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Acute renal failure owing to inadvertent vancomycin overdose. Vancomycin removal by continuous arteriovenous hemofiltration.

Acute renal failure developed in a patient who received 56 grams of vancomycin intravenously over a 10 day period. The resulting serum vancomycin level was 284 micrograms per ml and declined to 140 micrograms per ml in a linear fashion with the institution of continuous arteriovenous hemofiltration (CAVH). Our conclusion is that high blood vancomycin levels may be nephrotoxic and CAVH may be an effective means of vancomycin removal in patients with acute renal failure.

Acute Kidney Injury↗

Inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 56647) and five comparative antibiotics, used singly and in combination, against vancomycin-resistant and vancomycin-susceptible enterococci.

The inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 66647) were compared with those of gentamicin, ampicillin, erythromycin, azithromycin and vancomycin against 74 strains of enterococci (34 Enterococcus faecalis and 40 Enterococcus faecium) by agar dilution, broth dilution, time kill assays and postantibiotic effect (PAE). The telithromycin MIC(90) for vancomycin-sensitive (VSE) E. faecalis strains tested using the agar dilution method was 8 microg/ml. For a different group of VSE E. faecalis strains tested using the broth dilution method it was 0.06 microg/ml The telithromycin MIC(90)s for vancomycin-resistant (VRE) and VSE E. faecium strains, determined using the agar dilution method, were 4 and 8 microg/ml, respectively, while for a different set of VRE and VSE E. faecium strains tested using the broth macrodilution method, they were 32 and 16 microg/ml, respectively. Telithromycin MBC(90)s for E. faecalis were 4-6 tubes higher and for E. faecium 3-5 tubes higher, respectively, than the MIC(90)s. In time kill assays, telithromycin had bactericidal activity against only 1 of 7 E. faecium strains; for all other E. faecium and E. faecalis strains, only inhibitory activity was demonstrated. Neither synergy nor drug interference was observed when telithromycin was used in combination with ampicillin, vancomycin or gentamicin. At 10 times the MIC, the PAE of telithromycin against E. faecalis was 2.8 h, while for E. faecium it was 1.6 h. Telithromycin should be evaluated for therapy of enterococcal infections, including those caused by VRE organisms. However, because of the strain-to-strain variability in susceptibility to telithromycin, MIC determinations are important, especially for erythromycin-resistant strains.

Anti-Bacterial Agents↗

Antibacterial activity of phytochemicals isolated from Erythrina zeyheri against vancomycin-resistant enterococci and their combinations with vancomycin.

Six phytochemicals were isolated from the roots of Erythrina zeyheri (Leguminosae) by repeated silica gel column chromatography using various eluting solvents. Extensive spectroscopic studies revealed that all were isoflavonoids. The antibacterial activity of the six compounds against vancomycin-resistant enterococci (VRE) was estimated by determining the minimum inhibitory concentration (MIC). Of the six isoflavonoids, erybraedin A ((6aR, 11aR)-3,9-dihydroxy-4,10-di(gamma,gamma-dimethylallyl)pterocarpan) exhibited the highest growth inhibitory potency against VRE with an MIC value of 1.56-3.13 microg/mL, followed by eryzerin C ((3R)-7,2',4'-trihydroxy-6,8-di(gamma,gamma-dimethylallyl)isoflavan) (MIC 6.25 microg/mL). These compounds also inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.13-6.25 microg/mL. The antibacterial effects of the two compounds against VRE and MRSA were based on bacteriostatic action. When erybraedin A or eryzerin C was combined with vancomycin, the fractional inhibitory concentration (FIC) index against VRE ranged from 0.5306 to 1.0 and from 0.5153 to 0.75, respectively. The combinations also showed FIC indices of 0.6125-1.0 against MRSA. The results indicate that, depending on the case, both compounds act either synergistically or additively with vancomycin against VRE and MRSA. Erybraedin A and eryzerin C show evidence of being potent phytotherapeutic agents against infections caused by VRE and MRSA.

Anti-Bacterial Agents↗

Sudden increase of vancomycin-resistant enterococcal infections in a Korean tertiary care hospital: possible consequences of increased use of oral vancomycin.

A sudden increase in vancomycin-resistant enterococci (VRE) infections was noted in 1998 in a tertiary care hospital in Korea. All of the VRE isolated in 1998 in the hospital were VanA type and most were multidrug-resistant Enterococcus faecium. The increase in VRE was probably due to the increased use of oral vancomycin to treat Clostridium difficile infections and clonal as well as horizontal spread. More restricted oral vancomycin use and stricter infection control measures are required to achieve a better control of the spread of VRE.

Administration, Oral↗

Impact of flavophospholipol and vancomycin on conjugational transfer of vancomycin resistance plasmids.

The influence of vancomycin and flavophospholipol (FPL) on the transfer rate of conjugative plasmids harboring the vancomycin resistance operon vanA was determined in several clinical and animal isolates of Enterococcus faecium. FPL significantly inhibited the frequency of transfer of conjugative VanA plasmids up to 70-fold. Vancomycin had no significant effect on the transfer rate of VanA plasmids.

Anti-Bacterial Agents↗

Evidence for biliary excretion of vancomycin into stool during intravenous therapy: potential implications for rectal colonization with vancomycin-resistant enterococci.

Sixty-three stool samples and five bile samples were prospectively collected from 33 patients receiving intravenous vancomycin therapy and were quantitatively analyzed for vancomycin by a competitive immunoassay. Vancomycin was excreted via bile into the stools of almost all patients at concentrations of 3.3 to 94.8 microg/ml after >/=5 days of a therapy of 1 g every 12 h.

Anti-Bacterial Agents↗

Correlation between Reduced Daptomycin Susceptibility and Vancomycin Resistance in Vancomycin-Intermediate Staphylococcus aureus.

We present here findings of a strong positive correlation between reduced daptomycin susceptibility and vancomycin resistance in vancomycin-intermediate Staphylococcus aureus (VISA). This correlation is related to cell wall thickening, suggesting that, similar to the case with vancomycin resistance in VISA, the physical barrier of a thickened cell wall may contribute to daptomycin resistance in S. aureus.

Anti-Bacterial Agents↗

In vitro activity of chloramphenicol alone and in combination with vancomycin, ampicillin, or RP 59500 (quinupristin/dalfopristin) against vancomycin-resistant enterococci.

Using a checkerboard assay, ampicillin, vancomycin, and RP 59500, each in combination with chloramphenicol, were tested for synergy against 23 isolates of vancomycin-resistant enterococci. Additive effects were seen in 62.5% of the isolates when exposed to chloramphenicol plus RP 59500. Additive effects were observed in 20% and 15% of isolates with chloramphenicol plus vancomycin or ampicillin, respectively. No antagonism was noted.

Ampicillin↗

In vitro activities of six fluoroquinolones against Canadian isolates of vancomycin-sensitive and vancomycin-resistant Enterococcus species.

The in vitro activities of six fluoroquinolones were determined against 1482 Enterococcus species isolates collected as part of a 1996 Canadian surveillance study. Clinafloxacin MIC90s were 4 or 8 microg/mL, trovafloxacin and BAY 12-8039 MIC90s were 8 or 16 microg/mL, sparfloxacin MIC90s were 32 microg/mL, and ciprofloxacin and ofloxacin MIC90s were >32 microg/mL for the vancomycin-sensitive Enterococcus faecalis, vancomycin-sensitive Enterococcus faecium, and vancomycin-resistant E. faecium isolates collected.

Anti-Bacterial Agents↗

Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear modifications in the residue 3 asparagine.

The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitrile, rather than a carboxamide. Although this modification typically was detrimental to antimicrobial activity, hydrophobic vancomycin aglycon analogues that lack a lipid anchor as well as the disaccharide are detailed that exhibit unusual potency against VanB, but not VanA, resistant bacteria.

Anti-Bacterial Agents↗

Risk factors for development of vancomycin-resistant enterococcal bloodstream infection in patients with cancer who are colonized with vancomycin-resistant enterococci.

Vancomycin-resistant Enterococcus faecium (VRE) is a common nosocomial isolate, especially among patients with cancer. VRE infections have substantial attributable mortality among patients with cancer. The purpose of this study was to identify risk factors for developing bloodstream infection with VRE in patients with cancer who are colonized with VRE. VRE colonization was prospectively identified in 197 patients with cancer during 4-year period, of whom 179 (91%) had complete records for evaluation. Of these 179 patients, 24 (13.4%) developed hospital-acquired VRE bloodstream infections. Risk factors for VRE bloodstream infection included vancomycin use (relative risk [RR], 1.98; 95% confidence interval [CI], 1.25-3.14), diabetes mellitus (RR, 3.91; 95% CI, 1.20-12.77), gastrointestinal procedures (RR, 4.56; 95% CI, 1.05-19.7), and acute renal failure (RR, 3.10; 95% CI, 1.07-8.93). Strategies for preventing VRE bloodstream infection in VRE-colonized patients with cancer should include limiting vancomycin use and, perhaps, gastrointestinal procedures.

Bacteremia↗

Prescribing pattern of vancomycin in a community teaching hospital with low prevalence of vancomycin-resistant enterococci.

A 1-month prospective survey of all inpatients given vancomycin was performed in a community teaching hospital with a low prevalence of vancomycin-resistant enterococci. Only 20 of the 97 vancomycin orders written from August 1 to September 1, 1996, were consistent with Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines. Surgical prophylaxis accounted for 37 of the 77 orders inconsistent with HICPAC guidelines.

Drug Resistance, Microbial↗

In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium.

We assessed the in vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin (QD) against a contemporary challenge panel of 88 staphylococcal and 90 enterococcal isolates. The staphylococci selected included vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant S. aureus, and coagulasenegative staphylococci. Enterococcal isolates included vancomycin-resistant Enterococcus faecium (VREF) containing either vanA, vanB1, or vanD. The MICs of daptomycin, linezolid, and QD were determined using commercial broth microdilution panels. All three VISA isolates were susceptible to daptomycin, linezolid, and QD. QD was the most active agent against staphylococcal isolates (MIC50 < or = 0.5 microg/ml and MIC90 = 1 microg/ml), including those with decreased susceptibility to vancomycin. QD was also the most active agent against VREF (MIC90 < or = 0.5 microg/ml). No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD. Daptomycin was the most effective against E. faecalis. On the basis of manufacturer-suggested interpretive criteria, 92% of isolates were susceptible (MIC90 = 4 microg/ml). All isolates tested were susceptible to at least one antimicrobial agent for which interpretive criteria have been defined. Population analysis of three S. aureus isolates for which the daptomycin MICs were 8 microg/ml showed a pattern of homogeneous resistance.

Acetamides↗

Antibiotic activity against urinary tract infection (UTI) isolates of vancomycin-resistant enterococci (VRE): results from the 2002 North American Vancomycin Resistant Enterococci Susceptibility Study (NAVRESS).

BACKGROUND: The purpose of this study was to assess the prevalence of vancomycin-resistant enterococci (VRE) in urinary isolates in North America, and the activity of various antibiotics against VRE. MATERIALS AND METHODS: Twenty-eight medical centres in the United States and 10 centres in Canada assessed the prevalence of VRE in urinary isolates in 2002. Each study site was asked to collect up to a maximum of 50 consecutive VRE (Enterococcus faecium, Enterococcus faecalis only) urinary isolates. Susceptibility was determined by NCCLS broth microdilution. The prevalence of vanA and vanB resistance genotypes was determined by multiplex PCR. RESULTS: From the 28 US medical centres, a total of 697 VRE (616 [88.4%] E. faecium and 81 [11.6%] E. faecalis) were received. Approximately 75% of all VRE (E. faecium and E. faecalis) isolates demonstrated a VanA phenotype (resistance to both vancomycin and teicoplanin). PCR detection of vanA and vanB resistance determinants showed that the vanA genotype was present in 584 of 697 (83.8%) VRE isolates, whereas 113 (16.2%) isolates possessed the vanB gene. The most active agents were linezolid, nitrofurantoin and chloramphenicol, with 0.3%, 0.6% and 2.4% resistance, respectively. The majority (77.8%) of vancomycin-resistant E. faecium isolates displayed the VanA phenotype, and 538 of these 616 (87.3%) isolates were PCR-positive for vanA; the vanB genotype was detected in 78 (12.7%) isolates. Resistance was lowest with linezolid, chloramphenicol and nitrofurantoin at 0.3%, 0.3% and 0.5%, respectively. Only three genetically indistinguishable vanA-positive E. faecium were isolated from the 10 Canadian medical centres. CONCLUSION: VRE urinary isolates are common in the United States, are primarily of the vanA genotype and are very susceptible to linezolid, nitrofurantoin and chloramphenicol. In Canada, VRE urinary isolates remain uncommon.

Anti-Bacterial Agents↗

In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against Staphylococci and Enterococci, including vancomycin- intermediate and -resistant strains.

The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus (VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing > or =3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.

Acetamides↗

Survival of vancomycin-resistant and vancomycin-susceptible enterococci on dry surfaces.

We compared the abilities of Enterococcus faecium strains (three vancomycin-resistant enterococci [VRE] and five vancomycin-susceptible enterococci [VSE]) and Enterococcus faecalis strains (one VRE and 10 VSE) to survive under dry conditions. Bacterial suspensions of the strains were inoculated onto polyvinyl chloride and stored under defined conditions for up to 16 weeks. All strains survived for at least 1 week, and two strains survived for 4 months. A statistical model was used to distribute the 19 resulting survival curves between two types of survival curves. The type of survival curve was not associated with the species (E. faecalis versus E. faecium), the source of isolation (patient versus environment), or the susceptibility to vancomycin (VRE versus VSE). Resistance to dry conditions may promote the transmissibility of a strain, but VRE have no advantages over VSE with respect to their ability to survive under dry conditions.

Anti-Bacterial Agents↗

Interactions between methicillin and vancomycin in methicillin-resistant Staphylococcus aureus strains displaying different phenotypes of vancomycin susceptibility.

Vancomycin-sensitive, -intermediate, and -heterointermediate methicillin-resistant Staphylococcus aureus isolates were tested by using E-tests to explore the interaction of methicillin and vancomycin. For the vancomycin-intermediate and -heterointermediate strains both drugs showed antagonism at concentrations below their MICs but synergy at methicillin concentrations near the MIC. This property could be used to screen for heterointermediate S. aureus strains.

Anti-Bacterial Agents↗

The comparative in vitro activity of clinafloxacin and other antimicrobials against vancomycin-susceptible and vancomycin-resistant enterococci.

The susceptibilities of 50 unique vancomycin-susceptible (n = 15) and vancomycin-resistant (n = 35) enterococci to 6 antimicrobials were compared. Teicoplanin was consistently the most active agent for all strains. Ampicillin and imipenem were active primarily for vancomycin-sensitive Enterococcus faecalis. Clinafloxacin and ciprofloxacin showed poorer activity compared to prior studies, suggesting that the emergence of quinolone resistance is now occurring in enterococci.

Ampicillin↗