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PubMed1969

Specificity of combination between mucopeptide precursors and vancomycin or ristocetin.

Vancomycin and ristocetin formed complexes on being mixed with mucopeptide precursors from various bacteria, as shown by chromatography, electrophoresis and differential ultraviolet spectra. Equimolar proportions of antibiotic and peptide were present. The specificity of the reaction was studied and the smallest molecule found to react was acetyl-d-alanyl-d-alanine. This C-terminal dipeptide sequence must be present for complex-formation; change of configuration or esterification prevented it. Modified vancomycins that retained antibiotic activity also combined with appropriate peptides. The dissociation constants of the more stable complexes were estimated from the differential-absorption results. The relationship of complex-formation to antibiotic action is discussed. Penicillin, supposed to be an analogue of acyl-d-alanyl-d-alanine, also modified the spectrum of vancomycin; so, too, did sodium benzylpenicilloate.

Chemical Phenomena↗

PubMed1972

Reversal by a specific peptide (diacetyl-alpha gamma-L-diaminobutyryl-D-alanyl-D-alanine) of vancomycin inhibition in intact bacteria and cell-free preparations.

Vancomycin inhibited the growth of Bacillus megaterium, Staphylococcus aureus and Micrococcus lysodeikticus, and in cell-free preparations from B. megaterium it inhibited the formation of mucopeptide and enhanced the accumulation of the lipid intermediate in the biosynthetic pathway. All these inhibitory processes were reversed by the presence of a synthetic peptide analogous to un-cross-linked mucopeptide side chains, namely diacetyl-l-diaminobutyryl-d-alanyl-d-alanine. A considerable amount of vancomycin was found in recovering cells, whether recovery was caused by peptide or took place naturally because a low initial concentration of antibiotic was used. In cell-free preparations pretreated with vancomycin, continued inhibition of mucopeptide synthesis depended on the presence of cell-wall material. This inhibition was also reversible by added peptide.

Alanine↗

PubMed2003

Aminoglycoside and vancomycin serum concentration monitoring and mortality due to neonatal sepsis in Saudi Arabia.

OBJECTIVE: To assess the effectiveness of monitoring of serum concentration of aminoglycosides in neonates. METHOD: A retrospective evaluation of serum concentration monitoring of aminoglycosides (gentamicin and amikacin) and vancomycin in neonates treated for sepsis in a maternity and children hospital in Jeddah, Saudi Arabia, over the period 1998-2000. RESULTS: The total number of requests for monitoring increased sixfold in 1999 and 12-fold in 2000 relative to 1998. For aminoglycosides, the incidence of both subtherapeutic peak and toxic trough serum levels decreased significantly (P < 0.05) in 1999 and 2000 compared with 1998. Furthermore, the rate of neonatal mortality caused by sepsis showed reduction in both 1999 (34%) and 2000 (35%) in comparison with 1998 (45%). Vancomycin trough (effective) concentration monitoring revealed no change in the incidence (30%) of levels at subtherapeutic values (<5.0 microg/mL) between the compared years. Furthermore, the rate of toxic levels (>10 microg/mL) increased in both 1999 (31%) and 2000 (39%) relative to 1998 (25%). CONCLUSION: Therapeutic drug monitoring of vancomycin needs re-evaluation in the hospital to explain why existing methods are ineffective.

Amikacin↗

PubMed2001

Curtailing unnecessary vancomycin usage in a hospital with high rates of methicillin resistant Staphylococcus aureus infections.

AIMS: To implement and monitor the effectiveness of a strategy to curb unnecessary use of vancomycin and teicoplanin for inpatients in a teaching hospital/tertiary referral centre where 33% of S. aureus isolates (72% from ICU patients) were methicillin resistant. METHODS: A sample of 182 vancomycin/teicoplanin inpatient prescriptions surveyed, revealed that only 31 (17%) conformed with Centre for Disease Control (CDC) guidelines. Following education (ward-rounds, bulletins) on appropriate CDC based guidelines for prescribing glycopeptides directed at relevant clinicians, 'Immediate Concurrent Feedback' (ICF) was gradually deployed throughout the hospital. This entailed review of respective inpatient records on the next working day. If the indication was deemed not to conform with our guidelines, the prescriber was issued a memo (copied to the supervising doctor). Each memo detailed the 'errant' incident, listed appropriate indications and explicitly advised desisting from such prescribing and suggested alternative therapy if necessary. Corresponding glycopeptide usage data for our hospital and others in Hong Kong were retrieved and analysed as were samples of records of our inpatients with staphylococcal septicaemia (pre and during ICF). RESULTS: Compared with baseline values, during 2 years of ICF, inpatient prescribing of vancomycin and teicoplanin deemed to conform increased to 71% (773/1086); difference 54% (P < 0.0001, 95% CIs 47-62%). Corresponding average monthly usage (DDDs/1000 admissions) decreased from 76 (pre-ICF) to 45; mean difference 31 (P < 0.0001, 95% CIs 24, 38). Mortality from staphylococcal bacteraemia remained unchanged. No comparable changes in glycopeptide usage ensued in comparator hospitals. CONCLUSIONS: ICF can be used safely to curb irrational overuse of vancomycin and teicoplanin in a hospital with high methicillin resistant S. aureus infection rates.

Anti-Bacterial Agents↗

PubMed2002

The antibacterial activity of vancomycin towards Staphylococcus aureus under aerobic and anaerobic conditions.

AIMS: To investigate the antibacterial efficacy of vancomycin towards Staphylococcus aureus under aerobic and anaerobic conditions, and to assess the influence of oxygen on the duration of the post-antibiotic effect (PAE) after exposure to vancomycin. METHODS AND RESULTS: Culture-based techniques and flow cytometric measurements of 5-cyano-2,3-ditolyl tetrazolium chloride (an indicator of redox activity) and the membrane potential-sensitive fluorophore Sytox Green, were used to test four staphylococcal strains. The MICs for all strains, and the duration of PAE, were similar whether tested with or without oxygen. However, a fivefold logarithmic reduction in cell counts was observed in 10-15 h aerobically, depending on strain, compared with longer than 60 h in an anaerobic environment. Flow cytometric data correlated well with counts of colony-forming units under both aerobic and anaerobic conditions. CONCLUSIONS: The death rate of Staph. aureus exposed to vancomycin was greater in the presence of oxygen, although MIC values and PAE durations were similar whether tested aerobically or anaerobically. Also, flow cytometry provided a rapid and sensitive alternative to plate counts for the assessment of antibiotics in oxygen-free conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study underlines the need for further anaerobic testing using different strain/antibiotic combinations, the results of which will have clinical significance due to the anaerobic nature of some sites of infection.

Aerobiosis↗

PubMed1997

Susceptibility to vancomycin of enterococci isolated from dairy products.

The antibiotic vancomycin is often used in clinical therapy against multiple antibiotic-resistant bacteria. Twenty strains of enterococci, either Enterococcus faecium or Ent. faecalis, isolated from different cheeses were tested for resistance to vancomycin in liquid medium. Minimum inhibitory concentration (MIC) values ranged from less than 1 to 4 micrograms ml -1. A 399 bp intragenic fragment of the vanA gene was not observed after amplification of total DNA of the strains. It seems, therefore, that resistance to vancomycin, which is a common trait for enterococci of nosocomial origin, is not widespread among dairy isolates.

Anti-Bacterial Agents↗

PubMed1998

Vancomycin susceptibility as an aid to the identification of lactobacilli.

Forty strains of lactobacilli isolated from probiotic supplements or functional foods, and two clinical isolates, have been identified by API 50 CHL and tested for susceptibility to vancomycin. All the Lactobacillus acidophilus (16) and Lact. delbreuckii (two) strains were sensitive to vancomycin, while all the other strains (mainly Lact. rhamnosus, 15) were resistant. Susceptibility to other antibiotics was not species-specific. Differential susceptibility to vancomycin may be helpful in speciation of lactobacilli.

Anti-Bacterial Agents↗

PubMed2001

Cefepime versus vancomycin plus netilmicin therapy for continuous ambulatory peritoneal dialysis-associated peritonitis.

Cefepime is a cephalosporin with a broad spectrum of activity against most gram-positive and gram-negative pathogens. In this study, we attempted to compare the safety and efficacy of cefepime monotherapy against the potentially more toxic combination of vancomycin and netilmicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD)-associated bacterial peritonitis. Eighty-one consecutive CAPD patients who presented with peritonitis from January 1, 1998, to June 30, 2000, were recruited for study. Patients were randomized to be administered either intraperitoneal (IP) cefepime, 1 g once daily (group A), or intravenous vancomycin and netilmicin at conventional doses (group B) for 10 days. Bacterial growth was obtained in 52 episodes (66%), and pathogens identified included gram-positive organisms (30 episodes; 38%), gram-negative organisms (14 episodes; 18%), mixed organisms (2 episodes; 2.5%), and fungus (6 episodes; 8%). Eight patients were excluded after randomization for various reasons (6 patients, fungal peritonitis; 2 patients, wrong diagnoses). Because of the relatively low peritonitis rate after the use of a disconnect system, the sample size of this study was relatively small, giving a power of 0.45. There were no significant differences in primary response rates and cure rates (no relapse >28 days after completion of antibiotic therapy) between both groups of patients (group A versus group B, 82% [32 of 39 patients] versus 85% [29 of 34 patients] and 72% [28 of 39 patients] versus 76% [26 of 34 patients], respectively; P = not significant). No significant side effect was encountered in either group. Total peritonitis-related hospitalizations were 84 patient-days (1, 7, 8, 11, 20, and 37 patient-days) and 115 patient-days (3, 6, 9, 14, 21, 21, and 41 patient-days), whereas total costs per patient cure were estimated to be US $1,039 and US $1,371 in groups A and B, respectively. We conclude that once-daily 1-g IP cefepime monotherapy is a simple, safe, and cost-effective alternative to vancomycin and netilmicin therapy in the treatment of CAPD-associated bacterial peritonitis.

Adult↗

PubMed1999

Efficacy of hand disinfectants against vancomycin-resistant enterococci in vitro.

Vancomycin-resistant enterococci (VRE) may be spread within a hospital via the contaminated hands of the healthcare worker. Effective hand disinfectants are necessary to break chains of transmission. We determined the bactericidal activity of 1-propanol, chlorhexidine digluconate (0.5 and 4%). Sterillium (45% 2-propanol, 30% 1-propanol and 0.2% mecetronium etilsulphate), Skinsept F (70% 2-propanol, 0.5% chlorhexidine digluconate and 0.45% hydrogen peroxide) and Hibisol (70% 2-propanol and 0.5% chlorhexidine gluconate) against 11 clonally distinct enterococcal isolates in a quantitative suspension test. Four isolates were vancomycin susceptible, four were vanA and the remainder vanB positive. Eight isolates were identified as Enterococcus faecium, two as Enterococcus faecalis and one as Enterococcus gallinarum. The investigator was blinded to the species and the genotype. Four parallel experiments were carried out for each isolate, each preparation, each dilution and each reaction time. 1-Propanol (60%), Sterillium, Skinsept F and Hibisol were all highly bactericidal after 15 and 30 s against VRE and vancomycin-susceptible enterococci (VSE) with reduction factors (RF) > 6.4, even in dilution of 50% (v/v). No significant difference was observed between vanA isolates, vanB isolates and VSE. Chlorhexidine digluconate (0.5% and 4%) was found to be less bactericidal after 30, 60 and 300 sec (RF < or = 2.5). The vanB genotype isolates were found to be significantly more susceptible to chlorhexidine (0.5%) than the vanA isolates (60 sec; one-way ANOVA model; P = 0.05). After 300 sec the vanB genotype isolates were found to be significantly more susceptible to chlorhexidine (0.5%) than the other two genotype isolates (P = 0.016). The vanA isolates were found to be significantly more susceptible to chlorhexidine (4%) than the vanB isolates (300 s; P = 0.024). E. faecium was found to be less susceptible to chlorhexidine than E. faecalis at all concentrations and reaction times, but significant differences between RF were only observed at 60 sec for both chlorhexidine concentrations (P < 0.05; t-test for independent samples). Propanol is much more effective against enterococci than chlorhexidine and combination of the two may be useful in providing an immediate and long lasting effect.

Analysis of Variance↗

PubMed1999

Intrinsically vancomycin-resistant gram-positive organisms: clinical relevance and implications for infection control.

Intrinsic resistance to vancomycin in gram-positive bacteria presumably predates acquired vancomycin resistance in enterococci but it has only recently generated interest. Intrinsically resistant enterococci possessing the vanC gene and the non-enterococcal genera Leuconostoc, Lactobacillus, Pediococcus and Erysipelothrix are known to cause human infection. This review examines the available data on their identification, resistance mechanisms, epidemiology, clinical infections and antimicrobial susceptibility. Intrinsically vancomycin-resistant gram-positives are usually opportunistic pathogens. Although serious infections may occur, treatment options remain available. No additional infection control measures for the intrinsically resistant genera appear justified with currently available evidence, although vigilance should be maintained to detect future changes in susceptibility patterns.

Anti-Bacterial Agents↗

PubMed2000

Nosocomial cross transmission as a primary cause of vancomycin-resistant enterococci in Austria.

Stool specimens from 226 patients from intensive care units (N=69), general wards (N=112), and outpatient-clinics (N=45) at the Innsbruck University Hospital and from 433 healthy volunteers were inoculated on to Enterococcosel Agar supplemented with 5 microg/mL vancomycin and 4 microg/mL cefodizime. Faecal specimens from 105 dairy cows, 171 pigs and 47 egg-laying hens were processed the same way. Thirteen of 226 patients (5.8%) harboured 14 vancomycin-resistant enterococci (VRE) of the vanA genotype; 12 E. faecium (from 11 patients) and two E. faecalis (ICU patients: 5.8%, general ward patients: 5.4%, outpatients: 6.7%). None of the faecal specimens from healthy volunteers or animals yielded VRE. Nine of the 13 patients harbouring VRE had received antibiotic therapy during the previous four weeks (broad-spectrum cephalosporins: six patients; i.v. vancomycin: five patients). Of the 14 VRE (vanA type) isolates six strains were indistinguishable by PFGE using Sma I as restriction endonuclease, six strains formed three pairs, and only two single isolates showed unique patterns. The results of our study supports the view that nosocomial cross transmission is currently the main cause of colonization and infection with VRE in Austria.

Animals↗

PubMed2000

Vancomycin-resistant enterococci.

Over the last 2 decades, enterococci, formerly viewed as organisms of minimal clinical impact, have emerged as important hospital-acquired pathogens in immunosuppressed patients and intensive care units (ICUs). Vancomycin resistance in enterococci is increasing steadily. Vancomycin-resistant enterococci (VRE) composed 26% of nosocomial enterococci in 1999, a 47% increase from 1994 to 1998. More that 25% of ICU enterococci are resistant to vancomycin. Antimicrobial therapy is problematic for all VRE, but particularly when bactericidal activity is necessary. Quinipristin-dalfopristin and linezolid are 2 new approved antimicrobials for the treatment of recalcitrant infections caused byVRE. Control of the transmission of VRE, although successful in preventing infections, is neither simple nor inexpensive, and VRE has become endemic in many hospitals. However, endemicity poses serious risks to the health of current and future patients, and of itself, is expensive. Data on the cost-effectiveness of VRE prevention programs are currently lacking and urgently needed; however, because the added cost of a single VRE infection far exceeds those of gowns, gloves, and screening, it seems likely that such control programs represent significant cost savings for those hospitals willing to undertake them.

Cross Infection↗

PubMed2001

Vancomycin-resistant Enterococcus infected total knee arthroplasty.

Use of vancomycin to treat infections and hospital colonization with methicillin-resistant Staphylococcus aureus has contributed to the development of vancomycin resistance in Enterococcus. Postoperative infection with vancomycin-resistant Enterococcus developed in 2 patients after total knee arthroplasty, indicating that the infections were nosocomial. Both patients required multiple procedures. The infections were controlled with serial open débridements. One knee was fused successfully, and the other was managed with resection arthroplasty.

Adult↗

PubMedDate not supplied

[Preventive antibiotic administration for prevention of nosocomial septicemia in very small premature infants (VLBW infants)--preventive vancomycin administration against infections with coagulase negative streptococci--prevention of translocation with oral cefixime therapy in intestinal colonization with pathogenic gram-negative pathogens].

VLBW-infants below 1500 g of birth weight have a quite high risk to acquire a nosocomial sepsis. 20-40% of all infants exhibit signs of nosocomial infection once during neonatal intensive care. The rate of infection is related to technique and amount of used invasive devices as to gestational age. Coagulase-negative staphylococci (CONS) and gram-negative organisms contribute most to these cases of sepsis. In a three phase study we tried to demonstrate the efficacy of different mechanisms to change the rate of nosocomial sepsis. During the first phase a strict hygienical protocol was enforced as isolation, care with sterile gloves and aseptic techniques in introducing and maintaining i.v. lines. In a second phase we started a randomized controlled study of prophylactic vancomycin (10 mg/kg/day in two doses). In a third phase we added an oral antibiotic regime with cefixime for all patients with positive cultures for gramnegative organisms under the hypothesis of translocation from the gut as the way of infection. During the first phase 23.7% of 76 patients enrolled acquired CONS-sepsis, 0.52% gramnegative sepsis. During the second phase (41 patients) 6 patients in the control group acquired CONS-sepsis, none in the vancomycin-group. The rate of gramnegative infections was not different (4 and 3 cases). During the third phase (vancomycin plus cefixime eventually in cases of positive stool cultures) no case of nosocomial sepsis occurred (35 patients, 11 positive cultures). The management used in phase 3 reduced the rate of nosocomial infections in VLBW-infants drastically.

Anti-Infective Agents↗

PubMed1984

The use of intraventricular vancomycin in the treatment of CSF shunt-associated ventriculitis.

Ten cases of shunt-associated ventriculitis treated with intraventricular vancomycin are described. Eight were cured of their infection, one of these without shunt removal, though this failed in another instance. There were no toxic or untoward effects except in one case, where intravenous administration of vancomycin produced a histamine-like reaction. Intraventricular vancomycin, preferably combined with oral rifampicin, should be considered in cases of intractable or problematic shunt-associated ventriculitis due to Gram-positive organisms.

Cerebral Ventricles↗

PubMed1992

[A lethal course in pseudomembranous enterocolitis during the parenteral administration of vancomycin and imipenem].

A 48-year-old woman required mechanical ventilation after aortic valve replacement for decompensated aortic valve stenosis when bleeding complications developed and rethoracotomy had to be performed. Acute renal failure necessitated haemodialysis. Septic fever of unknown aetiology failed to respond to oxacillin, cefotaxim and tobramycin. The endotracheal cannula and central venous catheter were changed on the 24th postoperative day and the antibiotic treatment altered to 250 mg imipenem and 125 mg vancomycin three times daily intravenously. The fever soon subsided, but recurred on the 32nd postoperative day, accompanied by increasing leucocytosis. The patient was obstipated but had no intraabdominal signs. Four days later ultrasonography demonstrated thickening of the intestinal wall and coloscopy showed typical pseudomembranous colitis. Intestinal contents were positive for Clostridium difficile toxin. Despite immediate rectal and intragastric administration of 250 mg vancomycin four times daily the patient died of pseudomembranous colitis, confirmed at autopsy. The case demonstrates that vancomycin cannot always prevent the development of pseudomembranous colitis.

Colon↗

PubMed1998

In vivo characterization of the type A and B vancomycin-resistant enterococci (VRE) VanRS two-component systems in Escherichia coli: a nonpathogenic model for studying the VRE signal transduction pathways.

Escherichia coli reporter strains modeling the high-level type A and B vancomycin resistances of Enterococcus faecium BM4147 and Ent. faecalis have been developed to study the respective VanR-VanS two-component regulatory systems. PvanH-, PvanRa-, PvanY-, and PvanRb-lacZ fusions report on expression from the vancomycin-resistant enterococci promoters of the type A vanRSHAXYZ and type B vanRSYWHBX gene clusters. These strains also express from single-copy chromosomal genes vanRa, vanRb, or vanRSb behind their respective promoter (PvanRa or PvanRb) or vanSa or vanSb behind the rhamnose-inducible PrhaB. Results show that activation (phosphorylation) of the response regulator VanRa by its sensor kinase VanSa leads to transcriptional activation of both PvanH and PvanRa. Additionally, VanRb activates its cognate promoters PvanY and PvanRb, although this occurs only in the absence of VanSb and presumably is caused by VanRb phosphorylation by an unidentified endogenous E. coli kinase. Thus, VanSb interferes with activation of VanRb, probably by acting as a phospho-VanRb phosphatase. Although both VanRa and VanRb activate their cognate promoters, neither activates the heterologous PvanR, PvanH, or PvanY, arguing against the interchangeability of type A and B two-component regulatory switches in vancomycin-resistant enterococci. VanRa also is activated by the nonpartner kinase PhoR. Because this occurs in the absence of its inducing signal (Pi limitation), PhoR autophosphorylation apparently is regulated in vivo. Furthermore, the activation of VanRa caused by cross talk from PhoR in the absence of a signal allows distinction of cross talk from crossregulation as the latter, but not the former, responds to environmental cues.

Anti-Bacterial Agents↗

PubMed1996

Vancomycin and amikacin in cell cultures for virus isolation.

Contamination of cell cultures for virus isolation has been increasingly encountered. By reviewing and changing the antimicrobials incorporated in cell culture media, we aim to control this problem. Contaminated cell culture fluids were inoculated for bacterial and fungal isolation, identification and antibacterial susceptibility testing. Based on the above results, vancomycin and amikacin were chosen to replace the penicillin and gentamicin used conventionally. Analysis was carried out on various characteristics of cell culture with respect to antimicrobial change. All contaminating Gram-positive bacteria were susceptible to vancomycin while about 80% of the Gram-negative bacteria were sensitive to amikacin. The new antimicrobial combination was not toxic to cell cultures and both antimicrobials were found to remain stable in media for over six months. The virus isolation rate was maintained after antimicrobial change while the contamination rate was reduced from nearly 10% to 1.5%. We thus conclude that vancomycin and amikacin can well replace the conventional penicillin and gentamicin to be incorporated into maintenance and transport media to control the emerging problem of viral culture contamination.

Age Factors↗