Linezolid and quinupristin/dalfopristin resistance in vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus prior to clinical use in Turkey

The aim of this study was to determine the in vitro antimicrobial activity of recently licensed quinupristin/dalfopristin and linezolid which have not yet been in clinical use in Turkey against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains isolated from various clinical specimens by using the Etest. The results showed that all MRSA strains were fully susceptible to both the new compounds. All strains were inhibited by 1 mg/l quinupristin/dalfopristin (mode MIC 0.38 mg/l) and by 3 mg/l linezolid (mode MIC 1.5 mg/l). Four strains of Enterococcus faecium showed an increase of resistance of 2-3 mg/l to quinupristin/dalfopristin (susceptible mode MIC 0.38 mg/l). With linezolid, all strains except two fell within the range 0.75-2.0 mg/l.     

Nosocomial infections due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci at a university hospital in Taiwan from 1991 to 2003: resistance trends, antibiotic usage and in vitro activities of newer antimicrobial agents

A rapid increase of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection (from 39% in 1991 to 75% in 2003) and vancomycin-resistant enterococci (VRE) (from 1.2% in 1996 to 6.1% in 2003) at a university hospital in Taiwan was found. The noticeable rise of MRSA and VRE was significantly correlated with the increased consumption of glycopeptides, beta-lactam-beta-lactamase inhibitor combinations, extended-spectrum cephalosporins, carbapenems and fluoroquinolones (Pearson's correlation coefficient, P < 0.05). Minimum inhibitory concentrations (MICs) of 100 non-duplicate blood isolates of MRSA (in 2003) and of 25 non-duplicate isolates of vancomycin-resistant Enterococcus faecalis and 172 vancomycin-resistant Enterococcus faecium (in 1996-2003) causing nosocomial infection recovered from various clinical specimens of patients treated at the hospital to nine antimicrobial agents were determined by the agar dilution method. All of these isolates were susceptible to linezolid and were inhibited by 0.5mg/L of tigecycline, and all MRSA isolates were inhibited by daptomycin 1mg/L, including two isolates of MRSA with heteroresistance to vancomycin. Daptomycin had two-fold better activity against vancomycin-resistant E. faecalis (MIC90, 2 mg/L) than against vancomycin-resistant E. faecium (MIC90, 4 mg/L). Decreased susceptibilities of vancomycin-resistant E. faecium and MRSA to quinupristin/dalfopristin (non-susceptibility 25% and 8%, respectively) were found. Telithromycin had poor activity against the isolates tested (MIC90, 8 mg/L). Linezolid, daptomycin and tigecycline may represent therapeutic options for infections caused by these resistant Gram-positive organisms.     

In vitro activity of daptomycin against clinical isolates with reduced susceptibilities to linezolid and quinupristin/dalfopristin

An initiative was taken to determine the in vitro activity of daptomycin against 85 Gram-positive isolates with reduced susceptibilities to linezolid and quinupristin/dalfopristin. Daptomycin had potent activity against all strains, with a Staphylococcus spp. minimum inhibitory concentration (MIC) < or =2 microg/mL and an Enterococcus spp. MIC < or =8 microg/mL. Resistance to linezolid and quinupristin/dalfopristin appears to be independent of reduced susceptibility to daptomycin.     

Antimicrobial susceptibility of clinical isolates of aerobic gram-positive cocci and anaerobic bacteria in 2008

The activity of antibacterial agents against aerobic Gram-positive cocci (25 genus or species, 1029 strains) and anaerobic bacteria (21 genus or species, 187 strains) isolated from clinical specimens in 2008 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 59.6% and 81.2%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM), linezolid (LZD) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 microg/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 92.0% that was highest among our previous reports. Cefpirome, carbapenems, VCM, teicoplanin (TEIC), LZD and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 15.9% of E. faecalis strains and 1.2% of E. faecium strains showed intermediate to LZD. 17.1% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM was under 1 microg/mL, suggesting that VCM had excellent activity. Carbapenems showed good activity against Clostridiales, Bacteroides spp., and Prevotella spp., but one strain of Bacteroides fragilis showed resistant to carbapenems. And so, the susceptibility of this species should be well-focused in the future at detecting continuously.     

Antimicrobial activity of quinupristin/dalfopristin, a new injectable streptogramin with a wide Gram-positive spectrum

Quinupristin/dalfopristin (Synercid) is a new injectable streptogramin antibiotic proposed for the treatment of severe antimicrobial infections, that has been shown to be active against Gram-positive, multi-resistant cocci. We compared the in vitro activity of quinupristin/dalfopristin with that of amoxycillin, ampicillin, penicillin, cefixime, ceftriaxone, clindamycin, erythromycin, imipenem, meropenem, oxacillin, piperacillin/tazobactam, teicoplanin and vancomycin. The susceptibility of 37 Staphylococcus aureus (14 MS, 23 MR), 26 Staphylococcus epidermidis (16 MS, 10 MR), 20 Streptococcus pneumoniae, 33 Group A Streptococcus pyogenes, 15 Streptococcus agalactiae, 10 Enterococcus faecalis (1 vancomycin-resistant), 15 Enterococcus faecium (9 van A) was evaluated. Quinupristin/dalfopristin was active against all Gram-positive species tested, including met-R S. aureus (MIC < or = 2 mg/l), met-R S. epidermidis (MIC < or = 2 mg/l), S. pneumoniae (MIC < or = 1 mg/l), ery-R and ery-S streptococci (MIC < or = 1 mg/l). The strains of E. faecalis were generally less susceptible. Time-kill studies confirmed that quinupristin/dalfopristin at 4 x MIC concentration showed a complete bactericidal effect (3 log reduction) in about 4 6 h against all strains tested. A post-antibiotic effect (PAE) of 3.9-5.2 h was observed at 4 x MIC concentration of quinupristin/dalfopristin against staphylococci. A prolonged PAE was obtained for S. pneumoniae (8 h), S. pyogenes (9 h) and S. agalactiae (7 h), while the shortest PAE was seen for E. faecalis and E. faecium (about 4 h).     

In vitro antimicrobial activity of telavancin against methicillin-resistant Staphylococcus aureus clinical isolates from Japan (2006)

In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 microg/ml to 0.5 microg/ml and a MIC90 value of 0.5 microg/ml. The MIC90s of vancomycin and linezolid were 1.0microg/ml and 2 microg/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.     

Reduced susceptibility to quinupristin/dalfopristin in Enterococcus faecium in Greece without prior exposure to the agent

During 2005-2006, a total of 865 Enterococcus faecium isolated from patients from eight Greek hospitals were tested for susceptibility to quinupristin/dalfopristin (Q/D). Among them, 250 genetically unrelated strains (28.9%) were found to be intermediate-resistant to Q/D (minimum inhibitory concentration (MIC) 1.5-4 mg/L); all were resistant to dalfopristin (MIC=16-64 mg/L), whilst 69% were resistant to quinupristin, carrying the ermB gene. No strain was found to carry any of the known genes, such as vatE and vatD, involved in Q/D resistance, indicating that a non-transferable undetermined mechanism is responsible for the expression of low-level Q/D resistance. The high percentage of Q/D-intermediate-resistant E. faecium in Greece was not associated with prior consumption of the agent or with the veterinary use of virginiamycin.     

喹奴普丁-达福普汀治疗多重耐药革兰阳性细菌感染的研究进展

喹奴普丁-达福普汀是第一个经静脉给药的水溶性、半合成链阳性菌素(streptogramin)衍生物,其2种有效成分以30:70的比例混合,分别应用时只有抑菌作用,联合应用则有协同杀菌作用。该品对大多数革兰阳性细菌具有杀菌活性,对屎肠球菌只有抑菌作用。喹奴普丁和达福普汀分别与细菌50S核糖体亚单位23S RNA的不同部位结合,通过抑制细菌蛋白质合成而发挥抗菌作用。目前FDA仅批准该药用于治疗成人严重或致命性耐万古霉素屎肠球菌菌血症相关性感染、甲氧西林敏感性金黄色葡萄球菌及A组酿脓链球菌引起的皮肤及皮肤组织感染。儿童应用喹奴普丁-达福普汀的安全性及疗效尚未被充分证实。该药的主要不良反应为静脉刺激与肌痛/关节痛。虽然喹奴普丁-达福普汀不经肝脏细胞色素P450酶代谢,但其却是CYP 3A4酶抑制剂,与经过CYP 3A4代谢的药物合用时可发生明显的药动学相互作用,导致这些药物的血浆浓度升高。     

Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections

Quinupristin/dalfopristin is the first parenteral streptogramin antibacterial agent, and is a 30:70 (w/w) ratio of 2 semisynthetic pristinamycin derivatives. The combination has inhibitory activity against a broad range of gram-positive bacteria including methicillin-resistant staphylococci, vancomycin-resistant Enterococcus faecium (VREF), drug-resistant Streptococcus pneumoniae, other streptococci, Clostridium perfringens and Peptostreptococcus spp. The combination also has good activity against selected gram-negative respiratory tract pathogens including Moraxella catarrhalis, Legioniella pneumophila and Mycoplasma pneumoniae. Quinupristin/dalfopristin has poor activity against E. faecalis. The combination is bactericidal against staphylococci and streptococci, although constitutive erythromycin resistance can affect its activity. As for many other agents, quinupristin/dalfopristin is generally bacteriostatic against E. faecium. In patients with methicillin-resistant S. aureus (MRSA) or VREF infections participating in prospective emergency-use trials, quinupristin/dalfopristin 7.5 mg/kg every 8 or 12 hours achieved clinical or bacteriological success in > or =64% of patients. Emergence of resistance to quinupristin/dalfopristin was uncommon (4% of patients) in those with VREF infections. Quinupristin/dalfopristin 7.5 mg/kg 8- or 12-hourly also achieved similar clinical success rates to comparator agents in patients with presumed gram-positive complicated skin and skin structure infections or nosocomial pneumonia (administered in combination with aztreoman) in 3 large multicentre randomised trials. Systemic adverse events associated with quinupristin/dalfopristin include gastrointestinal events (nausea, vomiting and diarrhoea), rash and pruritus. Myalgias and arthralgias also occur at an overall incidence of 1.3%, although higher rates (2.5 to 31%) have been reported in patients with multiple comorbidities. Venous events are common if the drug is administered via a peripheral line; however, several management options (e.g. use of central venous access, increased infusion volume) may help to minimise their occurrence. Hyperbilirubinaemia has been documented in 3.1% of quinupristin/dalfopristin recipients versus 1.3% of recipients of comparator agents. Quinupristin/dalfopristin inhibits cytochrome P450 3A4 and therefore has the potential to increase the plasma concentrations of substrates of this enzyme. CONCLUSIONS: Quinupristin/dalfopristin, the first parenteral streptogramin, offers a unique spectrum of activity against multidrug-resistant gram-positive bacteria. In serious gram-positive infections for which there are other treatment options available, the spectrum of activity and efficacy of quinupristin/ dalfopristin should be weighed against its tolerability and drug interaction profile. However, in VREF or unresponsive MRSA infections, where few proven treatment options exist, quinupristin/dalfopristin should be considered as a treatment of choice for these seriously ill patients.     

Conformational constraint in oxazolidinone antibacterials. Synthesis and structure-activity studies of (azabicyclo[3.1.0]hexylphenyl)oxazolidinones

The oxazolidinones are a new class of synthetic antibacterials effective against a broad range of pathogenic Gram-positive bacteria, including multi-drug-resistant strains. Linezolid is the first drug from this class to reach the market and has become an important new option for the treatment of serious infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enteroccocus faecium (VRE). In the search for novel oxazolidinones with improved potency and spectrum, we have prepared and evaluated the antibacterial properties of conformationally constrained analogues in which the morpholine ring of linezolid is replaced with various substituted azabicyclo[3.1.0]hexyl ring systems. Several classes of azabicyclic analogues were identified with activity comparable or superior to that of linezolid. These include analogues bearing hydroxyl, amino, amido, or carboxyl groups on the azabicyclic ring. The azabicyclic acid analogue 50 was 4 times more potent than linezolid against key Gram-positive and fastidious Gram-negative pathogens (S. aureus, Streptococcus pneumoniae, and E. faecalis MICs < or = 1 microg/mL; Haemophilus influenzae MIC = 4 microg/mL).     

Evaluation of the in vitro activity of tigecycline against multiresistant Gram-positive cocci containing tetracycline resistance determinants

This study was undertaken to test the in vitro activity of tigecycline against 117 clinically relevant Gram-positive pathogens and to correlate this activity with their resistance gene content. Overall, tigecycline showed a minimal inhibitory concentration (MIC) range of 0.015-0.5mg/L, able to inhibit potently all multiresistant streptococci, enterococci and MR staphylococci. Tigecycline was active against methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, with MICs for 90% of the organisms (MIC(90)) of 0.25 mg/L and 0.12 mg/L, respectively, being more active than linezolid (MIC(90)=2 mg/L) and quinupristin/dalfopristin (MIC(90)=0.5 and 2-4 mg/L, respectively). Molecular characterisation of resistance determinants demonstrated the concomitant presence of different classes of genes: in particular, tet(M), erm(B) and erm(C) in Streptococcus agalactiae; tet(O), variably associated with different erm genes, in Streptococcus pyogenes; vanA, tet(M) and erm(B) in Enterococcus faecalis, and vanA and erm(B) in Enterococcus faecium. All the MRSA strains harboured SCCmec and erm genes and 50% possessed tet(K) with tet(M) genes. Staphylococcus epidermidis strains were only resistant to erythromycin. These results clearly demonstrate that tigecycline has a MIC(90) range of 0.015-0.5 mg/L both against tetracycline-susceptible and -resistant isolates carrying other resistance determinants, suggesting that this drug could play an important role in the treatment of infections caused by these multiresistant Gram-positive pathogens.     

Antimicrobial susceptibility of clinical isolates of aerobic Gram-positive cocci and anaerobic bacteria in 2006

The activity of antibacterial agents against aerobic Gram-positive cocci (26 species, 1022 strains) and anaerobic bacteria (23 species, 184 strains) isolated from clinical specimens in 2006 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 53.0% and 65.8%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 micrcog/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 87.6%. Ceftriaxone, cefpirome, cefepime, carbapenem antibiotics, VCM, teicoplanin, linezolid(LZD) and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 10.9% of E. faecalis strains or 3.5% of E. faecium strains showed intermediate or resistant to LZD. 24.4% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM were under 1 microg/mL, suggesting that VCM had excellent activity against C. difficile. Carbapenems showed good activity against Peptococcaceae, Bacteroides spp., and Prevotella spp. However since several strains of Bacteroides fragilis showed resistant to carbapenems and the susceptibility of this species should be well-focused in the future.     

Antibacterial activity of calozeyloxanthone isolated from Calophyllum species against vancomycin-resistant Enterococci (VRE) and synergism with antibiotics

Calozeyloxanthone ( 1) was re-isolated from the root bark of Calophyllum moonii, an endemic species of Sri Lanka, and found to be active against vancomycin-resistant Enterococci (VRE) and vancomycin-sensitive Enterococci (VSE) with MIC values of 6.25 microg/ml and 12.5 microg/ml, respectively. Further, a marked synergism between 1 and vancomycin hydrochloride (VCM) against VRE was also observed. These findings suggest that 1 in combination with VCM against VRE may be useful in controlling VRE infections.     

In vitro activity of RBx 7644 (ranbezolid) on biofilm producing bacteria

Biofilm associated infections are becoming more common. Treatment outcome of device related infections cannot be predicted by the results of a standard susceptibility test such as the MIC. Microorganisms involved in device related infections have a slow growth rate and adhere to surfaces. Activity against glass adherent bacteria has been shown to be correlated with treatment outcome in animal models of catheter related infections. Drug efficacy can be predicted if glass adherent staphylococci are killed by low drug concentration. The eradication of bacteria adhering to glass beads and inhibition of biofilm formation by ranbezolid and three other antibiotics (quinupristin/dalfopristin, vancomycin and linezolid) was studied. The results indicated that ranbezolid required only (2-4 x MIC) for total clearance of glass-adherent MRSA 562 and MRSE 879, compared with vancomycin (8 x), quinupristin/dalfopristin (1-4 x) and linezolid (4-16 x MIC). In addition ranbezolid inhibited biofilm formation to a greater extent at sub MIC and MIC level. In conclusion, this study indicated that ranbezolid had potent activity against adherent staphylococci isolates and may prove useful in the prevention and treatment of device related infections caused by staphylococci.     

Global in vitro activity of tigecycline and linezolid against Gram-positive organisms collected between 2004 and 2009

This study reports the antimicrobial activity of tigecycline and comparator antimicrobials, including linezolid, against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) between 2004 and 2009. Minimum inhibitory concentrations (MICs) were determined using broth microdilution methodology according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Antimicrobial susceptibility was determined according to CLSI criteria. For tigecycline, the US Food and Drug Administration (FDA)-approved criteria were used. Overall, 41.3% (8249/19 982) of S. aureus collected were meticillin-resistant S. aureus (MRSA). All MRSA were susceptible to linezolid and 99.98% were susceptible to tigecycline. A total of 2.3% of E. faecalis (201/8576) and 39.7% of E. faecium (1226/3088) were vancomycin-resistant. Linezolid and tigecycline MIC(90) values (MIC at which 90% of isolates inhibited) against the Enterococcus spp. were 2mg/L and ≤ 0.25 mg/L, respectively. All S. pneumoniae [including 6.2% (599/9618) penicillin-non-susceptible] were susceptible to linezolid and vancomycin; tigecycline MIC(90) values were ≤ 0.12 mg/L. This report demonstrates the continuing good activity of tigecycline and linezolid against Gram-positive isolates globally, including resistant organisms such as MRSA, vancomycin-resistant enterococci and penicillin-resistant S. pneumoniae, with antimicrobial activity maintained over the 6 years of isolate collection.     

Colorimetric in vitro susceptibility testing of penicillins, cephalosporins, macrolides, streptogramins, tetracyclines, and aminoglycosides against Borrelia burgdorferi isolates

The spectrum of antibiotic susceptibility of Borrelia burgdorferi has been only partially defined. In the present study the effectiveness of 12 antimicrobials, belonging to six different antibiotic classes have been tested against Borrelia burgdorferi s.s. (N=3), Borrelia garinii (N=3), Borrelia afzelii (N=3), Borrelia valaisiana (N=1), and Borrelia bissettii (N=1) isolates. These isolates were analysed by a new standardised colorimetric minimal inhibitory concentration (MIC) method based upon colour changes that result from actively metabolizing spirochaetes after 72 h of incubation. Piperacillin (MIC90: 0.08 mg/l), ceftriaxone (MIC90: 0. 04 mg/l), cefotaxime (MIC90: 0.15 mg/l), azithromycin (MIC90: 0.015 mg/l), roxithromycin (MIC90: 0.05 mg/l) and quinupristin/dalfopristin (MIC90: 0.12 mg/l) gave the lowest MIC values. Minimal inhibibitory activity of amoxycillin (MIC90: 1.04 mg/l), cefixime (MIC90: 1.33 mg/l), cefoperazone (MIC90: 0.83 mg/l) tetracycline (MIC90: 0.29 mg/l) and minocycline (MIC90: 0.30 mg/l) was slightly lower, whereas borrelia were resistant to amikacin (MIC90: >128 mg/l). Mean minimal borreliacidal concentrations (MBCs) were representatively determined for piperacillin (MBC: 1.8 mg/l), ceftriaxone (MBC: 2.0 mg/l), azithromycin (MBC: 0.82 mg/ml), roxithromycin (MBC: 1.8 mg/l), quinupristin/dalfopristin (MBC: 5.0 mg/l), minocycline (MBC: 5.8 mg/l), and amikacin (MBC: >128 mg/l) by using conventional subculture for three weeks in combination with dark-field microscopy. B. garinii proved to be the most susceptible of the genospecies tested. Our study showed excellent in vitro antimicrobial activity of all classes of antibiotics tested, except the aminoglycosides and hence their suitability for therapy of Lyme disease.     

Peritoneal dialysis fluid concentrations of linezolid in the treatment of vancomycin-resistant Enterococcus faecium peritonitis

OBJECTIVE: To determine linezolid concentrations in peritoneal dialysis fluid after multiple oral doses of the drug in a 46-year-old man with vancomycin-resistant Enterococcus faecium peritonitis who was undergoing peritoneal dialysis. METHODS: After administration of oral linezolid 600 mg twice/day was started, peritoneal dialysis fluid was collected at the end of several 4- and 8-hour dwell times and submitted for analysis of linezolid concentration. Before linezolid therapy was begun, and immediately after several peritoneal dialysis exchanges, 30 ml of expended peritoneal dialysis fluid was collected in a sterile container and immediately frozen at -70 degrees C until analysis by high-performance liquid chromatography. RESULTS: Peritoneal dialysis concentrations of linezolid greater than 4 microg/ml were achieved after the first dose of linezolid and maintained after repeated doses. During the course of therapy, mean linezolid concentrations in peritoneal dialysis fluid tended to increase (mean 7.60 pg/ml, range 3.54-16.2 microg/ml). All assayed peritoneal dialysis samples demonstrated linezolid concentrations greater than 4 microg/ml at the end of 4- or 8-hour dwell times, except for one level after a missed dose on linezolid treatment day 3. Duration of dwell times did not appear to correlate with linezolid concentrations. CONCLUSION: In this patient, linezolid 600 mg twice/day penetrated into peritoneal dialysis fluid at or above the concentrations necessary to treat common gram-positive bacteria. Linezolid therapy is likely to have a role in peritoneal dialysis-associated peritonitis based on its antimicrobial activity, pharmacokinetic properties, ease of administration, and tolerability.     

LC-MS/MS determination of Synercid injections

Synercid is a combination of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin in 30:70 (w/w) ratio. A rapid and specific high-performance liquid chromatography-mass spectrometry was developed for the determination of quinupristin and dalfopristin using positive electrospray tandem mass spectrometry (+ESI-MS/MS). Multiple reaction monitoring transitions at 1023.05>134.34 and 691.87>166.26 were selected for the quantitation of quinupristin and dalfopristin, respectively. The assay run cycle-time was approximately 2.0 min injection-to-injection. The assay was linear up to concentration of 4000 ng x ml(-1) quinupristin and 1920 ng x ml(-1) dalfopristin. The lowest limits of quantitation of quinupristin and dalfopristin were found to be 1000 and 480 ng x ml(-1), respectively. Quantitation was based on peak area measurement of quinupristin and dalfopristin using weighed linear regression. Linear relationships with correlation coefficients (r>0.99) were automatically computed for both constituents by MASSLYNX quantify program. The ratio of the slopes of the calibration curves of quinupristin and dalfopristin was found to be 0.425, which matches the nominal ratio composition of the antimicrobial compounds in Synercid. The %RSD ranges were 2.3-4.0% for dalfopristin and 1.3-4.2% for quinupristin, whereas the %DEV ranges were (-7.5+3.7) and (-1.2+9.1%), respectively, indicating appropriate precision and accuracy. Recoveries of 99.5-103.8% and 97.8-99.0% of quinupristin and dalfopristin, respectively, were computed from Synercid injection. The described method is recommended for rapid determination of the contents and for tracking the stability and compatibility of quinupristin and dalfopristin in Synercid injection.     

In vitro activity of WY-49605, a penem antimicrobial

The in vitro activity of the penem antimicrobial WY-49605 was compared with those of other agents available for oral administration. Based on concentrations inhibiting 90% of isolates (MIC(90)s), the penem inhibited methicillin-susceptible staphylococci (MIC(90) = 0.25 microg/ml), penicillin-susceptible streptococci (MIC(90) < or = 0.12 microg/ml) and several other Gram-positive genera at concentrations comparable or superior to the most active comparison agents. WY-49605 and cefpodoxime were the most active agents against members of the family Enterobacteriaceae. Most strains of Enterococcus faecalis and Bacteroides fragilis were susceptible to the new agent at concentrations < or =4microg/ml, while Pseudomonas aeruginosa, Enterococcus faecium, and methicillin-resistant Staphylococcus aureus were resistant to all agents tested.     

老年患者屎肠球菌感染的临床分布及耐药性分析

目的探讨老年患者屎肠球菌感染的临床分布特点,并分析其对临床常用抗菌药物的耐药性,为临床合理治疗屎肠球菌感染提供参考依据。方法采用回顾性分析及统计分析方法,收集我院2013年1月至2015年12月期间屎肠球菌感染的老年患者(≥65岁)的临床数据,对其进行感染现状及耐药性分析。结果3年内共检出屎肠球菌感染384例,其检出率呈逐年升高趋势。屎肠球菌感染的标本类型中尿液所占比例最高,达47.14%,其次为引流液和全血标本,分别占19.53%和16.15%。在科室分布中,标本主要分离于重症监护病房(ICU)、普通外科病房和呼吸内科病房,分别占23.96%、20.57%和16.41%。药敏结果显示:屎肠球菌对氨苄西林、红霉素、环丙沙星、克林霉素、莫西沙星、青霉素G、左氧氟沙星等抗菌药物的耐药性均超过90%,而对喹奴普汀/达福普汀、替加环素、万古霉素、利奈唑胺等药物具有高度敏感性。结论屎肠球菌对不同抗菌药物的敏感性不同,且其院内感染近年有增高趋势,对屎肠球菌感染的耐药性监测,有利于指导临床合理用药。