INTRODUCTIONCeftaroline is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) that was recently launched in Singapore. It received approval from the United States (US) Food Drug Administration (FDA) and European Commission for the treatment of adult patients with community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTI). This study aimed to review current published data and determine its clinical role, particularly in the local setting.

MATERIALS AND METHODSA literature review on published articles in English on ceftaroline, focusing in particular on clinical trials and other clinical reports. Susceptibility testing was also performed on a limited sample of local MRSA and Streptococcus pneumoniae isolates.

RESULTSCeftaroline has an extensive spectrum of activity, including coverage of MRSA and multidrug-resistant S. pneumoniae. However, it has limited activity against non-fermenting Gram-negative bacteria and is susceptible to hydrolysis by extended spectrum beta-lactamases. It is only available for intravenous delivery, with a reconstituted stability of just 6 hours, rendering it unavailable for use for outpatient antibiotic therapy. Clinical trials demonstrate non-inferiority compared to first-line comparators in the treatment of CAP and cSSTI. Published case reports/series suggest a potential greater role in the treatment of MRSA bacteremia and endocarditis. No resistance was found among local archived MRSA and S. pneumoniae isolates.

CONCLUSIONWe believe ceftaroline will occupy primarily niche roles for culture-directed treatment of various infections--in particular those caused by MRSA--until further clinical trial data become available. A variety of factors render it less useful or appealing for empirical treatment of CAP or healthcare-associated infections.

Cephalosporins ; pharmacology ; therapeutic use ; Humans ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Singapore ; Staphylococcal Infections ; drug therapy

To understand the clinical characteristics of Staphylococcus aureus bloodstream infection and the main risk factors affecting clinical prognosis, providing a reference for clinical prevention and control of Staphylococcus aureus bloodstream infection. In this study, the clinical data of 152 patients with Staphylococcus aureus bloodstream infection admitted to Guangdong Provincial People's Hospital from January 2019 to December 2021 were retrospectively analyzed by reviewing the electronic medical record system, including underlying diseases, clinical characteristics, risk factors, and bacterial resistance. Statistical methods such as Chi-Squared Test and t Test were used to analyze the related risk factors that may affect the clinical characteristics and prognosis of patients with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection, then the variables with P<0.05 in univariate analysis were included in the multivariate logistic regression model to analyze the independent risk factors of poor prognosis. The results showed among 152 patients with Staphylococcus aureus bloodstream infection, 50 patients (32.89%) were infected with MRSA. In comparison, 102 patients (67.11%) were infected with methicillin-sensitive Staphylococcus aureus (MSSA). Except for rifampicin, the resistance rate of MRSA to commonly used antibiotics was all higher than that of MSSA, and the difference was statistically significant (Chi-square values were 8.272, 11.972, 4.998, 4.776, respectively;all P-values are less than 0.05). Strains resistant to vancomycin, linezolid, and quinupristin/dalfopristin were not found. In the MRSA group, indwelling catheter and drainage tube, carbapenems, and β-lactamase inhibitor treatment were significantly higher than the MSSA group. The difference was statistically significant (P<0.05). The incidence of poor prognosis of bloodstream infection in the MRSA group was higher than that in the MSSA group (34.00% vs 13.73%), and the difference was statistically significant (χ²=8.495, P<0.05). No independent risk factors associated with poor prognosis were found in the included patients with MRSA bloodstream infection.Multivariate Logistic regression model analysis showed that solid malignant tumors (OR=13.576, 95%CI: 3.352-54.977, P<0.05), mechanical ventilation (OR=7.468, 95%CI: 1.398-39.884, P<0.05) were the most important independent risk factors for poor prognosis in patients with Staphylococcus aureus bloodstream infection. In summary, the poor prognosis rate of MRSA bloodstream infection is higher than that of MSSA. The clinical evaluation of related risk factors should be strengthened, targeted prevention and control interventions should be taken to improve the prognosis of patients with Staphylococcus aureus bloodstream infection, and the use of antibiotics should be rational and standardized, to control bacterial infection and drug resistance effectively .
Humans ; Methicillin-Resistant Staphylococcus aureus ; Staphylococcus aureus ; Retrospective Studies ; Prognosis ; Staphylococcal Infections/microbiology* ; Anti-Bacterial Agents/pharmacology* ; Methicillin/therapeutic use* ; Sepsis

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has become of great concern in both hospital and community settings. To evaluate the prevalence and risk factors for methicillin resistance among Staphylococcus aureus, blood isolates in our Emergency Department (ED) were collected. All patients with S. aureus bacteremia (SAB) who presented to the ED from January 2000 to August 2005 were included, and a retrospective study was performed. A total of 231 patients with SAB were enrolled (median age, 59 yr; M:F, 125:106). Among these patients, methicillin-resistant strains accounted for 27.3% (63 patients). Catheter-related infection was the most frequent primary site of SAB (39.0%), followed by skin and soft tissue infection (16.5%). In multivariate analysis, recent surgery (OR, 3.41; 95% CI, 1.48-7.85), recent hospitalization (2.17; 1.06-4.62), and older age (> or =61 yr) (2.39; 1.25-4.57) were independently associated with the acquisition of methicillin-resistant strains. When antimicrobial therapy is considered for the treatment of a patient with suspected SAB, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage for patients with risk factors: older age, recent hospitalization, and recent surgery.
Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Cross Infection/blood/drug therapy/microbiology ; Emergency Service, Hospital/statistics & numerical data ; Female ; Humans ; Male ; Methicillin/pharmacology/*therapeutic use ; *Methicillin Resistance ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; Risk Factors ; Staphylococcal Infections/blood/drug therapy/*microbiology ; Staphylococcus aureus/*drug effects/isolation & purification

Since its first isolation in 1997, vancomycin-intermediate Staphylococcus aureus (VISA) has been a clinical concern because it may lead to treatment failure. Up to the present, there were two reports of clinical VISA cases in Korea. We now report two additional cases of VISA with the minimum inhibitory concentration (MIC) of 4 microgram/mL. The first patient was a 59 yr-old man who had undergone total hip replacement arthroplasty in 1999 due to avascular necrosis of femur heads. He had recurrent episodes of infected hip caused by methicillin-resistant Staphylococcus aureus (MRSA) and was treated with vancomycin. He underwent replacement operation of prosthesis. Cultures of joint fluid and joint tissue grew S. aureus. Vancomycin MIC as determined by a broth microdilution method was 4 microgram/mL for the both isolates. The patient was treated with high enough doses of vancomycin to maintain serum trough concentrations at 20-25 microgram/mL for 52 days and was discharged. The second patient was a 57 yr-old man with diabetes. He lost consciousness from drinking. After recovery of consciousness, he was diagnosed with aspiration pneumonia. MRSA and Acinetobacter baumannii were cultured from sputum and the patient was treated with vancomycin and meropenem. During hospitalization, bed sores developed in his ankle and back. A wound culture from the sore grew S. aureus with vancomycin MIC of 4 microgram/mL. Since infection was localized, systemic antibiotics did not seem necessary, and the patient was transferred to another hospital for isolation and management.
Acinetobacter Infections/drug therapy ; Acinetobacter baumannii/isolation & purification ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Humans ; Joints/microbiology ; Male ; Methicillin-Resistant Staphylococcus aureus/*isolation & purification ; Microbial Sensitivity Tests ; Middle Aged ; Pressure Ulcer/microbiology ; Staphylococcal Infections/*drug therapy ; Thienamycins/pharmacology/therapeutic use ; Vancomycin/pharmacology/*therapeutic use ; *Vancomycin Resistance

BACKGROUND: We estimated the prevalence and clinical impact of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA). The concordance between macromethod and glycopeptide resistance detection (GRD) E tests was determined. In addition, predictors of clinical outcomes in hospitalized patients with S. aureus bacteremia (SAB) or pneumonia (SAP) were evaluated. METHODS: We obtained 229 consecutive S. aureus isolates from all hospitalized patients at two university hospitals located in Busan and Yangsan, Korea. Standard, macromethod, and GRD E tests were performed. Additionally, we reviewed the medical records of all patients. Among the 229 patients, predictors of clinical outcomes were analyzed for 107 patients with SAB and 39 with SAP. RESULTS: Among the 229 isolates, 34.5% of S. aureus isolates and 50.7% of methicillin-resistant S. aureus isolates exhibited the hVISA phenotype based on the macromethod E test. hVISA was nearly associated with treatment failure in patients with SAB (P=0.054) and was significantly associated with treatment failure in patients with SAP (P=0.014). However, hVISA was not associated with 30-day mortality in patients with SAB or SAP. The concordance between the macromethod and GRD E tests was 84.2%. CONCLUSIONS: hVISA is quite common in the southeastern part of Korea. hVISA is associated with treatment failure in patients with SAP.
Aged ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacteremia/drug therapy/epidemiology/microbiology ; Drug Resistance, Bacterial/*drug effects ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus/drug effects/isolation & purification ; Microbial Sensitivity Tests ; Middle Aged ; Phenotype ; Pneumonia/drug therapy/epidemiology/microbiology ; Prevalence ; Republic of Korea/epidemiology ; Staphylococcus aureus/*drug effects/isolation & purification ; Teicoplanin/pharmacology ; Vancomycin/pharmacology/*therapeutic use

Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; pharmacology ; Coal Mining ; Cross Infection ; complications ; microbiology ; Drug Therapy, Combination ; therapeutic use ; Humans ; Male ; Methicillin ; pharmacology ; Methicillin Resistance ; Microbial Sensitivity Tests ; Middle Aged ; Pneumonia ; drug therapy ; etiology ; Silicosis ; classification ; complications ; Staphylococcus aureus ; drug effects ; Treatment Outcome

BACKGROUNDOur pervious antibacterial studies on several traditional Chinese medicines have found that Patchouli oil from Pogostemon cablin had significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), which has spread worldwide and infected innumerable people. In order to find the more active natural substances in Patchouli oil, one of the major components, Pogostone, was isolated and its antibacterial activity was evaluated in vitro and in vivo in this study.

METHODSIn vitro test, Pogostone was screened for antimicrobial properties against 83 bacteria comprising 35 gram positive and 48 gram negative bacteria strains via the agar double dilution method. In vivo test, specific pathogen free (SPF) strain of both male and female white Kunming mice, weighing 18-22 g, were used to test the protective ability of Pogostone after being injected with the median lethal doses (MLDs) of the tested strains.

RESULTSIn vitro test, Pogostone could inhibit both gram negative bacteria (0.098-1 600 µg/ml) and gram positive bacteria (0.098-800 µg/ml). For Corynebacterium xerosis and some Chryseobacterium indologenes, the minimum inhibitory concentration (MIC) values of Pogostone were extremely low (<0.098 µg/ml). It was significant that Pogostone was also active against some drug-resistant bacteria like MRSA. Furthermore, Pogostone showed antibacterial activity in vivo against Escherichia coli (E. coli) and MRSA via intraperitoneal injection. Ninety percent of the mice infected with E. coil could be protected at the concentrations of 50 and 100 mg/kg, and 60% of the mice at 25 mg/kg, while the rate of protection for the mice infected with MRSA was 60% and 50% at doses of 100 and 50 mg/kg, respectively.

CONCLUSIONPogostone could be developed as a potential antibacterial agent for clinical therapy.

Animals ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Escherichia coli ; drug effects ; Escherichia coli Infections ; drug therapy ; Female ; Gram-Negative Bacteria ; drug effects ; Gram-Positive Bacteria ; drug effects ; Male ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Microbial Sensitivity Tests ; Oils, Volatile ; pharmacology ; therapeutic use ; Staphylococcal Infections ; drug therapy

To explore new agents of quinolone derivatives with high activity against Gram-positive and Gram-negative microorganisms, 7-(3-amino-4-alkoxyimino-1-piperidyl) quinolones were designed and synthesized, and their activity against Gram-positive and Gram- negative microorganisms were tested in vivo and in vitro. Twenty one target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. The target compounds possess different antimicrobial activities against both Gram-negative and Gram-positive microorganisms. Compounds 14a and 14m have broad spectral antibacterial activities. They show better antibacterial activities against 12 strains Gram-positive bacteria than three references. In particular, their activities against S. aureus and S. epidermidis (including MRSA and MRSE) were 4 - 16 times than that of gemifloxacin and balofloxacin, and 8 - 64 times than that of levofloxacin. The MIC values to S. aureus strains of compounds 14a and 14m were 0.25 - 1 mg x L(-1) and 0.125 - 1 mg x L(-1), to S. epidermidis strains were 0.5 - 4 mg x L(-1) and 1 - 8 mg x L(-1) respectively. The in vivo results showed that they have as good internal protection as gemifloxacin and moxifloxacin against systemic infection model in mice (P > 0.05).
Animals ; Anti-Bacterial Agents ; chemical synthesis ; pharmacology ; therapeutic use ; Female ; Gram-Negative Bacteria ; drug effects ; Gram-Positive Bacteria ; drug effects ; Male ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Microbial Sensitivity Tests ; Molecular Structure ; Pneumococcal Infections ; drug therapy ; Quinolones ; chemical synthesis ; pharmacology ; therapeutic use ; Random Allocation ; Staphylococcal Infections ; drug therapy