quinupristin-dalfopristin and Bacterial-Infections

Septic arthritis is a rheumatologic emergency as joint destruction occurs rapidly and can lead to significant morbidity and mortality. Accurate diagnosis can be particularly challenging in patients with underlying inflammatory joint disease. This review outlines the risk factors for septic arthritis and summarizes the causative bacterial organisms. We highlight advances in antibiotic management with a focus on new drugs for methicillin-resistant Staphylococcus aureus (MRSA) and discuss the use of adjunctive therapies for treatment of septic arthritis in adults.

Topics: Acetamides; Anti-Bacterial Agents; Arthritis, Infectious; Bacterial Infections; Ceftaroline; Cephalosporins; Daptomycin; Drug Therapy, Combination; Humans; Immunologic Factors; Linezolid; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Risk Factors; Staphylococcal Infections; Treatment Outcome; Virginiamycin

The advent of vancomycin-resistant enterococci in the 1990s and the threat posed by vancomycin resistance in Staphylococcus aureus led to the development of several new antimicrobial agents active against these pathogens. Quinupristin/dalfopristin was the first such drug to be commercially available but adverse effects have meant that the drug is now rarely used. Linezolid, the first antimicrobial of the oxazolidinone class, has met with more widespread use and has both an intravenous and an oral formulation. Daptomycin is a lipopeptide antimicrobial that is rapidly bactericidal against S. aureus. It is effective in the therapy of S. aureus bloodstream infections but is inactivated by pulmonary surfactant, making it of no use in the therapy of pneumonia. Tigecycline, by contrast, is bacteriostatic against most pathogens but has a broad spectrum of antimicrobial activity and has enhanced penetration into many tissues. Other new antibiotics (dalbavancin, telavancin, ceftobiprole and doripenem) are currently under clinical development and hold promise for widespread clinical use in the next decade.

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Infections; Daptomycin; Humans; Linezolid; Minocycline; Oxazolidinones; Staphylococcal Infections; Streptococcal Infections; Tigecycline; Virginiamycin

The increasing resistance among Gram-positive cocci have been accompanied by their increasing frequency as cause of severe infection. Thus new antimicrobial agents, TAZ/PIPC, synercid and linezolid, are in various stages of development. TAZ/PIPC, a combination drug of a new beta-lactamase inhibitor tazobactam and piperacillin at ratio in 1 to 4 has a broad spectrum of antimicrobial activity. Evidence from randomized clinical trials in adults in Japan has shown that TAZ/PIPC is superior to PIPC as a drug for complicated urinary tract infection. Synercid is a streptogramin antibiotic. The spectrum of activity of synercid is similar to vancomycin. Furthermore, most of E. faecium were susceptible. The efficacy of synercid in clinical trials in patients infected with VREF was 65-70%. Linezolid is a member of the oxazolidinones. The antimicrobial spectrum of linezolid is similar to that of vancomycin. In the US, patients with significant infection caused by resistant Gram-positive organisms(mostly VREF) were treated with linezolid. The efficacy of linezolid was about 75%. The clinical trials for everninomicin had been discontinued because of insufficient clinical data supporting its efficacy and safety.

Topics: Acetamides; Adult; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Drug Combinations; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Linezolid; Oxazolidinones; Penicillanic Acid; Penicillins; Piperacillin; Protein Synthesis Inhibitors; Tazobactam; Virginiamycin

It is easy to become overwhelmed by the amount of information available on the new antibiotics and difficult to keep abreast of the appropriate indications for each of them. For most patients with community-acquired infections, the first-line agent is usually not one of the newer agents, but a standard regimen, or at times, no antibiotic at all. The development of resistance is likely to parallel the extent to which these agents are prescribed. They should be used only when standard treatment fails, when compliance with treatment is a real and serious issue, or when the patient has a real allergic reaction to the standard regimen.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Cephalosporins; Fluoroquinolones; Fosfomycin; Humans; Macrolides; Virginiamycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Daptomycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Humans; Oxazolidinones; Protein Synthesis Inhibitors; Vancomycin; Virginiamycin

In recent years, the prevalence of multiple drug-resistant strains of common Gram-positive pathogens has grown in many regions of the world. Increasingly, methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, vancomycin-resistant enterococci, and penicillin-resistant pneumococci have been identified as causative organisms in serious and life-threatening infections. This increase in resistance highlights the need for new antimicrobial agents to expand the therapeutic armamentarium. Quinupristin/dalfopristin is the first of a unique class of antibiotics called streptogramins. It is characterized by a unique mechanism of action, intracellular activity, synergistic activity of its components, broad spectrum of activity against most Gram-positive cocci, common respiratory pathogens, and anaerobes, and demonstrated postantibiotic effect. Clinical evidence to date indicates that quinupristin/dalfopristin may be effective for the treatment of multidrug-resistant infections, especially those due to vancomycin-resistant enterococci and methicillin-resistant staphylococci. This article reviews the pharmacology, microbiology, and clinical experience with quinupristin/dalfopristin to date.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Virginiamycin

Macrolides are the primary drugs of choice for a number of clinically significant infections in children. The clinical aspects of newer macrolides such as roxithromycin, clarithromycin, dirithromycin, flurithromycin, miocamycin, rokitamycin, azithromycin and RP 59500 are discussed in different pediatric infections including streptococcal infections (e.g. pharyngitis, otitis, pneumonia, skin infections), staphylococcus soft tissue infections, mycoplasma pneumonia, chlamydial infections as well as legionellosis and campylobacter enteritis. Also, incidences of adverse events in pediatric patients receiving different macrolides are indicated as well as the dosages in children. The advantages of newer macrolides are: lower dosages, b.i.d. or once daily dosage regimens, good intracellular and tissue penetration, better activity against gram-negative microorganisms (some) and a low rate of adverse reactions.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Erythromycin; Humans; Infant; Virginiamycin

An emergency-use program forof Synercid (quinupristin/dalfopristin, Q/D) has been set up following the occurrence of Gram-positive infections with no therapeutic alternatives to the available antibiotic arsenal.. The experience in France is based on a collective of 88 infections analysed in 74 patients. The most frequent clinical indications were: central catheter-related bacteremia, bone and joint infection, endocarditis and, intraabdominal infection. The most frequently causative pathogens were: S. aureus (n = 26, including 24/26 meticillin-resistant), coagulase negative staphylococci (n = 28, including 24/28 meticillin-resistant), enterococci (n = 15), and others (n = 5). Q/D was administered most frequently by central venous infusion, 3 times a day (68/74 patients); the mean and median dose per infusion was 7.4 mg/kg and the mean duration of treatment was 15.6 days. A combined antibiotic therapy was used in 70/74 patients (a glycopeptide in 41/54 staphylococcal infections).. A Clinical success at the end of treatment was obtained in 40/74 patients (54%; CI 42.1%-65.7%) [the analysis included 25 patients (34%) with an indeterminate clinical response, categorized as failures] et and 39/73 patients (53%) at the follow-up [including 22 deaths (30%), categorized as failure at the follow-up]. The end-of-treatment success rate in patients with staphylococcal and enterococcal infections was respectively 30/54 (56%) and 8/15 (53%). The safety analysis indicated that 24/74 patients presented at least one treatment-related intercurrent event (possible or probable relationship), the most frequent ones being digestive disordersturbances, signs of venous intolerance, or diffuse or muscular pain.. Q/D has demonstrated a therapeutic potential in a variety of Gram-positive infections (staphylococcal and enterococcal) in patients with no therapeutic antibiotic alternative, and the type of the intercurrent events reported was consistent with those expected ones in this population of seriously ill patients.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Prescriptions; Drug Resistance, Microbial; Drug Therapy, Combination; Emergencies; Enterococcus; Follow-Up Studies; France; Humans; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Streptococcus; Time Factors; Virginiamycin

The use of antibiotics for animal growth promotion has been controversial because of the potential transfer of antibiotic resistance from animals to humans. Such transfer could have severe public health implications in that treatment failures could result. We have followed a risk assessment approach to evaluate policy options for the streptogramin-class of antibiotics: virginiamycin, an animal growth promoter, and quinupristin/dalfopristin, a antibiotic used in humans. Under the assumption that resistance transfer is possible, models project a wide range of outcomes depending mainly on the basic reproductive number (R(0)) that determines the potential for person-to-person transmission. Counter-intuitively, the benefits of a ban on virginiamycin were highest for intermediate values of R(0), and lower for extremely high or low values of R(0).

Topics: Animal Husbandry; Animals; Animals, Domestic; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Enterococcus faecium; Gram-Positive Bacterial Infections; Growth Substances; Health Policy; Humans; Models, Biological; Public Health; Risk Assessment; Streptogramins; Virginiamycin

Rhône-Poulenc Rorer (RPR) developed Synercid (RP-59500), an injectable synergistic combination of quinupristin and dalfopristin as a treatment for a variety of infections caused by Gram-positive anaerobic bacteria. The treatment was approved in the UK in July 1999, for use in patients with nosocomial pneumonia, skin and soft tissue infections and clinically significant infections due to Enterococcus faecium when there is no other active antibacterial agent [337556,335257]. It was launched in the UK and the US in September 1999 [342899]. In December 1999, Synercid successfully completed the Mutual Recognition Procedure in the EU under Aventis Pharma for use in patients with these infections [351525]. In September 2000, Merrill Lynch predicted first-year sales in 1999 of Euro 15 million, rising to Euro 171 million in 2004 [384874]. In January 1999, BT Alex Brown predicted sales of US $88 million in 1999 rising to US $450 million in 2002 [318220]. In April 1999, ABN Amro predicted annual sales of DM 30 million in 1999, rising to DM 150 million in 2002 [328676].

Topics: Animals; Bacterial Infections; Clinical Trials as Topic; Contraindications; Drug Therapy, Combination; Humans; Structure-Activity Relationship; Virginiamycin

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; United States; United States Food and Drug Administration; Vancomycin Resistance; Virginiamycin