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PubMed1988

Interaction of ciprofloxacin with ampicillin and vancomycin for Streptococcus faecalis.

Streptococcus faecalis is known to be resistant to killing by many of the commonly used antimicrobial agents. Ciprofloxacin, a member of the quinolone class of compounds, was studied for its ability to inhibit and to kill S. faecalis. The rate of killing by ciprofloxacin was slow and was comparable to that of ampicillin or vancomycin. The antimicrobial effect of combining ciprofloxacin with ampicillin or with vancomycin was also studied using checkerboard double-dilution and killing kinetics. There was no synergy or antagonism between ciprofloxacin and either cell wall active agent. Unlike the aminoglycosides, the addition of ciprofloxacin did not produce additional killing over that of ampicillin or of vancomycin alone.

Ampicillin↗
PubMedDate not supplied

Effect of human serum on the bactericidal activity of daptomycin and vancomycin against staphylococcal and enterococcal isolates as determined by time-kill kinetic studies.

The bactericidal activity of daptomycin and vancomycin alone in cation-supplemented Mueller-Hinton broth and in human serum against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis was evaluated by exposing replicating microorganisms to concentrations ranging from 2 to 128 micrograms/ml for 24 hr. In addition, the possibility of emergence of resistance, the stability of each agent in the respective medium, and the percent of protein binding by human serum for each agent was evaluated. We found that a concentration of less than or equal to 8 micrograms/ml of daptomycin was sufficient to achieve bactericidal activity (greater than or equal to 99.9% killing of the inoculum) in cation-supplemented Mueller-Hinton broth for all staphylococcal isolates tested; a concentration of less than or equal to 16 micrograms/ml of daptomycin was required for bactericidal activity in cation-supplemented Mueller-Hinton broth for enterococcal isolates. In human serum, comparable bactericidal activity with daptomycin was achieved only with concentrations 8-16 times higher. A similar but less pronounced effect in human serum was seen for vancomycin. Neither daptomycin nor vancomycin was appreciably degraded in human serum over a 24-hr period. It is likely that the clinical efficacy of daptomycin in humans would be enhanced by higher dosing than has been studied to date.

Anti-Bacterial Agents↗
PubMedDate not supplied

The bactericidal activity of ampicillin, daptomycin, and vancomycin against ampicillin-resistant Enterococcus faecium.

Ampicillin, daptomycin, and vancomycin, alone and in combination with gentamicin, were examined for bactericidal effects on ampicillin-resistant Enterococcus faecium using broth dilution minimum inhibitory concentrations (MICs) and time-kill studies. We tested 12 ampicillin-resistant isolates and demonstrated the following MICs and MBCs, respectively: ampicillin, greater than or equal to 32 micrograms/ml and greater than 256 micrograms/ml; daptomycin, less than or equal to 4 micrograms/ml and less than or equal to 16 micrograms/ml; and vancomycin, less than or equal to 4 micrograms/ml and greater than 64 micrograms/ml. Time-kill studies demonstrated that daptomycin alone had marked activity against the ampicillin-resistant E. faecium and that the addition of gentamicin resulted in synergistic killing. In addition, ampicillin and vancomycin were not bactericidal for the ampicillin-resistant isolates without the addition of gentamicin. The present study supports the consideration of daptomycin alone or in combination with an aminoglycoside as an alternative therapy for ampicillin-resistant enterococci, although additional clinical experience is now necessary.

Ampicillin↗
PubMed2005

Using surface plasmon resonance to directly identify molecules in a tripeptide library that bind tightly to a vancomycin chip.

This paper describes a procedure, based on direct binding, for identifying tight-binding ligands for a receptor immobilized on a sensor chip from an array of equimolar tripeptides using surface plasmon resonance. Vancomycin and a library of 96 tripeptides, with molecular weight ranging from 316 to 560 Da, were used as a model system to illustrate the procedure. A consensus structure of the strongest interacting peptides consisted of D-Ala at the C terminus and aromatic amino acid in the penultimate position. Ligands having this structure bound more tightly to vancomycin than the known D-Ala-D-Ala peptide. The throughput of our continuous assay is 96 compounds in 3.3 h, and the sample consumption is less than 2 microg per peptide and 1 ng for vancomycin. This procedure should be applicable to peptide libraries of greater complexity than that used here and to mixtures of small organic compounds.

Ligands↗
PubMed2005

Comparison of vancomycin-based stationary phases with different chiral selector coverage for enantioselective separation of selected drugs in high-performance liquid chromatography.

Two vancomycin-based chiral stationary phases (CSPs) with different coverage of the chiral selector vancomycin (Chirobiotic V and Chirobiotic V2) were compared. beta-Blockers and profens, as structurally diverse groups of drugs, were chosen as analytes. Retention and enantioseparation of beta-blockers were studied in reversed-phase (RP) and polar-organic (PO) separation modes. Higher retention and better enantioresolution were obtained on the CSP with higher coverage of vancomycin in the both separation modes. Baseline separation of four beta-blockers (eight enantiomers) in the PO mode was achieved on the Chirobiotic V2 column within 15 min. The enantioseparation of profens did not bring so excellent and easy to interpret results. Higher retention of profens on the Chirobiotic V2 column was not always accompanied by an improvement of their chiral separation in the RP mode. The polar-organic mode was not suitable for these derivatives at all. The most interesting result was obtained with flobufen; its chiral center is further away from the rigid part of the molecule, which mostly causes difficulties in enantioselective recognition. Nevertheless, the enantiomers of flobufen were shown to be much better (baseline) resolved on the CSP with lower coverage of the chiral selector (Chirobiotic V).

Chromatography, High Pressure Liquid↗
PubMed2005

Clinical isolates of Staphylococcus aureus from 1987 and 1989 demonstrating heterogeneous resistance to vancomycin and teicoplanin.

Fifty isolates of Staphylococcus aureus, obtained during a multicenter clinical trial evaluating the efficacy of teicoplanin that was performed between 1987 and 1992, underwent glycopeptide susceptibility testing, and 2 isolates were found to be capable of growth on agar containing 4 or 8 mg/L of vancomycin. Both of these isolates were from patients that had received prolonged teicoplanin therapy and were deemed clinical failures. Extended susceptibility testing combined with mecA gene probing revealed that one isolate was susceptible to oxacillin, the other was resistant, and both were susceptible to a variety of nonglycopeptide agents. Population analyses revealed heterogeneous vancomycin- and teicoplanin-susceptibility profiles. Both strains were differentiated from recent glycopeptide intermediately resistant Staphylococcus aureus isolates by pulse-field analysis and by the fact that the resistance phenotype was stable to multiple serial passages. To our knowledge, this is the earliest report of S. aureus clinical isolates having reduced vancomycin and teicoplanin susceptibility.

Analysis of Variance↗
PubMed2004

In vitro effect of levofloxacin and vancomycin combination against high level aminoglycoside-resistant enterococci.

The in vitro effects of levofloxacin and vancomycin in combination were evaluated against high level aminoglycoside-resistant (HLAR) enterococci using chequerboard and time-kill curve techniques. We examined 28 strains of enterococci comprising 17 Enterococcus faecalis, 10 E. faecium and one E. durans. The combination of vancomycin and levofloxacin had indifferent activity against all isolates according to chequerboard microdilution method, but was synergistic for two isolates, one E. faecium and one E. faecalis, using the time-kill curve method. Both strains were levofloxacin resistant and had high level aminoglycoside resistance to gentamicin and streptomycin. Antagonism was not detected in any strain. The results of this study suggested that the combination of vancomycin with levofloxacin does not often show synergistic effect against high level aminoglycoside-resistant enterococci.

Aminoglycosides↗
PubMed2005

Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA).

We compared the health outcomes in patients treated with linezolid or vancomycin for complicated skin and soft tissue infections (cSSTIs). This analysis is part of a randomised, open-label, multinational trial involving 1200 adult patients hospitalised with cSSTIs due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects received linezolid 600 mg intravenous (i.v.) or oral, or vancomycin 1g i.v. every 12 h. A test-of-cure was assessed at 7 days post therapy. Compared with vancomycin, linezolid treatment was associated with significantly shorter length of stay (all P < 0.01), decreased i.v. antibiotic treatment duration (all P < 0.0001) and higher discharge rates (all P < 0.05). Thus, linezolid has the potential to reduce medical resource use for the treatment of cSSTIs.

Acetamides↗
PubMed2006

Loading dose of vancomycin in critically ill patients: 15 mg/kg is a better choice than 500 mg.

Delays in antimicrobial therapy in high-risk patients with infection may have deleterious effects on clinical outcomes. Therefore, appropriate treatment must be initiated promptly. The objective of this prospective study was to determine the better loading dose of vancomycin in critically ill patients with suspected Gram-positive infections. Two groups of patients were studied successively: Group A, loading dose of 500 mg; and Group B, loading dose of 15 mg/kg. The mean post-loading dose serum vancomycin concentration was significantly higher in Group B than in Group A (19.1 +/- 7.4 mg/L versus 10.4 +/- 2.7 mg/L; P < 0.001), without producing toxic peak levels. Clinical cure rates were significantly different for infected patients in Group B compared with Group A: 93% (14 of 15 patients) versus 56% (10 of 18 patients), respectively. However, the proportion of patients surviving to Intensive Care Unit discharge was similar. Because vancomycin is believed to achieve maximum killing at concentrations in serum of four to five times the minimum inhibitory concentration for the infecting organism, our results suggest that the 15 mg/kg loading dose should be preferred.

Aged↗
PubMed2006

Heterogeneous resistance to vancomycin in Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains: characterisation of glycopeptide susceptibility profiles and cell wall thickening.

The population analysis profile (PAP) method as well as analysis of autolytic activity and cellular ultrastructure by transmission electron microscopy (TEM) were used to characterise Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains with reduced susceptibility to glycopeptides. All strains showed heterogeneous profiles to vancomycin and teicoplanin by the PAP method. Subpopulations that grew in the presence of high concentrations of each drug were selected from the PAP as derivative strains. Their glycopeptide minimal inhibitory concentrations (MICs) were determined and subsequently all parental and derivative strains were grown in one-half of the MIC of vancomycin or teicoplanin. An increase in cell wall thickness of all derivative strains was seen by TEM, with statistically significant values (P<0.01) compared with their respective parental strains. In general, variable rates of autolysis among the strains were observed. Cell wall thickness is an important factor involved in glycopeptide resistance and, in association with PAP results, confirmed the Brazilian coagulase-negative staphylococci clinical isolates as being heteroresistant to glycopeptides. Detection of these heteroresistant organisms is important in order to achieve more judicious use of vancomycin and teicoplanin in hospitals.

Anti-Bacterial Agents↗
PubMed2006

Molecular epidemiology of urinary tract isolates of vancomycin-resistant Enterococcus faecium from North America.

Vancomycin-resistant Enterococcus faecium (VRE) are a common cause of nosocomial infections and are important agents of gastrointestinal colonisation. As the prevalence of VRE in hospitalised patients continues to increase, implementation of appropriate infection control measures requires routine surveillance of VRE transmission patterns. The purpose of the present study was to investigate the molecular epidemiology of VRE isolates within the USA and Canada. Two hundred and eighty-three urinary tract isolates of VRE were collected in the year 2000 from ten Canadian hospitals and 28 US tertiary care medical centres representing seven of the nine geographic regions of the United States Bureau of the Census. The in vitro activity of vancomycin, teicoplanin and nine comparators was determined by broth microdilution. The genetic relatedness among isolates was evaluated by pulsed-field gel electrophoresis (PFGE). Resistance rates (intermediate and resistant) were 100% for vancomycin and 78.7% for teicoplanin. Resistance was lowest with linezolid, chloramphenicol and nitrofurantoin at 0.3%, 0.3% and 0.5%, respectively. PFGE revealed that genetic heterogeneity amongst isolates from each of the medical centres varied considerably. Despite some intracentre and intercentre VRE dissemination, the present study found no evidence for the emergence of a dominant clonal strain. This suggests that the spread of VRE within North America is a complex process involving both the horizontal transfer of glycopeptide resistance determinants and polyclonal dissemination.

Canada↗
PubMed2006

In vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.

Tigecycline is a glycylcycline with promising broad-spectrum activity, including resistant Gram-positive organisms. This study characterizes in vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae (QRSP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). An in vitro pharmacodynamic model generated specific bacterial kill profiles for tigecycline against clinical isolates of QRSP, MRSA and VRE. Tigecycline produced a 6.6 log total reduction and cleared QRSP from the pharmacodynamic model by 18 h. Tigecycline and vancomycin were unable to achieve 3-log reductions in the MRSA and VRE isolates; log reductions in MRSA and VRE were 1.5 and 1.2 logs for tigecycline and 2.8 and zero for vancomycin, respectively. Area under the concentration time curve to minimum inhibitory concentration (AUC/MIC) values for tigecycline ranged from 79 to 158 microg h/mL and tigecycline concentrations remained above the MIC (T>MIC) throughout the simulated dosing interval. Tigecycline showed in vitro activity against the QRSP, MRSA and VRE isolates studied. Low MIC values, prolonged elimination half-life and the associated post-antibiotic effect (PAE) observed with tigecycline are desirable attributes that make it a potentially attractive option for treating resistant Gram-positive organisms.

Anti-Bacterial Agents↗
PubMed2006

Genetic analysis of the balhimycin (vancomycin-type) oxygenase genes.

In the balhimycin biosynthesis three oxygenases OxyA, OxyB and OxyC are responsible for the oxidative phenol coupling reactions, which lead to the ring-closures between the aromatic amino acid side chains in the heptapeptide aglycone. These ring-closures constrain the peptide backbone into the cup-shaped conformation that is required for binding to the Lys-D-Ala-D-Ala-terminus of the cell wall precursor peptide and represent one of the essential features of glycopeptide antibiotics. In the balhimycin biosynthetic gene cluster the oxygenase genes oxyA, oxyB and oxyC have been identified downstream of the peptide synthetase genes. Reverse transcription (RT)-PCR analyses revealed that these oxygenase genes in Amycolatopsis balhimycina are co-transcribed. Non-polar mutants (NPoxyA, DeltaoxyB and DeltaoxyC) were constructed, cultivated in production medium and assayed for the presence of glycopeptides and glycopeptide precursors by HPLC-ESI-MS. The mutant NPoxyA produces mainly monocyclic, the mutant DeltaoxyB linear and the mutant DeltaoxyC bicyclic peptides. These results definitely confirm the sequence of the three oxidative ring-closing steps (OxyB-OxyA-OxyC). The heterologous complementation of the mutant strains with the corresponding oxygenase genes from the vancomycin producer A. orientalis restored the production of balhimycin, which proves the functional equivalence of the oxygenases from the balhimycin and vancomycin producer. For the first time it is now possible to combine the genetic data obtained from the balhimycin producer with the biochemical and structural data obtained from the vancomycin producer.

Actinomycetales↗
PubMed2006

Prospective randomized controlled trial of the effect of intracameral vancomycin and gentamicin on macular retinal thickness and visual function following cataract surgery.

PURPOSE: To investigate whether the use of vancomycin (20 microg/mL) and gentamicin (8 microg/mL) in the infusion fluid at the time of cataract surgery increases the incidence of macular thickening as measured with optical coherence tomography (OCT) following phacoemulsification. SETTING: A public teaching hospital in Western Australia. METHODS: Fourty-one patients (50 eyes) with cataracts between 50 and 85 years of age were randomized to receive no antibiotics in the infusion fluid at the time of cataract surgery (control group) or vancomycin (20 microg/mL) and gentamicin (8 microg/mL) in the infusion fluid (antibiotic group). Optical coherence tomography measurements were performed preoperatively and 1 day and 1 and 5 weeks postoperatively. A significant increase in macular thickness (mean of the central 1.0 mm diameter) on OCT was defined as 15 microm or greater. Five weeks postoperatively, the best corrected Snellen acuity and Pelli-Robson contrast sensitivity were measured. RESULTS: Twenty-five percent in the control group and 38% in the antibiotic group had a significant increase in macular thickness measured on OCT 5 weeks postoperatively (P = .34). The mean contrast sensitivity of patients with increased macular thickness on OCT was 1.26, and in those with no change it was 1.43 (P = .001). CONCLUSIONS: The use of intracameral vancomycin (20 microg/mL) and gentamicin (8 microg/mL) at the time of cataract surgery had no significant effect on macular thickness or visual function postoperatively. Overall, 31% of eyes showed an increase of 15 microm or greater in central retinal thickness. These patients had significantly reduced contrast sensitivity.

Aged↗
PubMed2004

[Heterogeneity of Brain Heart Infusion agar media (BHI): effects on the determination of the vancomycin and the teicoplanin minimal inhibitory concentrations (MIC) of Staphylococcus aureus strains].

The influence of BHI media commercially available on the results of glycopeptides MIC measured by E-test method was studied on 36 S. aureus isolates (21 MRSA and 15 MSSA). The MIC obtained with the vancomycin and the teicoplanin determined by the E-test method, on the ready prepared BHI plates (AES) and the plate prepared at the laboratory among the four dehydrated bases (AES, Biorad, Oxoid, and Becton Dickinson), were compared. The mean of the MIC showed variations from 3.14 (Biorad) to 5.25 mg/L (Oxoid) and from 3.33 (Biorad) to 9.75 mg/L (ready prepared AES) respectively for the vancomycin and for the teicoplanin. A variance analysis (Test de Friedman) showed a significant difference between the five media (p <0.001) with the two antibiotics. The comparison of media 2 by 2 allowed that all combinations excepted one (Biorad vs Becton with the vancomycin) were statistically different (p <0.001). The variation of the MIC observed in relation to the origin of the product of BHI media requires the inclusion of glycopeptide-intermediate S. aureus reference strains to control the prepared culture media.

Anti-Bacterial Agents↗
PubMed1997

Vancomycin-resistant enterococci.

Enterococci have been recognized as an important cause of nosocomial infections for almost 20 years and as a cause of endocarditis for almost a century. While long known for their capacity of displaying multiple antibiotic resistant traits, the extent to which this could occur was not fully appreciated until the emergence of enterococci with acquired resistance to vancomycin; this resistance has been particularly problematic because it often occurs in the uncommon subset of enterococci that are also highly resistant to ampicillin-a combination with devastating therapeutic consequences. The observation that vancomycin resistance can be transferred to and expressed in other gram-positive organisms, for which vancomycin is often considered the primary therapeutic alternative, is a chilling reminder of just how close we may be to a wide array of potentially untreatable "killer" microbes.

Anti-Bacterial Agents↗
PubMed1996

Coagulase-negative Staphylococcus endophthalmitis after cataract surgery with intraocular vancomycin.

PURPOSE: We studied a case of postoperative coagulase-negative Staphylococcus endophthalmitis in a 79-year-old man who had undergone cataract extraction in which vancomycin had been used intraoperatively in the infusion fluid. METHODS: The medical records were reviewed for the clinical history, ocular findings, and the vitreous and anterior chamber culture results. RESULTS: Acute, postoperative coagulase-negative Staphylococcus endophthalmitis developed in the patient in whom vancomycin had been used intraoperatively in the infusion fluid. CONCLUSIONS: Restraint is urged in the prophylactic use of vancomycin in the infusion fluids.

Acute Disease↗
PubMed2000

Rapid serum vancomycin assay by high-performance liquid chromatography using a semipermeable surface packing material column.

A new isocratic high-performance liquid chromatographic (HPLC) assay has been developed for vancomycin that uses direct injection of microquantities of serum into a separation column filled with octyl-C(8) silica support that has a semipermeable surface. A mixture of disodium hydrogen phosphate buffer (pH 7.0) and acetonitrile is used as the mobile phase, and vancomycin is directly detected at 240 nm. The minimum limit of detection was 0.5 microg/ml at a signal-to-noise ratio of 3:1. Linearity was established from 0 to 100 microg/ml. The coefficient of variation for within-run reproducibility was 1.1-2.7% for a concentration range of 2.9-52.5 microg/ml; for day-to-day reproducibility it was 4.0% and 3.1% for a concentration range of 5.8-26.4 microg/ml, and the recovery rate was 94-105%. There was no interference from 41 antibiotics or other drugs currently in use. The correlation coefficient between the fluorescence polarization immunoassay (x) and this method (y) was 0.995 with a linear equation, y = 1.06x - 0.924. This method is simple, rapid, and provides an economical quantification of serum vancomycin.

Anti-Bacterial Agents↗