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PubMed1989

High-level vancomycin-resistant enterococci causing hospital infections.

Nosocomial infection or colonization due to enterococci with high-level resistance to vancomycin (minimal inhibitory concentrations [MICs] between 64 and greater than 2000 mg/L) has occurred in 41 patients with renal disease. These vancomycin-resistant enterococci were cultured from many sources including blood. All but one strain contained one or more plasmids ranging in molecular weight from 1.0 to 40 Megadaltons (MDa). Vancomycin resistance was transferable by conjugation to a susceptible recipient strain of Enterococcus faecalis but this was not always associated with plasmid DNA. The emergence of transferable high-level vancomycin resistance in enterococci causing significant clinical infections is of particular importance since vancomycin is widely regarded as a reserve drug for the management of infections with multi-resistant Gram-positive organisms.

Acute Kidney Injury↗

PubMed2001

Detection and typing of vancomycin-resistance genes of enterococci from clinical and nosocomial surveillance specimens by multiplex PCR.

Ninety-three clinical isolates of vancomycin-resistant enterococci (VRE) collected from nine hospitals in Taiwan were examined for the presence of vanA, vanB, vanC1, or vanC2/vanC3 genes by a multiplex PCR. Forty-seven of these VRE isolates were vanA positive, 1 contained both vanC1 and vanA, 40 harboured vanB, 2 were vanC1, and 3 were identified to be vanC2/vanC3. Twenty-four vanA isolates were sensitive to teicoplanin and thus did not have a typical VanA phenotype. Five isolates with the VanC phenotype harboured vanB. None of the 40 clinically isolated vancomycin-susceptible E. faecium or E. faecalis and the vancomycin-resistant Leuconostoc and Pediococcus isolates were positive for any of the van genes. While performing nosocomial surveillance, VRE were isolated from 47 of 467 rectal swabs by culture. Compared with the conventional culture method, the sensitivity and specificity of the multiplex PCR for detecting and identifying vancomycin-resistance genes in enterococci directly from culture-positive broth were 97.9% and 100%, respectively. The results suggest that genotypic characterization of vancomycin-resistance is necessary for all clinical VRE isolates and that the multiplex PCR assay can be an alternative method for this purpose.

Bacterial Proteins↗

PubMed2001

The role of sugar residues in molecular recognition by vancomycin.

The sugar residues of the glycopeptide antibiotic vancomycin contribute to the cooperativity of ligand binding, thereby increasing ligand affinity and enhancing antimicrobial activity. To assess the structural basis for these effects, we determined a 0.98 A X-ray crystal structure of the vancomycin aglycon and compared it to structures of several intact vancomycin:ligand complexes. The crystal structure reveals that the aglycon binds acetate anions and forms back-to-back dimeric complexes in a manner similar to that of intact vancomycin. However, the four independent copies of the aglycon in each asymmetric unit of the crystal exhibit a high degree of conformational heterogeneity. These results suggest that the sugar residues, in addition to enlarging and strengthening the dimer interface, provide steric constraints that limit the vancomycin molecule to a relatively small number of productive conformations.

Carbohydrates↗

PubMed1983

Vancomycin kinetics during continuous ambulatory peritoneal dialysis.

To establish therapeutic guidelines for vancomycin usage in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied single-dose kinetics of vancomycin in CAPD patients. Vancomycin was studied after a 10-mg/kg dose was given intravenously (VAN-IV) or intraperitoneally (VAN-IP). VAN-IV provided a plasma concentration above 10 mg/l at 12 hr, with a t 1/2 of 81 hr. When VAN-IP was given, 65% was absorbed; peak plasma concentrations were only 6.3 mg/l, and t 1/2 was 66 hr. CAPD accounted for only 15% to 17% of total body clearance in both groups. The kinetic principle of superposition was used to predict plasma concentrations after repeated VAN-IP doses. A model with once-a-day dosing predicted that a loading dose of 30 mg/kg followed by 7 mg/kg would achieve steady-state plasma concentrations of 11 to 14.8 mg/l. Another model with vancomycin in each exchange predicted that a loading dose of 30 mg/kg followed by 1.5 mg/kg would provide plasma concentrations in excess of 10 mg/l at 180 hr. These data should be useful in vancomycin treatment of CAPD patients who have nonperitoneal gram-positive bacterial infections, as well as those who have peritonitis.

Adult↗

PubMed1994

Analysis of peptidoglycan precursors in vancomycin-resistant Enterococcus gallinarum BM4174.

Vancomycin resistance in enterococci is an increasing clinical problem, and several phenotypes have been identified. We demonstrate here that the resistance mechanism in the constitutively vancomycin-resistant Enterococcus gallinarum BM4174 involves an altered pathway of peptidoglycan synthesis and hydrolysis of the normal precursors in the vancomycin-sensitive pathway. A ligase encoded by the vanC gene catalyses synthesis of D-Ala-D-Ser and substitutes this dipeptide for D-Ala-D-Ala in peptidoglycan precursors. It is presumed that this substitution lowers the affinity of vancomycin for its target site. Destruction of D-Ala-D-Ala (D,D-peptidase activity) and of UDP-MurNAc-L-Ala-D-isoGlu-L-Lys-D-Ala-D-Ala by removal of the terminal D-Ala residue (D,D-carboxypeptidase activity) ensures that the normal vancomycin-sensitive pathway of peptidoglycan synthesis cannot function in the resistant strain.

Amino Acid Sequence↗

PubMed2002

The importance of pets as reservoirs of resistant Enterococcus strains, with special reference to vancomycin.

The purpose of the present study was to determine the prevalence of antibiotic resistance, with special attention to vancomycin, in 104 strains of Enterococcus, which is the sentinel bacterium isolated from dog and cat faeces samples. The phenotypic characterization of the isolates classified them as E. faecium (58%), E. avium (41%) and E. faecalis (1%). Sensitivity testing used the diffusion method according to the recommendations of CASFM (Comite de l'Antibiogramme de la Société Française de Microbiogie), to oxacillin, amoxycillin, amoxycilin + clavulanic acid, ampicillin, piperacillin, cefoperazone, imipenem, enrofloxacin, ciprofloxacin, ofloxacin, nalidixic acid, tetracycline, lincomycin, erythromicin and vancomycin. Minimum inhibitory concentration (MIC) determination by E test revealed a MIC to vancomycin of between 0.5 microg/ml and 3 microg/ml. All the strains were resistant to nalidixic acid, erythromycin, cefoperazone and oxacillin. We detected resistance to amoxycillin + clavulanic acid in 1.9% of isolates, to amoxycillin in 4.8%, to piperacillin in 13.5%, and to ampicillin in 21.2% of strains. A high prevalence of antibiotic resistance to lincomycin, tetracycline, enrofloxacin, ciprofloxacin and ofloxacin was found in 98.1%, 95.2%, 76.9%, 73.1% and 64.4% of strains, respectively. Resistance to vancomycin was not found, which indicates that there is no transmission risk of vancomycin-resistant enterococcal strains to man or transfer of their resistance genes to other bacteria belonging to the endogenous flora of humans.

Animals↗

PubMedDate not supplied

Indications for vancomycin in dialysis patients.

Resistance to vancomycin has emerged among Staphylococcus aureus, coagulase-negative staphylococci (CNS), and enterococci, and this emergence has particular prevalence in dialysis units. It has therefore become imperative that physicians use vancomycin judiciously. General recommendations regarding the appropriate use of vancomycin have been developed. Although in theory implementation of these guidelines should not be difficult, the medical community may be unable or unwilling to make the necessary adjustments in practice. The onslaught of cost constraints and bureaucratic encumbrance has occurred simultaneously with the increase in vancomycin resistance among pathogens commonly isolated among the dialysis population. When a patient responds to empiric antibiotic therapy and susceptibility data indicate that an antibiotic other than vancomycin would be appropriate, the clinician far too often does not make the change to this alternative. Previously there was no biological imperative to change the antibiotic. That complacency has infected an entire generation of physicians, and especially nephrologists. Furthermore, there is an active movement against change, driven by concerns such as malpractice accusations and frank errors in the interpretation of medical facts.

Anti-Bacterial Agents↗

PubMed1999

Rectal colonization with vancomycin-resistant enterococci among high-risk patients in an Israeli hospital.

The prevalence of rectal carriage of vancomycin-resistant enterococci (VRE) in two high-risk populations--61 patients admitted to ICU and 92 patients on renal dialysis--was studied longitudinally over a period of six months in a 650-bed general hospital. ICU patients were swabbed weekly and dialysis patients monthly. Enterococcal isolates were fully identified using the ATB identification system, and MICs were determined according to the NCCLS recommendations. Enterococci were isolated in 52 (83.6%) ICU patients and 86 (93.4%) dialysis patients. VRE were recovered at least once in 14 (27%) ICU patients and four (4.8%) dialysis patients. All VRE isolates (MIC of vancomycin > or = 256 micrograms/mL) were resistant to teicoplanin (MIC > or = 32 micrograms/mL; vanA phenotype), 87.5% were ampicillin-resistant, and 92% showed high-level resistance to gentamicin; 88% were E. faecium. The main risk factors for acquisition of VRE included duration of hospitalization in the six months preceding entry into the study and during the survey (P = 0.009 and 0.007 respectively, for ICU patients), and duration of antibiotic administration (P = 0.005, for ICU patients). The impact of vancomycin was most prominent (P = 0.005 for receipt and 0.06 for duration of administration, in ICU patients). Six of the 18 VRE carriers developed bacteraemia, six isolates being vancomycin-susceptible and one vancomycin-resistant (one patient had both). In this study, the first in Israel, a low rectal carriage rate occurred in renal dialysis patients and antibiotic use was the most important risk factor for VRE colonization.

Aged↗

PubMed2004

Large vancomycin overdose in two premature infants with minimal toxicity.

Two premature infants received 10-fold overdoses of vancomycin with resulting peak plasma concentrations > 300 microg/mL. Discontinuation of vancomycin and watchful waiting were employed, with no specific intervention to accelerate vancomycin clearance. Plasma vancomycin concentration < 40 microg/mL was attained at < 48 hours in one infant and < 72 hours in the other. Although one infant sustained a transient increase in serum creatinine to 1.4 mg/dL, no further evidence of renal, auditory, or other toxicity was detected in either infant acutely or long term. Contemporary preparations of vancomycin appear much less toxic than earlier formulations. Aggressive and invasive interventions to hasten clearance may be unnecessary following overdose in infants with normal or near-normal basal renal function, although careful surveillance for clearance and toxic effects still appear warranted.

Anti-Bacterial Agents↗

PubMed1985

Prophylactic vancomycin versus placebo in arterial prosthetic reconstructions.

Vascular reconstructive surgery with the placement of prosthetic material caudal to the diaphragm is occasionally associated with postoperative wound infection. These infections often lead to amputation and can be lethal. Only a few published reports contain information on the value of prophylactic antibiotic treatment with these operations, but its use is common throughout the world. To investigate this problem, a prospective, double blind, randomized study of vancomycin versus placebo in 128 vascular graft operations caudal to the diaphragm was conducted from June, 1982 to July, 1984. The difference in infection rate was significant (2 p = 0.0008) in favor of the vancomycin group. Fourteen wound infections (21.2%) were found in the placebo group, 3 of which (4.5%) were prosthesis infections. Among the 62 vancomycin-treated patients, one case of superficial wound infection (1.6%) and no cases of prosthesis infection were found. The most common pathogen was Staphylococcus aureus. The study has demonstrated that vancomycin, a narrow spectrum antibiotic, in an ultra-short regimen (one gram one hour before surgery and one gram 4 hours later) is an effective prophylactic agent against postoperative wound infection. Temporary and, in most cases, doses-related side effects were seen in 7.9% of the patients treated with vancomycin.

Arteries↗

PubMed1986

A double-blind comparative study of prophylactic antibiotic therapy in open heart surgery: penicillin G versus vancomycin.

A double-blind clinical study was carried out comparing the prophylactic effectivity of penicillin G with vancomycin in 113 adult patients undergoing open heart surgery. Eighty of these underwent valve replacement. A total of 14 of 52 penicillin-treated patients (26.9%) and 5 of 61 vancomycin-treated patients (8.2%) suffered from postoperative infection (0.005 less than p less than 0.02). Five patients in the penicillin group and none in the vancomycin group developed postoperative wound infection (0.01 less than p less than 0.02). No significant differences in blood culture and sepsis, tracheal culture and clinical respiratory tract infection, urine culture and clinical urinary tract infection, and colonization rate were found between the 2 groups. No cases of prosthetic valve endocarditis were diagnosed. Bacteriologic culture and resistance studies did not reveal significant changes concerning the resistance patterns; in particular, the emergence of a vancomycin-resistant strain of Staphylococcus albus was not seen. A decrease in the colonization rate with Staphylococcus albus from 53% in 1975 to 1977 to 34.6% and 31.1% in the penicillin and vancomycin groups, respectively, was found in the following 2 years.

Adult↗

PubMed1999

Lactoferrin increases the susceptibility of S. epidermidis biofilms to lysozyme and vancomycin.

PURPOSE: The tear cationic protein lactoferrin increases the activity of various antimicrobial agents against suspended bacterial cultures including Staphylococcus epidermidis, the predominant causative agent of intraocular lens biofilm infections. We investigated the ability of lactoferrin to enhance the activity of vancomycin and lysozyme against biofilms of a clinical S. epidermidis isolate. METHODS: Biofilms were prepared on soft contact lenses and cells released from the biofilm surface were collected from the surrounding broth. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against the intact biofilm, released cells and suspended bacteria were evaluated using vancomycin with and without lactoferrin. RESULTS: Lactoferrin induced a two-fold reduction in the MBC of vancomycin for biofilm (p < 0.01) and biofilm-released cells from 64 microg/ml to 32 microg/ml and similarly decreased the MIC for biofilm-released cells (p < 0.01) from 32 microg/ml to 16 microg/ml. With or without lactoferrin, the MIC of vancomycin for suspended cells (2 and 4 microg/ml respectively) was less (p < 0.01) than that of both the biofilm (32 and 32 microg/ml) and biofilm-released cells (16 and 32 microg/ml). Lactoferrin did not reduce the MIC of lysozyme, but, at a lysozyme concentration of 16 mg/ml, did significantly (p < 0.05) reduce the number of viable biofilm and biofilm-released cells. CONCLUSIONS: Lactoferrin displays potential as an adjunctive agent to vancomycin in the treatment of S. epidermidis biofilm infections, such as endophthalmitis, associated with intraocular lenses.

Anti-Bacterial Agents↗

PubMed2004

High versus standard dose vancomycin for osteomyelitis.

It is important to identify the optimal dosage and best method of infusion of parenteral vancomycin to be used over a several week period for the treatment of osteomyelitis. A retrospective study was undertaken to compare a high dose vancomycin treatment (HD: 40 mg/kg/d) with a standard dose treatment (SD: 20 mg/kg/d), and also to compare the modality of infusion using either intermittent vancomycin infusion (IVI) or continuous vancomycin infusion (CVI). 89 patients with Gram-positive cocci osteomyelitis requiring vancomycin treatment were followed, and the outcome and therapeutic safety were compared. There were significantly more adverse drug reactions (acute renal failure) in the IVI subgroup (HD-IVI vs SD-IVI, p-value 0.007). No cases of renal failure were found in the HD-CVI subgroup. The best outcome was found in the subgroup of patients who received HD-CVI (HD-CVI vs SD-IVI, overall log rank p-value 0.02). HD-CVI treatment appears to provide an improved outcome with fewer adverse drug reactions.

Aged↗

PubMed2005

The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia.

Persistence and recurrence of Staphylococcus aureus bacteraemia (SAB) have been linked primarily with difficult-to-eradicate foci of infection such as endocarditis, osteomyelitis or abscess formation. Although vancomycin therapy has been suggested as a predictor of relapse of SAB, it has never been shown to be associated with persistent SAB. The purpose of this study was to examine the possible association of vancomycin therapy and persistence of SAB. Two groups of patients were retrospectively studied. One group consisted of 124 patients who completed > or =10 d of appropriate anti-staphylococcal therapy (from among a total of 284 patients with SAB during 2 y, 1997-8). In this group, persistence of SAB (methicillin resistant and susceptible combined) for >3 d while on therapy, occurred in 11 (22%) of 55 vancomycin recipients and in none of 52 cloxacillin recipients (p = 0.002). When calculated for methicillin susceptible SAB alone, the numbers were 3 of 13 vs 0 of 52, respectively (p = 0.007). The second study group included all patients with persistence and/or relapse of SAB while on appropriate anti-staphylococcal therapy during 4 y (1997-2000). In this group, the persistence occurred while on vancomycin therapy, in 32 (94%) of 34 patients with >3 d of persistence of SAB. In the majority of these patients a secondary focus of infection serving as the site of persistence was identified in addition to the primary focus (or portal of entry). It was concluded that vancomycin is inferior to cloxacillin therapy in terminating SAB and therefore may predispose to prolonged bacteraemia and secondary seeding of infection during therapy.

Adult↗

PubMed2006

Retinal toxicity of intraocular vancomycin and ceftazidime in vitrectomized rabbit eyes.

The purpose of this study was to evaluate the retinal toxicity of vancomycin and ceftazidime combined into an infusion solution that was intraoculary given after or during vitrectomy. Forty albino rabbits were divided into 4 groups of 10 each. Vitrectomized right eyes of groups 1, 2, and 3 were given recommended doses of vancomycin and ceftazidime alone or combined, while right eyes in the fourth group were vitrectomized using an infusion solution to which was added ceftazidime and vancomycin combination. Toxicity was tested with electroretinography (ERG) and light microscopy. ERG and light microscopy did not show any toxicity signs associated with vancomycin or ceftazidime alone or with combined therapy. Vancomycin and/or ceftazidime can reliably and effectively be used combined in an infusion solution at recommended doses after and during vitrectomy. This treatment modality does not have any toxic effects to retinal structures and is an alternative method to separate injections of the two antimicrobial agents.

Animals↗

PubMedDate not supplied

A low-cost and simple method to stop intraoperative leakage-type bleeding: use of the vancomycin-oxidized regenerated cellulose (ORC) sandwich.

Intraoperative bleeding may cause life-threatening complications in patients if such bleeding cannot be brought under control. Various materials are available for stopping such bleeding. However, there are some difficulties in the acquisition and application of these materials. The aim of this study was to investigate the efficiency of the low-cost and simple-to-prepare vancomycin-oxidized regenerated cellulose (ORC) sandwich in surgical bleeding control. Thirty New Zealand rabbits were used for this purpose. The animals were separated into three groups as group 1 (n = 10), control group; group 2 (n = 10), oxidized regenerated cellulose (ORC) group; and group 3 (n = 10), vancomycin-ORC sandwich group. Left thoracotomies were performed on the rabbits under general anesthesia, and bleeding was created in the parietal pleura. The amount of bleeding in the groups was measured and compared. The amount of bleeding in the group in which the vancomycin-ORC sandwich was used was found to be less, compared to the other two groups. According to these results, we conclude that the vancomycin-ORC sandwich can be used safely in the control of intraoperative leakage-type bleeding, as the vancomycin-ORC sandwich is a low-cost, easily applied, and easily acquired material.

Animals↗

PubMed2000

Comparative safety of teicoplanin and vancomycin.

Although modern preparations of vancomycin are associated with a lower incidence of adverse events than the early preparations, a number of clinically significant problems remain. Consequently monitoring of serum concentrations is required. In a meta-analysis of comparative trials adverse events were significantly less likely to occur with teicoplanin (13.9%) than with vancomycin (21.9%) (P = 0.0003). This was particularly significant when nephrotoxicity was considered: 4.8% vs. 10.7%, for teicoplanin and vancomycin, respectively (P = 0.0005). Red man syndrome, which may be due to histamine release, occurs after rapid infusion of vancomycin but is very rare following teicoplanin administration. In USA trials, thrombocytopenia was more commonly seen with teicoplanin administration but this was almost exclusively in patients receiving much larger doses than are now recommended. The lower rate of adverse events supports the choice of teicoplanin over vancomycin in treating infections where the two antibiotics have similar efficacy.

Animals↗

PubMed2000

Quinupristin/Dalfopristin therapy for infections due to vancomycin-resistant Enterococcus faecium.

The efficacy and safety of quinupristin/dalfopristin for treatment of infections due to vancomycin-resistant Enterococcus faecium were evaluated in 24 hospitalized patients with documented infections (19 bacteremias, 5 localized infections) caused by vancomycin-resistant E. faecium that was susceptible to quinupristin/dalfopristin in vitro. Patients received iv quinupristin/dalfopristin at a dosage of either 7.5 mg/kg every 8 h or 5 mg/kg every 8 h. A favorable clinical response (cure or improvement) occurred in 19 (83%) of 23 evaluable patients; bacteriologic eradication occurred in 17 (74%) of 23 evaluable patients. A favorable clinical response was observed in 12 (80%) of 15 patients who were treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h and in 7 (88%) of 8 patients treated with 5 mg/kg of quinupristin/dalfopristin every 8 h. Two of four treatment failures were associated with a decrease in the in vitro susceptibility of vancomycin-resistant E. faecium to quinupristin/dalfopristin. Superinfections developed in 6 patients (26%), but only one was caused by Enterococcus faecalis that was resistant to quinupristin/dalfopristin. Myalgias and arthralgias were the only adverse events related to quinupristin/dalfopristin. These conditions occurred in 8 (33%) of 24 patients and were dose-related (8 cases in 16 patients treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h, no cases in 8 patients treated with 5 mg/kg every 8 h). Mortality associated with vancomycin-resistant E. faecium infection was 17% (4 of 23 patients), whereas mortality from other causes was 52% (12 of 23 patients). These results suggest that quinupristin/dalfopristin is effective as treatment for vancomycin-resistant E. faecium infections in critically ill patients with serious underlying conditions. Except for myalgias and arthralgias at higher dosages, the drug is well-tolerated.

Adolescent↗