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

Antimicrobial resistance of bacteria has become a worldwide problem. Available data suggest that the resistance problem is comparatively more serious in Korea. In large hospitals, the proportion of methicillin-resistant Staphylococcus aureus (MRSA) has been reported at over 70%, and of penicillin-nonsusceptible Streptococcus pneumoniae at around 70%. Infection or colonization of vancomycin-resistant enterococci has started to increase. Extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae has become widespread and even carbapenem-resistant Pseudomonas aeruginosa has been increasing. Community-acquired pathogens such as Salmonella, Shigella and Neisseria gonorrhoeae are often resistant to various antimicrobial agents. The prevalence of resistant bacteria can lead to erroneous empirical selection of either noneffective or expensive drugs, prolonging hospitalization and higher mortality. The emergence and spread of resistant bacteria are unavoidable unless antimicrobial agents are not used at all. The high prevalence of resistant bacteria in Korea seems to be related to antibiotic usage: 1) easy availability without prescription at drug stores, 2) injudicious use in hospitals, and 3) uncontrolled use in agriculture, animal husbandry, and fisheries. Nosocomial infection is an important factor in the spread of resistant bacteria. Antimicrobial resistance problems should be regarded as the major public health concern in Korea. It is urgently required to ban the sale of antibiotics without prescription, to use antibiotics more judiciously in hospitals by intensive teaching of the principles of the use of antibiotics, and to establish better control measures of nosocomial infections. Regulation of antimicrobials for other than human use should also be required. These issues are not easy to address and require the collective action of governments, the pharmaceutical industry, health care providers, and consumers.
Bacterial Infections/drug therapy ; Bacterial Physiology* ; Drug Resistance, Microbial/physiology* ; Enterococcus/drug effects ; Gram-Negative Bacterial Infections/drug therapy ; Human ; Korea ; Pneumococcal Infections/drug therapy ; Staphylococcal Infections/drug therapy

OBJECTIVETo investigate the prevalence and drug resistant patterns of community-acquired Methicillin-resistant Staphylococcus aureus (MRSA) in children.

METHODSSamples of sputum, blood, liquor puris/secretion of skin or stool in Beijing Children's Hospital between January, 2002 and March, 2005 were cultured. The characteristics of community-acquired MRSA infection were analyzed and compared with hospital-acquired MRSA infection.

RESULTSA total of 25 strains of MRSA were found during the study period and they accounted for 4.7% in 512 strains of Staphylococcus aureus. Of the 25 strains of MRSA, 20 strains were community-acquired but only 5 were hospital-acquired. The prevalence of MRSA infection in Staphyloccus aureus has kept rising over last two years, 3.1% in 2003, 5.4% in 2004 and 7.2% in the first season of 2005. There were no statistical differences in the results of antimicrobial susceptibility testing and multi-resistance testing between the groups of community-acquired and hospital-acquired MRSA. In both groups, all isolates were susceptible to vancomycin. The percentage of the patients with underlying disease in the hospital-acquired infection group was significantly higher than in community-acquired infection group (P < 0.05), but the onset age was not different.

CONCLUSIONSThe prevalence of community-acquired MRSA infection tends to increase in children. The drug resistant patterns of community-acquired MRSA were not significantly different from the hospital-acquired MRSA in children.

Child ; Child, Preschool ; Community-Acquired Infections ; drug therapy ; microbiology ; Humans ; Infant ; Infant, Newborn ; Methicillin Resistance ; Staphylococcal Infections ; drug therapy ; microbiology ; Staphylococcus aureus ; drug effects

In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.
Animals ; Anti-Bacterial Agents ; pharmacology ; Daptomycin ; pharmacology ; Liposomes ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Staphylococcal Infections ; drug therapy

OBJECTIVE: To investigate the current status of empirical antibiotic therapy for children with Staphylococcus aureus sepsis and the effect of therapeutic paradigm on prognosis based on a retrospective analysis. METHODS: A total of 78 children with Staphylococcus aureus sepsis who were admitted from January 2014 to August 2017 were enrolled. According to the preferred empirical antibiotics before the detection of Staphylococcus aureus by blood culture, these children were divided into a carbapenem group with 16 children, a β-lactam group with 37 children, a vancomycin group with 15 children and a vancomycin+β-lactam group with 10 children. A retrospective analysis was performed for related clinical data including general status, underlying diseases, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, history of use of immunosuppressant, drug resistance to methicillin and prognosis. A logistic regression analysis was used to investigate the effect of empirical antibiotic therapy on the clinical outcome and prognosis of children with Staphylococcus aureus sepsis. RESULTS: There were no significant differences among these groups in general status, underlying diseases, history of use of immunosuppressant, APACHE II score, nosocomial infection and detection rate of methicillin-resistant Staphylococcus aureus (P>0.05). There were significant differences in the incidence rate of septic shock and in-hospital mortality among these four groups (P<0.05). The carbapenem group had the highest incidence rate of septic shock and in-hospital mortality (69% and 50% respectively). The multivariate logistic regression analysis showed that empirical antibiotic therapy with different antibiotics had different risks for septic shock and in-hospital death in children with Staphylococcus aureus sepsis (P<0.05), and that an APACHE II score of ≥15 was an independent risk factor for septic shock in these children (P<0.05). The carbapenem group had significantly higher risks of septic shock and in-hospital death than the vancomycin group (P<0.05). CONCLUSIONS Inappropriate empirical use of antibiotics may lead to a poor prognosis in children with Staphylococcus aureus sepsis. Empirical use of carbapenems is not recommended for children suspected of Staphylococcus aureus sepsis.
Anti-Bacterial Agents ; therapeutic use ; Child ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Retrospective Studies ; Sepsis ; Staphylococcal Infections ; drug therapy ; Staphylococcus aureus

INTRODUCTIONSingapore saw a resurgence of dengue infections in 2005. Concurrent bacterial co-infections in dengue is rare.

CLINICAL PICTUREWe report a cluster of serious methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia or severe soft tissue infection in 5 epidemiologically linked construction workers presenting with dengue and non-resolving fever.

TREATMENTSurgical intervention was indicated in 4 of the 5 patients despite appropriate antistaphylococcal therapy.

OUTCOMEAll but 1 patient were eventually discharged. Clonality and Panton-Valentine leucocidin genes were not demonstrated. Epidemiological investigations suggested that occupational contact dermatitis could have predisposed the patients to this opportunistic co-infection.

CONCLUSIONClinicians need to be vigilant to unusual manifestations of dengue which may signal a concomitant aetiology.

Adult ; Cluster Analysis ; Dengue ; complications ; epidemiology ; Humans ; Male ; Methicillin ; pharmacology ; Occupations ; Singapore ; epidemiology ; Soft Tissue Infections ; transmission ; Staphylococcal Infections ; complications ; epidemiology ; therapy ; transmission ; Staphylococcal Skin Infections ; transmission ; Staphylococcus aureus ; drug effects

Primary community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) endocarditis has rarely been reported in healthy individuals without risk factors, such as skin and soft tissue infections, and intravenous drug abuse. We describe a case of infective endocarditis by CA-MRSA (ST72-PVL negative-SCCmec IVA) in previously healthy individuals with no underlying medical condition and CA-MRSA colonization in the family.
Adult ; Community-Acquired Infections/microbiology/transmission ; Endocarditis/*microbiology ; Family ; Female ; Humans ; *Methicillin Resistance ; Staphylococcal Infections/*diagnosis/drug therapy/*transmission ; Staphylococcus aureus/*drug effects

OBJECTIVETo analyze the change in drug resistance of Staphylococcus aureus (SAU) in the PLA general hospital from January 2008 to December 2012, and to provide solid evidence to support the rational use of antibiotics for clinical applications.

METHODSThe SAU strains isolated from clinical samples in the hospital were collected and subjected to the Kirby-Bauer disk diffusion test. The results were assessed based on the 2002 American National Committee for Clinical Laboratory Standards (NCCLS) guidelines.

RESULTSSAU strains were mainly isolated from sputum, urine, blood and wound excreta and distributed in penology, neurology wards, orthopedics and surgery ICU wards. Except for glycopeptide drugs, methicillin-resistant Staphylococcus aureus (MRSA) had a higher drug resistance rate than those of the other drugs and had significantly more resistance than methicillin-sensitive Staphylococcus aureus (MSSA) (P < 0.05). In the dynamic observation of drug resistance, we discovered a gradual increase in drug resistance to fourteen test drugs during the last five years.

CONCLUSIONDrug resistance rate of SAU stayed at a higher level over the last five years; moreover, the detection ratio of MRSA keeps rising year by year. It is crucial for physicians to use antibiotics rationally and monitor the change in drug resistance in a dynamic way.

Anti-Bacterial Agents ; pharmacology ; Drug Resistance, Multiple, Bacterial ; Humans ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Staphylococcal Infections ; drug therapy ; Staphylococcus aureus ; drug effects

BACKGROUNDPrevious studies have different viewpoints about the clinical impact of methicillin resistance on mortality of hospital-acquired bloodstream infection (BSI) patients with Staphylococcus aureus (S. aureus). The objective of this study was to investigate the mortality of hospital-acquired BSI with S. aureus in a military hospital and analyze the risk factors for the hospital mortality.

METHODSA retrospective cohort study was performed in patients admitted to the biggest military tertiary teaching hospital in China between January 2006 and May 2011. All included patients had clinically significant nosocomial BSI with S. aureus. Multivariate Logistic regression analysis was used to identify the risk factors for hospital mortality of patients with S. aureus BSI.

RESULTSOne hundred and eighteen patients of more than one year old were identified as clinically and microbiologically confirmed nosocomial bacteraemia due to S. aureus, and 75 out of 118 patients were infected with methicillin-resistant S. aureus (MRSA). The overall mortality of nosocomial S. aureus BSI was 28.0%. Methicillin resistance in S. aureus bacteremia was associated with significant increase in the length of hospitalization and high proportion of inappropriate empirical antibiotic treatment. After Logistic regression analysis, the severity of clinical manifestations (APACHE II score) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.12 - 1.34) and inadequacy of empirical antimicrobial therapy (OR 0.25, 95%CI 0.09 - 0.69) remained as risk factors for hospital mortality.

CONCLUSIONSNosocomial S. aureus BSI was associated with high in-hospital mortality. Methicillin resistance in S. aureus has no significant impact on the outcome of patients with staphylococcal bacteremia. Proper empirical antimicrobial therapy is very important to the prognosis.

Adult ; Aged ; Cross Infection ; drug therapy ; mortality ; Female ; Hospital Mortality ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus ; pathogenicity ; Middle Aged ; Retrospective Studies ; Risk Factors ; Staphylococcal Infections ; drug therapy ; mortality

OBJECTIVE: To establish a proper animal model of pyogenic spondylitis, to evaluate the efficacy of silver nanoparticles for treatment of spinal pyogenic infections, and to explore the distribution of the particles in the body of the animals. METHODS: Staphylococcus aureus was inoculated into intervertebral discs of rabbits to establish a spinal pyogenic infection model. These rabbits were divided into Group A [0.1 mg/(kg.d)], Group B [1 mg/(kg.d)], and a Control group. Groups A and B were injected with different doses of silver nanoparticles solution daily at locally infected side. Two weeks later, bacterial cultures, radiographic outcomes, histopathology were analyzed. Atomic absorption spectrometry was utilized to measure silver contents in some vital organs of the rabbits to detect the distribution and accumulation of silver particles. RESULTS: Staphylococcus aureus (100 CFU/mL), induced 100% pyogenic spondylitis. 1 mg/kg dose of silver nanoparticles solution could effectively inhibit the occurrence of spinal pyogenic infection with the effective rate of 75%. While the effect of 0.1 mg/kg dose of silver nanoparticles solution was less obvious, the efficiency was only 25%. Significant numbers of silver nanoparticles were observed to accumulate in the animal. In the 1 mg/kg group silver was deposited mainly in the spinal cord, liver, kidneys, spleen, and testicles, while in the 0.1 mg/kg group it accumulated only in the spinal cord. CONCLUSION Local administration of silver nanoparticles can effectively prevent and treat pyogenic spondylitis; the particles accumulate in the body commensurate with the administered drug concentration.
Animals ; Infusions, Intralesional ; Lumbar Vertebrae ; Male ; Metal Nanoparticles ; administration & dosage ; Rabbits ; Silver ; administration & dosage ; pharmacology ; Spondylitis ; drug therapy ; microbiology ; Staphylococcal Infections ; drug therapy