In vitro activity of vancomycin and teicoplanin against gram-positive cocci]

The activities of vancomycin and teicoplanin against 148 strains of Gram-positive cocci were tested using agar diffusion and liquid microdilution MIC determination. Tested strains included 84 staphylococci, 32 S. aureus, 52 coagulase-negative staphylococci (CNS), 52 enterococci, and 12 streptococci. Most strains (136) were susceptible to both agents, with inhibition diameters of 17 mm or more. MRSA strains exhibited lower geometric MIC means with teicoplanin (0.90 micrograms/ml) than with vancomycin (1.79 micrograms/ml); this difference was found for methicillin-susceptible S. aureus strains (1.07 and 1.38 micrograms/ml for teicoplanin and vancomycin, respectively). In contrast, methicillin-susceptible and methicillin-resistant strains of CNS exhibited similar MICs (1.60 micrograms/ml approximately). Enterococci were more susceptible to teicoplanin (MIC 0.25 micrograms/ml) than to vancomycin (MIC 1.35 micrograms/ml). Both vancomycin and teicoplanin were thus found to be consistently effective against Gram-positive cocci; however, teicoplanin proved more effective than vancomycin against enterococci and methicillin-resistant S. aureus strains and may therefore be a valuable therapeutic alternative for these multiresistant organisms.     

In vitro activity of antimicrobial agents against oxacillin resistant staphylococci with special reference to Staphylococcus haemolyticus

One hundred and sixty seven isolates of staphylococci isolated from the inpatients of a tertiary care referral hospital in South India were speciated and activity of oxacillin, glycopeptides, linezolid and quinupristin/dalfopristin against these isolates was tested by broth microdilution method. Of the 114 coagulase negative staphylococci (CoNS), 49.1 % were S. haemolyticus, isolated predominantly from urine (64.6%), while the rest belonged to 11 other species. More than half the isolates of S. aureus (52.8%) and 68.4% of the CoNS were oxacillin resistant. All the strains were uniformly susceptible to vancomycin, linezolid and quinupristin/dalfopristin; but 25.6% isolates of S. haemolyticus showed reduced susceptibility to teicoplanin (MIC: 8-16 mg/L). Our study demonstrates the high prevalence of oxacillin resistance among hospital isolates of S. aureus and CoNS in India. Vancomycin, along with the newer agents like linezolid and quinupristin/dalfopristin remains the drug of choice for treating multi drug resistant staphylococcal infections.     

The DUEL study: a multi-center in vitro evaluation of linezolid compared with other antibiotics in the Netherlands

Objective   To evaluate bacterial susceptibility to linezolid in the Netherlands in comparison with other antibiotics.
Methods   Bacterial strains were isolated between September 1999 and January 2000 from patients presumed to require antibiotic treatment. The in vitro activity of 1226 strains from 34 participating laboratories was tested against linezolid, vancomycin, teicoplanin, oxacillin, penicillin, erythromycin, ampicillin and other antibiotics against enterococci, coagulase-negative staphylococci, Staphylococcus aureus and Streptococcus pneumoniae . Minimal inhibitory concentrations (MIC) were obtained with the E test on Mueller-Hinton agar: every laboratory included control strains. For vancomycin and teicoplanin only, brain–heart infusion agar and an inoculum of 2.0 McFarland was used for Staphylococcus aureus , coagulase-negative staphylococci and enterococci to support a better growth and clear recognition of hetero-resistant colonies.
Results   The values of MIC₉₀ for linezolid were 1.5, 0.75, 0.75 and 1 mg/L for Staphylococcus aureus , coagulase-negative staphylococci, Streptococcus pneumoniae and enterococci, respectively. Six enterococcal strains with decreased susceptibility against vancomycin or teicoplanin were identified as Enterococcus faecium , E. gallinarum and E. casseliflavus (two strains each) and they were found to harbor vanA , vanC1 and vanC2/3 genes, respectively. Nine per cent of Streptococcus pneumoniae (an increase from 1% 4 years ago) showed decreased susceptibility to erythromycin, of both the ermB and mefE type; there was no cross-resistance with linezolid. Twelve coagulase-negative staphylococcal strains were resistant to teicoplanin.
Conclusion   Linezolid is a promising drug in the treatment of infections caused by Gram-positive cocci. Cross-resistance with other antibiotics tested was not found.     

Addressing resistance evolution in Pseudomonas aeruginosa using pharmacodynamic modelling: application to meropenem dosage and combination therapy

Isolates of Pseudomonas aeruginosa (n = 208) were collected from an 810-bed hospital in Connecticut, USA. A model employing the pharmacokinetic properties of meropenem, susceptibility results and Monte Carlo simulation was used to analyse four different dosing regimens of meropenem at pharmacodynamic endpoints. Cumulative fraction of response (CFR) was assessed at bacteriostatic and bactericidal endpoints for the entire population of isolates, as well as for isolates from principal anatomical sites. CFR was also evaluated at endpoints shown to suppress emergence of resistance in 'susceptible'P. aeruginosa with either monotherapy or combination therapy. The bacteriostatic/bactericidal CFR of meropenem 1 g every 8 h (q8h), 2 g q8h, 1 g q8h infused over 3 h (3-h INF), and 2 g q8h 3-h INF were 76%/73%, 80%/76%, 77%/75% and 79%/78%, respectively. At the monotherapeutic suppressive endpoint, CFRs against susceptible isolates were 21%, 35%, 32% and 50%, respectively. When combination therapy with an aminoglycoside was simulated, the CFRs for the same regimens were 50%, 64%, 65% and 79%, respectively. Bactericidal CFRs for all regimens against wound isolates were significantly higher (p <0.03 for each regimen) than CFRs for the entire population. Meropenem 2 g q8h with a 3-h infusion in combination with an aminoglycoside provides the greatest likelihood of P. aeruginosa coverage, and may help to prevent development of resistance, although local MIC data are essential to inform therapeutic decisions.     

In vitro activity of teicoplanin against gram-positive cocci

The glycopeptide susceptibility of 443 clinical isolates of gram-positive cocci collected from nine general hospitals in 1996 was determined according to the recommendations of the CA-SFM (the Antibiogram Committee of the French Society for Microbiology). In total, 234 isolates of Staphylococcus aureus, 84 isolates of coagulase-negative staphylococci (CNS), 98 enterococci and 27 streptococci were collected. The mecA gene confirming resistance to methicillin was found in 42.7% of S. aureus isolates and 51.2% of CNS isolates. No resistance to teicoplanin and vancomycin was found in S. aureus but four isolates of CNS had an MIC of teicoplanin > or = 8 mg/L. All isolates of Enterococcus faecalis tested were susceptible to both glycopeptides. This study confirms that teicoplanin has a very good in vitro activity against gram-positive cocci, isolated in France from nosocomial infections.     

Prevalence ofStaphylococcus aureus and coagulase-negative staphylococci with decreased sensitivity to glycopeptides as assessed by determination of MICs

The prevalence of staphylococci with decreased sensitivity to glycopeptides was assessed at a Paris hospital by determination of the MICs. The values obtained using the MIC method were compared to those obtained using the routine disk agar diffusion method. One hundred independently isolated strains were tested including 57Staphylococcus aureus isolates and 43 coagulase-negative staphylococci (CNS). For all strains vancomycin MICs were 4 mg/l but for 5.3 % of theStaphylococcus aureus isolates and 25.6 % of the CNS isolates teicoplanin MICs were high ( 8 mg/l). Moreover, teicoplanin MICs did not correlate well with zone sizes. The MIC method is therefore recommended for evaluating the susceptibility of staphylococci to teicoplanin.     

In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium

We assessed the in vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin (QD) against a contemporary challenge panel of 88 staphylococcal and 90 enterococcal isolates. The staphylococci selected included vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant S. aureus, and coagulasenegative staphylococci. Enterococcal isolates included vancomycin-resistant Enterococcus faecium (VREF) containing either vanA, vanB1, or vanD. The MICs of daptomycin, linezolid, and QD were determined using commercial broth microdilution panels. All three VISA isolates were susceptible to daptomycin, linezolid, and QD. QD was the most active agent against staphylococcal isolates (MIC50 < or = 0.5 microg/ml and MIC90 = 1 microg/ml), including those with decreased susceptibility to vancomycin. QD was also the most active agent against VREF (MIC90 < or = 0.5 microg/ml). No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD. Daptomycin was the most effective against E. faecalis. On the basis of manufacturer-suggested interpretive criteria, 92% of isolates were susceptible (MIC90 = 4 microg/ml). All isolates tested were susceptible to at least one antimicrobial agent for which interpretive criteria have been defined. Population analysis of three S. aureus isolates for which the daptomycin MICs were 8 microg/ml showed a pattern of homogeneous resistance.     

Ciprofloxacin- and Methicillin-Resistant Staphylococcus aureus Susceptible to Moxifloxacin, Levofloxacin, Teicoplanin, Vancomycin and Linezolid

 In order to determine the comparative efficacy of vancomycin, teicoplanin, levofloxacin, moxifloxacin, and linezolid against methicillin- and ciprofloxacin-resistant Staphylococcus aureus, each agent was tested against 65 genetically different strains using the microbroth dilution method. All of the isolates were typed using the enterobacterial repetitive intergenic consensus polymerase chain reaction to exclude multiple isolates of epidemic clones. Susceptibility testing revealed that all of the isolates were susceptible to vancomycin and teicoplanin. Linezolid exhibited minimum inhibitory concentration (MIC) levels ranging from 1 to 4 mg/l (MIC90, 4 mg/l). The MICs of moxifloxacin and levofloxacin ranged from 0.01 to 8 mg/l (MIC90, 8 mg/l) and 0.25 to 32 mg/l (MIC90, 16 mg/l), respectively. Thus, linezolid is active against methicillin- and ciprofloxacin-resistant Staphylococcus aureus, whereas moxifloxacin may need to be administered at a dose higher than recommended in order to successfully treat serious infections.     

Comparative in vitro activity of IY146032 (daptomycin), a new lipopeptide antimicrobial

The in vitro activity of LY146032, a new cyclic lipopeptide antibiotic, was compared with those of vancomycin, teicoplanin, and either oxacillin or ampicillin by determining agar dilution MIC values for 304 clinical gram-positive isolates. LY146032 had superior in vitro activity against oxacillin-resistant staphylococci when compared to vancomycin or teicoplanin. Against oxacillin-sensitive staphylococci, group JK-diphtheroids, streptococci,Listeria monocytogenes andClostridium difficile, LY146032 was equally or less active than vancomycin, teicoplanin, or the penicillins tested. When tested by macrobroth dilution MIC/MBC., LY 146032 showed good bactericidal activity against all organisms with the exception ofClostridium difficile.     

European survey of glycopeptide susceptibility in Staphylococcus spp.

Objectives: To reassess the relative potencies of teicoplanin and vancomycin following several years of clinical usage.
Methods: The glycopeptide susceptibilities of clinical isolates of staphylococci collected from 70 hospitals in 1995 were determined using NCCLS (National Committee for Clinical Laboratory Standards) methods.
Results: In total, 2885 isolates of Staphylococcus aureus and 1480 isolates of coagulase-negative staphylococci were collected. S. aureus was significantly less susceptible to vancomycin (MIC₅₀ 1 mg/L) than teicoplanin (MIC₅₀ 0.5 mg/L), but the reverse was the case for S. haemolyticus and S. epidermidis . No S. aureus isolate was resistant (≥32 mg/L) to either glycopeptide, but nine isolates of coagulase-negative staphylococci had an MIC of teicoplanin of 32 mg/L. Respiratory isolates of S. aureus were less susceptible to glycopeptides than those from other sites. Staphylococci from Belgium and Italy were less susceptible to teicoplanin than isolates from other countries.
Conclusions: This European survey shows that in 10 years of clinical use there have been no major changes in the susceptibility of staphylococci to the glycopeptides.     

Activity of the new quinolone WCK 771 against pneumococci

The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined. Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments. Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin. WCK 771 MIC50/90 values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid. WCK 771 MIC50/90 values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin. Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4 x MIC, as were the other quinolones tested. Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci. Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility.     

In vitro activity of daptomycin against <Emphasis Type="Italic">Staphylococci</Emphasis> isolated from bacteremia and community-onset skin and soft tissue infections in France: data from two nationwide studies

Staphylococci are a leading cause of skin and soft tissue infections (SSTIs) and bacteremia in France, a country with a high prevalence of oxacillin resistance. We evaluated the in vitro activity of daptomycin compared with reference compounds against 445 Staphylococcus aureus and 53 coagulase-negative Staphylococci (CNS) collected during two large nationwide studies performed in 2006 and 2007. The percentage of oxacillin resistance among S. aureus was 13.6% (SSTIs) and 30.7% (bacteremia). Daptomycin showed lower MIC₉₀ levels compared to vancomycin, teicoplanin, and linezolid (0.19 mg/L vs. 2, 1.5, and 1 mg/L, respectively), irrespective of oxacillin susceptibility. Amongst the CNS, 64.2% of the isolates originated from clinical bacteremia were resistant to oxacillin and 24.5% to teicoplanin; all but one Staphylococci were susceptible to daptomycin (MIC = 1.5 mg/l). As with linezolid, daptomycin seems to constitute an alternative option to treat some staphylococcal infections in the French context of high oxacillin resistance prevalence and high glycopeptides MIC.     

Resistance to vancomycin and teicoplanin: an emerging clinical problem.

Vancomycin and teicoplanin are glycopeptides active against a wide range of gram-positive bacteria. For 30 years following the discovery of vancomycin in 1956, vancomycin resistance was not detected among normally susceptible bacteria recovered from human specimens. Since 1986, however, bacteria resistant to vancomycin or teicoplanin or both have been described. Strains of the genera Leuconostoc, Lactobacillus, Pediococcus, and Erysipelothrix seem inherently resistant to glycopeptides. Species and strains of enterococci and coagulase-negative staphylococci appear to have acquired or developed resistance. There are at least two categories of glycopeptide resistance among enterococci, characterized by either high-level resistance to vancomycin (MIC, greater than or equal to 64 mg/liter) and teicoplanin (MIC, greater than or equal to 8 mg/liter) or lower-level vancomycin resistance (MIC, 32 to 64 mg/liter) and teicoplanin susceptibility (MIC, less than or equal to 1 mg/liter). The two categories appear to have similar resistance mechanisms, although genetic and biochemical studies indicate that they have arisen independently. Among coagulase-negative staphylococci, strains for which vancomycin MICs are up to 20 mg/liter or teicoplanin MICs are 16 to 32 mg/liter have been reported, but cross-resistance between these glycopeptides varies. The selective advantage accorded to glycopeptide-resistant bacteria and the observation that high-level resistance in enterococci is transferable suggest that such resistance may be expected to increase in incidence. Clinicians and microbiologists need to be aware of this emerging problem.     

A comparative microbiological and pharmacokinetic activity of vancomycin and teicoplanin]

Vancomycin and teicoplanin are two commercially available glycopeptide antibiotics. They have identical spectra of activity and similar mechanisms of action, and both are complex molecules. In vitro, vancomycin is more active against coagulase-negative staphylococci, while teicoplanin is more active against enterococci and pneumococci. The activity of the two antibiotics against Staphylococcus aureus is similar. The serum pharmacokinetics of vancomycin and teicoplanin are highly different, teicoplanin having a longer elimination half-life (40 hours versus 6-8 hours for vancomycin), but a higher degree of protein binding (90% versus 55%). We compared the two antibiotics on the basis of their inhibitory quotient kinetics, using the MIC90 values for the above bacterial species as the microbiological parameters, and the total and free (non-protein bound) serum concentrations as the pharmacokinetic parameters. The inhibitory quotient kinetics of vancomycin were always more favorable in terms of the free concentrations, even against those bacteria for which the teicoplanin MIC was lower.     

Comparative bactericidal activities of daptomycin, glycopeptides, linezolid and tigecycline against blood isolates of Gram-positive bacteria in Taiwan.

In-vitro MICs and minimum bactericidal concentrations (MBCs) of daptomycin, linezolid, tigecycline, vancomycin and teicoplanin against Gram-positive bacteria were determined using the broth microdilution method for ten blood isolates each of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), including two vancomycin-intermediate S. aureus (VISA), vancomycin-resistant Enterococcus faecium and Enterococcus faecalis. One strain of VISA was tested in a time-kill synergism assay of daptomycin combined with oxacillin, imipenem, rifampicin and isepamicin. Daptomycin showed excellent in-vitro bactericidal activity against all the isolates tested, with no tolerance or synergism effects when combined with other agents, except with rifampicin against VISA. Vancomycin had better bactericidal activity against MRSA and MSSA than did teicoplanin. Linezolid had the poorest bactericidal activity against the isolates tested, with 100% tolerance by the MSSA and VRE isolates, and 80% tolerance by the MRSA isolates. Tolerance towards tigecycline was exhibited by 40% of the MRSA isolates, 100% of the MSSA and vancomycin-resistant E. faecalis isolates, and 90% of the vancomycin-resistant E. faecium isolates.     

Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents,including ceftobiprole,nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006–2010

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n?=?517) exhibited MICs of 2 μg/ml and 0.3 % (n?=?6) demonstrated intermediate susceptibility (MICs of 4 μg/ml). Nearly all isolates (≥99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC₉₀ values were 2 μg/ml for ceftobiprole and 1 μg/ml for nemonoxacin. The MIC₉₀ values of mupirocin and tyrothricin were 0.12 and 4 μg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 μg/ml, the MIC₉₀ values were 2 μg/ml for teicoplanin, 0.5 μg/ml for daptomycin, and 0.5 μg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 μg/ml (2, 0.06, and 0.12 μg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n?=?6), teicoplanin (n?=?1), daptomycin (n?=?2), or tigecycline (n?=?1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 μg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.     

MIC distribution and inoculum effect of LY333328: A study of vancomycin-susceptible and VanA-type and VanC-type enterococci obtained from intensive care unit patient surveillance cultures

Objectives: To determine the in vitro activity and inoculum effect of LY333328, a semisynthetic glycopeptide, against vancomycin-susceptible and vancomycin-resistant enterococcal isolates.
Methods: One hundred and seventy-six enterococcal isolates (117 vancomycin-susceptible, 29 VanA-type and 30 VanC-type isolates) obtained from surveillance cultures of 139 intensive care unit patients were studied by the standard agar dilution method. Vancomycin resistance determinants were characterized by PCR.
Results: The activity of LY333328 was comparable (MIC range, 0.1–2 mg/L) to those of vancomycin (0.1–4 mg/L) and teicoplanin (0.06–1 mg/L) for vancomycin-susceptible isolates. LY333328 was more active (0.1–8 mg/L) than vancomycin (256 to >1024 mg/L) and teicoplanin (32–512 mg/L) against VanA-type isolates, and similar (0.2–1 mg/L) to teicoplanin (0.1–0.5 mg/L) against VanC-type isolates. The MIC distribution of LY333328 displayed a narrower range than that of vancomycin, with no clear distinction between susceptible and resistant populations. The increment in the inoculum size, from 10⁴ to 10⁶ CFU/spot, of susceptible isolates increased the MIC values of LY333328, vancomycin and teicoplanin by factors of 11.4, 1.6 and 3.8, respectively. The corresponding factors for LY333328 for VanA-type and VanC-type isolates were 3.5 and 6.4, respectively.
Conclusions: LY333328 displays an excellent in vitro activity against vancomycin-susceptible and -resistant enterococci. Nevertheless, the inoculum size used in susceptibility tests should be carefully controlled.     

New antimicrobial agents as therapy for resistant gram-positive cocci

Vancomycin- and methicillin-resistant gram-positive cocci have emerged as an increasingly problematic cause of hospital-acquired infections. We conducted a literature review of newer antibiotics with activity against vancomycin-resistant and methicillin-resistant gram-positive cocci. Quinupristin/dalfopristin, linezolid, daptomycin, and tigecycline have in vitro activity for methicillin-resistant staphylococci and are superior to vancomycin for vancomycin-resistant isolates. Dalbavancin, telavancin, and oritavancin are new glycopeptides that have superior pharmacodynamic properties compared to vancomycin. We review the antibacterial spectrum, clinical indications and contraindications, pharmacologic properties, and adverse events associated with each of these agents. Daptomycin has rapid bactericidal activity for Staphylococcus aureus and is approved for use in bacteremia and right-sided endocarditis. Linezolid is comparable to vancomycin in patients with methicillin-resistant S. aureus (MRSA) pneumonia and has pharmacoeconomic advantages given its oral formulation. Quinupristin/dalfopristin is the drug of choice for vancomycin-resistant Enterococcus faecium infections but has no activity against Enterococcus faecalis. Tigecycline has activity against both enterococcus species and MRSA; it is also active against Enterobacteriaceae and anaerobes which allows for use in intra-abdominal and diabetic foot infections. A review of numerous in vitro and animal model studies shows that interaction between these newer agents and other antistaphylococcal agents for S. aureus are usually indifferent (additive).     

Comparative in vitro activity of glycopeptides against coagulase negative staphylococci isolated in pediatric hospital units]

The minimum inhibitory concentrations (MICs) of vancomycin and teicoplanin were determined for 32 coagulase-negative staphylococci strains recovered from blood specimens from pediatric intensive care patients. All the strains were susceptible to vancomycin (MIC less than 4 mg/l). Sixteen strains were susceptible to teicoplanin (MIC less than 4 mg/l) and the sixteen remaining strains exhibited intermediate susceptibility, with MICs of 8 mg/l (10 strains) or 16 mg/l (6 strains). Inhibition zone diameters seen with vancomycin during agar diffusion susceptibility testing were consistently greater than 17 mm. Inhibition zones obtained with teicoplanin were 17 mm or more in diameter for 30 strains and under 17 mm in diameter for 2 strains. For 14 strains (44%), agar diffusion testing failed to detect the decreased susceptibility to teicoplanin revealed by MIC determinations. The agar diffusion method does not seem reliable for the determination of in vitro susceptibility to teicoplanin.     

Pharmacokinetic–pharmacodynamic evaluation of daptomycin, tigecycline, and linezolid versus vancomycin for the treatment of MRSA infections in four western European countries

Purpose

To evaluate the usefulness of daptomycin, tigecycline, and linezolid for the treatment of MRSA infection compared with vancomycin in Belgium, the United Kingdom/Ireland, and Spain.

Methods

The methodology included the following steps: acquisition of microbiological and pharmacokinetic data, Monte Carlo simulation, estimation of the probability of target attainment (PTA), and calculation of the cumulative fraction of response (CFR).

Results

We showed that differences in the susceptibility of MRSA strains among countries may justify differences in the antibiotic dose selection. Two, 3, and 4?g daily of vancomycin seem be adequate in Belgium, Spain, and United Kingdom/Ireland respectively. The CFR obtained with 50?mg tigecycline every 12?h was higher in Spain than in Belgium and the United Kingdom/Ireland, but with the highest dose (100?mg q12h) the CFR was always 100%. At least 8?mg/kg daptomycin is necessary in United Kingdom/Ireland, but 4?mg/kg may be sufficient in Spain, and probably in Belgium. Six hundred mg q12h linezolid may be adequate in the four countries.

Conclusion

Our study reinforces the idea that the local MIC distribution must be considered in order to increase the probability of success of empirical treatment and must be periodically updated.