Showing papers on "Dalfopristin published in 2001"
TL;DR: In this article, the SENTRY Antimicrobial surveillance program (SENTRY, 1998) collected 50 consecutive UTI pathogens from patients hospitalized in 31 medical centers (26 in the United States and five in Canada) and forwarded subcultures to the coordinating center.
221 citations
TL;DR: In this paper, a total of 189 isolates of lactic acid bacteria were examined for susceptibility to ampicillin, penicillin G, cephalothin, vancomycin, bacitracin, gentamicin, streptomycin, erythromycin, tetracycline, chloramphenicol, quinupristin/dalfopristin, ciprofloxacin, trimethoprim and sulphadiazine using Etest for MIC determination.
170 citations
TL;DR: The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of M. pneumoniae as the pH increased from 6.9 to 7.8 and a similar increase in susceptibility with increasing pH was also observed with ureaplasmas.
Abstract: The susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to eight new antimicrobial agents were determined by agar dilution. M. pneumoniae was susceptible to the new glycylcycline GAR-936 at 0.12 μg/ml and evernimicin at 4 μg/ml, but it was resistant to linezolid. It was most susceptible to dirithromycin, quinupristin-dalfopristin, telithromycin, reference macrolides, and josamycin. M. hominis was susceptible to linezolid, evernimicin, and GAR-936. It was resistant to macrolides and the ketolide telithromycin but susceptible to quinupristin-dalfopristin and josamycin. U. urealyticum was susceptible to evernimicin (8 to 16 μg/ml) and resistant to linezolid. It was less susceptible to GAR-936 (4.0 μg/ml) than to tetracycline (0.5 μg/ml). Telithromycin and quinupristin-dalfopristin were the most active agents against ureaplasmas (0.06 μg/ml). The new quinolone gatifloxacin was active against M. pneumoniae and M. hominis at 0.12 to 0.25 μg/ml and active against ureaplasmas at 1.0 μg/ml. The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of M. pneumoniae as the pH increased from 6.9 to 7.8. A similar increase in susceptibility with increasing pH was also observed with ureaplasmas. Tetracyclines showed a fourfold increase of activity as the pH decreased 1 U, whereas GAR-936 showed a fourfold decrease in activity with a decrease in pH.
164 citations
TL;DR: In vitro data indicate considerable potential for fosfomycin used in combination with other antistaphylococcal antimicrobials, especially linezolid or quinupristin/dalfopristin.
Abstract: Using the chequerboard technique we studied the in vitro activity of the broad spectrum antibiotic fosfomycin in combination with vancomycin, rifampicin, linezolid, quinupristin/ dalfopristin, cefazolin, meropenem and moxifloxacin against two Staphylococcus epidermidis strains (ATCC 12228, DSM 3269) and five Staphylococcus aureus isolates (ATCC 29213, DSM 683, DSM 46320, GISA 323/93, MRSA 3558/00). The phenomena of 'trailing' and 'skipped wells' did not present a problem. Synergy was the most common effect of all drugs tested in combination with fosfomycin; only combination with vancomycin showed antagonism for two of seven isolates. Using a killing-curve technique fosfomycin showed cidal activity, where increasing the drug concentration above the MIC did not enhance killing velocity. Inhibitory concentrations of vancomycin plus fosfomycin against DSM 46320 caused effects identical to those observed with vancomycin alone. The combination of fosfomycin plus linezolid exerted the bacteriostatic effect found with linezolid alone. Fosfomycin plus quinupristin/dalfopristin exhibited the bactericidal effect found with fosfomycin alone (in contrast to the rapidly bactericidal effect of quinupristin/dalfopristin). Electron microscopy showed that fosfomycin given in combination with linezolid, quinupristin/dalfopristin or moxifloxacin (substances that do not cause morphological alterations when given alone) resulted in 'cauliflower-shaped' distortion as caused by fosfomycin alone. Our in vitro data indicate considerable potential for fosfomycin used in combination with other antistaphylococcal antimicrobials, especially linezolid or quinupristin/dalfopristin.
128 citations
TL;DR: The activity of GAR-936 was particularly impressive against Gram-positive cocci when compared against the test results for vancomycin and the newer antimicrobial agents, linezolid and quinupristin/dalfopristin.
116 citations
TL;DR: The low prevalence and low level of resistance of these strains in human stool specimens suggest that the use of virginiamycin in animals has not yet had a substantial influence on E. faecium infections.
Abstract: Background The combination of the streptogramins quinupristin and dalfopristin was approved in the United States in late 1999 for the treatment of vancomycin-resistant Enterococcus faecium infections. Since 1974, another streptogramin, virginiamycin, has been used at subtherapeutic concentrations to promote the growth of farm animals, including chickens. Methods To determine the frequency of quinupristin-dalfopristin–resistant E. faecium, we used selective medium to culture samples from chickens purchased in supermarkets in Georgia, Maryland, Minnesota, and Oregon and stool samples from outpatients. Results Between July 1998 and June 1999, samples from 407 chickens from 26 stores in four states were cultured, as were 334 stool samples from outpatients. Quinupristin-dalfopristin–resistant E. faecium was isolated from 237 chicken carcasses and 3 stool specimens. The resistant isolates from stool had low-level resistance (minimal inhibitory concentration [MIC], 4 μg per milliliter; resistance was defined as ...
103 citations
TL;DR: 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.
103 citations
TL;DR: A case of vancomycin-resistant Enterococcus faecium endocarditis that failed to respond to sequential monotherapy with chloramphenicol and quinupristin/dalfopristin but was successfully treated with oral linezolid is reported.
Abstract: We report a case of vancomycin-resistant Enterococcus faecium endocarditis that failed to respond to sequential monotherapy with chloramphenicol and quinupristin/dalfopristin but was successfully treated with oral linezolid.
100 citations
TL;DR: In this severely ill patient population, quinupristin/dalfopristin was efficacious and demonstrated an acceptable safety profile in the treatment of VREF infection.
Abstract: Clinicians caring for patients with vancomycin-resistant Enterococcus faecium (VREF) infections face severe constraints in the selection of treatment. Quinupristin/dalfopristin (Synercid) is active in vitro against VREF, with a MIC(90) of 1.0 microg/mL. We investigated the clinical efficacy and safety of this agent in a multicenter, prospective, noncomparative, emergency-use study of 396 patients. Patients were included if they had signs and symptoms of active infection, including bacteremia of unknown origin, intra-abdominal infection, and skin and skin-structure infection, with no alternative antibiotic therapy available. The mean duration of treatment was 20 days (range, 4-40 days). The clinical response rate was 68.8% in the evaluable subset, and the overall response rate was 65.6%. The most common adverse events related to quinupristin/dalfopristin were arthralgias and myalgias. Related laboratory abnormalities were rare. In this severely ill patient population, quinupristin/dalfopristin was efficacious and demonstrated an acceptable safety profile in the treatment of VREF infection.
92 citations
TL;DR: Linezolid susceptibility pattern for US medical centers is indicative of the excellent and nearly complete in vitro activity against the key Gram-positive pathogens for which linezolid has received US Food and Drug Administration indications for clinical use.
88 citations
TL;DR: The current situation with Gram-positive infections, including the two primary consequences—failure to cure and resistance—relevant to the intensive care unit are summarized, including evidence of clinical failure in lower respiratory tract infection patients.
Abstract: This article summarizes the current situation with Gram-positive infections, including the two primary consequences-failure to cure and resistance-relevant to the intensive care unit. The past few years have seen Enterococcus faecium resistance to vancomycin increase from 10% of strains to approaching 60% of strains in some centers. Failure is now so frequent that vancomycin can no longer be safely used. This has lead to use of two new antibiotics, quinupristin/dalfopristin (Synercid), first marketed in the United States in September 1999, and linezolid (Zyvox), which reached the U.S. market in May 2000. Both of these agents are being used to treat culture-proven vancomycin-resistant E. faecium. The calculated areas under the inhibitory curve (AUIC) values of vancomycin, even when its minimal inhibitory concentration (MIC) is 4.0 microg/mL, show almost all vancomycin-resistant E. faecium have AUICs <125. This explains failure, as well as the further selection of this bacteria into subpopulations with progressively higher MICs. Less well defined, but potentially an even greater problem, is the poor efficacy of vancomycin against multiresistant Staphylococcus aureus. Here, there is evidence of clinical failure in lower respiratory tract infection patients, but in most cases the MIC values of the organism have not risen to the point where AUICs are <125. However, the minimum bactericidal concentration of this organism may be considerably higher than its MIC, and in other cases there may be a high inoculum effect or a protein-binding effect to explain the failure of vancomycin to kill multiresistant S. aureus. Besides the increasing use of the new agents, strategies to manage these two increasingly resistant Gram-positive infections include cephalosporin restriction, switch and streamlining when cultures come back from the lab, combination regimens, and cycling in selected intensive care units.
TL;DR: Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates and there was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance.
Abstract: Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.
TL;DR: Of 3,052 Staphylococcus aureus strains collected by the European SENTRY surveillance study, 35 were found to be nonsusceptible to quinupristin-dalfopristin (MIC of ≥2 mg/liter); these isolates originated from four hospitals in France and one in Spain.
Abstract: Of 3,052 Staphylococcus aureus strains collected by the European SENTRY surveillance study, 35 were found to be nonsusceptible to quinupristin-dalfopristin (MIC of ≥2 mg/liter). These isolates originated from four hospitals in France and one in Spain. In isolates from two Parisian hospitals exhibiting the same SmaI macrorestriction pattern, streptogramin resistance was based on vatA and vgbA. One isolate from a hospital in Lyon and 22 from a hospital in Lille were of the vatB vgaB streptogramin A resistance genotype and possessed ermA and/or ermC. As deduced from the loss of either streptogramin A or streptogramin B resistance determinants in particular isolates, resistance to quinupristin-dalfopristin requires mechanisms conferring resistance to both compounds. The SmaI macrorestriction patterns of strains from hospitals in Lille and Lyon were different; however, similarity analysis suggested a relatedness of 20 methicillin-resistant S. aureus strains from the Lille hospital, a finding confirmed by PCR typing based on three different genomic polymorphisms. These groups of isolates were found to be hetero-glycopeptide-intermediate susceptible S. aureus. Information about the failure of glycopeptide chemotherapy has not been available.
TL;DR: A total of 200 isolates of viridans group streptococci isolated from the oropharynx of healthy Greek children were studied, finding penicillin resistance occurred more frequently in Streptococcus mitis isolates, while macrolide resistance was more frequent in S. oralis.
TL;DR: Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicsoplanin-refracto-ry coagulase-negative staphylococci.
Abstract: BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL 62,476 (A40926), has excellent in vitro activity against a wide range of Gram-positive organisms In this extensive study, 630 contemporary (1998-2000) Gram-positive isolates were selected from various resistance surveillance studies for their resistance patterns to fluoroquinolones, macrolides-lincosamides-streptogramins, beta-lactams and glycopeptide agents The BI 397 spectrum of activity was similar to that of other glycopeptides with a MIC90 of 16-fold), viridans group streptococci (equal to >32-fold), and Corynebacterium spp including C jeikeium (8- to >16-fold) BI 397 was also more active than quinupristin/dalfopristin against all Gram-positive organisms tested with the exception of oxacillin-susceptible S aureus, against which it had equal activity BI 397 has little activity against Haemophilus influenzae (MIC90, 64 microg/ml) or other Gram-negative bacilli (MIC90, >64 microg/ml) BI 397 exhibited bacteriostatic activity (like the vancomycin control) versus most species, but was bactericidal against tested Streptococcus pneumoniae In vitro testing conditions with blood supplemented or free protein containing media elevated BI 397 MIC results, and the 30-microg disk seems acceptable for further disk diffusion test development Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicoplanin-refractory coagulase-negative staphylococci
Journal Article•
TL;DR: It is concluded that although the most commonly used antibiotics have little effect on human medicine, there is a widespread use of antibiotics that may select for critical forms of resistance in human pathogens in food-producing animals.
Abstract: There are increasing public health concerns about antibiotics used in food-producing animals that may contribute to the development of resistance in human pathogens. Such resistance may be critical to human medicine when resistance develops to drugs that treat certain pathogens of which there is no good alternative therapy. We surveyed 10 farms, eight feed mills, and one animal drug distributor in Taiwan to determine the major antibiotics used in food-producing animals, and the extent of use of five drugs that may select for resistance to antibiotics that are critical for human medicine. The five animal drugs, and the resistance of human drug/class they may select for, included avoparcin (vancomycin/glycopeptides), avilomycin (ziracin/envirninomycins), enrofloxacin (ciprofloxacin/fluoroquinolones), virginiamycin (quinupristin and dalfopristin combination/streptogramins), and kanamycin (gentamicin/aminoglycosides). Tetracyclines were the class of antibiotic that was most widely used in the greatest amounts. Over the past 12 months, the number of farms, chicken feed mills, and pig feed mills, that have respectively reported the use of avoparcin was 1 (10%), 5 (63%), 0; avilomycin 0, 0, 3 (50%); enrofloxacin 4 (40%), 1 (13%), 3 (50%); virginiamycin 2 (20%), 5 (63%), 0; and kanamycin 3 (30%), 1 (13%), 1 (17%). We conclude that although the most commonly used antibiotics (ie tetracyclines) have little effect on human medicine, there is a widespread use of antibiotics that may select for critical forms of resistance in human pathogens in food-producing animals.
TL;DR: Q-D-dalfopristin plus minocycline is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.
Abstract: Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D–MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.
TL;DR: The high level of resistance in this organism suggests that this reservoir of resistance may compromise the therapeutic potential of quinupristin-dalfopristin.
Abstract: The occurrence of resistance to the streptogramin quinupristin-dalfopristin in Enterococcus faecium isolates from chickens on the Eastern Seaboard, was evaluated. Quinupristin-dalfopristin resistance was found in 51 to 78% of E. faecium isolates from the food production environment. The high level of resistance in this organism suggests that this reservoir of resistance may compromise the therapeutic potential of quinupristin-dalfopristin.
TL;DR: The results of this in vitro, multicentre, multinational study demonstrate that evernimicin possesses high antimicrobial activity against Gram-positive organisms that compares favourably with established antibacterial treatments and newer agents such as quinupristin/dalfopristin.
Abstract: The antimicrobial activity of evernimicin (formerly SCH 27899), a novel oligosaccharide antimicrobial of the everninomicin class, was evaluated against four groups of Gram-positive pathogens: (i) Streptococcus pneumoniae (n � 1452); (ii) methicillin- or oxacillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CoNS; n � 1427); (iii) enterococci (n � 1517); and (iv) non-pneumococcal streptococci (n � 1388), using the Etest method at each study centre throughout Eastern and Western Europe, Scandinavia, South Africa, Turkey and North America. Comparative MICs were determined for a variety of reference compounds, including vancomycin, quinupristin/dalfopristin, chloramphenicol, penicillin, ampicillin, oxacillin, ceftriaxone and ciprofloxacin. Evernimicin was highly active against all strains tested, with MIC90 values 1.0 mg/L, ranging from 0.047 mg/L against S. pneumoniae to 1.0 mg/L against MRSA/MR-CoNS and enterococci. Compared with the reference agents, the MIC90 of evernimicin were lower against all species. Against MRSA and MR-CoNS the MIC90s of evernimicin, quinupristin/dalfopristin and vancomycin (the three most active agents) were 1.0, 1.5 and 3.0 mg/L, respectively. Against all species tested, the relative activities and spectra of these agents were: evernimicin > vancomycin > quinupristin/dalfopristin. The Etest proved to be reliable and reproducible, despite occasional interpretive difficulties caused by observer inexperience. Quality control results were excellent among the 33 participant sites. The results of this in vitro, multicentre, multinational study demonstrate that evernimicin possesses high antimicrobial activity against Gram-positive organisms that compares favourably with established antibacterial treatments and newer agents such as quinupristin/dalfopristin. Further clinical investigations of everninomicin class compounds appear warranted.
TL;DR: 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.
Abstract: 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.
TL;DR: The selection of a beta-lactam antibiotic for empirical therapy must be made with care, as repeated courses of certain agents may be more likely to select for viridans streptococci with diminished susceptibility.
Abstract: This study investigated the antibiotic susceptibilities of 67 isolates of viridans streptococci from 61 cases of bacteraemia in immunocompromised paediatric patients with malignancy. The majority of patients (87%) had received prior courses of empirical antibiotic therapy, which consisted of ceftazidime plus amikacin during period 1 and piperacillin/tazobactam plus amikacin during period 2. Susceptibility to vancomycin and quinupristin/dalfopristin was 100%. Susceptibility to beta-lactam antibiotics varied. For period 1, the geometric mean MICs of all beta-lactams tested against blood culture isolates (n = 31) exceeded those against isolates (n = 36) collected from blood after the change in empirical therapy (by 3.3-fold for ceftazidime, 2.8-fold for piperacillin/tazobactam and 1.6-fold for penicillin). The selection of a beta-lactam antibiotic for empirical therapy must be made with care, as repeated courses of certain agents may be more likely to select for viridans streptococci with diminished susceptibility.
TL;DR: The absence of cross-resistance to macrolides in many of these microorganisms and the rarity ofCross-Resistance between the two groups of antibiotics associated with the rapid bacterial killing are the principal features of the streptogramins, offering the possibility for treating the rising number of infections that are caused by multi-resistant Gram-positive bacteria.
Abstract: Streptogramins represent a unique class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally as secondary metabolites by a number of Streptomyces species and have been classified into two main groups. They consist of at least two structurally unrelated compounds, group A or M (macrolactones) and group B or S (cyclic hexadepsipeptides). Both groups bind bacterial ribosomes and inhibit protein synthesis at the elongation step and they act synergistically in vitro against many microorganisms. Streptogramins A and B act synergistically in vivo; the mixture of the two compounds is more powerful than the individual components and their combined action is irreversible. The pharmacokinetic parameters of group A and B streptogramins in blood are similar. The major gap, limiting the therapeutic use of the natural compounds, was represented by the lack dissolution in water. The synthesis of water-soluble derivatives of pristinamycin I(A) and II(B) has allowed the development of injectable, first represented by quinupristin/dalfopristin (Synercid) and oral formulations, represented by RPR-106972, streptogramins with fixed compositions. Streptogramins have demonstrated activity against Gram-positive microorganisms in vitro and in vivo, including those with multi-drug resistance. Moreover, the absence of cross-resistance to macrolides in many of these microorganisms and the rarity of cross-resistance between the two groups of antibiotics associated with the rapid bacterial killing are the principal features of the streptogramins, offering the possibility for treating the rising number of infections that are caused by multi-resistant Gram-positive bacteria.
TL;DR: It is concluded that the in vivo synergistic and bactericidal activity of the combination of Q-D and rifampin against S. aureus is predicted by the absence of resistance to quinupristin but not by in vitro combination studies.
Abstract: We evaluated the activities of quinupristin-dalfopristin (Q-D), alone or in combination with rifampin, against three strains of Staphylococcus aureus susceptible to rifampin (MIC, 0.06 μg/ml) and to Q-D (MICs, 0.5 to 1 μg/ml) but displaying various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics: S. aureus HM1054 was susceptible to quinupristin and dalfopristin (MICs of 8 and 4 μg/ml, respectively); for S. aureus RP13, the MIC of dalfopristin was high (MICs of quinupristin and dalfopristin for strain RP13, 8 and 32 μg/ml, respectively); and S. aureus HM1054R was obtained after conjugative transfer of macrolide-lincosamide-streptogramin B constitutive resistance to HM1054, and the MIC of quinupristin for this strain was high (MICs of quinupristin and dalfopristin, 64 and 4 μg/ml, respectively). In vitro time-kill curve studies showed no difference between Q-D and rifampin, at a concentration of four times the MIC, against the three strains. Rabbits with aortic endocarditis were treated 4 days with Q-D, rifampin, or their combination. In vivo, the combination was highly bactericidal and synergistic against strains susceptible to quinupristin (HM1054 and RP13) and sterilized 94% of the animals. In contrast, the combination was neither synergistic nor bactericidal against the quinupristin-resistant strain (HM1054R) and did not prevent the emergence of mutants resistant to rifampin. We conclude that the in vivo synergistic and bactericidal activity of the combination of Q-D and rifampin against S. aureus is predicted by the absence of resistance to quinupristin but not by in vitro combination studies.
TL;DR: Linezolid was the most active compound against these multiresistant enterococci, showing 100% inhibition at the susceptible breakpoints, and the molecular typing results suggest that there has been interhospital spread of vancomycin resistant E. faecium and E.Faecalis among Brazilian hospitals.
Abstract: The emergence of vancomycin-resistant enterococci (VRE) has been described recently in Brazil. This is in contrast to the USA and Europe, where the VRE appeared in the late 1980s. The progressive increase in VRE isolation poses important problems in the antimicrobial therapy of nosocomial infections. Treatment options and effective antimicrobial agents for VRE are often limited and the possibility of transfer of vancomycin genes to other Gram-positive microorganisms continues. In the search for antimicrobial agents for multiresistant Gram-positive cocci, compounds such as linezolid and quinupristin/dalfopristin have been evaluated. The present study was conducted to evaluate the in vitro activity of the oxazolidinone linezolid and 10 other antimicrobial agents, including quinupristin-dalfopristin, against multiresistant enterococci isolated in Brazilian hospitals. Thirty-three vancomycin resistant isolates (17 Enterococcus faecium and 16 E. faecalis), were analyzed. Strains were isolated from patients at Sao Paulo Hospital, Oswaldo Cruz Hospital, Hospital do Servidor Publico Estadual, Santa Marcelina Hospital, Santa Casa de Misericordia de Sao Paulo, and Hospital de Clinicas do Parana. The samples were tested by a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. All isolates were molecular typed using pulsed-field gel electrophoresis (PFGE). Linezolid was the most active compound against these multiresistant enterococci, showing 100% inhibition at the susceptible breakpoints. Quinupristin/dalfopristin and teicoplanin showed poor activity against both species. The molecular typing results suggest that there has been interhospital spread of vancomycin resistant E. faecium and E. faecalis among Brazilian hospitals. The results of this study indicate that linezolid is an appropriate therapeutic option for the treatment of vancomycin-resistant enterococci infections in Brazil.
TL;DR: The demonstrated quinupristin/dalfopristin activity against Enterococcus faecium was confirmed, but potential species identification errors with various commercial systems continue to confuse susceptibility statistics, even though some strains of E. faecia confirmed by PCR-based or other molecular identification techniques did have quin upristin-dalfo-based MICs of >e; 4 microg/ml.
Abstract: Gram-positive cocci are important causes of both nosocomial and community-acquired infections, and antimicrobial resistance among these pathogens has become an important problem worldwide. Since resistance among these organisms can vary substantially by geographic location, we conducted a multicenter surveillance study with isolates from five Latin American countries (15 medical centers). Quinupristin/dalfopristin (formerly RP-59500) is a novel streptogramin combination with focused activity against Gram-positive cocci, many exhibiting emerging resistance. The in vitro activity of quinupristin/dalfopristin and 12 other antimicrobial agents were evaluated against 1,948 strains including Staphylococcus aureus (747 strains), coagulase-negative staphylococci (CoNS;446 strains), enterococci (429 strains), and various Streptococcus spp. (326 strains). Oxacillin resistance was observed in 41% of S. aureus (MIC, e; 13 mm) and 40% of CoNS (MIC, e; 18 mm). Vancomycin, teicoplanin, and quinupristin/dalfopristin (MIC(90), 0.25 - 1 mg/ml) remained effective against all strains, but cross-resistance was high among other tested drugs. The quinupristin/dalfopristin MIC(50) for Streptococcus pneumoniae and other streptococci was only 0.5 mg/ml (13% to 28% were penicillin-resistant; 12% to 22% were macrolide-resistant). Enterococci demonstrated variable inhibition by quinupristin/dalfopristin depending upon identification and the susceptibility testing method used. The demonstrated quinupristin/dalfopristin activity against Enterococcus faecium was confirmed, but potential species identification errors with various commercial systems continue to confuse susceptibility statistics, even though some strains of E. faecium confirmed by PCR-based or other molecular identification techniques did have quinupristin/dalfopristin MICs of >e; 4 microg/ml. Most important, glycopeptide-resistant enterococci are rapidly emerging in Latin America, and quinupristin/dalfopristin appears active against many of these isolates as well as having potency against nearly all staphylococci and streptococci tested at e; 16 mm. Comparisons to GSMART results from other continents show nearly identical quinupristin/dalfopristin activity for each Gram-positive species tested. These results define the role of quinupristin/dalfopristin in Latin American medical centers and provide a benchmark for future in vitro comparisons.
Journal Article•
TL;DR: The first case, to the authors' knowledge, of vancomycin-resistant Enterococcus faecium vertebral osteomyelitis treated successfully with quinupristin-dalfopristin is reported.
Abstract: Vancomycin-resistant enterococci (VRE) have recently emerged as an increasing concern in the management of severe infections. Treatment of these life-threatening infections has been limited to quinupristin-dalfopristin and, more recently, linezolid therapy. We report the first case, to our knowledge, of vancomycin-resistant Enterococcus faecium vertebral osteomyelitis treated successfully with quinupristin-dalfopristin. We review the recent epidemiology of VRE and briefly outline the pharmacology and pharmacokinetics of quinupristin-dalfopristin.
TL;DR: A 44‐year‐old man was treated successfully for vancomycin‐resistant Enterococcus faecium (VREF) ventriculitis with intrathecal quinupristin‐dalfopristin 1 mg, 2mg, and 4 mg, and other intravenous antibiotics.
Abstract: A 44-year-old man was treated successfully for vancomycin-resistant Enterococcus faecium (VREF) ventriculitis with intrathecal quinupristin-dalfopristin 1 mg, 2 mg, and 4 mg, and other intravenous antibiotics. Cerebrospinal fluid samples were collected before and after the 1-mg and 2-mg doses to determine the concentrations of quinupristin-dalfopristin and its active metabolites. Concentrations were above the minimum inhibitory concentration for VREF immediately after unclamping the extraventricular drain and were quantifiable for at least 7 hours.
TL;DR: Quinupristin-dalfopristin (Q-D) and eight other antimicrobial agents were tested alone and in combination with Q-D in time-kill studies against 10 strains of macrolide-lincosamide-streptogramin B-resistant Staphylococcus aureus.
Abstract: Quinupristin-dalfopristin (Q-D) and eight other antimicrobial agents were tested alone and in combination with Q-D in time-kill studies against 10 strains of macrolide-lincosamide-streptogramin B-resistant Staphylococcus aureus. Although Q-D is normally a bactericidal drug, it was only bacteriostatic for these isolates. Gentamicin alone was bactericidal against 7 of the 10 strains, and Q-D did not alter that killing effect. However, when vancomycin, cefepime, ceftazidime, imipenem, piperacillin-tazobactam, and ciprofloxacin were bactericidal when tested alone, the killing rates were reduced when combined with Q-D. The clinical significance of this in vitro antagonism is unknown at this time, and more studies are needed.
TL;DR: Quinupristin/dalfopristin appears safe and efficacious in critically ill immunocompromised children with renal or hepatic impairment in paediatric liver transplant recipients.
Abstract: We describe our experience of quinupristin/dalfopristin for glycopeptide-resistant Enterococcus faecium (GREF) infections in 19 paediatric liver transplant recipients. The median patient age was 2 years and all were receiving immunosuppressive regimens. Quinupristin/ dalfopristin was well tolerated and complete resolution of infection was seen in 74% of patients. Side-effects included reversible elevation of serum alkaline phosphatase, skin rash, itching, diarrhoea and vomiting, but therapy was not withdrawn from any patient. Quinupristin/ dalfopristin appears safe and efficacious in critically ill immunocompromised children with renal or hepatic impairment.
TL;DR: Data suggest that at least three different macrolide-resistance determinants are prevalent in Germany and that mefA has spread rapidly into multiple clones of S. pyogenes.
Abstract: Macrolide-resistance was assessed in 216 consecutive Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany. Seventeen isolates were resistant to erythromycin: 12 isolates revealed a macrolide (M) phenotype and harbored mefA, and five strains expressed an inducible macrolide-lincosamide-streptogramin B (MLSB) phenotype of which four strains harbored ermA(TR) and one strain contained ermB(AM). Telithromycin (HMR 3647) and quinupristin/dalfopristin remained active particularly against the ermA(TR)-containing S. pyogenes isolates studied. Random amplified polymorphic DNA analysis identified multiple clones among erythromycin-resistant strains, but did not discriminate beyond the emm-type. mefA was present in three isolates either with emm2, emm12, or emm75, and in nine isolates with emm4. All four strains with ermA(TR) contained emm77, and the single strain with ermB(AM) harbored emm1. Despite the relative low rate of macrolide-resistance, these data suggest that at least thr...