Showing papers on "Dalfopristin published in 1998"
TL;DR: Alternative agents have been proposed in the prevention and treatment of device-related and glycopeptide-tolerant S. epidermidis infections and the emergence of resistance to the quinolones, particularly to ciprofloxacin.
Abstract: Previously, Staphylococcus epidermidis and other coagulase-negative staphylococci isolated from the blood of hospitalized patients were often considered contaminants. Now, coagulase-negative staphylococci are among the leading causes of nosocomial blood infections. Multidrug resistance could predict a true nosocomial infection rather than a blood culture contaminant. Recent studies indicated the emergence of resistance to the quinolones, particularly to ciprofloxacin. Tolerance and occasional resistance to vancomycin have been reported recently. In addition, several reports indicated that vancomycin and other glycopeptide antibiotics lose their effectiveness against S. epidermidis organisms embedded in the biofilm environment on the surface of medical devices. Alternative agents have been proposed in the prevention and treatment of device-related and glycopeptide-tolerant S. epidermidis infections. These agents include minocycline, rifampin, and, more recently, quinupristin/dalfopristin and the oxazolidinones.
243 citations
TL;DR: Overall, quinupristin-dalfopristin was consistently active against major Gram-positive pathogens in North America, regardless of resistance patterns to other drug classes and geographic location of their isolation.
161 citations
TL;DR: The in-vitro activity of linezolid was predominantly bacteriostatic; slow bactericidal activity was only observed at the higher concentration with streptococci, and an increase in inoculum on selected strains had little effect on the MICs.
Abstract: The in-vitro activity of linezolid, a novel oxazolidinone, was investigated in comparison with those of amoxycillin, cefuroxime, quinupristin/dalfopristin, trovafloxacin and vancomycin against 420 recent Gram-positive and anaerobic clinical isolates. Linezolid was equally active (MIC 90 1 mg/L) against methicillin-susceptible and -resistant Staphylococcus aureus. It demonstrated uniform activity against streptococci and enterococci and no cross-resistance with other agents. The time-kill kinetic data demonstrated that the in-vitro activity of linezolid was predominantly bacteriostatic; slow bactericidal activity was only observed at the higher concentration with streptococci. An increase in inoculum from 10 4 to 10 6 cfu on selected strains had little effect on the MICs (MIC 90 within one dilution step) of linezolid and an increase in inoculum from 10 5 to 10 7 cfu/mL had no notable effect on the in-vitro bactericidal activity. A tentative linezolid breakpoint of 2 mg/L was chosen after analysis of distribution of susceptibilities.
139 citations
TL;DR: A study of pneumonias in Latin American medical centers demonstrated a greatly increased prevalence of Acinetobacter spp. and higher resistance rates among Gram-negative bacilli when compared with similar controlled studies from North America.
130 citations
TL;DR: The ketolide and the streptogramin were both active against pneumococci with high-level MLSb resistance as well as those with low-level macrolide resistance (clindamycin-susceptible strains).
Abstract: Four different compounds belonging to the macrolide-lincosamide-streptogramin B (MLSb) class of antimicrobial agents were tested against 611 Streptococcus pneumoniae strains. The ketolide (HMR 3647, previously RU66647) and the streptogramin (quinupristin-dalfopristin) were both active against pneumococci with high-level MLSb resistance (clindamycin-resistant strains) as well as those with low-level macrolide resistance (clindamycin-susceptible strains).
71 citations
TL;DR: Multiple drug resistance was very common among these isolates of vancomycin-resistant E. faecium, while dalfopristin-quinupristin inhibited the majority at concentrations that are likely to be clinically relevant.
Abstract: In the course of clinical studies with the investigational streptogramin antimicrobial dalfopristin-quinupristin, isolates of vancomycin-resistant Enterococcus faecium were referred to our laboratory from across the United States. Seventy-two percent of the strains were of the VanA type, phenotypically and genotypically, while 28% were of the VanB type. High-level resistance to streptomycin or gentamicin was observed in 86 and 81%, respectively, of the VanA strains but in only 69 and 66%, respectively, of the VanB strains. These enterococci were resistant to ampicillin (MIC for 50% of the isolates tested [MIC50] and MIC90, 128 and 256 μg/ml, respectively) and to the other approved agents tested, with the exception of chloramphenicol (MIC90, 8 μg/ml) and novobiocin (MIC90, 1 μg/ml). Considering all of the isolates submitted, dalfopristin-quinupristin inhibited 86.4% of them at concentrations of ≤1 μg/ml and 95.1% of them at ≤2 μg/ml. However, for the data set comprised of only the first isolate submitted for each patient, 94.3% of the strains were inhibited at concentrations of ≤1 μg/ml and 98.9% were inhibited at concentrations of ≤2 μg/ml. Multiple drug resistance was very common among these isolates of vancomycin-resistant E. faecium, while dalfopristin-quinupristin inhibited the majority at concentrations that are likely to be clinically relevant.
67 citations
64 citations
TL;DR: SREF isolates from The Netherlands were examined for resistance to quinoprist in-dalfopristin and virginiamycin and for the presence of the two known streptogramin resistance genes in enterococci.
Abstract: Enteroccocci have emerged as an important cause of nosocomial infections. Infections caused by multiresistant enterococci are treated with vancomycin or another glycopeptide. In recent years the usage of vancomycin and the isolation rate of vancomycin-resistant enterococci (VRE) have steadily increased in both Europe and the United States (8). Despite the fact that VRE infections are a hospital problem and the human usage of glycopeptides is in hospitals, VRE have been isolated from the fecal flora of healthy humans without a known hospital connection, from animals, and from the environment (1, 5, 9). One of the few options for treatment of vancomycin-resistant Enterococcus faecium infection is quinopristin-dalfopristin, a mixture (30:70 ratio) of two streptogramins: dalfopristin (streptogramin A) and quinopristin (streptogramin B) (6). A related mixed compound virginiamycin has been used in Europe for many years as a feed additive to enhance growth in food animals. High numbers of virginiamycin-resistant E. faecium have been isolated from the feces of food animals, and these were also resistant to quinopristin-dalfopristin, indicating cross-resistance between virginiamycin and quinopristin-dalfopristin (2, 13, 15).
Two genes, satA and vgb, encoding streptogramin resistance in E. faecium have been detected in clinical isolates. The bacteria were determined to be streptogramin-resistant E. faecium (SREF) by an agar diffusion technique (3, 11). satA encodes resistance to the streptogramin A component (11), while vgb encodes resistance against the streptogramin B component (3). Streptogramin B resistance is also encoded by the erm genes referred to as “MLSB resistance genes” (14).
In this study we examined SREF isolates from The Netherlands for resistance to quinopristin-dalfopristin and virginiamycin and for the presence of the two known streptogramin resistance genes in enterococci. In addition, the genotypes were determined by pulsed-field gel electrophoresis (PFGE) after SmaI digestion (12). A total of 51 SREF isolates from fecal samples of healthy (sub)urban residents (n = 5), farmers (n = 19), poultry (n = 22), and pigs (n = 5) were tested. MICs were defined by agar diffusion methods according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) (10). The presence of satA and vgb was established by PCR with specific primers, giving amplicons of 272 bp for satA and 570 bp for vgb. Two isolates (KH 36syn and K 36syn) with identical PFGE patterns were from a poultry farmer (KH 36syn) and his animals (K 36syn).
All isolates were resistant to quinopristin-dalfopristin (MIC ≥ 32 mg/liter) and to virginiamycin (MIC ≥ 16 mg/liter). The breakpoint for quinopristin-dalfopristin has been suggested to be 4 mg/liter (7). Since virginiamycin is not used for therapy, no breakpoint has been established by NCCLS, but a breakpoint of 4 mg/liter for virginiamycin has been suggested because of the observed distribution of MICs in an E. faecium population (2). All strains were resistant to both quinopristin-dalfopristin and virginiamycin.
The satA gene was detected in 14 (58%) of the SREF isolates of human origin—10 farmers (52%) and 4 suburban residents (80%)—and in 5 (19%) isolates of animal origin—1 porcine isolate (20%) and 4 poultry isolates (18%). The two PFGE-identical SREF isolates both contained the satA gene. The vgb gene was found in a single isolate of human origin (KH 6syn). The study showed that the satA gene encoding streptogramin A resistance was present in SREF isolates of animal and human origins outside hospitals. The vgb gene encoding streptogramin B resistance was found in one human isolate only. These genes have previously been found only in SREF isolates from hospitalized patients (4, 11). satA was more frequently found among isolates from humans than among isolates from animals. The fact that PFGE-identical isolates with the satA genes were found in a farmer and his animals indicates that transfer of SREF between animals and humans occurs. Other resistance genes encoding streptogramin resistance were probably present in the remaining isolates. The erm genes, encoding resistance to streptogramin B compounds, also confer resistance to macrolides and lincosamides. As both groups of antibiotics are widely used in human and veterinary medicine and the macrolide tylosin as growth promoter, the selection for these genes must be high and needs further investigation.
62 citations
Journal Article•
TL;DR: New semisynthetic derivatives, in particular the injectable streptogramin quinupristin/dalfopristin, offer promise for treating the rising number of infections that are caused by multiply resistant bacteria.
Abstract: The streptogramins are a class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally, but the therapeutic use of the natural compounds is limited because they do not dissolve in water. New semisynthetic derivatives, in particular the injectable streptogramin quinupristin/dalfopristin, offer promise for treating the rising number of infections that are caused by multiply resistant bacteria. The streptogramins consist of two structurally unrelated compounds, group A and group B. The group A compounds are polyunsaturated macrolactones: the group B compounds are cyclic hexadepsipeptides. Modifications of the group B components have been mainly performed on the 3-hydroxypicolinoyl, the 4-dimethylaminophenylalanine and the 4-oxo pipecolinic residues. Semi-synthesis on this third residue led to the water-soluble derivative quinupristin. Water-soluble group A derivatives were obtained by Michael addition of aminothiols to the dehydroproline ring of pristinamycin IIA. Followed by oxidation of the intermediate sulfide into the sulfone derivatives (i.e., dalfopristin). Water-soluble derivatives (both group A and group B) can now be obtained at the industrial scale. Modified group B compounds are now also being produced by mutasynthesis, via disruption of the papA gene. Mutasynthesis has proved particularly useful for producing PIB, the group B component of the oral streptogramin RPR 106972. The streptogramins inhibit bacterial growth by disrupting the translation of mRNA into protein. Both the group A and group B compounds bind to the peptidyltransferase domain of the bacterial ribosome. The group A compounds interfere with the elongation of the polypeptide chain by preventing the binding of aa-tRNA to the ribosome and the formation of peptide bonds, while the B compounds stimulate the dissociation of the peptidyl-tRNA and may also interfere with the release of the completed polypeptide by blocking its access to the channel through which it normally leaves the ribosome. The synergy between the group A and group B compounds appears to result from an enhanced affinity of the group B compounds for the ribosome. Apparently, the group A compound induces a conformational change such that B compound binds with greater affinity. The natural streptogramins are produced as mixtures of the group A and B compounds, the combination of which is a more potent antibacterial agent than either type of compound alone. Whereas the type A or type B compound alone has, in vitro and in animal models of infection, a moderate bacteriostatic activity, the combination of the two has strong bacteriostatic activity and often bactericidal activity. Minimal inhibitory concentrations of quinupristin/dalfopristin range from 0.20 to 1 mg/l for Streptococcus pneumonae, from 0.25 to 2 mg/l for Staphylococcus aureus and from 0.50 to 4 for Enterococcus faecium, the principal target organisms of this drug. Quinupristin/dalfopristin also has activity against mycoplasmas, Neisseria gonorrhoeae, Haemophilus influenz, Legionella spp. and Moraxella catarrhalis. Bacteria develop resistance to the streptogramms by ribosomal modification, by producing inactivating enzymes, or by causing an efflux of the antibiotic. Dimethylation of an adenine residue in rRNA, a reaction that is catalyzed by a methylase encoded by the erm gene class, affects the binding of group B compounds (as well as the macrolides and lincosamides; hence, MLSB resistance), but group A and B compounds usually maintain their synergy and their bactericidal effect against MLSB-resistant strains. erm genes are widespread both geographically and throughout numerous bacterial genera. Several types of enzymes (acetyltransferases, hydrolases) have been identified that inactivate the group A or the group B compounds. Genes involved in streptogramin efflux have so far been found only in staphylococci, particularly in coagulase-negative species
60 citations
TL;DR: The findings replicated the development of resistance reported in humans and emphasized bacterial factors (drug susceptibility, high inoculum, organism growth phase) and infectious conditions (penetration barriers) which could increase chances for clinical resistance.
Abstract: Quinupristin-dalfopristin is a streptogramin antibiotic combination with activity against vancomycin-resistant Enterococcus faecium (VREF), but emergence of resistance has been recently reported. We studied the activity of quinupristin-dalfopristin against two clinical strains of VREF (12311 and 12366) in an in vitro pharmacodynamic model with simulated endocardial vegetations (SEVs) to determine the potential for resistance selection and possible strategies for prevention. Baseline MICs/minimal bactericidal concentrations (microg/ml) for quinupristin-dalfopristin, quinupristin, dalfopristin, and doxycycline were 0.25/2, 64/>512, 4/512, and 0.125/8 for VREF 12311 and 0.25/32, 128/>512, 2/128, and 0.25/16 for VREF 12366, respectively. Quinupristin-dalfopristin regimens had significantly less activity against VREF 12366 than VREF 12311. An 8-microg/ml simulated continuous infusion was the only bactericidal regimen with time to 99.9% killing = 90 hours. The combination of quinupristin-dalfopristin every 8 h with doxycycline resulted in more killing compared to either drug alone. Quinupristin-dalfopristin-resistant mutants (MICs, 4 microg/ml; resistance proportion, approximately 4 x 10(-4)) emerged during the quinupristin-dalfopristin monotherapies for both VREF strains. Resistance was unstable in VREF 12311 and stable in VREF 12366. The 8-microg/ml continuous infusion or addition of doxycycline to quinupristin-dalfopristin prevented the emergence of resistance for both strains over the 96-h test period. These findings replicated the development of resistance reported in humans and emphasized bacterial factors (drug susceptibility, high inoculum, organism growth phase) and infectious conditions (penetration barriers) which could increase chances for clinical resistance. The combination of quinupristin-dalfopristin with doxycycline and the administration of quinupristin-dalfopristin as a high-dose continuous infusion warrant further study to determine their potential clinical utility.
51 citations
TL;DR: All the agents were highly active against Legionella micdadei and Legionella bozemanii when compared with L. pneumophila.
Abstract: We evaluated a human monocyte cell line (HL-60) as a model for testing the intracellular activity of anti-Legionella antibiotics; 1.5 x 10 6 HL-60 cells/well were differentiated into adherent cells and infected with 1.5 x 10 7 cfu of Legionella pneumophila. The most active agents against L. pneumophila as judged by broth dilution MICs were (in order of activity) azithromycin, clarithromycin, roxithromycin, quinupristin/dalfopristin, erythromycin and dirithromycin. The most active inhibitors of L. pneumophila intracellular multiplication were (in order of activity) azithromycin, erythromycin, quinupristin/dalfopristin, roxithromycin, dirithromycin and clarithromycin. All the agents were highly active against Legionella micdadei and Legionella bozemanii when compared with L. pneumophila.
TL;DR: 1.I.
Abstract: I. Na'was TE, Hollis DG, Moss CW, Weaver RE: Comparison of biochemical characteristics of Centers for Disease Control fermentative coryneform groups 1, 2, and A-4. Journal of Clinical Microbiology (1987) 25:1351-1358 2. Pascual Ramos C, Foster G, Collins MD: Phylogenetic analysis of the genus Actinomyces based on 16S rRNA gene sequences: description of Arcanobacterium phocae sp. nov., Arcanobacwrium bernardiae comb. nov., and Arcanobacterium pyogenes comb. nov. International Journal of Systematic Bacteriology (1997) 47:46-53 3. Ieven M, Verhoeven J, Gentens P, Goosens H: Severe infection due to Actinornyces bernardiae: case report. Clinical Infectious Diseases (1996) 22:157-158 4. Heller R, Jaulhac B, Charles P, de Briel D, Vincent V, Bohner C, Pidmont Y, Monteil H: Identification of Mycobacterium shimoidei in a tuberculosis-like cavity by 16S ribosomal DNA direct sequencing. European Journal of Clinical Microbiology & Infectious Diseases (1996) 15:172-175 5. Schaa] KP: Genus Actinomyces. In: Sheath PHA, Mair NS, Sharpe ME, Holt JG (eds): Bergey's manual of systematic bacteriology. Williams & Wilkins, Baltimore (1986) pp. 1383-1418 6. Funke G, von Graevenitz A, Clarridge JE, Bernard KA: Clinical microbiology of coryneform bacteria. Clinical Microbiology Reviews (1997) 10:125-159 7. Hill MJ, Hudson MJ, Stewart M: The urinary bacterial flora in patients with three types of urinary tract diversion. Journal of Medical Microbiology (1983) 16:221-226
TL;DR: Time-kill kinetic studies revealed that like the macrolide compounds, the ketolides are bacteristatic at or near the MIC for both H. influenzae and M. catarrhalis.
TL;DR: Given its spectrum of activity, quinupristin/dalfopristin may provide a viable option for the treatment of severe respiratory and skin and skin-structure infections caused by gram-positive bacteria, especially when strains with known or suspected resistance to other commonly used antibiotics are present.
TL;DR: All oral cephalosporins except cefuroxime and cefpodoxime were less active than penicillin and none was satisfactory against pen-I or pen-R pneumococci.
Abstract: MICs of 16 non-beta-lactams were determined by agar dilution for 283 penicillin-susceptible, 122 intermediate and 23 fully penicillin-resistant isolates of pneumococci. Penicillin-resistant pneumococci were more likely to be resistant to tetracyclines, macrolides and related compounds. In the latter group, quinupristin/dalfopristin was the only compound whose activity was not influenced by penicillin resistance. Among the fluoroquinolones, clinafloxacin and trovafloxacin showed excellent activity. Strains resistant to macrolides, tetracycline and penicillin were concentrated in serogroups 6, 9, 14, 19 and 23.
TL;DR: The semisynthetic streptogramin quinupristin/dalfopristin (RP 59500), the first water-soluble member of this class, is under development for the treatment of severe infections caused by methamphetamine-resistant Staphylococcus aureus, methicillin- resistant Staphilococcus epidermidis, penicillin -resistant Streptococcus pneumoniae, glycopeptide-resistant Enterococcus faecium
Abstract: Antibiotics of the streptogramin class are an association of two types of chemically different compounds, group A molecules and group B molecules, acting in synergy. The combination of these molecules generally inhibits bacterial growth at a lower concentration than does either the group A or group B molecule alone and is often bactericidal against strains of bacteria for which each type of molecule alone is only bacteriostatic. The semisynthetic streptogramin quinupristin/dalfopristin (RP 59500), the first water-soluble member of this class, is under development for the treatment of severe infections caused by methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae, glycopeptide-resistant Enterococcus faecium, and other organisms. The streptogramins block the translation of mRNA into protein. Both group A and group B molecules bind to the peptidyl-transferase domain of the bacterial ribosome. The group B molecule stimulates the dissociation of peptidyl-tRNA from the ribosome and may interfere with the passage of the completed polypeptide away from the peptidyl-transferase centre. The group A molecule inhibits the elongation of the polypeptide chain by preventing both the binding of aminoacyl-tRNA to the ribosomal A site and the formation of the peptide bond. When the two types of molecule are used in combination, the binding of the group A molecule alters the conformation of the ribosome such that the affinity of the ribosome for the B molecule is increased. This accounts, in part or entirely, for the observed synergy. This synergy is unaffected by ribosomal modifications conferring resistance to the macrolides, lincosamides, and group B molecules alone.
TL;DR: The relationship between Q-D, quinupristin (Q), and/or dalfoprist in (D) susceptibility parameters and antibacterial activities against 22 clinical isolates of vancomycin-resistant Enterococcus faecium (VREF) is evaluated by using the concentration-time-kill-curve method and by measuring postantibiotic effects.
Abstract: Quinupristin-dalfopristin (Q-D) is a new water-soluble, semisynthetic antibiotic that is derived from natural streptogramins and that is combined in a 30:70 ratio. A number of studies have described the pharmacodynamic properties of this drug, but most have investigated only staphylococci or streptococci. We evaluated the relationship between Q-D, quinupristin (Q), and/or dalfopristin (D) susceptibility parameters and antibacterial activities against 22 clinical isolates of vancomycin-resistant Enterococcus faecium (VREF) by using the concentration-time-kill-curve method and by measuring postantibiotic effects. Q-D, Q, and D MICs and minimum bactericidal concentrations (MBCs) ranged from 0.125 to 1 and 0.25 to 64, 8 to 512 and >512, and 2 to 8 and 8 to 512 microgram/ml, respectively. There were no significant relationships between susceptibilities to the individual components and the susceptibilities to the Q-D combination product. In the time-kill-curves studies, Q-D at a concentration of 6 microgram/ml was at least bacteriostatic against all VREF tested. There was increased activity against more susceptible isolates when the isolates were grouped either by Q-D MBCs or by Q MICs. By multivariate regression analyses, the percent change in the inoculum from that at the baseline was significantly correlated with the Q MIC (R = 0.74; P = 0.008) and the Q-D concentration-to-MBC ratio (R = 0.58; P = 0.02) and was inversely correlated with the Q-D MBC-to-MIC ratio (R = 0.68; P = 0.003). A strong correlation existed between the killing rate and the Q-D concentration-to-MBC ratio (R = 0.99; P < 0.0001). Time to 99.9% killing was best correlated with the Q-D MBC (R = 0.96; P < 0.0001). The postantibiotic effect ranged from 0.2 to 3.2 h and was highly correlated with the Q-D concentration-to-MBC ratio (R = 0.96; P < 0.0001) and was less highly correlated with the Q MIC (R = 0.42; P = 0.04). Further study of these relationships with in vitro or in vivo infection models that simulate Q-D pharmacokinetics should further define the utility of these pharmacodynamic parameters in the prediction of Q-D activity for the treatment of VREF infections in humans.
TL;DR: 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.
Abstract: 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.
TL;DR: Quinupristin-dalfopristin produced postantibiotic effects (PAEs) and postantIBiotic sub-MIC effects of >2 h against 18 gram-positive cocci.
Abstract: Quinupristin-dalfopristin produced postantibiotic effects (PAEs) and postantibiotic sub-MIC effects of >2 h against 18 gram-positive cocci. Mean pneumococcal and staphylococcal PAEs were 2.8 and 4.7 h, respectively, with shorter PAEs for constitutively than inducibly macrolide-resistant staphylococci. Mean PAEs for vancomycin-susceptible and -resistant Enterococcus faecium were 8.5 and 2.6 h, respectively.
TL;DR: When staphylococci are constitutively resistant to B compounds, the in vitro activities of the mixtures should be evaluated, because they are better correlated than MICs with their efficacy in therapy.
TL;DR: The case of a neonate with vancomycin resistant E faecium (VRE) meningitis successfully treated with quinupristin/dalfopristin (a semisynthetic injectable streptogramin) and chloramphenicol is reported.
Abstract: Editor—Antimicrobial resistance in enterococci, particularly E faecium , may greatly restrict the choice of treatment. We report the case of a neonate with vancomycin resistant E faecium (VRE) meningitis successfully treated with quinupristin/dalfopristin (a semisynthetic injectable streptogramin) and chloramphenicol.
The patient underwent repair of obstructed infradiaphragmatic total anomalous pulmonary venous drainage on the first day of life. Recovery was complicated by an episode of necrotising enterocolitis for which cefotaxime and metronidazole were given. At the age of 13 days abdominal signs had resolved but the patient was febrile. Over the next three days six blood cultures yielded E faecium resistant to vancomycin, amoxycillin, …
TL;DR: Treatment with a combination of rifampin and nitrofurantoin for 6 weeks resulted in long-lasting cure in a 42-year-old liver transplant recipient of chronic prostatitis due to Enterococcus faecium resistant to vancomycin, ampicillin, ciprofloxacin and doxycycline.
Abstract: Prostatitis due to vancomycin-resistant enterococci has not been previously described. Reported here is a case of chronic prostatitis due to Enterococcus faecium, resistant to vancomycin, ampicillin, ciprofloxacin and doxycycline, in a 42-year-old liver transplant recipient. Treatment with a combination of rifampin and nitrofurantoin for 6 weeks resulted in long-lasting cure. Other antimicrobial agents active in vitro against vancomycin-resistant enterococci, such as quinupristin/dalfopristin and chloramphenicol, are unlikely to achieve sufficient prostatic tissue levels to be successfully utilized for treatment of this condition.
TL;DR: The in vitro activities of quinupristin-dalfopristin and streptogramin RPR 106972 were determined with 44 strains of Mycoplasma pneumoniae and compared to those of macrolides, minocycline, and quinolones.
Abstract: The in vitro activities of quinupristin-dalfopristin and streptogramin RPR 106972 were determined with 44 strains of Mycoplasma pneumoniae and compared to those of macrolides, minocycline, and quinolones. All isolates tested were highly susceptible to macrolides and to quinupristin-dalfopristin (MIC at which 90% of the isolates are inhibited [MIC90], 0.0625 microg/ml), followed by RPR 106972 (MIC90, 0.5 microg/ml), quinolones, and minocycline.
TL;DR: A specific and sensitive HPLC method was developed to measure simultaneously quinupristin-dalfopristin and their main metabolites in human plasma and its validated range of concentrations was 0.025-5000 mg l(-1) for RP 57669, RP 54476 and RP 12536.
TL;DR: Previously proposed interpretative criteria for quinupristin/dalfopristin disc diffusion susceptibility tests were confirmed and both streptogramins had essentially identical spectra of activity.
Abstract: The clinical isolates were collected during the winter months of 1996‐1997. The ten laboratories that contributed fresh isolates are listed in the Acknowledegments at the end of this report. The bacterial isolates represent consecutive collections, except that multiple isolates from the same patient episode were excluded. The species represented are identified in the Table. Appropriate biochemical tests were used to confirm the identity of each isolate when the original species identification was questioned because of unexpected colony morphology or antimicrobial resistance patterns.
TL;DR: There were differences in the quality of growth, but little difference in MICs or zone diameters was obtained on three different media: Mueller-Hinton (MHA), Iso-Sensitest (ISA), and Diagnostic Sensitivity Test (DST) agars.
Abstract: Quinupristin/dalfopristin and RPR 106972 were active in vitro against a wide range of aerobic Gram-positive organisms including Enterococcus faecium. However, most isolates of Enterococcus faecalis were resistant or of intermediate sensitivity. Against Staphylococcus aureus quinupristin/dalfopristin was more active but for all other species the range of activity of the two drugs was the same or RPR 106972 was more active. RPR 106972 was also more active against the respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis. Quinupristin/dalfopristin MICs for isolates of H. influenzae (1-8 mg/L) clustered around the breakpoint. There were differences in the quality of growth, but little difference in MICs or zone diameters was obtained on three different media: Mueller-Hinton (MHA), Iso-Sensitest (ISA), and Diagnostic Sensitivity Test (DST) agars. The addition of blood to the medium increased MICs 2- to 4-fold, with MHA showing the greatest increase, and reduced zone diameters around quinupristin/dalfopristin discs by 3-4 mm, with the greatest effect on ISA.
TL;DR: Quinupristin/dalfopristin was bactericidal for all six strains investigated after 2 h at a concentration of 4 mg/l and showed good activity against penicillin-susceptible/erythromycin-sUSceptible strains.
Abstract: Minimal inhibitory concentrations (MICs) of quinupristin/dalfopristin, penicillin, erythromycin, and clindamycin were determined by a standard agar dilution method for 93Streptococcus pneumoniae strains isolated from patients with invasive disease in Germany. Quinupristin/dalfopristin showed good activity against 32 penicillin-susceptible/erythromycin-susceptible strains (MIC90 0.5 mg/l; range 0.25–0.5 mg/l) and 31 penicillin-intermediate/erythromycin-susceptible strains (MIC90 0.5 mg/l; range 0.25–1 mg/l). Erythromycin-resistant strains (n=30) were slightly less susceptible (MIC90 1 mg/l; range 0.125–2 mg/l). Quinupristin/dalfopristin was bactericidal (99.9% killing) for all six strains investigated after 2 h at a concentration of 4 mg/l.
TL;DR: The MICs of a broad range of antimicrobial agents for 125 strains belonging to PFGE types 1, 2 and 3 were determined, finding that all of the isolates were susceptible to the glycopeptides, vancomycin and teicoplanin, the MICS of these agents remaining stable over the range 0.5–1 mg/L.
Abstract: Sir, We read with interest the recent report by Hiramatsu et al. of the first isolation of a strain of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin. To date, clinical isolates of S. aureus have been uniformly susceptible only to glycopeptide antibiotics which have consequently become the drugs of choice for the treatment of patients with MRSA infections. However, as vancomycin-resistant isolates of S. aureus are likely to become more widespread, alternative antibiotics with activities against MRSA are needed urgently. Although arbekacin and ampicillin/sulbactam were used successfully to eradicate the Japanese isolate, thereby demonstrating the efficacy of existing non-glycopeptide drugs, little is known about the stability of the MICs of alternative compounds over time. In order to assess this property in clonally related MRSA strains isolated in the Dusseldorf area, we determined the MICs of a broad range of antimicrobial agents for 125 such isolates recovered over a period of 3 years. The test isolates were selected from a collection of 489 MRSA strains from 183 different patients; the organisms had been referred to the Institute for Medical Microbiology and Virology, University Hospital Dusseldorf, between 1992 and 1995 by 11 regional hospitals. From these 489 strains, 183 were chosen for typing studies on the basis that they were the first isolates recovered from any site of a colonized or infected patient. All isolates were typed by pulsed-field gel electrophoresis (PFGE) which is regarded as the most discriminatory molecular technique for typing MRSA strains. This procedure identified 28 distinct MRSA types, of which the three most common were types 1, 2 and 3 (comprising 75, 38 and 12 isolates respectively); these have been shown to be the predominant PFGE types found in western Germany. Carriage of the mecA and coa genes by the 125 isolates belonging to the three PFGE types was confirmed with a multiplex PCR. Type 1 MRSA strains were isolated between July 1992 and June 1995 from 29 wards in five hospitals throughout the region. Those belonging to MRSA type 2 were isolated between November 1992 and April 1995 from 19 wards in three hospitals, while those belonging to MRSA type 3 were isolated between September 1994 and January 1995 from five wards in three hospitals. The MICs of 20 antimicrobial agents for the 125 strains belonging to PFGE types 1, 2 and 3 were determined by a microbroth dilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS); the inoculum was approximately 10 cfu/L. All of the isolates were resistant to penicillin (MICs 32 mg/L), ampicillin (MICs 32 mg/L), amoxycillin– clavulanate (MICs 32 mg/L), piperacillin–tazobactam (MICs 128 mg/L), oxacillin (MICs 64 mg/L), imipenem (MICs 16 mg/L), ceftriaxone (MICs 32 mg/L), gentamicin (MICs 16 mg/L), tetracycline (MICs 8 mg/L), rifampicin (MICs 2 mg/L), erythromycin (MICs 16 mg/L) and clindamycin (MICs 8 mg/L). The MICs of the remaining agents are shown in the Table. All of the isolates were susceptible to the glycopeptides, vancomycin and teicoplanin, the MICs of these agents remaining stable over the range 0.5–1 mg/L. Despite reports of the development of low-level vancomycin resistance in clinical isolates of coagulase-negative staphylococci and the first report of reduced susceptibility to vancomycin in S. aureus, no increase in the MICs of glycopeptides for MRSA strains isolated in Dusseldorf was observed. These antibiotics therefore remain the drugs of choice for patients with MRSA infections, both in the Dusseldorf area and, indeed, throughout western Germany where the same PFGE types predominate. The combination of quinupristin and dalfopristin (Synercid) was highly active against all of the MRSA isolates tested; moreover, the MICs were stable over the range 0.25–1 mg/L during the study period. As the combination is also active in vitro against strains exhibiting inducible MLS (macrolide, lincosamide and streptogramin-B) resistance, quinupristin and dalfopristin being poor inducers of the methylase (erm) genes, it shows promise as an alternative to the glycopeptides in patients with MRSA infections.
TL;DR: Although two patients died, this was due to underlying disease in one case and a gram-negative superinfection in another, and Quinupristin/dalfopristin therapy was not associated with significant adverse effects in any of the patients.