This study aimed to determine the in vitro activity of quinupristin-alfopristin against Streptococcus sp. isolated in China. This agent is not yet available for clinical use, but it has been tested against a high proportion of resistant Staphylococcus aureus strains. A total of 156 streptococcal isolates, which were recovered from various geographic areas and diseases, were tested using the Etest (AB Biodisk, Solna, Sweden). Quinupristin-alfopristin showed excellent activity against all of the tested streptococci isolates. These results provide useful data for the clinical use of quinupristin-alfopristin in China.
Anti-Bacterial Agents ; pharmacology ; China ; Microbial Sensitivity Tests ; Streptococcus ; drug effects ; Virginiamycin ; pharmacology

The emergence of multi-drug resistant gram-positive cocci such as methicillin-resistant (MR) staphylococci, vancomycin-resistant (VR) enterococci, and vancomycin-intermediate resistant S. aureus (VISA) has given new urgency to the development of new antimicrobial agents. One of these is quinupristin/dalfopristin (Q/D). We decided to determine the susceptibility of gram-positive cocci isolated at two university hospitals in Seoul to Q/D and compare the results with eight other antimicrobial agents. We investigated 120 isolates of S. aureus including 49 MRSAs and one VISA, 120 isolates of coagulase negative staphylococci (CNS), 64 E. faecalis and 56 E. faecium, including seven strains of VR E. faecium. Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) for several antimicrobials, including vancomycin and Q/D, were determined by broth microdilution. All S. aureus including VISA were susceptible to Q/D. Q/D MIC90 for both methicillin-susceptible S. aureus (MSSA) and MRSA was 0.25 g/mL. 49 (87.5%) of 56 E. faecium including six of seven VR E. faecium were susceptible to Q/D. E. faecalis were not susceptible to Q/D (only 1.5% susceptible), but were inhibited by ampicillin (94% susceptible) or vancomycin (95%). CNS was susceptible to Q/D (96% susceptible) and vancomycin (100% susceptible). One of 38 staphylococci and two of 17 E. faecium were tolerant to Q/D. In conclusion, Q/D showed excellent activity against all species of gram-positive cocci including MRSA, VISA, and VR E. faecium except E. faecalis, and may provide a valuable option for the treatment of infections caused by these emerging nosocomial pathogens of gram-positive cocci.
Antibiotics/pharmacology* ; Antibiotics, Peptide/pharmacology* ; Coagulase/analysis ; Enterococcus faecalis/drug effects ; Enterococcus faecium/drug effects ; Human ; Korea ; Microbial Sensitivity Tests* ; Staphylococcus/enzymology ; Staphylococcus/drug effects ; Staphylococcus aureus/drug effects ; Support, Non-U.S. Gov'tn ; Virginiamycin/pharmacology* ; Virginiamycin/analogs & derivatives*

BACKGROUND: To access the clinical usefulness of MicroScan(R) Synergies plus Combo Panels (Siemens, USA) for the identification and antimicrobial susceptibility test (AST) of Gram-negative bacteria (GNB) and Gram-positive cocci (GPC), we compared MicroScan(R) Synergies plus Combo Panels with MicroScan(R) conventional Combo Panels. METHODS: One-hundred four isolates of GNB were simultaneously tested with MicroScan(R) Synergies plus Neg Combo Type 2 Panel (SINC2) and MicroScan(R) Neg Combo Panel Type 44 (NC44). One-hundred isolates of GPC were simultaneously tested with MicroScan(R) Synergies plus Pos Combo 3 Panel (SIPC3) and MicroScan(R) Pos Combo 1A (PC1A). RESULTS: Of the GNB isolates, agreement rate of identification between SINC2 and NC44 were 92.3% to the species level and 93.3% to the genus level. Of the GPC isolates, agreement rate of identification between SIPC3 and PC1A were 85.0% to the species level and 100% to the genus level. Of the GNB isolates, agreement rate of AST according to antimicrobial agents between SINC2 and NC44 ranged from 86.5% to 100%. Among GPC isolates, agreement rate of AST according to antimicrobial agents between SIPC3 and PC1A were higher than 96.0% with the exception of gentamicin and quinupristin-dalfopristin. CONCLUSION: Compared with MicroScan(R) conventional Combo Panels (NC44, PC1A), MicroScan(R) Synergies plus Combo Panels (SINC2, SIPC3) showed high agreement rate of identification and AST, and had the advantage of more rapid reporting.
Anti-Infective Agents ; Gentamicins ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Gram-Positive Cocci ; Imidazoles ; Nitro Compounds ; Virginiamycin

A total of 58 vancomycin-resistant E. faecium (VREF) was isolated from 3 hospitals located in Daegu, Korea. The VREF isolates were evaluated for the antimicrobial susceptibility pattern and resistance determinants against vancomcin, aminoglycosides, and macrolides. The multilocus sequence types (MLST) were determined to characterize the clonal diversity of the VREF isolates. The VREF isolates were highly resistance to teicoplanin, erythromycin, ciprofloxacin, gentamicin, and streptomycin, whereas quinupristin-dalfopristin and linezolid were the most susceptible drugs. All isolates carried the vanA gene. The aac6'-aph2" (n=53) and aadE (n=27) genes were detected in the high-level aminoglycoside resistant (HLAR) isolates. The aac6'-aph2" gene was located in the conjugally transferable plasmids. The ermB and ermA genes were detected in the 54 and 3 VREF isolates, respectively. The VREF isolates showed 11 different sequence types (ST). The VREF isolates belonging to ST192 was the most prevalent (n=19), but detected in one hospital, whereas the isolates belonging to ST203 (n=11) were detected in 3 hospitals. These results suggest that the VREF isolates resistant to aminoglycosides and erythromycin are originated from different clones and specific VREF clones are spread in the study hospitals.
Acetamides ; Aminoglycosides ; Ciprofloxacin ; Clone Cells ; Enterococcus ; Enterococcus faecium ; Erythromycin ; Gentamicins ; Korea ; Linezolid ; Macrolides ; Multilocus Sequence Typing ; Oxazolidinones ; Plasmids ; Streptomycin ; Teicoplanin ; Virginiamycin

BACKGROUND: In Korea, a sudden increase in vancomycin-resistant enterococci (VRE) infection has been noted since the late 1990s. This study was conducted to describe the antimicrobial resistances of enterococcal blood isolates and to identify risk factors associated with VRE bacteremia in a tertiary care university hospital over a recent five-year period. METHODS: This study was conducted to analyze the antimicrobial susceptibilities of enterococcal blood isolates by year from January 2003 to December 2007. Multivariate logistic regression analysis was used to investigate factors associated with VRE bacteremia. RESULTS: A total of 225 enterococcal strains (44.7% Enterococcus faecalis, 42.4% Enterococcus facium, 5.9% Enterococcus casseliflavus, and 4.7% Enterococcus gallinarum) were detected in blood, 55 of which (21.6%) were resistant to vancomycin. In 2004 and 2005, the resistance rates for vancomycin and teicoplanin (33.3% and 27.3%; 34.4% and 23.0%, respectively) increased. In 2003, 2006, and 2007, the resistance rates for vancomycin and teicoplanin (8.7% and 8.7%; 19.0% and 14.3%; 13.5% and 11.5%, respectively) decreased relative to those of the previous years. When 55 patients with VRE bacteremia were compared with 55 patients with vancomycin-susceptible enterococcal bacteremia using multivariate analysis, E. faecium bacteremia (OR 12.624, P<0.001) and enterococcal bacteremia caused by species other than E. faecium and E. faecalis (OR 21.473, P=0.011) were found to be statistical risk factors. Among several infection control activities, the restricted uses of vancomycin and quinupristin-dalfopristin decreased the vancomycin resistance rate from 27.78% to 15.50% (P=0.0257). CONCLUSION: VRE bacteremia would be effectively controlled via infection control activities based on studies regarding risk factors associated with VRE bacteremia.
Bacteremia ; Enterococcus ; Enterococcus faecalis ; Humans ; Infection Control ; Korea ; Logistic Models ; Multivariate Analysis ; Risk Factors ; Teicoplanin ; Tertiary Healthcare ; Vancomycin ; Vancomycin Resistance ; Virginiamycin

Quinupristin/Dalfopristin is a new combination of streptogramin antibiotics designed specifically to treat clinically significant infections due to Vancomycin-resistant Enterococcus Faecium. Sweet's syndrome is characterized by painful skin plaques, which is associated with dermal neutrophilic infiltration, fever and peripheral blood leukocytosis. Drug-induced Sweet's syndrome has a temporal relationship between drug ingestion, clinical presentation and the temporally-related resolution of lesions following drug withdrawal or on treatment with systemic corticosteroids. A 63-year-old woman received Quinupristin/Dalfopristin for acute pyelonephritis developed fever, arthralgia, vomiting, and painful erythematous skin plaques. A skin biopsy showed neutrophilic dermatosis, and there was rapid resolution of the symptoms and cutaneous lesions after discontinuation of Quinupristin/Dalfopristin, consistent with drug-induced Sweet's syndrome. To date, there has been no reported case of Sweet's syndrome associated with the use of Quinupristin/Dalfopristin.
Anti-Bacterial Agents/administration & dosage/*adverse effects ; Female ; Human ; Middle Aged ; Skin/drug effects/pathology ; Sweet's Syndrome/*chemically induced/pathology ; Virginiamycin/administration & dosage/*adverse effects/*analogs & derivatives

There are relatively few novel antimicrobial agents despite the dramatic increase in antimicrobial resistance and multiple drug resistance of clinical isolates worldwide. Vancomycin is still the most widely used antibiotic for treating resistant Gram-positive coccal infections in children, especially for methicillin-resistant Staphylococcus aureus. For children with Gram-positive coccal infections where vancomycin is not effective or older therapeutic agents cannot be tolerated, linezolid, quinupristin-dalfopristin or daptomycin may be useful in the appropriate clinical setting. For Gram-negative infections, new carbapenems await clinical application. Tebipenem pivoxil is a novel oral carbapenem undergoing clinical trials for acute otitis media in pediatric patients. Antiviral drug development is now progressing at the pace of antibiotic development 30 years ago. Newer antiviral agents used for the treatment of herpes viruses and hepatitis C virus infections in children are included in this review.
Acetamides ; Anti-Bacterial Agents ; Anti-Infective Agents ; Antiviral Agents ; Carbapenems ; Child ; Daptomycin ; Drug Resistance, Multiple ; Hepacivirus ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Otitis Media ; Oxazolidinones ; Vancomycin ; Virginiamycin ; Linezolid

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of nosocomial infections, has been increasingly recognized in communities of the United States. This article will review the clinical spectrum and treatment of MRSA infections in children in the context of recent epidemiological changes of MRSA infections. In general, community-associated (CA) MRSA most frequently causes skin and soft tissue infections and has an increased association with invasive infections, particularly pneumonia and musculoskeletal infections. Hospital-associated (HA) MRSA strains tend to be associated with bloodstream infections, pneumonia, and surgical site infections. Different from the United States, CA-MRSA infections are not common in Korea (only 5.9%); however, there are some CA-MRSA clones that are different from HA- MRSA clones in Korea and from CA-MRSA clones in other countries. The treatment of MRSA infections should be guided by antimicrobial susceptibility testing, the site of infection, and the infection severity. Vancomycin is the treatment of choice for invasive MRSA infections. Other agents such as trimethoprim- sulfamethoxazole, clindamycin, linezolid, quinupristin-dalfopristin, and daptomycin have been used for some conditions.
Acetamides ; Child ; Clindamycin ; Clone Cells ; Cross Infection ; Daptomycin ; Humans ; Korea ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Oxazolidinones ; Pneumonia ; Skin ; Soft Tissue Infections ; Staphylococcus aureus ; Sulfamethoxazole ; United States ; Vancomycin ; Virginiamycin ; Linezolid

BACKGROUND: Scrub typhus, an infectious disease caused by Orientia tsutsugamushi, is endemic in Korea. With the introduction of tetracycline and chloramphenicol in clinical practice, the mortality due to scrub typhus has markedly decreased. In 1995, scrub typhus poorly responsive to doxycycline was reported in Thailand; the need for safe antibiotics for the treatment of scrub typhus acquired during pregnancy or for children is emerging; also, broader spectrum antibiotics having anti-Orientia activity may be preferred for empirical therapy of enteric fever syndrome and for complicated scrub typhus. The anti-Orientia activities of various antibiotics, including recently licensed antibiotics, were investigated by flow cytometry. MATERIALS AND METHODS: O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on 56-kDa major outer membrane protein of O. tsutsugamushi. Then the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). A concentration at which no further decrease in growth index occurred was defined as the minimal inhibitory concentration (MIC). Microbial susceptibilities to the following antibiotics were measured: quinupristin-dalfopristin (Synercid), levofloxacin, ciprofloxacin, moxifloxacin, metronidazole, linezolid, clindamycin, chloramphenicol, doxycycline, azithromycin, and rifampin. RESULTS: Considering the usual serum concentrations of rifampin (MIC=0.025-0.05 microg/mL), azithromycin (MIC=0.05-0.5 microg/mL) and doxycycline (MIC=0.05-0.1 microg/mL), these antibiotics exhibited very low MICs. Synercid (MIC=0.2-1.0 microg/mL), clindamycin (MIC=1.0 microg/mL) and chloramphenicol (MIC=1-2 microg/mL) exhibited moderately low MICs; moxifloxacin (MIC=8 microg/mL), ciprofloxacin (MIC=25.6 microg/mL or more) and levofloxacin (MIC=30 microg/mL) exhibited relatively high MICs; and cefotaxime (MIC>50 microg/mL), metronidazole (MIC>30 microg/mL) and linezolid (>30 microg/mL) exhibited high MICs. CONCLUSIONS: Among the new antibiotics, none was superior to doxycycline, azithromycin or rifampin with respect to anti-Orientia activity. Synercid, clindamycin, and moxifloxacin may show moderate therapeutic efficacies in human.
Acetamides ; Anti-Bacterial Agents ; Aza Compounds ; Azithromycin ; Cefotaxime ; Cell Line ; Child ; Chloramphenicol ; Ciprofloxacin ; Clindamycin ; Communicable Diseases ; Doxycycline ; Flow Cytometry ; Humans ; Korea ; Linezolid ; Membrane Proteins ; Metronidazole ; Ofloxacin ; Orientia tsutsugamushi ; Oxazolidinones ; Pregnancy ; Quinolines ; Rifampin ; Scrub Typhus ; Sprains and Strains ; Tetracycline ; Typhoid Fever ; Virginiamycin

BACKGROUND: Scrub typhus, an infectious disease caused by Orientia tsutsugamushi, is endemic in Korea. With the introduction of tetracycline and chloramphenicol in clinical practice, the mortality due to scrub typhus has markedly decreased. In 1995, scrub typhus poorly responsive to doxycycline was reported in Thailand; the need for safe antibiotics for the treatment of scrub typhus acquired during pregnancy or for children is emerging; also, broader spectrum antibiotics having anti-Orientia activity may be preferred for empirical therapy of enteric fever syndrome and for complicated scrub typhus. The anti-Orientia activities of various antibiotics, including recently licensed antibiotics, were investigated by flow cytometry. MATERIALS AND METHODS: O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on 56-kDa major outer membrane protein of O. tsutsugamushi. Then the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). A concentration at which no further decrease in growth index occurred was defined as the minimal inhibitory concentration (MIC). Microbial susceptibilities to the following antibiotics were measured: quinupristin-dalfopristin (Synercid), levofloxacin, ciprofloxacin, moxifloxacin, metronidazole, linezolid, clindamycin, chloramphenicol, doxycycline, azithromycin, and rifampin. RESULTS: Considering the usual serum concentrations of rifampin (MIC=0.025-0.05 microg/mL), azithromycin (MIC=0.05-0.5 microg/mL) and doxycycline (MIC=0.05-0.1 microg/mL), these antibiotics exhibited very low MICs. Synercid (MIC=0.2-1.0 microg/mL), clindamycin (MIC=1.0 microg/mL) and chloramphenicol (MIC=1-2 microg/mL) exhibited moderately low MICs; moxifloxacin (MIC=8 microg/mL), ciprofloxacin (MIC=25.6 microg/mL or more) and levofloxacin (MIC=30 microg/mL) exhibited relatively high MICs; and cefotaxime (MIC>50 microg/mL), metronidazole (MIC>30 microg/mL) and linezolid (>30 microg/mL) exhibited high MICs. CONCLUSIONS: Among the new antibiotics, none was superior to doxycycline, azithromycin or rifampin with respect to anti-Orientia activity. Synercid, clindamycin, and moxifloxacin may show moderate therapeutic efficacies in human.
Acetamides ; Anti-Bacterial Agents ; Aza Compounds ; Azithromycin ; Cefotaxime ; Cell Line ; Child ; Chloramphenicol ; Ciprofloxacin ; Clindamycin ; Communicable Diseases ; Doxycycline ; Flow Cytometry ; Humans ; Korea ; Linezolid ; Membrane Proteins ; Metronidazole ; Ofloxacin ; Orientia tsutsugamushi ; Oxazolidinones ; Pregnancy ; Quinolines ; Rifampin ; Scrub Typhus ; Sprains and Strains ; Tetracycline ; Typhoid Fever ; Virginiamycin