There have been conflicting data about the interactions between vancomycin and beta-lactam agents against Staphylococcus aureus strains with heterogeneous resistance to vancomycin. We evaluated the efficacy of these combinations against Mu 3 and heterogeneously vancomycin-resistant S. aureus (hetero-VRSA) strains which were isolated from Korean patients using a population analysis method. Antagonistic effects were observed when less than 1 g/mL of beta-lactam antibiotics was combined with vancomycin, whereas synergistic effects were noticed with more than 4 microgram/mL of beta-lactam antibiotics. The antagonistic effects at low concentrations of beta-lactams were most prominent at 2 microgram/mL of vancomycin, which were the vancomycin MICs of tested hetero-VRSA strains. This study showed the variable effects of vancomycin- beta-lactam combinations depending on the concentrations of beta-lactam antibiotics and this property could be used to develop screening methods for hetero-VRSA strains.
Anti-Bacterial Agents/*pharmacology ; Cefotaxime/pharmacology ; Drug Synergism ; Human ; In Vitro ; Microbial Sensitivity Tests ; Oxacillin/*pharmacology ; Staphylococcus aureus/*drug effects ; Vancomycin/*pharmacology ; Vancomycin Resistance ; beta-Lactam Resistance

BACKGROUNDThe infection rate of methicillin-resistant Staphylococcus aureus (MRSA) is increasing yearly due to the overprescription of antibiotics. Traditional Chinese compound medicines are less inclined to induce bacterial resistance in the clinical setting because of their multi-acting mechanisms. However, most current research is limited to bacteriostasis in vitro using single extracts or formulations. Plasma pharmacology is an in vitro method, using what is called "medicine serum". The aim of this study was to investigate whether the medicine serum of compound Qingre granules (QRKL) alone or in combination with antibiotics may treat MRSA infection in the clinic.

METHODSAn animal model of MRSA resistance was created by injecting rabbits with the standard strain of MRSA ATCC43300. Infected rabbits were treated with QRKL by intragastric administration. Sixty minutes after the last intragastric administration, serum was obtained from the rabbits by heart puncture to obtain what is termed "medicine serum". The minimum inhibitory concentration (MIC) of QRKL, medicine serum alone, or serum combined with antibiotics was assessed by agar dilution.

RESULTSwere compared with the growth of sixteen isolates of MRSA.

RESULTSThe MIC of QRKL to the standard strain ATCC43300 was 10.00 mg/ml. The MIC(90) of vancomycin was 1.00 microg/ml, which, when combined with QRKL, dropped to 0.50 microg/ml. The MIC(90) of cefuroxime alone was 512.00 microg/ml. This level also decreased to 256.00 microg/ml when combined with QRKL. The addition of QRKL thus significantly reduced the MIC of both cefuroxime and vancomycin compared with antibiotics alone (P < 0.01). The MIC(90) of vancomycin with medicine serum decreased to 0.50 microg/ml, and the MIC of vancomycin with medicine serum also descended compared with using vancomycin alone (P < 0.01).

CONCLUSIONSThe growth of MRSA can be inhibited by QRKL or medicine serum of QRKL in vitro. The addition of QRKL results in increased sensitivity of MRSA to vancomycin and this may provide a novel treatment for patients with MRSA infection.

Drugs, Chinese Herbal ; pharmacology ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Microbial Sensitivity Tests ; Vancomycin ; pharmacology

Vancomycin was enlisted as a drug of the last resort for the treatment of resistant gram-positive bacterial infections. However, the emergence of vancomycin-resistant bacteria has created an urgent need for new active analogues of vancomycin. Summing up the last ten years work of this field, the review introduced the antibiotic mechanism of vancomycin and summarized the vancomycin derivatives based on the modifications of vancomycin, dimmer of vancomycin and the vancomycin mimetics. The connection of modified location and function with antibacterial activity was also discussed.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Microbial Sensitivity Tests ; Molecular Structure ; Vancomycin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Vancomycin Resistance

BACKGROUNDVancomycin-resistant Enterococci (VRE) cause serious infections that are difficult to treat. We carried out this study to determine the mutant prevention concentration (MPC) of linezolid when combined with minocycline against VRE strains, to determine the mechanism of drug resistance in vitro, and to provide a theoretical basis for the rational use of drugs against VRE.

METHODSThe minimum inhibitory concentrations (MICs) of linezolid and minocycline against 30 Enterococci (E.) isolates (including 20 VRE strains) were determined by the broth microdilution method. Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies. Two vancomycin-susceptible strains N27 and N40 (linezolid MIC, 2 g/ml; minocycline MIC, 4 µg/ml) and control strains E. faecalis ATCC 29212 and ATCC 51299 were also tested. The MPCs of linezolid and minocycline (alone and combined) were determined using the agar dilution method. Strains showing stable resistance were analyzed by polymerase chain reaction (PCR) amplification of domain V of the 23S rRNA gene.

RESULTSCheckerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed. The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212, N40, and N27 before and after resistance screening, and MIC values increased with the number of G2576U mutations. The MPC of linezolid against E. decreased dramatically when combined with minocycline, and vice versa.

CONCLUSIONLinezolid or minocycline alone produce resistant strains; however, their joint use may reduce the MPC of each agent against VRE, thereby decreasing resistant mutants and bacterial infections.

Acetamides ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Anti-Infective Agents ; pharmacology ; Drug Therapy, Combination ; Enterococcus ; drug effects ; genetics ; Linezolid ; Microbial Sensitivity Tests ; Minocycline ; pharmacology ; Mutation ; Oxazolidinones ; pharmacology ; Vancomycin Resistance

The 5th year KONSAR surveillance in 2001 was based on routine test data at 30 participating hospitals. It was of particular interest to find a trend in the resistances of enterococci to vancomycin, of Enterobacteriaceae to the 3rd generation cephalosporin and fluoroquinolone, and of Pseudomonas aeruginosa and acinetobacters to carbapenem. Resistance rates of Gram-positive cocci were: 70% of Staphylococcus aureus to oxacillin; 88% and 16% of Enterococcus faecium to ampicillin and vancomycin, respectively. Seventy-two percent of pneumococci were nonsusceptible to penicillin. The resistance rates of Enterobacteriaceae were: Escherichia coli, 28% to fluoroquinolone; Klebsiella pneumoniae, 27% to ceftazidime, and 20% to cefoxitin; and Enterobacter cloacae, > or =40% to cefotaxime and ceftazidime. The resistance rates of P. aeruginosa were 21% to ceftazidime, 17% to imipenem, and those of the acinetobacters were > or =61% to ceftazidime, aminoglycosides, fluoroquinolone and cotrimoxazole. Thirty-five percent of non-typhoidal salmonellae were ampicillin resistant, and 66% of Haemophilus influenzae were -lactamase producers. Notable changes over the 1997-2001 period were: increases in vancomycin-resistant E. faecium, and amikacin- and fluoroquinolone-resistant acinetobacters. With the increasing prevalence of resistant bacteria, nationwide surveillance has become more important for optimal patient management, for the control of nosocomial infection, and for the conservation of the newer antimicrobial agents.
Anti-Bacterial Agents/*pharmacology ; Cephalosporins/pharmacology ; *Drug Resistance, Microbial ; Enterococcus faecium/metabolism ; Human ; Imipenem/pharmacology ; Klebsiella pneumoniae/metabolism ; Korea ; Pseudomonas aeruginosa/metabolism ; Time Factors ; Vancomycin/*pharmacology

The aim of this study was to investigate antimicrobial susceptibilities and macrolide resistance mechanisms of beta-hemolytic viridans group streptococci (VGS) in a tertiary Korean hospital. Minimum inhibitory concentrations (MICs) of seven antimicrobials were determined for 103 beta-hemolytic VGS isolated from various specimens. The macrolide resistance mechanisms of erythromycin-resistant isolates were studied by the double disk test and polymerase chain reaction (PCR). The overall resistance rates of beta-hemolytic VGS were found to be 47.5% to tetracycline, 3.9% to chloramphenicol, 9.7% to erythromycin, and 6.8% to clindamycin, whereas all isolates were susceptible to penicillin G, ceftriaxone, and vancomycin. Among ten erythromycin-resistant isolates, six isolates expressed a constitutive MLSB (cMLSB) phenotype, and each of the two isolates expressed the M phenotype, and the inducible MLSB (iMLSB) phenotype. The resistance rates to erythromycin and clindamycin of beta-hemolytic VGS seemed to be lower than those of non-beta-hemolytic VGS in our hospital, although cMLSB phenotype carrying erm(B) was dominant in beta-hemolytic VGS.
Ceftriaxone/pharmacology ; Chloramphenicol/pharmacology ; Clindamycin/pharmacology ; Cross Infection/*genetics ; *Drug Resistance, Bacterial ; Erythromycin/pharmacology ; Humans ; Immunoenzyme Techniques ; Korea ; Macrolides/*pharmacology ; Penicillin G/pharmacology ; Phenotype ; Polymerase Chain Reaction ; Tetracycline/pharmacology ; Vancomycin/pharmacology ; Viridans Streptococci/*genetics/*metabolism

Antimicrobial resistance surveillance is necessary to determine the size of the problem and to guide empirical selection of antimicrobial agents for treating infected patients. The aim of this study was to analyze the results of susceptibility tests performed by hospitals participating in the Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) program. The rates of oxacillin-resistant staphylococci, penicillin-nonsusceptible pneumococci, and ampicillin-resistant E. faecium were over 70%. Ampicillin-resistant H. influenzae increased to 68%. Expanded-spectrum cephalosporin-resistant K. pneumoniae, fluoroquinolone-resistant E. coli, and imipenem-resistant P. aeruginosa remained at 16% through 27%, depending on the species. The proportions of vancomycin-resistant E. faecium and imipenem-resistant P. aeruginosa were 18 - 24% and 19-21%, respectively, indicating the seriousness of antimicrobial resistance. In conclusion, the increasing prevalence of resistant bacteria indicates that more concerted effort is required to conserve the usefulness of precious new antimicrobial agents.
Anti-Bacterial Agents/*pharmacology ; Cephalosporins/*pharmacology ; *Drug Resistance, Microbial ; Enterococcus/*drug effects ; Gram-Negative Bacteria/*drug effects ; Human ; Imipenem/*pharmacology ; Korea ; *Vancomycin Resistance

OBJECTIVETo analyze the infection status and the drug resistance of enterococci in patients with severe hepatitis to guide future treatment.

METHODSAll bacteria from infected patients with severe hepatitis were cultured with BacT/Alert120 automation instrument (Aksu) and identified with Vitek-AMS60 (Biomerieux). Drug sensitivities of the isolated enterococci were tested with 11 antibacterial agents.

RESULTSAmong the 112 isolated enterococci, Enterococcus faecalis was the most preponderant bacterium, and the second was E. faecium. Their isolation rates were 79.5% and 14.3%, respectively. 57.1% of all the enterococci were found in the ascetic fluid of patients with severe hepatitis. Fifty-eight (51.8%) isolated enterococci were found to be high level aminoglycoside resistant (HLAR), 19 (17.0%) enterococci were ampicillin-resistant enterococcus (ARE) and 7 (6.3%) were both HLAR and ARE. The susceptive rates of the enterococci to vancomycin and teicoplanin were very high, namely 96.4% and 100%, respectively. No vancomycin or teicoplanin resistant enterococci were found, but 4 enterococci were mildly sensitive to vancomycin.

CONCLUSIONEnterococcus faecalis is the most prevalent species isolated in severe hepatitis patients infected with enterococcal infection. From our study, vancomycin and teicoplanin are the drugs of first choice to treat those infections.

Aminoglycosides ; pharmacology ; Ampicillin Resistance ; Drug Resistance, Bacterial ; Enterococcus faecalis ; drug effects ; Gram-Positive Bacterial Infections ; complications ; microbiology ; Hepatitis ; microbiology ; Humans ; Microbial Sensitivity Tests ; Teicoplanin ; pharmacology ; Vancomycin ; pharmacology

INTRODUCTIONVancomycin-resistant enterococcus (VRE) can cause serious infections in vulnerable, immunocompromised patients.

MATERIALS AND METHODSIn this article, we summarise current data on epidemiology, detection, treatment and prevention of VRE.

RESULTSVRE was first isolated in Singapore in 1994 and until 2004 was only sporadically encountered in our public hospitals. After 2 outbreaks in 2004 and in 2005, VRE has become established in our healthcare institutions. Multiple studies have shown that VRE spreads mainly via contaminated hands, cloths and portable equipment carried by healthcare workers.

CONCLUSIONSOnly a comprehensive programme (consisting of active surveillance, isolation of colonised/infected patients, strict adherence to proper infection control practices and anti-microbial stewardship) can limit the spread of these organisms. In addition to monitoring the compliance with traditional infection control measures, new strategies that merit consideration include pre-emptive isolation of patients in high-risk units and molecular techniques for the detection of VRE.

Anti-Bacterial Agents ; pharmacology ; Disease Outbreaks ; Disease Transmission, Infectious ; prevention & control ; Enterococcus ; drug effects ; isolation & purification ; Gram-Positive Bacterial Infections ; microbiology ; prevention & control ; transmission ; Humans ; Infection Control ; methods ; Singapore ; Vancomycin ; pharmacology ; therapeutic use ; Vancomycin Resistance

BACKGROUNDVancomycin-resistant enterococci (VRE) are a major and emerging hospital-acquired pathogen associated with high mortality, particularly among the critically ill and Intensive Care Units (ICUs) patients. This study aimed to determine the prevalence and demographic and clinical characteristics of VRE among patients admitted to a university hospital in Riyadh, Saudi Arabia.

METHODSA study was conducted during the period from September 2014 to November 2015 at King Khalid University Hospital, a tertiary care hospital in Riyadh, Saudi Arabia, including in-patients with VRE infection. Data were collected using laboratory results and the medical records of admitted patients and were analyzed using SPSS version 19.0 statistical software.

RESULTSIn a one-year period, 231 enterococci were isolated from blood, urine, exudates, sputum, stool, and body fluid. There were 191 (82.7%) vancomycin-sensitive enterococci (VSE) and 40 (17.3%) isolates were VRE. The Enterococcus species included E. faecalis 168 (72.7%), E. faecium, 53 (22.8%) E. gallinarum 5 (2.2%), and E. avium 5 (2.2%). VRE were more significant from blood specimens (P< 0.0001) while VSE were significantly more predominant from urine specimens (P< 0.0001). VRE were more commonly isolated from patients in ICUs and oncology unit (P = 0.0151 and P< 0.001, respectively) while VSE were more predominant in the medical and surgical areas (P = 0.0178 and P = 0.0178, respectively).

CONCLUSIONSThis study highlights the high prevalence of VRE in the hospital and the association of enterococcal infections with high-risk areas and oncology units, which warrant more studies looking for better management of these infections.

Adult ; Aged ; Anti-Bacterial Agents ; pharmacology ; Child, Preschool ; Enterococcus ; drug effects ; Female ; Hospitals, Teaching ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Saudi Arabia ; Vancomycin ; pharmacology ; Vancomycin-Resistant Enterococci ; drug effects ; isolation & purification ; pathogenicity