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PubMed1975

Initial membrane reaction in the biosynthesis of peptidoglycan. Spin-labeled intermediates as receptors for vancomycin and ristocetin.

Phospho-N-acetylmuramyl-pentapeptide translocase (UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla:undecaprenyl phosphate, phospho-MurNAc-pentapeptide transferase) catalyzes the initial membrane reaction in the biosynthesis of peptidoglycan. The spin-labeled nucleotide, UDP-MurNAc-Ala-DGlu-Lys (Nepsilon-2,2,5,5-tetramethyl-N-oxyl-pyrroline-3-carbonyl)-DAla-DAla, was used as a substrate by this enzyme for the synthesis of membrane-associated undecaprenyl-diphosphate-MurNAc-Ala-DGlu-Lys(Nepsilon-Tempyo)-DAla-DAla. The spin-labeled substrate and product complex with the antibiotics vancomycin and ristocetin. The association constants for the spin-labeled nucleotide are 6.2 times 10(5) and 6.2 times 10(4) M-1 for vancomycin and ristocetin, respectively. The association constants for the spin-labeled lipid intermediate are 3.0 times 10(4) and 2.1 times 10(4) M-1 for vancomycin and ristocetin, respectively. These results indicate that the acyl-DAla termini of membranes-associated spin-labeled undecaprenyl-diphosphate-MurNAc-pentapeptide are accessible to vancomycin and ristocetin and that the association constants are smaller than those determined for the corresponding antibiotic spin-labeled UDP-MurNAc-pentapeptide complexes.

Binding Sites↗

PubMed1978

Sensitive bioassay for vancomycin.

An accurate and sensitive assay for vancomycin in serum and body fluids has not been available. This paper reports an assay for vancomycin that can detect serum and fluid levels as low as 0.8 mug/ml. A disk diffusion technique was designed employing buffered glucose minimal salts agar and Bacillus subtilis as an indicator strain. A linear relationship was obtained between zone diameter and concentration for vancomycin standards from 0.8 to 50 mug/ml prepared in pooled human serum. Results were accurate (<10% error) and reproducible (within-sample standard deviation, 0.25 mug/ml) for concentrations of from 0.8 to 25 mug of vancomycin per ml. Zone diameters were at least 6 mm larger on minimal salts agar than on standard assay media. The increased sensitivity and accuracy of the assay make it possible to accurately measure levels in cerebrospinal fluid and dialyzate fluid as well as in serum.

Adult↗

PubMed1978

In vitro activity of rifampin alone and in combination with nafcillin and Vancomycin against pathogenic strains of Staphylococcus aureus.

Twenty strains of Staphylococcus aureus isolated from patients with endocarditis were examined in vitro for susceptibility to rifampin, nafcillin, and vancomycin and to combinations of rifampin with nafcillin or vancomycin. Minimum bactericidal concentrations of rifampin ranged from 0.0031 to 0.0125 mug/ml, of nafcillin ranged from 0.078 to 0.312 mug/ml, and of vancomycin ranged from 0.312 to 1.25 mug/ml. The combination of rifampin with nafcillin was synergistic for 12 strains; the combination of rifampin plus vancomycin was synergistic for 5 of the isolates.

Drug Synergism↗

PubMed1979

Role of vancomycin as a component of oral nonabsorbable antibiotics for microbial suppression in leukemic patients.

A total of 38 adult patients with acute leukemia who were undergoing remission induction chemotherapy in regular patient rooms were randomly allocated to one of two oral nonabsorbable antibiotic regimens for infection prophylaxis (gentamicin, vancomycin, and nystatin [GVN] or gentamicin and nystatin [GN]) to evaluate whether vancomycin was a necessary component. The patient population in both groups were comparable. Tolerance to GVN was less than GN but compliance was approximately equal (>85% in both groups). Patients receiving vancomycin demonstrated greater overall alimentary tract microbial suppression; however, acquisition of potential pathogens was approximately equal in both groups. The incidence of bacteremia, as well as the overall incidence of infection as related to the number of days at various granulocyte levels, was also approximately equal in both groups. Group D Streptococcus species were poorly suppressed by GN compared with GVN, although no patient developed an infection with these organisms. Colonization by newly acquired gram-negative bacilli was significantly less in the GN group (GN, 3 colonizations; GVN, 13 colonizations; P < 0.01). It is concluded that vancomycin may be safely eliminated from the GVN regimen provided microbiological data is monitored to detect resistant organisms.

Adult↗

PubMed1979

Peritoneal clearance and total body elimination of vancomycin during chronic intermittent peritoneal dialysis.

Vancomycin is a useful antimicrobial agent in patients undergoing chronic hemodialysis treatment; its efficacy in chronic peritoneal dialysis (CPD) has not been established. Serum (VS) and peritoneal fluid (VPF) vancomycin concentrations were measured in two CPD patients with staphylococcal peritonitis. Half-life of VS agreed with the half-life of VPF in each patient, and the VS/VPF ratio was 1.27 in both patients. Distribution volumes were 37.2 and 58.7 l, values approximating total body water in these patients. VS and VPF persisted in the therapeutic range (greater than 5 microgram/ml) for more than 16 days. In one patient, mean peritoneal clearacne was 9.8 ml/min, and overall drug clearance averaged 2.3 ml/min; in the other patient, overall clearance was 2.1 ml/min. These results indicate that therapeutic vancomycin levels can be maintained for more than 16 days with a single 1 g intravenous dose in patients receiving intermittent CPD, as is the case for hemodialysis patients. Because of this, parenteral vancomycin is useful in the treatment of staphylococcal peritonitis in CPD patients.

Adult↗

PubMed1978

Pseudomembranous colitis: isolation of two species of cytotoxic clostridia and successful treatment with vancomycin.

Lincomycin-resistant Clostridium sporogenes obtained from the stools of a patient with lincomycin-associated pseudomembranous colitis produced a heat-stable cytotoxin in low titre when grown in chopped meat medium. Vancomycin eradicated this strain and all other clostridia, and controlled the symptoms. When diarrhea recurred 7 days after treatment with vancomycin was stopped, clostridia including C. sporogenes and C. difficile were again isolated. The C. difficile produced a heat-labile cytotoxin in high titre that was unaffected by growth in various media and induced colitis in hamsters. Treatment with vancomycin, to which all the clostridia were sensitive, eradicated both toxic species and controlled the diarrhea. Antibiotic-induced pseudomembranous colitis may be associated with more than one species of toxin-producing clostridia. Vancomycin therapy should be continued for 10 days or more in patients with severe disease to eradicate the responsible organism.

Aged↗

PubMed1979

Synergy of vancomycin plus cefazolin or cephalothin against methicillin-resistance Staphylococcus epidermidis.

The in vitro activity of cephalothin, cefazolin, and vancomycin against 25 isolates of methicillin-resistant Staphylococcus epidermidis was determined by means of a broth dilution technique with two sizes of inoculum. The size of the inoculum had a marked effect on the minimal inhibitory concentrations and the minimal bactericidal concentrations of all three antibiotics. With a small inoculum, 100% of the isolates were inhibited by 3.12 micrograms of vancomycin/ml, 76% by 12.5 micrograms of cephalothin/ml, and 64% by 12.5 micrograms of cefazolin/ml. With a large inoculum 100% of the isolates were inhibited by 200 micrograms of vancomycin/ml, 40% by 12.5 micrograms of cephalothin/ml, and 12% by 12.5 micrograms of cefazolin/ml. As determined by a tube dilution checkerboard technique for both sizes of inoculum, the combination of vancomycin plus cephalothin was synergistic against methicillin-resistant S. epidermidis in 45 of 50 cases, and the combination of vancomycin plus cefazolin was synergistic in 39 or 50 cases. These data from in vitro studies suggest that these antibiotic combinations should be evaluated clinically in patients with severe infections caused by methicillin-resistant S. epidermidis.

Cefazolin↗

PubMed1979

High performance liquid chromatographic assay of vancomycin in serum.

A liquid chromatographic procedure is described for rapid and accurate quantitation of vancomycin in serum. Vancomycin is extracted from serum by using a CM-Sephadex column and is measured by reversed-phase chromatography with detection by UV absorption. Ristocetin is used as an internal standard. Concentration and instrument response are linearly related in the range of therapeutically useful concentrations. Results correlate well with those obtained by bioassay. The between-day coefficient of variation (n = 8) was less than 4%. Recovery of vancomycin from serum is nearly complete, and no substances that interfere with the procedure have been detected in clinical specimens.

Bacteria↗

PubMed1977

Synergism with aminoglycosides of penicillin, ampicillin and vancomycin against non-enterococcal group-D streptococci and viridans streptococci.

The antibiotic susceptibility of 10 strains of non-enterococcal group-D streptococci was compared with that of 20 strains of viridans streptococci. The minimal inhibitory concentrations of penicillin, ampicillin, oxacillin, nafcillin, cephalothin, vancomycin, erythromycin and clindamycin for the two groups of streptococci were very similar in range and median values. Both groups of streptococci were resistant to the aminoglycosides. The effect of the combination of penicillin, ampicillin or vancomycin with streptomycin, kanamycin, gentamicin or tobramycin on the in-vitro killing of the two groups of streptococci was compared. For all the antibiotic combinations tested, synergism was demonstrated against all strains of non-enterococcal group-D streptococci after one or more of the time-intervals 6, 24 and 48 h. Some or all of the antibiotic combinations were synergistic against all strains of viridans streptococci after one or more of the same time-intervals. The other aminoglycosides (kanamycin, gentamicin and tobramycin) offered no advantage over streptomycin in synergism with penicillin, ampicillin or vancomycin against nonenterococcal group-D streptococci or viridans streptococci. These results suggest that non-enterococcal group-D streptococcal endocarditis may be treated by the same regimen as endocarditis caused by the viridans streptococci.

Aminoglycosides↗

PubMed1975

Intravitreal injection of vancomycin in experimental staphylococcal endophthalmitis.

Toxicity, clearance, and therapeutic effectiveness of intravitreal vancomycin hydrochloride injection in experimentally induced staphylococcal endophthalmitis were evaluated. Vancomycin was found to be nontoxic in a single, 1 mg/0.1 ml intravitreal dose. Therapeutic levels of vancomycin were present in the vitreous for over 72 hours and in the aqueous during a period from 6 to 48 hours after injection. Injection of a methicillin-resistant Staphylococcus aureus produced a panophthalmitis in our systemically treated controls, whereas in the rabbits treated by intraocular injection, the course of the infection was significantly altered.

Animals↗

PubMed1977

Studies on the mechanism of ristocetin-induced platelet agglutination. Effects of structural modification of ristocetin and vancomycin.

The mechanism by which ristocetin induces platelet agglutination in the presence of the von Willebrand factor was studied by chemically altering ristocetin and a similar antibiotic, vancomycin, by reaction with a water-soluble carbodiimide in the presence of glycine methyl ester at pH 4.75. Altering ristocetin's phenolic groups (which are thought to be important in its peptide-binding properties) resulted in a loss of both platelet-agglutinating and antibiotic activities. Restoring the phenolic groups with hydroxylamine restored both activities. Vancomycin has antibiotic and peptide-binding properties similar to ristocetin's, but differs structurally in having a free carboxyl group and thus a less positive charge at neutral pH. It does not induce platelet agglutination and actually inhibits ristocetin-induced agglutination. Reacting vancomycin with the water-soluble carbodiimide resulted in alteration of phenolic groups and permanent conversion of the carboxyl to a neutral derivative. Restoring the phenolic groups with hydroxylamine (but leaving the carboxyl neutralized) produced a compound with charge properties similar to ristocetin's which induced platelet agglutination as ristocetin does. These data suggest both a binding requirement (mediated through phenolic groups) and a strong positive charge requirement for ristocetin-induced agglutination. The data are consistent with a model wherein positively charged ristocetin binds, via its phenolic groups, to sites on the platelet surface and reduces the platelet's negative charge. This could reduce the electrostatic repulsion between platelets and/or between platelets and the negatively charged von Willebrand factor, and permit the macromolecular von Willebrand factor to cause agglutination by bridging between platelets.

Carbodiimides↗

PubMed1976

Failure of vancomycin treatment in Staphylococcus aureus endocarditis. In vivo and in vitro observations.

In a case of staphylococcal endocarditis, we failed to eradicate Staphylococcus aureus from the blood stream with vancomycin hydrochloride therapy. The strain involved was sensitive to vancomycin by disk diffusion studies but showed a wide disparity between minimal inhibitory and minimal bactericidal concentrations. The lack of a bactericidal effect was probably responsible for the failure of treatment. A synergistic effect was demonstrated for the combination of gentamicin sulfate and methicillin sodium, and the patient was ultimately cured with this combination plus vancomycin. Bactericidal tests are important in choosing an antimicrobial agent for treatment of endocarditis.

Adult↗

PubMed2026

Emergence of a Novel, Phenotypically Difficult-to-Detect Vancomycin-Resistant Enterococcus faecium Clone (ST117/CT7799).

A significant increase of vancomycin-resistant Enterococcus faecium (VREfm) infections was observed in South-Eastern Austria since 2024. The prolonged outbreak is caused by a novel vanB-VREfm clone (ST117/CT7799, "VREfmstyr"). This study characterizes the atypical difficult-to-detect resistance phenotype and assesses the genomic relatedness of the isolates. Patient and outbreak characteristics were investigated including whole genome sequencing of the isolates. Sensitivity of broth microdilution (BMD), gradient tests (GT), disk diffusion (DD), and automated susceptibility testing (VITEK2) was compared. The performance of commercial screening media was evaluated. From sporadic detections in early 2024 case numbers began to rise during the year. In 30/31 (97%) of all cases, intra-hospital transmission was considered likely and an association with invasive procedures was identified in most cases. Core genome multilocus sequence typing revealed only six allelic differences between VREfmstyr isolates collected in a 12-month period, all belonging to the E. faecium ST117/CT7799 lineage. BMD detected vancomycin resistance (MIC > 4 mg/L) in no more than 16/31 (52%) of isolates after 24 h incubation, while GT and DD misclassified all isolates. Only prolonged incubation improved the performance of these assays. VITEK2 analysis, however, correctly classified all 31 isolates. Of four commercially available VRE-screening agars, only one was capable of detecting VREfmstyr after 24 h incubation. The emergence and clonal dissemination of VREfm ST117/CT7799 reveals a serious diagnostic gap as commonly used diagnostic algorithms fail to reliably detect this resistance phenotype. Our findings should help to further evaluate the true geographical distribution and clinical significance of this novel VREfm clone.

Enterococcus faecium↗

PubMed2026

Clinical Characteristics and Genomic Analysis of Vancomycin-Resistant Enterococcus faecium in a Tertiary Hospital in Huizhou.

OBJECTIVE: To characterize the clinical and genomic features of vancomycin-resistant enterococci (VRE) in a tertiary hospital in Huizhou and identify risk factors to inform local infection control. METHODS: A retrospective study included 58 VRE and 25 vancomycin-susceptible Enterococci (VSE) strains (August 2023-May 2025). Clinical data and antimicrobial susceptibility were analyzed; whole-genome sequencing (WGS) was performed on 54 VRE strains. RESULTS: Midstream urine was the primary VRE-positive specimen. ICU admission, polyantibiotic use (≥3 agents), and urinary catheterization were key risk factors for VRE. All VRE isolates were Enterococcus faecium and showed a predominantly clonal population structure, dominated by CC17/ST80 (68.8%) and CC2/ST106 (64.6%) under the two multilocus sequence typing schemes; five novel STs were ultimately identified in the latter scheme. VRE was universally resistant to ampicillin, with high resistance to penicillin, levofloxacin, and teicoplanin, while linezolid and tigecycline remained effective. Genotypically, 94.8% carried vanA, 100% carried virulence gene esp, and aminoglycoside and macrolide resistance genes were prevalent. A unique VRE strain (VRE48) showed resistance without canonical van genes, harboring a Ddl Ser210Tyr mutation.

Humans↗

PubMed1978

Staphylococcus aureus endocarditis. Combined therapy with vancomycin and rifampin.

Two children with persistent bacteremia and endocarditis due to Staphylococcus aureus failed to respond to vancomycin therapy, even though serum levels greatly exceeded the inhibitory concentrations. The Staphylococcus from one patient was resistant to methicillin; the other patient had a penicillin hypersensitivity. There was a wide disparity between the minimum inhibitory and the minimum bactericidal concentrations of vancomycin. Striking clinical and laboratory evidence of improvement was demonstrated with the addition of rifampin therapy.

Blood↗

PubMed1978

Structure of vancomycin and its complex with acetyl-D-alanyl-D-alanine.

Vancomycin, a broad-spectrum antibiotic, inhibits the growth of cell walls by complex formation with peptides terminating in D-alanyl-D-alanine. The structure of vancomycin was determined by X-ray analysis of the degradation product CDP-I. A model of the complex is proposed based on this study and spectroscopic data.

Dipeptides↗

PubMed1979

Vancomycin treatment of cerebrospinal fluid shunt infections. Report of two cases.

The successful use of vancomycin is reported in two children with shunt infections due to Staphylococcus epidermidis which failed to respond to shunt removal. The previously reported experience with this drug is reviewed. The use of vancomycin should be considered in cases of shunt infections due to susceptible microorganisms and refractory to other therapeutic measures.

Cerebrospinal Fluid Shunts↗

PubMed1978

Vancomycin revisited.

Vancomycin, virtually discarded after development of antistaphylococcal penicillins, has recently been receiving renewed attention. There are several clinical situations in which it appears to offer advantages over other available antimicrobial agents: infections due to methicillin-resistant staphylococci; bacterial endocarditis in patients allergic to penicillin; staphylococcal enterocolitis; staphylococcal infection in patients undergoing hemodialysis; infections caused by penicillin-resistant diphtheroids; and prophylaxis of bacterial endocarditis in patients with prosthetic valves or penicillin allergy. Its penetration into the cerebrospinal fluid suggests that vancomycin may be useful in treating certain infections of the central nervous system. Although its ototoxic and nephrotoxic potential cannot be ignored, these problems can be minimized by keeping the serum concentration at the proper level.

Bacteria↗