Wenzel_edit.qxp 28/1/09 11:19 am Page 88
Bacterial Infections
Table 1: Potential New Agents for Treating Infections Caused by Methicllin-resistant Staphylococcus aureus
Drug Approximate T
1/2
Efficacy Trials* Comments References
Second-generation
Glycopeptides
Dalbavancin 5–7 days Dalbavancin 1,000mg on day 1 and 500mg on No toxicity or red man syndrome reported. No 10–13
Eliminated by renal and day 8 (n=571) versus linezolid 600mg twice daily for evidence of cytochrome P450 enzyme involved in
non-renal routes 14 days (n=283) treating SSTIs (90% S. aureus; metabolism. Not active against VRE or VRSA.
50% MRSA).
Clinical success: 88.9 versus 91.2%, respectively.
Telavancin 8.8–9.1 hours Two phase III studies of telavancin (n=928) versus Similar rate of discontinuation to vancomycin 14–16
vancomycin (n=939) for SSTIs. Both met the end-point (8 versus 6%, respectively). Activity in biofilms
of non-inferiority with vancomycin. Clinical success in has been reported.
88 and 87%, respectively. Cure rates for MRSA Post-antibiotic effect reported: 0.4–6.7 hours
were 91 versus 86%, respectively. (A-973, p.20)
†
In a subset analysis of patients with
hospital-acquired pneumonia due to S. aureus with
vancomycin MICs >1µg/ml, cure rates with telavancin
versus vancomycin were 87 versuss 74%, respectively
(K-528, p.454).
†
Oritavancin 100 hours None published yet; two studies of SSTIs: No severe adverse events reported. Some nausea 17–18
1: Oritavancin 1.5mg/kg or 3mg/kg once daily for (14%), taste changes (8%) and insomnia reported.
3–7 days followed by placebo orally versus In a study of skin and SSTIs, clinical cure rates for
vancomycin 10–15mg/kg twice daily followed by oritavancin vs vancomycin were 78 versus 76%,
cephalexin 500–1,000mg twice daily. Low- versus respectively (L-1514, p.616).
†
high-dose oritavancin versus vancomycin had success
rates of 76, 76 and 80%, respectively.
2: Oritavancin 200mg daily followed by oral placebo
versus vancomycin 15mg/kg twice daily followed by
cephalexin 1,000mg twice daily. Clinical cure in 77
versus 76%, respectively.
Fourth-generation ESCs
Ceftobiprole 3.5 hours SSTIs: Ceftobiprole vs vancomycin: ceftabiprole was May not be suitable for Gram-negative rods 19–21
shown to be non-inferior to vancomycin. Ceftabiprole expressing ESBLs.
†
versuss vancomycin plus ceftazidime for phase III Cure rates for ceftobiprole vs ceftazidime plus linezolid
trial for lower respiratory infections under way. were 69 versus 72%, respectively, suggesting
Ceftobiprole 500mg twice daily was compared with non-inferiority (K-486, p.444).
†
vancomycin 1,000mg twice daily. Eighty per cent of
Gram-positive isolates were S. aureus, of which
one-third were MRSA. Clinical cure rates were similar
at 92 and 90%, respectively.
Ceftaroline fosamil 2.6 hours Two trials of ceftaroline fosamil versus vancomycin Ceftaroline is the active metabolite of ceftaroline 22–23
and aztreonam for SSTIs. Clinical cure rate was fosamil, the drug prescribed.
96.7% for ceftaroline (n=61) versus 88.9% for standard
therapy (n=27) in one study. A third trial of ceftaroline
fosamil versus ceftriaxone for community-acquired
pneumonia is under way.
Novel Diaminopyrimidine
Iclaprim 2.4 hours Two studies of SSTIs; the comparator is linezolid. A dihydrofolate reductase inhibitor. Synergy with 24–25
Iclaprim shown to be comparable to linezolid. sulphonamides. May not have reliable activity against
Iclaprim was dosed at 0.8mg/kg twice daily versus Streptococcus pyogenes. In complicated SSTIs, clinical
linezolid 600mg twice daily for 14 days. Clinical cure cure rates with iclaprim versus linezolid were 82 versus
83.1 versus 88.7%, respectively, in Assist-1 Study. 85%, respectively (K-1512, p. 615).
†
In a study of
Clinical cure 81.3 versus 81.9%, respectively, in intravenous iclaprim vsersus intravenous linezolid in
Assist-2 Study. patients with SSTIs, the mean change in QTc interval
was 4–6ms compared with linezolid (K-1513, p.615).
†
*Also see websites of manufacturers.
†
Abstracts of the 48th Annual ICAAC, IDSA 46th Annual Meeting, Washington, DC, 25–28 October 2008.
ESBL = extended-spectrum beta-lactamase; ESC = extended-spectrum cephalosporin; SSTI = skin and skin-structure infections; MRSA = methicillin-resistant Staphylococcus aureus;
VRE = vancomycin-resistant enterococcus; VRSA = vancomycin-resistant Staphylococcus aureus.
cost.
9
However, if the clinical presentation is primarily cellulitis, a condition novel second-generation glycopeptides or new fourth-generation,
caused frequently by Streptococcus pyogenes or S. aureus, it should be extended-spectrum cephalosporins (ESCs) – are equivalent to vancomycin
recognised that doxycycline and trimethoprim–sulphamethoxazole are not for the treatment of CA-MRSA SSTIs (see Table 1).
10–25
A major advantage
reliable antibiotics for treating S. pyogenes. of new glycopeptides over vancomycin is their rapid bactericidal activity and
long half-lives. For example, dalbavancin can be dosed at weekly intervals.
More recently, data in controlled studies show that new drugs – such as the All must be given parenterally.
88 EUROPEAN INFECTIOUS DISEASE
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116