Triple valve endocarditis (TVE) is a rare presentation of endocarditis often requiring multivalvular surgery. Here we report a case of S. aureus triple valve endocarditis in a patient with a history of intravenous drug use and provide a literature review of TVE identification, treatment, and prognosis.

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 2 g IV every 6 h or a continuous infusion of 8-10 g daily instead of 2 g IV every 8 h to optimize PK/PD properties.

Staphylococcus aureus remains an important human pathogen of concern, with mortality rates surpassing 30% in the case of severe systemic infections. Distinguishing methicillin-susceptible S. aureus from methicillin-resistant S. aureus (MRSA) is fundamental for therapeutic choices. A crucial emerging concept in the treatment of acute bacterial skin and skin structure infections is the availability of various approved agents with anti-MRSA activity, which allow a personalized approach based on the characteristics of any given patient while at the same time remaining in line with high certainty efficacy evidence from large randomized controlled trials. Regarding the treatment of S. aureus bloodstream infections (BSI), interesting aspects that may become relevant in the near future are the presence of both old and novel agents in phase-2 or phase-3 of clinical development for this indication, and the pressing need for high certainty evidence to guide the possible use of combination therapy in specific categories or phenotypes of patients with complicated MRSA BSI.

(1) Background: Ceftriaxone is a potential alternative for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) in acute care and outpatient parenteral antimicrobial therapy (OPAT) settings. We evaluated the effectiveness and safety of ceftriaxone for the treatment of MSSA BSIs. (2) Method: We searched PubMed, Embase, and Cochrane Library from their inception to October 30th 2021. Our outcomes included clinical cure, microbiological cure, 30- and 90-day mortality, 90-day hospital readmission, and adverse drug reactions (ADRs). We compared ceftriaxone against standard of care (SOC) therapy. We used the random-effects model for the meta-analysis, and our estimated effects were reported as odds ratios (ORs) with 95% confidence intervals (CI). (3) Results: Twelve retrospective cohort studies were included, comprising 1037 patients in the ceftriaxone arms and 2088 patients in the SOC arms. The clinical cure rate of the ceftriaxone regimen was not statistically different from SOC: OR 0.65 (95% CI: 0.29-1.45). Ceftriaxone was also not statistically different from SOC in microbiological cure: OR 1.48 (95% CI: 0.29-7.51); 30-day mortality: OR 0.79 (95% CI: 0.14-4.65); 90-day mortality: OR 0.82 (95% CI: 0.38-1.80); 90-day hospital readmission: OR 1.20 (95% CI: 0.92-1.56); and ADRs: OR 0.92 (95% CI: 0.39-2.18). (4) Conclusion: Ceftriaxone could provide an alternative for the treatment of MSSA BSIs in acute care and OPAT settings (except in patients whose BSIs were due to infective endocarditis).

Optimal therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections is unclear. The current standard of care consists of anti-staphylococcal antibiotics (ASA), such as nafcillin, oxacillin, and cefazolin. Ceftriaxone has been evaluated due to its advantage as a once-daily outpatient regimen. However, questions remain regarding efficacy compared to ASA. We aimed to conduct a review and synthesis of available literature for outcomes of patients treated with ceftriaxone or ASA for MSSA infections. We searched Cochrane Central Register of Controlled Trials, Embase, Ovid MEDLINE, Scopus, and Web of Science from 1990 to June 2021. Risk of bias for cohort studies was assessed by the Newcastle-Ottawa quality scale. We pooled risk ratios (RR) using the DerSimonian-Laird random effects model for outcomes of those who received ceftriaxone compared to ASA. Heterogeneity was assessed by the I2-index. From 459 identified studies, 7 were included in the quantitative synthesis totalling 1640 patients. Definitive therapy with ceftriaxone was associated with a lower risk of toxicity requiring alteration of therapy [RR 0.49 (95% confidence interval [CI] 0.27-0.88, I2=0%)]. There was no difference in terms of 90-day all-cause mortality [RR 0.93 (95% CI 0.46-1.88, I2=9%)], hospital readmission [RR 0.96 (95% CI 0.57-1.64, I2=0%)], or infection recurrence [RR 1.04 (95% CI 0.63-1.72, I2=0%)]. Current evidence suggests there is no difference in efficacy between ceftriaxone and ASA for MSSA infection, with a lower risk of toxicity with ceftriaxone. Within the limitations of available retrospective studies, ceftriaxone is a consideration for definitive therapy of MSSA infection. [Trial registration: PROSPERO ID: CRD42021259086].

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: Empirical treatment of patients with cellulitis/erysipelas usually targets both streptococci and methicillin-sensitive S. aureus (MSSA). However, the recommendation to empirically cover MSSA is weak and based on low-quality evidence.
UNASSIGNED: A systematic review was conducted in PubMed and clinical trial registries to assess the role of S. aureus in cellulitis/erysipelas and the need for empirical MSSA coverage.
RESULTS: Combined microbiological and serological data, and response to penicillin monotherapy suggest that streptococci are responsible for the vast majority of cases of cellulitis/erysipelas. However, most cases are non-culturable and the specificity of microbiological and serological studies is questionable based on recent studies using molecular techniques. According to epidemiological data and three randomized controlled trials, empirical coverage of methicillin-resistant S. aureus (MRSA) is not recommended for most patients, despite the high prevalence of MRSA in many areas. If MRSA is indeed not an important cause of uncomplicated cellulitis/erysipelas, then the same may apply to MSSA. Based on indirect comparison of data from clinical studies, cure rates with penicillin monotherapy (to which most MSSA are resistant) are comparable to the cure rates reported in many studies using wider-spectrum antibiotics.
CONCLUSIONS: Considering the limitations of microbiological studies in identifying the pathogens responsible for cellulitis/erysipelas, treatment needs to be guided by clinical trials. Trials comparing penicillin or amoxicillin monotherapy to MSSA-covering regimens are needed to definitively answer whether empirical coverage of MSSA is needed and to identify the subset of patients that can be safely treated with penicillin or amoxicillin monotherapy.

BACKGROUND: Spinal epidural abscess (SEA) is a rare but serious infection in the epidural space along the spinal cord. SEA should be considered in patients with backache, fever, neurological deficits and/or spinal tenderness. Early diagnosis is imperative to prevent permanent neurological sequelae.
METHODS: We report a case of lumbar SEA in a 13-year-old girl who was immunocompetent and presented with spinal tenderness, back pain and 4 days of fever. A lumbar magnetic resonance imaging demonstrated an epidural abscess from L3-S1. She had emergent surgical intervention. Cultures grew methicillin-susceptible Staphylococcus aureus. She was also given long-term systemic antibiotics and she made a complete recovery within 2 months.
CONCLUSIONS: SEA in an immunocompetent pediatric without risk factors is an extremely rare condition. In the English-language literature, there are only 30 reported cases in the past 19 years; our case brings the total to 31. Non-surgical treatment has been successful in both adult and pediatric patients under certain conditions. Still, there exists a risk of deterioration with non-surgical management, even in patients for whom treatment is begun in the absence of neurologic deficits. Tracking neurological deficits in children can be challenging, particularly in young children who are non-verbal and not yet ambulating, and a reliable neurologic examination is a critical component of non-surgical care. In consideration of these facts and the accelerated time frame of deterioration, once neurologic deficits are present, surgery plus systemic antibiotics remains the standard of care for pediatric SEA patients, with each individual case meriting review of the full clinical picture.

Recent studies and experience suggest that cefazolin might be equally as effective as antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus (MSSA), with a better safety profile and lower cost. The objective of these meta-analyses was to compare the safeties of antistaphylococcal penicillins and cefazolin. The PubMed, Embase, and International Pharmaceutical Abstracts databases and websites for clinical trial registries through 23 June 2017 were searched. In addition, recent abstracts from infectious disease and pharmacy conferences were reviewed. We estimated Peto odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models. One analysis focused on hospitalized patients, and the other focused on outpatients. Eleven retrospective studies of hospitalized patients and three retrospective studies of outpatients were included. In hospitalized patients, lower rates of nephrotoxicity (Peto OR, 0.225; 95% CI, 0.127 to 0.513), acute interstitial nephritis (Peto OR, 0.189; 95% CI, 0.053 to 0.675), hepatotoxicity (Peto OR, 0.160; 95% CI, 0.066 to 0.387), and drug discontinuation due to adverse reactions (Peto OR, 0.192; 95% CI, 0.089 to 0.414) were found with cefazolin. In outpatients, lower rates of nephrotoxicity (Peto OR, 0.372; 95% CI, 0.192 to 0.722), hepatotoxicity (Peto OR, 0.313; 95% CI, 0.156 to 0.627), and hypersensitivity reactions (Peto OR, 0.372; 95% CI, 0.201 to 0.687) were observed with cefazolin. Compared to antistaphylococcal penicillins, cefazolin was associated with significant reductions in nephrotoxicity and hepatotoxicity in hospitalized patients and outpatients. Additionally, cefazolin was associated with lower likelihoods of discontinuation due to side effects in hospitalized patients and hypersensitivity reactions in outpatients. Cefazolin should be considered a first-line option for patients with MSSA infections for which efficacy is presumed to be similar to that of antistaphylococcal penicillin therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is still a major global healthcare problem. Of concern is S. aureus bacteremia, which exhibits high rates of morbidity and mortality and can cause metastatic or complicated infections such as infective endocarditis or sepsis. MRSA is responsible for most global S. aureus bacteremia cases, and compared with methicillin-sensitive S. aureus, MRSA infection is associated with poorer clinical outcomes. S. aureus virulence is affected by the unique combination of toxin and immune-modulatory gene products, which may differ by geographic location and healthcare- or community-associated acquisition. Management of S. aureus bacteremia involves timely identification of the infecting strain and source of infection, proper choice of antibiotic treatment, and robust prevention strategies. Resistance and nonsusceptibility to first-line antimicrobials combined with a lack of equally effective alternatives complicates MRSA bacteremia treatment. This review describes trends in epidemiology and factors that influence the incidence of MRSA bacteremia. Current and developing diagnostic tools, treatments, and prevention strategies are also discussed.