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Synercid plus vancomycin for the treatment of severe methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections: evaluation of 5 cases.

Synercid (quinupristin/dalfopristin), the first semi-synthetic injectable streptogramin, is a promising alternative to glycopeptides against many Gram-positive multiresistant bacteria. Vancomycin is still considered an effective agent for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections but therapeutic failures with glycopeptides have been observed, even for the treatment of infections caused by S. aureus strains sensitive to vancomycin. Synercid, in combination with a glycopeptide, may address this problem without causing significant side effects due to the different toxicity patterns of the 2 antimicrobials. This study reports our experience with the combination of Synercid and vancomycin in 5 patients with severe infection caused by MRSA or methicillin-resistant coagulase-negative Staphylococcus.

Abdominal Abscess↗

Combination therapy with daptomycin, vancomycin, and rifampin for recurrent, severe bone and prosthetic joint infections involving methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are commonly treated with vancomycin (VAN) or another glycopeptide antibiotic. However, when vancomycin fails or infections recur, there are few other therapeutic options. Presented here are 2 cases where a novel combination of daptomycin, vancomycin, and rifampin resolved recurrent MRSA bone and prosthetic joint functions.

Anti-Bacterial Agents↗

Low faecal carrier rate of vancomycin resistant enterococci in Norwegian hospital patients.

The faecal carrier rate of vancomycin resistant enterococci (VRE) was surveyed among 616 patients in selected departments of 7 Norwegian hospitals. One Enterococcus gallinarum isolate harbouring a vanB2 element was recovered from a child with malignant disease treated with vancomycin and ceftazidime. No vancomycin resistant Enterococcus faecalis or Enterococcus faecium were detected and no VRE isolates of the VanA type were identified. The low level of VRE carriage corresponds to the limited use of glycopeptide antibiotics for human therapeutic purposes in Norway. It indicates a low risk of acquiring VRE infections in Norwegian hospitals.

Anti-Bacterial Agents↗

Vancomycin release from poly(D,L-lactide) and poly(lactide-co-glycolide) disks.

A biodegradable and biocompatible polymeric system was developed for the controlled release of vancomycin for the treatment of brain abscesses. Poly(D,L-lactic acid) (PLA) and its copolymers poly(lactide-co-glycolide) PLGA 90:10 and PLGA 70:30, were prepared. Polymer disks containing vancomycin (VN) were prepared by solvent casting from methylene chloride solutions. Degradation of the polymer disk was studied by scanning electron microscopy, NMR and GPC. SEM revealed an increasing degree of degradation with time with both PLGAs, the effect being more distinct in the PLGA with the higher glycolide content (PLGA 70:30), which was confirmed with GPC, which showed both a decrease in the molecular weights of PLGA and a decrease in the heterogeneity index (chain length distribution) upon incubation in isotonic phosphate buffer at 37 degrees C for up to 5 weeks. NMR showed a decrease in the CH2 contents of the copolymers, implying that the glycolide component of the copolymers is being preferentially degraded. In situ, vancomycin release behaviour of the disks in pH 7.4 phosphate buffer saline (PBS) was followed for approximately 2 months in a static system. It was observed that release was according to Higuchi kinetics (Q vs. t(1/2)), and introduction of low molecular weight PLA or hydrophilic compounds like PEG increased the release rate.

Algorithms↗

Controlled release of vancomycin from freeze-dried chitosan salts coated with different fatty acids by spray-drying.

The aim of this study was to describe a controlled drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan aspartate (CH-Asp), chitosan glutamate (CH-Glu) and chitosan hydrochloride (CH-HCl) were prepared by freeze-drying and coated with stearic, palmitic, myristic and lauric acids by spray-drying technique. Vancomycin hydrochloride was used as a peptidic model drug whose sustained release should minimize its inactivation in the upper part of the gastrointestinal tract. This study evaluated, in vitro, the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the freeze-dried and spray-dried systems at pH 2.0 and 7.4.

Anti-Bacterial Agents↗

Implantation of vancomycin microspheres in blend with human/rabbit bone grafts to infected bone defects.

In orthopaedic applications, allografts are used for restoration of bone defects. In order to combine the effects of bone repair and to prevent the infection, antibiotic-impregnated bone grafts are under current investigation with promising early results. In this study, to preserve the stability of antibiotics and to provide appropriate release profiles for 4-6 weeks, antibiotic-loaded microspheres were administered in combination with allografts and vancomycin was the antibiotic loaded to microspheres. Particle size, surface characteristics, loading capacity and in vitro release characteristics of the microspheres with and without allografts were determined. In vivo studies were performed on rabbits and antibiotic amount was determined by a fluorescence polarization immunoassay (FPIA) method from synovial fluid sample aspirated. According to the results, although the in vitro study demonstrated effective antibiotic release of vancomycin from antibiotic-impregnated allografts for 5 weeks, in vivo conditions led to an early instability of the antibiotic (in powder form) and contrary to the high initial loading dose an effective release could not be obtained from the allografts after the first week. Following these studies, it was determined that antibiotic release over a minimum inhibitory concentration (MIC) for 6 weeks was realized from vancomycin-loaded microspheres which were implanted in a blend with allografts in bone defects. In conclusion, preservation of the antibiotic in microspheres maintained the bioactivity and provided the controlled antibiotic release, thus implantation of microspheres in a blend with allografts seemed to be a promising carrier system for the orthopaedic applications.

Animals↗

Henoch-Schoenlein purpura and acute interstitial nephritis after intravenous vancomycin administration in a patient with a staphylococcal infection.

We describe a case of Henoch-Schoenlein purpura, associated with oliguric acute renal failure due to acute interstitial nephritis histologically proven, in a patient with a staphylococcal chest infection. The clinical syndrome appeared twice after vancomycin administration and yielded on the withdrawal of the drug. As pathogenetic mechanism we propose an anaphylactoid reaction either to vancomycin or to a staphylococcal glycoprotein released after breakdown of the microbial cells caused by vancomycin.

Acute Disease↗

Aztreonam plus vancomycin versus gentamicin plus piperacillin as empirical therapy for the treatment of fever in neutropenic patients: a randomised controlled study.

The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for fever in 61 neutropenic patients. Aztreonam plus vancomycin was as effective, but no more effective, than gentamicin plus piperacillin. Aztreonam showed excellent clinical and in vitro efficacy against Gram-negative pathogens. Failure to respond to aztreonam plus vancomycin was, in most cases, due to presumed or documented fungal infection; by contrast, failure to respond to gentamicin plus piperacillin was frequently to be due to resistant or superadded infection with Gram-positive bacteria.

Adult↗

Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study.

Linezolid, the first oxazolidinone, is active against gram-positive bacteria, including multidrug-resistant strains. This multinational, randomized, double-blind, controlled trial compared the efficacy, safety, and tolerability of linezolid with vancomycin in the treatment of nosocomial pneumonia. A total of 203 patients received intravenous linezolid, 600 mg twice daily, plus aztreonam, and 193 patients received vancomycin, 1 g intravenously twice daily, plus aztreonam for 7-21 days. Clinical and microbiological outcomes were evaluated at test of cure 12-28 days after treatment. Clinical cure rates (71 [66.4%] of 107 for linezolid vs. 62 [68.1%] of 91 for vancomycin) and microbiological success rates (36 [67.9%] of 53 vs. 28 [71.8%] of 39, respectively) for evaluable patients were equivalent between treatment groups. Eradication rates of methicillin-resistant Staphylococcus aureus and safety evaluations were similar between treatment groups. Resistance to either treatment was not detected. Linezolid is a well-tolerated, effective treatment for adults with gram-positive nosocomial pneumonia.

Acetamides↗

Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.

Linezolid, the first available member of a new antibiotic class, the oxazolidinones, is broadly active against gram-positive bacteria, including drug-resistant strains. In this randomized, open-label trial, hospitalized adults with known or suspected methicillin-resistant Staphylococcus aureus (MRSA) infections were treated with linezolid (600 mg twice daily; n=240) or vancomycin (1 g twice daily; n=220) for 7-28 days. S. aureus was isolated from 53% of patients; 93% of these isolates were MRSA. Skin and soft-tissue infection was the most common diagnosis, followed by pneumonia and urinary tract infection. At the test-of-cure visit (15-21 days after the end of therapy), among evaluable patients with MRSA, there was no statistical difference between the 2 treatment groups with respect to clinical cure rates (73.2% of patients in the linezolid group and 73.1% in the vancomycin group) or microbiological success rates (58.9% in the linezolid group and 63.2% in the vancomycin group). Both regimens were well tolerated, with similar rates of adverse events.

Acetamides↗

Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy.

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Adolescent↗

Prevalence and determinants of fecal colonization with vancomycin-resistant Enterococcus in hospitalized patients in The Netherlands.

OBJECTIVE: To determine the prevalence and determinants of fecal carriage of vancomycin-resistant enterococci (VRE) in intensive care unit (ICU), hematology-oncology, and hemodialysis patients in The Netherlands. DESIGN: Descriptive, multicenter study, with yearly 1-week point-prevalence assessments between 1995 and 1998. POPULATION: All patients hospitalized on the testing days in ICUs and hematology-oncology wards in nine hospitals in The Netherlands were included. METHODS: Rectal swabs obtained from 1,112 patients were screened for enterococci in a selective broth and subcultured on selective media with and without 6 mg/L vancomycin. Resistance genotypes were determined by polymerase chain reaction. Further characterization of VRE strains was done by pulsed-field gel electrophoresis (PFGE). We studied possible determinants of VRE colonization with a logistic regression analysis model. Determinants analyzed included gender, age, and log-transformed length of prior hospital stay. RESULTS: The results showed that 614 (55%) of 1,112 patients were colonized with vancomycin-sensitive enterococci, and 15 (1.4%) of 1,112 carried VRE. No increase in VRE colonization was observed from 1995 to 1998. Eleven strains were identified as Enterococcus faecium and four as Enterococcus faecalis. All E faecium and one E faecalis carried the vanA gene; the other E faecalis strains harbored the vanB gene. PFGE revealed that three vanB VRE isolated from patients hospitalized in one single ICU were related, suggesting nosocomial transmission. Though higher age seemed associated with VRE colonization, exclusion of patients with the nosocomial strain from the regression analysis decreased this relation to nonsignificant. Duration of hospital stay was not associated with VRE colonization. CONCLUSION: VRE colonization in Dutch hospitals is an infrequent phenomenon. Although nosocomial spread occurs, most observed cases were unrelated, which suggests the possibility of VRE acquisition from outside the hospital. Prolonged hospital stay, age, and gender proved unrelated to VRE colonization.

Adolescent↗

Stool colonization with vancomycin-resistant enterococci in healthcare workers and their households.

OBJECTIVE: To determine the prevalence of stool colonization with vancomycin-resistant enterococci (VRE) among healthcare workers (HCWs) and their families. DESIGN: Prospective assessment of fecal colonization with VRE. SETTING: A 603-bed, tertiary-care teaching hospital. PARTICIPANTS: Healthy volunteers recruited from hospital employees and their households were screened to exclude pregnancy, diabetes mellitus, immunosuppressive disorders, and recent use of antimicrobials. INTERVENTION: Self-obtained stool swabs were used to obtain cultures. Isolated enterococci were screened for vancomycin resistance and species were identified. Intra-household isolates were genotyped using pulsed-field gel electrophoresis (PFGE). RESULTS: The participants (n = 228; age range, 28 days to 80 years) were from 137 households with and 91 without employees who had contact with patients. Enterococcus species were isolated from 127 stool specimens (55.7%). VRE were detected in 12 individuals, representing 6 E. casseliflavus, 5 E. faecium, and 1 E. gallinarum. VRE were more commonly isolated in employees who had contact with patients (5 of 52 vs 0 of 40; relative risk [RR], 1.9; 95% confidence interval [CI95], 1.5 to 2.2; P = .07) and their household members (10 of 137 vs 2 of 91; RR, 3.3; CI95, 0.7 to 14.8; P = .13). In 2 households (2 adults in a physician's household and an adult plus a child in a nurse's household) PFGE analysis demonstrated identical intra-household strains of vancomycin-resistant E. faecium. CONCLUSIONS: VRE colonization was found in 5.3% of screened stools and was more prevalent in HCWs who had contact with patients and their households. Identical PFGE patterns between 2 employees who had contact with patients and their household members demonstrated probable intra-household spread. Although the mode of acquisition was uncertain, the association with employees who had contact with patients suggests possible occupational sources. These findings demonstrate the spread of VRE within the household and implicate occupational risk for its acquisition.

Adult↗

Impact of surveillance for vancomycin-resistant enterococci on controlling a bloodstream outbreak among patients with hematologic malignancy.

OBJECTIVE: To determine the impact of stool surveillance cultures of critically ill patients on controlling vancomycin-resistant enterococci (VRE) outbreak bacteremia. DESIGN: Stool surveillance cultures were performed on patients who had hematologic malignancy or were critically ill at the time of hospital admission to identify those colonized with VRE. Hence, contact isolation was initiated. SETTING: A tertiary-care cancer center with a high prevalence of VRE. PARTICIPANTS: All patients with hematologic malignancy who were admitted to the hospital as well as all of those admitted to the intensive care unit were eligible. RESULTS: Active stool surveillance cultures performed between 1997 and 2001 decreased the incidence density of VRE bacteremias eightfold while vancomycin use remained constant. In fiscal year (FY) 1997 and FY 1998, there were five and three VRE outbreak bacteremias, respectively. The outbreak clones were responsible for infection in 69% of those patients with VRE bacteremia. However, the stool surveillance program resulted in the complete control of VRE bacteremia by FY 1999 until the end of the study. CONCLUSION: Despite the steady use of vancomycin, the active surveillance program among high-risk patients with hematologic malignancy and those who were critically ill resulted in the complete control of VRE outbreak bacteremia at our institution.

Bacteremia↗

Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea.

BACKGROUND: Current antibiotic therapies for Clostridium difficile-associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile-associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high-molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option. METHODS: In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile-associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or < or = 2 stools of loose or watery consistency. RESULTS: In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0-6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day (median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0-3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0-3.0 days). Tolevamer administered at a dosage of 6 g per day was found to be noninferior to vancomycin administered at a dosage of 500 mg per day with regard to time to resolution of diarrhea (P = .02) and was associated with a trend toward a lower recurrence rate. Tolevamer was well tolerated but was associated with an increased risk of hypokalemia. CONCLUSIONS: Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C. difficile diarrhea and merits further clinical development.

Adult↗

DNA sequence resembling vanA and vanB in the vancomycin-resistant biopesticide Bacillus popilliae.

The origin of high-level vancomycin resistance in enterococci is unknown. Biopesticidal powders containing spores of Bacillus popilliae, which is vancomycin-resistant, have been used for >50 years in the United States for suppression of Japanese beetle populations. Using a polymerase chain reaction assay designed to amplify the vanB gene in enterococci, an amplicon in B. popilliae was identified and sequenced. The putative ligase gene in B. popilliae had 76.8% and 68.4%-68.9% nucleotide identity to the sequences of the vanA and vanB genes, respectively. There was 75.3% and 69.3%-69.9% identity between the translation of the putative ligase gene in B. popilliae and the translation of the vanA and vanB genes, respectively. We have identified a gene resembling vanA and vanB in B. popilliae. The gene in B. popilliae may have been a precursor to or have had an ancestral gene in common with vancomycin resistance genes in enterococci.

Amino Acid Sequence↗

Evaluation of vancomycin use in a pediatric teaching hospital based on CDC criteria.

This study was performed to determine whether vancomycin use at our pediatric hospital was consistent with modified Centers for Disease Control and Prevention guidelines. Vancomycin use was inappropriate in 54% of patients. Inappropriate use briefly decreased by 14% after educational efforts. Further education regarding vancomycin use was deemed necessary and is continuing.

Centers for Disease Control and Prevention, U.S.↗

Vancomycin-resistant enterococci in stool specimens submitted for Clostridium difficile cytotoxin assay.

The prevalence of, and clinical risk factors associated with, vancomycin-resistant enterococcal colonization were investigated in patients suspected of having Clostridium difficile infection. Stools submitted for C difficile cytotoxin testing were screened for vancomycin-resistant enterococci (VRE). Isolates were speciated and characterized further by antibiotic susceptibility testing, DNA fingerprinting, and DNA:DNA hybridization for detection of specific vancomycin resistance genes. Of the 79 evaluable patients identified during a 3-month period, 16.5% were VRE-positive. The VRE isolates were genetically heterogeneous, although all carried the vanA gene. DNA fingerprinting data suggest that patient-to-patient transmission occurred, implicating colonized patients as potential reservoirs for VRE transmission. A positive C difficile cytotoxin assay and diabetes mellitus were the only identifiable risk factors associated with VRE colonization. Patients at risk for C difficile infection therefore may serve as reservoirs for VRE.

Anti-Bacterial Agents↗