Antistaphylococcal Penicillins Research Articles

P-1888. Quantifying the Potential Impact of Dalbavancin on Health Care Metrics Associated with Outpatient Parenteral Antibiotic Therapy Management of Streptococcus and Staphylococcus Infections

Abstract Background Socially vulnerable patients often complete parenteral antibiotic courses in healthcare facilities due to injection drug use (IDU) history or unstable housing situations, which leads to significant personal and health system costs and prolonged hospitalization risks. Our aim was to assess the potential impact of dalbavancin (DBV) utilization on length of stay (LOS) and adverse outcomes in this patient population. Methods Retrospective study of patients ≥ 18 years old who were followed in the Johns Hopkins Health System Outpatient Parenteral Antibiotic Therapy (OPAT) program from 1/1/2021 to 6/30/2023 for Streptococcus and Staphylococcus bone/joint and endovascular infections (n = 900). Descriptive statistics were used to evaluate demographic, microbiologic, and clinical characteristics. Potential demand for DBV was quantified by estimating the impact of transitioning patients to DBV in terms of possible hospital days saved and OPAT-related complications avoided. Subanalyses were completed for patients with IDU history. Results Median patient age was 58 years (IQR 44-68 years) and 501/900 (56%) were male. Most patients received vancomycin (30%) followed by cefazolin (24.4%) or anti-staphylococcal penicillin (24.0%), which required central venous catheter placement in 86.6% of patients. The most common indication for OPAT was osteomyelitis (54.8%) followed by endovascular infection. The median LOS after finalization of antibiotic recommendations was 5 days (IQR 3-10 days) with 44.3% requiring skilled nursing facility (SNF) placement. 43.7% of patients experienced an OPAT-related adverse event, almost half of which involved a return to the hospital. Among OPAT patients, 16.4% had an IDU history and 75.8% of them injected within the last 6 months. These patients had longer LOS (8 vs 5 days) after finalization of antibiotic recommendations and more OPAT-related adverse events compared to patients without IDU history (48.0% vs 43.7%). Conclusion Patients, especially those with recent IDU, could benefit from DBV in lieu of parenteral antibiotics to complete prolonged treatment courses. Completion of deep-seeded gram-positive infection therapy with DBV vs OPAT has the potential to shorten hospital LOS and reduce the incidence of OPAT-associated adverse events. Disclosures All Authors: No reported disclosures

P-927. Clinical Outcome of Ampicillin plus Ceftriaxone Compared to Nafcillin or Cefazolin plus Gentamicin as an Empirical Treatment for Infective Endocarditis

Abstract Background A combination of anti-staphylococcal penicillin or cefazolin and gentamicin has been recommended as an empirical treatment regimen for native valve or late prosthetic valve infective endocarditis (NV/LPVIE), while the recent European Society of Cardiology Guidelines proposed ampicillin plus ceftriaxone (AMP+CRO) as an empirical option. However, clinical data supporting either regimen are scarce. Risk factors of composite outcome in a Cox proportional hazard model with overlap weighting. Methods A retrospective cohort study was conducted in a large tertiary care hospital. Adults aged ≥18 years who were diagnosed with NV/LPVIE by the modified Duke criteria from 2000 through 2022 were included. Patients were grouped by empirical antibiotic regimens including AMP+CRO versus nafcillin or cefazolin plus gentamicin (NAF/CFZ+GEN). Multiple logistic regression with overlap weighting was used to compare outcome between the two groups. Primary outcome was all-cause mortality or relapse within 6 months since diagnosis. Survival probabilities by empirical treatment regimen. (A) Observed survival without relapse, (B) probability of survival without relapse in the Cox proportional hazard model with overlap weighting. Results A total of 172 patients were included and divided into two groups by the empirical antibiotic regimens of AMP+CRO (n=102) or NAF/CFZ+GEN (n=70). Both groups exhibited similar baseline characteristics, including underlying diseases, preexisting valvular conditions, and involved valves. However, diabetes, cardiovascular diseases, and congestive heart failure were more common in the AMP+CRP group. Viridans group Streptococcus was the most frequently identified pathogen (33.3%) who were administered AMP+CRP, while Staphylococcus aureus was the most prevalent pathogen in the NAF/CFZ+GEN group (42.9%). In the AMP+CRO group, 6 (5.9%) met the composite outcome compared with 6 (8.6%) in the NAF/CFZ+GEN group (P = 0.551). There was also no statistically significant difference in the risk of composite outcome between the two groups in a multivariable analysis with overlap weighting (adjusted odds ratio, 0.27; 95% confidence interval, 0.05–1.43; P = 0.125). Factors associated with initial treatment with ampicillin + ceftriaxone in a logistic regression model Conclusion In the patients with NV/LPVIE, AMP+CRO as empirical antibiotic therapy showed no significant difference in the all-cause mortality or relapse within 6 months since diagnosis compared to NAF/CFZ+GEN. Our results suggest that AMP+CRO can be used as a primary empirical regimen for the treatment of NV/LPVIE. Covariate balance before and after overlap weighting Disclosures All Authors: No reported disclosures

β-Lactam Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus Infective Endocarditis

Infective endocarditis (IE) caused by Staphylococcus aureus is associated with high mortality, approximately 20% to 30%, mostly in the first month, with no improvement in recent decades. Current opinion is that antistaphylococcal penicillin and cefazolin are equally effective in treating methicillin-susceptible S aureus (MSSA) IE, and both are recommended as possible first-line treatments. Most MSSA strains carry the β-lactamase blaZ gene, and some blaZ-positive strains exhibit an inoculum effect, meaning increased minimum inhibitory concentrations at high inoculum. This reduced susceptibility to an antibiotic at high bacterial inoculum may be particularly relevant in IE, where vegetations have very high bacterial densities. To evaluate the association between phenotypic characteristics of S aureus isolates, β-lactam used, and outcome in patients with MSSA IE. This retrospective case series included MSSA cases treated at 3 French university hospitals between February 2016 and February 2022. The study included patients who had clinical isolates available and had definite or possible S aureus IE that involved native or prosthetic valves. Data were analyzed from July 2023 to June 2024. MSSA isolates were tested for the presence of blaZ and for inoculum effects to cefazolin and oxacillin. The association between first-month mortality and the β-lactam used, the presence of blaZ, and the presence of an inoculum effect to the treatment received was evaluated. This study included 216 patients with MSSA IE (median [IQR] age, 65 [49-73] years; 152 [70.4%] male) who were treated with antistaphylococcal penicillin (139 [64.4%]) or cefazolin (77 [35.6%]). One-month mortality of left-sided IE was 44 of 180 patients (24.4%), with no overall difference between patients treated with antistaphylococcal penicillin or cefazolin. However, 1-month mortality was higher in patients infected with blaZ-positive strains than with blaZ-negative strains (38 of 129 [29.5%] vs 6 of 51 [11.8%]; P = .01), and with strains with an inoculum effect to the β-lactam received than with strains without an inoculum effect (25 of 62 [40.3%] vs 13 of 67 [19.4%]; P = .005). On multivariable analysis, the presence of an inoculum effect was independently associated with first-month mortality (HR, 2.84; 95% CI, 1.28-6.30; P = .01). In this case series of MSSA IE, the presence of an inoculum effect to the β-lactam received was a risk factor for death in the first month. Phenotyping MSSA isolates for inoculum effect may guide β-lactam choice and improve outcomes.

Efficacy and safety of antistaphylococcal penicillin or cephazolin-based combinations versus monotherapy for methicillin-susceptible Staphylococcus aureus infective endocarditis: A propensity score analysis of nationwide prospective cohort

We aimed to evaluate the usefulness of antistaphylococcal penicillin (ASP) or cephazolin-based combinations versus monotherapy in patients with native-valve infective endocarditis (IE) caused by methicillin-susceptible Staphylococcus aureus (MSSA). Post-hoc analysis of a multicentre prospective cohort. We include patients from 2008 to 2022with definite native-valve, left-side IE due to MSSA treated primarily with ASP/cephazolin. Patients were categorized according to whether they initially received monotherapy or combination therapy for more than 72h. A propensity score-matched cohort was planned. Out of 420 included cases, 94 (22.4%) received monotherapy and 326 (77.6%) combination. Median combination duration was 14 days (interquartile range 10-20). Sixty-eight combination cases were matched with 68 monotherapy controls. Baseline characteristics were well balanced. There were no differences in in-hospital or one-year mortality between groups (OR 0.85, 95%CI 0.33-2.18 and HR 0.68, 95%CI 0.35-1.31, respectively). Endocarditis relapses and persistent bacteraemia rates were similar (0% vs 1.5%, p=1.000; and 19.1% vs 13.2%, p=0.352, respectively). Drug-related adverse events were more frequent in the combination group (15.0% vs 1.1%, p<0.001). Antibiotic combinations for patients with native valve left-sided MSSA endocarditis did not improve patient's outcomes. Drug-related adverse events were more frequent in combination patients.

Global practice variation of suppressive antimicrobial treatment for prosthetic joint infections: A cross-sectional survey study

ObjectivesTo identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI). MethodsAn online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups. ResultsRespondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n=134, 41%; Oceania n=112, 34%; North America, n=51, 16%; other, n=33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n=126, 38%), lowered for specific antibiotics (n=125, 38%) or lowered for all antibiotics (n=79, 24%). SAT was prescribed for a lifelong duration (n=43, 13%), a fixed duration (range 6 months–3 years) (n=104, 32%) or for an undetermined duration (n=154, 47%). ConclusionsApproach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.

Exploring combination treatment options for persistent methicillin-susceptible Staphylococcus aureus bacteremia.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. This review explores the management of persistent methicillin-susceptible Staphylococcus aureus bacteremia (SAB), emphasizing the importance of timely intervention due to SAB's association with metastatic dissemination, relapse, and mortality. The literature analysis first delves into risk factors for persistent SAB, highlighting the need for effective treatment strategies. The subsequent focus is on combination strategies for persistent SAB. Daptomycin, ertapenem, ceftaroline, fosfomycin, rifampin, and gentamicin are explored as adjuncts to cefazolin or antistaphylococcal penicillins. Daptomycin combination therapy is assessed through in vivo and clinical studies, indicating potential benefits, especially with higher-risk sources of infection. Ertapenem combination therapy has been demonstrated to have a synergistic effect with cefazolin, presenting a viable salvage option. Rifampin's ability to penetrate biofilm is examined, with discussion of inconclusive evidence on mortality benefits. The review also considers stewardship implications, discussing concerns such as resistance emergence, adverse events, and increased costs associated with combination therapy. Mathematical models suggest combination therapy as an effective approach to prevent resistance. Adverse events vary with each combination, and duration of therapy remains diverse across studies in the absence of well-established dosing guidelines. The review provides a thorough exploration of the literature on treatment of persistent SAB, underscoring the need for evidence-based guidelines, further studies, and clinical judgment in tailoring treatment strategies. The multifaceted analysis contributes valuable insights for clinicians managing this challenging condition.

Nafcillin-induced thrombocytopenia: An uncommon complication

Drug-induced thrombocytopenia is a challenging clinical dilemma that is often overlooked. Nafcillin is a beta-lactam anti-staphylococcal penicillin antibiotic used as a first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia and severe infections. Nafcillin has been associated with a higher rate of premature antibiotic discontinuation than cefazolin. Here we report a 58-year-old woman with multiple comorbid conditions who presented with a prosthetic right hip joint infection due to MSSA and was treated with nafcillin but developed profound thrombocytopenia due to a possible nafcillin side effect on the 14th day of therapy. Thrombocytopenia resolved after discontinuation of nafcillin, and the patient was treated successfully with cefazolin. Keywords: Nafcillin-induced thrombocytopenia, drug-induced thrombocytopenia, thrombocytopenia

Acute kidney injury in Staphylococcus aureus bacteraemia: a recurrent events analysis

ObjectivesTo estimate risk factors for acute kidney injury (AKI) and the effect of AKI on mortality in Staphylococcus aureus bacteraemia, while taking into account recurrent AKI episodes, competing risks, time-varying variables, and time-varying effects. MethodsWe performed an unplanned analysis using data from a multicentre cohort study of patients with Staphylococcus aureus bacteraemia (SAB). The primary outcome was cumulative incidence of AKI, according to Kidney Disease Improving Global Outcomes definitions. ResultsWe included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (hazard ratio (HR) 1.013, 95% CI 1.001–1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01–1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28–2.42), septic shock (HR 3.28, 95% CI 2.31–4.66), persistent bacteraemia (HR 1.53, 95% CI 1.08–2.17), and vancomycin therapy (HR 1.80, 95% CI 1.05–3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin, and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91–6.23). DiscussionThe incidence of AKI in SAB is high and a substantial proportion of patients develop recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. The clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.

Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study

ObjectivesThe empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis. MethodsA post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment. ResultsOf the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01). ConclusionsEmpirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.

2270. Dealing with an old foe –Assessment of Knowledge, Attitude, and Practices: A survey on management of Staphylococcus aureus bacteraemia among Indian Physicians

Abstract Background Staphylococcus aureus bacteraemia (SAB) is associated with high morbidity, mortality, and healthcare costs. Effective management of SAB significantly improves outcome. There is significant gap in the guidelines and clinical practice. This survey was conducted with aim to assess opinions and practice patterns in management of SAB among Indian clinicians. Methods We conducted a cross-sectional respondent-driven survey, using a 45-item, anonymous, voluntary, multiple-choice google form questionnaire among clinicians in India, after obtaining ethical approval from the institute. We distributed survey via social media, WhatsApp, and E-mail. Survey responses were analysed using SPSS, Version 25.0. Results The total of 125 practicing clinicians responded to this survey. Questions where systematically divided into treatment of choice for MSSA, MRSA, additional investigations, persistent bacteraemia, and adjunctive anti-toxin therapy. Around 57% of the respondents have 1-10 episodes of SAB every month. For suspected SAB, most respondents (74%) preferred vancomycin as empiric therapy. If MSSA was identified, 66.7% initiated on Anti staphylococcal penicillin, while in MRSA vancomycin was selected by majority (80%) (Figure 1 &amp; 2). Most clinicians (74%) perceived 1st generation cephalosporins non-inferior to ASPs. Infectious diseases referral for SAB was undertaken in only in about 56% of the cases, with 25% respondents citing non-availability of ID specialist in the institute. Repeat blood cultures and echocardiography was performed by most respondents. Lack of consensus was apparent in diagnosis and management of persistent bacteraemia and oral switch of therapy (Figure 1 &amp; 2).Most respondents managed SAB with at least 14 days of parenteral antibiotics in several scenarios. But, in patients with complicated SAB there was significant practice variation (Figure 3). Figure - 1 Drug of choice in MSSA, MRSA and management of persistent bacteraemia according to the respondents Figure 2 Persistent bacteraemia definition according to the respondents along with the additional tests performed Conclusion There were some areas of consensus, but this survey highlights considerable practice variation among clinicians. Although the value of ID consultation in SAB management has been established by multiple studies, this survey demonstrates that there remains ample opportunity to further define best practices and optimize management of this complex disease. Disclosures All Authors: No reported disclosures

2533. Cerebrospinal Fluid Penetration of Cefazolin and Flucloxacillin in Children

Abstract Background Effective treatment of methicillin-susceptible Staphylococcus aureus meningitis requires antimicrobial penetration into the CSF. Anti-staphylococcal penicillins, including flucloxacillin, are generally recommended as first-line treatment. However, some evidence suggests that the first-generation cephalosporin, cefazolin, may be an appropriate alternative. We investigated the CSF concentration of cefazolin and flucloxacillin in children. Methods CSF samples from children aged 0-18 years treated with cefazolin or flucloxacillin were collected when there was sample remaining after diagnostic tests were completed. Unbound antibiotic concentrations of cefazolin and flucloxacillin were measured. Results Overall, 222 CSF samples were collected from 163 children, median age 12 months (range 0.0-17.5 years). Of these, 157 were collected while the antibiotic was at steady state. For cefazolin, children ≤1 year had a higher median CSF concentration compared with those &amp;gt;1 year (1.8 versus 0.5 mg/L, p&amp;lt; 0.001), whereas for flucloxacillin the concentration was similar between the two age groups (0.2 versus 0.1 mg/L, p=0.9). In infants aged ≥ 1 month to 1 year, the CSF concentration of both antibiotics was higher in those with pleocytosis (WCC &amp;gt;5 x106/L) than those without (flucloxacillin 0.2 versus 0.065 mg/L, cefazolin 5.6 versus 1.06 mg/L). Notably, only those aged ≤1 year receiving cefazolin (7/12; 58%) achieved steady state CSF concentrations above the CLSI breakpoint for sensitive S. aureus (MIC ≤2 mg/L). Conclusion CSF penetration of cefazolin was higher in younger infants and for both antibiotics was higher in those with pleocytosis. In most children, the CSF concentrations in the CSF for either cefazolin or flucloxacillin were not above the S. aureus MIC. Disclosures All Authors: No reported disclosures

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

ObjectivesThis study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). MethodsProspective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. ResultsWe included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. ConclusionOur results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective.

Septic Arthritis of the Knee in Children.

Septic arthritis of the knee is the most common form of septic arthritis in children and can lead to irreversible damage to the joint. Staphylococcus aureus is the primary pathogen associated with septic arthritis, although other causative pathogens may be isolate in children with specific risk factors. The diagnosis of knee septic arthritis is based on comprehensive evaluation, including the patient's medical history, physical examination, blood tests, and arthrocentesis. Empirical treatment typically involves anti-staphylococcal penicillin or a first-generation cephalosporin, although modifications may be made based on local resistance patterns and clinical culture data. Surgical debridement, either through open surgery or arthroscopy, involving extensive debridement of the joint, is effective in eliminating the infection. In most cases, additional surgical intervention is not necessary.

Daptomycin Plus Oxacillin for Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia.

The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection. We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB. This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation. Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively. D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB.

A Retrospective Study of Staphylococcus aureus Bacteremia in a Tertiary Hospital and Factors Associated with Mortality.

Staphylococcus aureus bacteremia (SAB) is a severe infection frequently associated with significant morbidity and mortality. Recent studies have shown that SAB mortality has decreased during the last decades. However, about 25% of patients suffering from the disease will ultimately die. Hence, there is an urgent need for more timely and efficient treatment of patients with SAB. The aim of the present study was to retrospectively evaluate a cohort of SAB patients hospitalized in a tertiary hospital and to identify factors independently associated with mortality. All 256 SAB patients hospitalized from January 2005 to December 2021 in the University Hospital of Heraklion, Greece, were evaluated. Their median age was 72 years, while 101 (39.5%) were female. Most SAB patients were cared for in medical wards (80.5%). The infection was community-acquired in 49.5%. Among all strains 37.9% were methicillin-resistant S. aureus (MRSA), however, definite treatment with an antistaphylococcal penicillin was given only in 22% of patients. Only 14.4% of patients had a repeat blood culture after the initiation of antimicrobial treatment. Infective endocarditis was present in 8%. In-hospital mortality has reached 15.9%. Female gender, older age, higher McCabe score, previous antimicrobial use, presence of a central venous catheter, neutropenia, severe sepsis, septic shock, and MRSA SAB were positively associated with in-hospital mortality, while monomicrobial bacteremia was negatively associated. The multivariate logistic regression model identified only severe sepsis (p = 0.05, odds ratio = 12.294) and septic shock (p = 0.007, odds ratio 57.18) to be independently positively associated with in-hospital mortality. The evaluation revealed high rates of inappropriate empirical antimicrobial treatment and non-adherence to guidelines, as shown, by the lack of repeat blood cultures. These data underline the urgent need for interventions with antimicrobial stewardship, increased involvement of infectious diseases physicians, educational sessions, and creation and implementation of local guidelines for improvement of the necessary steps for timely and efficient SAB treatment. Optimization of diagnostic techniques is needed to overcome challenges such as heteroresistance that may affect treatment. Clinicians should be aware of the factors associated with mortality in patients with SAB to identify those who are at a higher risk and optimize medical management.

Retrospective Evaluation of the Association of Oxacillin MIC on Acute Treatment Outcomes with Cefazolin and Antistaphylococcal Penicillins in Methicillin-Susceptible Staphylococcus aureus Bacteremia.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 μg/mL compared to strains with MIC of oxacillin < 1 μg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 μg/mL and 176 isolates with an MIC < 1 μg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 μg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

BACTERIOLOGY AND ANTIMICROBIAL SUSCEPTIBILITY OF OSTEOARTICULAR INFECTIONS AT A REGIONAL PAEDIATRIC UNIT IN SOUTH AFRICA

Osteoarticular infections (OAI) are a common cause of morbidity in children, and as opposed to adults is usually caused by haematogenous spread. The bacteriology of OAI in children is not well described in the South African context, therefore this study was designed to determine the bacteriology of OAI in our population.All patients that underwent surgery for the treatment of OAI over a 3-year period were identified and those with positive cultures where organisms were identified from tissue, pus, fluid or blood were included. Duplicate cultures from the same patient were excluded if the organism and antibiotic susceptibility profile was the same. Patients were categorised according to age and class of infection (Septic arthritis, acute osteomyelitis, fracture related infection, post-operative sepsis and chronic osteomyelitis) and organisms were stratified according to these categories.We identified 132 organisms from 123 samples collected from 86 patients. Most cultured organisms were from children older than 3-years with acute haematogenous septic arthritis, osteomyelitis, or both. Methicillin sensitive Staphylococcus aureus accounted for 56% (74/132) of organisms cultured. There were no cases of MRSA. The Enterobacterales accounted for 17% (22/132) of organisms cultured, mostly in the fracture related and post-operative infection groups. Of these, 6 each were extended spectrum B-lactamase producers and AmpC producers. There were no carbapenemase producing Enterobacterales. Kingella kingae was not isolated in any patient.Methicillin sensitive S. aureus is the most common infecting organism in paediatric OAI and an anti-staphylococcal penicillin such as cloxacillin or flucloxacillin is the most appropriate empiric treatment for haematogenous OAI in our environment. In fracture related or post-operative infections, Enterobacterales were more frequently cultured, and treatment should be guided by culture and susceptibility results.

Cefazolin in the treatment of central nervous system infections: A narrative review and recommendation.

Infections of the central nervous system (CNS) are complex to treat and associated with significant morbidity and mortality. Historically, antistaphylococcal penicillins such as nafcillin were recommended for the treatment of methicillin-susceptible staphylococcal CNS infections. However, the use of antistaphylococcal penicillins presents challenges, such as frequent dosing administration and adverse events with protracted use. This narrative reviews available clinical and pharmacokinetic/pharmacodynamic (PK/PD) data for cefazolin in CNS infections and produces a recommendation for use. Based on the limited available evidence analyzed, dose optimized cefazolin is likely a safe and effective alternative to antistaphylococcal penicillins for a variety of CNS infections due to methicillin-susceptible Staphylococcus aureus. Given the site of infection and wide therapeutic index of cefazolin, practitioners may consider dosing cefazolin regimens of 2g IV every 6 h or a continuous infusion of 8-10g daily instead of 2g IV every 8 h to optimize PK/PD properties.

738. Outcomes of Ceftriaxone Versus Antistaphylococcal Penicillins or Cefazolin for Definitive Therapy of Methicillin-susceptible Staphylococcus aureus Bacteremia

Abstract Background Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia requires weeks of IV antimicrobial therapy for treatment with antistaphylococcal penicillins (ASP) and first-generation cephalosporins being mainstays of therapy. While effective, use of these agents in the outpatient setting requires frequent dosing along with close toxicity monitoring through the duration of therapy. Ceftriaxone is an appealing alternative given daily dosing and tolerability, but efficacy in this setting remains uncertain. We sought to review outcomes of patients who received ceftriaxone versus an ASP and first-generation cephalosporins for definitive therapy of MSSA bacteremia. Methods Following IRB approval, we reviewed medical records of a retrospective adult cohort diagnosed with MSSA bacteremia treated with ceftriaxone, cefazolin, or an ASP between January 2018 and December 2019 at Mayo Clinic campuses. Treatment was defined as the antibiotic used in the outpatient setting. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic relapse. Secondary outcomes were 30-day treatment failure and individual components of treatment failure. Multivariable Cox regression analysis was performed to analyze for an association between ceftriaxone use and the primary outcome after adjusting for factors that may also impact outcomes. Kaplan-Meier curves were compared utilizing a log-rank test for survival between groups. Results A total of 223 patients with the accompanying characteristics met study criteria (Table 1). Thirty-seven received ceftriaxone (16.5%) and 186 (83.4%) were treated with cefazolin or an ASP. Ninety and 30-day treatment failure were higher in those treated with ceftriaxone (27%, 8.1%) compared to cefazolin or an ASP (8.6%, 3.8%). Multivariable analysis for risk of 90-day treatment failure revealed a hazard ratio of 2.91 for ceftriaxone (Table 2) and a significant difference in event-free survival for those treated with ceftriaxone compared to cefazolin or an ASP (Figure 1). Conclusion Patients receiving definitive therapy with ceftriaxone for MSSA bacteremia experienced a higher rate of 90 and 30-day treatment failure and a lower rate of event-free survival as compared to those treated with cefazolin or an ASP. Disclosures All Authors: No reported disclosures.

Safety and Efficacy of Ceftriaxone in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections: A Noninferiority Retrospective Cohort Study.

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.