virginiamycin and Cross-Infection

Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) are among the main causes of nosocomial infections, which have caused major problems in recent years due to continuously increasing spread of various antibiotic resistance features. Apparently, vancomycin is still an effective antibiotic for treatment of infections caused by these bacteria but in recent years, additional resistance phenotypes have led to the accelerated introduction of newer agents such as linezolid, tigecycline, daptomycin, and quinupristin/dalfopristin (Q/D). Due to limited data availability on the global rate of resistance to these antibiotics, in the present study, the resistance rates of S. aureus, Methicillin-resistant S. aureus (MRSA), and CoNS to these antibiotics were collected.. Several databases including web of science, EMBASE, and Medline (via PubMed), were searched (September 2018) to identify those studies that address MRSA, and CONS resistance to linezolid, tigecycline, daptomycin, and Q/D around the world.. Most studies that reported resistant staphylococci were from the United States, Canada, and the European continent, while African and Asian countries reported the least resistance to these antibiotics. Our results showed that linezolid had the best inhibitory effect on S. aureus. Although resistances to this antibiotic have been reported from different countries, however, due to the high volume of the samples and the low number of resistance, in terms of statistical analyzes, the resistance to this antibiotic is zero. Moreover, linezolid, daptomycin and tigecycline effectively (99.9%) inhibit MRSA. Studies have shown that CoNS with 0.3% show the lowest resistance to linezolid and daptomycin, while analyzes introduced tigecycline with 1.6% resistance as the least effective antibiotic for these bacteria. Finally, MRSA and CoNS had a greater resistance to Q/D with 0.7 and 0.6%, respectively and due to its significant side effects and drug-drug interactions; it appears that its use is subject to limitations.. The present study shows that resistance to new agents is low in staphylococci and these antibiotics can still be used for treatment of staphylococcal infections in the world.

Topics: Anti-Bacterial Agents; Coagulase; Cross Infection; Daptomycin; Drug Resistance, Multiple, Bacterial; Global Health; Humans; Linezolid; Prevalence; Staphylococcus; Staphylococcus aureus; Tigecycline; Virginiamycin

Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including β-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed.

Topics: Animals; Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Teicoplanin; Vancomycin; Vancomycin Resistance; Virginiamycin

Gram-positive pathogens, primarily Staphylococcus aureus, coagulase-negative staphylococci, viridans group streptococci, and enterococci, are now the predominant causes of infection in neutropenic haematology/oncology patients, but are often resistant to multiple antibiotics. Glycopeptides have been the only alternative antibiotic treatments for multidrug-resistant Gram-positive infections to date. However, glycopeptides are not always effective or well tolerated, and can produce nephrotoxic or ototoxic effects. Quinupristin/dalfopristin is a recently introduced streptogramin antibiotic that is active in vitro against most of the major Gram-positive pathogens causing infection in neutropenic patients. Recent studies of the in vitro susceptibility of clinical isolates of Gram-positive pathogens to quinupristin/dalfopristin are summarized. Pre-clinical and clinical studies of the efficacy and safety of quinupristin/dalfopristin in the treatment of Gram-positive infections are reviewed. Quinupristin/dalfopristin is active in vitro against the vast majority of recent isolates of relevant Gram-positive pathogens, including methicillin-resistant staphylococci, viridans group streptococci, and vancomycin-resistant Enterococcus faecium, but excluding Enterococcus faecalis. Pre-clinical and clinical data indicate the efficacy of quinupristin/dalfopristin in infections caused by these organisms, including bacteraemia and catheter-related infections. Quinupristin/dalfopristin is not associated with nephrotoxicity or ototoxicity. Quinupristin/dalfopristin is a potential alternative to glycopeptides in haematology or oncology patients with multidrug-resistant Gram-positive infections, especially those who are unresponsive to, or intolerant of, glycopeptides.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hematologic Neoplasms; Humans; Male; Microbial Sensitivity Tests; Neutropenia; Randomized Controlled Trials as Topic; Risk Assessment; Sensitivity and Specificity; Treatment Outcome; Virginiamycin

Gram-positive cocci, including enterococci and Staphylococcus aureus, have become the leading cause of hospital-acquired infections, and their resistance to antibiotics is increasing. Two important new drugs-quinupristin/dalfopristin (Synercid) and linezolid (Zyvox)-were designed specifically to treat infections due to drug-resistant gram-positive cocci. But their use must be tempered by their cost, toxicity, and concerns about further development of resistant strains.

Topics: Acetamides; Anti-Bacterial Agents; Cross Infection; Drug Interactions; Drug Resistance, Microbial; Drug Therapy, Combination; Enterococcus; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Linezolid; Methicillin; Oxazolidinones; Virginiamycin

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.. 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.. 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.. 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.. 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.

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Drug Interactions; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Skin Diseases, Bacterial; Vancomycin Resistance; Virginiamycin

Topics: Acetamides; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Area Under Curve; Child; Cross Infection; Drug Combinations; Gram-Positive Bacterial Infections; Humans; Infant; Infant, Newborn; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Tissue Distribution; Virginiamycin

Changing patterns of pathogens and antibiotic susceptibility present clinicians with difficult choices for antimicrobial prescribing. In particular, multiresistant staphylococci, enterococci and pneumococci present problems in many settings. The number of predictably active antimicrobials is decreasing in many centres, with significant consequences for both patients and society as a whole. New antimicrobial options have been few in recent years and several promising quinolones have been compromised by formulation and/or toxicity issues. Nevertheless, the recent introduction of linezolid and quinupristin/dalfopristin provides clinicians with valuable new options against Gram-positive cocci. These options should further increase with the likely introduction of daptomycin, oritavancin and tigilcycline. A range of surveillance programmes helps monitor the ever-changing patterns of resistance and thus guides clinicians in their empirical prescribing. Empirical use of powerful newer agents may be justifiable in seriously ill patients in those settings, units and countries where there is a substantial background rate of resistance.

Topics: Acetamides; Anti-Bacterial Agents; Chemistry, Pharmaceutical; Cross Infection; Drug Resistance, Bacterial; Drugs, Investigational; Europe; Gram-Positive Bacterial Infections; Humans; Infection Control; Linezolid; Oxazolidinones; Practice Patterns, Physicians'; United States; Virginiamycin

Vancomycin-resistant enterococci is a worldwide threat not only in hospitals, but also in communities. Community-acquired infections play an important role in spreading VRE because the use of avoparcin, an antimicrobial growth promoter in food animals, is strongly suggested to cause the emergence of VRE. In particular, chickens imported into Japan have been reported to be highly contaminated with VRE, and this may be a key issue in the prevalence of VRE. Nosocomial VRE infections have become a serious problem in immuno-compromised patients throughout the world, and many VREs have been isolated in Japan in the last few years; however, fortunately, nosocomial outbreaks are still rare. VRE can survive for weeks in hospital environments, which makes infection control difficult and complicated, and strains of VRE resistant to almost all antimicrobial agents are a real threat. In outbreaks of VRE, prudent antimicrobial use and prompt effective infection control are important.

Topics: Ampicillin; Animals; Bacteremia; Community-Acquired Infections; Cross Infection; Drug Therapy, Combination; Enterococcus; Gentamicins; Humans; Immunocompromised Host; Risk Factors; Urinary Tract Infections; Vancomycin Resistance; Virginiamycin

Over recent years gram-positive bacterial pathogens have become dominant in many forms of nosocomial infections. The principal pathogens in severe infections are Staphylococcus aureus and enterococci. The utility of the traditional antibiotics used for nosocomial sepsis, particularly beta-lactam agents, has been severely compromised by the spread of resistance and there was, often, no therapeutic alternative to the glycopeptide antibiotics, vancomycin and teicoplanin, for empirical (and often also the specific) therapy of infections caused by methicillin-resistant S. aureus (MRSA) and Enterococcus spp. This reliance on glycopeptides, however, is now also threatened by acquired resistance. Vancomycin-resistant enterococci (VRE), particularly E. faecium, have become a therapeutic problem in many European cities and are now endemic in some hospital wards. The recent reports from several continents of MRSA with reduced glycopeptide-susceptibility (GISA) is of grave concern. New agents are needed to meet these threats and several classes of compounds are under development. One class is the streptogramins and the combination of quinupristin/dalfopristin (Synercid) is nearing licensing. Clinical trials and a compassionate use programme have already shown it to have considerable promise for the treatment of the most problematic forms of gram-positive nosocomial sepsis, including MRSA and vancomycin-resistant E. faecium infections that had failed therapy with other antibiotics.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Microbial; Gram-Positive Bacterial Infections; Humans; Sepsis; Staphylococcal Infections; Virginiamycin

A review of the literature suggests the following conclusions: 1) since its first practical use in 1965, namely over the past 10 years, there has been no drop in activity of Gentamicin on Staphylococcus aureus and on numerous other Staphylococcus and/or Micrococcus species. 2) In comparison with the other aminoglycosidic antibiotics employed up to the present, i.e. Streptomycin, Neomycin, Kanamycin, Amminosidine, and Framycetin, Gentamicin has demonstrated a much superior antistaphylococcic activity, and this has also been documented on numerous strains of staphylococci recalcitrant to Kanamycin, Streptomycin, Framycetin and Neomycin. This goes to prove the absence of any cross resistance between Kanamycin, Streptomycin, Framycetin and Neomycin on the one hand and Gentamycin on the other. 3) Along with Rifampicin, certain Cephalosporins (Cephalotine, Cephaloridine) and Pristinamycin-Virgimycin, Gentamicin must undoubtedly be considered a "greater" antibiotic as far as antistaphylococcic activity is concerned. It also has the advantage over other antistaphylococcic-acting antibiotics that only in exceptional cases does it give rise to resistant strains.

Topics: Cephalosporins; Cross Infection; Drug Resistance, Microbial; Framycetin; Gentamicins; Humans; Kanamycin; Microbial Sensitivity Tests; Neomycin; Paromomycin; Rifampin; Staphylococcal Infections; Staphylococcus; Streptomycin; Virginiamycin

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

Topics: Adult; Aged; Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Prospective Studies; Treatment Outcome; Vancomycin; Virginiamycin

Quinupristin/dalfopristin (Q/D) is a valuable alternative antibiotic to vancomycin for the treatment of multi-drug resistant Enterococcus faecium infections. However, resistance to Q/D in E. faecium clinical isolates and nosocomial dissemination of Q/D-resistant E. faecium have been reported in several countries and should be of concern.. From January 2012 to December 2015, 911 E. faecium clinical isolates were isolated from various specimens of inpatients at the first Affiliated Hospital of Wenzhou Medical University located in Wenzhou, east China. Of 911 E. faecium clinical isolates, 9 (1.0 %, 9/911) were resistant to Q/D, with the Q/D MIC values of 64 mg/L(1), 32 mg/L(1), 16 mg/L(3), 8 mg/L(1) and 4 mg/L(3) determined by broth microdilution. All Q/D-resistant isolates were susceptible to vancomycin, tigecycline and teicoplanin but resistant to penicillin, ampicillin and erythromycin. vatE was only found in one Q/D-resistant E. faecium isolate while vatD was not detected in any of the isolates tested. 8 of 9 Q/D-resistant E. faecium isolates were found be positive for both ermB and msrC. The combinations of Q/D resistance determinants were ermB-msrC (7 isolates) and ermB-msrC-vatE (one isolate). ST78, ST761, ST94, ST21 and ST323 accounted for 4, 2, 1, 1 and 1 isolate, respectively, among which ST78 was the prevalent ST.. Q/D-resistant E. faecium clinical isolates were first described in China. Carriage of vatE, ermB and msrC was responsible for Q/D resistance.

Topics: Anti-Bacterial Agents; Bacterial Proteins; China; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Enterococcus faecium; Genes, Bacterial; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Prevalence; RNA, Ribosomal, 16S; Vancomycin; Virginiamycin

The aims of the present study were to evaluate erythromycin, clindamycin, and streptogramin resistance rates, as well as the phenotypic and genotypic characteristics of erythromycin-resistant staphylococci in a Greek University Hospital. Macrolide, lincosamide, and streptogramin B-type resistance was investigated by double disk diffusion and the D-zone testing, while Minimal inhibitory concentration determination was performed among 656 erythromycin-resistant staphylococcal clinical consecutive isolates, too. The presence of the major genetic determinants ermA, ermB, ermC, and msrA were detected by polymerase chain reaction (PCR). The overall erythromycin resistance rate was 49·70%. One hundred and forty-six of the 322 Staphylococcus aureus were methicillin-resistant S. aureus (MRSA) (45·34%), whereas 176 were methicillin-susceptible S. aureus (54·66%). The macrolides, lincosamides, and streptogramin B-type antibiotics (MLSB)-constitutive phenotype was detected in 126 S. aureus strains (88·7%), whereas the inducible MLSB resistance phenotype was demonstrated in 16 S. aureus (11·3%). The MS phenotype was not detected. ErmC was the most frequently encountered gene responsible for macrolide resistance among S. aureus and coagulase negative staphylococci in this hospital. Pulsed-field gel electrophoresis (PFGE) analysis of SmaI DNA fragments revealed the presence of a single predominant clone among erythromycin-resistant S. aureus. The predominance of constitutive erythromycin resistance is a serious problem and limits the use of clindamycin for severe staphylococcal infections not only in this university hospital, but in many countries worldwide.

Topics: Anti-Bacterial Agents; Clindamycin; Cross Infection; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Erythromycin; Genes, Bacterial; Genotype; Greece; Hospitals, University; Humans; Microbial Sensitivity Tests; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Streptogramin B; Tertiary Healthcare; Virginiamycin

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Cross Infection; Daptomycin; Humans; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Pneumonia, Staphylococcal; Tigecycline; Vancomycin; Virginiamycin

This study updates the activity of telavancin against Gram-positive pathogens collected from USA hospitals (2007-2009). Telavancin (MIC(50/90), 0.12/0.25 μg/mL) was active against coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (100% susceptible), for which only daptomycin (MIC(50/90), 0.25/0.5 μg/mL; 99% susceptible) and quinupristin/dalfopristin (MIC(50/90), ≤ 0.25-0.5/0.5 μg/mL; 99% susceptible) exhibited similar activity. Telavancin (MIC(50/90), 0.25/0.5 μg/mL) inhibited 96.5% of Enterococcus faecalis at the Food and Drug Administration breakpoint (MIC, ≤ 1 μg/mL), where ampicillin (99.9% susceptible), daptomycin (99.9% susceptible), and linezolid (100% susceptible) also demonstrated high-level coverage. Telavancin inhibited, respectively, 100.0% and 91.7% of VanB-phenotype E. faecalis and E. faecium at ≤ 1 μg/mL, whereas it was less active against VanA strains. Telavancin was uniformly active against Streptococcus pneumoniae and resistant subsets, and demonstrated good potency (MIC(90), 0.06-0.12 μg/mL) against other streptococci, regardless of resistance to other drugs. This assessment reveals potent activity of telavancin against Gram-positive isolates collected from USA hospitals with no evidence of emergence of resistance.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Daptomycin; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitals; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; United States; Virginiamycin

The present study was carried out to assess the frequency of methicillin-resistant staphylococci (MRS) among racehorses (n=209) and veterinary personnel (n=13) as well as environmental surfaces (n=14) at an equine hospital in Adana, Turkey. In addition, species distribution, antimicrobial susceptibility, resistance genes, staphylococcal chromosomal cassette mec (SCCmec) type and clonality of these isolates were also investigated. MRS were identified by 16S rRNA sequencing, and typed by pulsed-field gel electrophoresis (PFGE). As a result, MRS was isolated in horses (48.3%), clinic staff (92.3%) and environmental samples (71.4%). Of the 123 MRS isolates, 118 isolates were identified as Staphylococcus lentus, and the remaining ones were found to be S. sciuri (n=3), S. intermedius (n=1) and S. fleuretti (n=1). All isolates were found to be susceptible against vancomycin, quinupristin-dalfopristin and rifampicin. Additionally, single or various combinations of resistance genes were detected among MRS isolates. SCCmec type II was identified in all isolates. Similar PFGE patterns were observed among MRS isolated from horses, humans, and environmental samples. Since MRS were concurrently isolated from horses and humans it is suggested that cross-transmission of MRS between horses and humans might occur. However, it cannot be ruled out that transmission is human to animal or animal to human.

Topics: Animal Technicians; Animals; Cross Infection; DNA Primers; Electrophoresis, Gel, Pulsed-Field; Genes, MDR; Horse Diseases; Horses; Humans; Methicillin Resistance; Polymerase Chain Reaction; Rifampin; Species Specificity; Staphylococcal Infections; Staphylococcus; Turkey; Vancomycin; Virginiamycin

Topics: Acetamides; Anti-Bacterial Agents; Cross Infection; Daptomycin; Drug Resistance, Bacterial; Enterococcus faecium; Glycopeptides; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Tigecycline; Virginiamycin

Nosocomial infections after spinal surgery are relatively uncommon but potentially serious. The goal of diagnostic evaluation is to determine the extent of infection and identify the microorganism involved. Neuroimaging provides accurate information on correct topography, localization and propagation of the infection. Microbiological data are able to give aetiological causes. In this patient with severe, chronic polymicrobial spine infection with epidural abscess and CSF fistula due to multidrug-resistant organisms, the cure was achieved with long-term antimicrobial specific therapy with quinupristin-dalfopristin (50 days) and linezolid (100 days) with mild side effects. This positive result was due to combined medical and surgical treatment.

Topics: Acetamides; Anti-Bacterial Agents; Bacteria; Cerebrospinal Fluid; Combined Modality Therapy; Cross Infection; Curettage; Device Removal; Discitis; Epidural Abscess; Female; Fistula; Fluconazole; Fungi; Humans; Internal Fixators; Laminectomy; Linezolid; Lumbar Vertebrae; Meropenem; Methicillin Resistance; Middle Aged; Osteomyelitis; Oxazolidinones; Parkinson Disease; Prosthesis-Related Infections; Reoperation; Skin Diseases; Spinal Diseases; Spinal Stenosis; Staphylococcal Infections; Thienamycins; Virginiamycin

To demonstrate nosocomial transmission of Enterococcus faecium resistant to quinupristin/dalfopristin and vancomycin/teicoplanin among paediatric patients in a German hospital ward.. Multiply-resistant E. faecium were isolated from three female patients aged 9 months, 2 and 15 years during a 10 day time span. Antibiotic susceptibilities were determined by microbroth dilution. Clonal relatedness among the isolates was investigated via SmaI-macrorestriction analysis by PFGE, multilocus sequence typing (MLST), and plasmid profiling. Presence of virulence and resistance determinants was tested by polymerase chain reaction (PCR). Selected resistance genes were localized by Southern hybridizations.. A single E. faecium isolate per patient was investigated. All exhibited resistances to quinupristin/dalfopristin, vancomycin/teicoplanin, streptomycin (high-level), penicillin/ampicillin, erythromycin, oxytetracycline, chloramphenicol, rifampicin and fusidic acid. The isolates were susceptible to linezolid only and intermediately resistant to fluoroquinolones including moxifloxacin. PFGE revealed identical patterns for all three isolates. PCRs for virulence determinants hyaluronidase and enterococcal surface protein, esp, were negative, whereas PCR for the enterocin A gene was positive. MLST identified clonal type [8-5-1-1-1-1-1] belonging to a clonal subgroup C1 of hospital- and outbreak-related E. faecium. Southern hybridizations located several resistance genes (erm(B), vat(D), vanA) on a large plasmid, which was transferable in mating experiments with an E. faecium recipient.. These data show routes of dissemination of resistance to multiple antibiotics including streptogramins and glycopeptides in E. faecium via vertical and/or horizontal gene transfer. The isolates spread in the absence of a direct selective pressure, as none of the patients had received earlier streptogramin or glycopeptide therapy.

Topics: Anti-Bacterial Agents; Child; Cross Infection; Drug Resistance; Enterococcus faecium; Female; Genes, Bacterial; Gram-Positive Bacterial Infections; Humans; Intensive Care Units, Pediatric; Microbial Sensitivity Tests; Phylogeny; Plasmids; Reverse Transcriptase Polymerase Chain Reaction; Vancomycin Resistance; Virginiamycin

Vancomycin-resistant Enterococcus faecium and faecalis (VRE) remains a major complication among critically ill patients. A 26-year-old patient with 65% total body surface area burns (TBSA) was infected with several E. faecium strains during his admission that were resistant to vancomycin. Because chloramphenicol was the standard treatment at this time, this drug was initiated until, the organism was identified as E. faecium and reported as susceptible to quinupristin-dalfopristin. Given these data, it was then decided to discontinue the chloramphenicol therapy. Quinupristin-dalfopristin therapy resulted in initial reduction of fever and white blood cell counts that continued over the next 5 days. However, on day 7 of quinupristin-dalfopristin therapy, a return of fever and elevation of the white blood cell count was noted and a repeated E. faecium blood culture demonstrated sudden resistance to quinupristin-dalfopristin (Bauer-Kirby zone size <14 mm). Chloramphenicol was restarted and the patient improved slowly over a period of 16 days. Our indigenous VRE had limited exposure to quinupristin-dalfopristin in the recent past; however, resistance emerged with the first commercial use of this agent in our burn treatment center. High-dose chloramphenicol treatment did not appear to impair engraftment of cultured epithelial autografts (CEA) in this patient.

Topics: Adult; Burns; Chloramphenicol; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterococcus faecium; Graft Survival; Gram-Positive Bacterial Infections; Humans; Male; Skin Transplantation; Vancomycin Resistance; Virginiamycin

Staphylococcus aureus strains resistant to a variety of antimicrobial agents are often found in the hospital environment and are responsible for many life-threatening infections. The activity of quinupristin/dalfopristin against 84 Staphylococcus aureus bloodstream isolates (both methicillin resistant and methicillin sensitive) was compared to the activity of vancomycin, teicoplanin, erythromycin, oxacillin, clindamycin, gentamicin, rifampicin. The Minimum Inhibitory Concentrations of these agents was evaluated with the Epsilometer Test. Quinupristin/dalfopristin inhibited all methicillin-sensitive strains at 1mg/L, and 75% of methicillin-resistant strains at 1.5mg/L. According to these results, quinupristin-dalfopristin shows promising in-vitro activity and may be a welcome alternative treatment for methicillin-resistant staphylococcal infections, resulting in reduced use of glycopeptides.

Topics: Anti-Bacterial Agents; Bacteremia; Clindamycin; Cross Infection; Erythromycin; Gentamicins; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Oxacillin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin; Virginiamycin

We describe an outbreak of vancomycin-resistant Enterococcus faecium (VRE) on the haematology ward of a Dutch university hospital. After the occurrence of three consecutive cases of bacteraemia with VRE, strains were genotyped and found to be identical. During the next 4 months an intensive surveillance programme identified 21 additional patients to be colonized with VRE, while two more patients developed bacteraemia. A case-control study was carried out to identify risk factors for VRE acquisition. In comparison with VRE-negative control patients (n=49), cases (n=24) had a longer stay on the ward during the year preceding the outbreak (25.8 versus 10.1 d, P=0.02), more cases with acute myeloid leukaemia [11 versus 4, odds ratio (OR) 9.5, 95% confidence interval (CI95) 2.4-32.2] and higher grades of mucositis (P=0.03). Logistic regression analysis identified antibiotic use within 1 month before admission (OR 13.0, CI95 2.1-80.5, P=0.006) and low albumin levels at baseline (OR 1.2, CI95 1.1-1.3, P=0.02) to be independent risk factors. Four patients with VRE-bacteraemia were successfully treated with quinupristin/dalfopristin (Synercid). Control of the outbreak was achieved by step-wise implementation of intensive infection control measures, which included the cohorting of patients, allocation of nurses and reinforcement of hand hygiene.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Cross Infection; Drug Therapy, Combination; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Hematology; Hospital Departments; Humans; Infection Control; Length of Stay; Logistic Models; Male; Middle Aged; Patient Isolation; Risk Assessment; Serum Albumin; Vancomycin Resistance; Virginiamycin

NOSOCOMIAL PNEUMONIA DUE TO GRAM-POSITIVE COCCI: In a randomized multicentric trial comparing Synercid with vancomycin, the cure rate (56.3% vs 58.3%) were equivalent in the 2 treatment arms. Treatment failures were also similar: 44% vs 42%. Mortality (25% vs 22%) was likewise comparable, as was tolerance. SKIN AND SOFT TISSUE INFECTIONS: For erysipela, infections requiring surgical dissection, post-trauma infections, postoperative wound infections, or diabetes-related infections, the rate of success obtained in 2 open randomized comparative multicentric trials was equivalent in the 2 treatment arms: 68.2% for Syncercid, 70.7% for the compared treatments. EMERGENCY PRESCRIPTION: For E. faecium, the success rate was 74% based on clinical assessment and 70.5% based on bacteriological assessment. For meti-S S. aureus infections, the clinical success rate was 74% for all patients and 80% for bacteriologically evaluable patients; the bacteriological success rate was 74% and 71% respectively. In case of infection due to C-MLSB meti-R S. aureus, the percentage of clinical success was 89% for bacteriologically evaluable patients.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Approval; Drug Resistance, Multiple; Drug Therapy, Combination; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Multicenter Studies as Topic; Pneumonia; Randomized Controlled Trials as Topic; Soft Tissue Infections; Virginiamycin

Antimicrobial resistance in gram-positive pathogens from 30 centres in the UK (ten Teaching, ten Associate Teaching and ten District General Hospitals) was studied over a 4 month period between October 1996 and January 1997. High-level resistance (HLR) and low-level resistance (LLR) to penicillin amongst pneumococci was 3.3% and 3.4%, respectively. However, considerable variation in resistance rates was observed depending on geographical location (LLR range 0-15.4% and HLR range 0-30.8%). Considerable variation in resistance rates was also observed for Staphylococcus aureus to methicillin, with rates ranging from 0% to 56.7% depending on locality. Using conventional MIC methodology, none of the isolates of S. aureus was considered as having reduced sensitivity to vancomycin. However, eight isolates grew on Brain Heart Infusion Agar containing vancomycin (4 mg/L) after prolonged incubation and are therefore worthy of further investigation by electron microscopy. With Enterococcus faecalis, resistance rates were similar between the three types of hospital and only four isolates were considered resistant to glycopeptide antibiotics (one vanA and three vanB phenotype).

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Microbial; Enterococcus faecium; Environmental Monitoring; Gram-Positive Bacteria; Hospitals; Humans; Microbial Sensitivity Tests; Staphylococcus; Streptococcus pneumoniae; United Kingdom; Vancomycin; Virginiamycin

Topics: Anti-Bacterial Agents; Biological Products; Bronchoscopes; Cross Infection; Disinfection; Drug Approval; Endoscopes; Equipment Contamination; Humans; Immunoglobulins, Intravenous; United States; United States Food and Drug Administration; Vancomycin Resistance; Virginiamycin

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Randomized Controlled Trials as Topic; Staphylococcus aureus; Streptococcus pyogenes; United Kingdom; Virginiamycin

Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a semisynthetic derivative of pristinamycins IA and IIB. The following properties of RP59500 were investigated: (i) its in-vitro activity against 164 hospital isolates of Staphylococcus aureus, 101 of which were methicillin-resistant (MRSA); (ii) its killing effect against 24 MRSA and seven methicillin-susceptible (MSSA) isolates; (iii) its interactions with rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant to both, at 1 x MIC, 2 x MIC and 4 x MIC. Rifampicin and ciprofloxacin were applied at a concentration equal to their mean serum levels in order to establish the clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and 2 mg/L for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and 0.25 mg/L for MSSA isolates. All isolates were inhibited by quinupristin/dalfopristin. Its killing effect varied with concentration and time, being optimal at 4 x MIC and after 24 h growth. Strains surviving 24 h exposure to this agent had much higher MICs than the parent strain, but only a limited number of them became resistant. Quinupristin/dalfopristin at 2 x MIC and 4 x MIC showed in-vitro synergy with rifampicin against highly resistant isolates mainly at 6 h and 24 h of growth involving 50-83% of MRSA isolates, and showed synergy with ciprofloxacin at 24 h involving 42-75% of isolates. The MIC increase in colonies surviving at 24 h was restricted by the presence of rifampicin or ciprofloxacin. In contrast, the above combinations acted synergically over the total number of MRSA strains susceptible to both rifampicin and ciprofloxacin. The above findings show that quinupristin/dalfopristin is a very potent antistaphylococcal agent, and that its activity against MRSA isolates is enhanced when it is combined with rifampicin or ciprofloxacin.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Cross Infection; Dose-Response Relationship, Drug; Drug Interactions; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Virginiamycin

In an Algerian hospital where pristinamycin (Pt) was extensively used for the treatment of chronic osteomyelitis and for prophylaxis in bone surgery, the prevalence of pristinamycin-resistant (PtR) staphylococci during a five-month period (20%) was higher than that among staphylococci isolated elsewhere in Algeria (4.5%). Analysis of 13 PtR staphylococci isolated in this hospital revealed a diversity of plasmids and genes conferring resistance to Pt and to related antibiotics. Most of the PtR staphylococci were unrelated: they belonged to either different taxa or types. Nevertheless, some of the unrelated staphylococci harboured structurally related plasmids carrying streptogramin resistance genes. Thus, these plasmids may have contributed to the dispersion of these genes.

Topics: Algeria; Anti-Bacterial Agents; Bacteriophage Typing; Bone and Bones; Cross Infection; Disease Outbreaks; DNA Primers; DNA, Bacterial; Drug Resistance, Microbial; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Osteomyelitis; Plasmids; Polymerase Chain Reaction; Prevalence; Staphylococcal Infections; Staphylococcus; Virginiamycin

Using a checkerboard assay, ampicillin, vancomycin, and RP 59500, each in combination with chloramphenicol, were tested for synergy against 23 isolates of vancomycin-resistant enterococci. Additive effects were seen in 62.5% of the isolates when exposed to chloramphenicol plus RP 59500. Additive effects were observed in 20% and 15% of isolates with chloramphenicol plus vancomycin or ampicillin, respectively. No antagonism was noted.

Topics: Ampicillin; Anti-Bacterial Agents; Chloramphenicol; Cross Infection; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Penicillins; Vancomycin; Virginiamycin

A significant increase in the incidence of isolates of methicillin-resistant Staphylococcus aureus (MRSA), that were also resistant to lincosamides and streptogramin A (LSA-MRSA), was observed in a French university hospital. Twenty-seven isolates from the outbreak were characterised, including 17 isolates from a plastic surgery ward and six control strains of MRSA. The strains were examined by antibiotyping and biotyping, and by three molecular methods: plasmid analysis, ribotyping and insertion sequence (IS) typing with IS256 sequence as a probe. Antibiotyping (five antibiotypes) was discriminatory because of the uncommon resistance phenotype of the epidemic strain. Biotyping (three biotypes), DNA plasmid analysis (four profiles) and ribotyping (two profiles) were poorly sensitive, in contrast to IS-typing (12 profiles). By the latter method, a coefficient of similarity (percentage similarity) compared to the predominant IS profile was calculated. Strains with a coefficient of similarity > or = to 82% were considered as highly related to the epidemic strain, while those with a coefficient of similarity < or = to 40% were regarded as distant. Results obtained with the five markers confirmed that an outbreak of hospital infection had occurred in the plastic surgery ward, with spread of the epidemic strain throughout the hospital.

Topics: Adult; Anti-Bacterial Agents; Bacterial Typing Techniques; Cross Infection; Disease Outbreaks; DNA Probes; DNA, Bacterial; DNA, Ribosomal; Drug Resistance, Microbial; Female; France; Hospital Units; Humans; Lincosamides; Macrolides; Male; Methicillin Resistance; Middle Aged; Nucleic Acid Hybridization; Polymorphism, Restriction Fragment Length; R Factors; Staphylococcal Infections; Staphylococcus aureus; Surgery, Plastic; Virginiamycin

In 1990, over a 6-month period, an increase from 1 to 10% in the incidence of pristinamycin resistance among coagulase-negative staphylococci was observed in four intensive care units of a Parisian hospital. Twenty-three such isolates, as well as 25 pristinamycin-susceptible Staphylococcus epidermidis isolates, were collected and typed by analyzing various bacterial constituents. Two structurally related plasmids of 7.3 and 14.3 kb, carrying the gene vga encoding resistance to pristinamycin, were detected in the 23 pristinamycin-resistant coagulase-negative staphylococci which were identified as S. epidermidis. Although related by numerous common characteristics, 20 of these 23 isolates could be divided into two types, A (17 isolates) and B (three isolates). These types were characterized on the basis of their plasmid contents and hybridization patterns obtained when the EcoRI-digested DNA was probed with plasmid pIP1551 containing an internal fragment of the insertion sequence IS256. These findings suggest that the dissemination of type A epidemic strains was, in large part, responsible for the outbreak.

Topics: Base Sequence; Cross Infection; DNA Probes; Drug Resistance, Microbial; Humans; Immunoblotting; Molecular Sequence Data; Nucleic Acid Hybridization; Paris; Phenotype; Plasmids; Staphylococcal Infections; Staphylococcus epidermidis; Virginiamycin

The in-vitro activity of RP 59500, a new semisynthetic injectable streptogramin, was compared with that of erythromycin, rifampicin and ciprofloxacin against 189 Legionella spp. Rifampicin was the most active agent tested. RP 59500 was found to be more active than erythromycin against most strains, but less active than ciprofloxacin. Legionella pneumophila serogroups 1, 3, 4, 5 and 6 were more susceptible to RP 59500 than were L. pneumophila serogroups 2, 7, and 8. Legionella micdadei was the least susceptible species to RP 59500 and erythromycin. RP 59500 was similar in activity against isolates obtained from both patients and environmental sources. This activity was generally better than that of erythromycin.

Topics: Ciprofloxacin; Cross Infection; Drug Resistance, Microbial; Erythromycin; Humans; In Vitro Techniques; Legionella; Microbial Sensitivity Tests; Respiratory Tract Infections; Rifampin; Virginiamycin