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PubMed1993

Reliability of the E test for detection of ampicillin, vancomycin, and high-level aminoglycoside resistance in Enterococcus spp.

By comparison with agar dilution results, the E test was investigated for the ability to detect high-level aminoglycoside (gentamicin and streptomycin), ampicillin, and vancomycin resistance among strains representing six enterococcal species. For ampicillin and vancomycin, disk diffusion results also were obtained. No false high-level aminoglycoside resistance occurred, and no false gentamicin susceptibility was noted. With the high-range streptomycin E test (2,048 micrograms), 24% of the 38 resistant strains were falsely susceptible. However, these discordances could likely be reconciled by adjustments in incubation duration and by using broth microdilution rather than agar screen breakpoint criteria, or by using the lower-range (1,024-micrograms) strip. For ampicillin, category results obtained by E test and disk diffusion showed good agreement with agar dilution; E test MICs were generally comparable to agar dilution MICs. The E test was more sensitive than disk diffusion for detecting vancomycin-intermediate strains, but for these strains and those exhibiting low-level vancomycin resistance (MIC, 32 to 128 micrograms/ml), disk diffusion and E test inhibition zones must be interpreted with caution. Given the reliability of E test for detecting resistance to anti-enterococcal agents, the decision to use this method should be based on convenience, cost, testing frequency, and satisfaction with currently used methods.

Agar↗

PubMed1995

Molecular characterization and multilaboratory evaluation of Enterococcus faecalis ATCC 51299 for quality control of screening tests for vancomycin and high-level aminoglycoside resistance in enterococci.

Studies were conducted to validate the use of Enterococcus faecalis ATCC 51299 (which is vancomycin resistant and resistant to high levels of gentamicin and streptomycin) and E. faecalis ATCC 29212 (which is susceptible to vancomycin and against which gentamicin or streptomycin and cell wall-active agents have synergistic kill activity) as controls in an agar screening test for vancomycin resistance and high-level streptomycin and gentamicin resistance and a broth microdilution screening test for high-level streptomycin and gentamicin resistance. Both organisms performed as expected in these tests and will serve as appropriate controls. However, E. faecalis ATCC 29212 was occasionally noted to produce light growth on the vancomycin screening plate with certain lots of agar. Quality control ranges for disk diffusion tests with disks with large amounts of streptomycin (300 micrograms) and gentamicin (120 micrograms) were established for E. faecalis ATCC 29212; zone limits are 16 to 22 mm for gentamicin and 14 to 19 mm for streptomycin. No zones for inhibition were seen when E. faecalis ATCC 51299 was tested with these high-content disks.

Aminoglycosides↗

PubMed1995

Investigation of the reformulated Remel Synergy Quad plate for detection of high-level aminoglycoside and vancomycin resistance among enterococci.

We investigated the accuracy of the recently released Remel Synergy Quad plate, a commercially available agar screening method for detecting high-level aminoglycoside and vancomycin resistance among enterococci that is based on the National Committee for Clinical Laboratory Standards recommended guidelines (National Committee for Clinical Laboratory Standards, M7-A3, 1993). The Synergy Quad correctly determined the gentamicin and streptomycin resistance status for > or = 97% of 147 Enterococcus faecalis and Enterococcus faecium isolates tested. Detection of vancomycin resistance also was reliable, as no false susceptibility occurred with 36 vancomycin-resistant E. faecalis and E. faecium strains and false resistance occurred only once with the 47 susceptible strains tested. One strain each of Enterococcus gallinarum and Enterococcus casseliflavus failed to grow on the screen, but because the true nature and significance of resistance in such isolates is unknown the implication of their screen negativity is uncertain. In summary, the Remel Synergy Quad provides a highly accurate and convenient method for susceptibility testing of enterococci against gentamicin, streptomycin, and vancomycin.

Aminoglycosides↗

PubMed1997

Rapid characterization schemes for surveillance isolates of vancomycin-resistant enterococci.

Surveillance cultures for vancomycin-resistant enterococci (VRE) and subsequent characterization of the isolates can be extremely burdensome and difficult. Therefore, efficient and reliable schemes for the characterization of surveillance isolates are needed. In this study, a commercial agar (bile esculin azide agar with 6 microg of vancomycin per ml [BEAA]; Remel, Lenexa, Kans.) was used in the initial screening step to establish relatively rapid (i.e., in < or = 24 h from the time of isolation) phenotype-based and PCR-based schemes for the detection and characterization of VRE. The phenotype-based scheme included Gram staining of growth on BEAA and subculture of cocci on sheep blood agar plates for vancomycin disk diffusion and pyrazinamidase (PYR) testing. For the PCR scheme, inocula for van gene detection were taken directly from the BEAA plates. The phenotypic approach was applied to 378 surveillance cultures that yielded growth on BEAA. Gram staining quickly eliminated gram-positive bacilli from further testing, and a negative PYR test classified 25 additional isolates as probable pediococci. A positive PYR test reliably identified 121 single-patient VRE isolates that included 83 Enterococcus faecium, 33 E. gallinarum, and 5 E. casseliflavus strains. The vancomycin inhibition zone size clearly distinguished VanA and VanB strains from VanC strains within 24 h of BEAA isolation. All VanA and VanB strains failed to produce zones of >6 mm, while only one VanC strain produced a zone of < 15 mm. Challenging this phenotypic scheme with 47 stock VRE isolates produced similar findings. In direct PCR analyses, false-negative vanA and vanB results occurred with 12% of the specimens. Many of the false-negative reactions also failed to produce an internal control product, which underscores the need for including control primers when a PCR scheme is used. In summary, the phenotype- and the PCR-based schemes provide efficient methods for characterizing VRE within 24 h of isolation.

Anti-Bacterial Agents↗

PubMed2002

Nosocomial spread of a Staphylococcus capitis strain with heteroresistance to vancomycin in a neonatal intensive care unit.

A premature infant in a neonatal intensive care unit (NICU) developed a bloodstream infection caused by coagulase-negative staphylococci (CoNS) sensitive to vancomycin. The infection persisted for 3 weeks, despite therapy with vancomycin and replacement of all intravenous catheters. The neonate died due to necrotizing enterocolitis which developed during the ongoing sepsis. We screened this strain and 216 other strains of CoNS from cultures of blood obtained from neonates between 1997 and 2000 for heteroresistance to vancomycin. Forty-eight isolates, including the strain that caused ongoing sepsis, proved heteroresistant. All isolates were identified as Staphylococcus capitis and were identical, just as their resistant stable subcolonies were, when they were genetically fingerprinted by amplified-fragment length polymorphism analysis. The heteroresistant phenotype of this endemic strain was confirmed by population analysis. We conclude that heteroresistance to vancomycin occurs in S. capitis and might be the cause of therapeutic failures in NICUs. Moreover, heteroresistant strains can become endemic in such units.

Cross Infection↗

PubMed2004

Emergence of vanA Genotype Vancomycin-Resistant Enterococci with Low or Moderate Levels of Teicoplanin Resistance in Korea.

In Korea, vancomycin-resistant enterococci have become important nosocomial pathogens since the late 1990s, and most vancomycin-resistant enterococcal isolates have been VanA phenotype-vanA genotype strains. In 2001, we experienced an outbreak of VanB phenotype-vanA genotype vancomycin-resistant enterococci at a university hospital. This is the first report of VanB-vanA vancomycin-resistant enterococci from humans in Korea.

Adolescent↗

PubMed2005

First nosocomial outbreak of vancomycin-resistant Enterococcus faecium expressing a VanD-like phenotype associated with a vanA genotype.

Although enterococci expressing acquired vancomycin resistance phenotype have been reported increasingly worldwide, they have been rarely reported in France. From August to December 2004 we faced an outbreak of vancomycin-resistant Enterococcus faecium (VRE) isolates in the nephrology department at Bicêtre Hospital (K.-Bicêtre, France). The expression of the glycopeptide resistance varied among the 26 VRE isolates, with vancomycin MICs ranging from 12 to >256 microg/ml, whereas teicoplanin MICs ranged from 4 to 48 microg/ml. However, several strains appeared to be susceptible to glycopeptides according to disk diffusion testing and expressed resistance only after subculture with glycopeptides. In addition, a heterogeneous expression of glycopeptide resistance was also observed. This so-called VanD-like phenotype of resistance (low-level resistance to vancomycin and mostly susceptibility to teicoplanin) was surprisingly associated with a vanA gene. Plasmid extraction and mating-out experiments indicated that the vanA gene was located on a 200-kb self-transferable plasmid. Pulsed-field gel electrophoresis identified mostly dissemination of a single clone, whereas diffusion of the VanA-positive plasmid in different genomic backgrounds had also occurred. The vanA gene was part of a vanA-type operon for expression of resistance located on a Tn1546-like transposon. Sequencing of this transposon identified insertion of insertion sequence IS16 in the vanY gene that encodes a d,d-carboxypeptidase that might explain in part the peculiar VanD-type phenotype of resistance. This report is the first description of a VRE outbreak in France and underlines the difficulty in detecting this organism due to variability on the expression of the glycopeptide resistance trait, if any.

Adult↗

PubMed1999

Pharmacokinetics and dose requirements of vancomycin in neonates.

AIMS: To design and evaluate dosing guidelines for vancomycin based on data collected during routine use of the drug. METHODS: Following the observation that 66% of neonatal vancomycin trough concentrations were outside the target range, new dose guidelines were developed using a population pharmacokinetic approach. NONMEM (non-linear mixed effects model) was used to analyse dose histories and 347 concentration measurements collected during routine therapeutic drug monitoring in 59 neonates. RESULTS: Postconceptual ages in the patient group ranged from 26-45 weeks, weights from 0. 57-4.23 kg, and creatinine concentrations from 18-172 micromol/l. The population estimate of vancomycin clearance (l/h/kg) was 3. 56/creatinine concentration (micromol/l) with an interpatient coefficient of variation (CV) of 22% and volume of distribution 0.67 l/kg with a CV of 18%. Residual error was 4.5 mg/l. When the new recommendations on dosing were used prospectively in a separate group of neonates the proportion of acceptable troughs increased from 33% to 72%. CONCLUSIONS: The pharmacokinetics of vancomycin in neonates and young infants depend on weight and serum creatinine. Preliminary results from the new guidelines indicate an improvement on previous practice, but also an ongoing need to monitor concentrations.

Anti-Bacterial Agents↗

PubMed1985

Double blind controlled trial of oral vancomycin as adjunctive treatment in acute exacerbations of idiopathic colitis.

A prospective double blind trial of vancomycin vs placebo was undertaken in 40 consecutive adult patients with exacerbation of idiopathic colitis (33 ulcerative colitis, seven Crohn's disease). Vancomycin or placebo (500 mg six hourly) was given for seven days in addition to routine medical therapy. Although there was no significant overall difference in outcome between the two groups, there was a trend towards a reduction in the need for operative intervention in patients with ulcerative colitis treated with vancomycin compared with controls. The efficacy of vancomycin was not attributable to its known action against C difficile, which was not isolated from any of the patients. The data suggest that microbiological factors may play a part in the pathogenesis of ulcerative colitis and that further studies using antimicrobials are desirable.

Adult↗

PubMedDate not supplied

Comparative in vitro activity of vancomycin and other antimicrobial agents against methicillin-resistant staphylococcus aureus and enterococcus faecium in the Tohoku district of Japan.

Susceptibility patterns of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium obtained from various hospitals of the Tohoku district were documented. MICs of 6 antimicrobial agents against a total of 480 strains (380 strains were MRSA and 100 were E. faecium) were estimated. All MRSAs were susceptible to vancomycin, teicoplanin and quinupristin/dalfopristin, but all of them were resistant to ampicillin and benzylpenicillin. None of the E. faecium strains were found to be resistant to vancomycin, teicoplanin and quinupristin/dalfopristin. Excluding these, almost all strains of E. faecium were resistant to the remaining drugs. These data suggest that despite the emergence of vancomycin resistance to E. faecium in Europe and in the United States, vancomycin, teicoplanin and quinupristin/dalfopristin will nevertheless provide effective bactericidal activity in the Tohoku area of Japan.

Ampicillin↗

PubMed2004

Addition of teicoplanin or vancomycin for the treatment of documented bacteremia due to gram-positive cocci in neutropenic patients with hematological malignancies: microbiological, clinical and economic evaluation.

A prospective, randomized, double-blind trial was conducted on 124 febrile patients with hematological malignancies to compare teicoplanin with vancomycin as an addition to the initial empiric amikacin-ceftazidime regimen after documented bacteremia due to gram-positive cocci. At enrollment, patients in both groups were comparable with respect to age, sex, underlying hematologic disorders and duration of neutropenia. Rates of therapeutic success were 55/63 (87.3%) in the teicoplanin group and 56/61 (91.8%) in the vancomycin group (p = 0.560). The mean duration of treatment was similar, being 12.2 and 11.4 days, respectively (p = 0.216). Patients treated with teicoplanin remained febrile for slightly longer than those treated with vancomycin (4.9 vs. 4.0 days) (p = 0.013). Thirteen patients experienced an adverse drug reaction, but without any significant difference in the two arms. Isolated staphylococci showed a progressive and significant decrease in susceptibility to both glycopeptides during the 8 study years. The economic analysis performed showed that the addition of vancomycin is cost-saving.

Adult↗

PubMed2006

Nephrotoxicity due to combination antibiotic therapy with vancomycin and aminoglycosides in septic critically ill patients.

UNLABELLED: The aim of this prospective observational study was to evaluate the incidence of nephrotoxicity due to combination therapy with vancomycin and aminoglycosides in septic critically ill patients admitted to the intensive care unit. METHODS: Thirty consecutive critically ill patients were treated with vancomycin concurrent with aminoglycosides for sepsis. Inclusion criteria were: the need for mechanical ventilation and the presence of severe infection due to bacteria susceptible to vancomycin and aminoglycosides. Exclusion criteria were: age <18 years, impaired renal function (24-hour creatinine clearance <90 ml/min) or previous adverse reaction to either drug. Serum creatinine and urea concentrations, creatinine clearance, 24-hour urinary excretion of proteins, beta2-microglobulin and enzymes were measured immediately before starting therapy and at different times thereafter. RESULTS: Eleven of the 30 patients had a transient and modest increase in serum urea, 15 patients presented with urinary excretion of beta2-microglobulin and tubular enzymes, and 14 patients had urinary proteins. In the only patient with severe acute renal failure (serum creatinine 8.2 mg/dl), the clinical course was complicated by prolonged hypotension. CONCLUSION: Concurrent administration of vancomycin and aminoglycosides to critically ill septic patients with normal renal function at baseline induced mainly slight and transient toxic tubular effects. The only clinically significant nephrotoxic event occurred in a patient with septic shock.

Aminoglycosides↗

PubMed1996

Effects of slowly performed daytime hemodialysis (slow HD) on the pharmacokinetics of vancomycin in hemodynamically unstable patients with renal failure.

Effects of slowly performed daytime hemodialysis (slow HD) using a high-flux hemodialyzer on the pharmacokinetics of vancomycin were determined in 5 critically ill patients with renal failure. Following intravenous administration of 0.5 g of vancomycin, concentrations in the serum and dialysate were monitored. Pharmacokinetic parameters were calculated after fitting individual concentration-time curves to a two-compartment model. The volume of distribution at steady state was 0.58 +/- 0.12 liters/kg. Total body clearance was 37.46 +/- 3.20 ml/min with an elimination phase half-life of 8.72 +/- 0.99 h. Slow HD clearance was 20.19 +/- 2.30 ml/min. During a 10-hour session of slow HD, the serum vancomycin concentration decreased from 44.2 +/- 3.8 to 10.0 +/- 5.0 mg/l and 30.10 +/- 5.34% of the dose was eliminated. Dialyzer clearance of this drug and urea was 18.71 +/- 1.40 and 28.77 +/- 1.77 ml/min, respectively. Slow HD may effectively eliminate vancomycin by a diffusive mechanism and this elimination should be taken into consideration for designing the dosage schedule during the treatment.

Aged↗

PubMed1986

Vancomycin pharmacokinetics in continuous ambulatory peritoneal dialysis patients with peritonitis.

Peritonitis has proven to be the major deterrent to the further growth of continuous ambulatory peritoneal dialysis (CAPD) as a treatment strategy for end-stage renal disease. The correct treatment of peritonitis remains unsettled as evidenced by the presence of advocates for oral, intravenous or intraperitoneal antibiotic administration. This study examines the pharmacokinetic parameters of intravenous vancomycin when employed in the therapy of peritonitis. One gram of intravenous vancomycin was administered during 7 episodes of peritonitis in 5 patients. Plasma and end-of-dwell dialysate levels were maintained above the minimum inhibitory concentration for Staphylococcus aureus and S. epidermidis for 7 days following this single dose of vancomycin. These data establish the existence of sustained intraperitoneal entry of intravenous vancomycin during peritonitis and raise for speculation its use as the sole therapy in most episodes of gram-positive peritonitis.

Adult↗

PubMed1981

Variable tolerance of a clinical isolate of Staphylococcus epidermidis from an infected hydrocephalus shunt for several beta-lactam antibiotics, vancomycin and fosfomycin.

A strain of Staphylococcus epidermidis isolated from an infected hydrocephalus shunt with associated ventriculitis in a 3-month-old infant proved variably tolerant for the beta-lactam antibiotics ampicillin, cephalothin, cefotaxime, cefoxitin, oxacillin, penicillin G, as well as vancomycin and fosfomycin. In contrast, Staphylococcus aureus control strain ATCC 25923 was regularly tolerant to the above stated beta-lactam antibiotics; however, this latter strain displayed variable tolerance for vancomycin and fosfomycin. The beta-lactam tolerance of both strains proved inoculum sizes. Penicillin G-tolerant variants were detected more readily among cells of the S. epidermidis strain in the stationary than in the logarithmic growth phase; in contrast, the yield of penicillin G-tolerant variants from S. aureus ATCC 25923 was independent of the growth phase. Tolerant variants of both staphylococcal strains failed to survive more than three successive passages in Mueller-Hinton broth with added beta-lactam antibiotics at concentrations identical to those which had originally served to select these tolerant variants. Gentamicin combined with vancomycin displayed additive bactericidal activity against both staphylococcal strains; conversely, the combination of rifampin plus vancomycin showed inadequate bactericidal activity against both strains.

Anti-Bacterial Agents↗

PubMed1988

Comparative killing activity and postantibiotic effect of streptomycin combined with ampicillin, ciprofloxacin, imipenem, piperacillin or vancomycin against strains of Streptococcus faecalis and Streptococcus faecium.

Nine strains of Streptococcus faecalis and Streptococcus faecium were studied with respect to ampicillin, ciprofloxacin, imipenem, piperacillin, vancomycin and streptomycin. Two strains were highly resistant (MIC greater than or equal to 2,000 micrograms/ml) to streptomycin. Evaluation and comparison of the killing activity with killing curves, and duration of the postantibiotic effect (PAE) after exposure for 1 h with regrowth curves was done with combinations of antibiotics or alone. The overall killing effect of ciprofloxacin with streptomycin was antagonistic, whereas synergism (greater than or equal to one log10 decrease in viable counts) was observed in streptomycin-susceptible strains with combinations of streptomycin and ampicillin, imipenem, piperacillin or vancomycin. In addition, prolongation of PAE (greater than or equal to 0.5 h) was seen only in streptomycin-susceptible strains. Thus, seven (100%) strains showed a synergistic increase in PAE to combinations with ampicillin and vancomycin, three (43%) to imipenem, four (57%) to piperacillin, but none to the combination of streptomycin and ciprofloxacin. A significant correlation was observed between the magnitude of increased killing and the extent of increase in recovery period with combinations of streptomycin with either ampicillin or vancomycin.

Ampicillin↗

PubMed1992

Prophylactic low-dose vancomycin treatment in very-low-birth-weight infants.

For the prophylaxis of septicemia with coagulase-negative staphylococci in a high-risk very-low-birth-weight population, we administered 5 mg/kg of vancomycin every 12 h. Distribution volume and half-life of vancomycin were determined. Serum peak and trough levels were obtained on day 3 of treatment. With this low-dose regimen, serum concentrations in the therapeutic range were achieved in 35 of the 45 patients. Distribution volume and half-life were 0.692 liters/kg and 7.4 h, respectively. The distribution volume was not related to the gestational age; the half-life in the group of patients with a gestational age < 30 weeks was considerably higher. The 10 small-for-gestational-age children had a significantly smaller distribution volume. The vancomycin trough levels correlated with the serum creatinine concentrations and, therefore, with the gestational age. Our study indicates that this low vancomycin dose is sufficient in very-low-birth-weight infants to achieve therapeutic serum levels, being suitable for both prophylaxis and sepsis therapy.

Creatinine↗

PubMed2001

The influences of renal function and maturation on vancomycin elimination in newborns and infants.

The purpose of this study was to describe the maturation of vancomycin (V) clearance and the influence of altered renal function in infants on vancomycin using population pharmacokinetic methods. A population pharmacokinetic model was developed using NONMEM from clinical data obtained from 374 newborns and infants < 2 years of age (median age = 27 days) from four institutions. A total of 1103 serum V concentrations were used in the model development, including 311 with elevated serum creatinine (CR) (> 0.8 mg/dl) and more than 104 evaluations in infants older than 2 months of age. The final model was evaluated against a second data set of 160 concentrations from 67 infants at one of the institutions and then used to develop dosing guidelines. The data were best described by a two-compartment model. Weight and CR greatly influenced vancomycin elimination, while postnatal age and prematurity (< 28 weeks) were significant but less important predictors of V elimination. For the typical study infant (age = 27 days, CR = 0.6, WT= 1.8 kg, gestational age = 33.5 weeks), this results in VdSS = 0.79 l/kg and Cl = 0.066 l/h/kg. The validation data set showed the model to be unbiased. Dosing guidelines from this model, based on serum creatinine and gestational age at birth, performed better than published guidelines based on postconceptional age. Vancomycin clearance is initially reduced in premature infants and increases with postnatal age. Most of the age-related changes could be predicted by the concomitant fall in serum creatinine. Dosing guidelines that incorporate these factors are more likely to produce therapeutic V concentrations in infants.

Algorithms↗