiotics (in case of erythromycin, clindamycin and ciprofloxacin: p<0.001, gentamicin: p=0.023, sulfamethoxazole/trimethoprim: p=0.027, rifampin: p=0.037). In the CV tube adherence-assay, 37% (n=56) of MSSA and 39% (n=58) of MRSA isolates were positive for biofilm-production, while during the use of CRA plates, 41% (n=61) of MSSA and 44% (n=66) of MRSA were positive; no associations were found between methicillin-resistance and biofilm-production. On the other hand, erythromycin, clindamycin and rifampin resistance was associated with biofilm-positivity (p=0.004, p<0.001 and p<0.001, respectively). Biofilm-positive isolates were most common from catheter-associated infections.
UNASSIGNED: Our study emphasizes the need for additional experiments to assess the role biofilms have in the pathogenesis of implant-associated and chronic S. aureus infections.

BACKGROUND: Despite high mortality rates, physicians can alter the course of the Staphylococcus aureus bacteraemia (SAB) by following recommended standards of care. We aim to assess the adherence of these guidelines and their impact on mortality.
METHODS: Substudy from a prospective cohort of hospitalized patients with SAB from three hospitals from Peru. Hazard ratios were calculated using Cox proportional regression to evaluate the association between 30-day mortality and the performance of standards of care: removal of central venous catheters (CVC), follow-up blood cultures, echocardiography, correct duration, and appropriate definitive antibiotic therapy.
RESULTS: 150 cases of SAB were evaluated; 61.33% were MRSA. 30-day attributable mortality was 22.39%. CVC removal was done in 42.86% of patients. Follow-up blood cultures and echocardiograms were performed in 8% and 29.33% of cases, respectively. 81.33% of cases had appropriate empirical treatment, however, only 22.41% of MSSA cases were given appropriate definitive treatment, compared to 93.47% of MRSA. The adjusted regression for all-cause mortality found a substantial decrease in hazards when removing CVC (aHR 0.28, 95% CI: 0.10 - 0.74) and instituting appropriate definitive treatment (aHR 0.27, 95% CI: 0.08 - 0.86), while adjusting for standards of care, qPitt bacteraemia score, comorbidities, and methicillin susceptibility; similar results were found in the attributable mortality model (aHR 0.24, 95% CI: 0.08 - 0.70 and aHR 0.21, 95% CI: 0.06 - 0.71, respectively).
CONCLUSIONS: Deficient adherence to standards of care was observed, especially definitive treatment for MSSA. CVC removal and the use of appropriate definitive antibiotic therapy reduced the hazard mortality of SAB.

BACKGROUND: Staphylococcus aureus bloodstream infections (BSI) cause significant morbidity and mortality due to the frequent antibiotic resistance, toxin and adhesin production of the bacterium. These characteristics differ significantly in methicillin resistant (MRSA) and methicillin sensitive S. aureus (MSSA) and also among isolates of different MRSA clones, contributing to the outcome of S. aureus bacteraemia.
METHODS: In this study, all MRSA BSI isolates from Semmelweis University, Budapest, Hungary, isolated between 2011-2016 and the same number of matched MSSA (overall 306 isolates) were characterised in terms of antibiotic susceptibility, virulence genes, clonality and their association with all-cause 30-day mortality. Effect of patient related variables, such as age, gender and comorbidities were also investigated.
RESULTS: ST22-MRSA-IV and ST5-MRSA-II were the most prevalent clones in our study. SCCmec I isolates showed the highest resistance rates and SCCmec II carried most virulence genes. Infections caused by SCCmec IV isolates were associated with the highest mortality rate (42.2%), despite the similar comorbidity rates of the different patient groups. All-cause 30-day mortality was 39.9% in the MRSA and 30.7% in the MSSA group. Increased teicoplanin MIC was associated with high mortality rate. Resistance to ciprofloxacin, erythromycin and clindamycin was common in MRSA, whereas MSSA isolates were more sensitive to all antibiotics with the exception of doxycycline. All MRSA isolates were sensitive to glycopeptides and linezolid; resistance to rifampicin and sulfamethoxazole-trimethoprim was low. MRSA isolates carried more adhesion genes, superantigens were more frequent in MSSA. Panton-Valentine leukocidin was found in 2.3% of the isolates.
CONCLUSIONS: This study provides insight into the clonal composition and associated mortality of BSI S. aureus isolates in Hungary. The results suggest that the outcome of the infection is determined by the antibiotic resistance, genotype of the bacterium, and patient-related factors; rather than the virulence factors carried by the bacteria.