Dalfopristin

About: Dalfopristin is a research topic. Over the lifetime, 696 publications have been published within this topic receiving 26621 citations. The topic is also known as: RP-54476 & Dalfopristina.

Comparative In Vitro Activity of Quinupristin/Dalfopristin and Seven Other Antimicrobials Against Methicillin-Susceptible and Methicillin-Resistant Nosocomial Staphylococcus aureus Bloodstream Isolates

Abstract: 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.

Liofilchem(®) Chromatic VRE and vancomycin MIC Test Strip detected glycopeptide resistance in a vanB neonatal Enterococcus faecium isolate showing alternate vancomycin susceptibility and resistance with bioMérieux Vitek2.

Abstract: A 1-month old male child with fever (37.5°C) underwent urine culture that yielded rare Enterococcus-like α-hemolytic colonies. Although considered to be of no clinical relevance, the strain was identified to the species level and screened for antimicrobial resistance with the purpose to detect van elements, if any [1-3]. Particularly, the strain showed group D antigen agglutination that was detected by both the Oxoid streptococcal grouping kit (Thermo Fisher, USA) and the Strep-Check kit (Liofilchem®, Italy) and identification as Enterococcus faecium was achieved by Vitek2 GP card (bioMerieux, France) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using Bruker Biotyper software 2.0 (Bruker Daltonics, Germany) as well as by sequencing of a 16S rRNA gene 900-bp amplicon (100% identity to the E. faecium strain {"type":"entrez-nucleotide","attrs":{"text":"KF358453.1","term_id":"540073930","term_text":"KF358453.1"}}KF358453.1 was obtained). Antibiotic susceptibility testing performed with Vitek2 AST592 card (along with cards AST632 and AST586) showed the strain to be alternatively vancomycin susceptible or resistant, with MIC (Minimum Inhibitory Concentration) values ranging between ≤ 0.5 and 8 μg/mL. Disc test (Liofilchem®) for vancomycin produced a 19 mm inhibition zone diameter, that was in the susceptibility range according to the European Committee for Antibiotic Susceptibility Testing [EUCAST] 2014 guidelines. Nevertheless, a fuzzy zone edge otherwise microcolonies within the inhibition area were observed (Figures 1, ​,2),2), meaning resistance to the glycopeptide (based on EUCAST criteria). Accordingly, vancomycin MIC Test Strip (MTS-Liofilchem®) provided a 2 μg/mL MIC value at 24 h incubation (in the susceptibility range based on EUCAST), but microcolonies grew inside the elliptic inhibition zone, clearly confirming resistance (Figure 3). Accordingly, the isolate formed blue colonies on Liofilchem® Chromatic VRE (Figure 4), a chromogenic medium where such a color indicates glycopeptide resistant E. faecium. As a confirmation of vancomycin resistance, a real-time polymerase chain reaction (PCR) targeting the vanA and vanB genes [2,3] was performed with the Xpert vanA/vanB Assay on a GeneXpert® Instrument system (Cepheid, US) that detected the vanB element [3]. Figure 1 Fuzzy zone edge obtained with vancomycin (Liofilchem®) on Mueller Hinton II agar (Liofilchem®). Figure 2 Microcolonies within the vancomycin (VA disc) halo - microcolonies are absent in the teicoplanin (TE disc) inhibition zone (discs and Mueller Hinton II agar are provided by Liofilchem®). Figure 3 Microcolonies within the vancomycin (VA strip) halo - microcolonies are absent in the teicoplanin (TE strip) inhibition zone (strips and Mueller Hinton II agar by Liofilchem®). Figure 4 Colonies of the studied isolate on Liofilchem® Chromatic VRE medium. Enterococci inhabit gut of humans and animals and are among the major agents of hospital-acquired infections [2,3]. Recently, the wide use of antibiotics and immunosoppressive treatments along with the increasing use of invasive therapeutic procedures, have brought these organisms, notably E. faecium, to gain emerging clinical relevance [2]. Enterococcus has been known to be intrinsically resistant to cephalosporins, and is considered not to respond to aminoglycosides, under treatment. In fact, even though these classes of drugs may display in vitro activity, they are expected to fail in vivo [2]. Again, multidrug resistance has been widely reported within the genus and, as antimicrobial resistance varies among Enterococcus species, precise identification is necessary for clinical strains, as it supports selection of proper antibiotics [2]. In particular, a significantly higher prevalence of resistance to penicillin, ampicillin, rifampicin, ciprofloxacin, levofloxacin, fosfomycin, erythromycin and nitrofurantoin is found in E. faecium rather than Enterococcus faecalis, whereas that to chloramphenicol, quinupristin/dalfopristin, minocycline and tetracycline is mostly observed in the second (quinupristin/dalfopristin, in particular, is intrinsically poorly effective versus E. faecalis) [2]. Furthermore, a low prevalence of linezolid, vancomycin and teicoplanin resistance in both species is reported, globally, and the mentioned three compounds are then currently and widely used for treatment [2]. Resistance to glycopeptides is however described and mainly due to alteration of the peptidoglycan precursors, which leads to drug failure in inhibiting the cell wall synthesis [2,3]. The vanA gene may be transferred to Staphylococcus aureus, too, therefore care is needed when vancomycin is administered to manage enterococci [2]. Detection of the underlying gene for a resistance trait is important in the laboratory practice, although unfortunately molecular methodologies usually require skilled operators and are time-consuming and expensive, then not suitable for the routine activity. Based on the manufacturer’s instructions and indications, the Cepheid Xpert vanA/vanB Assay is a qualitative in vitro diagnostic test designed for fast detection of vancomycin-vanA/vanB genes directly from rectal and perianal swabs; the assay is in fact particularly dedicated to patients at risk for gut colonization by glycopepide-resistant enterococci (mostly vancomycin resistant entercocci [VRE]) through an automated real-time PCR targeting the mentioned genes. As the spread of VRE is through contact with colonized or infected individuals within healthcare facilities, and given the need of identifying and isolating their carriers, the test is mostly intended to screen patients by perianal or rectal swabs at admission, once a week after admission, after antibiotics receipt and, finally, upon discharge. GeneXpert Instrument Systems automate and integrate sample purification, nucleic acid amplification, and target detection sequence in simple or complex samples by using real-time PCR, that therefore, and interestingly, needs no particularly skilled operators. Agar methodologies, such as Liofilchem® discs, MTS and Chromatic VRE, are however cost-effctive and reliable and permit an accurate diagnostics of Enterococcus glycopeptide resistance. In particular, it is crucial to evaluate not only disc-generated inhibition zone diameters and MICs produced by MTS, but to look for microcolonies and/or a fuzzy zone edge, if present, based on EUCAST indications. Again, we suggest to screen all clinical isolates through the chromogenic medium and agar-based assays, as it emerges from this communication that, due to both inducibility of vanB gene and its potentially heterogeneous expression (along with variability of phenotypically observed vanB-mediated vancomycin resistance), this trait may not be detected by Vitek2; with automated systems, in fact, it is likley that the bacterial population that displays the resistance trait may go underecognized. Moreover, it should be kept in mind that the Cepheid Assay is designed to detect vanA/B genes only; nevertheless, vanA/B is exclusively harboured by E. faecalis (vanA/B), E. faecium (vanA/B) and Enterococcus durans (vanA) [3]; again, E. faecium and E. faecalis may carry vanD (E. faecium and E. faecalis), vanE (E. faecalis), vanG (E. faecalis) and vanM (E. faecium) genes, that may confer glycopeptide resistance, but are missed with GeneXpert® [3]; then, working with enterococcal species other than those mentioned or with E. faecalis/E. faecium carrying glycopeptide resistance traits other than vanA/B would provide negative results with this system, in spite of the harboured genetic element potentially encoding resistance. Enterococci have been considered in the past to cause endogenous infections; later, it became clear that they could commonly spread through colonized healthcare operators. Therefore, VRE-carrying patients, even healthy, should be carefully recognized as they may behave as reservoirs for vancomycin and teicoplanin resistance [3]. Finally, resistance may be expressed by a restricted number of bacterial cells within a given microbial population (the phenomenon is called heteroresistance), therefore it might not be observed with Vitek2, as was in this case, and it is required that agar methods be routinely carried out to support a reliable detection of glycopeptide resistance among clinical enterococci.

Prevalence and molecular epidemiology of ceftaroline non-susceptible methicillin-resistant Staphylococcus aureus isolates, first clinical report from Iran.

Abstract: Background Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major pathogens in Iran with a high prevalence and a high level of antibiotic resistance. Ceftaroline is a fifth generation cephalosporin binding and inhibiting penicillin binding protein (PBP2a). Methods In the present study, 228 clinical MRSA isolates were collected from four cities of Iran and their susceptibility to ceftaroline was evaluated by E-test and the disk diffusion method. Results Our results showed a high susceptibility rate (97.3%) to ceftaroline in MRSA strains from Iran. Six isolates were found to be ceftaroline non-susceptible (CPT-NS) with Minimum inhibitory concentration (MIC) ≥2 µg/mL. All CPT-NS isolates were isolated from blood and tracheal aspirate and belonged to SCCmec type III as well as agr type I and were all susceptible to vancomycin. Out of six isolates, three, two and one belonged to spa type t030, t4864, and t969, respectively. Vancomycin, quinupristin/dalfopristin, linezolid, chloramphenicol, and tigecycline were the most active agents against CPT-NS isolates. Conclusion Due to the broad-spectrum activity and low toxicity of ceftaroline as well as the increased rate of vancomycin resistance among MRSA strains in recent years, ceftaroline can be considered as a novel approach to treat MRSA-induced infections.

Characterization of coagulase-negative staphylococci isolated from cases of ostitis and osteomyelitis.

Abstract: Coagulase-negative staphylococci (CoNS) are often responsible for cases of chronic ostitis and osteomyelitis, especially in patients with orthopedic prosthesis/implants. The aim of this study was to characterize CoNS isolated from ambulatory patients with chronic ostitis/osteomyelitis and to compare them by PFGE (pulsed-field gel electrophoresis). Out of 263 bacterial strains isolated from wounds/sinuses of patients with chronic ostitis/osteomylitis, 41 were identified as CoNS. Twenty methicillin-resistant strains were selected for this study. Our results confirm the superior performance of cefoxitin disk test to detect methicillin resistance in heterogenous population of CoNS. High level of antibiotic resistance was observed among the studied strains: majority of CoNS were resistant to tetracycline and erythromycin and also to clindamycin and ciprofloxacin. Importantly, in 15 out of 20 studied CoNS different phenotypes of macrolides, lincosamides and streptogramin--MLS resistance was suggested. Eight strains demonstrated resistance to both erythromycin and clindamycin, suggesting constitutive MLS(B) phenotype. Seven remaining strains presented resistance to erythromycin and susceptibility to clindamycin with negative D-test results, suggesting the presence of macrolides and streptogramines type A efflux pump. All studied strains were sensitive to vancomycin (MIC 0.75-2.0 microg/ml), teicoplanin (MIC 0.125-8.0 microg/ml), and quinupristin/dalfopristin (MIC 0.19-1.0 microg/ml). No clonal relatedness was observed in PFGE patterns.