This article reviews the advance in the research of both the mechanism of photodynamic antimicrobial chemotherapy (PACT) based on the principle of photodynamic therapy and the application of PACT in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. Nowadays an inexorable prevalence of resistant bacteria observed worldwide, among which MRSA strains typically have a high potential of provoking outbreaks with intractability, makes it a pressing issue to develop new germicidal strategies. PACT is an emerging photochemistry-based technology. In the presence of oxygen, PACT, with the aid of the activation of photosensitizers to generate reactive oxygen species by the wavelength-specific light, destroys the structure of bacteria selectively and efficiently, with much lower bacterial resistance level than that of antibiotics. We expect that further research would elucidate the mechanism and develop clinical applications of PACT, and it may become a novel approach to solve the problem of MRSA infection in the future.
Methicillin-Resistant Staphylococcus aureus ; Photochemotherapy ; Staphylococcal Infections ; microbiology ; therapy

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

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

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

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

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

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

Pyogenic spondylitis involving only the posterior element of a vertebra is rare. To the best of our knowledge, there have been no reports of osteomyelitis of the transverse process. We report here on a 45-year-old male with a one month history of swelling associated with lower back pain. The magnetic resonance imaging showed a paraspinal soft tissue mass, and computed tomography revealed a fine osteolytic lesion in the right transverse process of the 5th lumbar spine, and this was all consistent with chronic osteomyelitis. A mixed staphylococcal infection was identified. Open drainage, resection of the transverse process and intravenous injection of anti-staphylococcal antibiotics resolved the back pain and reduced the erythrocyte sedimentation rate to normal. Pyogenic osteomyelitis of the transverse process is extremely rare, which can cause a misdiagnosis or a delayed diagnosis. Careful consideration of this disease is needed when evaluating patients who complain of back pain.
Chronic Disease ; Humans ; *Lumbar Vertebrae ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Osteomyelitis/*diagnosis/therapy ; Spinal Diseases/*diagnosis/therapy ; Staphylococcal Infections/*diagnosis/therapy ; Tomography, X-Ray Computed

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