To evaluate the effectiveness of ceftaroline vs. vancomycin or daptomycin in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections (BSIs) (MRSA-BSIs).

This multicentre retrospective study conducted in 15 Spanish hospitals included data from the first MRSA-BSIs of adult patients between January 2019 and December 2022. The ceftaroline group included patients who received ceftaroline for ≥72 hours within the first week of BSI onset; the standard-of-care (SOC) group included patients who received vancomycin or daptomycin ≥72 hours after BSI onset. Primary outcome was 30-day all-cause mortality; secondary outcomes included 90-day mortality and incidence of adverse events (AEs). Propensity-score matching and Cox proportional hazards analyses were performed.

A total of 429 MRSA-BSIs were included: 133 in the ceftaroline group and 296 in the SOC group. More patients in the ceftaroline group had a Sequential Organ Failure Assessment score >2 (51.1% vs. 36.5%; p < 0.01), complicated BSI (66.2% vs. 42.2%; p < 0.01), infective endocarditis (18.8% vs. 6.4%; p < 0.01) and prescribed in combination treatment (65.4% vs. 11.5%; p < 0.01), with no statistically significant differences in 30-day mortality: 23.3% ceftaroline (95% CI, 16.1-30.5%) vs. 16.2% SOC (95% CI, 12.0-20.4%), p 0.08. There were no statistically significant differences in 90-day mortality (33.1% ceftaroline vs. 26.7% SOC; p 0.17). After propensity-score matching, 105 patients treated with ceftaroline were matched with 105 controls: the 30-day mortality rates were 21.9% and 16.2% (p 0.38). Cox regression analysis of the entire cohort (n = 429) revealed that age (hazard ratio [HR], 1.05; 95% CI, 1.03-1.07) and Sequential Organ Failure Assessment score >2 (HR, 2.34; 95% CI, 1.50-3.65) were associated with 90-day mortality risk, although ceftaroline treatment did not demonstrate a significant effect (HR, 1.00; 95% CI, 0.97-1.02). Incidence of AEs was 12.0% in ceftaroline vs. 4.4% in the SOC group (p < 0.01). Most AEs occurred when ceftaroline was used in combination vs. monotherapy (17.2% vs. 2.2%; p 0.01).

Ceftaroline was an effective treatment for MRSA-BSIs but was commonly prescribed in combination showing a higher incidence of AEs.

Bloodstream infections (BSIs) caused by Staphylococcus aureus are common worldwide, representing one of the most relevant issues in clinical infectious diseases practice. In particular, BSIs by methicillin-resistant S. aureus (MRSA-BSI) are still today a challenge since mortality burden remains elevated although decades of research.

The following topics regarding MRSA-BSI were reviewed and discussed by resorting to best available evidence retrieved from PubMed/MEDLINE up to October 2024: i) epidemiology; ii) microbiology; iii) classification, with a focus on complicated and not complicated forms; iv) the structured approach to the patient; v) pharmacokinetics and pharmacodynamics of the main antimicrobial options; vi) controversies regarding the best therapeutic approach.

Despite ongoing efforts to better stratify and manage MRSA-BSI, there is no universally accepted classification system accurately distinguishing between uncomplicated/low risk and complicated/high risk forms. Biomarkers such as interleukin(IL)-10 hold promise in order to enable a more precise stratification, premise for an appropriate treatment plan. There is a theoretical rationale for implementing a combination therapy including a beta-lactam agent upfront, especially for patients considered at higher risk of unfavorable outcomes, but further data are necessary, and the same applies to newer adjuvants. Novel microbiological techniques may help in guiding antimicrobial duration.

Staphylococcus aureus, a gram-positive bacterium, is the leading cause of death from bacteremia worldwide, with a case fatality rate of 15% to 30% and an estimated 300 000 deaths per year.

Staphylococcus aureus bacteremia causes metastatic infection in more than one-third of cases, including endocarditis (≈12%), septic arthritis (7%), vertebral osteomyelitis (≈4%), spinal epidural abscess, psoas abscess, splenic abscess, septic pulmonary emboli, and seeding of implantable medical devices. Patients with S aureus bacteremia commonly present with fever or symptoms from metastatic infection, such as pain in the back, joints, abdomen or extremities, and/or change in mental status. Risk factors include intravascular devices such as implantable cardiac devices and dialysis vascular catheters, recent surgical procedures, injection drug use, diabetes, and previous S aureus infection. Staphylococcus aureus bacteremia is detected with blood cultures. Prolonged S aureus bacteremia (≥48 hours) is associated with a 90-day mortality risk of 39%. All patients with S aureus bacteremia should undergo transthoracic echocardiography; transesophageal echocardiography should be performed in patients at high risk for endocarditis, such as those with persistent bacteremia, persistent fever, metastatic infection foci, or implantable cardiac devices. Other imaging modalities, such as computed tomography or magnetic resonance imaging, should be performed based on symptoms and localizing signs of metastatic infection. Staphylococcus aureus is categorized as methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) based on susceptibility to β-lactam antibiotics. Initial treatment for S aureus bacteremia typically includes antibiotics active against MRSA such as vancomycin or daptomycin. Once antibiotic susceptibility results are available, antibiotics should be adjusted. Cefazolin or antistaphylococcal penicillins should be used for MSSA and vancomycin, daptomycin, or ceftobiprole for MRSA. Phase 3 trials for S aureus bacteremia demonstrated noninferiority of daptomycin to standard of care (treatment success, 53/120 [44%] vs 48/115 [42%]) and noninferiority of ceftobiprole to daptomycin (treatment success, 132/189 [70%] vs 136/198 [69%]). Source control is a critical component of treating S aureus bacteremia and may include removal of infected intravascular or implanted devices, drainage of abscesses, and surgical debridement.

Staphylococcus aureus bacteremia has a case fatality rate of 15% to 30% and causes 300 000 deaths per year worldwide. Empirical antibiotic treatment should include vancomycin or daptomycin, which are active against MRSA. Once S aureus susceptibilities are known, MSSA should be treated with cefazolin or an antistaphylococcal penicillin. Additional clinical management consists of identifying sites of metastatic infection and pursuing source control for identified foci of infection.

Staphylococcus aureus bacteraemia had a higher mortality rate than average at Kingston Health Sciences Centre (KHSC). Infectious diseases specialist consultation has been shown to improve outcomes for S. aureus bacteraemia by increasing adherence to evidence-based care practices. Yet, infectious disease specialists were not involved in many cases at KHSC.

To improve adherence to evidence-based care practices by increasing the proportion of patients with S. aureus bacteraemia who receive a formal infectious diseases consultation.

A multimodal intervention consisting of (1) daily automated email of positive blood culture results to the infectious diseases team; (2) standardisation of prompts attached to positive blood culture results on the electronic medical record; (3) policy of mandatory infectious diseases consultation and (4) education of resident physicians.

The outcome measure was adherence to evidence-based care practices, defined as echocardiography, repeating blood cultures and treatment with a first-line antibiotic. A secondary outcome measure was 90-day mortality. The process measure was the proportion of patients receiving formal infectious diseases consultation. A balancing measure was hospital length of stay. All measures were monitored semimonthly using statistical process control charts for time periods before and after intervention.

There were 171 and 186 patients with S. aureus bacteraemia in the preintervention and postintervention period, respectively. Between these two periods, the proportion of those who received evidence-based care practices increased from 73% to 82% (p=0.031) and demonstrated special cause variation. Mortality changed from 29% to 24% (p=0.400). The proportion of patients receiving an infectious diseases consultation increased from 47% to 90% (p<0.001) and demonstrated special cause variation. The median (IQR) length of stay was 18 (11-30) days and 17 (11-42) days in the preintervention and postintervention period, respectively (p=0.442).

A multimodal intervention that implemented mandatory infectious diseases consultation significantly improved evidence-based care practices for S. aureus bacteraemia.

 Nosocomial pneumonia, encompassing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), remains a major cause of morbidity and mortality in hospitalized adults. In response to evolving pathogen profiles and emerging resistance patterns, this updated S3 guideline (AWMF Register No. 020-013) provides an evidence-based framework to enhance the diagnosis, risk stratification, and treatment of nosocomial pneumonia.

 The guideline update was developed by a multidisciplinary panel representing key German professional societies. A systematic literature review was conducted with subsequent critical appraisal using the GRADE methodology. Structured consensus conferences and external reviews ensured that the recommendations were clinically relevant, methodologically sound, and aligned with current antimicrobial stewardship principles.

 For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to non-bronchoscopic sampling in terms of main outcomes. Combination antibiotic therapy is now reserved for patients in septic shock and high risk for multidrug-resistant pathogens, while select patients may be managed with monotherapy (e. g., meropenem). In clinically stabilized patients, antibiotic therapy should be de-escalated and focused, as well as duration shortened to 7-8 days. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid.

 This updated S3 guideline offers a comprehensive, multidisciplinary approach to the management of nosocomial pneumonia in adults. By integrating novel diagnostic modalities and refined therapeutic strategies, it aims to standardize care, improve patient outcomes, and enhance antimicrobial stewardship to curb the emergence of resistant pathogens.

The prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in skin and soft tissue infections (SSTI) has significantly changed in recent decades. We conducted a literature review to determine whether this microorganism, which became increasingly common as a cause of SSTI in the 2000s, still plays a significant role in these infections today.

Over the past 30 years, there has been a pattern of increase and then decrease in these infections. The highest frequency was observed in the United States, to the extent that guidelines recommended empirical antibiotic treatment for this pathogen in SSTI. Clone USA300 is the primary causative agent in the United States. In Europe, SSTI are much less common than in the United States, and the presence of this clone has been significantly lower. A decrease in the frequency of SSTI and CA-MRSA has been observed in developed countries. However, the spread of specific clones in Latin America, Asia and Africa highlights the need for rigorous global surveillance.

In recent years, the prevalence of CA-MRSA SSTI has decreased in developed countries. However, globalisation, immigration and intercontinental travel have favoured the spread of some clones with epidemic potential. It remains to be seen whether the current lower frequency will be maintained or whether these clones will give rise to a new wave.

To evaluate diagnostic performance of four diagnostic methods for rapid determination of methicillin resistance in S. aureus positive blood cultures (BCs).

Clinical and spiked BCs were subjected to the evaluation of the following methods and protocols: a. Eazyplex® MRSA Plus loop-mediated isothermal amplification (LAMP) assay directly from BC fluid; b. MALDI-TOF MS subtyping on BC pellet extracted with Rapid Sepsityper® protocol and on 4-h short-term subculture; c. Clearview™ Culture Colony PBP2a SA immunochromatography assay on BC pellet and on 4-h short-term subculture; d. EUCAST RAST cefoxitin screen test performed directly from BC and including reading times at 4-h, 6-h and 16-20-h.

Eazyplex® MRSA plus exhibited the best performance, showing 100% sensitivity, specificity, positive predictive value, and negative predictive value, followed by PBP2a SA Culture Colony Clearview assay and EUCAST RAST cefoxitin screen. MALDI-TOF MS subtyping showed the lowest diagnostic accuracy (59.8 and 65.7% directly from BC and from 4-h subculture, respectively). In detail, sensitivity and specificity ranged from 24.3% to 20.4% and from 88.9% to 98.3% for protocols performed from BC pellet and 4-h subculture, respectively.

The Eazyplex® MRSA Plus and the immunochromatographic Clearview™ PBP2a SA Culture Colony methods can provide reliable results within 1 h from the start of positive BC processing. MALDI TOF MS subtyping showed unacceptable specificity by performing analysis from BC pellets, while its sensitivity depends on the prevalence of PSM-positive MRSA strains. The EUCAST RAST, based on disc diffusion, showed excellent performance with a time-to-result of at least 4 h.

Recurrent or persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia presents significant clinical challenges. Comprehensive genomic-scale studies on the genetic changes in MRSA that correspond to refractory bacteremia are lacking.

From 2011 to 2019, MRSA blood isolates were collected from patients with persistent or recurrent bacteremia at a teaching hospital in southern Taiwan. Whole-genome sequencing (WGS) captured the genomic changes in strains responsible for refractory bacteremia, and the altered susceptibilities to specific antimicrobial agents were assessed through measurements of minimal inhibitory concentrations (MICs).

A total of 35 MRSA blood isolates from 15 patients with recurrent or persistent bacteremia were analyzed. Reduced susceptibilities to at least one anti-MRSA agent developed in strains from seven (46.7 %) patients. Of them, a non-synonymous mutation on a global regulator mgrA was associated with reduced daptomycin susceptibility, while an increase in vancomycin MIC was linked to mutations in genes encoding LCP family protein. A 16-fold increase in MIC to fusidic acid was connected to a mutation in the elongation factor G. These recurrent strains commonly exhibited a loss or acquisition of adhesion genes that were involved in biofilm formation, including fnbA, fnbB, and sdrD, and easG series genes of type VII secretion system.

Changes in the susceptibility of successive strains to common anti-MRSA agents were frequently observed in recurrent MRSA bacteremia. These changes were linked to modifications in genes of regulatory cascade, peptidoglycan binding, adhesion, and type VII secretion system.

Sepsis is a severe and often life-threatening condition which can lead to widespread organ dysfunction, septic shock, and even death. Antimicrobials are critical in improving outcomes for patients with sepsis. This chapter details the general principles of antimicrobial therapy, appropriate selection and de-escalation of antimicrobials, and challenges in antimicrobial stewardship.

Expert reports analyze medical malpractice in urology based on selected case studies and assess their medical and legal implications. Common sources of error include noncompliance with clinical guidelines, inadequate patient information, insufficient diagnostics, and a lack of interdisciplinary coordination. The cases include, among others, incorrect biopsy techniques, delayed stroke diagnoses, failure to communicate pathological findings, and problematic coercive measures in pediatric patients. The legal assessments highlight the importance of thorough documentation and effective patient communication in mitigating liability risks. In several cases, diagnostic errors result in a reversal of the burden of proof in favor of the patient. The expert report emphasizes the necessity of a structured, evidence-based, and interdisciplinary approach to minimize treatment errors and their consequences.

To develop and validate a novel artificial intelligence model for predicting the initial empiric dose of vancomycin, with the aim of achieving an area under the concentration-time curve (AUC) of 400-600 mg∙h/L, using individual clinical data.

Machine learning models were developed and validated internally and externally using data from adult patients who received intravenous vancomycin treatment between November 2020 and June 2023, using records from July to September 2023, sourced from two hospitals. This study included 205, 44, and 35 patients in the training, internal validation, and external validation sets, respectively. The Random Forest, XGBoost, and Ensemble models were evaluated based on the mean squared error, root mean squared error, R-squared value, and accuracy (±20 % of the actual dose).

In internal validation, the Random Forest model achieved the highest 20% Accuracy at 56.8%, while the XGBoost model achieved 56.8% and Voting Ensemble models attained 54.5% accuracy. In external validation, the XGBoost model achieved the highest 20% Accuracy at 74.3%, followed by Random Forest and Voting Ensemble, both also achieving 74.3% accuracy. The estimated glomerular filtration rate was the most significant predictor in all models, with body weight, serum creatinine, height, and age also prominently influencing the XGBoost model's predictions.

The proposed model is capable of accurately predicting the optimal dose of vancomycin, which could aid physicians in making more informed treatment decisions regarding early therapy, particularly when AUC estimation systems are not accessible or readily available in routine clinical practice.

The overuse of antibiotics may lead to complications such as increased resistance, adverse events, and toxicities. Literature demonstrates a negative Methicillin-resistant Staphylococcus aureus (MRSA) nares polymerase chain reaction (PCR) may be used to streamline antibiotic therapy prior to respiratory culture results based on a negative predictive value (NPV) of 95-99%. Additional literature supports a high NPV when MRSA nares PCR is evaluated in non-respiratory cultures; however, this use in critically ill patients has not been studied.

The purpose of this study was to evaluate the clinical utility of MRSA nares PCR in non-respiratory cultures in critically ill patients.

This was a single centre, retrospective, cohort evaluation. Outcomes evaluated were NPV, positive predictive value (PPV), sensitivity, and specificity of MRSA nares PCR in critically ill patients. A sub-group analysis based on the site of culture (blood, urine, and wound) was also conducted.

Of the 325 patients screened, 200 critically ill patients were included for analysis. A total of 259 cultures were evaluated with blood being the most common source (n = 124). The MRSA nares PCR was positive in 34 (17%) patients and thirteen (5%) of the 259 cultures were positive for MRSA. For all cultures, the MRSA nares PCR demonstrated an NPV 99%, PPV 28%, sensitivity 77%, and specificity 85%. The subgroup analysis for the individual culture types reflected similar findings.

A negative MRSA nares PCR may be used to withhold initiation or allow for timely de-escalation of anti-MRSA antibiotics in critically ill patients if clinically applicable.

Bacteraemia and sepsis have traditionally required continued intravenous (IV) antibiotics.

This study aims to evaluate if early transition to oral antibiotics is non-inferior to continued IV antibiotic therapy in treating patients with bacteraemia and sepsis.

Data sources include MEDLINE, Embase, Web of Science, the Cochrane Library, and Wanfang databases from inception to 13 July 2024, along with clinical trial registries and Google.com.

Study eligibility criteria include randomized controlled trials (RCTs) and cohort studies.

Participants include patients with bacteraemia and sepsis.

Interventions include early transition to oral antibiotics vs. continued IV antibiotics. Early oral switch was defined as 5-9 days for uncomplicated Staphylococcus aureus bacteraemia, <4 weeks for complicated S. aureus bacteraemia, 3-7 days for uncomplicated Streptococcus bacteraemia, and 3-5 days for uncomplicated Enterobacterales bacteraemia.

Assessment of risk of bias includes Cochrane risk of bias tool and Newcastle-Ottawa Scale.

Random-effect models were used to pool the data. The primary outcome was treatment failure. The non-inferiority margin for treatment failure was 10%. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to rate the certainty of the evidence.

In total, 38 studies (6 RCTs, 10 adjusted cohorts, and 22 unadjusted cohorts) involving 11 566 patients were included. A primary analysis of 6 RCTs and 10 adjusted cohorts comprised 7102 patients. High-certainty evidence from six RCTs showed that early transition to oral antibiotics was non-inferior to continued IV therapy for treatment failure (n = 529; OR 0.89; 95% CI: 0.54-1.48). Low-certainty evidence from five adjusted cohorts also found no significant difference in treatment failure between the two groups (n = 929; OR 0.60; 95% CI: 0.29-1.72). Moderate-certainty evidence showed that oral switch therapy significantly reduced hospital stay (n = 2041; mean difference: -5.19 days; 95% CI: -8.16 to -2.22).

Early transition to oral antibiotics was non-inferior to continued IV antibiotic treatment for bacteraemia and sepsis.

Burns intensive care units (BICUs) have reduced mortality in patients with burns, but infections and sepsis remain the leading causes of death. Infections with multidrug-resistant (MDR) bacteria increase the risk of death in patients with burns, whose risk of acquiring such infections is higher due to various factors, including prolonged hospitalization and invasive procedures.

A retrospective study was performed in a French BICU over 8 years to analyze the epidemiology and risk factors for bloodstream infections (BSIs).

In total, 1402 patients were admitted to the BICU. Thermal burns were the most common cause of injury, and the median total body surface area burned was 10%. Patients had various comorbid conditions, particularly smoking and hypertension. BSI occurred in 303 (21%) patients. When compared with patients without BSI, patients with BSI were older, had higher severity scores and a larger total body surface area burned, and were more likely to develop complications. The prevalence of monomicrobial and polymicrobial BSI remained stable during hospitalization, with gram-positive pathogens such as Staphylococcus aureus most common during the first week but with gram-negative pathogens, particularly MDR Pseudomonas aeruginosa, becoming more prevalent after 15 days. The distribution of microorganisms remained stable throughout the study, except for a significant decrease in Acinetobacter baumannii rates and an increase in MDR P aeruginosa rates after 2015.

An understanding of the epidemiology of BSI-causing microorganisms over time is crucial for sepsis management to ensure the selection of appropriate empirical antimicrobial therapy and to highlight the need for infection prevention and antimicrobial stewardship.

Vancomycin is commonly dosed using standard weight-based methods before dose adjustments are made through therapeutic drug monitoring (TDM). However, variability in initial dosing can lead to suboptimal therapeutic outcomes. A predictive model that personalizes initial dosing based on patient-specific pharmacokinetic factors prior to administration may enhance target attainment and minimize the need for subsequent dose adjustments.

This study aimed to develop and evaluate a machine learning (ML)-based algorithm to predict whether an initial vancomycin dose falls within the therapeutic range of the 24-hour area under the curve to minimum inhibitory concentration, thereby optimizing the initial vancomycin dosage.

A retrospective cohort study was conducted using hospitalized patients who received intravenous vancomycin and underwent pharmacokinetic TDM consultation (n=415). The cohort was randomly divided into training and testing datasets in a 7:3 ratio, and multiple ML techniques were used to develop an algorithm for optimizing initial vancomycin dosing. The optimal algorithm, referred to as the OPTIVAN algorithm, was selected and validated using an external cohort (n=268). We evaluated the performance of 4 ML models: gradient boosting machine, random forest (RF), support vector machine (SVM), and eXtreme gradient boosting (XGB). Additionally, a web-based clinical support tool was developed to facilitate real-time vancomycin TDM application in clinical practice.

The SVM algorithm demonstrated the best predictive performance, achieving an area under the receiver operating characteristic curve (AUROC) of 0.832 (95% CI 0.753-0.900) for the training dataset and 0.720 (95% CI 0.654-0.783) for the external validation dataset. The gradient boosting machine followed closely with AUROC scores of 0.802 (95% CI 0.667-0.857) for the training dataset and 0.689 (95% CI 0.596-0.733) for the validation dataset. In contrast, both XGB and RF exhibited relatively lower performance. XGB achieved AUROC values of 0.769 (95% CI 0.671-0.853) for the training set and 0.707 (95% CI 0.644-0.772) for the validation set, while RF recorded AUROC scores of 0.759 (95% CI 0.656-0.846) for the test dataset and 0.693 (95% CI 0.625-0.757) for the external validation set. The SVM model incorporated 7 covariates: age, BMI, glucose, blood urea nitrogen, estimated glomerular filtration rate, hematocrit, and daily dose per body weight. Subgroup analyses demonstrated consistent performance across different patient categories, such as renal function, sex, and BMI. A web-based TDM analysis tool was developed using the OPTIVAN algorithm.

The OPTIVAN algorithm represents a significant advancement in personalized initial vancomycin dosing, addressing the limitations of current TDM practices. By optimizing the initial dose, this algorithm may reduce the need for subsequent dosage adjustments. The algorithm's web-based app is easy to use, making it a practical tool for clinicians. This study highlights the potential of ML to enhance the effectiveness of vancomycin treatment.

Infectious diseases have emerged as a significant global concern, posing a substantial burden in terms of high morbidity and mortality and presenting considerable challenges in clinical diagnosis and treatment. Therefore, it is highly desired to develop new strategies for sensitive and accurate bacteria detection to address the global epidemic of antibiotic resistance. In this study, a new technique utilizing a dual proximity ligation mediated chain extension and displacement strategy was developed for precise identification and highly sensitive detection of Methicillin-Resistant Staphylococcus aureus (MRSA). The antibodies recognize both protein A and PBP2a on the surface of MRSA, leading to the initiation of proximity ligation and signal amplification processes. The signal amplification procedure generated a substantial number of G-quadruplex sequences, which subsequently bind with thioflavin T (ThT) to significantly amplify its fluorescence, enabling the detection of MRSA with a low detection limit of 3.5 cfu mL-1. In this method, dual proximity ligation assays were integrated to mediate the signal amplification process, thus endowing the method with a greatly elevated specificity in both MRSA identification and signal amplification. Due to its non-label format, high selectivity, and sensitivity, this method can serve as a practical and versatile approach for detecting different bacteria in the early stages of infectious diseases.

Background/Objectives: In the race to develop new antibiotics to combat multidrug-resistant bacteria, particularly the ESKAPE pathogens which pose a significant threat to public health, silver nanoclusters (AgNCs) have emerged as a promising alternative. This article focuses on the potential of novel silver nanoclusters as an antimicrobial agent against Staphylococcus aureus, a high-priority pathogen known for its ability to cause persistent nosocomial infections and develop protective biofilms. Methods: In this study, we successfully synthesized AgNCs at pH 7 using an eco-friendly photoreduction method with poly acrylic acid (PAA) and poly methacrylic acid (PMAA) as stabilizers. This methodology produced fluorescent AgNCs, demonstrating their stability in aqueous solutions for at least three months and highlighting the effectiveness of PAA and PMAA as stabilizing agents. The AgNCs were incubated with S. aureus suspension, and the antimicrobial capability at different concentrations and times of incubation were determined. Also, the AgNCs hemocompatibility was studied by exposing the clusters to rat blood cells. Results: The in vitro assays revealed that AgNCs capping with PAA or PMAA has antimicrobial activity in low doses (the determination of minimum inhibitory concentration (MIC): 0.2 µg/mL, and the determination of minimum bactericidal concentration (MBC): 2 µg/mL) and without cytotoxicity (hemolysis less than 10%) to rat blood cells until 1 µg/mL. In the presence of both AgNCs (5 µg/mL), bacterial growth was completely inhibited within just 3 h. Conclusions: The findings of this study highlight the potential of silver nanoclusters as effective antimicrobial agents against S. aureus. Their stability, low toxicity, and rapid bactericidal activity make them promising candidates for further development in antimicrobial applications.

Antibiotics constitute the majority of prescriptions for women during pregnancy. Common bacterial infections, including urinary tract infections, skin and soft tissue infections, and upper and lower respiratory tract infections, are expected in pregnancy, similar to the general public. These infections carry additional risks to both the woman and fetus; thus, antibiotics are often prescribed. Antibiotics, like other drugs, are not benign and may carry additional risks to the fetus beyond commonly encountered adverse drug events seen across most patient populations. Since 2014, 19 new antibiotics have been approved by the United States Food and Drug Administration. Additionally, in 2018, the previously held pregnancy category rating expired, and all manufacturers' labeling was updated with new narrative language reflecting safety in pregnancy, lactation, and males and females of reproductive potential. This review provides a comprehensive summary of available data and an update to the 2015 publication regarding the safe use of antibiotics in pregnancy. The primary focus of this review is on newly approved antibiotics, along with any additional published evidence on previously reviewed antibiotics. Data on lactation or antiviral or antifungal use in pregnancy are not included. Clinicians should remain updated on current available evidence and vigilant to provide safe and effective antibiotic decision-making in pregnant women.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant concern for skin and soft tissue infections. Apart from biofilm formation, these bacteria can reside intracellularly in phagocytic and nonphagocytic mammalian cells, complicating treatment with conventional antibiotics. Lipid-polymer hybrid nanoparticle (LPN) systems, combining the advantages of polymeric nanoparticles and liposomes, represent a new generation of nanocarriers with the potential to address these therapeutic challenges. In this study, gentamicin (Gen) and vancomycin (Van) were encapsulated in LPNs and evaluated for their ability to eliminate intracellular MRSA in phagocytic macrophage RAW-Blue cells and nonphagocytic epithelial HaCaT cells. Compared to free antibiotics at 100 μg/mL, LPN formulations significantly reduced intracellular bacterial loads in both cell lines. Specifically, LPN-Van resulted in approximately 0.7 Log CFU/well reduction in RAW-Blue cells and 0.3 Log CFU/well reduction in HaCaT cells. LPN-Gen showed a more pronounced reduction, with approximately 1.26 Log CFU/well reduction in RAW-Blue cells and 0.45 Log CFU/well reduction in HaCaT cells. In vivo, LPN-Van at 500 μg/mL significantly reduced MRSA biofilm viability compared to untreated controls (p < 0.001), achieving 98% eradication based on median values. In comparison, free vancomycin achieved a nonstatistically significant 79.2% reduction in biofilm viability compared to control. Prophylactically, LPN-Van at 500 μg/mL decreased MRSA levels to the limit of detection, resulting in a ∼3.5 Log reduction in the median CFU/wound compared to free vancomycin. No acute dermal toxicity was observed for LPN-Van based on histological analysis. These data indicate that LPNs show promise as a drug delivery platform technology to address intracellular infections.

Sepsis remains a leading cause of mortality in intensive care units (ICUs), with methicillin-resistant Staphylococcus aureus (MRSA) infections presenting significant treatment challenges. The impact of MRSA co-infection on sepsis outcomes necessitates further exploration.

We conducted a retrospective observational cohort study using the Medical Information Mart for Critical Care IV (MIMIC-IV-2.2) database. This cohort study included sepsis patients, scrutinizing baseline characteristics, MRSA co-infection, antimicrobial susceptibility, and their relations to mortality through Cox regression and Kaplan-Meier analyses.

Among 453 sepsis patients analyzed, significant baseline characteristic differences were observed between survivors (N = 324) and non-survivors (N = 129). Notably, non-survivors were older (70.52 ± 14.95 vs. 64.42 ± 16.05, P < 0.001), had higher lactate levels (2.82 ± 1.76 vs. 2.04 ± 1.56 mmol/L, P < 0.001), and higher SOFA scores (8.36 ± 4.18 vs. 6.26 ± 3.65, P < 0.001). Cox regression highlighted SOFA score (HR = 1.122, P = 0.003), body temperature (HR = 0.825, P = 0.048), and age (HR = 1.030, P = 0.004) as significant predictors of 28-day mortality. MRSA co-infection was found in 98.7% of cases without a significant effect on 28-day mortality (P = 0.9). However, sensitivity to cephalosporins, meropenem, and piperacillin/tazobactam was associated with reduced mortality. The area under the ROC curve for the combined model of age, SOFA, and body temperature was 0.73, indicating a moderate predictive value for 28-day mortality.

While MRSA co-infection's direct impact on 28-day sepsis mortality is minimal, antimicrobial sensitivity, especially to cephalosporins, meropenem, and piperacillin/tazobactam, plays a critical role in improving outcomes, underscoring the importance of antimicrobial stewardship and personalized treatment strategies in sepsis care.

Holocord pathologies are diseases that include the entire spinal cord, and, in most instances, neurological cancers are the most common cause of holocord pathologies. However, in some rare instances, there are cases in which bacterial infections can extend into deeper spaces, causing spinal epidural abscesses (SEA), holocord SEA (HSEA), or even rarer spinal subdural abscesses (SSA). Current discussions surrounding the management of HSEA, SEA, or SSA primarily involve early surgical intervention and subsequent antibiotics. However, in this case, we present a patient with methicillin-resistant Staphylococcus aureus (MRSA) holocord subdural abscess, along with epidural and paraspinal abscesses who was treated with intravenous antibiotics and no surgical intervention. A discussion regarding this rare disease, along with the treatment of MRSA holocord, is also included.

Using data from the large and geographically diverse Military Health System (MHS) beneficiary population, we aimed to characterize and update the epidemiology and microbiology of pediatric orbital cellulitis given previous data are limited to small, single-center studies.

Following institutional review board approval, we performed a retrospective analysis using the Military Health System admissions, microbiology, and pharmacy data between June 2009 and September 2019. Patients less than 22 years of age with radiological confirmation of orbital cellulitis were included. Demographic data, presence of sinusitis, advanced imaging reports, blood and wound culture results with antibiotic susceptibilities, and antibiotic prescriptions were collected. Descriptive statistics were used to summarize demographic characteristics. Imaging findings were grouped by Chandler's stage (CS), an imaging-based measure of the progressive severity of orbital involvement. A Cochran-Armitage trend test was used to evaluate the relationship between CS and likelihood of positive confirmatory culture.

There was a male predominance (66.9%) and 55.5% of subjects had comorbid sinusitis. Of the 130 subjects included, 33.8% had one or more positive cultures, 30.8% had a positive wound culture, and 4.6% had a positive blood culture. The most identified organism was coagulase-negative staphylococci (23.3%), followed by Staphylococcus aureus (18.9%), Streptococcus intermedius (17.8%), and strict anaerobes as a group (13.3%). Gram-negative organisms were rare. Twenty-five percent of S. aureus were methicillin-resistant. Clindamycin resistance was identified in 9% of all S. aureus, 50% of coagulase-negative staphylococci, and 25% of S. intermedius. Clindamycin plus ceftriaxone was the most prescribed empiric antibiotic regimen (36.2%). Likelihood of a positive culture significantly increased with advancing CS.

Orbital cellulitis occurs most frequently in males with sinusitis. Likelihood of positive wound culture is increased with a more advanced CS. Staphylococcus and Streptococcus spp. and anaerobes are the most identified pathogens in orbital cellulitis, while gram-negative organisms are rare. Empiric antibiotic selection should include an anti-methicillin-resistant S. aureus agent combined with a broad-spectrum beta-lactam and anaerobic coverage.

Vancomycin (VCM) induces nephrotoxicity in a dose-dependent manner, and patients with risk factors for nephrotoxicity have been reported to develop nephrotoxicity even within the effective concentration range. In the present study, we investigated measures to set an appropriate AUCss for each case by assessing the risk of developing nephrotoxicity using logistic regression curves, separating patients into a High-risk group with risk factors associated with nephrotoxicity when VCM is used and a Low-risk group without risk factors.

A multivariate logistic regression analysis was used to identify risk factors for nephrotoxicity. The AUCss threshold was selected by a CART analysis and ROC curves, and a logistic regression analysis was used to examine the relationship between AUCss and the probability of developing nephrotoxicity.

The incidence of nephrotoxicity was 31.7% (33/104) in the High-risk group and 13.0% (14/108) in the Low-risk group, and was significantly higher in the former (p = 0.001). The AUCss threshold was set at 575 mg·h/L for the High-risk group and 650 mg·h/L for the Low-risk group. The probability of developing nephrotoxicity in the High-risk group (104 patients) was high: AUCss 400 mg·h/L (16.8%), 500 mg·h/L (23.3%), and 575 mg·h/L (29.3%). The target concentration range was newly set at 400 ≤ AUCss < 500, suggesting that the target AUCss needs to be considered for each patient based on the balance between therapeutic efficacy and the prevention of adverse effects. The probability of developing nephrotoxicity in the Low-risk group (108 patients) was AUCss 500 mg·h/L (4.7%), 575 mg·h/L (8.4%), and 650 mg·h/L (14.6%). Since the Low-risk group has a high safety profile, the target concentration range was newly set at 400 ≤ AUCss < 650, suggesting the safe administration of the drug up to AUCss 650 mg·h/L while aiming for AUCss 600 mg·h/L from the initial dose design.

In the present study, the risk of nephrotoxicity for each AUCss was quantitatively analyzed using logistic regression curves for the High- and Low-risk groups. This allowed for the proposal of strategic individual target concentrations based on the balance between risk and benefit.

Staphylococcus aureus is a common pathogen, often recovered from children's infections. Βiofilm formation, antimicrobial resistance and production of adhesins and toxins contribute to its virulence. As resistance to antimicrobials rises worldwide, alternative therapies like bacteriophages (among them the well-studied Bacteriophage K) can be helpful. The aim of this study was to determine the bacteriophage and antimicrobial susceptibility and the presence of virulence genes among S. aureus from infections in children and adolescents. Eighty S. aureus isolates were tested for biofilm formation and antimicrobial susceptibility. The presence of two genes of the ica operon (icaA, icaD), adhesin's (fnbA, fnbB, sasG) and toxin's genes (PVL, tst, eta, etb) was tested by PCRs. Susceptibility to Bacteriophage K was determined using a spot assay. Thirteen isolates were methicillin-resistant (MRSA) and 41 were multi-resistant. Twenty-five S. aureus (31.3%) were resistant to Bacteriophage K, mostly from ocular and ear infections. Twelve S. aureus (15%) were PVL-positive, seven (8.8%) positive for tst, 18 (22.5%) were eta-positive and 46 were (57.5%) etb-positive. A total of 66 (82.5%) isolates carried fnbA, 16 (20%) fnbB and 26 (32.5%) sasG. PVL, tst and sasG carriage were more frequent in MRSA. Bacteriophage-susceptible isolates carried more frequently eta (32.7%) and etb (69.1%) compared to phage-resistant S. aureus (0% and 32%, respectively). Although mainly methicillin-sensitive, S. aureus from pediatric infections exhibited high antimicrobial resistance and carriage of virulence genes (especially for exfoliative toxins and fnbA). MRSA was associated with PVL, tst and sasG carriage, whereas Bacteriophage susceptibility was associated with eta and etb. The high level of Bacteriophage K susceptibility highlights its potential use against staphylococcal infections.

The increasing incidence of antibiotic resistance in Staphylococcus aureus (S. aureus) poses a substantial threat to global public health. In recent decades, the evolution of bacteria and the misuse of antibiotics have led to a progressive development in drug resistance of S. aureus, resulting in a worldwide rise in methicillin-resistant S. aureus (MRSA) infection rates. Understanding the molecular mechanisms underlying staphylococcal drug resistance, the treatments for staphylococcal infections, and the efficacy of nanomaterials in addressing multi-drug resistance is crucial. This review explores the resistance mechanisms, which include limiting drug uptake, target modification, drug inactivation through the production of degrading enzymes, and active efflux of drugs. It also examines the current therapeutic strategies, such as antibiotic combination therapy, phage therapy, monoclonal antibody therapy, and nanoparticle therapy, with a particular emphasis on the role of silver-based nanomaterials. Nanoparticles possess the ability to overcome multi-drug resistance, offering a novel avenue for the management of drug-resistant bacteria. The nanomaterials have demonstrated potent antibacterial activity against S. aureus through various mechanisms, including cell membrane disruption, generation of reactive oxygen species (ROS), and inhibition of essential cellular processes. It also highlights the need for further research to optimize nanoparticle design, enhance their antibacterial potency, and ensure their biocompatibility and biodegradability. The review ultimately concludes by emphasizing the importance of a multifaceted approach to treatment, including the development of new antibiotics, investment in stewardship programs to prevent antibiotic misuse, and the exploration of natural compounds and bacteriocins as potential antimicrobial agents.

It has been reported that the protein binding rate of vancomycin (VCM) varies among individual patients. So, the authors investigated relevant factors that may affect free VCM concentration and target attainment of free area under the concentration-time curve (fAUC).

Thirty-nine patients were included. Multiple regression analysis was performed to determine the valuable factors in the free VCM concentration, and the target attainment of area under the concentration-time curve (AUC) 400-600 mg・h/L and fAUC200-300 mg・h/L was calculated.

We found total protein was significant covariate for free VCM. Among 18 patients who were investigated for AUC and fAUC estimation, 9 patients (50.0%) and 12 patients (66.7%) reached AUC > 600 mg・h/L, and fAUC > 300 mg・h/L (p = 0.310), respectively.

Total protein is a significant predictor for free VCM estimation. And the fAUC-guided TDM for VCM TDM may contribute to more strict dosing than the AUC-guided TDM in hyper- or hypo-proteinemic population.

Retrospectively registered.

Pathophysiologic changes in the early and late phases of septic shock affect the pharmacokinetic (PK) parameters, varying dose adjustments may be necessary. This study aimed to create the PK models of vancomycin in the early and late phases of septic shock and to describe the association between the area under the curve from 0 to 24 h (AUC0-24) and acute kidney injury (AKI). The data from patients with septic shock receiving vancomycin was collected either prospectively or retrospectively. A nonlinear mixed-effects modeling approach was used to develop the PK models. A total of 208 septic shock patients were enrolled and classified into the early (n = 96) and the late phase (n = 112). A two-compartment PK model is the best base model for both phases of septic shock. The model that best predicted the clearance (CL) of both phases was the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, which was not indexed to body surface area (BSA). Albumin (ALB) was a covariate associated with vancomycin CL only in the late phase. The typical values of CL and volume of distribution (Vd) in the early phase were 1.71 L/h and 68.94 L. In the late phase, CL was 1.65 L/h, and Vd was 66.36 L. The AKI was observed in patients with a high simulated AUC0-24. The population PK model of vancomycin in the early and late phases of septic shock has been established. The CKD-EPI not indexed to BSA predicts vancomycin CL in both phases. ALB was associated with CL in the late phase.

Rifampin is commonly used to treat device-related infections (DRIs) due to its activity against biofilms, despite a history of limited clinical evidence to support its use. Evidence published since 2011 regarding rifampin use for DRIs is reviewed to describe the contemporary findings and ongoing considerations for rifampin use in these infections.

A literature review was performed by searching PubMed and Google Scholar to identify relevant studies evaluating systemic rifampin use for the treatment of DRIs published from 2011 to 2023. References of identified studies were also screened for additional pertinent studies. Sixty-eight studies were identified, and 48 met the inclusion criteria. Rifampin efficacy was evaluated as both a primary outcome for cardiac device infections (n = 3) and prosthetic joint infections (n = 21) and as a nonprimary outcome (n = 24). Overall, the studies were primarily retrospective (n = 36) and small, with sample sizes ranging from 14 to 842 patients, and varied greatly with respect to prosthesis site, surgical intervention, pathogen, infection time frame, and antibiotic combination and duration. Efficacy outcome results varied greatly, with statistically significant evidence for the efficacy of rifampin combination in DRIs limited to a single study of prosthetic vascular graft infections and 13 studies of prosthetic joint infections.

The modern literature provides conflicting results regarding the benefit and lack of benefit with rifampin combination therapy in DRIs. Additional, robust research is imperative to solidify the ongoing role of rifampin in DRIs.

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.

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern due to its resistance to conventional antibiotics. This study evaluated the efficacy of liposome-encapsulated vancomycin against MRSA using phospholipids extracted from egg yolk. Liposomes were prepared via the freeze-thaw method, yielding vesicles with an average diameter of 157.01 ± 33.04 nm and a polydispersity index (PDI) of 0.0442, indicating uniformity and stability. Antibacterial activity was assessed using the microdilution method. Liposome-encapsulated vancomycin demonstrated complete bacterial growth inhibition (100%) against MRSA ATCC 2758 at dilutions of 101 and 102, compared to only 50% inhibition by free vancomycin at 101. At higher dilutions (103), liposome-encapsulated vancomycin maintained 70% inhibition, whereas free vancomycin was ineffective. In vivo studies using a murine wound infection model revealed that wounds treated with liposome-encapsulated vancomycin achieved superior healing, with complete tissue regeneration observed by day 14. Histological analysis showed reduced inflammation and enhanced tissue recovery in liposome-encapsulated vancomycin-treated groups, compared to fibrosis and persistent necrosis in free vancomycin-treated groups. By enabling sustained drug release and improved bioavailability, liposomal formulations minimized required dosages and systemic toxicity, reducing the risk of resistance development. This study highlights the clinical potential of liposome-encapsulated vancomycin as a scalable, cost-effective treatment for MRSA, particularly in resource-limited settings.

Preterm and low-birth-weight neonates are particularly susceptible to methicillin-resistant Staphylococcus aureus (MRSA) colonization, whereas MRSA infection is associated with significant neonatal morbidity and mortality globally. The objective of our study was to examine the current body of knowledge about molecular traits, epidemiology, risk factors, clinical presentation, decolonization techniques, and available treatments for MRSA infection in neonates. MRSA strains that predominate in neonatal units, namely healthcare-associated (HA)-MRSA, differ from community-acquired (CA)-MRSA strains in molecular characteristics, toxin synthesis, including Panton-Valentine leukocidin, and resistance to antibiotics. Colonization with MRSA predisposes neonates to infection. The clinical impact of MRSA infection includes bacteremia, sepsis, pneumonia, endocarditis, osteomyelitis, septic arthritis, skin and soft tissue infections, and toxic shock syndrome. To reduce MRSA transmission, colonization, and infection, customized approaches are required, including continuous surveillance of MRSA epidemiology, new techniques for detecting MRSA resistance, and the application of basic preventive measures. Antimicrobial susceptibility monitoring is essential to identify the best empirical antimicrobial treatments. The growing antibiotic resistance of MRSA remains challenging, and vancomycin is still the best option. Further extensive research and surveillance are warranted to explore the genetic diversity and prevalence of MRSA.

We conducted a systematic review of randomized, controlled trials (RCTs) to generate more precise estimates of the efficacy and safety of oral versus intravenous antibiotic therapy for Staphylococcus aureus bacteremia or endocarditis.

MEDLINE, Embase, the Cochrane Library, and Web of Science databases were searched through February 2024. RCTs were included if they compared oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis and appropriately reported outcomes for each group. Risk of bias was assessed using the revised Cochrane tool for assessing risk of bias in randomized trials. Heterogeneity between studies was evaluated with Cochran's Q-statistic and I2 test. Treatment effects were summarized with pooled risk ratios using a random effects model meta-analysis (PROSPERO CRD42024481512).

Only four RCTs met criteria for inclusion in meta-analysis. Among participants assessed for treatment failure, there was no difference between oral and intravenous therapy groups (risk ratio [RR], 0.99; 95% confidence interval [CI], .63-1.57; I2 = 0%). There was also no significant difference in adverse events between oral and intravenous therapy groups (RR, 0.65; 95% CI, .07-5.94; I2 = 74%); however, the confidence interval was wide, and heterogeneity was high.

In this systematic review of RCTs comparing oral with intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, few studies met the eligibility criteria for inclusion. Meta-analysis of these studies suggests that transitioning from intravenous to oral therapy is likely effective in a subgroup of carefully selected patients. Additional randomized trials are necessary before transition to oral therapy can be routinely recommended.

The latest consensus recommends using the ratio between the area under the curve over 24 h (AUC0-24) and minimal inhibitory concentration (MIC) as the therapeutic target for vancomycin in clinical practice, with a Bayesian approach and population pharmacokinetic (popPK) model being particularly recommended. While using both post-dose peak concentration (Cpeak) and pre-dose concentration (Ctrough) is more accurate than Ctrough alone, the optimal sampling strategy for estimating AUC0-24 is still unclear. The objective of this study was to determine the best sampling time(s) to estimate AUC0-24 using the Bayesian approach in these specific adult hematologic cancer patients.

A virtual population (n = 7000) was simulated based on the distribution of the significant covariates (ideal body weight and estimated glomerular filtration rate) from the population used to develop the previous pharmacokinetic model. The dosing regimens from the Le Blanc et al. nomogram were used to generate, with NONMEM® (v.7.5), simulated pharmacokinetic (PK) profiles of one loading dose followed by three maintenance doses (steady state). Strategies involving two samples taken during earlier maintenance doses and one sample taken at steady state were tested using the Bayesian approach to predict PK parameters. These strategies were then evaluated for their ability to predict AUC0-24 at steady state (AUC0-24,ss) RESULTS: For single-sample strategies, a sample taken anytime from 4 h post-dose can estimate AUC0-24,ss with precision similar to Ctrough (R2 ≈ 0.75), regardless of renal function (R2 ≈ 0.73-0.77). For two-sample strategies, taking samples at least midway through the dosing interval provides the highest precision for estimating AUC0-24,ss during the first two maintenance doses (R2 ≈ 0.75-0.77). In both strategies, using Cpeak did not yield as precise results as sampling midway through the dosing interval or at Ctrough.

This study is the first to test multiple limited sampling strategies using a dosing nomogram stratified by renal function. The results show that vancomycin sampling can extend beyond traditional Cpeak and Ctrough without compromising the accuracy of maximum a posteriori Bayesian estimation of AUC0-24,ss, thereby providing an opportunity to investigate these limited sampling strategies combined with model-informed precision dosing in a clinical setting.

Clindamycin is a lincosamide antibiotic for the treatment of staphylococcal, streptococcal, and anaerobic bacterial infections. We conducted a single-center, single-dose, 2-preparation, 2-period, 2-sequence, randomized, open-label, 2 × 2 crossover study to evaluate the pharmacokinetics (PKs) and safety of the test and reference clindamycin hydrochloride capsules in healthy Chinese subjects under both fasted and fed conditions. Forty-eight subjects were enrolled in the study totally, with 24 subjects in each group. All subjects were asked to take a test or reference preparation, under either fasted or fed condition, and their blood samples were collected and assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. PK parameters including maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last concentration, and area under the plasma concentration-time curve from time 0 to infinity were estimated with noncompartmental model and analyzed. Results showed that the PK profiles of the 2 preparations were consistent and met the bioequivalence criteria. Food was identified as a factor that had an impact on clindamycin absorption. The safety of clindamycin hydrochloride capsules was satisfactory. This study proved that the 2 clindamycin hydrochloride capsules were bioequivalent in healthy Chinese subjects under both fasted and fed conditions.

The Gram-positive cocci Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. are the most frequent causative organisms of bloodstream infections and infective endocarditis. "Complicated bacteremia" is a term used in S. aureus bloodstream infections and originally implied the presence of metastatic infectious foci (i.e. complications of S. aureus bacteremia). These complications demand longer antimicrobial treatment durations and, frequently, interventional source control. Several risk factors for the incidence of bacteremia complications have been identified and are often used for the definition of complicated bacteremia. Here, we discuss management and diagnostic approaches and treatment options for patients with complicated bacteremia, with particular focus on infective endocarditis. We also summarize the available evidence regarding imaging modalities and the choice of antimicrobial mono- or combination therapy according to resistance patterns for these pathogens as well as treatment durations and optimized application routes. Finally, we synopsize current and future areas of research in complicated bacteremia and infective endocarditis.

Children with acute hematogenous osteomyelitis (AHO) from methicillin-resistant Staphylococcus aureus (MRSA) are treated with vancomycin despite the risk of acute kidney injury (AKI). This study evaluates the rate of AKI and resource utilization for children with or without AKI when vancomycin is used in this setting.

Children with MRSA AHO treated with vancomycin were retrospectively studied. AKI was assessed by clinical diagnosis and Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cohorts of children with or without AKI were compared for differences in treatment, resource utilization, and outcomes. Multivariate logistic regression analysis assessed factors associated with risk for AKI. Cost analysis was performed using the Pediatric Health Information System and Healthcare Cost and Utilization Project databases.

Among 85 children studied, 14 (16.5%) had chart-diagnosed AKI and 24 (28.2%) met KDIGO criteria. Children with AKI had more febrile days and higher thrombosis rates. They had longer vancomycin treatment (8 vs 5 d), higher troughs (27.8 vs 17.5 mg/L), and prolonged hospitalization (19.9 vs 11.1 d). Multivariate analysis found a maximum vancomycin trough level (odds ratio: 1.05, P = 0.003) with a cutoff of 21.7 mg/L predicted AKI.Only 2 of 20 (10%) children who had MRSA isolates with a minimum inhibitory concentration of 2 achieved therapeutic vancomycin levels. Pediatric Health Information System data of 3133 children with AHO treated with vancomycin identified 75 (2.4%) with AKI who had significantly longer lengths of stay (13 vs 7 d) and higher billed charges ($117K vs $51K) than children without AKI.

Chart documentation of AKI (16.5%) grossly underestimated KDIGO-defined occurrence (28.2%). This study showed that vancomycin-associated AKI required substantially greater resource utilization and higher health care costs. Lowering the targeted trough range, shortening the duration of vancomycin therapy, and considering alternative antibiotics when minimum inhibitory concentration ≥2 will reduce the risk and cost of AKI among children with MRSA AHO.

Level III-retrospective comparative therapeutic study.

Septic arthritis of the pubic symphysis is a rare postpartum infection characterized by severe pelvic pain, fever, and elevated inflammatory markers. It is often underdiagnosed due to its rarity and nonspecific symptoms. It is commonly caused by Staphylococcus aureus, with methicillin-resistant Staphylococcus aureus (MRSA) septic being a rare but concerning pathogen.

We report the case of a 36-year-old woman who developed septic arthritis of the pubic symphysis caused by MRSA after spontaneous vaginal delivery.

Differentiating between diastasis and septic arthritis of the pubic symphysis is crucial for treatment. Noninfective pubic osteitis can mimic septic arthritis, presenting a diagnostic challenge. Imaging, laboratory data, and cultures are essential for accurate diagnosis. MRSA colonisation during pregnancy and postpartum trauma may facilitate infection. MRI is the most sensitive imaging modality for early detection and monitoring.

Septic arthritis of the pubic symphysis secondary to MRSA is a rare cause of postpartum pelvic pain. Prompt diagnosis and treatment are essential for favourable outcomes.

Classification of patients with Staphylococcus aureus bacteremia as complicated versus uncomplicated is based on a combination of clinical and microbiologic variables. Whether daily body temperature and common laboratory tests such as C-reactive protein (CRP) and white blood cell (WBC) can improve risk stratification algorithms is unclear.

We conducted a post hoc secondary analysis of the CAMERA2 trial, which enrolled hospitalized adult patients with methicillin-resistant S aureus bacteremia and prospectively collected daily body temperature and peripheral blood WBC and CRP. We evaluated the prognostic relevance of each parameter by calculating crude and adjusted odds ratios for 90-day all-cause mortality comparing patients with the abnormal parameter of interest versus those with normal parameters on each day of illness.

A total of 345 patients were included in this analysis, of whom 63 (18.3%) died within 90 days. Fever (body temperature ≥38.0 °C) was associated with increased odds of 90-day mortality from day 4 and onwards. Fever later in the illness course was associated with higher adjusted odds of mortality (8.78; 95% confidence interval, 2.78-27.7 on day 7 vs adjusted odds ratio 3.70; 95% CI, 1.58-8.67 on day 4). In contrast, CRP and abnormal WBC count did not demonstrate a consistent or temporal association with mortality.

Persistent fever after 72 hours is associated with increased mortality in patients with methicillin-resistant S aureus bacteremia, supporting recommendations that this should be kept as a criterion for classifying patients as either "high-risk" or "complicated." Within this dataset, there was limited additional predictive value in WBC or CRP.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality rates. Optimal antibiotic dosage plays a crucial role in reducing MRSA burden; thus, the use of therapeutic drug monitoring (TDM) in the clinical practice, especially of new drugs such as ceftobiprole, ceftaroline, dalbavancin, and oritavancin, should be implemented.

We aim to examine and summarize the available evidence about TDM of anti-MRSA molecules, with a focus on pneumonia, endocarditis and vascular infections, and bone and joint infections.

We applied 'therapeutic drug monitoring' and 'Staphylococcus aureus' as search terms in PubMed, considering a time frame of 24 years (2001-2024). Articles in English language, non-duplicated, evaluating antibiotic therapeutic target, and role of TDM were included in the study.

In this review, available data for therapeutic target and TDM were critically analysed and summarized and suggestions about the use of old and new anti-MRSA antibiotics were provided, focusing on optimal dosages, tissue penetration according to infection types, and toxicity. Limitations to the widespread use of TDM in clinical practice were discussed.

The use of TDM may play an important role for the optimal management of patients with MRSA infections and may impact on patient outcomes by increasing efficacy and reducing the risk of adverse events. TDM may be implemented in clinical practice; however, several limitations such as the wide variability in the methodology and the need for skilled personnel need to be considered.

Blood cultures obtained in the emergency department (ED) may become positive after discharge. Healthcare professionals must determine if these results represent true infection or a likely contaminant. An institutional algorithm was developed to assist with healthcare professional response to positive blood cultures for S. aureus and coagulase-negative staphylococci (CoNS) in these situations.

We conducted a single system, multisite cohort study comparing before and after implementation of an ED decision-making algorithm from November 2022 to December 2023. Adults were included if they were discharged from the ED before blood cultures became positive for Staphylococcus species. The primary outcome was the difference in rates of patients called back to the ED pre- and postalgorithm implementation. Secondary endpoints evaluated algorithm adherence and safety.

A total of 253 patients, 188 pre- and 65 postimplementation, were enrolled. There was a 7.3% reduction in patients called back to the ED after algorithm implementation (95% CI [-21.1 to 6.3], P = .3). Algorithm adherence after implementation was 84.6% with a difference in actual and algorithm-based callback rates of 4.6%. After algorithm implementation, no patients deemed to have a contaminant experienced an infectious-related safety event.

This time-saving algorithm was well received by our ED professionals and served as a helpful tool in safely and effectively triaging patients who had positive blood cultures for Staphylococcus species after discharge to determine who should be called back for further evaluation. There was a nonstatistically significant but clinically meaningful reduction in callback rates. Postimplementation algorithm adherence was high, and the majority of callback decisions were appropriate.

To analyze the associations between adherence to quality indicators (QIs) in the treatment of bloodstream infections caused by methicillin-susceptible Staphylococcus (S.) aureus (MSSA) and in-hospital mortality.

A retrospective observational study was conducted in patients admitted between 2019 and 2023 to Hospital St. Georg in Leipzig, Germany, with at least one positive blood culture for S. aureus. Ten QIs were categorized into four groups based on blood culture results, echocardiography, antibiotic treatment, and other parameters such as infectious disease (ID) specialist consultation. Propensity score (PS) matching was used to compare in-hospital mortality between MSSA patients treated with flucloxacillin and those treated with cefazolin. Multivariate Cox regression analysis was performed to determine risk factors associated with in-hospital mortality.

Of the 637 patients with S. aureus bloodstream infections, 495 patients with MSSA infection (77.8%) were included in the study. After the introduction of mandatory ID consultation in 2020, the median QI score increased to 9 out of a maximum of 10 points and was significantly higher in surviving cases than in fatal cases in subsequent years. There was a non-significant decrease in in-hospital mortality from 2019 (28.8%) to 2023 (22.7%) (p = 0.432). Based on PS matching, cefazolin had a favorable hazard ratio of 0.44 (95% CI 0.28-0.71; p < 0.001) for in-hospital mortality. The results of multivariate Cox regression analysis showed a significantly higher survival rate in patients who received QI-based management, including transesophageal echocardiography and antibiotic therapy initiated within 24 h.

ID consultation is associated with better adherence to quality improvement measures. Targeted MSSA therapy with cefazolin, early initiation of antibiotic therapy, and adherence to antimicrobial treatment protocols increased survival rates in our study setting.