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

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

BACKGROUND: Ureaplasma urealyticum and Mycoplasma hominis are associated with an increased risk of pregnancy complications, such as preterm birth and premature membrane rupture. The purpose of this study was to determine the isolation rates and antimicrobial susceptibilities of genital mycoplasma in a sample of pregnant women from Jinju, Korea. METHODS: Vaginal swabs were obtained from 258 pregnant women between 2004 and 2008 and tested for the presence of U. urealyticum and M. hominis at Gyeongsang National University Hospital. The identification and antimicrobial susceptibilities of U. urealyticum and M. hominis were determined with a commercially available kit, the Mycoplasma IST2 Kit (bioMe- rieux, Marcy-l'Etoile, France), and evaluated according to standards set by the Clinical and Laboratory Standards Institute (CLSI). RESULTS: U. urealyticum only was detected in 105 specimens (38.6%), while M. hominis only was detected only in 2 specimens (1.8%). Seven specimens (6.7%) were positive both for U. urealyticum and M. hominis. Susceptibilities of U. urealyticum to azithromycin, erythromycin, clarithromycin, and doxycycline were 75.2%, 82.9%, 88.6%, and 88.6%, respectively, while almost all of the isolates were susceptible to josamycin (99.0%) and pristinamycin (100%). The susceptibility of U. urealyticum to ofloxacin and ciprofloxacin was 56.2% and 15.2%, respectively. CONCLUSION: The rate of isolation of genital mycoplasma in pregnant women was 44.2% in Jinju; most of the mycoplasma were U. urealyticum. U. urealyticum and M. hominis were highly resistant to quinolones, but susceptible to josamycin. Therefore, empirical treatment without prior identification and determination of the antimicrobial susceptibility of genital mycoplasma will fail in many cases.
Azithromycin ; Ciprofloxacin ; Clarithromycin ; Doxycycline ; Erythromycin ; Female ; Humans ; Josamycin ; Korea ; Membranes ; Mycoplasma ; Mycoplasma hominis ; Ofloxacin ; Pregnancy Complications ; Pregnant Women ; Premature Birth ; Pristinamycin ; Quinolones ; Rupture ; Ureaplasma ; Ureaplasma urealyticum

BACKGROUND: While 7.6% of cultured genital Mycoplasmataceae was identified as Ureaplasma urealyticum, most of them were Ureaplasma parvum (80.3%). This is the first study differentiating between these two species. We investigated the prevalence and antimicrobial resistance of genital Mycoplasmataceae in Korean women. METHODS: A total of 150 specimens submitted to the laboratory for culture of M. hominis and Ureaplasma spp. were included. Detection and antimicrobial susceptibility tests were performed with the Mycoplasma IST2 kit (bioMérieux, France). The identification of Ureaplasma spp. was performed by PCR, and mutations in drug resistance genes were investigated by PCR and sequencing. RESULTS: In total, 66 specimens (44.0%) were positive for genital Mycoplasmatacea: U. parvum, 53 (80.3%); U. urealyticum, 5 (7.6%); M. hominis, 2 (3.0%); mixed infection, 6 (9.1%). Susceptibilities of Ureaplasma spp. to erythromycin, azithromycin, clarithromycin, and doxycycline were 86.0%, 80.7%, 98.2%, and 94.7%, respectively. The susceptibility of Ureaplasma spp. to ofloxacin and ciprofloxacin was 47.4% and 17.5%, respectively. The S83L mutation was found in the ParC subunit of the ofloxacin-resistant (5/7, 71.4%) and the ciprofloxacin-resistant isolates (7/14, 50.0%). One M. hominis isolate showed resistance to erythromycin, azithromycin, and clarithromycin but susceptibility to josamycin, pristinamycin, fluoroquinolones, and tetracyclines. CONCLUSION: The prevalence of genital Mycoplasmataceae in Korean women was 44.0%; most of them were identified as U. parvum. As more than 10% of Ureaplasma spp. showed non-susceptibility to erythromycin and azithromycin (15.5%, 20.7%), a susceptibility test is needed prior to use of these antibiotics. Further study is needed about the clinical features of infections caused by U. urealyticum vs. U. parvum and their associated resistance mechanisms.
Anti-Bacterial Agents ; Azithromycin ; Ciprofloxacin ; Clarithromycin ; Coinfection ; Doxycycline ; Drug Resistance ; Erythromycin ; Female ; Fluoroquinolones ; Humans ; Josamycin ; Mycoplasma ; Mycoplasmataceae* ; Ofloxacin ; Polymerase Chain Reaction ; Prevalence* ; Pristinamycin ; Tetracyclines ; Ureaplasma ; Ureaplasma urealyticum

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

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