Purulent pericarditis caused by methicillin-sensitive Staphylococcus aureus bacteriuria.

BACKGROUND: Purulent pericarditis (PP)- a purulent infection involving the pericardial space-requires a high index of suspicion for diagnosis as it often lacks characteristic signs of pericarditis and carries a mortality rate as high as 40% even with treatment. Common risk factors include immunosuppression, diabetes mellitus, thoracic surgery, malignancy, and uremia. Most reported cases of PP occur in individuals with predisposing risk factors, such as immunosuppression, and result from more commonly observed preceding infections, such as pneumonia, osteomyelitis, and meningitis. We report a case of PP due to asymptomatic bacteriuria in a previously immunocompetent individual on a short course of high-dose steroids. CASE PRESENTATION: An 81-year-old male presented for severe epigastric pain that worsened with inspiration. He had been on high-dose prednisone for presumed inflammatory hip pain. History was notable for urinary retention requiring intermittent self-catheterization and asymptomatic bacteriuria and urinary tract infections due to methicillin-sensitive Staphylococcus aureus (MSSA). During the index admission he was found to have a moderate pericardial effusion. Pericardial fluid cultures grew MSSA that had an identical antibiogram to that of the urine cultures. A diagnosis of purulent pericarditis was made. CONCLUSION: PP requires a high index of suspicion, especially in hosts with atypical risk factors. This is the second case of PP occurring as a result of asymptomatic MSSA bacteriuria. Through reporting this case we hope to highlight the importance of early recognition of PP and the clinical implications of asymptomatic MSSA bacteriuria in the setting of urinary instrumentation and steroid use.

Antimicrobial resistance in ocular infection: A review.

Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin-resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up-to-date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS.

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

OBJECTIVES: The 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. METHODS: A 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. RESULTS: Of 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). CONCLUSIONS: Empirical 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.

Does Topical Vancomycin Powder Use in Fracture Surgery Change Bacteriology and Antibiotic Susceptibilities? An Analysis of the VANCO Trial.

OBJECTIVE: To determine whether intrawound vancomycin changes the bacteriology of surgical site infection pathogens and investigate the emergence of antibiotic-resistant pathogens. DESIGN: Secondary analysis of phase III, prospective, randomized clinical trial. SETTING: Thirty-six US trauma centers. PATIENT SELECTION CRITERIA: Patients who became infected after fixation of tibial plateau or pilon fracture. OUTCOME MEASURES AND COMPARISONS: Pathogen types and bacterial susceptibilities as determined from routine clinical culture in the operating room. RESULTS: Seventy-four patients were studied who were 67.5% male with a mean age of 48.6 years. A lower proportion of gram-positive cocci was observed in the vancomycin powder compared with the standard-of-care group (3.7% vs. 8.0%, P = 0.01). Methicillin-resistant Staphylococcus aureus infection incidence was comparable in both the vancomycin powder and the standard-of-care groups, but rates of methicillin-susceptible S. aureus infections were lower in the treatment group (1.4% vs. 4.8%, P = 0.01). The incidence of coagulase-negative Staphylococci and gram-negative rod infections were similar in both groups. There was no significant difference in susceptibilities between groups in rates of vancomycin-resistant enterococcus. CONCLUSIONS: Topical vancomycin powder decreases the likelihood of gram-positive infections consistent with the biologic activity of vancomycin. Fewer methicillin-susceptible S. aureus and coagulase-negative Staphylococci infections were observed in the group treated with vancomycin powder. An effect of vancomycin powder on methicillin-resistant S. aureus infection risk was not detected given the low incidence in both the intrawound vancomycin and the standard-of-care groups. There was no emergence of gram-negative rod infections or increased resistance patterns observed. Use of topical vancomycin powder does not seem to produce infections in these patients with greater antibiotic resistance than would have occurred without its use. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

[Prevalence and risk factors for methicillin-resistant Staphylococcus aureus infection in children]. / Prevalencia y factores de riesgo de infección por Staphylococcus aureus resistente a meticilina en niños.

OBJECTIVE: The objectives of this work were to know the prevalence of methicillin-resistant S. aureus (MRSA) infections in the paediatric population of our health department, to describe the risk factors for infection by MRSA compared to those produced by methicillin-susceptible S. aureus (MSSA) and to know the antibiotic sensitivity profile of MRSA and MSSA isolates. METHODS: A retrospective, descriptive and analytical study of infections produced by MRSA versus those produced by MSSA was carried out during the years 2014 to 2018. Risk factors for MRSA infection were studied using a binary logistic regression model. RESULTS: 162 patients with S. aureus infections were identified. Of these, 25 (15.4%) were MRSA. The highest percentages of MRSA infection occurred among children who required hospital admission (23.4%). In the univariate analysis the need of hospital admission, antibiotic treatment in the last 3 months, the kind of infection and past MRSA infection or colonisation reached statistical significance. However, only the need of hospital admission and antibiotic treatment in the last 3 months maintained statistical significance in the binary logistic regression model. Correct antibiotic treatment was only prescribed in 26.7% of the MRSA infection cases admitted to the hospital. CONCLUSIONS: Our results suggest the need to review empirical local treatment regimen using drugs active against MRSA in infections of probable staphylococcal origin admitted to the hospital, especially if they have received antibiotic treatment in the last 3 months.

Evaluation of antimicrobial photodynamic action of a pluronic and pectin based film loaded with methylene blue against methicillin resistantStaphylococcus aureus.

Antimicrobial wound dressings play a crucial role in treatment of wound infections. However, existing commercial options fall short due to antibiotic resistance and the limited spectrum of activity of newly emerging antimicrobials against bacteria that are frequently encountered in wound infections. Antimicrobial photodynamic therapy (aPDT) is very promising alternative therapeutic approach against antibiotic resistant microbes such as methicillin resistantStaphylococcus aureus (MRSA). However, delivery of the photosensitizer (PS) homogeneously to the wound site is a challenge. Though polymeric wound dressings based on synthetic and biopolymers are being explored for aPDT, there is paucity of data regarding theirin vivoefficacy. Moreover, there are no studies on use of PS loaded, pluoronic (PL) and pectin (PC) based films for aPDT. We report development of a polymeric film for potential use in aPDT. The film was prepared using PL and PC via solvent casting approach and impregnated with methylene blue (MB) for photodynamic inactivation of MRSAin vitroandin vivo. Atomic force microscopic imaging of the films yielded vivid pictures of surface topography, with rough surfaces, pores, and furrows. The PL:PC ratio (2:3) was optimized that would result in an intact film but exhibit rapid release of MB in time scale suitable for aPDT. The film showed good antibacterial activity against planktonic suspension, biofilm of MRSA upon exposure to red light. Investigations on MRSA infected excisional wounds of mice reveal that topical application of MB loaded film for 30 min followed by red light exposure for 5 min (fluence; ∼30 J cm-2) or 10 min (fluence; ∼60 J cm-2) reduces ∼80% or ∼92% of bioburden, respectively. Importantly, the film elicits no significant cytotoxicity against keratinocytes and human adipose derived mesenchymal stem cells. Taken together, our data demonstrate that PS-loaded PL-PC based films are a promising new tool for treatment of MRSA infected wounds.

Epidemiology and impact of methicillin-sensitive Staphylococcus aureus with ß-lactam antibiotic inoculum effects in adults with cystic fibrosis.

Staphylococcus aureus is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced ß-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive S. aureus (MSSA) isolates were screened at standard (5 × 105 CFU/mL) and high (5 × 107 CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal ß-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent blaZ sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥105 CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed. blaZ A associated with cefazolin IE (P = 0.0011), whereas blaZ C associated with piperacillin-tazobactam IE (P < 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying blaZ genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP) Bloodstream Infection Annual Report 2022.

From 1 January to 31 December 2022, fifty-five institutions across Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP). The aim of ASSOP 2022 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 3,214 SAB episodes were reported, of which 77.5% were community-onset. Overall, 15.0% of S. aureus were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 21.4%, which was significantly different to the 16.8% all-cause mortality associated with methicillin-susceptible SAB (p = 0.02). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the ß-lactams, approximately 31% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 13% to tetracycline; 11% to gentamicin; and 2% to co-trimoxazole. One MRSA isolate, with a daptomycin MIC of 1.5 mg/L, harboured the A302V mprF and A23V cls2 mutations. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in one MRSA isolate. Resistance to vancomycin or linezolid was not detected. Resistance to non-ß-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and to the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired resistance to multiple antimicrobials including ciprofloxacin, clindamycin, erythromycin, gentamicin, and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 86% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 72% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST97-IV [2B]; ST953-IV [2B]; and ST8-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia.

Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S. aureus infection with osseointegration in murine models of implant-associated osteomyelitis.

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve "target-and-release" drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Community-acquired S. aureus infection in childhood: a multi-center study.

BACKGROUND: The prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) has been increasing worldwide. We aimed to investigate the prevalence of MRSA in community-acquired S. aureus infections, the risk factors for CA-MRSA infection and the clinical features of CA-MRSA. METHODS: A multi-center study with prospective and retrospective sections was conducted. Patients ≥ 3 months old and ≤18 years of age who were diagnosed with community-acquired S. aureus infections were included in this study and the patients` information were reviewed from the medical and microbiological database of the hospital. A standard question form about living conditions and exposure risk factors was administered to the parents of patients. The CA-MRSA infections were compared with the methicillin-susceptible S. aureus (CAMSSA) infections in terms of the queried risk factors and clinical variables. RESULTS: We identified 334 pediatric patients with S. aureus infection, 58 (17.4%) had an infection with CAMRSA. The refugee rate was higher in the CA-MRSA group. There was no significant difference regarding the exposure risk. The treatment modalities and outcomes were similar. CONCLUSIONS: The study was not able to show reliable clinical variables or epidemiological risk factors except for being a refugee for CA-MRSA infections. Empirical antibiotic treatment should therefore be determined according to the local CA-MRSA prevalence in patients presenting with a possible staphylococcus infection.

Microbiological and Clinical Outcomes of Methicillin-Susceptible Staphylococcus aureus Isolated in Lung Transplant Perioperative Donor and Recipient Respiratory Cultures.

Staphylococcus aureus is one of the most common organisms isolated from respiratory secretions in lung transplant donors and recipients perioperatively. Within the first 90 days after lung transplantation, methicillin-susceptible Staphylococcus aureus (MSSA) infections have been associated with increased mortality and acute and chronic rejection. However, it is unclear whether respiratory cultures positive for MSSA at the time of transplantation can lead to clinically significant infection. The aim of this study was to assess the microbiological and clinical outcomes for lung transplant recipients (LTRs) with positive perioperative donor or/and recipient respiratory cultures for MSSA. A retrospective study was conducted evaluating MSSA-positive respiratory cultures at the time of lung transplantation from donors and/or recipients from January 1, 2008, to December 30, 2019. Patients who did not have a bronchoalveolar lavage at 2 weeks after the lung transplant or died within 2 weeks of lung transplant were excluded. The main outcome was MSSA eradication at 2-week bronchoscopy. Recipients were evaluated for MSSA infections at the 12-week period after the transplant. Of the 1,678 individuals who underwent lung transplantation, 218 LTRs had S. aureus isolated in perioperative donor or recipient respiratory cultures, and 29 were subsequently excluded. Of the remaining 189 LTRs, MSSA eradication at the 2-week bronchoscopy was achieved in 186 (98.4%) recipients. During the 12-week follow-up, 15 (7.9%) recipients were diagnosed with MSSA pneumonia; concurrent MSSA bacteremia was noted in one recipient. No anastomotic infection, empyema, or lung abscess related to MSSA was diagnosed during the follow-up period.In LTRs, the rate of MSSA eradication at 2-week post-transplant recipients is high, and it is associated with a low rate of infectious complication within the first 12 weeks after transplant. Most of the recipients received a combination therapy with at least one agent active against MSSA. More studies to evaluate the optimal antimicrobial stewardship policies regarding the regimen and duration of antibiotic therapy for these patients are needed.

Early switching from intravenous to oral antibiotic therapy in bone and joint infections associated with methicillin-susceptible Staphylococcus aureus bacteremia.

OBJECTIVES: We aimed to evaluate the clinical outcomes of patients with bone and joint infection (BJI) associated with methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) treated with early oral switch to oral antibiotics (before day 14) versus later or no switch. PATIENTS AND METHODS: We included all cases reported between January 2016 and December 2021 in the University Hospital of Reims. RESULTS: Among 79 patients with BJI associated with MSSAB, 50.6% had an early switch to oral antibiotics, with median duration of intravenous antibiotics of 9 (IQR 6-11) days. The overall cure rate was 81% with follow-up of 6 months, and was 85.7% after excluding the 9 patients whose death was not related to BJI infection. Failure to control BJI did not differ between the two groups. CONCLUSION: An early (before day 14) switch to oral antibiotics may be a safe therapeutic option in BJI associated with MSSAB.

Detecting the performance of methicillin-resistant Staphylococcus aureus by a molecular diagnostic assay in positive blood culture: Influence of coexistence of mecA-positive bacteria and diversity in orfX-SCCmec junction region in methicillin-susceptible S. aureus.

BACKGROUND: In blood cultures that test positive for staphylococcal bacteria, rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-susceptible Staphylococcus aureus (MSSA) by molecular assay is useful for appropriate antimicrobial treatment of bloodstream infections. Although the Xpert MRSA/SA BC assay is widely available in clinical settings in Japan, its efficacy has not yet evaluated thoroughly. METHODS: We retrospectively studied 100 blood culture cases positive for S. aureus at Sapporo Medical University Hospital between March 2019 and May 2022. Cycle threshold (CT) values for target genes from the Xpert MRSA/SA BC assay were compared to phenotypic results. Genotyping and genetic analysis of the orfX-SCCmec junction region was performed for selected isolates. RESULTS: We analyzed 25 and 75 isolates assigned to MRSA and MSSA, respectively, using the Xpert MRSA/SA BC assay. Of these, 99 isolates from agar cultures showed compatible susceptibility to oxacillin. One genetically misidentified case of MRSA was found to be caused by the mixed growth of MSSA and methicillin-resistant S. hominis on agar culture. Of the 73 MSSA with pure growth on agar culture, 45 (61.6%) were found to be orfX-SCCmec-positive, spa-positive, and mecA-negative in this assay. These MSSA belong to diverse spa and coa types. CONCLUSION: The Xpert MRSA/SA BC assay accurately identified MRSA and MSSA in positive blood cultures. However, over half of the MSSA isolates showed positive results for orfX-SCCmec, presumably due to genetic diversity in the orfX-associated region of MSSA. Therefore, the coexistence of MSSA and mecA-harboring coagulase-negative staphylococci may cause confusion about identification of MRSA.

Severe atypical Lemierre syndrome caused by methicillin-sensitive Staphylococcus aureus: Two pediatric case reports.

BACKGROUND: Lemierre syndrome is typically associated with ear, nose, and throat (ENT) infections caused by Fusobacterium necrophorum. Since 2002, cases of atypical Lemierre-like syndrome secondary to Staphylococcus aureus have been reported. CASES: We report two pediatric cases of atypical Lemierre syndrome with a similar presentation: exophthalmia, absence of pharyngitis, metastatic lung infection, and intracranial venous sinus thrombosis. Both patients had a favorable outcome following treatment with antibiotics, anticoagulation, and corticosteroids. CONCLUSION: Regular therapeutic monitoring of antibiotic levels helped to optimize antimicrobial treatment in both cases.

Comparison of diagnosis and treatment of MSSA and MRSA osteomyelitis in children: a case-control study of 64 patients.

BACKGROUND: We aimed to compare the clinical characteristics of acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) in children. METHODS: We retrospectively analyzed the data of 64 children treated between September 2017 and June 2021. Based on the bacterial culture results, they were divided into MRSA and MSSA infection groups. Both groups were treated with debridement and vacuum-assisted closure for negative pressure drainage. Parameters including clinical manifestations, number of operations, length of hospital stay, inflammatory indicators, and concurrent arthritis were compared between the two groups. RESULTS: In the MRSA infection group, there was one case each of residual joint stiffness and pathological fracture. Conversely, the MSSA group had two cases of residual joint stiffness. The MRSA infection group was more prone to high fever (t = 3.61, P = 0.001), white blood cell count elevation (t = 2.41, P = 0.022), arthritis (X2 = 7.48, P = 0.013), metastatic abscess (X2 = 4.78, P = 0.042), and a shorter length of progression from onset to admission (t = - 2.04, P = 0.046); however, it required more surgeries (t = 2.68, P = 0.009) and longer hospital stay (t = 2.04, P = 0.045). CONCLUSIONS: Pediatric acute osteomyelitis caused by MRSA is more prone to cause high fever and markedly elevated of white blood cell count, and is often accompanied with suppurative infection of adjacent joints and metastatic abscesses, thus requiring more surgeries and longer hospital stay.

Comparative effectiveness of ß-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study.

OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. RESULTS: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. CONCLUSIONS: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.

Evaluation of the performance of GeneSoC®, a novel rapid real-time PCR system, to detect Staphylococcus aureus and methicillin resistance in blood cultures.

Staphylococcus aureus bacteremia results in substantial mortality. Rapid identification and the determination of methicillin susceptibility are crucial for immediate treatment with appropriate antibiotics. In the present study, we aimed to evaluate the basic assay performance of GeneSoC®, a novel rapid quantitative polymerase chain reaction (qPCR) method, for the detection of methicillin-susceptible (MS) or -resistant (MR) S. aureus in blood culture (BC) bottles. qPCR pimers and probes were desinged for femA and mecA genes to diagnose S. aureus and its methicilline-resistance status. GeneSoC® system can detect target genes within 12 min per sample using microfludic thermal cycling. A total of 100 BC-positive samples, showing clusters of gram-positive cocci using microscopy, were tested. The analytical sensitivity was demonstrated for the target sequence of femA and mecA genes at 10 copies/µL, respectively. The detection limit of the MRSA bacterial burden using this system was 104 and 103 CFU/mL for femA and mecA, respectively. Compared with culture-based identification and susceptibility testing, the sensitivity and specificity for the detection of femA (+)/mecA (+) MRSA using GeneSoC® were 90.9 and 98.9%, respectively, whereas the sensitivity and specificity for detection of femA (+)/mecA (-) MSSA were 96.2% and 97.3%, respectively. In conclusion, although this was a small sample and pilot study, the GeneSoC® system is beneficial for rapid, reliable, and highly sensitive real-time testing of MRSA and MSSA in BC bottles.

Post-treatment outcomes of ceftriaxone versus antistaphylococcal penicillins or cefazolin for definitive therapy of methicillin-susceptible Staphylococcus aureus bacteremia.

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with poor outcomes. Ceftriaxone offers logistical advantages over other standard therapies, though in vitro studies have questioned its efficacy and clinical studies of ceftriaxone in MSSA bacteremia are conflicting.We performed a multicenter, retrospective cohort study of adult patients who received ceftriaxone, cefazolin, or antistaphylococcal penicillins as definitive therapy for MSSA bacteremia from 2018 to 2019. Definitive therapy was defined as the antibiotic used in the outpatient setting. Patients were excluded if they received less than 7 days of outpatient therapy. Follow-up started on the date of definitive therapy completion. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic recurrence. This was analyzed with multivariable Cox regression. A total of 223 patients were included, 37 (16.6%) of whom received ceftriaxone. The most common ceftriaxone dose was 2 g daily (83.8%). The most common primary site of infection was skin/soft tissue (37.2%), unknown (21.1%), and catheter-related (15.2%). Twenty-six (11.7%) developed infective endocarditis. Median total duration of treatment was 31.0 days, and median outpatient duration was 24.0 days. Twenty-six (11.7%) developed 90-day treatment failure. After adjusting for Charlson comorbidity index, duration of therapy, and use of transesophageal echocardiography, definitive treatment with ceftriaxone was associated with treatment failure (hazard ratio 2.66, 95% confidence interval 1.15-6.12; p=0.022). Among patients with MSSA bacteremia, definitive treatment with ceftriaxone was associated with a higher risk of treatment failure within 90 days as compared to cefazolin or antistaphylococcal penicillins.