Antimicrobial Therapy of Multidrug-Resistant Streptococcus pneumoniae, Vancomycin-Resistant Enterococci, and Methicillin-Resistant Staphylococcus aureus
ABSTRACT Antibiotic resistance among pneumococci, enterococci, and staphylococci has become increasingly important in recent decades. Clinicians should be familiar with the nuances of antibiotic susceptibility testing and interpretation in selecting antibiotics for these infections. The clinical significance of penicillin-resistant Streptococcus pneumoniae, macrolide-resistant S pneumoniae, and multidrug-resistant S pneumoniae is discussed. The clinical spectrum and therapeutic approach to Enterococcus faecalis (i.e., vancomycin-sensitive enterococci) and E faecium (i.e., vancomycin-resistant enterococci) are discussed. Differences in therapeutic approach between methicillin-sensitive Staphylococcus aureus and methicillin-resistant S aureus (MRSA) infections are reviewed. Differences between in vitro susceptibility testing and in vivo effectiveness of antibiotics for hospital-acquired MRSA (HA-MRSA) are described. Finally, the clinical features of infection and therapy of HA-MRSA and community-acquired MRSA (CA-MRSA) infections are compared.
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ABSTRACT: Antibacterial resistance in Streptococcus pneumoniae is increasing worldwide, affecting principally beta-lactams and macrolides (prevalence ranging between approximately 1% and 90% depending on the geographical area). Fluoroquinolone resistance has also started to emerge in countries with high level of antibacterial resistance and consumption. Of more concern, 40% of pneumococci display multi-drug resistant phenotypes, again with highly variable prevalence among countries. Infections caused by resistant pneumococci can still be treated using first-line antibacterials (beta-lactams), provided the dosage is optimised to cover less susceptible strains. Macrolides can no longer be used as monotherapy, but are combined with beta-lactams to cover intracellular bacteria. Ketolides could be an alternative, but toxicity issues have recently restricted the use of telithromycin in the US. The so-called respiratory fluoroquinolones offer the advantages of easy administration and a spectrum covering extracellular and intracellular pathogens. However, their broad spectrum raises questions regarding the global risk of resistance selection and their safety profile is far from optimal for wide use in the community. For multi-drug resistant pneumococci, ketolides and fluoroquinolones could be considered. A large number of drugs with activity against these multi-drug resistant strains (cephalosporins, carbapenems, glycopeptides, lipopeptides, ketolides, lincosamides, oxazolidinones, glycylcyclines, quinolones, deformylase inhibitors) are currently in development. Most of them are only new derivatives in existing classes, with improved intrinsic activity or lower susceptibility to resistance mechanisms. Except for the new fluoroquinolones, these agents are also primarily targeted towards methicillin-resistant Staphylococcus aureus infections; therefore, demonstration of their clinical efficacy in the management of pneumococcal infections is still awaited.Drugs 02/2007; 67(16):2355-82. DOI:10.2165/00003495-200767160-00005 · 4.13 Impact Factor
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ABSTRACT: There is little consensus on the most appropriate duration of antibiotic treatment for community-acquired pneumonia. The goal of this study is to systematically review randomized controlled trials comparing short-course and extended-course antibiotic regimens for community-acquired pneumonia. We searched MEDLINE, Embase, and CENTRAL, and reviewed reference lists from 1980 through June 2006. Studies were included if they were randomized controlled trials that compared short-course (7 days or less) versus extended-course (>7 days) antibiotic monotherapy for community-acquired pneumonia in adults. The primary outcome measure was failure to achieve clinical improvement. We found 15 randomized controlled trials matching our inclusion and exclusion criteria comprising 2796 total subjects. Short-course regimens primarily studied the use of azithromycin (n=10), but trials examining beta-lactams (n=2), fluoroquinolones (n=2), and ketolides (n=1) were found as well. Of the extended-course regimens, 3 studies utilized the same antibiotic, whereas 9 involved an antibiotic of the same class. Overall, there was no difference in the risk of clinical failure between the short-course and extended-course regimens (0.89, 95% confidence interval [CI], 0.78-1.02). In addition, there were no differences in the risk of mortality (0.81, 95% CI, 0.46-1.43) or bacteriologic eradication (1.11, 95% CI, 0.76-1.62). In subgroup analyses, there was a trend toward favorable clinical efficacy for the short-course regimens in all antibiotic classes (range of relative risk, 0.88-0.94). The available studies suggest that adults with mild to moderate community-acquired pneumonia can be safely and effectively treated with an antibiotic regimen of 7 days or less. Reduction in patient exposure to antibiotics may limit the increasing rates of antimicrobial drug resistance, decrease cost, and improve patient adherence and tolerability.The American journal of medicine 10/2007; 120(9):783-90. DOI:10.1016/j.amjmed.2007.04.023 · 5.30 Impact Factor