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PubMed2001

Quinupristin/dalfopristin: a therapeutic review.

BACKGROUND: The proliferation of multidrug-resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium (VREF), has created a pressing need for effective alternative antibiotics. Quinupristin/dalfopristin is a new combination streptogramin product with a selective spectrum of antibacterial activity, mainly against gram-positive aerobic bacteria. It has been assessed primarily in emergency-use protocols, in hospitalized patients with skin and skin-structure infections, and in patients with VREF bacteremia. OBJECTIVES: The objectives of this review were to summarize important results of in vitro microbiologic studies; to provide information on relevant pharmacokinetic parameters, drug interactions, and Y-site compatibility; and to assess efficacy and safety data from clinical studies of quinupristin/dalfopristin. METHODS: Articles included in this review were identified by a MEDLINE search of the literature published between 1966 and September 2000 using the terms Synercid, quinupristin, and dalfopristin. Additional articles were retrieved from the reference lists of articles identified in the MEDLINE search. RESULTS: In vitro analysis of the spectrum of activity of quinupristin/dalfopristin has confirmed its relatively selective coverage of gram-positive aerobic bacteria. Both quinupristin and dalfopristin undergo hepatic metabolism and are extensively excreted in the feces. Combination quinupristin/dalfopristin inhibits the cytochrome P450 3A4 pathway, and caution is warranted with concomitant use of other medications eliminated via this pathway. In trials in patients with VREF infections, treatment success with quinupristin/dalfopristin varied depending on the site of infection, ranging from 51.9% in bacteremia of unknown origin to 88.9% in urinary tract infections. The results of comparative clinical trials suggest that quinupristin/dalfopristin has similar efficacy to that of commonly used antibiotics, including cefazolin, oxacillin, and vancomycin, in patients with skin and skin-structure infections or nosocomial pneumonia. The most frequently reported adverse effects with administration of quinupristin/dalfopristin were infusion-site inflammation, pain, and edema; other infusion-site reactions; and thrombophlebitis. Arthralgia, myalgia, nausea, diarrhea, vomiting, and rash occurred in 2.5% to 4.6% of patients and were the most frequently reported systemic adverse events. CONCLUSIONS: Outcomes data from clinical trials indicate that quinupristin/dalfopristin has the potential to play an important role in the treatment of bacteremia, complicated skin and skin-structure infections, and nosocomial pneumonia caused by VREF. Issues of bacterial resistance to quinupristin/dalfopristin and other appropriate uses of this combination agent remain to be elucidated.

Anti-Bacterial Agents↗

PubMed2006

2004 Lowbury Lecture: the Western Australian experience with vancomycin-resistant enterococci - from disaster to ongoing control.

The first hospital outbreak of a vancomycin-resistant enterococcus (VRE) in Western Australia (WA) started in the Royal Perth Hospital in July 2001 and initially involved the Intensive Care Unit (ICU) and the Nephrology and Dialysis Units. The outbreak was caused by vancomycin-resistant Enterococcus faecium (VREF) of the vanB genotype. Pulsed-field gel electrophoresis and plasmid analysis of the isolates demonstrated a single-strain outbreak. Despite the isolation of carriers and implementation of all the additional precautions recommended to control VRE, VREF spread rapidly. Two months after the index patient was detected, the epidemic strain had spread to 22 wards and units and one outpatient unit (Satellite Dialysis). Four patients were infected and 64 were colonized. A Hospital VRE Executive Group, which included the Chief Executive and Directors of Clinical Services and Nursing, was formed to eradicate the outbreak and to prevent the epidemic strain from becoming endemic in the hospital. The WA Department of Health agreed to provide substantial extra funding to enable the hospital to use expensive enhanced infection control practices, as follows. Control was handicapped by the slowness of conventional laboratory methods, which took four to five days to identify VRE and allowed environmental contamination and nosocomial transmission to occur before carriers were detected and isolated. A laboratory procedure to make rapid provisional identification of VRE within 30-48h was developed by performing multiplex polymerase chain reaction (PCR) for vanA and vanB genes directly on 24-h selective enrichment broth cultures. On average, four rectal swabs, each collected on separate days, were needed to detect >90% of carriers. In total, 1977 ward contacts were screened after discharge from hospital and 54 (2.73%) were found to be carrying VREF. The electronic labelling and active follow-up of ward contacts resulted in a significant number of carriers being detected who otherwise posed a risk of initiating further outbreaks in hospital if they were re-admitted. The outbreak was terminated after five months and the cost of the enhanced infection control practices was 2,700 000 Australian dollars (1,000,000 pounds sterlings). Ongoing control has been facilitated by targeted active surveillance cultures: on admission to high-risk units (ICU, Burns, Nephrology, Haematology, Bone Marrow Transplant Unit), on transfer out of the ICU to other hospital units, by monthly screening of patients regularly attending Dialysis Units, and by opportunistic laboratory screening of inpatient faecal specimens submitted for Clostridium difficile culture and toxin. Vigilance needs to be maintained as the epidemic strain of VREF remains in the Perth community. Ward contacts of the first outbreak have caused small outbreaks in two hospitals, and seven to 19 sporadic new carriers have been detected annually since the first outbreak. The key elements of the VRE control programme are as follows: To date, this programme has prevented VRE from becoming established in any WA hospital.

Bacterial Proteins↗

PubMed2004

Quantifying human health risks from virginiamycin used in chickens.

The streptogramin antimicrobial combination Quinupristin-Dalfopristin (QD) has been used in the United States since late 1999 to treat patients with vancomycin-resistant Enterococcus faecium (VREF) infections. Another streptogramin, virginiamycin (VM), is used as a growth promoter and therapeutic agent in farm animals in the United States and other countries. Many chickens test positive for QD-resistant E. faecium, raising concern that VM use in chickens might compromise QD effectiveness against VREF infections by promoting development of QD-resistant strains that can be transferred to human patients. Despite the potential importance of this threat to human health, quantifying the risk via traditional farm-to-fork modeling has proved extremely difficult. Enough key data (mainly on microbial loads at each stage) are lacking so that such modeling amounts to little more than choosing a set of assumptions to determine the answer. Yet, regulators cannot keep waiting for more data. Patients prescribed QD are typically severely ill, immunocompromised people for whom other treatment options have not readily been available. Thus, there is a pressing need for sound risk assessment methods to inform risk management decisions for VM/QD using currently available data. This article takes a new approach to the QD-VM risk modeling challenge. Recognizing that the usual farm-to-fork ("forward chaining") approach commonly used in antimicrobial risk assessment for food animals is unlikely to produce reliable results soon enough to be useful, we instead draw on ideas from traditional fault tree analysis ("backward chaining") to reverse the farm-to-fork process and start with readily available human data on VREF case loads and QD resistance rates. Combining these data with recent genogroup frequency data for humans, chickens, and other sources (Willems et al., 2000, 2001) allows us to quantify potential human health risks from VM in chickens in both the United States and Australia, two countries where regulatory action for VM is being considered. We present a risk simulation model, thoroughly grounded in data, that incorporates recent nosocomial transmission and genetic typing data. The model is used to estimate human QD treatment failures over the next five years with and without continued VM use in chickens. The quantitative estimates and probability distributions were implemented in a Monte Carlo simulation model for a five-year horizon beginning in the first quarter of 2002. In Australia, a Q1-2002 ban of virginiamycin would likely reduce average attributable treatment failures by 0.35 x 10(-3) cases, expected mortalities by 5.8 x 10(-5) deaths, and life years lost by 1.3 x 10(-3) for the entire population over five years. In the United States, where the number of cases of VRE is much higher, a 1Q-2002 ban on VM is predicted to reduce average attributable treatment failures by 1.8 cases in the entire population over five years; expected mortalities by 0.29 cases; and life years lost by 6.3 over a five-year period. The model shows that the theoretical statistical human health benefits of a VM ban range from zero to less than one statistical life saved in both Australia and the United States over the next five years and are rapidly decreasing. Sensitivity analyses indicate that this conclusion is robust to key data gaps and uncertainties, e.g., about the extent of resistance transfer from chickens to people.

Animal Husbandry↗

PubMed2004

Analysis of etiology and drug resistance of biliary infections.

The bile was collected from fro patients with biliary infections, with the bacterium isolated to study the sensitivity of each kind of the bacterium to several antibiotics in common use. Except G- bacterium, we also found some kinds of G+ bacterium in infection bile. G- bacterium were not sensitive to Clindamycin, G+ bacterium were sensitive to Ciprofloxacin. Escherichia coli, Xanthomonas maltophilia, Enterobacter cloacae, Pseudomonas aeruginosa were sensitive to Ampicillin. G+ bacterium were not sensitive to Azactam. Enterococcus faecalis, Enterococcus faecium, Enterobacter cloacae were not sensitive to Ceftazidime. Enterococcus faecalis, Staphylococcus coagulase negative, Staphylococcus epidermidis, Pseudomonas aeruginosa were not sensitive to Ceftriaxone Sodium. We didn't found any bacterium resistance Imipenem. The possibility of the existence of G+ bacterium as well as drug resistance should be considered n patients with biliary infections. The value of susceptibility test should be respected to avoid drug abuse of antibiotics.

Adult↗

PubMed1997

In vitro antimicrobial activity and MIC quality control guidelines of RPR 106972 (RPR 112808/RPR106950): a novel orally administered streptogramin combination. The Quality Control Study Group.

RPR 106972 is a novel oral streptogramin combination with reported therapeutic potency against Gram-positive and certain respiratory tract pathogens. MICs for RPR 106972, quinupristin/dalfopristin, and seven comparison drugs were determined by the reference methods against 337 strains selected to define spectrum and potency. RPR 106972 demonstrated antimicrobial activity against oxacillin-susceptible and -resistant Staphylococcus aureus (MIC ranges of 0.12 to 2 micrograms/ml and 0.5 to 2 micrograms/ml, respectively), and coagulase-negative staphylococci were also inhibited by RPR 106972 (MIC90, < or = 0.5 microgram/ml) and quinupristin/dalfopristin (MIC90, < or = 0.25 microgram/ml). Against all streptococcal strains tested (including penicillin-resistant pneumococcus), RPR 106972 was highly active with MIC results at < or = 1 microgram/ml. RPR 106972 inhibited Corynebacterium jeikeium (MIC90, 0.5 microgram/ml). Moraxella catarrhalis (MIC90, 0.25 microgram/ml), and some Haemophilus influenzae (MIC50, 2 micrograms/ml). RPR 106972 and quinupristin/dalfopristin demonstrated little activity against Enterococcus faecalis (MIC90s, 4 to 32 micrograms/ml) as compared to Enterococcus faecium (MIC90s, 0.5 to 1 microgram/ml) and other Enterococcus ssp. (MIC90s, 1 microgram/ml). Studies to establish MIC quality-control guidelines indicated the following ranges: for E. faecalis ATCC 29212, 0.5 to 4 micrograms/ml; for S. aureus ATCC 29213, 0.25 to 1 microgram/ml; and for Streptococcus pneumoniae ATCC 49619, 0.06 to 0.5 microgram/ml. The results of this study indicate that the in vitro activity of RPR 106972 against Gram-positive bacteria and selected Gram-negative respiratory organisms is promising and warrants additional studies of pharmacokinetics, and in vivo infection model dynamics.

Administration, Oral↗

PubMed1998

Survival of vancomycin-resistant and vancomycin-susceptible enterococci on dry surfaces.

We compared the abilities of Enterococcus faecium strains (three vancomycin-resistant enterococci [VRE] and five vancomycin-susceptible enterococci [VSE]) and Enterococcus faecalis strains (one VRE and 10 VSE) to survive under dry conditions. Bacterial suspensions of the strains were inoculated onto polyvinyl chloride and stored under defined conditions for up to 16 weeks. All strains survived for at least 1 week, and two strains survived for 4 months. A statistical model was used to distribute the 19 resulting survival curves between two types of survival curves. The type of survival curve was not associated with the species (E. faecalis versus E. faecium), the source of isolation (patient versus environment), or the susceptibility to vancomycin (VRE versus VSE). Resistance to dry conditions may promote the transmissibility of a strain, but VRE have no advantages over VSE with respect to their ability to survive under dry conditions.

Anti-Bacterial Agents↗

PubMed2005

Enterococcal meningitis caused by Enterococcus casseliflavus. First case report.

BACKGROUND: Enterococcal meningitis is an uncommon disease usually caused by Enterococcus faecalis and Enterococcus faecium and is associated with a high mortality rate. Enterococcus casseliflavus has been implicated in a wide variety of infections in humans, but never in meningitis. CASE PRESENTATION: A 77-year-old Italian female presented for evaluation of fever, stupor, diarrhea and vomiting of 3 days duration. There was no history of head injury nor of previous surgical procedures. She had been suffering from rheumatoid arthritis for 30 years, for which she was being treated with steroids and methotrexate. On admission, she was febrile, alert but not oriented to time and place. Her neck was stiff, and she had a positive Kernig's sign. The patient's cerebrospinal fluid was opalescent with a glucose concentration of 14 mg/dl, a protein level of 472 mg/dl, and a white cell count of 200/muL with 95% polymorphonuclear leukocytes and 5% lymphocytes. Gram staining of CSF revealed no organisms, culture yielded E. casseliflavus. The patient was successfully treated with meropenem and ampicillin-sulbactam. CONCLUSIONS: E. casseliflavus can be inserted among the etiologic agents of meningitis. Awareness of infection of central nervous system with Enterococcus species that possess an intrinsic vancomycin resistance should be increased.

Aged↗

PubMed2006

Isolation and characterization of lactic acid bacteria from dochi (fermented black beans), a traditional fermented food in Taiwan.

AIMS: To isolate, characterize and identify lactic acid bacteria (LAB) in dochi (fermented black beans), a traditional fermented food in Taiwan. METHODS AND RESULTS: A total of 30 samples were collected from three different dochi producers and analysed after different periods of storage. Fifty-two cultures of LAB were isolated from dochi samples and the isolates were divided into classes by phenotype and then into groups by restriction fragment length polymorphism analysis and sequencing of 16S ribosomal DNA. Phenotypic and biochemical characteristics identified six different bacterial groups (A-F) and showed that the majority of the isolates were homofermentative LAB. Enterococcus faecium was the most abundant of the dochi-isolated LAB. All isolated LAB were able to grow in MRS broth containing 6% NaCl, but only Enterococcus, Pediococcus and Tetragenococcus species could grow in MRS broth containing 10% NaCl. Furthermore, antibacterial activities of isolates were determined, and four isolates showed inhibitory activities against the indicator strain Lactobacillus sakei JCM 1157(T). CONCLUSIONS: These results suggest that Ent. faecium is the main LAB present during the fermentation of dochi. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report describing the distribution and varieties of LAB that exist in the dochi fermentation process.

Antibiosis↗

PubMed2003

Species composition and antimicrobial resistance genes of Enterococcus spp, isolated from integrated and traditional fish farms in Thailand.

Integrated fish farming uses the manure from animal husbandry as fertilisers in the fish ponds. A total of 410 enterococcal isolates, from integrated and traditional fish farms in Thailand, were collected to assess whether the input of manure from chickens receiving feed containing growth promoters and antimicrobial treatments influenced the species composition and the bacterial antimicrobial resistance in the fish pond environment. Enterococcus faecium and E. faecalis were the predominate species isolated from the integrated farms, whereas E. casseliflavus and E. mundtii isolates were most prevalent in traditional farms. Enterococcus faecalis and E. faecium demonstrated the highest prevalence of resistance, whereas E. mundtii isolates were susceptible to all antimicrobials tested. All the enterococci species isolated from the integrated farms, generally demonstrated higher resistance phenotypes to the tested antimicrobials compared with the same species from traditional farms. The erm(B) and tet(M) genes, associated with resistance to erythromycin and tetracycline, respectively, were found in 87% of the erythromycin-resistant and 95% of the oxytetracycline-resistant enterococci isolates respectively. These results suggest that the species composition and antimicrobial resistance of enterococci in tropical aquatic environments are influenced by faecal and antimicrobial pollution.

Animal Husbandry↗

PubMed2003

Identification of lactic acid bacteria isolated from human vaginal secretions.

A total of 57 lactic acid bacteria were isolated from the vaginal secretions of 259 patients. Of these strains, 37 were isolated from patients attending pre-natal clinics and the remaining strains from patients attending post-natal clinics. The strains were identified by using simple physiological and biochemical tests and their phenotypic relatedness determined by numerical analysis of total soluble cell protein patterns. The genotypic relatedness of representative strains selected from each of the protein profile clusters was determined by numerical analysis of the DNA banding patterns obtained from RAPD-PCR. The majority of lactobacilli isolated belonged to the species Lactobacillus pentosus, Lactobacillus fermentum and Enterococcus faecium. A few strains of Lactobacillus plantarum and Weissella viridescens were also isolated. One strain, TV 1029, grouped into the same protein profile cluster as E. faecium, but revealed a DNA banding pattern closer related to Enterococcus faecalis. This is the first report of W. viridescens associated with the human vagina.

Bacterial Proteins↗

PubMed2003

Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci.

BAL9141 has been reported to have inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), many enterococci, and streptococci with various resistant patterns. BAL9141 potency was assessed by time-kill curves alone or with subinhibitory concentrations of gentamicin (MIC/4). BAL9141 exhibited bactericidal activity alone against all the streptococci and staphylococci. Among ampicillin-susceptible enterococci, BAL9141 was bactericidal against some strains, but no BAL9141 inhibition was observed of ampicillin-resistant Enterococcus faecium. The activity of BAL9141 with gentamicin was slightly enhanced (not synergy) or indifferent against staphylococci. BAL9141 demonstrated bactericidal action alone against Enterococcus faecalis and some E. faecium strains (-4.8 to -6.0 log10 CFU/mL), but static effects were also noted. Drug interactions with gentamicin showed early synergy (4-8 h) for all enterococci, and indifference or synergy at 24 h (no antagonism). BAL9141 (< or = 8 mg/L) showed promising bactericidal activity alone and synergy with gentamicin against some of the vancomycin-resistant enterococci tested.

Anti-Bacterial Agents↗

PubMed2005

Contribution of enterococci to the spread of antibiotic resistance in the production chain of swine meat commodities.

Thirty-six samples, including fecal specimens, dry feedstuffs, raw and processed pork meat products, and dry fermented sausages, were collected from two production chains of swine meat commodities and analyzed for the presence of 11 antibiotic resistance (AR) genes. Specific PCR assays carried out on DNA extracted directly from the samples revealed a high incidence of the genes tet(K) (80.5%), ermB (66.7%), and tet(M) (66.7%). Feces and feedstuffs gave the largest number of positive amplifications. To elucidate the contribution of enterococci to the occurrence and spread of AR, 146 resistant enterococci were isolated, and their identity, genetic fingerprints, and AR gene profiles were determined by means of molecular techniques. Enterococcus faecalis and Enterococcus faecium were the predominant isolated species (43.8 and 38.4%, respectively); Other Enterococcus species identified were E. durans (8.9%), E. hirae (2.7%), E. gallinarum (2.1%), E. mundtii (2.1%), and E. casseliflavus (2.1%). A number of isolates displayed a complex AR gene profile comprising up to four different resistance determinants. The genes tet(M) and ermB were highly diffused, being present in 86.9 and 84.9%, respectively, of the isolates. The application of amplified fragment length polymorphism fingerprinting was particularly valuable to monitor the resistant enterococcal isolates along the production chain and to individuate steps in which contamination might occur. In fact, isolates of E. faecalis and E. faecium showing the same amplified fragment length polymorphism profile and AR gene pattern were detected in samples taken at different steps of the food chain suggesting three cases of bacterial clonal spread.

Animals↗

PubMed2005

Molecular characterization of vanB elements in naturally occurring gut anaerobes.

Previously, we reported the isolation of 10 vancomycin-resistant gram-positive anaerobic bacilli carrying the vanB ligase gene from nine hemodialysis patients (S. A. Ballard et al., Antimicrob. Agents Chemother. 49:77-81, 2005; T. P. Stinear et al., Lancet 357:855-856, 2001). In the present study, the molecular and evolutionary relationship of the vanB resistance element within these 10 anaerobes and two vancomycin-resistant Enterococcus faecium strains were examined. PCR analysis and nucleotide sequencing demonstrated that all 12 isolates carried the vanB operon associated with an element identical to Tn1549 and Tn5382 of Enterococcus. Restriction fragment length polymorphism analysis of the vanB operon in these isolates revealed two distinct patterns, and sequencing showed that minor base differences existed. PCR amplification of the joint region of a circular intermediate was demonstrated in nine of these organisms, a finding indicative of an ability to excise and circularize, an intermediate step in transposition and conjugative transfer. Southern hybridization with a vanB-vanX(B) probe suggests that there is one insert of the transposon in all isolates. Sequence analysis of the integration site revealed distinct sequences: the Tn1549/5382 element within E. faecium was inserted within the host chromosome, whereas nucleotide sequences surrounding the Tn1549/5382 element in the 10 anaerobes showed no significant homology to sequences in the GenBank database. We demonstrate considerable similarity between the Tn1549/5382 element identified in 10 anaerobe isolates with that found in enterococci. The homology and potential to transpose suggest a recent horizontal transfer event may have occurred. However, the original direction of transposition and the mechanism involved remains unknown.

Anti-Bacterial Agents↗

PubMed2004

[Antibiotic susceptibility analysis of Enterococcus spp. isolated from urine].

Recently increase of enterococcal infections has been observed. These bacteria, mainly Enterococcus faecalis and Enterococcus faecium are members of the normal flora of gastrointestinal tract but also are typical opportunistic pathogens. Enterococci are characterized by natural resistance to numerous antibiotics (among them cephalosporins), and also by easy acquired resistance to antibiotics. Infections caused by multiresistant strains are difficult in treatment, chronic, recurrent and sometimes fatal are described. Enterococcal infections are caused often by E. faecalis, rarely by E. faecium. In the last years other species of enterococci have been isolated from different clinical materials (E. casseliflavus, E. avium, E. durans, E. gallinarum). The aim of this study was to analyze the antibiotics susceptibility of Enterococcus spp. isolated from urine of children with urinary tract infection (UTI), hospitalized in the Upper Silesian Health Center of Child and Mother or treated ambulatory. Susceptibility of the 130 strains of E. faecalis and 41 E. faecium to: penicillin, tetracycline, high level of aminoglycoside (gentamycin 120 microg and streptomycin 300 microg), glycopeptides (vancomycin and teicoplanin), ciprofloxacin and nitrofurantoin was estimated. All isolated strains of E. faecalis (100%) were sensitive to glycopeptides (vancomycin and teicoplanin) and to nitrofurantoin, 96% strains were sensitive to penicillin, 43% to ciprofloxacin and 28% to tetracycline. All strains of E. faecium were sensitive to glycopeptides (vancomycin and teicoplanin), 32% strains were sensitive to penicillin, 19% to tetracycline 14% to ciprofloxacin and 50% to nitrofurantoin. Twenty two strains of E. faecalis (17%) and twelve strains of E. faecium (29%) were demonstrated high level resistance to aminoglycosides (HLAR). Among HLAR strains of enterococci, were observed strains of high level resistance only to streptomycin, high level resistance only to gentamycin and high level resistance to both aminoglycosides. The HLAR strains of E. faecalis and E. faecium were also resistant to other antibiotics: penicillin, tetracycline and ciprofloxacin. The most frequent cause of child urinary tract infection was E. faecalis, with high sensitivity to penicillins, glycopeptides and nitrofurantoin. The increased role of E. faecium and other strains of enterococci also has been shown. These species demonstrated sensitivity to glycopeptides, but resistance to other antibiotics, routinely used for treatment of UTI as well as to nitrofurantoin.

Anti-Bacterial Agents↗

PubMed1993

Ability of clinical laboratories to detect antimicrobial agent-resistant enterococci.

To test the ability of clinical laboratories to detect antimicrobial resistance among enterococci, we sent four vancomycin-resistant enterococcal strains and one beta-lactamase-producing enterococcus to all 93 nongovernment, hospital-based clinical laboratories in New Jersey; 76 (82%) participated in the study. Each organism was tested by the laboratory's routine antimicrobial susceptibility testing method. The proportion of laboratories that correctly reported that an isolate was resistant to vancomycin varied according to the resistance level of the isolate: high-level resistance (MIC for Enterococcus faecium = 512 micrograms/ml), 96% of laboratories correct; moderate-level resistance (MIC for E. faecium = 64 micrograms/ml), 27% correct; low-level resistance (MIC for Enterococcus faecalis = 32 micrograms/ml), 16% correct; and intrinsic low-level resistance (MIC for Enterococcus gallinarum = 8 micrograms/ml), 74% correct. The beta-lactamase-producing E. faecalis isolate was identified as resistant to penicillin and ampicillin by 66 and 8% of laboratories, respectively, but only three laboratories recognized that it was a beta-lactamase producer. This survey suggests that many laboratories may fail to detect antimicrobial agent-resistant enterococci.

Ampicillin Resistance↗

PubMed1998

Association between decreased susceptibility to a new antibiotic for treatment of human diseases, everninomicin (SCH 27899), and resistance to an antibiotic used for growth promotion in animals, avilamycin.

The emergence of multiresistant bacteria has increased the need for new antibiotics or modifications of older antibiotics. One promising agent might be the everninomicin SCH 27899, an oligosaccharide antibiotic recently developed by Schering Plough. However, another oligosaccharide, avilamycin, that is structurally very similar has been used as a growth promoter for food animals in the EU for several years, and a very frequent occurrence of resistance to avilamycin has been found among Enterococcus faecium isolates from broilers in Denmark. This study was conducted to investigate whether the resistance to avilamycin was associated with decreased susceptibility to everninomicin. From broilers, a total of 31 avilamycin susceptible and 55 avilamycin resistant (MIC >16 microg/mL) E. faecium isolates were selected. From pigs, 21 avilamycin-susceptible and eight avilamycin-resistant Enterococcus faecalis and 50 avilamycin-susceptible and two avilamycin-resistant E. faecium isolates were selected. All isolates were tested for susceptibility to everninomicin by E-test. The avilamycin-susceptible enterococci isolates had MICs to everninomicin from 0.064 to 0.75 microg/mL (MIC50 = 0.38 microg/mL) and the avilamycin-resistant isolates had MICs from 1.5 to 16 microg/mL (MIC50 = 3 microg/mL). Complete agreement between decreased susceptibility to avilamycin and everninomicin was found. This study showed that the use of avilamycin as a growth promoter for broilers and pigs has created a reservoir of E. faecium and E. faecalis isolates with decreased susceptibility to everninomicin among food animals already before this antibiotic have been finally developed for human use.

Aminoglycosides↗

PubMed2002

Antimicrobial activity of quinupristin-dalfopristin combined with other antibiotics against vancomycin-resistant enterococci.

Interactions between quinupristin-dalfopristin and six other antimicrobials were examined by checkerboard arrays against 50 clinical isolates of vancomycin-resistant Enterococcus faecium selected to represent a range of susceptibilities to individual agents. Unequivocal synergistic or antagonistic interactions at clinically relevant concentrations were infrequently encountered when the streptogramin was combined with chloramphenicol, ampicillin, imipenem, vancomycin, or teicoplanin. Combinations with doxycycline resulted in synergistic inhibition in 36% of checkerboards. Against 10 strains of Enterococcus faecalis, synergistic interactions were found when quinupristin-dalfopristin was combined with doxycycline (four strains), either glycopeptide (three strains), or ampicillin (two strains). Combination with quinupristin-dalfopristin increased the ampicillin MIC from 1 to 4 microg/ml for one strain. For 10 strains of E. faecium, interactions were also assessed by time-kill methods using concentrations of the agents attainable in human serum. Most of these antimicrobials augmented killing by quinupristin-dalfopristin to a minor degree. Against 2 of the 12 strains in this collection that were not highly resistant to gentamicin, the combination of quinupristin-dalfopristin (2 microg/ml) plus gentamicin (5 microg/ml) resulted in killing approaching 3 log(10) CFU/ml. With the exception of doxycycline, inhibitory interactions between quinupristin-dalfopristin and other agents tested against vancomycin-resistant strains of E. faecium were uncommon at clinically relevant concentrations.

Anti-Bacterial Agents↗

PubMed1998

[Opsonin requirements for phagocytosis of Enterococcus spp. by human polymorphonuclear leukocytes].

BACKGROUND: Interaction of Enterococcus spp. and host defense mechanisms is not well known. Opsonic requirements of Enterococcus faecalis and Enterococcus faecium to be phagocyted by human polymorphonuclear leukocytes (PMN) were evaluated. METHODS: Twenty strains (10 E. faecalis and 10 E. faecium) were studied. Phagocytosis was determined by a radiometric assay. Bacterial cells were labelled with 3H-adenine and opsonized with: a) 10% of human pool sera (HPS); b) 10% of decomplemented HPS, and c) albumin and fibronectin. RESULTS: Phagocytosis of Enterococcus spp. by PMN in the presence of HPS was significantly higher than that in the absence of opsonins. The phagocytosis of E. faecium was higher than that of E. faecalis. A strain-dependent effect of complement in the phagocytosis of Enterococcus spp. was observed. Neither albumin nor fibronectin showed an opsonic activity on Enterococcus spp. CONCLUSIONS: A great heterogeneity in the opsonic requirements of Enterococcus spp. was observed. Serum opsonins show a critical role in the phagocytosis of E. faecalis and E. faecium by PMN, this effect being more relevant with E. faecium. A strain-dependent opsonic activity of complement was observed.

Adult↗