quinupristin-dalfopristin and Bacteremia

To review the literature on the pharmacotherapy of bloodstream infections (BSI) caused by vancomycin-resistant enterococci (VRE).. A MEDLINE literature search was performed for the period 1946 to May 2014 using the search terms Enterococcus, enterococci, vancomycin-resistant, VRE, bacteremia, and bloodstream infection. References were also identified from selected review articles.. English-language case series, cohort studies, and meta-analyses assessing the options in the pharmacotherapy of VRE BSIs in adult patients were evaluated.. Studies were identified that utilized linezolid, quinupristin/dalfopristin (Q/D), and daptomycin. In all, 8 comparative retrospective cohort studies, 2 meta-analyses of daptomycin and linezolid, and 3 retrospective comparisons of linezolid and Q/D were included for review. Mortality associated with VRE BSIs was high across studies, and the ability to determine differences in outcomes between agents was confounded by the complex nature of the patients included. Two meta-analyses comparing daptomycin with linezolid for VRE BSIs found modest advantages for linezolid, but these conclusions may be hampered by heterogeneity within the included studies.. VRE BSIs remain a difficult-to-treat clinical situation. Differences in toxicity between the agents used to treat it are clear, but therapeutic differences are more difficult to discern. Meta-analyses suggest that a moderate advantage for linezolid over daptomycin may exist, but problems with the nature of studies that they included make definitive conclusions difficult.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Gram-Positive Bacterial Infections; Humans; Linezolid; Oxazolidinones; Vancomycin; Vancomycin-Resistant Enterococci; Virginiamycin

Quinupristin-dalfopristin and linezolid demonstrate in vitro activity against a wide range of gram-positive bacteria, including many isolates resistant to earlier antimicrobials. Quinupristin-dalfopristin is inactive against Enterococcus faecalis but has been effective for treatment of infections due to vancomycin-resistant Enterococcus faecium associated with bacteremia. In comparative trials, linezolid proved to be equivalent to comparator agents, resulting in its approval for several clinical indications. The almost-complete bioavailability of linezolid permits oral administration. Each agent can cause adverse effects that may limit use in individual patients. Resistance to these drugs has been encountered infrequently among vancomycin-resistant E. faecium. Resistance to quinupristin-dalfopristin is rare among staphylococci in the United States, and resistance to linezolid is very rare. Whether there is any benefit to use of these agents in combination regimens, and whether there are circumstances in which they might be alternatives to cell-wall active antibiotics for treatment of bone or endovascular infections, are questions that deserve further study.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Vancomycin Resistance; 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

Synercid (RP 59500), the first injectable streptogramin antibiotic, is composed of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin. Individually, each component has bacteriostatic activity against staphylococci and streptococci, but together, the agents exhibit synergy, leading to bactericidal activity. The combination drug, however, is bacteriostatic against Enterococcus faecium and has poor activity against Enterococcus faecalis. Despite a short half-life, an extended postantibiotic effect allows the agent to be dosed every 8-12 hours. Both drugs are largely hepatically metabolized and excreted in bile. Although not metabolized by cytochrome P450 3A4, quinupristin-dalfopristin can inhibit agents that are metabolized through this pathway. Dosage adjustments may be necessary in patients with hepatic dysfunction. Alterations in renal function have minimal effects on the agent's pharmacokinetics. Adverse events include arthralgia, myalgias, and infusion-related pain. Based on available data, quinupristin-dalfopristin appears to have a role in treating severely ill patients with infections due to multiresistant gram-positive pathogens.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; 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

The rise in the number of multidrug-resistant gram-positive bacteria that has occurred in recent years has resulted in the development of infections that are difficult to treat, and also in severely restricted treatment options. In particular, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) has increased, with strains shown to cause up to 21% of skin infections and 59.6% of nosocomial pneumonia. Recently, strains of S. aureus with reduced susceptibility to vancomycin (glycopeptide-intermediate S. aureus or GISA) are causing great concern, particularly as vancomycin has been the agent of choice in the treatment of infection caused by MRSA. GISA has been identified in Japan, the USA and Europe. New agents that have anti-MRSA activity are now being investigated. These include the novel streptogramin, quinupristin/dalfopristin. This report examines the activity of quinupristin/dalfopristin against strains of S. aureus and coagulase-negative staphylococci, including multidrug-resistant MRSA and GISA.

Topics: Anti-Bacterial Agents; Bacteremia; Humans; Methicillin Resistance; Staphylococcal Infections; Vancomycin; Virginiamycin

Intravenous administration of quinupristin/dalfopristin outside the hospital setting has not been reported previously. We describe 37 outpatients receiving quinupristin/dalfopristin iv for infections including osteomyelitis, bacteraemia, abscesses and cellulitis. The most frequent aetiological pathogens found were Enterococcus faecium, Staphylococcus aureus and coagulase-negative staphylococci. Patients received an average of 9 days therapy as inpatients and 22 days as outpatients. Quinupristin/dalfopristin was administered using various access devices, most commonly peripherally inserted central catheters and tunnelled central catheters. The bacteriological and clinical success rates were both 89.2%. Five patients were readmitted to hospital; one patient developed catheter-related bacteraemia. The most frequently reported non-venous adverse events were nausea (18.9% of patients), myalgia (18.9%) and arthralgia (13.5%). Sixteen patients experienced venous access-related events, most commonly infusion pain, oedema and phlebitis. In this group of patients, for those who had difficult-to-treat infections, intravenous quinupristin/dalfopristin therapy was generally effective and safe outside the hospital setting.

Topics: Abscess; Adult; Aged; Aged, 80 and over; Ambulatory Care; Bacteremia; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Middle Aged; Osteomyelitis; Treatment Outcome; Virginiamycin

Serious infection with vancomycin-resistant Enterococcus faecium (VREF) strains has no proven effective antimicrobial therapy. We compared the clinical and bacteriological outcomes of 20 patients with VREF bacteraemia treated with quinupristin/dalfopristin (RP 59500), an investigational streptogramin, with a historical cohort of 42 patients with VREF bacteraemia treated with other agents. Quinupristin/dalfopristin demonstrated in-vitro bacteriostatic activity against all 20 initial VREF blood isolates (MIC range 0.03-0.50 mg/L) by macrobroth dilution. The clinical characteristics of both groups were comparable for major outcome-dependent variables. There were five cases of recurrent VREF bacteraemia in the quinupristin/dalfopristin-treated cohort and 21 in the controls (P = 0.11); persistence of VREF at the primary site was found in six and 18 of the evaluable patients with follow-up cultures in these two cohorts (P = 0.06). In-hospital mortality was high in both groups: 65% in the quinupristin/dalfopristin group and 52% in the control group; however, VREF-associated mortality was significantly lower in the quinupristin/dalfopristin group (five and 17 respectively; P = 0.05). Follow-up susceptibility testing of five VREF isolates in the quinupristin/ dalfopristin group did not demonstrate resistance to quinupristin/dalfopristin. Quinupristin/ dalfopristin may be a useful agent for the therapy of serious VREF infection. Further clinical investigations are warranted to confirm or refute its clinical efficacy.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cohort Studies; Drug Resistance, Microbial; Enterococcus faecium; Female; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Treatment Outcome; Vancomycin; Virginiamycin

Multicenter surveillance of antimicrobial susceptibility was performed for 235 vancomycin-resistant Enterococcus faecium (VREfm) isolates from 18 Taiwanese hospitals. The minimum inhibitory concentrations (MICs) of eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics were determined using the broth microdilution method. Nearly all isolates of VREfm were not susceptible to teicoplanin, dalbavancin, and telavancin, with susceptibility rates of 0.5%, 1.7% and 0.5%, respectively. Tigecycline and eravacycline were active against 93.2% and 89.7% of the VREfm isolates, respectively. Moreover, the susceptibility rates of quinupristin/dalfopristin, tedizolid, and linezolid were 59.1%, 84.2%, and 77.4%, respectively. Additionally, 94% of the VREfm isolates were classified as susceptible to daptomycin, and the MICs of omadacycline required to inhibit VREfm growth by 50% and 90% were 0.12 and 0.5 mg/L, respectively. Susceptibility rates of VREfm isolates to synthetic tetracyclines and daptomycin were slightly lower and to oxazolidinone-class antibiotics were much lower in Taiwan than those in other parts of the world. Continuous monitoring of VREfm resistance to novel antibiotics, including synthetic tetracyclines, oxazolidinone-class antibiotics, and daptomycin, is needed in Taiwan.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Resistance, Bacterial; Enterococcus faecium; Epidemiological Monitoring; Gram-Positive Bacterial Infections; Humans; Linezolid; Lipoglycopeptides; Microbial Sensitivity Tests; Oxazolidinones; Taiwan; Tetracyclines; Tetrazoles; Tigecycline; Vancomycin; Vancomycin-Resistant Enterococci; Virginiamycin

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Genes, Bacterial; Humans; Linezolid; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Phylogeny; Rifampin; Staphylococcal Infections; Tetracycline; Turkey; Vancomycin; Vancomycin Resistance; Virginiamycin

Quinupristin-dalfopristin and linezolid are widely used for the treatment of vancomycin-resistant Enterococcus faecium (VREF) infections. Increasing resistance of VREF to quinupristin-dalfopristin and linezolid is a cause for concern. To determine the efficacy of and the rate of development of resistance to quinupristin-dalfopristin and linezolid, we analyzed all episodes of clinically significant VREF bacteraemia at a tertiary-care hospital from January 2003 to June 2007. The main outcomes were rates of 30-day mortality, microbiological response, and development of resistance. Fifty-two patients were treated with quinupristin-dalfopristin and 61 were treated with linezolid. Baseline demographic and clinical characteristics were similar between the 2 groups. There were no significant between-group differences in 30-day mortality (48% in the quinupristin-dalfopristin group vs 41% in the linezolid group; p = 0.45) or microbiological response (60% vs 66%; p = 0.51). However, prolonged bacteraemia (18% of 45 evaluable cases vs 4% of 55 evaluable cases; p = 0.04) and development of resistance in blood isolates (11% vs 0%; p = 0.02) were more frequently observed in the quinupristin-dalfopristin group than in the linezolid group. There was no significant difference between the efficacy of quinupristin-dalfopristin and linezolid. However, prolonged bacteraemia and the development of resistance were more common in quinupristin-dalfopristin-treated patients.

Topics: Acetamides; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Chi-Square Distribution; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Linezolid; Logistic Models; Male; Middle Aged; Oxazolidinones; Prognosis; Risk Factors; Treatment Outcome; Vancomycin Resistance; Virginiamycin

Following an initial response to vancomycin therapy, a patient with meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia developed endocarditis, failed a second course of vancomycin and then failed daptomycin therapy. An increase in the vancomycin minimum inhibitory concentrations of four consecutive MRSA blood isolates from 2 microg/mL to 8 microg/mL was shown by Etest. Population analysis of four successive blood culture isolates recovered over the 10-week period showed that the MRSA strain became progressively less susceptible to both vancomycin and daptomycin. Retrospectively, the macro Etest method using teicoplanin indicated a decrease in vancomycin susceptibility in the second blood isolate. The patient improved after treatment with various courses of trimethoprim/sulfamethoxazole, quinupristin/dalfopristin and linezolid. Early detection of vancomycin-heteroresistant S. aureus isolates, which appeared to have clinical significance in this case, continues to be a challenge for the clinical laboratory. Development of suitable practical methods for this should be given priority. Concurrent development of resistance to vancomycin and daptomycin, whilst rare, must be considered in a patient who is unresponsive to daptomycin following vancomycin therapy.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Resistance, Bacterial; Endocarditis, Bacterial; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; Virginiamycin

The impact of antibiotic resistance on the clinical outcome of patients with vancomycin-resistant Enterococcus (VRE) bacteremia remains unclear. There are limited data comparing patient outcomes during the early era of vancomycin resistance with the period of more-potent antibiotic availability.. A retrospective review was conducted of 113 patients with VRE bacteremia at a single institution from August 1993 to September 2005. Patients were assigned to a group on the basis of initial antibiotic choice for treatment of VRE (linezolid, quinupristin-dalfopristin, or combinations of other agents, before newer options were available). Outcome measurements were examined for the initial episode of VRE bacteremia, and multiple logistic regression analysis was performed to compare group outcomes.. Overall mortality was 37.2% (42 of 113 patients). VRE bacteremia caused or significantly contributed to death in 29 (69%) of 42 patients. Seventy-one patients were initially treated with linezolid, 20 with quinupristin-dalfopristin, and 22 with combinations of other agents. Univariate analysis indicated significantly more deaths in the quinupristin-dalfopristin group (odds ratio, 5.45; 95% confidence interval, 1.89-15.9) and in the other-agents group (odds ratio, 2.94; 95% confidence interval, 1.09-7.94) than in the linezolid group. However, after adjustment for severity of illness, treatment group was not a significant independent factor.. Despite the development of antimicrobial agents with greater potency against VRE, a significant change in clinical outcome was not observed. This suggests that vancomycin resistance does not significantly influence mortality and points to the continued need for prospective, randomized clinical trials.

Topics: Acetamides; Adult; Anti-Bacterial Agents; Bacteremia; Enterococcus; Female; Gram-Positive Bacterial Infections; Humans; Linezolid; Male; Oxazolidinones; Retrospective Studies; Treatment Outcome; Vancomycin Resistance; Virginiamycin

A retrospective observational study in Taiwan, 1998-2004, identified 92 patients with group G streptococcal bacteremia; 86 had Streptococcus dysgalactiae subspecies equisimilis. The most common diagnosis was cellulitis (48 cases), followed by primary bacteremia (34 cases). Infection recurred in 9 patients. Mortality rate was low (3.3%); resistance to quinupristin-dalfopristin was high.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cellulitis; Child; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Streptococcal Infections; Streptococcus; Taiwan; Virginiamycin

To report the successful treatment of vancomycin-resistant Enterococcus (VRE) bacteremia using the combination of quinupristin/dalfopristin and high-dose ampicillin.. A 38-year-old African American woman with relapsed acute myeloid leukemia and neutropenic fever developed VRE bacteremia following 3 successive courses of vancomycin for methicillin-resistant staphylococcal infections. Treatment with linezolid was initiated; however, after 9 days of therapy, blood cultures continued to reveal VRE and the patient became febrile. The patient was subsequently switched to quinupristin/dalfopristin and high-dose ampicillin. The fever resolved and all subsequent blood cultures were negative after the initiation of combination therapy.. The emergence of VRE infections presents a treatment challenge in immunocompromised patients. When treating VRE infections in this patient population, the effectiveness of linezolid and quinupristin/dalfopristin is limited by their bacteriostatic activity when used as monotherapy. Recent in vitro data suggest synergistic activity with quinupristin/dalfopristin when used in combination with other antimicrobials in selected isolates of VRE.. Persistent VRE bacteremia was successfully treated in this neutropenic patient using the combination of high-dose ampicillin and quinupristin/dalfopristin. Case reports and in vitro data suggest that concomitant therapy with high-dose ampicillin may be an effective treatment alternative for VRE infections not responding to standard therapy.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Enterococcus faecium; Female; Humans; Leukemia, Myeloid, Acute; Neutropenia; Staphylococcal Infections; Vancomycin Resistance; Virginiamycin

Quinupristin-dalfopristin (Q-D) is a mixture of quinupristin and dalfopristin, which are semisynthetic antibiotics of streptogramin groups B and A, respectively.. We compared the effect of Q-D to that of vancomycin (VCM) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA).. Treatment with Q-D resulted in a significant decrease in the number of viable bacteria in the lungs of mice in an MRSA infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 2.99 +/- 0.44, 6.38 +/- 0.32, 5.75 +/- 0.43 and 8.40 +/- 0.14 log10 CFU/lung, respectively]. Compared with VCM, high-dose Q-D significantly reduced the number of bacteria detected in the VISA hematogenous infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 5.17 +/- 0.52, 7.03 +/- 0.11, 7.10 +/- 0.49 and 7.18 +/- 0.36 log10 CFU/lung, respectively]. Histopathological examination confirmed the effect of Q-D.. Our results suggest that Q-D is potent and effective in the treatment of MRSA and VISA hematogenous pulmonary infections.

Topics: Animals; Bacteremia; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Japan; Lung; Male; Methicillin Resistance; Mice; Mice, Inbred Strains; Pneumonia, Staphylococcal; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus aureus; 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

In a prospective multicenter study (1996 to 1999), 156 episodes of bacteremic streptococcal infections of neutropenic patients were evaluated. Streptococcus oralis (26.3%), S. pneumoniae (26.3%), S. agalactiae (11.5%), S. mitis (9%), and S. pyogenes (5.8%) were the predominant species. Four strains (2.6%) were found to be intermediately resistant to penicillin. One strain (0.6%) was found to be highly resistant to penicillin (MIC, 8 mg/liter). Reduced susceptibility to penicillin was detected among S. oralis (14.6%), S. mitis (7.1%), and S. pneumoniae (4.9%) isolates but was not recorded among S. agalactiae and S. pyogenes. Resistance rates and intermediate resistance rates for other antimicrobials were as follows (all species): amoxicillin, 1.3 and 3.2%; erythromycin, 16 and 2.6%; clindamycin, 5.8 and 0%; ciprofloxacin, 1.9 and 7.7%. Quinupristin-dalfopristin showed good in vitro activity against most streptococcal isolates (MIC at which 50% of the isolates were inhibited [MIC(50)], 0.5 mg/liter; MIC(90), 1 mg/liter, MIC range, 0.25 to 4 mg/liter).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Blood; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Prospective Studies; Streptococcal Infections; Streptococcus; Virginiamycin

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Bone Marrow Transplantation; Drug Administration Schedule; Drug Therapy, Combination; Enterococcus faecium; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Leukemia, Myeloid, Acute; Linezolid; Male; Middle Aged; Oxazoles; Oxazolidinones; Postoperative Complications; Treatment Failure; Treatment Outcome; Vancomycin Resistance; Virginiamycin

Antibiotic-resistant gram-positive bacteria have become an increasing problem in the last two decades. In order to evaluate the prevalence of antibiotic resistance in staphylococcal bloodstream isolates in Germany, 2,042 staphylococci collected in 21 tertiary-care hospitals were investigated during a 3-year period (March 1996 to March 1999). Altogether, 1,448 S. aureus isolates and 594 coagulase-negative staphylococci (CoNS) that comprised 13 different species were included. Furthermore, the antistaphylococcal activities of quinupristin-dalfopristin were compared with those of eight other compounds by the broth microdilution method. The rates of oxacillin resistance in Staphylococcus aureus, S. epidermidis, S. haemolyticus, and other CoNS were 13.5, 69, 90, and 34%, respectively. In oxacillin-resistant strains high rates of resistance (up to 100%) to erythromycin, clindamycin, ciprofloxacin, and gentamicin were also observed. However, no strain appeared to be resistant to vancomycin or quinupristin-dalfopristin. The streptogramin combination exhibited excellent in vitro activity against all staphylococcal species tested, regardless of the patterns of resistance to other drug classes. In terms of MICs at which 90% of the isolates are inhibited, quinupristin-dalfopristin was 2 times more active against S. aureus isolates, 4 to 16 times more active against S. haemolyticus, and 8 to 32 times more active against S. epidermidis than vancomycin or teicoplanin.

Topics: Anti-Bacterial Agents; Bacteremia; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Germany; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus; Virginiamycin

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteremia; Enterococcus faecium; Fluoroquinolones; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic; Vancomycin Resistance; Virginiamycin

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Microbial; Drug Resistance, Multiple; Echocardiography; Enterococcus faecium; Gram-Positive Bacterial Infections; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Vancomycin; Virginiamycin

The susceptibility of clinical isolates of methicillin-susceptible and -resistant staphylococci from cancer patients with central venous catheter bacteremia to quinupristin/dalfopristin, a semisynthetic streptogramin, was determined in vitro. Susceptibility of these isolates to nine other antistaphylococcal antibiotics was also determined for comparison. A total of 197 staphylococcal strains were tested from 1983 to 1992. Quinupristin/dalfopristin was bactericidal against all isolates, independent of their resistance to methicillin. Its activity was similar to that of vancomycin but superior to that of teicoplanin. Quinupristin/dalfopristin may prove to be an important addition to our armamentarium against catheter-related staphylococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Bacteremia; Catheterization, Central Venous; Cefamandole; Cephalosporins; Ciprofloxacin; Clindamycin; Daptomycin; Humans; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Neoplasms; Novobiocin; Oxacillin; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Vancomycin; Virginiamycin

The bactericidal activity of RP 59500, a semisynthetic streptogramin, was compared with that of vancomycin against Staphylococcus aureus. This activity was evaluated in vitro by the kill curve method and in vivo using a model of mouse septicaemia. In vitro, RP 59500 (MIC = 0.12 mg/L) was more rapidly bactericidal against S. aureus IP 8203 than was vancomycin (MIC = 1 mg/L). In vivo, RP 59500 (120 mg/kg) was bactericidal against staphylococci in the blood of infected mice 1 h after administration, an effect which lasted for up to 7 h, whereas vancomycin at the same dose was bactericidal only 4 h after administration. The serum concentrations of vancomycin were higher than those of RP 59500 for at least 4 h after administration, and the Cmax and AUC of vancomycin were 4.8 and 8.3 times higher, respectively, than those of RP 59500 (Cmax = 13.2 mg/L; AUC0(-1) = 15.2 mg/L/h), although the agents had similar elimination half-lives (about 0.5 h). RP 59500 was also administered to mice as a fractionated dose (30 mg/kg x 4, 40 mg/kg x 3, 60 mg/kg x 2). The onset of its bactericidal effect was delayed by fractionating the dose, but the suppression of bacteria in the blood was prolonged.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Serum Bactericidal Test; Software; Staphylococcal Infections; Vancomycin; Virginiamycin