OBJECTIVES: Genetic determinants conferring resistance to macrolide, lincosamide, and streptogramin B (MLSB) via ribosomal modification such as, erm, msrA/B and ereA/B genes are distributed in bacteria. The main goals of this work were to evaluate the dissemination of MLSB resistance phenotypes and genotypes in methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from clinical samples. METHODS: A total of 106 MRSA isolates were studied. Isolates were recovered from 3 hospitals in Tehran between May 2016 to July 2017. The prevalence of MLSB-resistant strains were determined by D-test, and then M-PCR was performed to identify genes encoding resistance to macrolides, lincosamides, and streptogramins in the tested isolates. RESULTS: The frequency of constitutive resistance MLSB, inducible resistance MLSB and MSB resistance were 56.2%, 22.9%, and 16.6%, respectively. Of 11 isolates with the inducible resistance MLSB phenotype, ermC, ermB, ermA and ereA were positive in 81.8%, 63.6%, 54.5% and 18.2% of these isolates, respectively. In isolates with the constitutive resistance MLSB phenotype, the prevalence of ermA, ermB, ermC, msrA, msrB, ereA and ereB were 25.9%, 18.5%, 44.4%, 0.0%, 0.0%, 11.1% and 0.0%, respectively. CONCLUSION: Clindamycin is commonly administered in severe MRSA infections depending upon the antimicrobial susceptibility findings. This study showed that the D-test should be used as an obligatory method in routine disk diffusion assay to detect inducible clindamycin resistance in MRSA so that effective antibiotic treatment can be provided.
Bacteria ; Clindamycin ; Diffusion ; Drug Resistance ; Genotype ; Lincosamides ; Macrolides ; Methicillin-Resistant Staphylococcus aureus ; Methods ; Phenotype ; Prevalence ; Staphylococcus aureus ; Staphylococcus ; Streptogramin B ; Streptogramins

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

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

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

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

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: 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

Virginiamycin acetyltransferase D (VatD) plays a vital rule in streptogramins resistance by chemically inactivating streptogramin A. Therefore, it is desirable to discover novel small molecular weight inhibitors of VatD via state-of-the-art virtual screening techniques. This "cocktail" strategy by combining VatD inhibitor with streptogramins may provide new therapeutic opportunity for resistant bacteria infections. Structure-based virtual screening method (molecular docking) was applied to rank and score a chemical database containing 300 000 commercially available compounds against the VatD substrate binding site. Twenty six out of the 200 top scored compounds from the docking calculation were selected and submitted to the VatD enzymatic inhibition assay. The plasmid pRSET B/vatD was constructed and transformed into E. coli (trxB) host cells for over-expression, and VatD enzyme was purified and validated by showing acetyltransferase activity to Virginiamycin M1. Three out of these 26 tested compounds showed enzymatic inhibition on VatD with IC50 168.6, 91.0 and 55.2 micromol x L(-1), separately. Other compounds could not be dissolved in the system and/or had little effect on the enzyme (IC50 > 200 micromol x L(-1)). To our knowledge, it is first time that small molecular weight organic compounds were identified as VatD inhibitors. It is expected that the VatD inhibitors identified at present study could serve as lead compounds for the further development of the novel therapeutic agents to overcome streptogramins resistance.
Acetyltransferases ; antagonists & inhibitors ; genetics ; metabolism ; Catalysis ; drug effects ; Drug Design ; Drug Resistance, Bacterial ; Enzyme Inhibitors ; chemistry ; metabolism ; pharmacology ; Escherichia coli ; genetics ; Genetic Vectors ; Kinetics ; Molecular Structure ; Plasmids ; Streptogramin Group A ; chemistry ; metabolism ; pharmacology ; Transformation, Genetic